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Background: A Krukenberg tumour (KT) is defined as an ovarian metastasis from a gastrointestinal adenocarcinoma and suggests a terminal condition. This study aimed to identify the prognostic factors affecting the survival of patients with KTs of colorectal origin who receive cytoreductive surgery. Methods: Medical records of patients who had received cytoreductive surgery and had been pathologically diagnosed with KT of colorectal origin in two centres were reviewed. Information about the patients' clinicopathological features and follow-up visit were collected. Factors influencing patient survival were analysed. Results: Fifty-seven patients were included in this study. The median survival time was 35 months. Five-year overall survival was 25%. Patients who had recurrence 2 years after resection of the primary tumour, achieved complete cytoreduction, had metastases confined to the pelvis, had no lymph node involvement, and received systemic chemotherapy had a significantly longer median survival than those who had recurrence at the same time as resection of the primary tumour (P = 0.027), received incomplete cytoreduction (P < 0.001), had metastases beyond the pelvis (P < 0.001), had lymph node involvement (P = 0.011), and did not receive systemic chemotherapy (P = 0. 006) on log-rank test. Less extensive metastatic disease, achievement of complete cytoreduction, and use of systemic chemotherapy were significantly associated with improved prognosis on multivariate analysis. Conclusions: Cytoreductive surgery may confer survival benefits in patients with KTs of colorectal origin who attain complete cytoreduction and whose metastases are confined to the pelvis and when combined with active systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Axillary lymph node status, which was routinely assessed by axillary lymph node dissection (ALND) until the 1990s, is a crucial factor in determining the stage, prognosis, and therapeutic strategy used for breast cancer patients. Axillary surgery for breast cancer patients has evolved from ALND to minimally invasive approaches. Over the decades, the application of noninvasive imaging techniques, machine learning approaches and emerging clinical prediction models for the detection of axillary lymph node metastasis greatly improves clinical diagnostic efficacy and provides optimal surgical selection. In this work, we summarize the historical axillary surgery and updated perspectives of axillary management for breast cancer patients., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Sarcopenia in patients with non-small cell lung cancer (NSCLC) is often indicative of a more aggressive disease course and a poorer prognosis. Nevertheless, there have been limited studies that specifically examined clinical parameters to predict sarcopenia in individuals with malignant pleural effusion (MPE). Our objective is to investigate the potential correlations between commonly utilized clinical variables and reduced muscle mass in NSCLC patients who also have MPE., Methods: This retrospective study examined the clinicopathological data and imaging characteristics of NSCLC patients admitted to the hospital with MPE. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was employed to select the most appropriate variables for model creation, effectively reducing the chance of overfitting. Logistic regression analysis was conducted to pinpoint the independent factors predicting sarcopenia in NSCLC patients with MPE. Subsequently, a nomogram was formulated to estimate the sarcopenia risk for individual patient. The efficacy of this nomogram was assessed through various metrics, including the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA)., Results: A total of 139 patients, with an average age of 66 years and a majority being male (56.8%), were included in this study. Multivariate logistic regression analysis revealed that age, body mass index (BMI), albumin (Alb), and cytokeratin-19-fragment (CY21-1) were all independent predictors of sarcopenia in NSCLC patients with MPE. A nomogram was developed to facilitate personalized prediction of sarcopenia for individual patient. The ROC curve demonstrated that the nomogram model incorporating these predictive factors achieved an area under the curve (AUC) of 0.889, indicating its discriminatory power in predicting sarcopenia. The calibration curve demonstrated a strong concordance between the actual and the anticipated sarcopenia risk. DCA further confirmed that the nomogram showed good clinical applicability and net benefits in sarcopenia prediction., Conclusions: Certain commonly used clinical characteristics were found to be associated with decreased skeletal muscle mass. Specifically, age, BMI, Alb, and CY21-1 levels emerged as predictive indicators for sarcopenia among NSCLC patients with MPE. These indicators have the potential to serve as effective alternatives to traditional computed tomography (CT) evaluation in assessing sarcopenia., Competing Interests: Declarations. Ethical approval: The research protocol was approved by the Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University School of Medicine (No. XJTU1AF2023LSK-2019-217) based on the Helsinki Declaration. Consent to participate: All patients signed a written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: Osteoarthritis (OA) causes significant musculoskeletal pain. This study assessed the efficacy and safety of fasinumab, an investigational nerve growth factor inhibitor, in patients with moderate-to-severe OA pain of the knee/hip., Methods: In this Phase 3, randomized, double-blind, placebo- and non-steroidal anti-inflammatory drug (NSAID)-controlled study, patients with OA (Kellgren-Lawrence grade ≥ 2; Western Ontario and McMaster Universities Arthritis Index [WOMAC] pain score ≥ 4) received (2:1:1:1) fasinumab 1 mg every 4 weeks, diclofenac 75 mg twice daily, celecoxib 200 mg daily, or placebo for 24 weeks. Co‑primary endpoints were change in WOMAC pain and physical function scores to Week 24 versus placebo. For safety, joints were imaged in all patients at pre‑specified times, regardless of symptoms., Results: Of 4531 patients screened, 1650 were randomized. At Week 24, greater improvements were observed for fasinumab versus placebo; least-squares mean difference: -0.63 (p = 0.0003) for WOMAC pain and -0.64 (p = 0.0003) for physical function. Improvements were numerically greater for fasinumab versus NSAIDs for physical function (-0.64 versus -0.31; nominal p < 0.05) and pain (-0.63 versus - 0.39; p = NS). Adjudicated arthropathies occurred in 1.6% of placebo-treated, 1.5% of NSAID-treated, and 5.6% of fasinumab-treated patients; joint replacements occurred in 3.6% of placebo-treated, 4.8% of NSAID-treated, and 3.4% of fasinumab-treated patients., Conclusion: Fasinumab significantly improved WOMAC pain and physical function scores versus placebo in < 24 weeks in difficult-to-treat patients with pain due to OA of the knee/hip. Adjudicated arthropathies were more frequent with fasinumab; there were no differences in the proportions of patients with joint replacements., Trial Registration: Clinicaltrials.gov NCT03304379. Date of first registration: October 2, 2017., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with consensus ethical principles derived from international guidelines, including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines and applicable International Council for Harmonisation Good Clinical Practice Guidelines. The institutional review board or independent ethics committee at each study center reviewed and approved the protocol, protocol amendments, informed consent form, and any other relevant documents (see the Supplementary Appendix for details). All participants provided written informed consent to participate in the study. During routine blinded monitoring, prior to database lock, the sponsor suspected and identified non-compliance with good clinical practice at four sites comprising 219 patients. Patients from these sites were subsequently excluded from the modified full analysis set, as prespecified in the statistical analysis plan (see the Supplementary Appendix for details). Consent for publication: Not applicable. Competing interests: SJD, HG, GPG, and PD are all employees of and shareholders in Regeneron Pharmaceuticals, Inc. who report having three patents pending with Regeneron Pharmaceuticals, Inc. SE, CE, TH, HEH, KCT, JC, YP, LB, NT, GM, and NB are all employees of and shareholders in Regeneron Pharmaceuticals, Inc. GV has served as a consultant for AbbVie, Celgene, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Sanofi/Regeneron, and UCB; and as an Investigator for AbbVie, Image Analysis, Bristol Myers Squibb, Janssen, Lilly, Merck, MLKCDT, Novartis, Pfizer, and Sanofi/Regeneron. TF owns equity in Clario, Inc, and has received grants or contracts from various pharmaceutical and biotechnology companies developing new drugs to treat osteoarthritis. JDD is an employee of and shareholder in Regeneron Pharmaceuticals, Inc. who reports having two patents pending with Regeneron Pharmaceuticals, Inc. SZ has no conflict of interest to disclose. MF is an employee of Teva Pharmaceuticals; has been funded by Teva Pharmaceuticals for travel and attendance at investigator meetings; and has received and holds stocks or stock options., (© 2025. The Author(s).)

