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Abstract Background Distal tibial fractures represent common lower limb injuries, frequently accompanied by significant soft tissue damage. The optimal surgical approach for managing these fractures remains a topic of considerable debate. The aim of this study was to perform a comparative analysis of the outcomes associated with retrograde intramedullary tibial nails (RTN) and minimally invasive plate osteosynthesis (MIPO) in the context of treating extra-articular distal tibial fractures. Methods A retrospective review was conducted on a cohort of 48 patients who sustained extra-articular distal tibial fractures between December 2019 and December 2021. Patients underwent either RTN or MIPO procedures. Various parameters, including operative duration, intraoperative fluoroscopy exposure, time to union, duration until full weight-bearing, American Orthopedic Foot and Ankle Society (AOFAS) scores, and complications, were recorded and compared between the two treatment groups. Results No statistically significant differences were observed in operative duration, time to union, angulation of the distal tibial coronal plane, or AOFAS scores between the RTN and MIPO groups. However, the RTN group had a higher average number of intraoperative fluoroscopy images (8.2 ± 2.3) compared to the MIPO group (4.1 ± 2.0). The RTN group demonstrated shorter average hospital stays (7.1 ± 1.4 days) and a quicker return to full weight-bearing (9.9 ± 1.3 weeks), which were significantly superior to the MIPO group (9.0 ± 2.0 days and 11.5 ± 1.5 weeks, respectively). In terms of complications, the RTN group had one case of superficial infection, whereas the MIPO group exhibited two cases of delayed union and nonunion, two occurrences of deep infection, and an additional three cases of superficial infection. Conclusions Both RTN and MIPO are effective treatment options for extra-articular distal tibial fractures. However, RTN may offer superior outcomes in terms of decreased inpatient needs, faster return to full weight-bearing capacity, and a lower rate of complications.

Abstract Background This study aimed to clarify medical-nonmedical difference on the relationship between social capital, mental health and digital health literacy of university students in China, and furtherly provide evidence-based suggestions on the improvement of the digital health literacy for the university students. Methods The snowball sampling method was used to collect data from the university students (including medical students and nonmedical students) through online questionnaires, and finally 1472 university students were included for the data analysis, of whom, 665 (45.18%) were medical students, 807 (54.82%) were nonmedical students; 462 (31.39%) were male, 1010 (68.61%) were female. Mean value of the age was 21.34 ± 2.33 for medical students vs. 20.96 ± 2.16 for nonmedical students. Descriptive analysis, chi-square test analysis, one-way Analysis of Variance (conducted by SPSS) and structural equation modeling (conducted by AMOS) were employed to explore the difference on the relationship between social capital, mental health and digital health literacy between the medical students and nonmedical students. Results The mean value of the digital health literacy was 36.27 (37.33 for medical students vs. 35.39 for nonmedical students). The SEM analysis showed that there was a statistically positive correlation between social capital and digital health literacy (stronger among the nonmedical students (0.317) than medical students (0.184)). Mental health had a statistically positive impact on the digital health literacy among medical students (0.242), but statistically significant correlation was not observed in nonmedical students (0.017). Social capital was negatively correlated with the mental health for both medical students and NMS (stronger among the nonmedical students (0.366) than medical students (0.255)). And the fitness indices of SEM were same between medical students and nonmedical students (GFI = 0.911, AGFI = 0.859, CFI = 0.922, RMSEA = 0.074). Conclusion The digital health literacy of the university student was relatively high. Both social capital and mental health could exert a positive effect on digital health literacy, while social capital was found to be positively associated with mental health. Statistical difference was found between medical students and nonmedical students on the above correlations. Implications were given on the improvement of the digital health literacy among university students in China.

Abstract Previous studies have shown that the heterogeneity of tumor-associated fibroblasts (CAFs) in the tumor microenvironment may play a critical role in tumorigenesis; however, the biological function of CAFs in pancreatic cancer is still controversial. In this study, we found that CD105-positive (CD105+) CAF-derived exosomes significantly promoted the proliferative and invasive metastatic abilities of pancreatic cancer cells. Furthermore, RNA-seq and qRT‒PCR experiments revealed circAMPK1 as a key molecule in exosomes from CD105+ CAFs that mediates the malignant progression of pancreatic cancer. Furthermore, we demonstrated that circAMPK1 encodes a novel protein (AMPK1-360aa) in pancreatic cancer cells. This protein competes with AMPK1 to bind to the ubiquitination ligase NEDD4, which inhibits AMPK1 protein degradation and ubiquitination and thereby increases AMPK1 levels. Finally, we demonstrated that AMPK1-360aa induces cellular autophagy via NEDD4/AMPK1 to promote the proliferation and invasion of pancreatic cancer cells. In summary, circAMPK1 in CD105+ CAF-derived exosomes may mediate pancreatic cancer cell proliferation and invasive metastasis by inducing autophagy in target cells. Moreover, circAMPK1 may competitively bind to ubiquitinating enzymes through the encoded protein AMPK1-360aa, which in turn inhibits the ubiquitination-mediated degradation of AMPK1 and contributes to the upregulation of AMPK1 expression, thus inducing cellular autophagy to mediate the malignant progression of pancreatic cancer.

Abstract Background A cross-sectional population-based survey in the Beichen district of Tianjin was conducted to estimate the prevalence of dry eye disease (DED) among the population over 50 years old with Dry Eye Workshop (DEWS) II and Chinese expert consensus (CEC) criteria. Methods A total of 5791 subjects over 50 years old were enrolled. Ocular surface disease index (OSDI) questionnaire, lipid layer thickness (LLT), partial blink ratio (PBR), fluorescein tear film breakup time (FBUT), Schirmer I test (SIT), fluorescein staining, meibomian gland dropout, meibomian gland expression scores (MES) and quantity scores (MQS) was assessed. Additionally, basic information, weight, disease history, living habits, anxiety, and depression condition were collected. Results According to the CEC, the prevalence of DED was 39.0%, whereas 44.0% based on DEWS II. The prevalence of DED increased with age and was substantially greater among women (41.1%, 95% CI, 39.5-42.6%) than males (35.1%, 95% CI, 33.1 -37.2%) (p

Abstract Objectives To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC’s etiology and further support the development of therapeutic strategies. Methods A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. Results UC patients demonstrated significantly higher native T1 (p

