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Abstract Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by multilineage immune dysregulation, which subsequently causes inflammation, fibrosis, and even cirrhosis of liver. Due to the limitation of traditional assays, the local hepatic immunopathogenesis of PBC has not been fully characterized. Here, we utilize single-cell RNA sequencing technology to depict the immune cell landscape and decipher the molecular mechanisms of PBC patients. We reveal that cholangiocytes and hepatic stellate cells are involved in liver inflammation and fibrosis. Moreover, Kupffer cells show increased levels of inflammatory factors and decreased scavenger function related genes, while T cells exhibit enhanced levels of inflammatory factors and reduced cytotoxicity related genes. Interestingly, we identify a liver-resident Th1-like population with JAK-STAT activation in the livers of both PBC patients and murine PBC model. Finally, blocking the JAK-STAT pathway alleviates the liver inflammation and eliminates the liver-resident Th1-like cells in the murine PBC model. In conclusion, our comprehensive single-cell transcriptome profiling expands the understanding of pathological mechanisms of PBC and provides potential targets for the treatment of PBC in patients.

Abstract Background Although gray matter (GM) volume alterations have been extensively documented in previous voxel-based morphometry studies on vestibular migraine (VM), little is known about the impact of this disease on the topological organization of GM morphological networks. This study investigated the altered network patterns of the GM connectome in patients with VM. Methods In this study, 55 patients with VM and 57 healthy controls (HCs) underwent structural T1-weighted MRI. GM morphological networks were constructed by estimating interregional similarity in the distributions of regional GM volume based on the Kullback–Leibler divergence measure. Graph-theoretical metrics and interregional morphological connectivity were computed and compared between the two groups. Partial correlation analyses were performed between significant GM connectome features and clinical parameters. Logistic regression (LR), support vector machine (SVM), and random forest (RF) classifiers were used to examine the performance of significant GM connectome features in distinguishing patients with VM from HCs. Results Compared with HCs, patients with VM exhibited increased clustering coefficient and local efficiency, as well as reduced nodal degree and nodal efficiency in the left superior temporal gyrus (STG). Furthermore, we identified one connected component with decreased morphological connectivity strength, and the involved regions were mainly located in the STG, temporal pole, prefrontal cortex, supplementary motor area, cingulum, fusiform gyrus, and cerebellum. In the VM group, several connections in the identified connected component were correlated with clinical measures (i.e., symptoms and emotional scales); however, these correlations did not survive multiple comparison corrections. A combination of significant graph- and connectivity-based features allowed single-subject classification of VM versus HC with significant accuracy of 77.68%, 77.68%, and 72.32% for the LR, SVM, and RF models, respectively. Conclusion Patients with VM had aberrant GM connectomes in terms of topological properties and network connections, reflecting potential dizziness, pain, and emotional dysfunctions. The identified features could serve as individualized neuroimaging markers of VM.

Abstract The occurrence of multiple primary lung cancer (MPLC) has witnessed a significant surge in recent years within the Chinese population. MPLC is distinguished by its potential genetic susceptibility and notable genetic heterogeneity. Investigating the etiology of MPLC holds substantial clinical importance.The whole genome sequencing (WGS) and genome-wide linkage analysis were performed in a family affected by a dominant form of lung abnormalities. Specifically, five family members were diagnosed with MPLC, while nine members had pulmonary nodules and one normal member. To confirm the potential pathogenic germline mutations sites, Sanger sequencing was performed in an additional 162 MPLC family patients. Furthermore, molecular biology experiments were conducted to investigate the function and the mechanism of the identified pathogenic mutation site in lung cancer A549 and H322, both in vitro and in vivo. Linkage analysis revealed the presence of shared genomic regions among affected family members. Subsequent exome sequencing identified a deleterious variant within these linkage intervals, specifically a heterozygous mutation in ETS-oncogene transcription factors 4 (ETV4). This particular variant was found in affected family members at a rate of 13 out of 15 individuals. Furthermore, ETV4 P433L mutation could be detected in an additional MPLC family patients and mutation frequency was 3.7% (6 out of 162). The ETV4 P433L mutations site was introduced into lung cancer cell lines, resulting in altered migration and stem-like properties of the cancer cells. Further investigation revealed that the activation of the Wnt/β-catenin signaling pathway, which is associated with stemness, could be attributed to the presence of the ETV4 P433L mutation, suggesting its involvement in tumor promotion. A novel pathogenic germline mutation, ETV4 P433L, was identified in a dominant MPLC family, with a mutation rate of 3.7% among MPLC family patients. The ETV4 P433L mutation was found to impact the stem-like properties and migration of tumors through Wnt/β-catenin signaling pathway.

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

Abstract Background The tumor microenvironment (TME) is a dynamic system orchestrated by intricate cell-to-cell crosstalk. Specifically, macrophages within the TME play a crucial role in driving tumor progression. Exosomes are key mediators of communication between tumor cells and the TME. However, the mechanisms underlying exosome-driven crosstalk between tumor cells and macrophages during colorectal cancer (CRC) progression remain incompletely elucidated. Methods Single-cell RNA sequencing were analyzed using the Seurat package. Exosomes were isolated using ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blot. miRNAs differentially expressed in exosomes were analyzed using the limma package. CD206 expression in CRC tissues, exosomes tracing, and exosomal miR-106a-5p transport were observed through immunofluorescence. Macrophage polarization was assessed via qRT-PCR, ELISA, and flow cytometry. The interactions between miR-106a-5p, hnRNPA1, and SOCS6 were evaluated using miRNA pull-down, RIP, and dual-luciferase reporter assays. Transwell assays and liver metastasis model explored the role of exosomal miR-106a-5p-induced M2 macrophages in promoting CRC liver metastasis. Result The proportion of M2 macrophages is increased in CRC with liver metastasis compared to those without. Highly metastatic CRC cells release exosomes enriched with miR-106a-5p, which promote macrophages M2 polarization by suppressing SOCS6 and activating JAK2/STAT3 pathway. These M2 macrophages reciprocally enhance CRC liver metastasis. hnRNPA1 regulate the transport of miR-106a-5p into exosomes. Clinically, elevated miR-106a-5p in plasma exosomes correlated with liver metastasis and poor prognosis. Conclusion CRC-derived exosomal miR-106a-5p plays a critical role in promoting liver metastasis and is a potential biomarker for the prevention and treatment of CRC liver metastasis.