Background: Bovine coronavirus (BCoV) is a causative agent of enteric and respiratory diseases in cattle and is responsible for severe economic losses. Recently, a novel BCoV variant with 12-nucleotide deletion or insertion in the hemagglutinin-esterase (HE) receptor-binding domain (RBD) has emerged. However, the biological consequences of these deletions/insertions and the prevalence of these variants remain unknown. Here, 47 diarrheal and 47 nasal swab samples were collected from five cattle farms in various Ningxia, China regions to detect and isolate BCoV., Results: Eleven complete HE genes and eight complete S genes were amplified from 34 BCoV-positive samples using RT-PCR. Eight BCoV strains were successfully isolated using HRT-18 cells, and four underwent genome sequencing. Three HE genes contained a 12-nucleotide insertion in the RBD, and a single HE gene contained a novel 12-nucleotide deletion. Phylogenetic analysis of genomes revealed that these HE-deletion/insertion variants do not share a common most recent ancestor with those reported from the US. Molecular docking results showed that the insertion of four additional amino acids between F211 and L212 increased the affinity of HE protein to O-acetylated sialic acid, which may be favorable for virion-particle attachment. Growth kinetics suggest that the HE-deletion variant had a non-cytopathic effect and lower virus titer., Conclusions: These findings suggest that BCoV HE deleted/inserted variants are prevalent in cattle and exhibit various biological characteristics. We should be alert to these HE-variants with insertions or deletions in the RBD, which may increase the possibility of interspecies transmission., Competing Interests: Declarations. Ethics approval and consent to participate: The animal study was reviewed and approved by Executive ethics committee of Laboratory Animal Management and Ethics Inspection of Northwest A&F University (XN2021-0601), Xianyang, China. Written informed consent was obtained from the owners for the participation of their animals in this study. Consent for publication: NA. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: In previous studies, elevated expression of UBE2L3 has been observed in osteosarcoma cells, and silencing UBE2L3 has been shown to promote oxidative stress and induce necroptosis. However, the exact molecular mechanisms underlying these findings remain unclear., Objective: The purpose of this study is to investigate the molecular mechanisms by which interfering with UBE2L3 expression promotes necroptosis and impacts the progression of osteosarcoma, building upon previous in vitro cell experiments., Methods: Osteosarcoma cells were transfected with shNC and shUBE2L3 plasmids, and the cells were injected into the right tibia of nude mice to establish a tumor xenograft model. The growth rate, changes in body weight, and tumor volume of the mice in each group were observed. After 15 days, the mice were sacrificed, and the tumors were dissected and analyzed for tumor volume. Immunohistochemical staining was performed to detect changes in the expression of necroptosis-related proteins, such as PCNA, p-MLKL, and p-RIP1. Additionally, U2OS and HOS cells were transfected with UBE2L3-silencing plasmids, and immunoprecipitation was performed to investigate the interaction between UBE2L3 and the necroptosis protein MLKL. By combining these experiments, we aim to evaluate the impact of UBE2L3 on necroptosis both in vitro and in vivo and elucidate its specific role in targeting MLKL to regulate necroptosis as a therapeutic approach for osteosarcoma., Results: After interfering with UBE2L3, the growth rate of tumors in nude mice significantly slowed down, accompanied by a notable reduction in tumor volume and weight. These findings suggest that inhibiting the expression of UBE2L3 can suppress the growth of osteosarcoma. Furthermore, immunohistochemical analysis revealed that following UBE2L3 interference, the intensity of staining for the necrotic proteins p-MLKL and p-RIP1 was increased and PCNA staining was decreased, indicating that interfering with UBE2L3 expression can promote necroptosis. Moreover, through transfection of UBE2L3 silencing plasmids into osteosarcoma cells in vitro, immunoprecipitation and ubiquitination results demonstrated that UBE2L3 can specifically bind to MLKL. Overexpression of UBE2L3 promoted the ubiquitination of MLKL and reduced its expression. Thus, down-regulation of UBE2L3 could modulate downstream MLKL expression and promote necrosis of osteosarcoma cells., Conclusion: UBE2L3 selectively binds to MLKL, exerting ubiquitination-mediated regulation on downstream MLKL. Decreased expression of UBE2L3 modulates MLKL expression and promotes necrosis, thereby inhibiting osteosarcoma growth., Competing Interests: Declarations. Ethics approval and consent to participate: Approval was obtained from the respective ethics committee (The Second Hospital of Shandong University) No.KYLL2024349. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. The consents were given voluntarily by study participants and the approvals were obtained from all participants. Consent for publication: Informed consent was obtained from all individuals participating in the study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Trimester-specific reference intervals (TSRIs) for maternal lipid profiles should be determined, and the impact of dyslipidemia on adverse pregnancy outcomes (APOs) should be estimated., Methods: Data from 25,081 pregnant women in a large Southeast Chinese cohort were collected. Serial lipid profiling was performed throughout gestation, with measurements obtained during the first, second, and third trimesters, as well as within 24 h of delivery. The truncated maximum likelihood (TML) method, the Hoffman method, and inverse modelling were employed to establish TSRIs for lipids, with TML as the primary method. The associations of dyslipidemia with APOs were investigated by logistic regressions within the setting of TSRIs for various lipids., Results: The TSRIs established by the TML method were as follows: 3.36-6.06, 4.19-7.89, 4.60-8.97, and 4.41-8.79 mmol/L for total cholesterol; 0.66-2.32, 1.11-3.75, 1.49-4.77, and 1.61-6.14 mmol/L for triglycerides; 1.42-3.61, 1.94-5.13, 1.95-5.39, and 1.86-5.50 mmol/L for low-density lipoprotein cholesterol; 1.11-2.31, 1.30-2.75, 1.24-2.59, and 1.20-2.65 mmol/L for high-density lipoprotein cholesterol; 1.89-4.20, 2.59-5.85, 2.87-6.17, and 2.88-6.78 mmol/L for non-high-density lipoprotein cholesterol; 1.04-1.96, 1.25-2.41, 1.23-2.46, and 1.25-2.47 g/L for apolipoprotein A1; 0.43-0.82, 0.63-1.17, 0.65-1.55, and 0.79-1.77 g/L for apolipoprotein B; and 0.27-0.79, 0.35-0.94, 0.39-1.11, and 0.40-1.15 for the apolipoprotein B and apolipoprotein A1 ratio from the first trimester to the delivery period, respectively. The results of the Hoffman and inverse modelling methods closely aligned with those of the TML method. In pregnant women, lipid levels that deviate above or below the established TSRIs are significantly associated with the occurrence of APOs., Conclusion: TSRIs are recommended for the identification and management of dyslipidemia during pregnancy. Inappropriate maternal blood lipid levels are associated with an increased risk of APOs., Competing Interests: Declarations. Ethical approval and consent to participate: According to the Declaration of Helsinki, studies involving humans were reviewed and approved by the Research Ethics Committee of Fujian Maternal and Child Health Hospital (approval number: 2017KR-030). Participants provided written informed consent to participate in this study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Stroke is a prevalent neurological disorder globally, often resulting in post-stroke depression (PSD). The cardiometabolic index (CMI) is a novel marker for assessing cardiovascular and metabolic health, but its association with PSD has not been adequately investigated. This study aims to explore the relationship between CMI and PSD, providing a basis for clinical prevention and treatment., Methods: We utilized data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES) in this cross-sectional analysis. Multivariable logistic regression and restricted cubic spline (RCS) models were applied to assess the independent and linear relationships between CMI and PSD. To minimize confounding, propensity score matching (PSM) was employed. Subgroup analyses and interaction tests were also conducted to further explore potential effect modifications., Results: A total of 1082 participants were included, with 18.67% diagnosed with PSD. Higher CMI levels were positively associated with PSD in stroke patients. In the fully adjusted model, the association between CMI and PSD remained significant (OR = 1.06; 95% CI 1.01-1.12). RCS analysis indicated a linear relationship between CMI and PSD (nonlinearity P = 0.334). Subgroup analyses showed that this association persisted across different groups (all P for trend > 0.05). After covariate balance through PSM, the positive association between CMI and PSD was further supported., Conclusion: This study demonstrates a positive association between CMI and PSD. CMI may serve as a useful tool for evaluating the risk of depressive symptom in stroke patients, potentially aiding in targeted clinical interventions., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Mobile applications, as innovative tools for promoting bystander cardiopulmonary resuscitation (CPR), have demonstrated potential to improve outcomes for patients experiencing out-of-hospital cardiac arrest (OHCA). This meta-analysis sought to systematically review the technical features of existing mobile applications and evaluate their impact on OHCA patient outcomes under various emergency response strategies. The findings aimed to guide the development and optimization of prehospital public emergency response systems., Methods: A systematic search was conducted in databases including China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Database (VIP), SinoMed, PubMed, Embase, Web of Science, and the Cochrane Library, from inception to August 2023. The included studies involved notifying citizens via text messages or smartphone applications to act as first responders or volunteers in OHCA cases. Using a random effects model and subgroup analysis, we synthesized the results to identify sources of heterogeneity and assess outcomes., Results: Thirteen mobile applications were included, with an average activation rate of 35.3% among patients and a volunteer arrival rate of 53.3%. Compared to traditional emergency medical services, mobile applications significantly improved survival to discharge or 30-day survival rates (RR = 1.34, 95% CI: 1.24-1.44; P < 0.05), return of spontaneous circulation (ROSC) rates upon hospital admission (RR = 1.23, 95% CI: 1.09-1.40; P < 0.05), bystander CPR rates (RR = 1.25, 95% CI: 1.13-1.37; P < 0.05), and bystander defibrillation rates (RR = 1.23, 95% CI: 1.00-1.51; P = 0.05). Subgroup analyses revealed consistent results for bystander CPR rates and survival outcomes, while variations in defibrillation rates and ROSC at admission were observed, indicating potential influences of application design and operational parameters., Conclusions: This study highlighted the significant potential of mobile applications in enhancing bystander interventions and improving patient outcomes. Addressing challenges such as improving access to automated external defibrillators and raising public awareness remained essential to maximizing their overall effectiveness. PROSPERO REGISTRATION NUMBER: CRD42023477676., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The Highly Pathogenic Island (HPI) found in Yersinia pestis can be horizontally transferred to E. coli, enhancing its virulence and pathogenicity. Ubiquitin (Ub) acts as an activator of the NF-κB pathway and plays a critical role in the inflammatory response. However, the precise mechanism by which Ub and the regulated TLR4/NF-κB pathway contribute to HPI-induced intestinal inflammation in E. coli remains unclear., Results: In this study, we established Ub overexpression models of small intestinal epithelial cells (in vitro) and BALB/c mice (in vivo) and infected these models with HPI-rich E. coli. We investigated the role of the Ub-regulated TLR4/NF-κB pathway in E. coli HPI-induced intestinal inflammation through qPCR, ELISA, immunofluorescence, immunohistochemistry, and H&E staining. Our findings confirmed that E. coli HPI promoted the expression of Ub, TLR4, and NF-κB in IPEC-J2 cells and induced the translocation of NF-κB p65 protein to the nucleus. Further investigations revealed that Ub overexpression enhanced epithelial cell damage induced by E. coli HPI. This was accompanied by up-regulation of mRNA levels of TLR4, MyD88, NF-κB, IL-1β, and TNF-α, as well as increased release of the inflammatory factors IL-1β and TNF-α. In a mouse model with Ub overexpression infected with E. coli HPI, we observed that Ub overexpression promoted E. coli HPI-induced intestinal inflammation. Mechanistically, E. coli HPI induced intestinal epithelial cell damage by inducing Ub overexpression and modulating the TLR4/NF-κB pathway., Conclusions: In conclusion, this study sheds light on the significant role of the Ub-regulated TLR4/NF-κB pathway in E. coli HPI-induced duodenitis, offering novel insights into the pathogenesis of E. coli infections., Competing Interests: Declarations. Ethics approval and consent to participate: The experiment’s design was authorized by Yunnan Agriculture University’s Institutional Animal Care and Use Committee (protocol code: 202303006, 3 March 2023). The animals are being grown and maintained in compliance with the requirements outlined in Yunnan Province’s Rules for the Administration of Laboratory Animals. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Kawasaki disease (KD) primarily affects young children and can lead to coronary artery lesions. Intravenous immunoglobulin (IVIG) treatment is essential; however, it may fail in 10-20% of cases, increasing the risk of complications. Complete blood count (CBC) tests can help assess disease severity and predict risks. This study investigated the impact of IVIG on peripheral blood cells, including neutrophil count, platelet-lymphocyte ratio, hemoglobin level, mean platelet volume (MPV), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), in children with KD complicated by coronary artery lesions (CALs)., Methods: This retrospective analysis included children diagnosed with typical KD. The neutrophil count, hemoglobin level, platelet-lymphocyte ratio, MPV, ESR, and CRP were compared between those with (CAL + ) and without (CAL - ) CALs during the acute phase, as well as at 7 days, 1 month, and 2 months after normalizing body temperature with IVIG., Results: A total of 76 children with KD were analyzed, including 30 with CAL + . CAL + and CAL - patients exhibited elevated neutrophil counts during the acute phase, with no significant differences (P > 0.05) between groups. After IVIG treatment, CAL - patients demonstrated a more pronounced reduction in neutrophil count (P < 0.05) than CAL + patients. Hemoglobin levels differed significantly during the acute phase (P < 0.05) but were comparable post-treatment (P > 0.05) between CAL + and CAL - patients. The platelet-lymphocyte ratio varied significantly between groups during the acute phase and 1-month post-treatment (P < 0.05). Mean ESR and CRP levels were significantly elevated at all time points in the CAL + group compared with the CAL - group. No significant differences in MPV were observed between groups., Conclusions: After IVIG treatment, CAL - patients demonstrated a more important reduction in neutrophil count than CAL + patients after IVIG. Pediatric patients with KD and CAL + showed lower hemoglobin and platelet-lymphocyte ratio and higher ESR and CRP compared with CAL - , suggesting that they may serve as indicators for CAL in pediatric patients with KD., Competing Interests: Declarations. Ethics approval and consent to participate: This work has been carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association. This work was supported by the Medical Ethics Committee of Hebei Children’s Hospital (202222-103). Legal guardians of participating children provided informed consent. Consent for publication: Not applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2025. The Author(s).)