Abstract Li metal batteries have been widely expected to break the energy‐density limits of current Li‐ion batteries, showing impressive prospects for the next‐generation electrochemical energy storage system. Although much progress has been achieved in stabilizing the Li metal anode, the current Li electrode still lacks efficiency and safety. Moreover, a practical Li metal battery requires a thickness‐controllable Li electrode to maximally balance the energy density and stability. However, due to the stickiness and fragile nature of Li metal, manufacturing Li ingot into thin electrodes from conventional approaches has historically remained challenging, limiting the sufficient utilization of energy density in Li metal batteries. Aiming at the practical application of Li metal anode, the current issues and their initiation mechanism are comprehensively summarized from the stability and processability perspectives. Recent advances in robust and ultra‐thin Li metal anode are outlined from methodology innovation to provide an overall insight. Finally, challenges and prospective developments regarding this burgeoning field are critically discussed to afford future outlooks. With the development of advanced processing and modification technology, we are optimistic that a truly great leap will be achieved in the foreseeable future toward the industrial application of Li metal batteries.

Abstract Background The undergraduate tutorial system (UTS) is a crucial measure in China for adhering to the principle of prioritizing foundational education, innovating the undergraduate talent training mode, and building a powerful country of higher education. This study investigated undergraduate students’ satisfaction with UTS and the influencing factors, aiming to promote the healthy and sustainable development of UTS and provide practical implications and suggestions for universities. Methods Based on relevant theories, we conducted a survey study and leveraged structural equation modeling to assess students’ satisfaction with UTS and explore the influencing factors. Results Our Pearson correlation analysis showed that students’ satisfaction with mentors was positively correlated with dimensions such as humanistic care (r = 0.844, P

Abstract Background Compared with moderate-intensity continuous training (MICT), high-intensity interval training (HIIT) has at least a comparable effect on inhibiting an increase in fat. However, few studies have been conducted to examine the effects of detraining on body fat in rats fed a high-fat diet. The present study aimed to compare the effects of 10 weeks of HIIT or MICT as well as 6 weeks of detraining on body fat in rats fed a high-fat diet. Methods After being fed a high-fat diet for 8 weeks, 54 female rats were randomly assigned to six groups: (1) CON-10, sedentary control for 10 weeks; (2) MICT-10, 10 weeks of MICT; (3) HIIT-10, 10 weeks of HIIT; (4) CON-16, sedentary control for 16 weeks; (5) MICT-16, 10 weeks of MICT followed by 6 weeks of training cessation; and (6) HIIT-16, 10 weeks of HIIT followed by 6 weeks of training cessation. The training was performed 5 days/week. The subcutaneous adipose tissue (inguinal; SCAT), visceral adipose tissue (periuterine; VAT) and serum lipid profile were analysed after 10 or 16 weeks. Adipose tissue triglyceride lipase (ATGL) protein expression in VAT was assessed by western blotting. Results HIIT-10 and MICT-10 prevented the increase in SCAT, VAT and serum lipid levels seen in the CON group. During the 6-week detraining period, HIIT continued to prevent the increase in adipose tissue mass observed in the CON group, whereas MICT at least maintained this inhibition. The inhibition of fat mass increase was mainly the result of preventing adipocyte hypertrophy. The HIIT-10 and HIIT-16 groups showed the highest ATGL protein expression. Conclusions HIIT has a comparable effect to MICT on inhibiting fat accumulation in female rats; however, the inhibition of SCAT and VAT increase by HIIT is superior to MICT after short-term training cessation. Graphical Abstract

Abstract Background Given the significant role of immune-related genes in uterine corpus endometrial carcinoma (UCEC) and the long-term outcomes of patients, our objective was to develop a prognostic risk prediction model using immune-related genes to improve the accuracy of UCEC prognosis prediction. Methods The Limma, ESTIMATE, and CIBERSORT methods were used for cluster analysis, immune score calculation, and estimation of immune cell proportions. Univariate and multivariate analyses were utilized to develop a prognostic risk model for UCEC. Risk model scores and nomograms were used to evaluate the models. String constructs a protein-protein interaction (PPI) network of genes. The qRT-PCR, immunofluorescence, and immunohistochemistry (IHC) all confirmed the genes. Results Cluster analysis divided the immune-related genes into four subtypes. 33 immune-related genes were used to independently predict the prognosis of UCEC and construct the prognosis model and risk score. The analysis of the survival nomogram indicated that the model has excellent predictive ability and strong reliability for predicting the survival of patients with UCEC. The protein-protein interaction network analysis of key genes indicates that four genes play a pivotal role in interactions: GZMK, IL7, GIMAP, and UBD. The quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and immunohistochemistry (IHC) all confirmed the expression of the aforementioned genes and their correlation with immune cell levels. This further revealed that GZMK, IL7, GIMAP, and UBD could potentially serve as biomarkers associated with immune levels in endometrial cancer. Conclusion The study identified genes related to immune response in UCEC, including GZMK, IL7, GIMAP, and UBD, which may serve as new biomarkers and therapeutic targets for evaluating immune levels in the future.

High-precision positioning and navigation are necessary for autonomous driving. GNSS RTK and INS integrated system is commonly used in vehicular navigation. But it suffers from severe signal reflections and blockages of GNSS signals and error accumulation of INS with MEMS-IMU in GNSS-challenging environment. In addition, high-definition (HD) maps in vector format and light detection and ranging (LiDAR) are two common options for intelligent vehicles. A tightly coupled localization method with vector HD map, LiDAR, GNSS RTK, and INS is proposed to take advantage of their complementary characteristics to accurately navigate a vehicle in a GNSS-challenging environment. The method is based on a particle filter (PF) framework. Lateral positions of particles are constrained by LiDAR measurements and lane information in the vector HD map. A constrained and damped LAMBDA searching method is proposed to update particle weights, aiming to find accurate longitudinal localization. Experimental results prove that our method can maintain sub-meter level horizontal positioning accuracy in GNSS-challenging environment, with improvements of (77%, 75%, 64% and 65%), regarding to three-dimensional position and yaw, compared to traditional GNSS-RTK/INS integration, while the improvement of the popular GNSS-RTK/INS/LiDAR integrated framework LIO-SAM is (16%, 53%, 48% and 51%).