The design idea of emphasizing application and neglecting defense leads to the lack of endogenous security attributes at the beginning of the design of transmission control protocol/Internet protocol (TCP/IP) architecture. Public key infrastructure (PKI), as an authoritative security governance framework to realize the authenticity, integrity, confidentiality and non-repudiation of communication between different entities on the Internet, has attracted much attention since it was proposed, which has also become the focus of researchers in recent years because of single point of failure and single trust and other security threats caused by the centralized mechanism of PKI. With the gradual application of blockchain technology in the field of information security, it has become a research direction and focus to use the characteristics of decentralization, distributed ledger, tamper-proof, openness and transparency of blockchain to solve various security problems arising in the native PKI and its evolution. According to the application and development of PKI and blockchain, the methods to solve PKI security are divided into the solutions based on Web of trust (WoT) technology and certificate transparency (CT) mechanism, which do not rely on blockchain, the centralized PKI solutions integrated with blockchain technology, which retain the core function of certificate authority (CA), and the decentralized PKI schemes based on blockchain, which completely replace the CA function with blockchain. Firstly, the security status of the original PKI is introduced, and the methods using WoT technology and CT mechanism to transform the security of the original PKI are discussed respectively. Then, the design ideas of centralized PKI integrated with blockchain technology and decentralized PKI based on blockchain are analyzed. Some typical application scenarios are selected to analyze their implementation methods and application characteristics. Finally, the application research of blockchain in PKI security is prospected.

Abstract Asthma and lung cancer are both significant public health concerns worldwide. Previous observational studies have indicated a potential link between asthma and an increased risk of lung cancer, whereas the causal relationship remains uncertain. We aimed to investigate the potential causal relationship between asthma and lung cancer risk utilizing Mendelian randomization (MR) design.The present study employed a two-sample MR analysis utilizing summary statistics from genome-wide association studies (GWAS) with European descent of asthma and lung cancer. The MR analysis was performed using inverse variance weighting (IVW), supplemented with MR-Egger regression and weighted median method to investigate the potential causality between asthma and lung cancer. Furthermore, Sensitivity analyses were also conducted to ensure the reliability of the findings. The MR analysis showed that genetically predicted asthma had suggestive causal association with the elevated risk of lung cancer [odds ratio (OR), 1.05 (95%Cl,1.01–1.09), P = 0.01]. The consistent direction of effects observed in the three methods further supported this finding. In addition, sensitivity analyses demonstrated the reliability of the results. This study provided potential evidence supporting a causal association between asthma and lung cancer. These findings highlighted the importance of early detection and prevention strategies for lung cancer in individuals with asthma. Further research was needed to elucidate the underlying mechanisms linking asthma and lung cancer.

Abstract Objective We aim to investigate the association between prognosis and outcomes following myocardial ischemia-reperfusion injury, as well as peripheral blood levels of NLRP3 and the triglyceride-glucose index (TyG). Methods A total of 100 patients who underwent emergency coronary intervention following myocardial infarction confirmed by coronary angiography at our hospital between October 2021 and May 2023 were included in this study. Patients were stratified into two groups based on their prognoses: the control group (n = 73), which did not experience new myocardial infarctions or require hospitalization for heart failure or suffer sudden cardiac death post-interventional treatment; and the observation group (n = 27), which experienced one or more cardiovascular events post-treatment. Patient demographics were obtained from clinical records while biochemical analyses assessed peripheral blood triglycerides, blood glucose levels, and TyG index. Additionally, ELISA measurements determined levels of NLRP3 as well as inflammatory factors IL-6, TNF-α, and CRP in peripheral blood samples. Cardiac function was evaluated according to NYHA standards. Univariable Cox regression analysis identified factors influencing patient prognosis while Pearson correlation analysis examined relationships among prognosis, outcomes following myocardial ischemia-reperfusion injury, TyG index, and peripheral blood NLRP3. Results No significant differences were observed in the general characteristics between the two patient groups (P > 0.05). However, the observation group exhibited higher levels of peripheral blood triglycerides, blood glucose, and TyG index compared to the control group (P

Abstract Background To investigate the association between serum branched chain amino acids (BCAAs), mammalian target of rapamycin (mTOR) levels and the risk of gestational diabetes mellitus (GDM) in pregnant women. Methods 1:1 matched case–control study was conducted including 66 GDM patients and 66 matched healthy pregnant women (± 3 years) in 2019, in China. Fasting bloods of pregnant women were collected in pregnancy at 24 ~ 28 weeks gestation. And the serum levels of valine (Val), leucine (Leu), isoleucine (Ile) and mTOR were determined. Conditional logistic regressions models were used to estimate the associations of BCAAs and mTOR concentrations with the risk of GDM. Results Concentrations of serum Val and mTOR in cases were significantly higher than that in controls (P

Abstract Objective To delineate the clinical characteristics of preterm birth (PTB) in the context of gestational diabetes mellitus (GDM). Methods A retrospective cohort study was conducted, including 14,314 pregnant women with GDM who delivered at Fujian Provincial Maternity and Children’s Hospital from January 1, 2018, to December 31, 2021. PTB was stratified into late PTB (34–36 weeks of gestation) and early PTB (

Objective·To investigate the effects of multiple sevoflurane exposures on the proliferation and differentiation of primary oligodendrocytes.Methods·Oligodendrocyte precursor cells (OPCs) were extracted from the cortex of rats on the day of birth and cultured in vitro. The cells were divided into control and sevoflurane groups. To simulate the clinical situation of sevoflurane exposure, cells in the sevoflurane group were exposed to 3% sevoflurane for 3 consecutive days, 2 h for each time. After the OPCs were differentiated and matured, immunofluorescence staining and Western blotting were used to detect the expression of myelin basic protein (MBP) and the myelin-associated glycoprotein (MAG). Cell proliferation assays (BrdU and Ki67) and a cell viability assay (CCK8) were used to detect the effects of sevoflurane on the proliferation ability of OPCs and the survival rate of oligodendrocytes. Western blotting was used to detect the protein content of caspase-3. Lentiviral transfection technology was used to overexpress YTH N6-methyladenosine RNA binding protein F1 (YTHDF1) in OPCs, and then CCK8 was used to detect cell proliferation and survival.Results·Immunofluorescence results showed that multiple sevoflurane exposures led to a decrease in the number of primary oligodendrocytes expressing mature myelin surface markers (MBP, MAG); Western blotting results showed that these exposures led to upregulation of caspase-3 expression in primary OPCs; CCK8 results showed that the survival rate of primary OPCs decreased with the increase in the number of sevoflurane treatments; however, BrdU and Ki67 staining results showed that the proliferation ability of primary OPCs was enhanced after sevoflurane exposure. In addition, overexpression of YTHDF1 could partially improve the decreased survival rate of primary OPCs caused by multiple sevoflurane exposures (all P

