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Senecavirus A (SVA) is an emerging pathogen that causes idiopathic vesicular infections in pig herds, posing a potential threat to their production performance. Heat shock protein 70 (Hsp70) is a molecular chaperone that plays an important role in host homeostasis under both physiological and stress conditions. However, the effects of Hsp70 on SVA infection and its underlying regulatory mechanisms remain unclear. Here, we confirmed that Hsp70 expression promotes SVA infection, as evidenced by the expression of viral proteins, viral titers, and the number of rSVA-eGFP-infected cells. This positive regulatory role of Hsp70 is mainly involved in post-entry stages of SVA. Viral proteins that interacted with Hsp70 were screened, and co-immunoprecipitation (co-IP) shows an interaction between Hsp70 and SVA L and 3D proteins. Subsequently, we determined that the expression of Hsp70 is beneficial for the stability of the SVA L and 3D proteins. Additionally, the substrate-binding domain (SBD) of Hsp70 plays an important role in the interaction between Hsp70 and SVA L or 3D proteins; and the deletion of this domain results in the loss of the stabilizing effect of Hsp70 on SVA L and 3D proteins and the positive regulatory effect of Hsp70 on SVA replication. These results reveal that Hsp70 promotes SVA infection by stabilizing viral L and 3D proteins and provides a strategy for preventing and controlling SVA infection., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Triple-negative breast cancer (TNBC) is currently the most aggressive subtype of breast cancer, characterized by high heterogeneity and strong invasiveness, and currently lacks effective therapies. PRMT5, a type II protein arginine methyltransferase, is upregulated in numerous cancers, including TNBC, and plays a critical role, marked it as an attractive therapeutic target. PROTAC (Proteolysis Targeting Chimeras) is an innovative drug development technology that utilizes the ubiquitin-proteasome system (UPS) to degrade target proteins, which is characterized by higher activity, enhanced safety, lower resistance, and reduced toxicity, offering significant value for clinical translation., Methods: This study utilizes the PROTAC technology to develop potential degraders targeting PRMT5 in vitro and in vivo., Results: Through the design, synthesis and screening of a series of targeted compounds, we identified YZ-836P as an effective compound that exerted cytotoxic effects and reduced the protein levels of PRMT5 and its key downstream target protein KLF5 in TNBC after 48 h. Its efficacy was significantly superior to the PRMT5 PROTAC degraders that had been reported. YZ-836P induced G1 phase cell cycle arrest and significantly induced apoptosis in TNBC cells. Additionally, we demonstrated that YZ-836P promoted the ubiquitination and degradation of PRMT5 in a cereblon (CRBN)-dependent manner. Notably, YZ-836P exhibited pronounced efficacy in inhibiting the growth of TNBC patient-derived organoids and xenografts in nude mice., Conclusions: These findings position YZ-836P as a promising candidate for advancing treatment modalities for TNBC., Trial Registration: Ethics Committee of Yunnan Cancer Hospital, KYCS2023-078. Registered 7 June 2023., Competing Interests: Declarations. Ethics approval and consent to participate: The animal experiment followed the ARRIVE guidelines and had been approved by the Animal Ethics Committee of the Kunming Medical University (kmmu20240729). Additionally, the patient-derived organoids assays conformed the Declaration of Helsinki and had been approved by the Ethics Committee of Yunnan Cancer Hospital (KYCS2023-078). Consent for publication: All the authors consent for publication. Competing interests: The authors declare no potential conflicts of interest., (© 2024. The Author(s).)

Background: Easy-to-use, rapid, scalable, high-throughput, and cost-effective HPV tests are urgently needed for low-resource settings. Atila Biosystems' high-throughput, cost-effective, and clinically validated ScreenFire HPV Risk Stratification (RS) assay identifies 13 high risk HPV (hrHPV) in 4 groups based on their oncogenic risk (i.e., HPV16, HPV18/45, HPV31/33/35/52/58, and HPV51/59/39/56/68). The current standard format is subject to laboratory contamination, which is common for any molecular PCR test. To overcome this drawback, Atila has recently upgraded it into an innovative, contamination-free Zebra BioDome format. The contamination-free feature makes this novel assay format more suitable for large-scale community- and population-based cervical screening. This study evaluated the analytical performance of the Zebra BioDome format., Methods: We conducted a study to test the analytical performance of Zebra Biodome format in comparison to the results of using the ScreenFire HPV RS assay standard format on Biorad CFX-96 real-time PCR instrument. We used overall agreement rate and unweighted kappa value to compare the performance., Results: The overall agreement for detection of hrHPV was 96.0% with unweighted kappa value 0.94 (95% confidence interval: 0.90-0.98). The agreement rates between hrHPV genotype 16 and risk stratification genotype group (HPV18/45, HPV31/33/35/52/58, and HPV51/59/39/56/68) were all > 97.5%., Conclusion: The innovative ScreenFire HPV RS assay Zebra BioDome format produced highly concordant results with the standard format. The shared features by the two assay formats, such as easy-to-use, high throughput, cost-appropriate, and no requirements for DNA extraction. The unique contamination-prevention feature along with no requirement of preparation of reagents make the Zebra BioDome format more suitable for large-scale HPV screening to reduce global cervical cancer burden., Competing Interests: Declarations. Ethics approval and consent to participate: This study is covered under IRB approval (STU00207051) at Northwestern University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Premature infants are more prone to brain injuries owing to incomplete nervous system development and poor adaptation outside the mother's body. Without timely intervention, premature infants with brain injuries often develop intellectual disabilities, causing significant burdens on families and the society. Multiple studies have shown that gut dysbiosis can affect the nervous system, and vice versa. This study aimed to explore the changes in gut microbiota of typical premature infants and those with brain injuries on the third and seventh days after birth using 16 S rRNA technology., Methods: Fecal samples from typical premature infants (non-brain injury group, n = 17) and those with brain injuries (brain injury group, n = 21) were collected on days 1, 3, and 7 after birth for 16 S rRNA sequencing. Alpha diversity analysis was used to evaluate the diversity of gut microbiome. LEfSe and DESeq2 were used to analyze of the microorganisms' characteristics and differentiate the microorganisms between the two groups., Results: At the phylum level, Firmicutes, Proteobacteria, and Actinobacteria were the dominant flora in both groups. At the genus level, the proportion of Enterococcus in fecal samples of the brain injury group was higher than that of the non-brain injury group on day three after birth; however, the opposite was observed on day seven. Rothia and Lactobacillales were characteristic bacteria of the non-brain injury group on days three and seven after birth, whereas Enterococcus and Bifidobacteria were characteristic bacteria of the brain injury group on days three and seven after birth, respectively. Three days after birth, the Shannon and Simpson indices of the non-brain injury group were significantly higher than those of the brain injury group., Conclusion: Premature infants with brain injuries have a unique gut microbiota that is different from that of typical premature infants, indicating correlation between brain injuries and gut microbiota., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Beichuan Medical College (No. 2020ER038-1). All methods were carried out in accordance with relevant guidelines and regulations. Informed consent was obtained from each guardian. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: This study was designed to compare the clinical data of vesicoureteral reflux (VUR) in children with and without an allergic constitution., Methods: The clinical data of patients hospitalized with VUR due to a urinary tract infection (UTI) between September 1, 2019, and December 31, 2020, were retrospectively analyzed. The patients were divided into two groups: an anallergic constitution group (AC group) and a non-allergic constitution (NAC group), and their UTIs and VUR were compared at baseline and during the follow-up period., Results: (1) Between September 1, 2019, and December 31, 2020, a total of 284 children were hospitalized at Shengjing Hospital Affiliated to China Medical University due to a UTI. These children included 37 cases with primary VUR and 247 cases without VUR (including 59 cases of non-VUR urinary malformation). The proportion of children with an allergic constitution was significantly higher in the patients with VUR than it was in those without VUR or with other urinary malformations (72.97% vs. 48.18% vs. 50.85%, P = 0.005, 0.032). (2) At baseline, the levels of immunoglobulin and immunoglobulin E in the AC group were significantly higher than those in the NAC group (P = 0.042, 0.017). (3) During the follow-up period, the number of recurrent UTI cases in the AC group was significantly higher than that in the NAC group (0.70 ± 0.91 vs. 0.10 ± 0.32, P= 0.005). The difference between the two groups in the VUR remission rate was not statistically significant (40% vs. 50%, P = 0.563). (4) During the follow-up period, the differences in the remission rates of recurrent UTIs and VUR in the two groups were not statistically significant., Conclusions: The incidence of having an allergic constitution is high in patients with VUR, and patients with an allergic constitution present with a higher frequency of recurrent UTIs., (© 2024. The Author(s).)

