Search

Abstract The otopetrin (OTOP) proteins were recently characterized as extracellular proton-activated proton channels. Several recent OTOP channel structures demonstrated that the channels form a dimer with each subunit adopting a double-barrel architecture. However, the structural mechanisms underlying some basic functional properties of the OTOP channels remain unresolved, including extracellular pH activation, proton conducting pathway, and rapid desensitization. In this study, we performed structural and functional characterization of the Caenorhabditis elegans OTOP8 (CeOTOP8) and mouse OTOP2 (mOTOP2) and illuminated a set of conformational changes related to the proton-conducting process in OTOP. The structures of CeOTOP8 reveal the conformational change at the N-terminal part of TM12 that renders the channel in a transiently proton-transferring state, elucidating an inter-barrel, Glu/His-bridged proton passage within each subunit. The structures of mOTOP2 reveal the conformational change at the N-terminal part of TM6 that exposes the central glutamate to the extracellular solution for protonation. In addition, the structural comparison between CeOTOP8 and mOTOP2, along with the structure-based mutagenesis, demonstrates that an inter-subunit movement at the OTOP channel dimer interface plays a central role in regulating channel activity. Combining the structural information from both channels, we propose a working model describing the multi-step conformational changes during the proton conducting process.

Abstract This study investigates how dynamic fluctuations in matrix stiffness affect the behavior of cardiac fibroblasts (CFs) within a three-dimensional (3D) hydrogel environment. Using hybrid hydrogels with tunable stiffness, we created an in vitro model to mimic the varying stiffness of the cardiac microenvironment. By manipulating hydrogel stiffness, we examined CF responses, particularly the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation. Our findings reveal that increased matrix stiffness promotes the differentiation of CFs into myofibroblasts, while matrix softening reverses this process. Additionally, we identified the role of focal adhesions and integrin β1 in mediating stiffness-induced phenotypic switching. This study provides significant insights into the mechanobiology of cardiac fibrosis and suggests that modulating matrix stiffness could be a potential therapeutic strategy for treating cardiovascular diseases.

Abstract Excessive scar formation such as hypertrophic scars and keloids, resulting from trauma or surgical procedures, present a widespread concern for causing disfigurement, discomfort, and functional limitations. Macrophages play pivotal roles in maintaining tissue homeostasis, orchestrating tissue development, repair, and immune responses, and its transition of function and phenotype plays a critical role in regulating the balance between inflammation and tissue regeneration, which is central to cutaneous scar formation. Recent evidence suggests the involvement of Sonic Hedgehog (SHH) in the induction of anti-inflammatory M2-like macrophage phenotypes within tumor microenvironments. In our study, we observed increased SHH expression in human hypertrophic scars, prompting an investigation into its influence on macrophage polarization, efferocytosis, and cutaneous scar formation. Our findings reveal that SHH can enhance oxidative phosphorylation (OXPHOS) in macrophages, augment macrophage efferocytosis, and promote M2 polarization, finally contributing to the progression of cutaneous scar formation. Notably, targeting SHH signaling with vismodegib exhibited promising potential in mitigating scar formation by reversing the effects of enhanced OXPHOS and M2 polarization in macrophages. In conclusion, this study underscores the critical roles of macrophage metabolism, particularly OXPHOS, efferocytosis and SHH signaling in cutaneous scar formation. Understanding these mechanisms provides new avenues for potential interventions and scar prevention strategies.