Abstract Breast cancer is the most common malignant tumor among women worldwide and remains one of the leading causes of death among women. Its incidence and mortality rates are continuously rising. In recent years, with the rapid advancement of deep learning (DL) technology, DL has demonstrated significant potential in breast cancer diagnosis, prognosis evaluation, and treatment response prediction. This paper reviews relevant research progress and applies DL models to image enhancement, segmentation, and classification based on large-scale datasets from TCGA and multiple centers. We employed foundational models such as ResNet50, Transformer, and Hover-net to investigate the performance of DL models in breast cancer diagnosis, treatment, and prognosis prediction. The results indicate that DL techniques have significantly improved diagnostic accuracy and efficiency, particularly in predicting breast cancer metastasis and clinical prognosis. Furthermore, the study emphasizes the crucial role of robust databases in developing highly generalizable models. Future research will focus on addressing challenges related to data management, model interpretability, and regulatory compliance, ultimately aiming to provide more precise clinical treatment and prognostic evaluation programs for breast cancer patients.

We introduce a diffusive predator-prey system with the double Allee effect, focusing on the stability and sufficient conditions for the coexistence of prey and predator. Subsequently, we derived the amplitude equation and explore secondary-order dynamic properties using methods such as Taylor series expansion and multiscaling. The novel approach outlined above provides a precise means to thoroughly analyze the predator-prey model. Through this analysis, we demonstrated that the inclusion of the Allee effect and diffusion leads to the system exhibiting more intricate dynamic behaviors compared to systems lacking these factors. On one hand, in the diffusive system without the Allee effect, the pattern formation regarding the distribution of species was relatively scattered, whereas in the diffusive system with the Allee effect, it is more intensive. On the other hand, the system with the Allee effect transitioned from unstable to stable when the diffusion parameter in prey increased, and the aggregation degree of pattern formation in the system with the Allee effect was higher than in the system without it. These findings highlight the significant roles played by the Allee effect and diffusion in determining the dynamic behaviors of prey and predator within the system.

Abstract Background The general education course, Oral Science, has been offered by Guanghua School of Stomatology, Sun Yat-sen University for many years in order to improve students' knowledge of oral health. Information about the oral health knowledge, status, and behaviors among undergraduates who had taken Oral Science was collected to evaluate the impact of this course, and to provide a basis for further improvement of the course teaching quality. Methods Undergraduates taking Oral Science as an elective course were selected as the research subjects. The research time is the second semester of the 2022 academic year, from February 2023 to June 2023. Undergraduates who had not taken the course served as the control group. To investigate the oral health knowledge, status, and behaviors among undergraduate students who have taken the general education course of Oral Science, course students and non-course students were asked to fill out the same questionnaire at both the beginning and end of semester. The answer scores and accuracy of these two groups were compared and analyzed. Before and after the first lesson, and at the end of the semester, course students were asked to fill out the same oral knowledge questionnaire. Another questionnaire was released in week 10 to collect the data of the course students' oral health status and behaviors. The control group completed the same oral knowledge questionnaire at the beginning and end of the semester, respectively. SPSS 20.0 statistical software was used to analyze the data. Statistical significance level was set at 0.05 for all tests. Results At the beginning of the semester, there was no significant difference in the accuracy of the 16 questions nor the scores between two groups (P > 0.05). After one semester of learning, the accuracy of the 16 questions answered by the course students at the end of the semester was significantly higher (P

Abstract Background Febrile respiratory syndrome (FRS) is often associated with viral infections. The aim of this study was to identify the viral pathogens responsible for FRS in Liaoning Province, China. Methods We tested eight respiratory viruses, namely, influenza virus (IFV), rhinovirus (RV), human adenovirus (HAdV), human bocavirus (HBoV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV), using reverse transcription-polymerase chain reaction (RT-PCR). Statistical analyses were performed using SPSS version 25.0, and the data were plotted using RStudio 4.2.1 software. Results IFV was the most frequently identified pathogen, followed by RV, HAdV, HBoV, HPIV, HCoV, RSV, and HMPV. RSV/HBoV coinfection occurred most frequently among the mixed cases. The rate of respiratory virus detection was highest in children under one year of age and decreased significantly with age. Seasonal trends showed a peak in virus detection during the winter months. Conclusions IFV is the leading cause of FRS in Liaoning Province, China, with single-virus infections prevailing over coinfections. Observations indicate a differential virus detection rate across age groups and seasons, highlighting the need for focused preventive strategies to mitigate the transmission of respiratory viruses, particularly among susceptible populations in the colder season.

Abstract Objectives To propose a magnetic resonance imaging (MRI) classification of brucellosis spondylitis (BS) to determine a standard treatment method and a standard of post-treatment MRI follow-up. Methods This is a multicenter retrospective cohort study. All patients diagnosed with BS at six hospitals for 12 years, were included in the study. Data were collected retrospectively from the medical records of the patients. The classification of the cases was based on MRI. We analyzed MRI features of BS was categorized them into three types. Results Six hundred fifteen patients were included in the study, 78.9% of whom were males. The mean age was 53.05 ± 11.06 years. Involvement of single vertebrae occurred in 6.2% of patients, while 72.7% involved two vertebrae and 21.1% involvement of more than two vertebrae. The most common of the lumbar spine was 64.6%. The main findings of MRI were affected vertebral endplate 2/3 above (60.7%), intervertebral space narrow (77.9%), intervertebral disc involvement (83.6%), paravertebral abscess (50.9%), disc abscess (49.6%), epidural abscess (43.3%), vertebra height change (22.1%), psoas abscess (22.0%), and abnormal vertebral accessory (10.2%). MR imaging of BS was categorized into three types. Type I: 57 (9.3%) patients; Type II: 526 (85.5%) patients, including IIa (26.5%), IIb (36.9%), and IIc (22.1%); Type IV: vertebral appendage type, 63 (10.2%) cases; Type III: 32 (5.2%) patients. Conclusions MRI features of multicenter data can provide theoretical support for diagnosing BS. MRI classification of BS can afford better help for clinical treatment and follow-up after clinical treatment.