Background: There is no optimal reconstruction technique after proximal gastrectomy. The esophagogastrostomy (EG) is a rather simple procedure technically, but the incidences of reflux esophagitis and anastomotic stricture are higher. While the double-tract reconstruction (DTR) can lessen postoperative reflux esophagitis, it is technically complex with a long operation time. The purpose of this study was to evaluate the quality of life (QoL) and short-term outcomes of the two reconstruction techniques., Methods: We retrospectively collected consecutive patients with upper-third gastric adenocarcinoma and adenocarcinoma of the esophagogastric junction (AEG) at our center between 2019 June and 2023 May. Patients who underwent laparoscopic proximal gastrectomy (LPG) with EG or DTR were included in this study. A comparison was made between the clinical and pathological characteristics of patients and their surgical parameters, postoperative complications, and its 1-year QoL in two groups. The QoL of the two groups was assessed by Visick grading, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-STO22 scales at 1 year after operation. The nutritional status of the two groups was evaluated by BMI, hemoglobin and serum albumin., Results: AII the qualified patients were divided EG group (n = 63) and DTR group (n = 93). Compared to the DTR group, the blood loss volume of EG group was more (p = 0.001). There were no significant differences in operation duration, number of lymph nodes dissected, and postoperative length of stay between the two groups(p > 0.05). No statistical differences were observed in terms of the incidence of early complications and Clavien-Dindo classification as well(p > 0.05). After one year, the Visick grade of the DTR group was better than EG group (p = 0.040). The multivariable logistic regression analysis showed the only independent risk factor for reflux esophagitis was the reconstruction method. According to the EORTC QLQ-C30 questionnaire, patients in the DTR group had a better global health status(p = 0.001) and complained less about nausea and vomiting(p = 0.033), and appetite loss (p = 0.022). Patients in the DTR group complained less about reflux (p = 0.030) based on the EORTC QLQ-STO22 questionnaire. The multiple linear regression analysis revealed that the reconstruction method, reflux esophagitis and age had a linear relationship with the global health status score. Regarding nutritional status, BMI of the two groups both decreased 1 year after operation, and BMI decline value of the DTR group was lower than EG group (p = 0.001). There is no statistically significant difference between the two groups as for postoperative change in hemoglobin and serum albumin., Conclusion: Our findings suggest that it is possible for skilled surgeons to achieve minimal blood loss volume without significantly increasing operation duration when performing DRT, which does not raise risk. In terms of anti-reflux, postoperative QoL and BMI maintenance, 1-year postoperative follow-up outcomes reveal the DTR is superior to EG, which deserve further research and promotion., (© 2024. The Author(s).)

Background: Factor XII (FXII or F12) deficiency is a rare inherited disorder, typically lacking haemorrhagic symptoms. There is limited literature exists on FXII deficiency and mutations within the Chinese population. This study aimed to characterize the spectrum of F12 gene mutations in a Chinese cohort and to investigate the relationship between FXII mutations and clinical phenotypes., Methods: Genetic and clinical data from 51 unrelated probands with FXII deficiency, along with their families, were meticulously collected and analysed., Results: Genetic analysis revealed that 94.1% of probands carried genetic defects, with 29 mutations pinpointed in the F12 gene. Of these, 18 mutations were previously reported for the first time by our research group, including c.303_304delCA, c.1078G > A, c.1285 C > T, among others. Of the mutations, 17 are missense, constituting 58.6% of the total. Additionally, 11 are deletions or insertions, of which 8 result in frameshifts, while the remaining one is a nonsense mutation. These mutations were predominantly concentrated in two crucial regions: the catalytic domain and the kringle domain. The most frequently observed mutations were c.1681G > A, closely followed by c.1561G > A and c.1078G > A, indicating a dominance among these mutations. Additionally, a prevalent polymorphism at position 46 was observed in the majority of probands, with 47.1% having the 46T/T genotype and 13.7% having the 46 C/T genotype, which may potentially impact FXII activity. The broad spectrum of asymptomatic FXII deficiency observed within the Han population of East China., Conclusions: We speculate on the potential impact of recurrent mutations on the efficacy of new drugs being developed to target FXII for thrombosis prevention and treatment. Furthermore, it is important to explore their influence on FXII-related pathways beyond the activation of the contact pathway in the coagulation cascade., (© 2024. The Author(s).)

Background: Our study aims to examine stress-strain data of the four major knee ligaments-the anterior cruciate ligament (ACL), the posterior cruciate ligament (PCL), the medial collateral ligament (MCL), and the lateral collateral ligament (LCL)-under transient impacts in various knee joint regions and directions within the static standing position of the human body. Subsequently, we will analyze the varying biomechanical properties of knee ligaments under distinct loading conditions., Methods: A 3D simulation model of the human knee joint including bone, meniscus, articular cartilage, ligaments, and other tissues, was reconstructed from MRI images. A vertical load of 300 N was applied to the femur model's top surface to mimic the static standing position, and a 134 N load was applied to the impacted area of the knee joint. Nine scenarios were created to examine the effects of anterior, posterior, and lateral external forces on the upper, middle, and lower regions of the knee joint., Results: The PCL exhibited the highest stress levels among the four ligaments when anterior loads were applied to the upper, middle, and lower parts of the knee, with maximum stresses at the PCL-fibula junction measuring 59.895 MPa, 27.481 MPa, and 28.607 MPa, respectively. Highest stresses on the PCL were observed under posterior loads on the upper, middle, and lower knee areas, with peak stresses of 57.421 MPa, 38.147 MPa, and 26.904 MPa, focusing notably on the PCL-tibia junction. When a lateral load was placed on the upper knee joint, the ACL showed the highest stress 32.102 MPa. Likewise, in a lateral impact on the middle knee joint, the ACL also had the highest stress of 29.544 MPa, with peak force at the ACL-tibia junction each time. In a lateral impact on the lower knee area, the LCL had the highest stress of 22.279 MPa, with the highest force at the LCL-fibula junction. Furthermore, the maximum stress data table indicates that stresses in the ligaments are typically higher when the upper portion of the knee is affected compared to when the middle and lower parts are impacted., Conclusions: This study recommends people avoid impacting the upper knee and use the middle and lower parts of the knee effectively against external forces to minimize ligament damage and safeguard the knee., (© 2024. The Author(s).)

Senecavirus A (SVA), an emerging virus that causes blisters on the nose and hooves, reduces the production performance of pigs. RSAD2 is a radical S-adenosylmethionine (SAM) enzyme, and its expression can suppress various viruses due to its broad antiviral activity. However, the regulatory relationship between SVA and RSAD2 and the mechanism of action remain unclear. Here, we demonstrated that SVA infection increased RSAD2 mRNA levels, whereas RSAD2 expression negatively regulated viral replication, as evidenced by decreased viral VP1 protein expression, viral titres, and infected cell numbers. Viral proteins that interact with RSAD2 were screened, and the interaction between the 2 C protein and RSAD2 was found to be stronger than that between other proteins. Additionally, amino acids (aa) 43-70 of RSAD2 were crucial for interacting with the 2 C protein and played an important role in its anti-SVA activity. RSAD2 was induced by type I interferon (IFN-I) via Janus kinase signal transducer and activator of transcription (JAK-STAT), and had antiviral activity. Ruxolitinib, a JAK-STAT pathway inhibitor, and the knockdown of JAK1 expression substantially reduced RSAD2 expression levels and antiviral activity. Taken together, these results revealed that RSAD2 blocked SVA infection by interacting with the viral 2 C protein and provide a strategy for preventing and controlling SVA infection., (© 2024. The Author(s).)

Background: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China., Methods: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1., Results: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL., Conclusions: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity., (© 2024. The Author(s).)

Background: Glucose metabolic disorder is associated with the risk of heart failure (HF). Adiposity is a comorbidity that is inextricably linked with abnormal glucose metabolism in older individuals. However, the effect of adiposity on the association between glucose metabolic disorder and HF risk, and the underlying mechanism remain unclear., Methods: A total of 13,251 participants aged ≥ 60 years from a cohort study were categorized into euglycemia, prediabetes, uncontrolled diabetes, and well-controlled diabetes. Adiposity was assessed using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA). Adiposity-associated metabolic activities were evaluated using adiponectin-to-leptin ratio (ALR), homeostatic model assessment of insulin resistance (HOMA-IR), and triglyceride-glucose index (TyG). The first occurrence of HF served as the outcome during the follow-up period., Results: A total of 1,138 participants developed HF over the course of an average follow-up period of 10.9 years. The rate of incident HF occurrence was higher in prediabetes, uncontrolled diabetes, and well-controlled diabetes participants compared to that in euglycemia participants. However, the high rates were significantly attenuated by BMI, VFA, and WHR. For WHR in particular, the hazard ratio for incident HF was 1.18 (95% confidence interval (CI): 1.03, 1.35, P adj. =0.017) in prediabetes, 1.59 (95% CI: 1.34, 1.90, P adj. <0.001) in uncontrolled diabetes, and 1.10 (95% CI: 0.85, 1.43, P adj. =0.466) in well-controlled diabetes. The population attributable risk percentage for central obesity classified by WHR for incident HF was 30.3% in euglycemia, 50.0% in prediabetes, 48.5% in uncontrolled diabetes, and 54.4% in well-controlled diabetes. Adiposity measures, especially WHR, showed a significant interaction with glucose metabolic disorder in incident HF (all P adj. <0.001). ALR was negatively associated and HOMA-IR and TyG were positively associated with BMI, WHR, VFA, and incident HF (all P adj. <0.05). ALR, HOMA-IR, and TyG mediated the associations for BMI, WHR and VFA with incident HF (all P adj .<0.05)., Conclusions: Adiposity attenuated the association of glucose metabolic disorder with incident HF. The results also showed that WHR may be an appropriate indicator for evaluating adiposity in older individuals. Adiposity-associated metabolic activities may have a bridging role in the process of adiposity attenuating the association between glucose metabolic disorder and incident HF., Trial Registration: retrospectively registered number: ChiCTR-EOC-17,013,598., (© 2024. The Author(s).)

Background: SOX2 is a determinant transcription factor that governs the balance between stemness and differentiation by influencing transcription and splicing programs. The role of SOX2 is intricately shaped by its interactions with specific partners. In the interactome of SOX2 in mouse embryonic stem cells (mESCs), there is a cohort of heterogeneous nuclear ribonucleoproteins (hnRNPs) that contributes to multiple facets of gene expression regulation. However, the cross-talk between hnRNPs and SOX2 in gene expression regulation remains unclear., Results: Here we demonstrate the indispensable role of the co-existence of SOX2 and heterogeneous nuclear ribonucleoprotein K (hnRNPK) in the maintenance of pluripotency in mESCs. While hnRNPK directly interacts with the SOX2-HMG DNA-binding domain and induces the collapse of the transcriptional repressor 7SK small nuclear ribonucleoprotein (7SK snRNP), hnRNPK does not influence SOX2-mediated transcription, either by modulating the interaction between SOX2 and its target cis-regulatory elements or by facilitating transcription elongation as indicated by the RNA-seq analysis. Notably, hnRNPK enhances the interaction of SOX2 with target pre-mRNAs and collaborates with SOX2 in regulating the alternative splicing of a subset of pluripotency genes., Conclusions: These data reveal that SOX2 and hnRNPK have a direct protein-protein interaction, and shed light on the molecular mechanisms by which hnRNPK collaborates with SOX2 in alternative splicing in mESCs., (© 2024. The Author(s).)