Background: Ferroptosis is a non-apoptotic form of regulated cell death that involves an imbalance in the homeostasis of two elements: iron and lipid hydroperoxides. The accumulation of lipid hydroperoxide serves as a key trigger for initiating ferroptosis. Recent studies have identified ferroptosis as a critical pathophysiology contributing to kidney disease progression. However, the specific mechanisms underlying the role of ferroptosis in chronic kidney disease (CKD) have not been elucidated., Methods: Tubular epithelial cells (TECs) ferroptosis was evaluated in unilateral ureteral obstruction (UUO) models and in TGF-β-treated HK-2 cells to explore the relationship between ferroptosis and fibrosis. Ferroptosis inhibitors (ferrostatin-1) and TECs-targeted glutathione peroxidase 4 (GPX4) overexpression in vivo and in vitro were used to investigate the effect and mechanism of TECs ferroptosis on fibrosis progression., Results: Our findings indicate that ferroptosis is persistently activated during various states of the UUO model. As the results, ferroptosis was identified as a core facilitator of renal interstitial fibrosis in TECs during UUO. The reduction in TECs ferroptosis significantly ameliorated renal fibrosis and maintained the structure in the proximal tubules. Persistent activation of TECs ferroptosis effectively aggravated fibrosis progression through the TGF-β/Smad pathway., Conclusions: Inhibiting ferroptosis effectively rescues the accumulation of profibrotic cytokines, thereby alleviating renal fibrosis. The profibrotic mechanism of ferroptosis is closely related to the TGF-β/Smad pathway, and targeting ferroptosis and increasing GPX4 expression could be an effective strategy for treating CKD., Competing Interests: Declarations. Ethics approval and consent to participate: This paper does not describe studies involving human participants, human data or human tissue. All animal interventions were approved by the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Aspiration pneumonia (AP) is a type of lung inflammation caused by the aspiration of food, oropharyngeal secretions, or gastric contents. This condition is particularly common in older adults and individuals with impaired swallowing or consciousness. While the diagnosis of AP relies on clinical history, swallowing assessments, and imaging, these methods have significant limitations, often leading to underdiagnosis or misdiagnosis. Reliable biomarkers for AP diagnosis are lacking, making early detection and treatment challenging., Methods: Nineteen patients diagnosed with pneumonia were included in this study, divided into two groups: AP (n = 10) and non-AP (n = 9). Biological fluid samples, including bronchoalveolar lavage fluid (BALF), saliva, serum, sputum, and urine, were analyzed using non-targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS). Differential metabolites were identified using fold change analysis, statistical significance, and receiver operating characteristic (ROC) curve analysis to evaluate their diagnostic potential. Spearman correlation was used to examine the relationship between selected metabolites and clinical parameters., Results: Significant metabolic differences were found between AP and non-AP patients, with many different metabolites identified across biological fluids. Dehydroepiandrosterone sulfate (DHEAS), Androstenediol-3-sulfate (ADIOLS), and beta-muricholic acid were identified as key biomarkers through fold change analysis and ROC curve analysis, showing consistent increasing or decreasing trends in BALF, sputum, and serum samples. DHEAS was found to be negatively correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) (r = - 0.619, p = 0.005) in BALF sample. The area under curve (AUC) values showed that these molecules could serve as effective biomarkers for AP., Conclusions: This study identifies DHEAS, ADIOLS and beta-muricholic acid as promising biomarkers for AP, with the potential to improve early diagnosis and treatment. These findings underscore the clinical value of metabolomics in developing diagnostic tools for AP, facilitating better clinical management and patient outcomes. Further research is required to validate these biomarkers in larger cohorts and explore their mechanistic roles in AP pathophysiology., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Scientific Research Review, the Second Affiliated Hospital of Fujian Medical University (No.2022 −500). The written informed consent of each participant was obtained. This study was performed in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The prevalence of type 2 diabetes mellitus (T2DM) remains high and biomarkers related to T2DM are needed to be investigated. This study aimed to investigate the association between neutrophil percentage-to-albumin ratio (NPAR) with all-cause mortality and the risk of cardiovascular disease (CVD) mortality in community-dwelling individuals with T2DM., Methods: This prospective cohort study included 3602 adults aged 20 or above who were diagnosed with diabetes by the American Diabetes Association criteria in the US National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2016, and followed up until 2019. Multivariable Cox proportional hazards regression models were utilized to determine the relationship between NPAR with all-cause mortality and cardiovascular disease (CVD) mortality. Restricted cubic spline regression analyses were employed to explore the nonlinear relationship between NPAR and cardiovascular disease (CVD) mortality. The assessment of nonlinearity was conducted using the likelihood ratio test., Results: After adjustment, the risk ratio for all-cause mortality in the highest NPAR group (≥ 15.40) compared to the lowest serum NPAR reference group (< 13.30) was 1.62 (95% CI, 1.36, 1.94) with P values < 0.001. Nevertheless, the risk ratio for cardiovascular disease (CVD) mortality in the highest NPAR group (≥ 15.40) versus the lowest serum NPAR reference group (< 13.30) was 1.41 (95% CI, 0.99, 2.00) with a P value of 0.06. Among patients with T2DM, serum NPAR levels exhibited a nonlinear correlation with both CVD mortality risk and all-cause mortality risk, with P values < 0.001 for both., Conclusions: This study identified a significant association between elevated levels of the neutrophil percentage-to-albumin ratio (NPAR) and an increased risk of all-cause mortality among individuals with type 2 diabetes mellitus (T2DM). Conversely, no correlation was found between NPAR levels and CVD mortality., Competing Interests: Declarations. Ethics approval and consent to participate: The National Center for Health Statistics’ Research Ethics Review Board reviewed and approved all data collection protocols. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most harmful pathogens in the swine industry. Our previous studies demonstrated that the small extracellular domain (ECL2) of CLDN4 effectively blocks PRRSV infection. In this study, we explored the in vivo administration of swine ECL2 (sECL2) and found that it blocked HP-PRRSV infection and alleviated histopathological changes in organs. Notably, sECL2 stimulated cytokine production in the lungs. We observed that CLDN4 upregulated the expression of IFN-β at low doses of GP3. While high doses of GP3 inhibited the activity of the IFN-β promotor, regardless of whether CLDN4 was present. GP3 also downregulated IFN-β by decreasing the phosphorylation of TBK1 and IRF3. These findings highlight functional differences in GP3 under quantity control, which account for the variations in IFN-β induction during the early and late stages of infection. Our results indicate that sECL2 is a promising candidate drug for developing treatments to control PRRS., Competing Interests: Declarations. Ethics approval and consent to participate: All animal protocols were reviewed and approved by the Shandong Agricultural University Animal Care and Use Committee (Approval Number: SDAUA-2020–027) and performed in strict accordance with the Animal Ethics Procedures and Guidelines of the People’s Republic of China. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: The impact of radiation-related lymphocyte recovery on prognosis in locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains unclear., Methods: Patients with stage II-IVa ESCC who received definitive RT were screened. Collect absolute lymphocyte counts (ALCs) before, during, and after RT. The recovery status of lymphocytes was observed at one-month post-RT (P1) and three months post-RT (P3). Patients with relatively lower lymphocyte recovery levels at P1 were divided into Group a and those with higher levels were divided into Group b. Patients with relatively lower lymphocyte recovery levels at P3 were divided into Group A and those higher were divided into Group B. Kaplan-Merier's analysis and Cox analysis were conducted to compare survival outcomes. Binary logistic regression analyses was employed to ascertain factors associated with lymphocyte recovery., Results: 116 patients were enrolled. During RT, ALCs reached the bottom 5 weeks after RT started and 70.7% of patients experienced G3 lymphopenia. The median OS for Group a and Group b were 38.1 months and 14.4 months, p = 0.097. The median PFS for Group a and Group b were 14.2 months and 10.0 months, p = 0.037. Whereas, the median OS for Group A and Group B was 14.5 months and 22.2 months, p = 0.019. The median PFS for Group A and Group B were 8.4 months and 12.4 months, p = 0.021. Cox multivariable analysis revealed that higher lymphocyte recovery level at P3 was significantly associated with superior OS (p = 0.040, HR0.636) and PFS (p = 0.028, HR0.627). The logistic analysis identified a positive association between G4 lymphopenia during RT (p = 0.012, OR 7.742) and PTV dose < 60 Gy (p = 0.014, OR 2.655) with lymphocyte recovery., Conclusions: The prognostic value of lymphocyte recovery status at P3 appears to be greater than that of lymphocyte recovery status at P1 for locally advanced ESCC patients. Radiation-related lymphocyte recovery might serve as a valuable prognostic factor in LA-ESCC., Competing Interests: Declarations. Ethical approval and consent to participate: This retrospective analysis was approved by the appropriate institutional review board. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Pragmatic language refers to using spoken language to convey messages effectively across diverse social communication contexts. However, minimal longitudinal research has focused on defining early predictors of pragmatic development in children with autism spectrum disorder (ASD)., Methods: In the present study, 71 children with ASD and 38 age- and gender- matched 24- to 30-month-old typically developing (TD) children were enrolled. Social-communication, language, and parent‒child interaction measures were collected for the ASD group at baseline. Three years later, all subjects were assessed for pragmatic ability via the Chinese version of the Language Use Inventory (LUI-Mandarin). First, the differences in pragmatic performance between the ASD and TD groups at follow-up were analyzed. Second, pragmatic performance was correlated with autism symptomatology at follow-up, as well as the structural language difficulties and joint engagement (JE) levels at baseline in the ASD group. Furthermore, hierarchical multiple regression analyses and machine learning techniques were performed to explore the effects of early potential predictors of pragmatic development in the ASD group., Results: First, our results revealed that performance was significantly lower in the ASD than in the TD group with respect to the LUI-Mandarin total scores and subscale scores (except for subscale C). Second, correlation analysis revealed that more severe symptoms of ASD at follow-up were associated with lower LUI-Mandarin total scores and better language performance on the Gesell Developmental Schedules (GDS). Additionally, increased proportions of supported JE (SJE) states were associated with higher LUI-Mandarin total scores. In contrast, increased proportions of unengaged (UE) states were associated with lower LUI-Mandarin total scores in the ASD group. Third, hierarchical multiple regression analyses and machine learning techniques indicated that the proportions of SJE during parent‒child interactions, as well as the degree of social symptoms and structural language impairments, were significant contributors to pragmatic development for the ASD group in the prediction models., Conclusion: In summary, our findings suggest that pragmatic language difficulties are present in children with ASD as early as preschool age. Additionally, given the close correlation between the LUI-Mandarin score and symptom severity on the ADOS/ADI-R, the LUI-Mandarin might be a good way to triage children who need to wait a long time for a more