Abstract Cardiovascular disease remains the leading cause of death worldwide, with air pollution’s impact on cardiovascular health being closely monitored. However, the specific effects of air pollution on the risk of hospital readmission for heart failure (HF) in patients with unstable angina (UA) have not been fully explored. We conducted a retrospective study involving 12,857 consecutive patients diagnosed with acute coronary syndrome (ACS) between January 2015 and March 2023. After rigorous screening, we included 8,737 patients with UA in the analysis. Furthermore, we used a Cox proportional hazards regression model to examine the relationship between air quality indicators and hospital readmission for HF in patients with UA. Additionally, a decision tree model identified air quality indicators levels that had the most significant impact on readmission for HF risk. After adjusting for confounding factors, we found that elevated levels of PM10 [hazard ratio (HR) = 1.003, 95% confidence interval (CI): 1.000-1.005, p = 0.04453] and CO (HR = 1.013, 95% CI: 1.005–1.021, p = 0.00216) were associated with an increased risk of hospital readmission for HF in UA patients. Specifically, patients exposed to PM10 levels above 112.5 µ g/m3 had a 1.61-fold higher risk of readmission for HF in UA patients. (HR = 1.609, 95% CI: 1.190–2.176, p = 0.00201), and those exposed to CO levels above 37.5 mg/m3 had a 2.70-fold higher risk of readmission for HF in UA patients. (HR = 2.681, 95% CI: 1.731–4.152, p

Abstract Selecting appropriate global climate models (GCMs) is crucial for minimizing uncertainty in regional climate projections under future scenarios. Previous studies have predominantly assessed the modeling capability of GCMs for regional precipitation climatology and its long-term patterns based on annual and seasonal precipitation data. Building upon these, we primally evaluated the performance of five GCMs from phase 3b of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3b) in simulating precipitation concentration and its variations in the Southwest River Basin (SWRB) of China using the precipitation concentration index (PCI). The results indicate that: (1) The 5 GCMs generally capture the spatial distribution of annual average precipitation in the SWRB but significantly overestimate its magnitude, with a maximum regional average deviation of 207.80 mm. Furthermore, all models tend to overestimate the overall drying trend in the SWRB and show limited capability in simulating interdecadal variations of annual precipitation. (2) While the 5 GCMs reasonably simulate the spatial distribution of annual average PCI in the SWRB, they tend to overestimate its values, with a maximum regional average deviation of 1.54. Additionally, their simulation performance in capturing PCI trends and interdecadal variations is also limited. (3) The 5 GCMs tend to overestimate seasonal precipitation in the SWRB, with the best simulation performance for the distribution of autumn precipitation, followed by spring and summer, and the poorest for winter. Significant differences exist in the simulation performance of the models for seasonal precipitation proportions, which result in discrepancies in the models’ representation of PCI. Moreover, the models’ poor simulation performance of PCI trends is partly due to their inadequate modeling of trends in seasonal precipitation proportions. The findings will contribute to laying the foundation for meteorological hydrological research and water resource management in the SWRB.

Abstract Exploring efficient and easily implementable prenatal screening strategies aims at birth defect prevention and control. However, there have been limited economic evaluations of non-invasive prenatal screening (NIPS) strategies in China. Furthermore, these studies were predominantly confined to local or geographically proximate provinces and lacked universality and representativeness. This study assesses the health economics of current prenatal screening strategies and NIPS as first-line screening programs, analyzing their efficacy to determine an optimal strategy. From the perspective of health economics, cost-effectiveness, cost-benefit, and single-factor sensitivity were conducted for five different screening strategies using a decision tree model. Among pregnant women aged

Abstract Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

Abstract Background Accumulating evidence suggests that exposure to air pollution acts as a potential trigger for neurological diseases (NDs), yet the current knowledge regarding the impact of ambient nitrogen dioxide (NO2) on the patients with NDs remains limited. In this study, we conducted a time-series study to evaluate the association between short-term exposure to NO2 and hospital visits for NDs in Xinxiang, China. Methods An over-dispersed Poisson generalized additive model was used to analyze the association between ambient NO2 concentrations and daily outpatient visits for NDs from January 1, 2015 to December 31, 2017. The model adjusted for meteorological factors, temporal trends, day of the week, and public holidays. The concentrations of air pollutants were collected from four air quality stations in Xinxiang. Results A total of 38, 865 outpatient visits for NDs were retrieved during the study period. 86.5% of the patients were below the age of 65 years. It was revealed that a 10 µg/m3 increase in NO2 at lag 0 was associated with a significant rise of 1.50% (95% CI: 0.45–2.56%) in outpatient visits for NDs, which was stronger during the cold season. However, the overall results from stratified analyses did not reach statistical significance. Conclusions Short-term exposure to NO2 is associated with increased outpatient visits for NDs. These findings underscore the need for implementing mitigating measures to reduce the neurological health effects of air pollutants.