Purpose: To investigate aqueous humor cytokine levels in neovascular age-related macular degeneration (nAMD) patients with subretinal fibrosis and to explore the relationship between cytokine levels and disease severity., Methods: The aqueous humor samples were collected from 16 eyes with subretinal fibrosis due to nAMD (SRFi group), 33 eyes with nAMD without subretinal fibrosis (nAMD group) and 28 eyes with cataract patients (control group). Clinical samples were analyzed for 5 cytokines,including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor-α (TGF-α), platelet-derived growth factor-BB (PDGF-BB)., Results: Aqueous humor cytokines VEGF and bFGF were significantly higher in nAMD patients than controls (all P < 0.05), and VEGF, bFGF and TGF-α levels were significantly higher in SRFi patients than controls (all P < 0.05). No significant differences in 4 cytokine levels were observed between nAMD and SRFi patients in aqueous humor. We also identified a positive correlation between the aqueous humor levels of IL-6 and VEGF in the SRFi group, while bFGF and TGF-α in the nAMD group. Moreover, VEGF levels were strongly related to BCVA, and bFGF levels were positively related to the maximum thickness of subretinal hyperreflective material (SHRM) in fibrosis due to nAMD., Conclusion: VEGF and bFGF levels in aqueous humor were elevated in macular neovascularization with and without subretinal fibrosis. TGF-α levels exclusively differed in neovascular AMD with fibrosis. Cytokines are distributed differently and play a synergistic role in different stages (angiogenesis and fibrogenesis) of nAMD. The bFGF levels could predict the negative prognosis in fibrosis due to nAMD., (© 2024. The Author(s).)

Background: We aimed to investigate the post-cessation T2DM risk in male NAFLD and NAFLD-free smokers in a 7-year cohort study., Methods: The study population was male adults who underwent annual health checkups in a 7-year cohort study. Recent quitters were categorized into four groups based on their weight gain during follow-up: < 0 kg, 0-1.9 kg, 2.0-3.9 kg, and ≥ 4.0 kg. Cox proportional hazard models, adjusted for various variables, were used to estimate hazard ratios (HRs) for the association between post-cessation weight gain and incident T2DM in NAFLD and NAFLD-free individuals., Results: At baseline, we included 1,409 NAFLD and 5150 NAFLD-free individuals. During a total of 39,259 person-years of follow-up, 222 (15.8%) NAFLD patients and 621 (12.1%) NAFLD-free participants quit smoking, with the corresponding means (standard deviations) of post-cessation weight gain being 2.24 (3.26) kg and 1.15 (3.51) kg, respectively. Among NAFLD individuals, compared to current smokers, the fully adjusted HRs (95% CI) for incident T2DM were 0.41 (0.06-3.01), 2.39 (1.21-4.70), 4.48 (2.63-7.63), and 6.42 (3.68-11.23) for quitters with weight gains < 0 kg, 0.0-1.9 kg, 2.0-3.9 kg, and ≥ 4.0 kg, respectively. For NAFLD-free individuals, we only observed a significant association between post-cessation weight gain ≥ 4.0 kg and the risk of incident T2DM (P < 0.001). Further analysis revealed that the impact of post-cessation weight gain on T2DM risk was not affected by alcohol consumption or obesity status at baseline., Conclusions: Mild post-cessation weight gain significantly increased the risk of T2DM in male NAFLD patients but not in male NAFLD-free individuals. Therefore, it is recommended that individuals with NAFLD manage their weight after quitting smoking., (© 2024. The Author(s).)

With childhood hypertension emerging as a global public health concern, understanding its associated factors is crucial. This study investigated the prevalence and associated factors of hypertension among Chinese children. This cross-sectional investigation was conducted in Pinghu, Zhejiang province, involving 2,373 children aged 8-14 years from 12 schools. Anthropometric measurements were taken by trained staff. Blood pressure (BP) was measured in three separate occasions, with an interval of at least two weeks. Childhood hypertension was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ age-, sex-, and height-specific 95th percentile, across all three visits. A self-administered questionnaire was utilized to collect demographic, socioeconomic, health behavioral, and parental information at the first visit of BP measurement. Random forest (RF) and multivariable logistic regression model were used collectively to identify associated factors. Additionally, population attributable fractions (PAFs) were calculated. The prevalence of childhood hypertension was 5.0% (95% confidence interval [CI]: 4.1-5.9%). Children with body mass index (BMI) ≥ 85th percentile were grouped into abnormal weight, and those with waist circumference (WC) > 90th percentile were sorted into central obesity. Normal weight with central obesity (NWCO, adjusted odds ratio [aOR] = 5.04, 95% CI: 1.96-12.98), abnormal weight with no central obesity (AWNCO, aOR = 4.60, 95% CI: 2.57-8.21), and abnormal weight with central obesity (AWCO, aOR = 9.94, 95% CI: 6.06-16.32) were associated with an increased risk of childhood hypertension. Childhood hypertension was attributable to AWCO mostly (PAF: 0.64, 95% CI: 0.50-0.75), followed by AWNCO (PAF: 0.34, 95% CI: 0.19-0.51), and NWCO (PAF: 0.13, 95% CI: 0.03-0.30). Our results indicated that obesity phenotype is associated with childhood hypertension, and the role of weight management could serve as potential target for intervention., (© 2024. The Author(s).)

Objectives: To investigate the potential mechanisms of shikonin in preventing and treating periodontitis using network pharmacology and molecular docking methods., Materials and Methods: The targets of shikonin were obtained in TCMSP and SEA databases, and targets of periodontitis were gathered from the OMIM, GeneCards and Drugbank Databases. The intersecting targets were entered into the DAVID database to obtain the relevant biological functions and pathways by GO and KEGG enrichment analysis. The obtained targets were analysed the protein-protein interaction (PPI) in STRING platform. In Cytoscape 3.8.0, the network analysis function with the MCODE plug-in were used to obtain the key targets, of shikonin and periodontitis. Molecular docking and molecular dynamics simulation (MD) were used to assess the affinity between the shikonin and the key targets., Results: Shikonin was screened for 22 targets and periodontitis was screened for 944 targets, the intersecting targets were considered as potential therapeutic targets. The targets played important roles in cellular response to hypoxia, response to xenobiotic stimulus and positive regulates of apoptotic process by GO enrichment analysis. 10 significant pathways were analyzed by KEGG, such as human cytomegalovirus infection and PI3K-Akt signaling pathway, etc. Cytoscape software screened the key genes including AKT1, CCL5, CXCR4, PPARG, PTEN, PTGS2 and TP53. Molecular docking and MD results showed that shikonin could bind stably to the targets., Conclusions: The present study enriched the molecular mechanisms in periodontitis with shikonin, providing potential therapeutic targets for periodontitis., (© 2024. The Author(s).)

Background: Z-DNA binding protein 1 (ZBP1) is a nucleic acid sensor that is involved in multiple inflammatory diseases, but whether and how it contributes to osteoarthritis (OA) are unclear., Methods: Cartilage tissues were harvested from patients with OA and a murine model of OA to evaluate ZBP1 expression. Subsequently, the functional role and mechanism of ZBP1 were examined in primary chondrocytes, and the role of ZBP1 in OA was explored in mouse models., Results: We showed the upregulation of ZBP1 in articular cartilage originating from OA patients and mice with OA after destabilization of the medial meniscus (DMM) surgery. Specifically, knockdown of ZBP1 alleviated chondrocyte damage and protected mice from DMM-induced OA. Mechanistically, tumor necrosis factor alpha induced ZBP1 overexpression in an interferon regulatory factor 1 (IRF1)-dependent manner and elicited the activation of ZBP1 via mitochondrial DNA (mtDNA) release and ZBP1 binding. The upregulated and activated ZBP1 could interact with receptor-interacting protein kinase 1 and activate the transforming growth factor-beta-activated kinase 1-NF-κB signaling pathway, which led to chondrocyte inflammation and extracellular matrix degradation. Moreover, inhibition of the mtDNA-IRF1-ZBP1 axis with Cyclosporine A, a blocker of mtDNA release, could delay the progression of DMM-induced OA., Conclusions: Our data revealed the pathological role of the mtDNA-IRF1-ZBP1 axis in OA chondrocytes, suggesting that inhibition of this axis could be a viable therapeutic approach for OA., (© 2024. The Author(s).)