Subclinical hypothyroidism (SCH) is closely related to insulin resistance, and thyroid-stimulating hormone (TSH) level is an independent factor for insulin resistance associated with subclinical hypothyroidism. This study aims to explore the effects of TSH levels on insulin signal transduction in adipocytes and to establish the role of endoplasmic reticulum (ER) stress in this process. In this study, the SCH mouse model was established, and 3T3-L1 adipocytes were treated with TSH or tunicamycin (TM), with or without 4-phenylbutyric acid (4-PBA), an inhibitor of ER stress. Subclinical hypothyroidism mice exhibited impaired glucose tolerance, inactivation of the IRS-1/AKT pathway, and activation of the IRE1/JNK pathway in adipose tissue, which can all be alleviated by 4-PBA. Supplementation with levothyroxine restored the TSH to normal, alongside alleviated ER stress and insulin resistance in SCH mice, which is characterized by improved glucose tolerance, decreased mRNA expression of IRE1, and decreased phosphorylation of JNK in adipose tissue. In 3T3-L1 adipocytes, TSH induces insulin resistance, leading to a decrease in glucose uptake. This effect is mediated by the downregulation of IRS-1 tyrosine phosphorylation, reduced AKT phosphorylation, and inhibited GLUT4 protein expression. Notably, all these effects can be effectively reversed by 4-PBA. Moreover, TSH induced TNF-α and IL-6 production and upregulated the expression of ER stress markers. Similarly, these changes can be recovered by 4-PBA. These findings indicate that TSH has the capability to induce insulin resistance in adipocytes. The mechanism through which TSH disrupts insulin signal transduction appears to involve the ER stress–JNK pathway.

Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized primarily by cognitive impairment. The motivation of this paper is to explore the impact of the visual information transmission pathway (V–H pathway) on AD, and the following feature were observed: Hemoglobin expression on the V–H pathway becomes dysregulated as AD occurs so as to the pathway becomes dysfunctional. According to the feature, the following conclusion was proposed: As AD occurs, abnormal tau proteins penetrate bloodstream and arrive at the brain regions of the pathway. Then the tau proteins or other toxic substances attack hemoglobin molecules. Under the attack, hemoglobin expression becomes more dysregulated. The dysfunction of V–H pathway has an impact on early symptoms of AD, such as spatial recognition disorder and face recognition disorder.

Abstract The Sox gene family, a collection of transcription factors widely distributed throughout the animal kingdom, plays a crucial role in numerous developmental processes. Echinoderms occupy a pivotal position in many research fields, such as neuroscience, sex determination and differentiation, and embryonic development. However, to date, no comprehensive study has been conducted to characterize and analyze Sox genes in echinoderms. In the present study, the evolution and expression of Sox family genes across 11 echinoderms were analyzed using bioinformatics methods. The results revealed a total of 70 Sox genes, with counts ranging from 5 to 8 across different echinoderms. Phylogenetic analysis revealed that the identified Sox genes could be categorized into seven distinct classes: the SoxB1 class, SoxB2 class, SoxC class, SoxD class, SoxE class, SoxF class and SoxH class. Notably, the SoxB1, SoxB2, and SoxF genes were ubiquitously present in all the echinoderms studied, which suggests that these genes may be conserved in echinoderms. The spatiotemporal expression patterns observed for Sox genes in the three echinoderms indicated that various Sox members perform distinct functional roles. Notably, SoxB1 is likely involved in echinoderm ovary development, while SoxH may play a crucial role in testis development in starfish and sea cucumber. In general, the present investigation provides a molecular foundation for exploring the Sox gene in echinoderms, providing a valuable resource for future phylogenetic and genomic studies.

Abstract Background Ankylosing spondylitis (AS) with radiographic damage is more prevalent in men than in women. IL-17, which is mainly secreted from peripheral blood mononuclear cells (PBMCs), plays an important role in the development of AS. Its expression is different between male and female. However, it is still unclear whether sex dimorphism of IL-17 contribute to sex differences in AS. Methods GSE221786, GSE73754, GSE25101, GSE181364 and GSE205812 datasets were collected from the Gene Expression Omnibus (GEO) database. Differential expressed genes (DEGs) were analyzed with the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods. CIBERSORTx and EcoTyper algorithms were used for immune infiltration analyses. Machine learning based on the XGBoost algorithm model was used to identify the impact of DEGs. The Connectivity Map (CMAP) database was used as a drug discovery tool for exploring potential drugs based on the DEGs. Results According to immune infiltration analyses, T cells accounted for the largest proportion of IL-17-secreting PBMCs, and KEGG analyses suggested an enhanced activation of mast cells among male AS patients, whereas the expression of TNF was higher in female AS patients. Other signaling pathways, including those involving metastasis-associated 1 family member 3 (MAT3) or proteasome, were found to be more activated in male AS patients. Regarding metabolic patterns, oxidative phosphorylation pathways and lipid oxidation were significantly upregulated in male AS patients. In XGBoost algorithm model, DEGs including METRN and TMC4 played important roles in the disease process. we integrated the CMAP database for systematic analyses of polypharmacology and drug repurposing, which indicated that atorvastatin, famciclocir, ATN-161 and taselisib may be applicable to the treatment of AS. Conclusions We analyzed the sex dimorphism of IL-17-secreting PBMCs in AS. The results showed that mast cell activation was stronger in males, while the expression of TNF was higher in females. In addition, through machine learning and the CMAP database, we found that genes such as METRN and TMC4 may promote the development of AS, and drugs such as atorvastatin potentially could be used for AS treatment.