目的 研究以年龄、血压、临床特征、症状持续时间、糖尿病、双重TIA和影像（age，blood pressure，clinical features，duration，diabetes，double transient ischemic attack，image；ABCD3-I）评分联合血清组织蛋白酶L（cathepsin L，CatL）水平预测TIA患者短期发生脑梗死的价值。 方法 回顾性连续收集2019年10月—2022年6月西北大学第一医院收治的TIA患者资料，根据发病后90 d是否发生急性脑梗死分为脑梗死组和对照组。比较两组患者的ABCD3-I评分、血清CatL水平及其他临床资料的差异，采用多因素logistic回归分析TIA患者90 d发生脑梗死的独立危险因素，采用ROC曲线分析ABCD3-I评分、血清CatL水平对TIA患者短期发生脑梗死的预测价值。 结果 共纳入115例TIA患者，脑梗死组22例，对照组93例。脑梗死组的ABCD3-I评分[7.0（6.0～7.0）分 vs. 5.0（4.5～6.0）分，P＜0.001]、血清CatL水平[（6.1±0.9）μg/L vs.（4.8±0.9）μg/L，P＜0.001]及LDL-C水平[（3.6±0.5）mmol/L vs.（3.4±0.6）mmol/L，P=0.039]均高于对照组。多因素logistic回归分析显示，ABCD3-I评分高（OR 4.843，95%CI 2.301～10.193，P＜0.001）、血清CatL水平升高（OR 2.099，95%CI 1.332～3.308，P=0.001）是TIA患者发生急性脑梗死的独立危险因素。ROC曲线分析显示，ABCD3-I评分、血清CatL水平预测TIA患者发生急性脑梗死的AUC值分别为0.829（95%CI 0.749～0.909）和0.867（95%CI 0.796～0.938），对应截断值分别为7.0分和5.3 μg/L，两者联合预测的AUC值提升至0.911（95%CI 0.848～0.974）。 结论 ABCD3-I评分联合血清CatL水平对TIA患者短期发生急性脑梗死具有较好的预测价值。 Abstract: Objective To study the value of age, blood pressure, clinical features, duration, diabetes, double transient ischemic attack, image (ABCD3-I) score combined with serum cathepsin L (CatL) level in predicting the short-term cerebral infarction in patients with TIA. Methods The data of TIA patients admitted to the Northwest University First Hospital from October 2019 to June 2022 were retrospectively and continuously collected. The patients were divided into the cerebral infarction group and the control group according to whether acute cerebral infarction occurred at 90 d follow-up. The differences in ABCD3-I score, serum CatL level, and clinical data between two groups of patients were compared. The independent influencing factors of short-term cerebral infarction in TIA patients were analyzed by multivariate logistic regression. The predictive value of ABCD3-I score and serum CatL level on the occurrence of short-term cerebral infarction in TIA patients was analyzed by the ROC curve. Results A total of 115 patients with TIA were enrolled, including 22 patients in the cerebral infarction group and 93 patients in the control group. The ABCD3-I score [7.0 (6.0-7.0) points vs. 5.0 (4.5-6.0) points, P＜0.001], serum CatL level [(6.1±0.9) μg/L vs. (4.8±0.9) μg/L, P＜0.001], and LDL-C level [(3.6±0.5) mmol/L vs. (3.4±0.6) mmol/L, P=0.039] of the cerebral infarction group were higher than those of the control group. Multivariate logistic regression analysis showed that the elevated ABCD3-I score (OR 4.843, 95%CI 2.301-10.193, P＜0.001) and the elevated serum CatL level (OR 2.099, 95%CI 1.332-3.308, P=0.001) were independent risk factors for the occurrence of acute cerebral infarction in TIA patients. ROC curve analysis showed that the AUC value of ABCD3-I score and serum CatL level in predicting acute cerebral infarction of TIA patients were 0.829 (95%CI 0.749-0.909) and 0.867 (95%CI 0.796-0.938), respectively, and the corresponding cutoff value were 7.0 points and 5.3 μg/L, respectively. The AUC value of the combination of the two indicators was 0.911(95%CI 0.848-0.974). Conclusions The combination of ABCD3-I score and serum CatL level has good predictive value on the occurrence of short-term cerebral infarction in TIA patients.

Determining the chemical characteristics of atmospheric precipitation and its source contributions is critical for improving atmospheric environmental quality and water security. In this study, we analyzed the pH, Electrical Conductivity (EC), and major ion concentrations of precipitation from 2000 to 2021 at 29 monitoring stations in the Pearl River Delta (PRD), which typically experiences acid rain. Correlation analysis, the Positive Matrix Factorization (PMF) model, and other statistical methods were used to analyze the correlations between the major ion concentrations and their source contributions. The results indicate that the pH, EC, and Fractional Acidity (FA) of precipitation from 2000 to 2021 ranged from 4.66 ± 0.18 to 5.91 ± 0.45, from 1.63 ± 0.59 to 5.49 ± 1.62 mS/m, and from 0.05 ± 0.06 to 0.19 ± 0.13, respectively. The pH exhibited interannual variations (first decreasing and then increasing), whereas EC and FA exhibited the opposite trend. The total ion concentrations in precipitation ranged from 166.63 ± 46.56 to 631.48 ± 212.83 μeq/L, which first increased and then decreased. The weighted equivalent ion concentrations were in order of SO42- > Ca2+ > NH4+ > NO3- > Cl- > Na+ > K+ > Mg2+ > F-. SO42-, NO3-, Ca2+, and NH4+ were the main ions, accounting for 72.98% of the total concentration. The ratio of the SO42- concentration to the total concentration decreased from 32.71% in 2000 to 14.33% in 2021, whereas NO3- increased from 9.03% to 13.74% during the same period. The ratio of SO42- to NO3- concentrations (SO42-/NO3-) decreased by 65.95% from 2000 to 2021. After 2008, the SO42-/NO3- values ranged from 0.5 to 3, and precipitation shifted from a sulfuric acid type to a mixed sulfuric-nitric acid type. This change indicates that increased NOx emissions in the PRD under urbanization and agricultural intensification altered the structure of precipitation pollution and further increased the complexity of regional air pollution. The ions were highly significantly positively correlated, of which NO3- and SO42- had the strongest positive correlation (r=0.69‒0.74). Generally, NOx and SO2 are emitted together and enter precipitation via overlapping pathways. Of the six ion sources, coal combustion had the highest contribution rates (a>60%) to SO42- and F-, while secondary inorganic salts contributed 82.30% of the NO3-. Agriculture, sea salt, biomass combustion, and dust contributed > 70% of the NH4+, Na+, K+, and Ca2+. The contribution rates of secondary inorganic salts to SO42-, Cl-, and NH4+ were also greater than 25%. Owing to the increase in motor vehicles driven by urbanization, the impacts of secondary inorganic salt sources on ions in precipitation have become more extensive, and controlling NOx emissions to effectively control secondary pollution sources is urgently required.