Background: In the tumor microenvironment (TME), a bidirectional relationship exists between hypoxia and lactate metabolism, with each component exerting a reciprocal influence on the other, forming an inextricable link. The aim of the present investigation was to develop a prognostic model by amalgamating genes associated with hypoxia and lactate metabolism. This model is intended to serve as a tool for predicting patient outcomes, including survival rates, the status of the immune microenvironment, and responsiveness to therapy in patients with lung adenocarcinoma (LUAD)., Methods: Transcriptomic sequencing data and patient clinical information specific to LUAD were obtained from comprehensive repositories of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A compendium of genes implicated in hypoxia and lactate metabolism was assembled from an array of accessible datasets. Univariate and multivariate Cox regression analyses were employed. Additional investigative procedures, including tumor mutational load (TMB), microsatellite instability (MSI), functional enrichment assessments and the ESTIMATE, CIBERSORT, and TIDE algorithms, were used to evaluate drug sensitivity and predict the efficacy of immune-based therapies., Results: A novel prognostic signature comprising five lactate and hypoxia-related genes (LHRGs), PKFP, SLC2A1, BCAN, CDKN3, and ANLN, was established. This model demonstrated that LUAD patients with elevated LHRG-related risk scores exhibited significantly reduced survival rates. Both univariate and multivariate Cox analyses confirmed that the risk score was a robust prognostic indicator of overall survival. Immunophenotyping revealed increased infiltration of memory CD4 + T cells, dendritic cells and NK cells in patients classified within the high-risk category compared to their low-risk counterparts. Higher probability of mutations in lung adenocarcinoma driver genes in high-risk groups, and the MSI was associated with the risk-score. Functional enrichment analyses indicated a predominance of cell cycle-related pathways in the high-risk group, whereas metabolic pathways were more prevalent in the low-risk group. Moreover, drug sensitivity analyses revealed increased sensitivity to a variety of drugs in the high-risk group, especially inhibitors of the PI3K-AKT, EGFR, and ELK pathways., Conclusions: This prognostic model integrates lactate metabolism and hypoxia parameters, offering predictive insights regarding survival, immune cell infiltration and functionality, as well as therapeutic responsiveness in LUAD patients. This model may facilitate personalized treatment strategies, tailoring interventions to the unique molecular profile of each patient's disease., (© 2024. The Author(s).)

Background: Omicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high transmissibility and immune evasion. Early identification of Omicron cases in clinical settings is crucial for controlling its spread. Previous studies have indicated that changes in hematological parameters can be used to predict the severity of coronavirus disease 2019 (COVID-19). However, the role of hematological parameters in non-severe and asymptomatic cases remains unknown. This study aimed to investigate the role of hematological parameters in non-severe and asymptomatic Omicron variant infections., Methods: Hematological parameters and results were analyzed and compared in symptomatic (n = 356) and asymptomatic (n = 171) groups respectively, and between these two groups with positive COVID-19 tests. The utility of hematological parameters for predicting positive COVID-19 tests was analyzed using receiver operating characteristic curves., Results: Individuals with non-severe cases exhibited decreased levels of platelets, lymphocytes, eosinophils, basophils, lymphocytes (%), eosinophils (%), and basophils (%), while exhibiting elevated counts of monocytes, neutrophils (%), monocytes (%), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) when compared to suspected cases or asymptomatic carriers. In asymptomatic patients, positive carriers had lower leukocyte, neutrophil, and lymphocyte counts but higher monocyte, monocyte (%), PLR, and CRP levels than negative carriers. Basophil counts combined with lymphocytes or the PLR demonstrated a more significant predictive value in screening non-severe cases earlier compared to other parameters. The combined assessment of the monocyte (%) and the PLR had the highest area under the curve for diagnosing asymptomatic carriers., Conclusions: Circulating basophils, alone or in combination with other hematological parameters, may be used as efficient biomarkers for early screening of non-severe Omicron cases., (© 2024. The Author(s).)

Aims: The Stress Hyperglycemia Ratio (SHR) potently predicts adverse outcomes in patients with cardiovascular and cerebrovascular diseases. However, the relationship between SHR and short-term mortality risk in patients with a first diagnosis of acute myocardial infarction (AMI) remains contentious. This study sought to understand better the relationship between SHR and short-term mortality risk in patients with a first diagnosis of AMI., Methods: We conducted a cohort study using data from 1961 patients with a first diagnosis of AMI from the MIMIC-IV (version 2.2) database. Patients were divided into three groups based on SHR tertiles. The Cox proportional hazards model and a two-segmented Cox proportional hazards model were used to elucidate the nonlinear relationship between SHR in patients with a first diagnosis of AMI and mortality., Results: Of the surveyed population, 175 patients (8.92%) died within 90 days, and 210 patients (10.71%) died within 180 days. After multivariate adjustments, elevated SHR levels were significantly and non-linearly associated with a higher risk of 90-day and 180-day mortality in patients with a first diagnosis of AMI, showing a J-shaped correlation with an inflection point at 0.9. Compared to participants with SHR levels below the inflection point, those with higher SHR levels had a fivefold increased risk of 90-day mortality (hazard ratio [HR] 5.74; 95% confidence interval [CI] 3.19, 10.33) and a fourfold increased risk of 180-day mortality (HR 4.56; 95% CI 2.62, 7.95). In the subgroup analysis, patients with pre-diabetes mellitus (pre-DM) and higher SHR levels had increased 90-day (HR 6.90; 95% CI  1.98, 24.02) and 180-day mortality risks (HR 5.30; 95% CI  1.96, 14.27)., Conclusion: In patients with a first diagnosis of AMI, there is a J-shaped correlation between SHR and 90-day and 180-day mortality, with an adverse prognostic inflection point of SHR at 0.9., (© 2024. The Author(s).)

Background: White matter injury (WMI) represents a significant etiological factor contributing to neurological impairment subsequent to Traumatic Brain Injury (TBI). CD36 receptors are recognized as pivotal participants in the pathogenesis of neurological disorders, including stroke and spinal cord injury. Furthermore, dynamic fluctuations in the phenotypic polarization of microglial cells have been intimately associated with the regenerative processes within the injured tissue following TBI. Nevertheless, there is a paucity of research addressing the impact of CD36 receptors on WMI and microglial polarization. This investigation aims to elucidate the functional role and mechanistic underpinnings of CD36 in modulating microglial polarization and WMI following TBI., Methods: TBI models were induced in murine subjects via controlled cortical impact (CCI). The spatiotemporal patterns of CD36 expression were examined through quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescence staining. The extent of white matter injury was assessed via transmission electron microscopy, Luxol Fast Blue (LFB) staining, and immunofluorescence staining. Transcriptome sequencing was employed to dissect the molecular mechanisms underlying CD36 down-regulation and its influence on white matter damage. Microglial polarization status was ascertained using qPCR, Western blot analysis, and immunofluorescence staining. In vitro, a Transwell co-culture system was employed to investigate the impact of CD36-dependent microglial polarization on oligodendrocytes subjected to oxygen-glucose deprivation (OGD)., Results: Western blot and qPCR analyses revealed that CD36 expression reached its zenith at 7 days post-TBI and remained sustained at this level thereafter. Immunofluorescence staining exhibited robust CD36 expression in astrocytes and microglia following TBI. Genetic deletion of CD36 ameliorated TBI-induced white matter injury, as evidenced by a reduced SMI-32/MBP ratio and G-ratio. Transcriptome sequencing unveiled differentially expressed genes enriched in processes linked to microglial activation, regulation of neuroinflammation, and the TNF signaling pathway. Additionally, bioinformatics analysis pinpointed the Traf5-p38 axis as a critical signaling pathway. In vivo and in vitro experiments indicated that inhibition of the CD36-Traf5-MAPK axis curtailed microglial polarization toward the pro-inflammatory phenotype. In a Transwell co-culture system, BV2 cells treated with LPS + IFN-γ exacerbated the damage of post-OGD oligodendrocytes, which could be rectified through CD36 knockdown in BV2 cells., Conclusions: This study illuminates that the suppression of CD36 mitigates WMI by constraining microglial polarization towards the pro-inflammatory phenotype through the down-regulation of the Traf5-MAPK signaling pathway. Our findings present a potential therapeutic strategy for averting neuroinflammatory responses and ensuing WMI damage resulting from TBI., (© 2024. The Author(s).)

Background: Ochrobactrum anthropi is widely distributed and primarily infects patients with compromised immune functions . Historically, O. anthropi has been considered to possess low toxicity and pathogenicity; however, recent studies suggest that it may in fact cause severe purulent infections. In this case study, we examine a case of O. anthropi infection following corneal transplantation, exploring the occurrence and outcomes of such post-operative infections., Case Presentation: A retrospective analysis of cases involved examinations, genetic testing for diagnosis, and subsequent treatment. In patients undergoing partial penetrating keratoplasty with a fungal corneal ulcer perforation, anterior chamber exudation and purulence were observed post-surgery. Despite antifungal treatment, genetic testing of the anterior chamber fluid and purulent material confirmed O. anthropi infection. The use of antimicrobial treatment specifically targeting O. anthropi was found to be effective in treating the infection., Conclusion: Inflammatory reactions following corneal transplantation should be should be monitored for the presence of other infections. Genetic testing has significant implications for clinical diagnosis and treatment., (© 2024. The Author(s).)

Background: Evidence of the optimal blood pressure (BP) target for older adults with disability in long-term care is limited. We aim to analyze the associations of BP with mortality in older adults in long-term care setting with different levels of disability., Methods: This prospective cohort study was based on the government-led long-term care programme in Chengdu, China, including 41,004 consecutive disabled adults aged ≥ 60 years. BP was measured during the baseline survey by trained medical personnel using electronic sphygmomanometers. Disability profile was assessed using the Barthel index. The association between blood pressure and mortality was analyzed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality., Results: The associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild-moderate disability group (Barthel index ≥ 40), and a reversed J-shaped in severe disability group (Barthel index < 40). In mild-moderate disability group, SBP < 135 mmHg was associated with elevated all-cause mortality risks (HR 1.21, 95% CI, 1.10-1.33), compared to SBP between 135 and 150 mmHg. In severe disability group, SBP < 150 mmHg increased all-cause mortality risks (HR 1.21, 95% CI, 1.16-1.27), compared to SBP between 150 and 170 mmHg. The associations were robust in subgroup analyses in terms of age, gender, cardiovascular comorbidity and antihypertensive treatment. Diastolic blood pressure (DBP) < 67 mmHg (HR 1.29, 95% CI, 1.18-1.42) in mild-moderate disability group and < 79 mmHg (HR 1.15, 95% CI, 1.11-1.20) in severe disability group both demonstrated an increased all-cause mortality risk., Conclusion: The optimal SBP range was found to be higher in older individuals in long-term care with severe disability (150-170mmHg) compared to those with mild to moderate disability (135-150mmHg). This study provides new evidence that antihypertensive treatment should be administered cautiously in severe disability group in long-term care setting. Additionally, assessment of disability using the Barthel index can serve as a valuable tool in customizing the optimal BP management strategy., Trial Registration: Chinese Clinical Trial Registry (Registration Number: ChiCTR2100049973)., (© 2024. The Author(s).)