Abstract Introduction To explore the diagnostic value of high-resolution ultrasound combined with multi-slice computer tomography (MSCT) for pediatric intra-abdominal hernias (IAHs), and to analyze the potential causes for missed diagnosis and misdiagnosis of IAHs in children. Methods A retrospective analysis was conducted on 45 children with surgically confirmed IAHs. The diagnostic rate of IAHs by preoperative high-resolution ultrasound combined with MSCT was compared with that of intraoperative examination, and the potential causes for missed diagnosis and misdiagnosis by the combination method were analyzed. Results Forty-five cases of pediatric IAHs were categorized into primary (25/45, 55.5%) and acquired secondary hernias (20/45, 44.5%). Among children with primary hernias, mesenteric defects were identified as the predominant subtype (40%). Acquired secondary hernias typically resulted from abnormal openings in the abdominal wall or band adhesions due to trauma, surgery, or inflammation. In particular, adhesive band hernias were the major type in children with acquired secondary hernias (40%). The diagnostic rate of high-resolution ultrasound was 77.8%, with “cross sign” as a characteristic ultrasonic feature. Among 10 cases of missed diagnosis or misdiagnosis, 5 were finally diagnosed as IAHs by multi-slice computer tomography (MSCT). Overall, the diagnostic rate of pediatric IAHs by preoperative ultrasound combined with radiological imaging reached 88.9%. Discussion IAHs in children, particularly mesenteric defects, are prone to strangulated intestinal obstruction and necrosis. High-resolution ultrasound combined with MSCT greatly enhances the diagnostic accuracy of pediatric IAHs.

Abstract Background Pretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging. Methods We investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM−)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman’s analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection. Results In the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM−) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM−) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = − 0.399; radial, r = − 0.362; circumferential, r = − 0.389) (all P

Abstract This study probes the utility of biomarkers for microsatellite instability (MSI) detection and elucidates the molecular dynamics propelling colorectal cancer (CRC) progression. We synthesized a primer panel targeting 725 MSI loci, informed by The Cancer Genome Atlas (TCGA) and ancillary databases, to construct an amplicon library for next-generation sequencing (NGS). K-means clustering facilitated the distillation of 8 prime MSI loci, including activin A receptor type 2A (ACVR2A). Subsequently, we explored ACVR2A’s influence on CRC advancement through in vivo tumor experiments and hematoxylin–eosin (HE) staining. Transwell assays gauged ACVR2A’s role in CRC cell migration and invasion, while colony formation assays appraised cell proliferation. Western blotting illuminated the impact of ACVR2A suppression on CRC’s PI3K/AKT/mTOR pathway protein expressions under hypoxia. Additionally, ACVR2A’s influence on CRC-induced angiogenesis was quantified via angiogenesis assays. K-means clustering of NGS data pinpointed 32 MSI loci specific to tumor and DNA mismatch repair deficiency (dMMR) tissues. ACVR2A emerged as a pivotal biomarker, discerning MSI-H tissues with 90.97% sensitivity. A curated 8-loci set demonstrated 100% sensitivity and specificity for MSI-H detection in CRC. In vitro analyses corroborated ACVR2A’s critical role, revealing its suppression of CRC proliferation, migration, and invasion. Moreover, ACVR2A inhibition under CRC-induced hypoxia markedly escalated MMP3, CyclinA, CyclinD1, and HIF1α protein expressions, alongside angiogenesis, by triggering the PI3K/AKT/mTOR cascade. The 8-loci ensemble stands as the optimal marker for MSI-H identification in CRC. ACVR2A, a central element within this group, deters CRC progression, while its suppression amplifies PI3K/AKT/mTOR signaling and angiogenesis under hypoxic stress.

Abstract Background Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. Methods Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. Results RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. Conclusion In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa.

Abstract Objectives To explore the value of radiomic features derived from pericoronary adipose tissue (PCAT) obtained by coronary computed tomography angiography for prediction of coronary rapid plaque progression (RPP). Methods A total of 1233 patients from two centers were included in this multicenter retrospective study. The participants were divided into training, internal validation, and external validation cohorts. Conventional plaque characteristics and radiomic features of PCAT were extracted and analyzed. Random Forest was used to construct five models. Model 1: clinical model. Model 2: plaque characteristics model. Model 3: PCAT radiomics model. Model 4: clinical + radiomics model. Model 5: plaque characteristics + radiomics model. The evaluation of the models encompassed identification accuracy, calibration precision, and clinical applicability. Delong’ test was employed to compare the area under the curve (AUC) of different models. Results Seven radiomic features, including two shape features, three first-order features, and two textural features, were selected to build the PCAT radiomics model. In contrast to the clinical model and plaque characteristics model, the PCAT radiomics model (AUC 0.85 for training, 0.84 for internal validation, and 0.81 for external validation; p 0.05). Conclusion Radiomic feature analysis derived from PCAT significantly improves the prediction of RPP as compared to clinical and plaque characteristics. Radiomic analysis of PCAT may improve monitoring RPP over time. Critical relevance statement Our findings demonstrate PCAT radiomics model exhibited good performance in the prediction of RPP, with potential clinical value. Key Points Rapid plaque progression may be predictable with radiomics from pericoronary adipose tissue. Fibrous plaque volume, diameter stenosis, and fat attenuation index were identified as risk factors for predicting rapid plaque progression. Radiomics features of pericoronary adipose tissue can improve the predictive ability of rapid plaque progression. Graphical Abstract

Abstract Neurofibromatosis Type 1 (NF1) is caused by loss of function variants in the NF1 gene. Most patients with NF1 develop skin lesions called cutaneous neurofibromas (cNFs). Currently the only approved therapeutic for NF1 is selumetinib, a mitogen -activated protein kinase (MEK) inhibitor. The purpose of this study was to analyze the transcriptome of cNF tumors before and on selumetinib treatment to understand both tumor composition and response. We obtained biopsy sets of tumors both pre- and on- selumetinib treatment from the same individuals and were able to collect sets from four separate individuals. We sequenced mRNA from 5844 nuclei and identified 30,442 genes in the untreated group and sequenced 5701 nuclei and identified 30,127 genes in the selumetinib treated group. We identified and quantified distinct populations of cells (Schwann cells, fibroblasts, pericytes, myeloid cells, melanocytes, keratinocytes, and two populations of endothelial cells). While we anticipated that cell proportions might change with treatment, we did not identify any one cell population that changed significantly, likely due to an inherent level of variability between tumors. We also evaluated differential gene expression based on drug treatment in each cell type. Ingenuity pathway analysis (IPA) was also used to identify pathways that differ on treatment. As anticipated, we identified a significant decrease in ERK/MAPK signaling in cells including Schwann cells but most specifically in myeloid cells. Interestingly, there is a significant decrease in opioid signaling in myeloid and endothelial cells; this downward trend is also observed in Schwann cells and fibroblasts. Cell communication was assessed by RNA velocity, Scriabin, and CellChat analyses which indicated that Schwann cells and fibroblasts have dramatically altered cell states defined by specific gene expression signatures following treatment (RNA velocity). There are dramatic changes in receptor-ligand pairs following treatment (Scriabin), and robust intercellular signaling between virtually all cell types associated with extracellular matrix (ECM) pathways (Collagen, Laminin, Fibronectin, and Nectin) is downregulated after treatment. These response specific gene signatures and interaction pathways could provide clues for understanding treatment outcomes or inform future therapies.