Abstract Introduction This study aimed to analyze the risk factors associated with isoniazid-resistant and rifampicin-susceptible tuberculosis (Hr-TB) in adults. Method The clinical data of 1,844 adult inpatients diagnosed with culture-positive pulmonary tuberculosis (PTB) in Nanjing Second Hospital from January 2019 and December 2021 were collected. All culture positive strain from the patient specimens underwent drug susceptibility testing (DST). Among them, 166 patients with Hr-TB were categorized as the Hr-TB group, while the remaining 1,678 patients were classified as having drug-susceptible tuberculosis (DS-TB). Hierarchical logistic regression was employed for multivariate analysis to identify variables associated with Hr-TB. Results: Multivariate logistic regression analysis revealed that individuals with diabetes mellitus (DM) (OR 1.472, 95% CI 1.037–2.088, p = 0.030) and a history of previous tuberculosis treatment (OR 2.913, 95% CI 1.971–4.306, p = 0.000) were at higher risk of developing adult Hr-TB, with this risk being more pronounced in male patients. Within the cohort, 1,640 patients were newly treated, and among them, DM (OR 1.662, 95% CI 1.123–2.461, p = 0.011) was identified as risk factors for Hr-TB. Conclusions: Diabetes mellitus is a risk factor for Hr-TB in adults, and the contribution of diabetes as a risk factor was more pronounced in the newly treatment or male subgroup. And previous TB treatment history is also a risk factor for Hr-TB in adults.

For engineering structures with saline soil as a filling material, such as channel slope, road subgrade, etc., the rich soluble salt in the soil is an important potential factor affecting their safety performance. This study examines the Atterberg limits, shear strength, and compressibility of carbonate saline soil samples with different NaHCO3 contents in Northeast China. The mechanism underlying the influence of salt content on soil macroscopic properties was investigated based on a volumetric flask test, a mercury intrusion porosimetry (MIP) test, and a scanning electron microscopic (SEM) test. The results demonstrated that when NaHCO3 contents were lower than the threshold value of 1.5%, the bound water film adsorbed on the surface of clay particles thickened continuously, and correspondingly, the Atterberg limits and plasticity index increased rapidly as the increase of sodium ion content. Meanwhile, the bonding force between particles was weakened, the dispersion of large aggregates was enhanced, and the soil structure became looser. Macroscopically, the compressibility increased and the shear strength (mainly cohesion) decreased by 28.64%. However, when the NaHCO3 content exceeded the threshold value of 1.5%, the salt gradually approached solubility and filled the pores between particles in the form of crystals, resulting in a decrease in soil porosity. The cementation effect generated by salt crystals increased the bonding force between soil particles, leading to a decrease in plasticity index and an improvement in soil mechanical properties. Moreover, this work provides valuable suggestions and theoretical guidance for the scientific utilization of carbonate saline soil in backfill engineering projects.

Abstract Product assembly involves extensive production data that is characterized by high dimensionality, multiple samples, and data imbalance. The article proposes an edge computing-based framework for monitoring product assembly quality in industrial Internet of Things. Edge computing technology relieves the pressure of aggregating enormous amounts of data to cloud center for processing. To address the problem of data imbalance, we compared five sampling methods: Borderline SMOTE, Random Downsampling, Random Upsampling, SMOTE, and ADASYN. Finally, the quality monitoring model SMOTE-XGBoost is proposed, and the hyperparameters of the model are optimized by using the Grid Search method. The proposed framework and quality control methodology were applied to an assembly line of IGBT modules for the traction system, and the validity of the model was experimentally verified.

Abstract Objective This study aimed to compare the per OPU clinical outcomes for transfer of Day 3 double cleavage-stage embryos (DET) and Day 5 single blastocyst-stage (SBT) in patients with five or fewer good quality embryos on day 3 per occyte pick-up cycle (OPU) in antagonist cycles with consideration of blastocyst formation failure. Methods This was a retrospective, observational cohort study of 2,116 cases of OPU treated with antagonist protocol in the affiliated Chenggong Hospital of Xiamen University between January 2013 and December 2020. DET was performed in 1,811cycles and SBT was performed in 305 cycles. The DET group was matched to the SBT group by propensity score (PS) matching according to multiple maternal baseline covariates. After PS matching, there were 303 ET cycles in each group. The primary outcomes were the cumulative live birth rate (CLBR), cumulative multiple pregnancy rate(CMPR)per OPU and the number of ET to achieve live birth per OPU. Secondary outcomes were the percentage of clinical pregnancy(CPR), live birth rate(LBR), multiple pregnancy rate(MPR). Results Following PS mating, the CLBR was slightly higher (48.8% versus 40.3% ; P = 0.041) and the CMPR was significantly higher in the DET group compared to SBT group(44.2% versus 7.9%, P

BackgroundThe standardized extract of milk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)-induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms.MethodsA model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (Reactive Oxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides.ResultsPM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II.ConclusionSilibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II.