Pleiotropy is frequently detected in agronomic traits of wheat (Triticum aestivum). A locus on chromosome 4B, QTn/Ptn/Sl/Sns/Al/Tgw/Gl/Gw.caas-4B, proved to show pleiotropic effects on tiller, spike, and grain traits using a recombinant inbred line (RIL) population of Qingxinmai × 041133. The allele from Qingxinmai increased tiller numbers, and the allele from line 041133 produced better performances of spike traits and grain traits. Another 52 QTL for the eight traits investigated were detected on 18 chromosomes, except for chromosomes 5D, 6D, and 7B. Several genes in the genomic interval of the locus on chromosome 4B were differentially expressed in crown and inflorescence samples between Qingxinmai and line 041133. The development of the KASP marker specific for the locus on chromosome 4B is useful for molecular marker-assisted selection in wheat breeding., (© 2024. The Author(s).)

Introduction: Long-term exposure to high-risk human papillomavirus (Hr-HPV) is a well-known necessary condition for development of cervical cancer. The aim of this study is to screen for Hr-HPV using vaginal self-sampling, which is a more effective approach to improve women's adherence and increase screening rates., Methods: This pilot study included a total of 100 Women living with HIV (WLWHIV), recruited from the Center for Listening, Care, Animation, and Counseling of People Living with HIV in Bamako. Hr-HPV genotyping was performed on Self-collected samples using the Cepheid GeneXpert instrument., Results: The median age of WLWHIV was 44 (interquartile range [IQR], 37-50) years. Approximately 92% of the study participants preferred self-sampling at the clinic, and 90% opted to receive result notifications via mobile phone contact. The overall prevalence of Hr-HPV among study participants was 42.6%, and the most frequent Hr-HPV sub-types observed were HPV18/45 (19.1%), HPV31/35/33/52/58 (13.8%), and HPV39/68/56/66 (12.8%), followed by HPV16 (5.3%), and HPV51/59 (5.3%). WLWHIV under 35 years of age had a higher frequency of Hr-HPV compared to their older counterparts, with rates of 30% versus 11.1% (p = 0.03). The duration of antiretroviral treatment showed an inverse association with Hr-HPV negativity, with patients on treatment for 15 (IQR, 10-18) years versus 12 (IQR = 7-14) years for Hr-HPV positive patients (95% CI [1.2-5.8], t = 3.04, p = 0.003). WLWHIV with baseline CD4 T-Cell counts below 200 exhibited a higher frequency of Hr-HPV compared to those with baseline CD4 T-Cell counts above 200 (17.9% versus 1.9%, p = 0.009). However, other demographics and clinical factors, such as marital status, age of sexual debut, parity, education, history of abortion, history of preeclampsia, and cesarean delivery, did not influence the distribution of Hr-HPV genotypes., Conclusion: Our findings indicate that WLWHIV under the age of 35 years old exhibited the highest prevalence of Hr-HPV infection, with HPV18/45 being the most prevalent subtype. Additionally, WLWHIV with baseline CD4 T-Cell counts below 200 showed the highest infection rates., (© 2024. The Author(s).)

Background: The lifestyle transition from autotrophy to heterotrophy often leads to extensive degradation of plastomes in parasitic plants, while the evolutionary trajectories of plastome degradation associated with parasitism in hemiparasitic plants remain poorly understood. In this study, phylogeny-oriented comparative analyses were conducted to investigate whether obligate Loranthaceae stem-parasites experienced higher degrees of plastome degradation than closely related facultative root-parasites and to explore the potential evolutionary events that triggered the 'domino effect' in plastome degradation of hemiparasitic plants., Results: Through phylogeny-oriented comparative analyses, the results indicate that Loranthaceae hemiparasites have undergone varying degrees of plastome degradation as they evolved towards a heterotrophic lifestyle. Compared to closely related facultative root-parasites, all obligate stem-parasites exhibited an elevated degree plastome degradation, characterized by increased downsizing, gene loss, and pseudogenization, thereby providing empirical evidence supporting the theoretical expectation that evolution from facultative parasitism to obligate parasitism may result in a higher degree of plastome degradation in hemiparasites. Along with infra-familial divergence in Loranthaceae, several lineage-specific gene loss/pseudogenization events occurred at deep nodes, whereas further independent gene loss/pseudogenization events were observed in shallow branches., Conclusions: The findings suggest that in addition to the increasing levels of nutritional reliance on host plants, cladogenesis can be considered as another pivotal evolutionary event triggering the 'domino effect' in plastome degradation of hemiparasitic plants. These findings provide new insights into the evolutionary trajectory of plastome degradation in hemiparasitic plants., (© 2024. The Author(s).)

Background: Rheumatoid arthritis (RA) is an autoimmune disease.However, there are few cases of Charcot Neuro-osteoarthropathy (CN) caused by rheumatoid diseases in clinical reports. It is not easy to pay attention to the diagnosis of CN in the complications of rheumatoid disease, which greatly increases the probability of misdiagnosis and missed diagnosis. This case reported a rare complication of rheumatoid arthritis, Charcot arthritis, and the molecular mechanism and diagnosis and treatment of CN caused by RA were systematically discussed., Case Presentation: The patient, a 79-year-old woman, was hospitalized due to bilateral shoulder pain, limited activity for half a year, aggravated for 4 months to the hospital. During this period, the symptoms did not improve after treatment with acupuncture and Chinese medicine. The patient was previously diagnosed with rheumatoid arthritis for more than 3 years and intermittent irregular use of methylprednisolone and methotrexate for 2 years. She had a history of osteoporosis., Physical Examination: symmetrical malformed swelling of the finger joints of both hands; Bilateral supraspinatus and deltoid muscle atrophy, tenderness at the acromion, and attachment of the long head tendon of the biceps brachii were observed. The left Dugas test and the right Dugas test were positive.Blood test: anti-cyclic citrullinated peptide antibody (A-CCP) 33.10U/ml (normal range: 0-5RU/ml); antinuclear antibody quantification (ANA) 47.40AU/ml (normal range: Negative or < 32); anti-double stranded DNA IgG antibody quantification (dsDNA) 31.00 IU/ml (normal range: 0-100 IU/ml); D-Dimer 6.43 µg/ml (normal range: 0-0.5 mg/L); erythrocyte sedimentation rate (ESR) was 27 mm/h (normal range: < 20 mm/60 min). C-reactive protein (CRP) 39.06 mg/L(0.068-8 mg/L).MRI 3.0 T enhancement of bilateral shoulder joints, cervical spine and thoracic spine showed: 1.Large bone destruction, cartilage injury, multiple effusion, synovitis, obvious on the right side. 2.Intervertebral disc degeneration, cervical 3/4, 4/5, 5/6, 6/7 disc herniation, with cervical 3/4 obvious, posterior central herniation; CONCLUSIONS: Rheumatoid arthritis complicated with Charcot's joint is rare. Clinically, patients with rheumatoid diseases should not ignore Charcot's joint complications because of rareness. Early blood inflammatory markers, neuro electrophysiology, and imaging MRI of rheumatoid CN are of great significance for the diagnosis of this mild or early neurovascular inflammation. Early diagnosis and treatment are helpful to prevent further joint injury. The clinical diagnosis, treatment, and molecular mechanism of osteolysis in RA and peripheral sensory nerve injury remain to be further revealed., (© 2024. The Author(s).)

Objective: For traumatic lower extremity artery injury, it is unclear whether it is better to perform endovascular therapy (ET) or open surgical repair (OSR). This study aimed to compare the clinical outcomes of ET versus OSR for traumatic lower extremity artery injury., Methods: The Medline, Embase, and Cochrane Databases were searched for studies. Cohort studies and case series reporting outcomes of ET or OSR were eligible for inclusion. Robins-I tool and an 18-item tool were used to assess the risk of bias. The primary outcome was amputation. The secondary outcomes included fasciotomy or compartment syndrome, mortality, length of stay and lower extremity nerve injury. We used the random effects model to calculate pooled estimates., Results: A total of 32 studies with low or moderate risk of bias were included in the meta-analysis. The results showed that patients who underwent ET had a significantly decreased risk of major amputation (OR = 0.42, 95% CI 0.21-0.85; I 2 =34%) and fasciotomy or compartment syndrome (OR = 0.31, 95% CI 0.20-0.50, I 2  = 14%) than patients who underwent OSR. No significant difference was observed between the two groups regarding all-cause mortality (OR = 1.11, 95% CI 0.75-1.64, I 2  = 31%). Patients with ET repair had a shorter length of stay than patients with OSR repair (MD=-5.06, 95% CI -6.76 to -3.36, I 2  = 65%). Intraoperative nerve injury was just reported in OSR patients with a pooled incidence of 15% (95% CI 6%-27%)., Conclusion: Endovascular therapy may represent a better choice for patients with traumatic lower extremity arterial injury, because it can provide lower risks of amputation, fasciotomy or compartment syndrome, and nerve injury, as well as shorter length of stay., (© 2024. The Author(s).)