extensive evaluation. Furthermore, this study provides new insights into potential targets for pragmatic interventions, and interventions can be designed to promote SJE between caregivers and children in future work., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Nanjing Brain Hospital affiliated with the Nanjing Medical University Ethics Committee, participants were consented by an informed consent process that was reviewed by the Ethics Committee of Nanjing Medical University and certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki, and informed consent was obtained from the parents or legal guardians of the participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The benefits of improving coverage and timeliness of varicella vaccination need to be quantified in countries where varicella vaccine (VarV) has not yet been included in national immunization programs. This longitudinal study analyzed the vaccine effectiveness (VE) of the varicella vaccination program implemented in Changzhou City during the transitional period (2017-2022)., Methods: Using the Immunization Information System and National Notifiable Infectious Disease Surveillance System registry data, this retrospective case-cohort study assessed the VEs of varicella vaccination for Changzhou children born from 2016 to 2021. The subcohort was sampled using inverse probability weighting for the survival analysis design to evaluate the VEs under different dosages and cost types, eliminating confounding by age and location area. Sensitivity analysis for the exclusion part assessed the study's robustness., Results: A total of 5,172 children (1.12%) were sampled to the subcohort for studies, including 2,299 cases. VEs significantly rose with each successive dose, reaching 82.54% and 97.91%. VEs were lower for the single-dose subgroups until 2020, with significant increases in VEs in all subgroups in 2020 and after that. Most children who did not benefit from the "1-4" Vaccination Program had lower VEs due to delayed vaccination., Conclusion: Improving 2-dose VarV vaccine coverage and timely vaccination could enhance the immune barrier for susceptible children. During the transitional period, the "1-4" Vaccination Program of VarV positively impacted coverage and timeliness in Changzhou., Competing Interests: Declarations. Ethics approval and consent to participate: The study was undertaken in accordance with the Declaration of Helsinki. Data used in this study were obtained from the immunization information system and the National Notifiable Disease Surveillance System, and all data were unidentified. And the protocol was approved by the Ethics Committee of Changzhou Institute for Advanced Study of Public Health, Nanjing Medical University, and it was found that utilization of disease surveillance did not require informed consent, and the need for informed consent was waived by the Ethics Committee of Changzhou Institute for Advanced Study of Public Health, Nanjing Medical University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Acute Kidney Injury (AKI) is a sudden and often reversible condition characterized by rapid kidney function reduction, posing significant risks to coronary artery disease (CAD) patients. This study focuses on developing accurate predictive models to improve the early detection and prognosis of AKI in CAD patients., Methods: We used Electronic Health Records (EHRs) from a nationwide CAD registry including 54 429 patients. Initially, univariate analysis identified potential predictors. Subsequently, a stepwise multivariate logistic model integrated clinical significance and data distribution. To refine predictor selection, we applied a random forest algorithm. The top 10 variables, including admission to the surgical department, EGFR, hemoglobin, and others, were incorporated into a logistic regression-based prediction model. Model performance was assessed using the area under the curve (AUC) and calibration analysis, and a nomogram was developed for practical application., Results: During hospitalization, 2,112 (3.88%) patients in the overall population of both the development and validation groups experienced AKI within 30 days. The final prediction model exhibited strong discrimination with an AUC of 0.867 (95% CI: 0.858 to 0.876) and well calibration capability in both the development and validation groups. Key predictors included surgical department admission, eGFR, hemoglobin, chronic kidney disease history, male sex, white blood cell count, age, left ventricular ejection fraction, acute myocardial infarction at admission, and congestive heart failure history. Bootstrap resampling confirmed model stability (Harrell's optimism-correct AUC = 0.866). The nomogram provided a practical tool for AKI risk assessment., Conclusion: This study introduced a refined AKI risk prediction model for CAD patients. This model showed adaptability to subgroups and held the potential for early AKI alerts and personalized interventions, thereby enhancing patient care., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in adhered to the Declaration of Helsinki. This project was approved by the central ethics committee at Beijing Anzhen Hospital, Capital Medical University. Written informed consent was obtained from all patients or their legal representatives. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Nocardia are widely present in nature and considered opportunistic pathogens. They can result in hematogenous spread infection through the ruptured skin or respiratory tract when the host's immune system is compromised. Currently, 119 species of Nocardia have been identified, with 54 capable of causing infections in humans. Nocardial brain abscesses are a rare intracranial lesion that accounts for only 2% of all brain abscesses, but have a mortality rate of 20-55%. This article reports a successfully cured case of mediastinal Nocardia infection with disseminated brain abscess., Case Presentation: The patient presented with intermittent chills, shivering, and fever, with the highest temperature of 39˚C, accompanied by shoulder and back pain, dizziness, and headaches. A chest-enhanced computed tomography (CT) revealed multiple enhanced nodulars in the bilateral hilum and mediastinum. A head-enhanced CT revealed scattered multiple ring-enhanced nodules in both cerebral hemispheres and the left cerebrum, accompanied by extensive surrounding edema. The mediastinal puncture tissue culture confirmed the growth of Nocardia. After twice discussions with multidisciplinary team (MDT) to rule out the possibility of mediastinal and intracranial metastatic tumors, we promptly initiated treatment with a triple-drug antibiotic regimen consisting of imipenem/cilastatin sodium, linezolid dextrose, and Trimethoprim-sulfamethoxazole (TMP-SMX). The patient ultimately achieved complete remission., Conclusions: Mediastinal nocardiosis with disseminated brain abscesses is a rare condition that can be difficult to differentiate from brain metastases caused by lung cancer. Bacterial culture results, imaging features, and MDT discussions are crucial for accurate diagnosis and treatment. A triple-drug antibiotic regimen has been found to be effective in treatment with acceptable levels of toxicity., Competing Interests: Declarations. Ethics approval and consent to participate: This is an observational description of a clinical case. The Ethics Committee of the General Hospital of Western Theatre Command has confirmed that no ethical approval is required. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The patient has given written informed consent for his personal and clinical details. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Among hypertensive cohorts across different nations, the relationship between the triglyceride-glucose index (TyG) and its conjunction with obesity metrics in relation to cardiovascular disease (CVD) incidence and mortality remains to be elucidated., Methods: This study enrolled 9,283, 164,357, and 5,334 hypertensives from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKBB), and Shanghai Pudong cohort. The related outcomes for CVD were defined by multivariate Cox proportional hazards models, Generalized Additive Models and Mendelian randomization analysis. Mediation analysis explored the mediating role of inflammatory markers in the above relationships., Results: Five measures of insulin resistance were linked to CVD and related death in a U-shaped pattern, with the highest group having different risk increases. Higher glucose triglyceride-waist height ratio (TyG-WHTR) was linked to higher all-cause mortality (UKBB: HR 1.21, 95%CI 1.16-1.26, NHANES: HR 1.17, 95%CI 1.00-1.36), CVD mortality (UKBB: HR 1.36, 95%CI 1.23-1.49, NHANES: HR 1.32, 95%CI 1.00-1.72) risks. In the China Pudong cohort, higher triglyceride/high-density lipoprotein-cholesterol (TG/HDL&#95;C) ratio was associated with higher risks of CVD and stroke (HR 1.31, 95%CI 1.00-1.73 and 1.67, 1.06-2.63). Inflammation markers like systemic inflammatory response index (SIRI) and C-reactive protein (CRP) partially explained these links, with CRP having a stronger effect. Genetically predicted TyG was also linked to stroke (OR 1.26, 95%CI 1.10-1.45) risk., Conclusions: An elevated TyG index and its related indices are significantly correlated with an increased risk of CVD and related mortality across three national cohorts. These indices are anticipated to serve as valid predictors of incident CVD and mortality in individuals with hypertension., Competing Interests: Declarations. Ethical approval and consent to participate: The UK Biobank received ethical approval from the North West Multi-center Research Ethics Committee (Approved Research ID: 89871, Approval date September 20th 2022). All participants gave written informed consent before enrollment in the study, which was conducted in accordance with the principles of the Declaration of Helsinki. The National Center for Health Statistics and Ethics Review Board approved the protocol for NHANES, and all participants provided written informed consent. Research ethics approval was obtained from the Center for Disease Control and Prevention of the Pudong New Area, Shanghai, China. Each participant provided a written consent. All participants were informed and agreed to participate in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Integrating multi-layered information can enhance the accuracy of genomic prediction for complex traits. However, the improvement and application of effective strategies for genomic prediction (GP) using multi-omics data remains challenging., Methods: We generated 11 feature sets for sequencing variants from genomics, transcriptomics, metabolomics, and epigenetics data in beef cattle, then we assessed the contribution of functional variants using genomic restricted maximum likelihood (GREML). We next estimated and ranked variant scores for 43 economically important traits, and compared the prediction accuracy of the top and bottom sets using genomic best linear unbiased prediction (GBLUP) and BayesB model. In addition, we annotated the variants from GWAS with functional feature sets and performed enrichment analysis., Results: We observed significant enrichments for 32 functional categories in 11 feature sets. The evolutionary related sets (conservation regions and selection signatures) contributed significantly to heritability (31.78-fold and 14.48-fold enrichment), while metabolomics and transcriptomics showed low heritability enrichments. We observed a significant increase in prediction accuracy using the top feature set variants compared to whole-genome sequencing (WGS) data. The prediction accuracy based on the top 10% variant set showed an average increase of 11.6% and 7.54% using BayesB and GBLUP across traits, respectively. Notably, the greatest increase of 31.52% was obtained for spleen weight (SW) using BayesB. Also, we found that the top 10% of variants show strong enrichment with weight related QTLs based on the Cattle QTL database., Conclusions: Our findings suggest that integrating biological prior information from multiple layers can enhance our understanding of the genetic architecture underlying complex traits and further improve genomic prediction in beef cattle., Competing Interests: Declarations. Ethics approval and consent to participatel: All animals were treated following the guidelines for experimental animals which were established by the Council of China. The study involving the use of tissue samples was approved by the ethics committee of the Science Research Department of the Institute of Animal Science, Chinese Academy of Agricultural Sciences under IAS2020-48. Consent for publication: All authors have approved the final manuscript. Competing interests: The authors declare no conflict of interest., (© 2024. The Author(s).)