ObjectiveNanotechnology offers many advantages in various fields of cancer therapy. This study describes a new method of self-forming nanoparticles (self-nano) using ferric chloride (FeCl₃) and hydrogen peroxide (H2O2) to form the self-nanoparticles in an in vivo tumor. The treatment effect is evaluated.MethodA solution of 3% FeCl3 (0.5 mL) and 1.8% H2O2 (1.0 mL) was injected into the tumor. At various time points post-injection, tumors were collected, and sections were prepared for electron microscopy to evaluate the size of the self-nano particles. Single-cell RNA sequencing (scRNA-seq) was used to analyze the immune changes and their effect on tumor growth.ResultThe formation of self-nano in vitro was observed and confirmed, with particles averaging 421 nm in size for the FeCl3 + H2O2 solution. Over time points ranging from 1 to 14 days, the formed self-nano remained stable at a regular size of 421 ± 8 nm. The self-nano, primarily consisting of iron, induced ferroptosis under the influence of an external magnetic field, leading to tumor growth control through iron-induced cell death and immune reactions. These self-nanoparticles also showed stronger enrichment of pathways related to CD8+ T effect cells (Teff), T cell activation, and regulation of T cell proliferation.ConclusionThe FeCl3 + H2O2 solution can form Fe₂O₃-based self-nanoparticles within tumors through H2O2-incubated oxidation of FeCl3. The self-nano remains effective for over 14 days, inducing ferroptosis and upregulating immune cells under magnetic field treatment. This method offers a novel approach for cancer treatment that can be combined with other modalities.

BackgroundSystemic immune-inflammation index (SII) is associated with increased risk in a wide range of illnesses. However, few studies have explored the associations between SII and the risk of malnutrition. Therefore, this study aimed to investigate the association between SII and malnutrition in a nationwide, multicenter, cross-sectional study involving Chinese hospitalized patients.DesignFrom August 2020 to August 2021, a total of 40,379 hospitalized patients met the inclusion and exclusion criteria. Detailed demographic data, diagnoses, as well as physical and laboratory examination results were recorded. The diagnosis of malnutrition was used with two distinct methods: the Malnutrition Screening Tool 2002 (NRS 2002) + Global Leaders Initiative on Malnutrition (GLIM) criteria and the controlling nutritional status (CONUT) score. The risk factors for malnutrition were analyzed using binary logistic regression and multiple logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI). Restricted cubic spline (RCS), linear spline, and receiver operating characteristic (ROC) analysis were also used.ResultsThe prevalence of malnutrition diagnosed by the two methods was 13.4% and 14.9%, respectively. In the NRS 2002 + GLIM diagnostic model, lnSII showed statistical significance between the malnutrition and non-malnutrition group (6.28 ± 0.78 vs. 6.63 ± 0.97, p

Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.

ObjectiveThe aim of this is to explore changes in cross-modal reorganization within the auditory–visual cortex after cochlear implantation, examining their influence on auditory and speech functions along with their underlying mechanisms.MethodsTwenty prelingually deaf children who received cochlear implantation and rehabilitation training at our hospital between February 2022 and February 2023 comprised the prelingual deaf group. Simultaneously, 20 healthy children served as the control group. The prelingual deaf group underwent brain cortical activity assessment and evaluation of auditory-speech recovery pre-surgery, at postoperative weeks 1 and 2, and at months 1, 3, 6, 9, and 12. The control group underwent parallel assessments and evaluations. We analyzed the correlation between cortical activity in the auditory–visual cortex of patients and their auditory-speech functional recovery.ResultsThe group with prelingual deafness displayed elevated levels of auditory and visual cortical electromagnetic intensity compared to the control group, both prior to and 9 months after surgery. However, by the 12-month mark post-surgery, there was no discernible distinction between the two groups. Following surgery, the prelingually deaf group exhibited a progressive improvement in both Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR), initially lagging behind the control group. Notably, a negative correlation emerged between auditory and visual cortical electromagnetic intensity values and CAP/SIR scores at the 12-month post-surgery assessment.ConclusionCochlear implantation in prelingually deaf children results in elevated activity within the auditory and visual cortices, demonstrated by heightened electromagnetic intensity readings. Cross-modal reorganization is observed temporarily at 3 months post-surgery, which resolves to baseline levels by 12 months post-surgery. This phenomenon of reversal correlates with the restoration of auditory and speech functions in these children.