In this study, we sought to investigate the mechanisms of action of miR-195-5p in the osteogenic differentiation of vascular smooth muscle cells (VSMCs), and thereby provide novel insights and a reference for the targeted therapy of arterial media calcification. VSMC differentiation was induced using sodium β-glycerophosphate, and we investigated the effects of transfecting cells with miR-195-5p mimics, vectors overexpressing Smad7, and the Wnt/β-catenin pathway inhibitor (KYA1797K) on VSMC differentiation by determining cell viability and apoptosis, and the mRNA and protein expression of factors associated with osteogenic differentiation and the Wnt/β-catenin pathway. The results revealed that miR-195-5p mimics enhanced the osteogenic differentiation of VSMCs induced by β-glycerophosphate, whereas the overexpression of Smad7 reversed this phenomenon. In addition, KYA1797K was found to promote the effects of Smad7 overexpression. In conclusion, by targeting, Smad7, miR-195-5p promotes the Wnt/β-catenin pathway. and thus the osteogenic differentiation of VSMCs. These findings will provide a reference for elucidating the mechanisms whereby miR-195-5p regulates osteogenic differentiation., (© 2024. The Author(s).)

Background: The career intentions of students play a crucial role in shaping the growth of the hospitality and tourism industry. Previous research underlines the significance of future work self in predicting outcomes related to one's career. However, there is limited knowledge regarding the precise ways, timing, and conditions under which the future work self of undergraduate students can enhance their employability., Methods: This paper aims to address the existing research gap by employing career construction theory and self-determination theory to propose a moderated mediation model-i.e., career exploration serves as a mediator and job market knowledge functions as a moderator in the relationship between future work self and employability. We conducted two independent studies (i.e., an experimental study and a time-lagged field study) to test the proposed model. Specifically, in Study 1 we employed an experimental research design to recruit 61 students majoring in tourism management to participate. They were randomly assigned to two scenarios (future work self: high vs. low), and we manipulated different levels of future work self by means of scenario descriptions. In Study 2, we used the time-lagged research design to collect data via submitting questionnaires among 253 Chinese undergraduates who majored in hospitality and tourism at a university in the middle area of China., Results: The results indicate a positive correlation between undergraduates' future work self and their employability. Furthermore, this relationship is mediated by a mediator of career exploration. It is important to note that this mediating relationship is also contingent upon the moderator variable of undergraduates' job market knowledge when considering the impact of career exploration on employability., Conclusion: The findings contribute to enriching the current understanding of the positive effects of future work self on undergraduates' desirable outcomes in employability., (© 2024. The Author(s).)

Modulating macrophages presents a promising avenue in tumor immunotherapy. However, tumor cells have evolved mechanisms to evade macrophage activation and phagocytosis. Herein, we introduced a bispecific antibody-based nanoengager to facilitate the recognition and phagocytosis of tumor cells by macrophages. Specifically, we genetically engineered two single chain variable fragments (scFv) onto cell membrane: anti-CD40 scFv for engaging with macrophages and anti-Claudin18.2 (CLDN18.2) scFv for interacting with tumor cells. These nanoengagers were further constructed by coating scFv-anchored membrane into PLGA nanoparticle core. Our developed nanoengagers significantly boosted immune responses, including increased recognition and phagocytosis of tumor cells by macrophages, enhanced activation and antigen presentation, and elevated cytotoxic T lymphocyte activity. These combined benefits resulted in enhancing antitumor efficacy against highly aggressive "cold" pancreatic cancer. Overall, this study offers a versatile nanoengager design for immunotherapy, achieved through genetically engineering to incorporate antibody-anchored membrane., (© 2024. The Author(s).)

Background: Some studies have suggested that hepatitis B virus (HBV) infection had a negative association with semen quality, but the conclusions have been inconsistent. The purpose of our study was to systematically assess the association between HBV infection and semen parameters., Methods: We searched electronic databases for studies published from January 1980 to August 2023. Eleven studies were included in the analysis. Primary outcomes were semen volume, sperm concentration, sperm morphology, sperm motility and sperm progressive motility. We also conducted a subgroup analysis between China and other countries., Result: Compared with the semen quality of HBV-negative men, HBV infection had a negative association with semen volume (MD: -0.20 mL, 95%CI: -0.32 to - 0.09, P = 0.0004), sperm concentration (MD: -4.46 × 10 6 /mL, 95%CI: -7.09 to - 1.84, P = 0.0009), sperm morphology (MD: -2.49%, 95%CI: -4.35 to - 0.64, P = 0.008), sperm motility (MD: -6.85%, 95%CI: -11.53 to - 2.18, P = 0.004), and sperm progressive motility (MD: -6.63%, 95%CI: -10.24 to - 3.02, P = 0.0003). However, HBV infection had no significant association with total sperm count (MD: -31.50 × 10 6 , 95%CI: -74.11 to 11.10, P = 0.15). The association between HBV and semen quality were inconsistent between the subgroups., Conclusion: HBV infection had a negative association with sperm concentration, motility, morphology, and semen volume. However, The association between HBV and total sperm count remain unclear. This metaanalysis suggests that we should pay attention to the adverse effect of HBV on sperm quality, and several studies have reported the relevant mechanisms. But due to the significant heterogeneity among studies on some semen parameters, further large and well-designed researches are needed before introducing clinical management recommendations., (© 2024. The Author(s).)

Objective: To analyze the changes of plantar pressure in amateur marathon runners with flexor halluics longus (FHL) tendon injury using the Medtrack-Gait plantar pressure measurement system, and to explore whether the plantar pressure data can be used as an index for the diagnosis of injury., Methods: A total of 39 healthy amateur marathon runners without any ankle joint symptoms were recruited. Dynamic and static plantar pressure data were measured using the pressure plate of Medtrack-Gait. According to MRI imaging findings, whether the FHL tendon was injured or not was judged, and the dynamic and static data were divided into the injury group and control group. The data with statistically significant differences between the two groups were used to make the receiver operating characteristic (ROC) curve., Result: The maximum contact area (PA) of the first metatarsal(M1) region, the maximum load-bearing peak value (PW) and the time pressure integral (PMPTI) of the second metatarsal(M2) region in the injury group were lower than those in the control group, respectively (P < 0.05). The maximum contact area (PA) of the fifth metatarsal(M5) region was higher than that in the control group (P < 0.05). The area under curve (AUC) value of the ROC curve of the PA of M1 region, the PW and PMPTI of M2 region were statistically (P < 0.05)., Conclusion: FHL tendon injury resulted in decreased PA in M1, decreased PW and PMPTI in M2, and increased PA in the M5 region, suggesting that FHL tendon injury resulted in a force shift from the medial to the lateral side of the foot. The PA of M1, PW and PMPTI of M2 have certain diagnostic value for early FHL injury in amateur marathon runners., (© 2024. The Author(s).)

Background: High HIV prevalence, and lack of organized screening for the indigent population receiving care and treatment within HIV clinics in low-resource settings increases cervical cancer incidence. We sought to determine predictors of cervical precancer in women living with HIV and receiving cervical cancer screening in Jos, Nigeria., Methods: A cross-sectional study of women living with HIV and receiving care and treatment in adult HIV/AIDS clinics in Jos-Metropolis, Nigeria between June 2020 and April 2023. Ethical approvals were obtained from the ethics committee in Jos, Nigeria and Northwestern University IRB, USA. Informed consent was obtained from eligible participants, and data on socio-demographics, cancer risk factors, and cytology reports were collected. The outcome variables were cervical precancer lesions. The independent variables were prior Pap smear status, socio-demographics, income, educational, and other reproductive health factors. Descriptive statistics was done to obtain means ± sd, frequencies, and percentages for the variables. Univariate and bivariate analyses were done to determine predictors of cervical dysplasia. Analyses were performed using R software., Results: Of 957 women screened, 570 were living with HIV and 566 women had cytology report and were included in the final analysis. The mean age was 45.08 ± 8.89 years and 81.6% had no prior evidence of Pap test (under-screened). Prevalence of cervical dysplasia was 24% (mild and severe dysplasia were 12.9% and 11.1%, respectively). Age above 45 years (aOR = 3.48, p = 0.009), postmenopausal status (aOR = 7.69, p = 0.000), and women with no history of prior IUCD use (aOR = 5.94, p = 0.0001), were predictors for severe dysplasia. Women who had history of STI (aOR = 0.17, p = 0.000), prior use of IUCD (aOR = 0.32, p = 0.004), prior use of condom (aOR = 2.50, p = 0.003) and had co-morbidities (aOR = 0.46, p = 0.009) were more likely to have had a Pap test in the past., Conclusions: The majority of indigent women receiving care at HIV clinics had their first Pap test screening, and lack of organized screening among older and post-menopausal women with HIV, puts women at a higher risk of developing severe cervical precancer lesions., (© 2024. The Author(s).)

Cultivated peanut (Arachis hypogaea L.) represents one of the most important oil and cash crops world-widely. Unlike many other legumes, peanuts absorb nitrogen through their underground pods. Despite this unique feature, the relationship between yield and nitrogen uptake within the pod zone remains poorly understood. In our pot experiment, we divided the underground peanut part into two zones-pod and root-and investigated the physiological and agronomic traits of two peanut cultivars, SH11 (large seeds, LS) and HY23 (small seeds, SS), at 10 (S1), 20 (S2), and 30 (S3) days after gynophores penetrated the soil, with nitrogen application in the pod zone. Results indicated that nitrogen application increased pod yield, kernel protein content, and nitrogen accumulation in plants. For both LS and SS peanut cultivars, optimal nitrogen content was 60 kg·hm - 2 , leading to maximum yield. LS cultivar exhibited higher yield and nitrogen accumulation increases than SS cultivar. Nitrogen application up-regulated the expression of nitrogen metabolism-related genes in the pod, including nitrate reductase (NR), nitrite reductase (NIR), glutamine synthetase (GS), glutamate synthase (NADH-GOGAT), ATP binding cassette (ABC), and nitrate transporter (NRT2). Additionally, nitrogen application increased enzyme activity in the pod, including NR, GS, and GOGAT, consistent with gene expression levels. These nitrogen metabolism traits exhibited higher up-regulations in the large-seeded cultivar than in the small-seeded one and showed a significant correlation with yield in the large-seeded cultivar at S2 and S3. Our findings offer a scientific basis for the judicious application and efficient utilization of nitrogen fertilization in peanuts, laying the groundwork for further elucidating the molecular mechanisms of peanut nitrogen utilization., (© 2024. The Author(s).)