Abstract Background Sepsis is a common and severe disease with a high mortality rate in intensive care unit (ICU). The hemoglobin (HGB) level is a key parameter for oxygen supply in sepsis. Although HGB is associated with the progression of inflammation in sepsis patients, its role as a marker following sepsis treatment remains unclear. Here, we studied the correlation between early temporal changes in HGB levels and long-term mortality rates in septic patients. Method In this retrospective study of data on patients with sepsis from the Medical Information Mart for Intensive Care (MIMIC) IV database, the outcome was long-term mortality. Patients were divided based on the cut-off of the HGB percentage for receiver operating characteristic (ROC) curve calculation. Kaplan–Meier (KM) survival curves and Cox proportional hazards regression models were used to analyse the associations between groups and outcomes. Propensity score matching (PSM) was used to verify the results. Results In this study, 2042 patients with sepsis and changes in HGB levels at day 4 after admission compared to day 1 were enrolled and divided into two groups: group 1 (n = 1147) for those with reduction of HGB

Abstract Purpose In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays. Methods Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared. Results Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P

Abstract Emotion recognition based on Electroencephalogram (EEG) has been applied in various fields, including human–computer interaction and healthcare. However, for the popular Valence-Arousal-Dominance emotion model, researchers often classify the dimensions into high and low categories, which cannot reflect subtle changes in emotion. Furthermore, there are issues with the design of EEG features and the efficiency of transformer. To address these issues, we have designed TPRO-NET, a neural network that takes differential entropy and enhanced differential entropy features as input and outputs emotion categories through convolutional layers and improved transformer encoders. For our experiments, we categorized the emotions in the DEAP dataset into 8 classes and those in the DREAMER dataset into 5 classes. On the DEAP and the DREAMER datasets, TPRO-NET achieved average accuracy rates of 97.63%/97.47%/97.88% and 98.18%/98.37%/98.40%, respectively, on the Valence/Arousal/Dominance dimension for the subject-dependent experiments. Compared to other advanced methods, TPRO-NET demonstrates superior performance.

This study presents the initial sequencing and characterization of the complete mitochondrial genome (mitogenome) of Hyalinocerus flavoscutatus, making the first comprehensive exploration of the mitogenome in the Hyalinocerus. Utilizing next-generation sequencing techniques, we identified a circular DNA molecule spanning 15,307 bp. The mitogenome comprises 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a primary non-coding region. Maximum likelihood phylogenetic evaluation, based on 13 protein-coding genes and two ribosomal RNA genes, robustly supports H. flavoscutatus as the basal group within Idiocerini. This research unveils valuable insights into the mitogenome of H. flavoscutatus and enhances our understanding of phylogenetic placement within the broader context of related tribes.

Abstract Quantum computing has already demonstrated great computational potential across multiple domains and has received more and more attention. However, due to the connectivity limitations of Noisy Intermediate-Scale Quantum (NISQ) devices, most of the quantum algorithms cannot be directly executed without the help of inserting SWAP gates. Nevertheless, more SWAP gates lead to a longer execution time and, inevitably, lower fidelity of the algorithm. To this end, this paper proposes an optimized qubit mapping algorithm based on a dynamic look-ahead strategy to minimize the number of SWAP gates inserted. Firstly, a heuristic algorithm is proposed based on maximizing physical qubit connectivity to generate the optimal initial qubit mapping, which reduces the need for logical qubit shifts during subsequent SWAP gate insertion. Secondly, in the form of directed acyclic graphs, we identify quantum gates that violate the constraints of physical coupling and insert SWAP gates to remap qubits, thereby overcoming the limitations of qubit interactions. Finally, the optimal SWAP gate insertion strategy is built by comparing the cost of different SWAP gate insertion strategies through a multi-window look-ahead strategy to reduce the number of SWAP gates inserted. The experimental results show that the strategy in this paper decreases the number of SWAP gate insertions and significantly reduces the depth of quantum circuits when performing qubit mapping compared with state-of-the-art methods.

AIM: To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy (DR) and in patients with or without diabetic macular edema (DME). METHODS: The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study. The severity of DR patients was graded as mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) according to the international clinical diabetic retinopathy (ICDR) disease severity scale classification, and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods. The presence of DME was determined by optical coherence tomography (OCT), and differences in vascular morphological characteristics were compared between patients with and without DME. RESULTS: Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99% and a Dice metric of 0.76. Compared with the healthy group, the DR group had smaller vessel angles (33.68±3.01 vs 37.78±1.60), smaller fractal dimension (Df) values (1.33±0.05 vs 1.41±0.03), less vessel density (1.12±0.44 vs 2.09±0.36) and fewer vascular branches (206.1±88.8 vs 396.5±91.3), all P

A detrimental feedback loop between hypoxia and oxidative stress consistently drives macrophage polarization toward a pro-inflammatory M1 phenotype, thus persistently aggravating rheumatoid arthritis (RA) progression. Herein, an enzyme-catalyzed nanoplatform with synergistic hypoxia-relieving and reactive oxygen species (ROS)-scavenging properties was developed using bovine serum albumin-bilirubin-platinum nanoparticles (BSA-BR-Pt NPs). Bilirubin was employed to eliminate ROS, while platinum exhibited a synergistic effect in scavenging ROS and simultaneously generated oxygen. In mice RA model, BSA-BR-Pt NPs treatment exhibited superior effects, resulting in significant improvements in joint inflammation, cartilage damage, and bone erosion, compared to methotrexate, the most widely used antirheumatic drug. Mechanistically, RNA-sequencing data and experimental results elucidated that BSA-BR-Pt NPs induced a re-polarization of hypoxic M1 macrophages to M2 macrophages via switching glycolysis to oxidative phosphorylation through the inhibition of HIF-1α pathway. Collectively, this research for the first time elaborated the underlying mechanism of enzyme-catalyzed nanoplatform in orchestrating macrophage polarization, and identified a novel therapeutic strategy for RA and other inflammatory disorders.