With water resource shortages becoming a global concern, water conservation is one of the key factors in the sustainable development of watershed ecosystems. However, previous studies of water conservation have focused on annual mean water conservation, which does not reflect changes in water conservation on shorter time scales. Shorter time scales have more significant responses than longer timescales. An annual scale reflects the supply function of the water culverts, whereas a shorter time scale reflects the function of stagnant flood replenishment. Thus, we analyzed the annual, monthly, and daily changes in water conservation in the Zengjiang River Basin, an important water source area and ecological barrier in Guangzhou, from 1959 to 2018. The WEP-L distributed hydrological model and water-balance equations were used to explore the supply, regulation, and peak reduction and replenishment of the water conservation dryness functions. The results indicate that the annual mean water conservation in the Zengjiang River Basin was 685.7 mm from 1959 to 2018, with a non-significant decreasing rate (-1.30 mm/a) during this period. This decreasing trend indicates that the water supply capacity of the basin decreased, which is not conducive to the water security of the basin and downstream areas. Therefore, relevant policies should be formulated and measures should be taken to improve the water conservation capacity of the basin. The multi-year average monthly water conservation in the Zengjiang River Basin was positive in January‒September and negative in October‒December, with non-significant increases in water conservation in January, March, June, November, and December, and non-significant decreases in the other months. The trend ranged from -0.04 to -0.67 mm/a during the entire study period. Water conservation changes in the Zengjiang River Basin during pre-flood, post-flood, and dry-water periods indicate that the basin's ability to regulate water conservation runoff weakened. The maximum 1-day, 3-day, 5-day, and 7-day periods in the Zengjiang River Basin were positive, whereas the minimum 1-day, 3-day, 5-day, and 7-day periods were negative. Except for the minimum 5-day and 7-day periods, the other six daily extreme water conservation indicators exhibited non-significant increasing trends. The maximum water conservation values indicate that the peak reduction capacity increased, while the minimum water conservation values indicate that the capacity to replenish depletion decreased in 1- and 3-day periods and increased in 5- and 7-day periods. Spatially, the annual water conservation trend was low in the southeastern and northern parts of the basin, and high in the southwestern part of the basin. Annual, monthly, and daily water conservation levels in the Zengjiang River Basin from 1959 to 2018 embodied its supply, regulation, peak reduction, and replenishment of depletion functions, respectively. The correlation coefficients between water conservation and precipitation were significantly higher than those between evapotranspiration and surface runoff, thereby indicating that precipitation was the most important factor influencing water conservation. The findings of this study reveal multi-temporal evolutionary processes and functional differences in water conservation and provide a scientific basis for ecological protection and construction.

Reservoir-type drinking water sources in the Pearl River Delta ensure a safe urban water supply; thus, land-use changes are important factors affecting these aquatic environments. In this study, we investigated the water source areas of medium and large reservoirs in the Pearl River Delta to determine the contributions and trends of land-use changes within reservoir drinking water source areas to the reservoir water quality. First, we analyzed dynamic land-use changes in reservoir-type water sources in the Pearl River Delta region from 1980 to 2020. We then used the gray relational analysis method to determine the relationship between land use and water quality changes. We analyzed changes in the main water quality factors in the Dajingshan Reservoir (Zhuhai) and determined the relationship between changes in land use and the reservoir water quality index over the past 20 years using correlation and redundancy analyses. The results indicate that paddy fields, dry land, forest land, and water areas were the main land-use types around reservoir-type drinking water sources in the Pearl River Delta. Although construction land and water areas expanded, paddy fields, dry land, and forest land areas decreased. The land transfer trend was mainly from forest and cultivated land to production and living land (e.g.1980-2020), construction land) and water areas. With the implementation of the policy, the aforementioned land-use transformation began to slow. Regionally, the risk sources of non-point source pollution in the study area gradually decreased, but still accounted for 9.48% of total land use in 2020. The water quality of reservoir sources in the Pearl River Delta improved; however, nitrogen pollution remains problematic. Gray relational analysis indicates that land-use changes and water quality were correlated (in order of decreasing strength): construction land > agricultural land > forest land. Non-point source pollution caused by land use remains an important influencing factor. The Dajingshan Reservoir water quality is seriously polluted, as the total nitrogen exceeded the standard during several months, and nitrogen and phosphorus pollution gradually increased over time. Nitrogen and phosphorus were the main pollutants in the reservoir. Big mountain reservoir redundancy, correlation, and partial least squares regression analyses indicate that the land use type and water quality index were correlated, forest land and the nitrogen/phosphorus water quality index were negatively correlated, and construction and agricultural land were significantly positively correlated, which had a positive effect on the total nitrogen concentration. The influence of land-use patterns on non-point source pollution remains an uncontrollable factor. The specific effects of land-use changes on water quality are complex; therefore, further modeling should investigate the mechanism by which the water supply quality is influenced to improve reservoir water quality, ensure the safety of the regional water supply, and provide support for ecological restoration measures in protected areas.

Abstract Background Premature infants requiring mechanical ventilation and supplemental oxygen for respiratory support are at increased risk for bronchopulmonary dysplasia (BPD), wherein inflammation have been proposed as a driver of hyperoxia-induced injuries, including persistent loss of endothelial progenitor cells (EPCs), impaired vascularization and eventual alveolar simplification in BPD lungs. However, the underlying mechanisms linking these phenomena remain poorly defined. Methods We used clodronate liposomes to deplete macrophages in a mouse model of neonatal hyperoxia-induced lung injury to evaluate if EPC loss in BPD lungs could be an effect of macrophage infiltration. We further generated in vitro culture systems initiated with cord blood (CB)-derived CD34+ EPCs and neonatal macrophages either polarized from CB-derived monocytes or isolated from tracheal aspirates of human preterm infants requiring mechanical ventilation and oxygen supplementation, to identify EV-transmitted molecular mechanism that is critical for inhibitory actions of hyperoxic macrophages on EPCs. Results Initial experiments using mouse model identified the crucial role of macrophage infiltration in eliciting significant reduction of c-Kit+ EPCs in BPD lungs. Further examination of this concept in human system, we found that hyperoxia-exposed neonatal macrophages hamper human CD34+ EPC maintenance and impair endothelial function in the differentiated progeny via the EV transmission of miR-23a-3p. Notably, treatment with antagomiR-23a-3p to silence miR-23a-3p in vivo enhances c-Kit+ EPC maintenance, and increases capillary density, and consequently mitigates simplified alveolarization in BPD lungs. Conclusion Our findings highlight the importance of pulmonary intercellular communication in the pathophysiology of BPD, by identifying a linkage through vesicle transfer of miR-23a-3p from hyperoxic macrophages to EPCs, and thus demonstrating potential for novel therapeutic target in BPD.