The food lifestyle has evolved from the regional differences that were previously shaped by different geographic locations to the pluralistic complexity of food styles that are now influenced by different user consciousnesses. The field of food design has assumed a greater social responsibility, while also facing the challenge of sustainable development. Consequently, it is of paramount importance to devise or refine the methodology of food design innovation. This study makes a significant contribution to the field of sustainable food design by combining design methodology with sociological concepts such as “Field and Habitus” to construct the “F-U-BVF” food lifestyle analysis framework. This study examines the applicability of the F-U-BVF analytical framework, exemplified by tofu, through the refinement and translation of user needs, among other methods. The objective is to guide users toward sustainable lifestyles based on a design methodology, thereby creating multiple values conducive to food sustainability. At the same time, the deconstruction of the structural relationship, process, and methodology of sustainable food design based on the F-U-BVF analytical framework is intended to break through the barriers of traditional design science. This is to provide a new systematic research paradigm for sustainable food design, as well as to provide a new perspective on the experience and interactive relationship between people and food. Finally, it is also to provide effective food design innovation solutions for relevant multi-stakeholders. This is of great significance for the development of sustainable food design.

IntroductionAngong Niuhuang Wan (AGNHW), developed during the Qing dynasty (18th century) for the treatment of consciousness disturbances caused by severe infections, has been used to treat brain edema caused by ischemia‒reperfusion. However, it remains unclear whether AGNHW can ameliorate vascular-origin brain edema caused by lipopolysaccharides (LPS). This study explored the ameliorative effects of AGNHW on LPS-induced cerebrovascular edema in mice, as well as the potential underlying mechanisms.MethodsA cerebrovascular edema model was established in male C57BL/6N mice by two intraperitoneal injections of LPS (15 mg/kg), at 0 and 24 h. AGNHW was administered by gavage at doses of 0.2275 g/kg, 0.455 g/kg, and 0.91 g/kg, 2 h after LPS administration. In control mice, normal saline (NS) or AGNHW (0.455 g/kg) was administered by gavage 2 h after intraperitoneal injection of NS. The survival rate, cerebral water content, cerebral venous FITC-dextran leakage, Evans blue extravasation, and expression of vascular endothelial cadherin (VE-cadherin), zonula occludens-1 (ZO-1), claudin-5, phosphorylated caveolin-1 (CAV-1), and cytomembrane and cytoplasmic aquaporin 1 (AQP1) and aquaporin 4 (AQP4) were evaluated. The cerebral tissue phosphoproteome, blood levels of AGNHW metabolites, and the relationships between these blood metabolites and differentially phosphorylated proteins were analyzed.ResultsAGNHW inhibited the LPS-induced decrease in survival rate, increase in cerebral water content, decrease in VE-Cadherin expression and increase in phosphorylated CAV-1 (P-CAV-1). AGNHW treatment increased the expression of AQP4 on astrocyte membrane after LPS injection. AGNHW also inhibited the LPS-induced increases in the phosphorylation of 21 proteins, including protein kinase C-α (PKC-α) and mitogen-activated protein kinase 1 (MAPK1), in the cerebral tissue. Eleven AGNHW metabolites were detected in the blood. These metabolites might exert therapeutic effects by regulating PKC-α and MAPK1.ConclusionAGNHW can ameliorate cerebrovascular edema caused by LPS. This effect is associated with the inhibition of VE-Cadherin reduction and CAV-1 phosphorylation, as well as the upregulation of AQP4 expression on the astrocyte membrane, following LPS injection.