In the development of mineral resources and engineering construction in the western region, sandstone is one of the main engineering geological aquifers, and the freezing and thawing environment affects the mechanical and deformation characteristics of sandstone. In order to study the deterioration and damage characteristics of mechanical properties of loaded rocks under the influence of freeze-thaw environment, red fine sandstone in Shaanxi province was taken as the research object, and freeze-thaw cycle tests and uniaxial compression tests were carried out for 0, 5, 10, 20 and 30 times, and the stress-strain curve and mechanical characteristic parameters of the whole uniaxial compression process of frozen-thawed sandstone were obtained. The mechanical characteristic parameters of frozen-thawed rocks were analyzed, and the deterioration model of rock mechanical properties under freeze-thaw environment was established. Based on the influence of freeze-thaw environment on rock damage, considering the characteristics of rock compaction stage in deformation stage, a modified statistical damage constitutive model considering compaction stage is established. The results show that with the increase of freeze-thaw cycles, the proportion of rock compaction stage is increasing, and the peak value should also increase gradually. Brittle failure occurs in the first 30 freeze-thaw cycles, and the brittleness of rock is obviously weakened after 30 freeze-thaw cycles, and the strain softening stage is obvious. The loss rate of mechanical characteristic parameters increased rapidly in the first 10 times of freeze-thaw cycle, and then slowed down obviously. After 30 freeze-thaw cycles, the peak strength loss rate is 47.27% and the elastic modulus loss rate is 60.35%. Among them, the loss rate of mechanical characteristic parameters increases linearly with the number of freeze-thaw cycles, and the mechanical properties of rocks decrease exponentially after freeze-thaw. The peak strength and elastic modulus of rocks under freeze-thaw environment can be accurately predicted by using the pore characteristics of rocks under freeze-thaw environment. The modified statistical damage constitutive model considering the compaction stage has a higher fitting degree with the test curve, and the modified theoretical model can provide reference for the deterioration of mechanical properties and damage prediction of frozen-thawed rocks.

Laser powder bed fusion (LPBF) technology enables personalized customization of medical implants. However, the clinical titanium alloy is biologically inert and can't address bacterial infections. It has been proved that Copper (Cu) -bearing titanium alloys exhibit excellent antibacterial ability and potentials for clinical application. However, it still unclear that the effect of Cu content on the comprehensive properties of LPBF-produced titanium alloy which usually has high strength but poor ductility and corrosion resistance caused by its α′ martensite. This study systematically investigates the effects of Cu content (x = 2, 5, 8 wt%) on the microstructure, mechanical properties, corrosion resistance, antibacterial properties, and cytrocompatibility of the LPBF-produced Ti-xCu alloys. These results prove that the LPBF produced Ti–5Cu alloy possesses the optimal comprehensive performance and has promising clinical application prospects as implant materials.

Abstract Purpose The duration of type 2 diabetes mellitus (T2DM) and blood glucose levels have a significant impact on the development of T2DM complications. However, currently known risk factors are not good predictors of the onset or progression of diabetic retinopathy (DR). Therefore, we aimed to investigate the differences in the serum lipid composition in patients with T2DM, without and with DR, and search for potential serological indicators associated with the development of DR. Methods A total of 622 patients with T2DM hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Xi’an JiaoTong University were selected as the discovery set. One-to-one case–control matching was performed according to the traditional risk factors for DR (i.e., age, duration of diabetes, HbA1c level, and hypertension). All cases with comorbid chronic kidney disease were excluded to eliminate confounding factors. A total of 42 pairs were successfully matched. T2DM patients with DR (DR group) were the case group, and T2DM patients without DR (NDR group) served as control subjects. Ultra-performance liquid chromatography–mass spectrometry (LC–MS/MS) was used for untargeted lipidomics analysis on serum, and a partial least squares discriminant analysis (PLS-DA) model was established to screen differential lipid molecules based on variable importance in the projection (VIP) > 1. An additional 531 T2DM patients were selected as the validation set. Next, 1:1 propensity score matching (PSM) was performed for the traditional risk factors for DR, and a combined 95 pairings in the NDR and DR groups were successfully matched. The screened differential lipid molecules were validated by multiple reaction monitoring (MRM) quantification based on mass spectrometry. Results The discovery set showed no differences in traditional risk factors associated with the development of DR (i.e., age, disease duration, HbA1c, blood pressure, and glomerular filtration rate). In the DR group compared with the NDR group, the levels of three ceramides (Cer) and seven sphingomyelins (SM) were significantly lower, and one phosphatidylcholine (PC), two lysophosphatidylcholines (LPC), and two SMs were significantly higher. Furthermore, evaluation of these 15 differential lipid molecules in the validation sample set showed that three Cer and SM(d18:1/24:1) molecules were substantially lower in the DR group. After excluding other confounding factors (e.g., sex, BMI, lipid-lowering drug therapy, and lipid levels), multifactorial logistic regression analysis revealed that a lower abundance of two ceramides, i.e., Cer(d18:0/22:0) and Cer(d18:0/24:0), was an independent risk factor for the occurrence of DR in T2DM patients. Conclusion Disturbances in lipid metabolism are closely associated with the occurrence of DR in patients with T2DM, especially in ceramides. Our study revealed for the first time that Cer(d18:0/22:0) and Cer(d18:0/24:0) might be potential serological markers for the diagnosis of DR occurrence in T2DM patients, providing new ideas for the early diagnosis of DR.