Background: Diabetes mellitus (DM) is a metabolic disorder with increasing prevalence and poor control rates, leading to adverse events. Prognostic nutritional value (PNI) has been identified as a protective factor in DM, but its role in uncontrolled DM remains unclear., Methods: This study based on the representative cohort of National Health and Nutrition Examination Survey from 2005 to 2018. A total of 3,313 participants with uncontrolled DM were included in our analyses. PNI was calculated as 5×lymphocyte count (10 9 /L)+ 10×serum albumin (g/L). The endpoints were DM-related and cardiovascular mortality, which were obtained from National Death Index. Univariable and multivariable cox proportional hazard regression were performed to investigate prognostic value of PNI., Results: Among 3,313 patients with uncontrolled DM (mean age of 61.75 ± 12.78 years, 53.4% male), PNI level was negatively associated with inflammatory markers and positively associated with metabolic markers of lipid and protein. During a median follow-up of 77 months, 247 DM-related deaths and 205 cardiovascular deaths occurred. Higher PNI levels independently predicted low DM-related (adjusted Hazard ratio [HR] = 0.872, 95% confidence interval [CI] 0.840-0.906, P < 0.001) and cardiovascular mortality (adjusted HR = 0.872, 95% CI 0.834-0.912, P < 0.001). The prognostic value of PNI significantly varied across different DM treatment conditions, which was more pronounced in patients receiving antidiabetic treatments (adjusted HR: insulin + oral antidiabetic drugs [OADs]: 0.832; insulin: 0.863; OADs: 0.894, all adjusted P < 0.001), but was absent in those without antidiabetic treatment., Conclusions: A higher PNI level is an independent protective predictor for DM-related and cardiovascular mortality in uncontrolled DM patients. Evaluation of PNI level in uncontrolled DM patients could conduce to stringent intervention. Improvement of PNI could enhance the effective of antidiabetic therapy, especially the insulin therapy, and reduce DM-related mortality., Competing Interests: Declarations. Ethical approval: Ethnic approval was obtained from the institutional review board of the NCHS, and written consent for publication was obtained from all participants in NHANES. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The classification of major adverse cardiovascular event (MACE) endpoints in patients with type 2 diabetes mellitus (T2DM) and either confirmed coronary artery disease (CAD) or high CAD risk, as well as the extent of the association between T2DM and coronary plaque characteristics, remains uncertain., Purpose: This meta-analysis aims to compare MACE endpoints between patients with diabetes and patients without diabetes based on coronary artery plaques., Methods: We searched studies from Web of Science, PubMed, Embase, and the Cochrane Library up until September 1, 2023. Two independent researchers evaluated the quality and bias of the included studies. We used odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI) to assess the effect of individual lesion parameters and coronary artery plaque characteristics on MACE endpoints., Results: Seven studies covered 1218 patients with diabetes and 3038 patients without diabetes. The follow-up time ranged from 2 to 5.4 years. The pooled results indicated that in all CAD lesions, DM was more strongly associated with MACE, myocardial infarction (MI), revascularization, and rehospitalization for unstable or progressive angina. The pooled OR was 1.82 (95% CI: 1.42 to 2.33, I 2  = 0%, P < 0.00001) for MACE, 2.36 (95% CI: 1.47 to 3.79, I 2  = 0%, P = 0.0004) for MI, 1.83 (95% CI: 1.33 to 2.53, I 2  = 0%, P = 0.0002) for revascularization, and 1.65 (95% CI: 1.20 to 2.27, I 2  = 0%, P = 0.002) for rehospitalization respectively. Subgroup analysis of culprit lesions (CLs) revealed significant differences between DM and non-DM for MACE, MI, revascularization, and stent thrombosis. While non-culprit lesions (NCLs) showed differences for MACE, MI, revascularization, and rehospitalization between the two groups., Conclusion: The rates of MACE, MI, and revascularization are greater in DM than in non-DM patients in terms of all lesions, CLs, and NCLs. Except for CLs, the readmission rate is greater for unstable or progressive angina. Plaque characteristics are similar between patients with and without diabetes. Prospero registration number CRD42023474226., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. This is an retrospective study. The Nantong University Research Ethics Committee has confirmed that no ethical approval is required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The composition and function of animal gut microbiota are shaped by various factors, among which diet is one of the major factors. Diet is affected by seasonal shifts and geographical differences, which in turn impact the host's nutritional levels. To adapt to these environmental changes, the gut microbiome often produces matching responses. Understanding the relationships among the environment, diet, host and the gut microbiome is helpful for exploring the environmental adaptation of wildlife. Here, we chose wild sika deer (Cervus nippon), which is composed natural allopatric populations, to explore how the environment shapes the gut microbiome and affects the relationship between microbiota composition and function and the mutual adaptation of the seasonal living environment to seasonal dietary changes. To this purpose we used DNA metabarcoding, 16S RNA gene amplification sequencing, metagenomic shotgun sequencing and nutritional analyses to comprehensively examine the relationships among the forage plant, nutrient status and host gut microbiome. Our analyses showed spatiotemporal differences in diet between the Tiebu and Hunchun regions, which ultimately led to varying intakes of protein, cellulose, and soluble sugar. The microbiome composition and function showed unique characteristics in each group, and significant differences were detected at the gene level for the protein absorption and metabolism pathway, the carbohydrate metabolic absorption pathway, and cellulase enzyme function, which are related to nutrition. We also found differences in the pathogenic bacteria and resistance mechanisms genes of the gut microbiota in different groups. Our results showed that the gut microbiome of allopatric populations adapts to changes in food composition and nutrition in different seasons and areas to help the host cope with spatiotemporal changes in the living environment. At the same time, varying levels of human activity can have potential health impacts on wild animals., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

African swine fever virus (ASFV) is a DNA virus that has significantly impacted the global swine industry. Currently, there are no effective therapies or vaccines against ASFV. Stress granules (SGs), known for their antiviral properties, are not induced during ASFV infection, even though reactive oxygen species (ROS) are generated. The mechanism by which ASFV regulates SGs formation remains unclear. This study demonstrates that ASFV antagonises SGs formation and increases intracellular levels of reduced glutathione (GSH) levels. The use of the GSH inhibitor BSO and the activator NAC confirmed that the ASFV-induced increase in GSH helps to suppress SGs formation and influences viral replication. Additionally, this study revealed that ASFV enhances GSH by upregulating the antioxidant transcription factor NRF2, as well as factors involved in GSH synthesis and regeneration, such as GCLC, and those related to the ferroptosis pathway, such as SLC7A11. Furthermore, the study uncovered that ASFV manipulates intracellular GSH levels by activating the mitochondrial protein AIFM1. This regulatory mechanism helps the virus inhibit the formation of intracellular SGs, thereby creating an optimal environment for viral replication. These findings provide new insights into the molecular strategies employed by ASFV., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Sugar transporters (STs) play a critical role in the transportation of sugar, participating in plant growth and development, stress/defense responses, and signal transduction processes. Dendrobium catenatum (also known as Dendrobium officinale, hereinafter referred to as D. catenatum) is an important traditional Chinese medicinal herb with remarkable medicinal properties and possessing high economic value. Polysaccharides are the primary active components in D. catenatum, exhibiting diverse pharmacological activities. Sugar transporters function as material supplier and may play the essential roles in the polysaccharide biosynthesis, as well as the key reulators in the signaling and responses to abiotic stresses in Dendrobium plants. However, a comprehensive analysis of sugar transporters in D. catenatum remains elusive, thereby hindering our understanding of sugar partitioning within this species., Results: In this work, the members belonging to MST, SUT, and SWEET gene families were identified in four Dendrobium plants. A comprehensive study of sugar transporters was conducted in D. catenatum, including phylogenetic relationship, structural arrangement, regulatory networks, expression profiles, and potential functions analysis. Seven sugar transporters were found to be involved in the process of polysaccharide biosynthesis in D. catenatum. Red-blue light is an effective way to enhance the accumulation of polysaccharides, and exerts an influence on the expression of polysaccharide biosynthesis related genes., Conclusions: This study provide insight into the evolution and functional annotation of sugar transporters in Dendrobium, and establishing a foundation for future functional research of sugar transporters involved in polysaccharide biosynthesis and stress response., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interest: The authors declare no competing interests., (© 2024. The Author(s).)

In the field of chemical structure recognition, the task of converting molecular images into machine-readable data formats such as SMILES string stands as a significant challenge, primarily due to the varied drawing styles and conventions prevalent in chemical literature. To bridge this gap, we proposed MolNexTR, a novel image-to-graph deep learning model that collaborates to fuse the strengths of ConvNext, a powerful Convolutional Neural Network variant, and Vision-TRansformer. This integration facilitates a more detailed extraction of both local and global features from molecular images. MolNexTR can predict atoms and bonds simultaneously and understand their layout rules. It also excels at flexibly integrating symbolic chemistry principles to discern chirality and decipher abbreviated structures. We further incorporate a series of advanced algorithms, including an improved data augmentation module, an image contamination module, and a post-processing module for getting the final SMILES output. These modules cooperate to enhance the model's robustness to diverse styles of molecular images found in real literature. In our test sets, MolNexTR has demonstrated superior performance, achieving an accuracy rate of 81-97%, marking a significant advancement in the domain of molecular structure recognition.Scientific contributionMolNexTR is a novel image-to-graph model that incorporates a unique dual-stream encoder to extract complex molecular image features, and combines chemical rules to predict atoms and bonds while understanding atom and bond layout rules. In addition, it employs a series of novel augmentation algorithms to significantly enhance the robustness and performance of the model., Competing Interests: Declarations. Competing interests: The authors declare no competing financial interest. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s).)