The purpose of this paper was to introduce several $ b $-generalized contractive mappings in the framework of cone $ b $-metric spaces over Banach algebras. The obtained contractions generalized and extended the counterparts in metric spaces, cone metric spaces, and $ b $-metric spaces. Moreover, via weakening the completeness of the spaces, we gave some fixed point theorems for asymptotically regular mappings without considering the orbital continuity and $ k $-continuity of the mappings. Those who need a specification is our results do not rely on the continuity of $ b $-metric and the normality of cones. In addition, some nontrivial examples were presented to illustrate the superiority of our fixed point theorems.

Abstract. Background:. Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve. Methods:. Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University. Results:. 3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) (n = 2) or risk of compression coronary artery (n = 2). Concerning sizing, we found that an oversize of 2–5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P

Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.

Abstract Since probability hypothesis density (PHD) filters do not need explicit data association, they have recently been widely used in radar multi-target tracking (MTT). However, in existing PHD filters, sampling times are generally considered the same for all targets. Due to the limitation of antenna beam width in radar applications, the same sampling time for all targets will lead to a mismatch between the predicted data and measurement data, reducing the accuracy of radar MTT. In order to eliminate the estimation error with less computational cost, a radar nonlinear multi-target tracking method with a parallel PHD filter is proposed in this article. The measurement area is divided into several subspaces according to the beam width of the radar antenna, and the PHD of all subspaces is calculated in parallel. Then, multi-feature information in radar echo assists tracking and improves real-time performance. Experimental results in various scenarios illustrate that the proposed method can eliminate the estimation errors introduced by sampling time diversity at the cost of less computation cost, especially in cluttered environments.

Abstract Objective The medical instruments used in the emergency department have a wide coverage and prominent importance. The study was aimed to observe the effect of joint commission international (JCI) standard combined with 6S management mode in emergency medical equipment. Methods Medical equipment and nursing staff in the emergency department of our hospital were the subjects of the research. We compared the management status (standard placement, good cleaning, good maintenance, complete records) of medical equipment after the application of JCI standard combined with 6S management mode was compared with that before the application. Working time associated with medical equipment, equipment repair ratio, nurses' satisfaction with medical equipment use and management were also compared. Results After the application of JCI standard combined with 6S management mode, the proportion of instances meeting standards for placement, cleaning, maintenance, and record‐keeping was higher than before the application (p 0.05). Conclusion JCI standard combined with 6S management mode can standardize the use of emergency medical instruments, reduce the risk of instrument damage, increase work efficiency, improve nurses' satisfaction with medical instrument management, and are therefore worthy of clinical application.

Objective The objective of this study was to thoroughly investigate the clinical value of triglyceride glucose-body mass index (TyG-BMI) in patients diagnosed with non-alcoholic fatty liver disease (NAFLD). Specifically, we aimed to determine its association with non-alcoholic steatohepatitis (NASH) and the progression of liver fibrosis.Methods The study included 393 patients diagnosed with NAFLD after liver biopsy. The patients were divided into two distinct cohorts: a training cohort (N = 320) and a validation cohort (N = 73). The training cohort was further divided into four groups based on TyG-BMI quartiles. The clinical characteristics of the patients in each group were compared in detail, and the association between TyG-BMI and NASH, NAFLD Activity Score (NAS) ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis was analyzed using multiple models. Additionally, we generated receiver operating characteristic (ROC) curves to evaluate the predictive ability of TyG-BMI for NASH and fibrosis staging in patients with NAFLD.Results Patients with higher TyG-BMI values had a significantly higher prevalence of NASH, NAS ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis (all p

AbstractBackground and Aim This study aims to validate the efficacy of the conventional non-invasive score in predicting significant fibrosis in metabolic-associated fatty liver disease (MAFLD) and to develop a non-invasive prediction model for MAFLD.Methods This cross-sectional study was conducted among 7701 participants with MAFLD from August 2018 to December 2023. All participants were divided into a training cohort and a validation cohort. The study compared different subgroups’ demographic, anthropometric, and laboratory examination indicators and conducted logistic regression analysis to assess the correlation between independent variables and liver fibrosis. Nomograms were created using the logistic regression model. The predictive values of noninvasive models and nomograms were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).Results Four nomograms were developed for the quantitative analysis of significant liver fibrosis risk based on the multivariate logistic regression analysis results. The nomogram’s area under ROC curves (AUC) was 0.710, 0.714, 0.748, and 0.715 in overall MAFLD, OW-MAFLD, Lean-MAFLD, and T2DM-MAFLD, respectively. The nomogram had a higher AUC in all MAFLD participants and OW-MAFLD than the other non-invasive scores. The DCA curve showed that the net benefit of each nomogram was higher than that of APRI and FIB-4. In the validation cohort, the AUCs of the nomograms were 0.722, 0.750, 0.719, and 0.705, respectively.Conclusion APRI, FIB-4, and NFS performed poorly predicting significant fibrosis in patients with MAFLD. The new model demonstrated improved diagnostic accuracy and clinical applicability in identifying significant fibrosis in MAFLD.

BackgroundHepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a syn-drome with a high short-term mortality rate, and its prognosis is critical in clinical management. This study aimed to investigate the clinical significance of glutathione peroxidase 4 (GPX4) in the occurrence and development of HBV-ACLF and its prognostic value for 90-day mortality.MethodsThe expression levels of GPX4, oxidative stress-related molecules and inflammatory cytokines in serum or peripheral blood mononuclear cells (PBMCs) of 289 participants were determined by RT-qPCR or ELISA, and the methylation level of GPX4 promoter in PBMCs was determined by MethyLight.ResultsThe expression levels of GPX4 in the PBMCs and serum of HBV-ACLF patients were lower than those in non-HBV-associated acute-on-chronic liver failure (non-HBV ACLF) patients, patients with chronic hepatitis B (CHB) and healthy control (HC) individuals, while the methylation level of the GPX4 promoter was greater. In HBV-ACLF patients, the methylation level of the GPX4 promoter is correlated with oxidative stress, inflammation-related molecules, and some clinicopathological indicators. The methylation level of the GPX4 promoter was identified as an independent risk factor for 90-day mortality in HBV-ACLF patients and yielded a larger area under the receiver operating characteristic curve (AUROC) than the model for end-stage liver disease (MELD) score in predicting 90-day mortality.ConclusionThe GPX4 promoter methylation level has promising potential as a predictor of 90-day mortality in patients with HBV-ACLF.

This paper aims to comprehensively define village social capital, assess its multifaceted dimensions in relation to farmers’ entrepreneurial decision-making, and investigate the mediating role of rural development. The research sample consists of 14,133 farmers selected through a multi-stage proportional-to-size unequal probability sampling method. Data collection was carried out using questionnaires as part of the “Chinese Thousand Village Survey” project. Empirical analysis was conducted using binary logit and basic linear regression models, supplemented by probit models and other robustness testing methods. The findings indicate that village social capital exerts a significant and favorable influence on farmers’ entrepreneurial decision-making. Controlling for other variables, a unit increment in farmers’ village social network, village social participation, and village social trust is associated with a respective increase in farmers’ odds of entrepreneurial decision-making by 3.96, 5.42, and 16.28%. Village social trust emerges as the most influential factor. Additionally, rural harmony and rural economy partially mediate the relationship between village social capital and farmers’ entrepreneurial decision-making. This study contributes to a deeper understanding of the complex interplay between village social capital and farmers’ entrepreneurial decision-making, offering valuable guidance for farmers looking to leverage village social capital in their entrepreneurial endeavors. It lays a theoretical foundation for relevant entities to strengthen village social capital and cultivate a supportive environment for rural entrepreneurship. To our knowledge, this paper is among the earlier studies that investigate farmers’ entrepreneurial decision-making. Besides, the relationship between village social capital and rural development is rarely studied in the literature as two determinants of farmers’ entrepreneurial decision-making.

This study aims to investigate the influence of pre-entrepreneurial career mobility frequency and job changes among returning migrant workers (RMWs) on the innovation level of enterprises, with a particular focus on the mediating role of urban social capital accumulated by RMWs. Using data from the “current entrepreneurial status of RMWs”, we applied an ordered probit model to validate our hypotheses. To address endogeneity, a recursive bivariate probit model was used, and stepwise regression combined with bootstrap methods was employed to ascertain the mediating influence of urban social capital. Our results demonstrate a significant positive correlation (P