Abstract Background Gut bacteria, which serve as essential modulators, exert a significant impact on insect physiology and behavior and have substantial application potential in pest management. The dynamics of gut bacteria and their impact on Phortica okadai behavior remain unclear. Methods In this study, the dynamics of gut bacteria at different developmental stages in P. okadai were analyzed using 16S ribosomal RNA (rRNA) gene sequencing, and the species and abundance of gut bacteria that affect host behavior were examined via behavioral experiments. Results A total of 19 phyla, 29 classes, 74 orders, 101 species, and 169 genera were identified. The results of the behavioral experiments indicated that the species Lactiplantibacillus argentoratensis, Acetobacter tropicalis, Leuconostoc citreum, and Levilactobacillus brevis effectively influenced the feeding preference of P. okadai, and the single-bacterium-seeded P. okadai exhibited feeding preferences distinct from those of the germ-free (GF) and wild-type P. okadai. Conclusions The species and relative abundance of gut bacteria together positively impact P. okadai behavior. Lactiplantibacillus argentoratensis, as the most attractive bacteria to P. okadai, presents opportunities for novel pest control strategies targeting this vector and agricultural pest. Graphical Abstract

Abstract Temperature is one of the seven fundamental physical quantities. The ability to measure temperatures approaching absolute zero has driven numerous advances in low-temperature physics and quantum physics. Currently, millikelvin temperatures and below are measured through the characterization of a certain thermal state of the system as there is no traditional thermometer capable of measuring temperatures at such low levels. In this study, we develop a kind of diamond with sp 2-sp 3 composite phase to tackle this problem. The synthesized composite phase diamond (CPD) exhibits a negative temperature coefficient, providing an excellent fit across a broad temperature range, and reaching a temperature measurement limit of 1 mK. Additionally, the CPD demonstrates low magnetic field sensitivity and excellent thermal stability, and can be fabricated into probes down to 1 micron in diameter, making it a promising candidate for the manufacture of next-generation cryogenic temperature sensors. This development is significant for the low-temperature physics researches, and can help facilitate the transition of quantum computing, quantum simulation, and other related technologies from research to practical applications.

Background: Hemoglobin (Hb) has been reported as a prognostic factor in many cancer patients. However, its effect on the prognosis of patients with advanced cancer receiving palliative treatment is still unclear. Objective: The aim of this study was to assess whether Hb can be used as a prognostic indicator for patients with advanced cancer receiving palliative treatment. Methods: From July 2013 to October 2015, 368 consecutive patients were treated in the Palliative Treatment Center of Shanghai Cancer Center, Fudan University. The data of 105 patients were extended in the follow-up. The cutoff value selected for Hb was 100?g/L. Results: The median survival time of patients with low hemoglobin (LHb) was shorter than that of patients with high hemoglobin (HHb; 41 days vs. 84 days). In addition, in the follow-up readmission cohort (n?=?105), the median survival time of patients with HHb (HHb ? HHb) was 3.44 times longer than that of patients with LHb (HHb ? LHb). To sum up, both LHb and descending Hb were identified as independent prognostic factors for poor prognosis. Conclusions: In palliative treatment, Hb can be used as a stratification factor to judge poor prognosis in advanced cancer patients.

Abstract Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.

This study investigates the complex dynamics governing free convection flow in nanofluids under Magnetohydrodynamics (MHD) within a porous medium along an infinite vertical surface. We specifically focus on scenarios involving constant and uniform heat flux as well as heat sources. The governing equations, incorporating the Boussinesq approximation, continuity, and momentum equations, are formulated and solved using Caputo-Fabrizio derivatives and Laplace transforms. This comprehensive approach integrates the Boussinesq approximation and Caputo-Fabrizio fractional derivatives, while the use of Laplace transforms enables precise analytical solutions. Additionally, our investigation highlights the significant impact of nanometer-sized copper particles on fluid properties, transforming the behavior from Newtonian (water-like) to non-Newtonian. This transformation profoundly affects thermal conductivity and velocity behavior within the system. Overall, this research establishes a robust foundation for future studies and provides a framework for exploring non-Newtonian nanofluid systems in the context of MHD-driven free convection flow.

Objective: The objective of this study was to decipher chemical interactions between Danshen and Danggui using liquid chromatography–mass spectrometry (LC-MS) and explore the mechanisms of Danshen–Danggui against stroke using network pharmacology and molecular docking. Materials and Methods: First, the chemical compounds of Danshen–Danggui were profiled using ultra-high-performance liquid chromatography (HPLC)-quadrupole time-of-flight MS. Accurately characterized compounds in various proportions of Danshen–Danggui were quantified using HPLC combined with triple quadrupole electrospray tandem MS. Network pharmacology was used to uncover the essential mechanisms of action of Danshen–Danggui against stroke. Discovery Studio Software was used for the molecular docking verification of key active chemicals and stroke-related targets. Results: A total of 53 compounds were characterized, and 22 accurately identified constituents (10 phenolic acids, 8 phthalides, and 4 tanshinones) were quantified in 15 proportions of Danshen–Danggui. The quantification results showed that Danggui significantly increased the dissolution of most phenolic acids (compounds from Danshen), whereas Danshen promoted the dissolution of most phthalides (compounds from Danggui). Overall, the combination of Danshen and Danggui at a 1:1 ratio resulted in the maximum total dissolution rate. Further network pharmacology and molecular docking results indicated that Danshen–Danggui exerted anti-stroke effects mainly by regulating inflammation-related (tumor necrosis factor, hypoxia-inducible factor, and toll-like receptor) signaling pathways, which ranked among the top three pathways based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Conclusion: The chemical compounds in Danshen–Danggui could interact with each other to increase the dissolution of the most active compounds, which could provide a solid basis for uncovering the compatibility mechanisms of Danshen–Danggui and Danshen–Danggui-based formulae.

Abstract Aim To explore the predictive value of lactate-to-albumin ratio (LAR) on 28-day mortality in patients with exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to the Intensive Care Unit (ICU). Methods According to ICD-9 and ICD-10 diagnosis codes, patients diagnosed with AECOPD in the Medical Information Mart for Intensive Care IV (v.2.2) database were selected. The primary endpoint was 28-day mortality after ICU admission. We used receiver operating characteristic (ROC) curve, Kaplan–Meier (K–M) survival curve, logistic regression analyses and subgroup analysis to assess predictive power of LAR. Results 606 patients were included in this study. The 28-day mortality was 29.7%. The area under the ROC curves (AUC) for LAR were 0.641 [95% confidence interval (CI) 0.592–0.689], which was comparable with OASIS (AUC: 0.662; 95% CI 0.616–0.709; p = 0.471) and SOFA (AUC: 0.660; 95% CI 0.612–0.708; p = 0.500). The cutoff value of LAR was 0.645 by ROC curve. The high-LAR group showed a bad prognosis in K–M analysis (p

Abstract Background Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI. Methods Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism. Results Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C、sK122R、sI126T、sT131P、and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A、sG10D、sF20S、and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure. Conclusions HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.