Background: Breast cancer (BC) is the most frequent malignancy in the world. Chemotherapy (CT) is a common treatment for BC but is accompanied by toxicity and side effects. Shenqi Fuzheng Injection (SFI) is an adjuvant therapy with promising results in improving efficacy and reducing toxicity in clinical studies. This overview of systematic reviews and meta-analysis (SRs/MAs) aimed to summarize the benefits and evaluate the quality of evidence supporting SFI adjuvant as CT for BC., Methods: A systematic search for SRs/MAs of randomized controlled trials (RCTs) on SFI treatment for BC was performed by searching PubMed, Web of Science, EMbase, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases from inception to October 1, 2022. The quality of SRs/MAs was evaluated using AMSTAR-2, PRISMA 2020, ROBIS, and GRADE by two reviewers. The corrected covered area (CCA) was used to quantify the degree of duplication of the original SRs/MAs. Finally, quantitative analysis of RCTs was conducted using RevMan 5.4 software. This study was registered with PROSPERO, CRD42022377290., Results: Six SRs/MAs including 61 RCTs with 5593 patients were included in this study. Studies were published between 2015 and 2019, the original RCTs ranged from 7-49, with sample sizes ranging from 336-1989. The quantitative meta-analysis found that adjuvant CT of SFI improved the clinical response rate (RR=1.37, 95% CI=1.28, 1.46; P<0.00001) and the KPS score (RR=1.66, 95% CI 1.54, 1.79, P<0.00001) of patients with BC. In terms of immune function, CD3+ (SMD=1.51, 95% CI 0.91, 2.10; P<0.00001), CD4+ (SMD=1.87, 95% CI 1.18, 2.56; P<0.00001), CD4+/CD8+ (SMD=0.86, 95% CI 0.48, 1.23; P<0.00001), and NK cell levels (SMD=0.94, 95% CI 0.63, 1.24; P<0.00001) in the adjuvant CT group SFI were better than those with CT alone. Adverse reactions following SFI adjuvant CT showed reduced incidence of leukopenia (RR=0.53, 95% CI 0.46, 0.62; P<0.00001) and gastrointestinal reactions (RR=0.48, 95% CI 0.39, 0.58; P<0.00001). However, the GRADE results showed 'very low' to 'moderate' evidence for the 42 outcomes, without high-quality evidence supporting them, limited mainly by deficiencies in the design of RCTs (42/42, 100.00%), inconsistency (19/42, 45.24%), publication bias (41/42, 97.62%), and inaccuracy (3/42, 7.14%). The unsatisfactory results of AMSTAR-2, PRISMA 2020, and ROBIS were limited to lack of registration of study protocols, explanation of inclusion basis of RCTs, description of funding sources for the included studies, incomplete search strategy and screening process, addressing heterogeneity and sensitivity, and reporting potential conflicts of interest., Conclusion: Adjuvant CT with SFI for BC had better benefits and a lower risk of adverse events. The methodology and quality of the evidence are generally low, highlighting a need of greater attention during study implementation. More objective and high-quality studies are needed to verify the efficacy of adjuvant CT with SFI in clinical decision-making for BC., (© 2024. The Author(s).)

Objective: This study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017-2022 in China., Research Design and Methods: Single-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L., Results: The median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8-10.0 years; 51.83% male). The mean annual incidence of T1DM was 2.98 per 1,000,000 child years. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020-2022 group and 2017-2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The frequency of DKA among the entire cohort was 57.93% (n = 95), and peaked in 2020 at 78.9% (15/19 patients). The frequency of DKA was not significantly higher in the 2020-2022 group compared with the 2017-2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020-2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2-0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2-0.6 ng/ml) in patients without DKA (p = 0.044)., Conclusions: This study showed the annual incidence of T1DM was 2.98 per 1,000,000 child years, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020-2022 in China compared with the previous 3 years. Furthermore, the frequency of DKA was peaked in 2020, and were not significantly different between patients who were negative vs. positive for auto-antibodies., (© 2023. The Author(s).)

Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and melanoma malignancies, with a median survival timeframe nearing six months. Existing therapeutic regimens yield suboptimal outcomes; however, burgeoning insights into the tumor microenvironment, particularly the immunosuppressive milieu engendered by tumor-brain interplay, posit immunotherapy as a promising avenue for ameliorating brain metastases. In this review, we meticulously delineate the research advancements concerning the microenvironment of brain metastases, striving to elucidate the panorama of their onset and evolution. We encapsulate three emergent immunotherapeutic strategies, namely immune checkpoint inhibition, chimeric antigen receptor (CAR) T cell transplantation and glial cell-targeted immunoenhancement. We underscore the imperative of aligning immunotherapy development with in-depth understanding of the tumor microenvironment and engendering innovative delivery platforms. Moreover, the integration with established or avant-garde physical methodologies and localized applications warrants consideration in the prevailing therapeutic schema., (© 2023. The Author(s).)

Background: Fungi play a crucial role in ecosystems, and they have been widely considered a promising source for natural compounds that are crucial for drug discovery. Fungi have a high diversity, but about 95% of them remain unknown to science. The description rate of fungi is very low, mainly due to the inability of most fungi to grow in artificial media, which could not provide a sufficiently similar environment to their natural habitats. Moreover, many species in nature are in a state of low metabolic activity which cannot readily proliferate without proper resuscitation. Previously developed culturomics techniques are mostly designed and applicable for bacteria, with few attempts for fungal isolation because of their significantly larger cell size and hyphal growth properties., Results: This study attempted to isolate previously uncultured and rare fungi from mangrove sediments using newly developed fungal enrichment culture method (FECM) and fungal isolation chips (FiChips). Comparison of fungal community composition at different enrichment stages showed that FECM had great influence on fungal community composition, with rare taxa increased significantly, thus improving the isolation efficiency of previously uncultured fungi. Similarly, in situ cultivation using FiChips has a significant advantage in detecting and culturing rare fungi, as compared to the conventional dilution plate method (DPM). In addition, based on morphological comparisons and phylogenetic analyses, we described and proposed 38 new ascomycetous taxa, including three new families, eight new genera, 25 new species, and two new combinations (presented in additional file 1)., Conclusions: Our study demonstrated that mangrove sediments harbor a high diversity of fungi, and our new isolation approaches (FECM and FiChips) presented a high efficiency in isolating hitherto uncultured fungi, which is potentially usable for fungal isolation in other similar environments. Video Abstract., (© 2023. The Author(s).)

Background: This study aimed to investigate the association between the intake of different dietary carbohydrate components and the long-term outcomes of non-alcoholic fatty liver disease (NAFLD)., Methods: We used prospective data from 26,729 NAFLD participants from the UK Biobank cohort study. Dietary information was recorded by online 24-hour questionnaires (Oxford WebQ). Consumption of different carbohydrate components was calculated by the UK Nutrient Databank Food Composition Table. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). A substitution model was used to estimate the associations of hypothetical substitution for free sugars., Results: During a median of 10.5 (IQR: 10.2-11.2) years and a total of 280,135 person-years of follow-up, 310 incident end-stage liver disease (ESLD) and 1750 deaths were recorded. Compared with the lowest quartile, the multi-adjusted HRs (95% CI) of incident ESLD in the highest quartile were 1.65 (1.14-2.39) for free sugars, 0.51 (0.35-0.74) for non-free sugars, and 0.55 (0.36-0.83) for fiber. For overall mortality, the multi-adjusted HRs (95% CI) in the highest quartile were 1.21 (1.04-1.39) for free sugars, 0.79 (0.68-0.92) for non-free sugars, and 0.79 (0.67-0.94) for fiber. Substituting free sugars with equal amounts of non-free sugars, starch or fiber was associated with a lower risk of incident ESLD and overall mortality., Conclusions: A lower intake of free sugars and a higher intake of fiber are associated with a lower incidence of ESLD and overall mortality in NAFLD patients. These findings support the important role of the quality of dietary carbohydrates in preventing ESLD and overall mortality in NAFLD patients., (© 2023. The Author(s).)

Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host-parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host-parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host-parasite interactions as a potential vaccine candidate., (© 2023. The Author(s).)

Background: Eurasian pigs have undergone lineage admixture throughout history. It has been confirmed that the genes of indigenous pig breeds in China have been introduced into Western commercial pigs, providing genetic materials for breeding Western pigs. Pigs in Taihu Lake region (TL), such as the Meishan pig and Erhualian pig, serve as typical representatives of indigenous pig breeds in China due to their high reproductive performances. These pigs have also been imported into European countries in 1970 and 1980 s. They have played a positive role in improving the reproductive performances in European commercial pigs such as French Large White pigs (FLW). However, it is currently unclear if the lineage of TL pigs have been introgressed into the Danish Large White pigs (DLW), which are also known for their high reproductive performances in European pigs. To systematically identify genomic regions in which TL pigs have introgressed into DLW pigs and their physiological functions, we collected the re-sequencing data from 304 Eurasian pigs, to identify shared haplotypes between DLW and TL pigs., Results: The findings revealed the presence of introgressed genomic regions from TL pigs in the genome of DLW pigs indeed. The genes annotated within these regions were found to be mainly enriched in neurodevelopmental pathways. Furthermore, we found that the 115 kb region located in SSC16 exhibited highly shared haplotypes between TL and DLW pigs. The major haplotype of TL pigs in this region could significantly improve reproductive performances in various pig populations. Around this genomic region, NDUFS4 gene was highly expressed and showed differential expression in multiple reproductive tissues between extremely high and low farrowing Erhualian pigs. This suggested that NDUFS4 gene could be an important candidate causal gene responsible for affecting the reproductive performances of DLW pigs., Conclusions: Our study has furthered our knowledge of the pattern of introgression from TL into DLW pigs and the potential effects on the fertility of DLW pigs., (© 2023. The Author(s).)