Hepatitis B virus (HBV) is a hepatotropic DNA virus that can cause acute or chronic hepatitis, representing a significant global health concern. By 2019, approximately 296 million individuals were chronically infected with HBV, with 1.5 million new cases annually and 820,000 deaths due to HBV-related cirrhosis and liver cancer. Current treatments for chronic hepatitis B include nucleotide analogs (NAs) and interferons (IFNs), particularly IFN-α. NAs, such as entecavir and tenofovir, inhibit viral reverse transcription, while IFN-α exerts antiviral effects by directly suppressing viral replication, modulating viral genome epigenetics, degrading cccDNA, and activating immune responses. Despite its potential, IFN-α shows limited clinical efficacy, partly due to HBV's interference with the IFN signaling pathway. HBV encodes proteins like HBc, Pol, HBsAg, and HBx that disrupt IFN-α function. For example, HBV Pol inhibits STAT1 phosphorylation, HBsAg suppresses STAT3 phosphorylation, and HBx interferes with IFN-α efficacy through multiple mechanisms. Additionally, HBV downregulates key genes in the IFN signaling pathway, further diminishing IFN-α's antiviral effects. Understanding these interactions is crucial for improving IFN-α-based therapies. Future research may focus on overcoming HBV resistance by targeting viral proteins or optimizing IFN-α delivery. In summary, HBV's ability to resist IFN-α limits its therapeutic effectiveness, highlighting the need for new strategies to enhance treatment outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Hypertensive intracerebral hemorrhage (HICH) stands out as a critical complication of primary hypertension. Consequently, investigating messenger RNA (mRNA) biomarkers becomes imperative, offering potential targets. This study is conducted for elucidating the expression profile of blood mRNA biomarkers in HICH., Methods: Twenty-five HICH patients were constituted the HICH group.Twenty-two healthy volunteers recruited and comprised the control group. Peripheral blood cells were extracted to identify candidate mRNA. The identified differential expressions of genes between the two groups were validated, and the potential associations between these differentially expressed genes and adverse events were analyzed. GO and KEGG enrichment of DEGs, Weighted Gene Co-expression Network and Protein Interaction Network were established. target mRNA was screened., Results: The study identified 3163 differentially expressed genes in HICH. 8 candidate mRNA (SPI1, HK3, HCK, SYK, CD14, FCER1G, CYBB, FGR) were pinpointed. Associations with pathways affecting HICH development included HIF-1 signaling, NF-kappa B signaling, and C-type lectin receptor signaling. In the HICH group, higher expressions of HK3, HCK, SYK, CD14, FCER1G, CYBB, and FGR, and lower SPI1 expression compared to the control group. HICH patients experienced high rates of complications: pulmonary infection (84%), epilepsy (16%), enlarged hematoma (20%), gastrointestinal bleeding (48%), malnutrition (84%), and lower limb deep vein thrombosis (DVT) (12%). Factors contributing to pulmonary infection included age and elevated expression of HCK, SYK, CD14, and FGR. SPI1 was associated with epilepsy, while its lower expression correlated with hematoma enlargement. Gastrointestinal bleeding was linked to increased cerebral hemorrhage. Malnutrition was associated with higher age, and expressions of HK3, HCK, SYK, CD14, FCER1G, CYBB, and FGR. Patients with lower limb DVT had elevated expressions of the identified genes., Conclusion: In hypertensive intracerebral hemorrhage, there are elevated expressions of HK3, HCK, SYK, CD14, FCER1G, CYBB, and FGR, along with reduced expression of SPI1. Furthermore, age, along with elevated expressions of HCK, SYK, CD14, and FGR, serves as influencing factors contributing to pulmonary infection in patients., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Zhengzhou University Fifth Affiliated Hospital (Y2021052). Consent for publication: All authors agree to submit and publish. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Amyloid myopathy often occurs in the context of systemic amyloidosis, as a rare manifestation of "light chain" (AL) amyloidosis, accounting for 1% of its incidence. A 58-year-old man with two years history of weakness and edema of lower extremity, elevated creatine kinase (CK), and inflammatory lesions from muscle biopsy which was misdiagnosed as inflammatory myopathy. After immunotherapy, the original symptoms worsened. We later confirmed the disease through MRI, Congo red staining and bone marrow puncture results. Our purpose is that to increase awareness of amyloid myopathy to minimize the risk of misdiagnosis and emphasize the importance of Congo red staining in diagnosing similar conditions., Competing Interests: Declarations. Ethics approval and consent to participate: The study involved human participants and was reviewed and approved by the Ethics Committee of Tongji Hospital of Huazhong University of Science and Technology. Patients provided written informed consent to participate in the study and to publish any potentially identifiable images or data contained in this article. Consent for publication: Written informed consent for publication was obtained from the patients and there legal guardians for publication of identifying information and images in an online open-access publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: To assess and compare the therapeutic outcomes of 0.05% Cyclosporine A (CsA) ophthalmic solution versus 0.1% Fluorometholone (FML) eyedrops in Chinese patients with mild dry eye disease (DED) unresponsive to conventional artificial tears (AT)., Methods: A total of 43 patients with mild DED, who have failed to respond to conventional AT therapy for over 3 months, were randomly assigned to receive either 0.05% CsA or 0.1% FML twice daily for 6-months. In addition, all the patients were instructed to use 0.1% SH 4 times a day as supplementary therapy. Dry eye examination, including Ocular Surface Disease Index (OSDI) questionnaire, non-invasive tear break-up time (NIBUT), Schirmer scores, corneal fluorescein staining (CFS) scores, and conjunctival goblet cell (CGC) density, intraocular pressure (IOP), Best corrected visual acuity (BCVA) was conducted at baseline and then evaluated at 1, 3, and 6 months after treatment. Corneal endothelial cell density, corneal dendritic cells (DCs) and nerves were assessed by in vivo confocal microscopy at baseline and 6 months after treatment., Results: At 3 and 6 months after treatment, OSDI scores in the 0.05% CsA group showed more improvement than those in the 0.1% FML group. CFS was significantly lower and Schirmer scores were significantly higher in 0.05% CsA group compared with 0.1% FML group. NIBUT improved significantly in both groups, with greater improvement in the 0.05% CsA group at the 1-, 3-, and 6-month visits. Throughout the duration of the study, the 0.1% FML group exhibited no notable enhancement in CGC density. Conversely, a substantial elevation in CGC density was observed in the 0.05% CsA group. After 6 months of treatment, significantly reduced corneal DC density and area were obtained in 0.05% CsA group as compared to 0.1% FML group, while there were no significant changes in cornea nerve fiber density, cornea nerve fiber length and cornea nerve fiber width in both groups. Additionally, after 6 months of treatment, neither group showed any statistically significant changes in IOP, BCVA or in corneal endothelial cell density., Conclusion: The administration of 0.05% CsA proved effective in managing mild DED, offering a supplementary advantage in improving Schirmer scores, restoring CGC density and reducing corneal DC density compared to 0.1% FML eyedrops. Consequently, 0.05% CsA eyedrops are recommended as a safe and efficacious therapeutic alternative for patients with mild DED who fail to respond to conventional tear substitutes therapy., Clinical Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR2200066441, Registered 06 December 2022-Retrospectively registered., Competing Interests: Declarations. Ethics approval and consent to participate: The research was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (ethics approval number: 2021KY-17). Written informed consent was obtained from all enrolled participants. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life., Methods: This multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800 ml total bacterial count) or the low-dose group (400 ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48 weeks, including mortality and quality of life., Discussion: If either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48 weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications., Trial Registration: NCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022., Competing Interests: Declarations. Ethics approval and consent to participate {24}: Ethical approval for this study has been granted by the Ethics Committee of Shulan (Hangzhou) Hospital (Reference Approval No. KY2022083). Informed consent to participate will be obtained from all participants. Consent for publication {32}: This is not applicable—no identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. The participant information materials and informed consent form are available from the corresponding author on request. Competing interests {28}: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Genomic mating (GM) can effectively control the growth rate of inbreeding in population and achieve long-term sustainable genetic progress. However, the design of GM method and assessment of its effects during long-term selection have not been fully explored in beef cattle breeding., Results: In this study, we constructed a simulated population based on the real genotypes of Huaxi cattle, where five generations of simulated breeding were carried out using the genomic optimal contribution selection (GOCS), genetic algorithms strategy and three traditional mating strategies. During the breeding process, genetic parameters including average genomic estimated breeding value (GEBV), genetic gain values ( Δ G ), the rate of inbreeding values ( Δ F ) were calculated and compared across generations. Our results showed that the GM method could significantly improve the genetic gain while effectively controlling the inbreeding accumulation within the population. When using the GM method, there was an increase in genetic gain for Huaxi cattle ranging from 1.1% to 25.6% compared to traditional mating strategy, with inbreeding decreasing in the range of 5.8% to 36.2%. Validation using the real dataset from Huaxi cattle further confirmed our findings from the simulated study, offspring populations using the GM strategy exhibited a 7.3% increase in genetic gain compared to positive assortative mating., Conclusions: These findings suggest that the GM method shows potential for achieving sustainable genetic gain and could be utilized during long-term selection in beef cattle breeding., Competing Interests: Declarations. Ethics approval and consent to participate: All of the animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) at the Institute of Animal Science, Chinese Academy of Agricultural Sciences. All animal procedures were performed in strict accordance with the guidelines proposed by the China Council on Animal Care and the Ministry of Agriculture of the People's Republic of China. We obtained informed consent from the owner of the Huaxi cattle farm to take sample. All methods were carried out in accordance with relevant guidelines and regulations. No euthanasia or anesthesia was used in this study as no invasive procedures or treatments that would require such methods were performed. This study was carried out in compliance with the ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The intake of dietary antioxidants and glycolipid metabolism are closely related to chronic kidney disease (CKD), particularly among individuals with abdominal obesity. Nevertheless, the cumulative effect of multiple comorbid risk factors on the progression and complications of CKD remains inadequately characterized., Methods: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) dat abase (2005-2018), to examine potential factors related to CKD, including glycolipid metabolism, dietary antioxidant intake, and pertinent medical history. To explore the associations between these variables and CKD, the present study used a multivariable-adjusted least absolute shrinkage and selection operator (LASSO) regression model, along with a restricted cubic spline (RCS) model. Furthermore, an optimal predictive model was developed for CKD using ten machine learning algorithms and enhanced model interpretability with the Shapley Additive Explanations (SHAP) method., Results: A cohort