Abstract Background Bromadiolone is a wide-use long-acting anticoagulant rodenticide known to cause severe coagulation dysfunction. At present, there have been no detailed reports of acute kidney injury (AKI) resulting from bromadiolone poisoning. Case presentation A 27-year-old woman was admitted to the hospital due to severe coagulopathy and severe AKI. Coagulation test revealed a prothrombin time exceeding 120 s and an international normalized ratio (INR) greater than 10. Further examination for coagulation factors showed significantly reduced level of factors II, VII, IX and X, indicating a vitamin K deficiency. The AKI was non-oliguric and characterized by gross dysmorphic hematuria. Following the onset of the disease, the patient’s serum creatinine rose from 0.86 to 6.96 mg/dL. Suspecting anticoagulant rodenticide poisoning, plasma bromadiolone was identified at a concentration of 117 ng/mL via gas chromatography/mass spectrometry. All other potential causes of AKI were excluded, except for the presence of a horseshoe kidney. The patient’s kidney function fully recovered after the coagulopathy was corrected with high doses of vitamin K and plasma transfusion. At a follow-up 160 days post-discharge, the coagulation function had normalized, and the serum creatinine had returned to 0.51 mg/dL. Conclusion Bromadiolone can induce AKI through a severe and prolonged coagulation disorder. Kidney function can be restored within days following treatment with high-dose vitamin K1.

Abstract Ulinastatin, a broad-spectrum inflammatory inhibitor widely employed in the management of severe pancreatitis and sepsis, has not been extensively investigated for its therapeutic potential in bacterial meningitis. This study aims to assess the neuroprotective effects of ulinastatin on bacterial meningitis and elucidate its underlying mechanism. The rat model of bacterial meningitis was established by intracerebral injection of Escherichia coli. 3-week-old SD rats were randomly divided into 5 groups with 8 rats in each group, including control group, E.coli group, E.coli + UTI group (ulinastatin 50000IU/kg), E.coli + UTI + PMA group (ulinastatin 50000IU/kg + PMA 200 ug/kg), and E.coli + PMA group(PMA 200 ug/kg). Behavioral changes were assessed by Loeffler neurobehavioral score. Histomorphologic changes and apoptosis were assessed by hematoxylin and eosin staining, Nissl staining and TUNEL staining. Immunohistochemistry and immunofluorescence and western blotting were used to detect the expression levels of zonula occludens-1 (ZO-1) and phosphorylation protein kinase C (PKCα).It was found that ulinastatin treatment in Escherichia coli meningitis rats improved neurological function, alleviated meningeal inflammatory infiltration, reduced neuronal death, promoted the integrity of the blood–brain barrier structure. Moreover, phorbol myristate acetate (PMA, a protein kinase C activator), blocked the effective action of ulinastatin. These findings suggest that ulinastatin had neuroprotective effects on bacterial meningitis by inhibiting PKCα phosphorylation and reducing ZO-1 degradation, demonstrating that ulinastatin may be a promising strategy in the treatment of bacterial meningitis.

Abstract Many studies have shown that drinking coffee and tea may be associated with the risk of hypertension and dementia. Limited research exists on their impact on dementia risk in hypertensive patients. This study aimed to determine the association between coffee and tea consumption and the risk of dementia development in hypertensive population by utilizing Cox proportional risk modeling with 453,913 participants from a UK biobank. Our findings reveal a J-shaped and U-shaped association between the risk of all-cause dementia and the consumption of coffee and tea respectively in hypertensive people. The hypertensive patients who drink 0.5–1 cup of coffee or 4–5 cups of tea per day have the lowest risk of dementia. A U-shaped relationship was observed between daily caffeine consumption and the risk of developing all-cause dementia and vascular dementia in the hypertensive population. Furthermore, the significant association between the amount of coffee and tea consumed and the risk of all-cause and vascular dementia were more likely to be found in hypertensive patients than in the non-hypertensive population.

Abstract Background Stage IB-IIA Cervical Squamous Cell Carcinoma (CSCC) presents diverse clinical outcomes, the mechanisms that cause recurrence in CC patients remain unclear. The goal of this study was to identify predictive biomarkers leading to tumor recurrence in IB-IIA CSCC after surgical treatment by comparing the transcriptional and immune landscape between the recurrence and non-recurrence group. Methods We performed mRNA sequencing and multiplexed immunohistochemistry (mIHC) analysis among stage IB-IIA patients with or without recurrence after surgical resection and were followed-up for a median of three years. Results Integrated analysis indicates that the upregulated gene expression in zinc finger proteins, the activation of the PI3K/Akt pathway, and the low infiltration level of T follicular helper cells and B-cells may serve as potential recurrent biomarkers for CSCC. We also observed significant differences in the immune and genomic landscape between two groups. Conclusions These findings provide new insights into the relapse mechanisms of CSCC, which could potentially guide clinical exploration of drug targets.

Abstract Rap2b, a proto-oncogene upregulated in colorectal cancer (CRC), undergoes protein S-palmitoylation at specific C-terminus sites (C176/C177). These palmitoylation sites are crucial for Rap2b localization on the plasma membrane (PM), as mutation of C176 or C177 results in cytosolic relocation of Rap2b. Our study demonstrates that Rap2b influences cell migration and invasion in CRC cells, independent of proliferation, and this activity relies on its palmitoylation. We identify ABHD17a as the depalmitoylating enzyme for Rap2b, altering PM localization and inhibiting cell migration and invasion. EGFR/PI3K signaling regulates Rap2b palmitoylation, with PI3K phosphorylating ABHD17a to modulate its activity. These findings highlight the potential of targeting Rap2b palmitoylation as an intervention strategy. Blocking the C176/C177 sites using an interacting peptide attenuates Rap2b palmitoylation, disrupting PM localization, and suppressing CRC metastasis. This study offers insights into therapeutic approaches targeting Rap2b palmitoylation for the treatment of metastatic CRC, presenting opportunities to improve patient outcomes.