Abstract Without intervention, a considerable proportion of patients with metabolism‐associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism‐associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1 + Ccr2 + monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1 + Ccr2 + Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1 + Ccr2 + Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

Abstract In classical field theory, radiation does not reflect off of reflectionless kinks. In quantum field theory, radiation quanta, called mesons, can be reflected. We provide a general analytical formula for the leading order amplitude and probability for the elastic scattering of mesons off of reflectionless quantum kinks. In the case of the Sine-Gordon model we verify that, due to a cancellation of six contributing processes, our general formula yields an amplitude of zero, as is required by integrability.

Abstract This study investigated the effects of Lactobacillus-fermented low-protein diet on the growth performance, nitrogen balance, fecal microbiota, and metabolomic profiles of finishing pigs. A total of 90 finishing pigs were assigned to one of three dietary treatments including a normal protein diet (CON) as well as two experimental diets in which a low-protein diet supplemented with 0 (LP) or 1% Lactobacillus-fermented low-protein feed (FLP). In comparison with CON, the LP and FLP significantly increased average daily gain (P = 0.044), significantly decreased feed to gain ratio (P = 0.021), fecal nitrogen (P

Abstract Objective To compare the fluid resuscitation effect of sodium acetate Ringer’s solution and sodium bicarbonate Ringer’s solution on patients with traumatic haemorrhagic shock. Method We conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer’s solution group and sodium acetate Ringer’s solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients’ vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3 −), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation. Results The post-resuscitation heart rate of the sodium bicarbonate Ringer’s solution group was significantly lower than that of the sodium acetate Ringer’s solution group (p

Abstract B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb–defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb–defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb–defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage–associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb–defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.

This study aims to propose a decision-making method based on artificial potential fields (APFs) and finite state machines (FSMs) in emergency conditions. This study presents a decision-making method based on APFs and FSMs for emergency conditions. By modeling the longitudinal and lateral potential energy fields of the vehicle, the driving state is identified, and the trigger conditions are provided for path planning during lane changing. In addition, this study also designed the state transition rules based on the longitudinal and lateral virtual forces. It established the vehicle decision-making model based on the finite state machine to ensure driving safety in emergency situations. To illustrate the performance of the decision-making model by considering APFs and finite state machines. The version of the model in the co-simulation platform of MATLAB and CarSim shows that the developed decision model in this study accurately generates driving behaviors of the vehicle at different time intervals. The contributions of this study are two-fold. A hierarchical vehicle state machine decision model is proposed to enhance driving safety in emergency scenarios. Mathematical models for determining the transition thresholds of lateral and longitudinal vehicle states are established based on the vehicle potential field model, leading to the formulation of transition rules between different states of autonomous vehicles (AVs).

Abstract Background The prognosis of patients with light‐chain amyloidosis (AL) has improved markedly in the past decade in China; whether the current staging systems are suitable to predict the overall survival (OS) of the patients remains undetermined. Methods Based on 980 biopsy‐proved AL patients with 5‐year follow‐up from China Registration Network for Light‐chain Amyloidosis, we evaluated the efficacy of existing staging systems and developed a new stratification model. This involved analyzing parameters such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) thresholds and estimated glomerular filtration rate (eGFR). Results We found that 30% patients were classified as stage I, 25% as stage II, 26% as stage III, and 19% as stage IV disease using the Mayo 2012 staging system, with varying median OS values. However, the observed median OS values were notably higher than previously reported. By incorporating NT‐proBNP thresholds and eGFR values, we developed a four‐stage score system. With this new model, 41.6% patients were reclassified to stage I, 34.3% to stage II, 17.8% to stage III, and 6.3% to stage IV disease, with adjusted median OS values. Conclusion The new stratification model exhibited improved consistency compared to traditional staging systems. It effectively identified patients with the best and worst prognoses, even among those receiving comprehensive treatment. Specifically, NT‐proBNP levels exceeding 9000 pg/mL combined with an eGFR less than 60 mL/min/1.73 m2 proved superior in prognosticating patient outcomes. Overall, the median OS of AL amyloidosis patients in China has significantly improved, underscoring the need for tailored prognostic models in clinical practice.

Objective: DNA damage response (DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation (DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor (ICI) therapy in gastrointestinal (GI) cancer. Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts. Results: The DRIA signature includes three genes (CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients (81.8% vs. 8.8%; P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve (AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer. Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pan-cancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Accurate atmospheric 3D wind observations are one of the top priorities for the global scientific community. To address this requirement, and to support researchers’ needs to acquire and analyze wind data from multiple sources, the System for Analysis of Wind Collocations (SAWC) was jointly developed by NOAA/NESDIS/STAR, UMD/ESSIC/CISESS, and UW-Madison/CIMSS. SAWC encompasses the following: a multi-year archive of global 3D winds observed by Aeolus, sondes, aircraft, stratospheric superpressure balloons, and satellite-derived atmospheric motion vectors, archived and uniformly formatted in netCDF for public consumption; identified pairings between select datasets collocated in space and time; and a downloadable software application developed for users to interactively collocate and statistically compare wind observations based on their research needs. The utility of SAWC is demonstrated by conducting a one-year (September 2019–August 2020) evaluation of Aeolus level-2B (L2B) winds (Baseline 11 L2B processor version). Observations from four archived conventional wind datasets are collocated with Aeolus. The recommended quality controls are applied. Wind comparisons are assessed using the SAWC collocation application. Comparison statistics are stratified by season, geographic region, and Aeolus observing mode. The results highlight the value of SAWC’s capabilities, from product validation through intercomparison studies to the evaluation of data usage in applications and advances in the global Earth observing architecture.

Abstract Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to pose a severe global health burden. Thus, we developed a chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 and influenza virus. When used as a standalone vaccine, intranasal immunization with AdC68-HATRBD induced comprehensive and potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, and memory T cells, which protected the mice from BA.5.2 and pandemic H1N1 infections. When used as a heterologous booster, AdC68-HATRBD markedly improved the protective immune response of the licensed SARS-CoV-2 or influenza vaccine. Therefore, whether administered intranasally as a standalone or booster vaccine, this combination vaccine is a valuable strategy to enhance the overall vaccine efficacy by inducing robust systemic and mucosal immune responses, thereby conferring dual lines of immunological defenses for these two viruses.