Background: Serum remnant cholesterol levels are being increasingly acknowledged as a causal risk factor for atherosclerotic disease, regardless of conventional lipid parameters. The positive association between remnant cholesterol and nonalcoholic fatty liver disease (NAFLD) has been revealed in previous studies. However, whether remnant cholesterol is associated with the severity of NAFLD remains unknown. This study aimed to explore the association between serum remnant cholesterol and the risk of NAFLD severity., Methods: This cross-sectional study included a total of 6,053 participants who attended health checkups. The severity of hepatic steatosis was evaluated by liver ultrasound transient elastography. Univariable and multivariable logistic regression analyses were performed to calculate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between remnant cholesterol and the severity of hepatic steatosis. To explore whether the association between remnant cholesterol and NAFLD severity was independent of conventional lipid parameters, we further investigated this association in individuals with normal values of low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides., Results: In total, 36.9% of individuals had mild steatosis, and 5.9% had moderate-to-severe steatosis. The serum level of remnant cholesterol in nonsteatosis, mild steatosis and moderate-to-severe steatosis gradually increased (0.71 ± 0.33, 0.97 ± 0.52 and 1.07 ± 0.63 mmol/L, respectively). In the multivariable mode, remnant cholesterol was positively associated with mild hepatic steatosis (OR: 1.730, 95% CI: 1.541 - 1.941, P < 0.001) and moderate-to-severe steatosis (OR: 2.342, 95% CI: 1.765 - 3.109, P < 0.001). These associations were not significantly altered in individuals with normal triglycerides, HDL-C and LDL-C (OR: 1.664, 95% CI: 1.448 - 1.911, P < 0.001; OR: 2.269, 95% CI: 1.619 - 3.180, P < 0.001, respectively)., Conclusions: Higher levels of serum remnant cholesterol were associated with more severe hepatic steatosis, regardless of conventional lipid parameters. Individuals with higher remnant cholesterol may need more attention in regular surveillance of NAFLD., (© 2023. The Author(s).)

Background: Metastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear., Methods: Expression of NUAK1 in ESCC was detected by real-time quantitative RT-PCR (qRT-PCR), Western blotting and immunohistochemical staining. MTT, colony formation, wound-healing and transwell assays were used to determine the role NUAK1 in vitro. Metastasis was evaluated by use of an experimental pulmonary metastasis model in BALB/c-nu/nu mice. The mechanisms were assessed by using coimmunoprecipitation, immunofluorescence and dual-luciferase reporter gene experiments., Results: NUAK1 was highly expressed in ESCC tissues compared with the adjacent normal esophageal epithelial tissues. Moreover, the elevated expression of NUAK1 positively correlated with tumor invasion depth, lymph node metastasis, pathological TNM stage, and poor survival in ESCC patients. Further experiments showed that NUAK1 overexpression did not change the cell viability and colony formation of ESCC cells, while remarkably promoted the migration and invasion in vitro and experimental pulmonary metastasis in vivo. Mechanistically, NUAK1 enhanced the transcription level of Slug, which enhanced the migratory and invasive capability of ESCC cells. Consistently, silencing Slug almost completely diminished the migration and invasion of NUAK1-overexpressing ESCC cells. Further studies demonstrated that NUAK1 upregulated the transcription activity of Slug through activating the JNK/c-Jun pathway., Conclusion: These results demonstrated that NUAK1 promoted the metastasis of ESCC cells through activating JNK/c-Jun/Slug signaling, indicating NUAK1 is a promising therapeutic target for metastatic ESCC., (© 2023. The Author(s).)

Background: The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders., Methods: Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods., Results: Univariable MR analyses provide evidence that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD) (based on p<7.14×10 -4 ), respectively. However, after performing multivariable MR, only age at first sexual intercourse has direct effects on five psychiatric disorders (Depression, Attention deficit or hyperactivity disorder, Bipolar disorder, Posttraumatic stress disorder and schizophrenia) when accounting for other reproductive behaviors with significant effects in univariable analyses., Conclusion: Our findings suggest that reproductive behaviors predominantly exert their detrimental effects on psychiatric disorders and age at first sexual intercourse has direct effects on psychiatric disorders., (© 2023. The Author(s).)

Introduction: Invasive cervical cancer (ICC) is an HIV-associated cancer that is preventable and precancerous stages including early ICC stages could be detected through screening offering opportunities for treatment and cure. The high incidence in women living with HIV and late presentation often at advanced stages of ICC with limited treatment facilities often result in early mortality. We sought to compare the epidemiologic characteristics and survival differences in HIV status of ICC patients in Nigeria., Methods: We conducted a cohort study at two federal academic hospital-based research sites in Jos University Teaching Hospital, and Lagos University Teaching Hospital Nigeria, between March 2018 and September 2022. We enrolled women with histologically confirmed ICC with known HIV status, and FIGO staging as part of the United States of America's National Institutes of Health/National Cancer Institute funded project titled 'Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria'. The primary outcome was all-cause mortality with assessment of overall survival (OS) and time to death after ICC diagnosis. OS distribution was estimated using the method of Kaplan-Meier and compared between groups using the log-rank test., Results: A total of 239 women with confirmed ICC were enrolled and included in this analysis, of whom 192 (80.3%) were HIV-negative (HIV-/ICC +), and 47 (19.7%) were HIV-positive (HIV +/ICC +). The HIV +/ICC + patients were younger with median age 46 (IQR: 40-51) years compared to 57 (IQR: 45-66) among HIV-/ICC + (P < 0.001). Squamous cell carcinoma was the commonest histopathologic variant in 80.4% of ICC diagnosis, moderately differentiated tumor grade in 68.1% in both groups. HIV +/ICC + diagnosis was at FIGO advanced stages in 64.9% compared to 47.9% in HIV-/ICC +. The HIV-/ICC + women had better OS compared to HIV +/ICC + participants (p = 0.018), with 12-month OS 84.1% (95%CI 75-90%) and 67.6% (95%CI 42-84%) respectively., Conclusion: ICC is diagnosed at a relatively young age in women living with HIV, with a significantly lower overall survival probability compared to women without HIV. The trend of presentation and diagnosis at advanced stages in women living with HIV could partly explain the differences in overall survival., (© 2023. The Author(s).)

Objective: Sjögren's syndrome (SS) is a rare disease with unclear diagnostic criteria among the children and adolescents. The purpose of this study is to describe the clinical features of pediatric Sjögren's syndrome and validate with Japanese diagnostic guidelines criteria of 2018., Methods: We conducted a retrospective analysis of the clinical data of a cohort of 54 patients with pediatric Sjögren's syndrome admitted to our hospital over a total of 10 years from September 2013 to September 2022., Results: The ratio of females to males was 49:5 among the 54 children (34 cases of primary SS and 20 cases of secondary SS), the average age of onset of symptoms for the first time was 9.9 years, and the average age at diagnosis was 10.2 years. In terms of subjective symptoms, 7 cases (13.0%) presented with dry mouth and 5 cases (9.3%) reported dry eyes. The positive rates were 9.3% for Schirmer I test, 70.4% for salivary gland function test, and 55.6% for salivary gland ultrasonography. The positive rates were 94.4% for Anti-Ro/SSA antibodies, 66.7% for Anti-La/SSB antibodies, 88.9% for ANA, 59.3% for RF, and the elevation rate of IgG was 63.0%. Among the EULAR Sjögren's syndrome disease activity index (ESSDAI) domains, the biological, constitutional, glandular, cutaneous, and lymphadenopathy domains were most involved. Treatment consisted of glucocorticoids in 88.9% of the patients in our study and hydroxychloroquine in 92.6%. As per the Japanese version of the clinical practice guidance for Sjögren's Syndrome in pediatric patients (2018), 5 cases were identified as Definite SS, 35 cases as Probable SS, and 14 cases as Possible SS. With respect to primary and secondary SS, there was essentially no significant difference between the groups in any of the above aspects., Conclusions: Patients with pediatric SS presented with a wide spectrum of clinical features, a low prevalence of reported symptoms of dry mouth and dry eyes, and various clinical manifestations with multi-system involvement. These are similar to other pediatric study cohorts in terms of epidemiology, auxiliary investigation results, disease activity scores, and treatment. The coincidence between our study and the Japanese version of the clinical practice guidance for Sjögren's Syndrome in pediatric patients (2018) is good for the diagnosis of pediatric SS., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Whether intrauterine transmission of COVID-19 occurs remains uncertain, and it remains unclear whether the disease affects fetuses. We present a case of intrauterine transmission of SARS-CoV-2 infection and the prenatal ultrasonographic findings of the fetus in a pregnant woman with mild COVID-19., Case Presentation: A 30-year-old woman was admitted to our hospital for ultrasound examination in January 2023 at 26 + 3 weeks' gestation. Twenty-one days prior, her COVID-19 nucleic acid test was positive, and she had mild symptoms, including fever (38.3 °C), headache, chills, ankle pain and cough. After receiving symptomatic treatment, she fully recovered. Prenatal ultrasound revealed that the placenta was diffusely distributed with punctate echogenic foci, hepatomegaly, and the volume of bilateral lungs decreased significantly, with enhanced echo. In addition, we found that the surface of the fetal brain demonstrated widened gyri with a flattened surface. The prenatal MRI confirmed these fetal abnormalities. Amniotic fluid was tested for SARS-CoV-2, and the sample tested was positive for the virus. After careful consideration, the pregnant woman decided to terminate the pregnancy., Conclusion: The intrauterine transmission of COVID-19 is certain. Moreover, the intrauterine transmission of COVID-19 may cause abnormalities in various organs of the fetus., (© 2023. BioMed Central Ltd., part of Springer Nature.)