comprising 8,764 eligible individuals (52% male, including 1,839 CKD patients) with abdominal obesity aged 20-85 years were included. The findings revealed significant positive correlations in patients with abdominal obesity between the presence of CKD and age, a history of heart failure, hypertension, diabetes, elevated lipid accumulation product (LAP) and triglyceride glucose-waist circumference (TyG-WC) levels. Conversely, negative correlations were identified between CKD and variables such as sex, high-density lipoprotein cholesterol (HDL-C) levels, and the composite dietary antioxidant index (CDAI). In parallel, RCS regression analysis revealed significant nonlinear associations between the CDAI, HDL-C, TyG-WC, and CKD among patients with abdominal obesity aged 60-80 years. The development of predictive models demonstrated that the CatBoost model surpassed other models, achieving an accuracy of 86.74% on the validation set. The model's area under the receiver operator curve (AUC) and F1 score were 0.938 and 0.889, respectively. The SHAP values revealed that age was the most significant predictor, followed by diabetes history, hypertension, HDL-C levels, CDAI index, TyG-WC, and LAP., Conclusion: CatBoost models, along with glycolipid metabolism indexes and dietary antioxidant intake, are effective for early CKD detection in patients with abdominal obesity., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All contributing authors were consent for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Methods for estimating variance components (VC) using restricted maximum likelihood (REML) typically require elements from the inverse of the coefficient matrix of the mixed model equations (MME). As genomic information becomes more prevalent, the coefficient matrix of the MME becomes denser, presenting a challenge for analyzing large datasets. Thus, computational algorithms based on iterative solving and Monte Carlo approximation of the inverse of the coefficient matrix become appealing. While the standard average information REML (AI-REML) is known for its rapid convergence, its computational intensity imposes limitations. In particular, the standard AI-REML requires solving the MME for each VC, which can be computationally demanding, especially when dealing with complex models with many VC. To bridge this gap, here we (1) present a computationally efficient and tractable algorithm, named the augmented AI-REML, which facilitates the AI-REML by solving an augmented MME only once within each REML iteration; and (2) implement this approach for VC estimation in a general framework of a multi-trait GBLUP model. VC estimation was investigated based on the number of VC in the model, including a two-trait, three-trait, four-trait, and five-trait GBLUP model. We compared the augmented AI-REML with the standard AI-REML in terms of computing time per REML iteration. Direct and iterative solving methods were used to assess the advances of the augmented AI-REML., Results: When using the direct solving method, the augmented AI-REML and the standard AI-REML required similar computing times for models with a small number of VC (the two- and three-trait GBLUP model), while the augmented AI-REML demonstrated more notable reductions in computing time as the number of VC in the model increased. When using the iterative solving method, the augmented AI-REML demonstrated substantial improvements in computational efficiency compared to the standard AI-REML. The elapsed time of each REML iteration was reduced by 75%, 84%, and 86% for the two-, three-, and four-trait GBLUP models, respectively., Conclusions: The augmented AI-REML can considerably reduce the computing time within each REML iteration, particularly when using an iterative solver. Our results demonstrate the potential of the augmented AI-REML as an appealing approach for large-scale VC estimation in the genomic era., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: The potential roles of viral infections in neurodevelopmental disorders (NDDs) have been suggested based on previous studies. Given the high prevalence of human herpesviruses (HHVs), the associations between HHVs infection and the risk of NDDs warrant explored., Methods: Our study employs a two-sample Mendelian randomization (MR) analysis and systematic review with meta-analysis to investigate whether genetically predicted HHVs infection are linked to three main childhood NDDs-autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS). We utilized genetic variants associated with HHV infections in genome-wide association study (GWAS) summary datasets of European populations to establish instrumental variables and statistics for three NDDs obtained from Psychiatric Genomics Consortium. MR analysis was performed using inverse-variance weighted, MR Egger, weighted median, simple median, weighted mode, and MR-PRESSO. In addition, publications associating HHVs infection with three NDDs were systematically searched using PubMed, Web of Science, and three Chinese databases for meta-analyses., Results: The MR results found no evidence to support a link between genetically predicted HHVs infection and the risk of NDDs based on existing datasets. Twenty-seven observational studies on children with HHVs infection and NDDs were considered eligible. Meta-analysis showed that cytomegalovirus and HHV-6 infection were related with ASD, while Epstein-Barr virus and cytomegalovirus infection were associated with TD in Chinese population., Conclusions: These results contribute to a comprehensive understanding of the possibilities underlying HHV infections in affecting childhood NDDs. Further research is necessary to include larger and more robust statistics of HHV infections and NDDs., Trial Registration: This systematic review was registered at PROSPERO as CRD42024554169. Retrospectively registered 26 July 2024., Competing Interests: Declarations. Ethics approval and consent to participate: The data used in this study are publicly available from previous studies with relevant participant consent and ethical approval. Competing interests: The authors declare that there is no conflict of interest. Consent for publication: Not applicable., (© 2024. The Author(s).)

Background: Infection is the cause of diarrhoea, and rotaviruses and adenoviruses are important pathogens in children., Methods: A retrospective study was conducted on 144,067 children with diarrhoea between 2014 and 2023 in China. We used the colloidal gold method to detect intestinal adenovirus and rotavirus A antigens in faeces. The epidemiological characteristics of these viruses and the impact of meteorological factors on them were analysed before and after coronavirus disease 2019 (COVID-19) pandemic., Results: During this decade, the positive rate of adenovirus infection was 6.41%, while the positive rate of rotavirus A infection was 11.81%, higher than that of adenovirus infection. The positive rate of adenovirus and rotavirus A coinfection was 1.92%. The positive rates of adenovirus, rotavirus A and coinfection showed a fluctuating trend, and suddenly decreased in 2020. There was an apparent decrease of positive rate of rotavirus A, with a decrease of 57.27%, during 2020-2023. Surprisingly, the positive rate of adenovirus infection exceeded that of rotavirus A infection in 2021 and 2023. During the COVID-19 pandemic, the proportion of female patients and children over two years of age infected with adenovirus or rotavirus A increased, while the proportion of cases in winter decreased. In addition, we found that the positive rate of rotavirus A infection was related to average temperature and sunshine, and the positive rate of adenovirus and rotavirus A coinfection was only related to sunshine. However, these correlations disappeared during the COVID-19 pandemic., Conclusions: This study revealed the recent prevalence of adenovirus and rotavirus A infections in children with diarrhoea in south-central China and provided a theoretical basis for the prevention and control of viral diarrhoea., Competing Interests: Declarations Ethics approval and consent to participate The project was approved by the Ethics Committee of Guangzhou Women and Children’s Medical Center, and the ethical number is 2021-24B01. The data used in this study was anonymized and there was no known risk to participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Retinitis pigmentosa is a neurodegenerative disease with major pathologies of photoreceptor apoptosis and immune imbalance. Mesenchymal stem cells (MSCs) have been approved for clinical application for treating various immune-related or neurodegenerative diseases. The objective of this research was to investigate the mechanisms underlying the safeguarding effects of MSC-derived exosomes in a retinal degenerative disease model., Methods: Interferon gamma-stimulated exosomes (IFNγ-Exos) secreted from MSCs were isolated, purified, and injected into the vitreous body of RCS rats on postnatal day (P) 21. Morphological and functional changes in the retina were examined at P28, P35, P42, and P49 in Royal College of Surgeons (RCS) rats. The mechanism was explored using high-throughput sequencing technology and confirmed in vitro., Results: Treatment with IFNγ-Exo produced better protective effects on photoreceptors and improved visual function in RCS rats. IFNγ-Exo significantly suppressed the activated microglia and inhibited the inflammatory responses in the retina of RCS rats, which was also confirmed in the lipopolysaccharide-activated microglia cell line BV2. Furthermore, through tRNA-derived small RNA (tsRNA) sequencing, we found that IFNγ-Exos from MSCs contained higher levels of Other-1&#95;17-tRNA-Phe-GAA-1-M3, Other-6&#95;23-tRNA-Lys-TTT-3, and TRF-57:75-GLN-CGG-2-m2 than native exosomes, which mainly regulated inflammatory and immune-related pathways, including the mTOR signaling pathway and EGFR tyrosine kinase inhibitor resistance., Conclusions: IFNγ stimulation enhanced the neuroprotective effects of MSC-derived exosomes on photoreceptors of the degenerative retina, which may be mediated by immune regulatory tsRNAs acting on microglia. In conclusion, IFNγ-Exo is a promising nanotherapeutic agent for the treatment of retinitis pigmentosa., Competing Interests: Declarations Ethics approval and consent to participate The authors declare that they have consented to the scientific content and authorship of this study. This study was approved by the Institutional Animal Care and Use Committee of Army Medical University, Chongqing, China. All animal trials were approved by the Army Medical University Institutional Review Board, and all trials met guidelines. The production certificate number for our laboratory animal is SCXK-PLA-20120011, and the occupancy permit number is SYXK-PLA-20120031. All procedures in this study were approved. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma which possess highly aggressive and heterogeneous. Despite advances in understanding heterogeneity and development of novel targeted agents, the prognosis of DLBCL patients remains unsatisfied. Lipids are crucial components of biological membranes and signal transduction while accumulating evidence has supported the vital roles of abnormal lipid metabolism in tumorigenesis. Furthermore, some related pathways could serve as prognostic biomarkers and potential therapeutic targets. However, the clinical significance of abnormal lipid metabolism reprogramming in DLBCL has not been investigated. In the current study, we developed a prognostic risk model for DLBCL based on the abnormal expressed lipid metabolism genes and moreover based on our risk model we classified patients with DLBCL into novel subtypes and identified potential drugs for DLBCL patients with certain lipid metabolism profiles., Methods: We utilized univariate Cox regression analysis to identify the prognosis-related lipid metabolism genes, and then performed LASSO Cox regression to identify prognostic related lipid metabolism related genes. Multivariate cox regression was used to establish the prognostic model. Patients were divided in to high and low risk groups based on the median risk score. Immune cell infiltration and GSEA were used to identify the pathways between high and low risk groups. Oncopredict algorithm was utilized to identify potential drug for high-risk patients. In vitro cell apoptosis and viability analysis were employed to verify the specific tumor inhibition effects of AZD5153., Results: Nineteen survival related lipid metabolism genes TMEM176B, LAYN, RAB6B, MMP9, ATAD3B, SLC2A11, CD3E, SLIT2, SLC2A13, SLC43A3, CD6, SIRPG, NEK6, LCP2, CTTN, CXCL2, SNX22, BCL6 and FABP4 were identified and subjected to build the prognostic model which was further verified in four external microarray cohorts and one RNA seq cohorts. Tumor immune microenvironment analysis and GSEA results showed that the activation of MYC targets genes rather than immunosuppression contribute to the poor survival outcome of patients in the high-risk group. AZD5153, a novel bivalent BET bromodomain inhibitor which could inhibit the transcription of MYC and E2F exhibited specific antitumor function for cells with high-risk score., Conclusions: Our results provide the first lipid metabolism-based gene signature for predicting the survival of patients with DLBCL. Furthermore, by determining novel subtypes with our lipid metabolism prognostic model we illustrated that drugs that compromising MYC target genes rather than immune checkpoint inhibitors may be beneficial to DLBCL patients with certain lipid metabolism profiles., Competing Interests: Declarations Ethics approval and consent to participate For analyses of data from a public database, approval and informed consent from the local ethics committee were not required. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: In recent years, the hypervirulent and carbapenem-resistant Klebsiella pneumoniae has been increasingly reported worldwide. The objective of this study was to compare the antibiotic resistance and virulence profiles of carbapenem-resistant hypervirulent K.pneumoniae (CR-hvKP) and hypervirulent carbapenem-resistant K.pneumoniae (hv-CRKP) and identify the prevailing strain in clinical settings., Methods: In this study, hv-CRKP or CR-hvKP were identified based on the results of whole-genome analysis (WGS), multilocus sequence typing (MLST) and the antimicrobial susceptibility testing. We then compared antibiotic resistance and virulence profiles between CR-hvKP and hv-CRKP through the antimicrobial susceptibility testing and a series of virulence experiments including biofilm formation ability detection method, the resistance test against human serum, siderophore production test, neutrophil phagocytosis assay and Galleria mellonella infection model. Additionally, pathway enrichment analysis was conducted to assess the effect of SNPs on the phenotype., Results: In this study, we categorized 17.4% of hypervirulent and carbapenem-resistant K. pneumoniae strains as CR-hvKP and 82.6% as hv-CRKP. Among them, 84.2% (16/19) of CR-hvKP strains harboring carbapenemase genes exhibited lower imipenem and meropenem MIC values compared to hv-CRKP strains. The virulence potential of hv-CRKP and CR-hvKP was confirmed by using virulence experiments in vitro and in vivo, showing that virulence of the CR-hvKP strains was comparable to that of hv-CRKP strains. Notably, the 90 hv-CRKP strains were classified into 3 different ST types and 8 capsule types, each showing varying degrees of resistance and virulence. We observed that subclonal replacement was within the predominant hv-CRKP clone, with the ST11-KL64 strain, characterized by high-level resistance and virulence emerging as the currently prevailing subclone, replacing ST11-KL47. KEGG enrichment analysis showed that pathways associated with the citrate cycle (TCA cycle), glycolysis/gluconeogenesis, glutathione metabolism, two-component regulatory system, and folate metabolism were significantly enriched among the group expressing different levels of capsular polysaccharides., Conclusions: The hv-CRKP strains exhibited a greater survival advantage in the hospital environment than CR-hvKP strains. Notably, the ST11-KL64 hv-CRKP strain which displayed a high level of resistance and hypervirulence, warrants the most clinical vigilance., Clinical Trial Number: Not applicable., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the ethics committees of the First Affiliated Hospital of Wenzhou Medical University (WYYY-AEC-2022-025). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Xinglong buffalo, as an indigenous breed in Hainan province of China, possesses characteristics such as high humidity tolerance, disease resistance and high reproductive capacity. Combined with whole genome sequencing technology, comprehensive investigation can be undertaken to elucidate the genomic characteristics, functions and genetic variation of Xinglong buffalo population., Results: Xinglong buffalo has the highest genetic diversity, lowest runs of homozygosity average length, and fasted decay of linkage disequilibrium in our study population. Phylogenetic tree results revealed that Xinglong buffalo was gathered together with Fuzhong buffalo firstly. The population genetic structure analysis indicates that at K = 3, the Xinglong buffalo for the first time showed a distinct ancestral origin from other water buffalo. Furthermore, compared to different populations, candidate genes displaying significantly distinct patterns of single nucleotide polymorphisms (SNPs) (e.g., RYR2, COX15, PCDH9, DTWD2, FCRL5) distribution have been identified in the Xinglong buffalo., Conclusions: Based on the whole genome sequencing data, this study identified a substantial number of SNPs and assessed the genetic diversity and selection signatures within the Xinglong buffalo population. These results contribute to understanding the genomic characteristics of Xinglong buffalo and their genetic evolutionary status. However, the practical significance of these signatures for genetic enhancement still requires confirmation through additional samples and further experimental validation., (© 2024. The Author(s).)

Background: Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem)., Method: Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence., Results: In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001)., Conclusion: Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem., (© 2024. The Author(s).)

Introduction: The role of complement system in late stage of IgA nephropathy (IgAN) remains unknown. We therefore investigated the effects of complement system on worsening kidney function in advanced (stage 4 CKD) IgAN., Methods: Renal specimens of 69 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2021, were stained using immunofluorescence (IF) and immunohistochemistry (IHC) for glomerular complement components. The primary outcome was progression to end-stage renal disease (ESRD). Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses., Results: During a median follow-up of 18.0 months, 26 (37.7%) patients progressed to ESRD and none died. C1q and C3 deposition were detected in 12 and 66 patients, respectively. Higher eGFR [hazards ratio (HR), 0.852, 95% confidence interval (CI), 0.756-0.959; P = 0.008], higher C3 intensity (HR, 2.955, 95%CI, 1.063-8.220; P = 0.038) and T1-2 score (HR, 2.576, 95%CI, 1.205-5.576, P = 0.015) were predictive of time to ESRD in CKD 4 stage IgAN. Significant expressions of C1q (P = 0.005), C4d (P < 0.001), factor B (P < 0.001), C3 (P = 0.042) and C5b-9 (P = 0.004) were identified in ESRD group than in non-ESRD group by IHC, while MBL expression was low. Although they were not associated with baseline 24 h-UP, higher factor B and C1q expressions were both correlated with a lower baseline eGFR (P < 0.001 and = 0.04, respectively) and the deterioration of kidney function during follow-up (P = 0.046 and 0.015, respectively)., Conclusion: Complement deposition in IgAN patients with stage 4 CKD portends a faster deterioration of kidney function. Activation of classical and alternative complement pathways plays a major role in this stage., (© 2024. The Author(s).)

Background: Leaves are important sites for photosynthesis and can convert inorganic substances into organic matter. Photosynthetic performance is an important factor affecting crop yield. Leaf colour is closely related to photosynthesis, and leaf colour mutants are considered an ideal material for studying photosynthesis., Results: We obtained a yellow-green leaf mutant jym165, using ethyl methane sulfonate (EMS) mutagenesis. Physiological and biochemical analyses indicated that the contents of chlorophyll a, chlorophyll b, carotenoids, and total chlorophyll in the jym165 mutant decreased significantly compared with those in Jiyu47 (JY47). The abnormal chloroplast development of jym165 led to a decrease in net photosynthetic rate and starch content compared with that of JY47. However, quality traits analysis showed that the sum of oil and protein contents in jym165 was higher than that in JY47. In addition, the regional yield (seed spacing: 5 cm) of jym165 increased by 2.42% compared with that of JY47 under high planting density. Comparative transcriptome analysis showed that the yellow-green leaf phenotype was closely related to photosynthesis and starch and sugar metabolism pathways. Genetic analysis suggests that the yellow-green leaf phenotype is controlled by a single recessive nuclear gene. Using Mutmap sequencing, the candidate regions related of leaf colour was narrowed to 3.44 Mb on Chr 10., Conclusions: Abnormal chloroplast development in yellow-green mutants leads to a decrease in the photosynthetic pigment content and net photosynthetic rate, which affects the soybean photosynthesis pathway and starch and sugar metabolism pathways. Moreover, it has the potentiality to increase soybean yield under dense planting conditions. This study provides a useful reference for studying the molecular mechanisms underlying photosynthesis in soybean., (© 2024. The Author(s).)

Background: Malnutrition is a complication of chronic kidney disease (CKD). Whether malnutrition, assessed via the geriatric nutritional risk index (GNRI), is associated with the incidence and risk of CKD in older individuals remains unclear., Methods: Data from the National Health and Nutrition Examination Survey and the UK Biobank database were used. Older participants over 60 years old with available data for GNRI assessment and CKD diagnosis were enrolled. Logistic regression models and Cox regression models were used to assess associations between the geriatric nutritional risk index and the risk of and mortality associated with CKD., Results: This study enrolled 13,162 participants from the NHANES and 66,326 participants from the UK Biobank. We identified 6,135 and 16,662 CKD patients in the NHANES and UK Biobank, respectively, with the majority being male (74% in the NHANES and 52% in the UK Biobank). The average age of CKD patients was 72.3 (SD 7.2) years in the NHANES and 64.9 (SD 2.9) years in the UK Biobank. The median follow-up times of older CKD patients were 81 months and 162 months in the NHANES and UK Biobank, respectively. According to the cross-sectional analysis, individuals with a lower GNRI had an increased likelihood of having CKD, with odds ratios of 1.38 (95% CI: 1.05-1.80, P = 0.020) in the NHANES and 2.35 (95% CI: 1.89-2.92, P < 0.001) in the UK Biobank. According to our analysis of the risk of incident CKD in the UK Biobank, a lower GNRI was associated with a greater incidence of CKD (HR: 1.11, 95% CI: 1.04-1.18; P = 0.002). According to the analysis of the risk of mortality, a lower GNRI was associated with an increased risk of death among older CKD patients (NHANES: HR: 1.69, 95% CI: 1.13-2.53, P = 0.011; UK Biobank: HR: 2.28, 95% CI: 1.94-2.69, P < 0.001)., Conclusion: Malnutrition assessed by the GNRI was significantly and independently associated with the incidence of CKD. Moreover, CKD patients with malnutrition also have a high risk of mortality., (© 2024. The Author(s).)

The interplay between gut microbiota and host is crucial for maintaining host health. When this balance is broken, various diseases can arise, including colorectal cancer (CRC). However, the mechanism by which gut microbiota and host interactions mediate CRC development remains unclear. Here, we found that Gasdermin D (GSDMD), an inflammasome effector responsible for forming membrane pores to mediate cell pyroptosis, was upregulated in both human and mouse intestinal tumor samples. GSDMD deficiency significantly suppressed intestinal tumor development in Apc min/+ mice, a spontaneous CRC mouse model. Apc min/+ Gsdmd -/- mice exhibited reduced IL-1β release in the intestine, and the administration of recombinant mouse IL-1β partially restored intestinal tumor development in Apc min/+ Gsdmd -/- mice. Moreover, 16s rRNA sequencing showed a substantial increase in Lactobacillus abundance in the feces of Apc min/+ Gsdmd -/- mice compared to Apc min/+ mice. Concurrently, Kynurenine (Kyn), a metabolite derived from host tryptophan (Trp) metabolism, was significantly decreased in the feces of Apc min/+ Gsdmd -/- mice, as shown by metabolite analysis. Additionally, Kyn levels were inversely correlated with Lactobacillus abundance. Furthermore, the administration of exogenous Kyn also promoted intestinal tumor development in Apc min/+ Gsdmd -/- mice. Thus, GSDMD promotes spontaneous CRC development through increasing IL-1β release and Kyn production. Our data suggest an association between GSDMD, gut microbiota, the host Trp/Kyn pathway, and CRC development., (© 2024. The Author(s).)