ObjectiveTo explore the independent risk factors that affect the overall survival (OS) of elderly patients with hepatocellular carcinoma (HCC, ≥60 years old) and build a nomogram prediction model. MethodsClinical data of all elderly patients with HCC from the SEER database from 2005 to 2020 were downloaded from SEER database. In accordance with the inclusion and exclusion criteria, the screened patients were randomly assigned to a training group (70%) and a validation group (30%). The independent risk factors of elderly patients with HCC were determined by univariate and multivariate Cox regression analyses and further validated by Kaplan-Meier survival analysis. On the basis of the determined variables, nomograms were developed and verified to predict the OS of elderly patients with HCC at 6, 12, and 24 months. The consistency index (C index), calibration curve, receiver’s operating characteristic (ROC) curve, and area under curve (AUC) were used to evaluate the prediction efficiency and discrimination ability of the prediction model, and decision curve analysis (DCA) was used to evaluate the potential clinical application value of the nomogram. ResultsA total of 1134 elderly patients with HCC were included, with 793 in the training group and 341 in the validation group. Seven variables, including age, clinical grade, clinical stage, M stage, tumor size classification, and radiotherapy, were identified as independent prognostic factors of this population. The constructed nomogram shows excellent prediction performance, with C indices of 0.745 in the training group and 0.704 in the validation group. The AUC values of the training group at 6, 12, and 24 months were 0.785, 0.788, and 0.798, respectively, and those of the validation group were 0.780, 0.725, and 0.607, respectively. The calibration curve shows good consistency from the predicted survival probability to the actual probability. The ROC curve and DCA show that the nomogram proposed in this study has good prediction ability. ConclusionAge, clinical grade, clinical stage, M stage, tumor size classification, and radiotherapy are important influencing factors for the survival of elderly patients with HCC. The prediction model of prognosis nomogram constructed in this study has good predictive value, and it can be used to predict the OS of elderly patients with HCC, which could be helpful for individualized survival assessment and clinical management of these patients.

Abstract Background The interplay between intrauterine and early postnatal environments has been associated with an increased risk of cardiovascular diseases in adulthood, including pulmonary arterial hypertension (PAH). While emerging evidence highlights the crucial role of mitochondrial pathology in PAH, the specific mechanisms driving fetal-originated PAH remain elusive. Methods and results To elucidate the role of mitochondrial dynamics in the pathogenesis of fetal-originated PAH, we established a rat model of postnatal catch-up growth following intrauterine growth restriction (IUGR) to induce pulmonary arterial hypertension (PAH). RNA-seq analysis of pulmonary artery samples from the rats revealed dysregulated mitochondrial metabolic genes and pathways associated with increased pulmonary arterial pressure and pulmonary arterial remodeling in the RC group (postnatal catch-up growth following IUGR). In vitro experiments using pulmonary arterial smooth muscle cells (PASMCs) from the RC group demonstrated elevated proliferation, migration, and impaired mitochondrial functions. Notably, reduced expression of Mitofusion 2 (Mfn2), a mitochondrial outer membrane protein involved in mitochondrial fusion, was observed in the RC group. Reconstitution of Mfn2 resulted in enhanced mitochondrial fusion and improved mitochondrial functions in PASMCs of RC group, effectively reversing the Warburg effect. Importantly, Mfn2 reconstitution alleviated the PAH phenotype in the RC group rats. Conclusions Imbalanced mitochondrial dynamics, characterized by reduced Mfn2 expression, plays a critical role in the development of fetal-originated PAH following postnatal catch-up growth after IUGR. Mfn2 emerges as a promising therapeutic strategy for managing IUGR-catch-up growth induced PAH.

Abstract Background The relationship between A Body Shape Index (ABSI) and female infertility is not well understood. ABSI, a novel anthropometric measure, is gaining recognition for its ability to more accurately capture visceral fat characteristics than traditional metrics like BMI. This study aims to explore the association between ABSI and female infertility, considering its potential applications in medical screening and risk assessment. Methods This cross-sectional study analyzed data from the NHANES from 2013 to 2020. Female infertility was assessed through reproductive health questionnaires, and ABSI was calculated using waist circumference, BMI, and height. Weighted logistic regression models and trend tests were used to evaluate the association between ABSI and female infertility. Restricted cubic splines (RCS) were employed to explore potential nonlinear relationships. Subgroup analyses were conducted to examine the consistency of the association across various demographic and health-related factors. Sensitivity analyses were also performed, including the exclusion of participants with missing covariate data, the application of propensity score matching, and restricting the analysis to women aged 20–45 years. Results The study included 3,718 participants, 433 of whom were diagnosed with infertility. Higher ABSI was associated with an increased risk of female infertility (OR = 1.56, 95% CI: 1.21-2.00, P = 0.001), as demonstrated by weighted logistic regression and trend tests. Women in the highest ABSI quartile had a significantly higher prevalence of infertility compared to those in the lowest quartile (OR = 1.73, 95% CI: 1.27–2.37, P = 0.001). RCS curves indicated a linear positive relationship between ABSI and infertility risk, with a critical value at 0.079. Subgroup and sensitivity analyses confirmed the stability of these findings. Conclusion This study demonstrates a positive linear relationship between ABSI and the risk of female infertility. The use of a simple, non-invasive ABSI measurement could facilitate the early identification of high-risk individuals in large-scale screenings, potentially helping to prevent or reduce the incidence of infertility.

Antinutritional factors in feedstuffs may limit their utilization in livestock production, but fermentation process can be used to improve feed quality; however, studies on fermented soybeans for laying hens remain limited. We investigated the effect of fermented soybean meal (FSBM) at various inclusion levels as a partial replacement for soybean meal (SBM) on egg production, egg quality, amino acid digestibility, gut morphology and microbiota, antioxidant capacity and immune response of young laying hens. A total of 360 Hy-line Brown laying hens aged 18 weeks were selected and divided into 5 groups of 6 replicates each and 12 birds per replicate. The control group received a basal diet while the trial group received the basal diet with FSBM included at 2.5%, 5.0%, 7.5% and 10.0%, respectively, for 12 weeks. Our findings revealed that the nutritional value of FSBM was higher compared to that of SBM in terms of reduced content of trypsin inhibitors and increased contents of crude protein, amino acids and minerals. FSBM enhanced egg production (P

Relation extraction, as a key task in natural language processing, plays a significant role in deepening language understanding, constructing knowledge graphs, and optimizing information retrieval systems. However, traditional supervised learning methods are not well-suited for real-world scenarios due to the continuous emergence of new relations and the lack of large annotated datasets. Although the advent of large language models has significantly improved the performance of many natural language processing tasks, they still cannot effectively address the challenges of few-shot continual relation extraction. To fully leverage the semantic knowledge of large language models to mitigate catastrophic forgetting and overfitting issues, a novel few-shot continual relation extraction method, LAFA (large language model augmentation and feature alignment), is proposed. This method enhances representation alignment through various strategies such as relation instance rewriting, semantic expansion, and enhanced relation representation. It effectively improves the model adaptability to new relations and the retention of old knowledge while maintaining low data and computational costs. Experimental validation on two relation extraction datasets, FewRel and TACRED, demonstrates that LAFA outperforms existing methods in few-shot continual relation extraction tasks, particularly achieving the best results in incremental stages. Ablation experiments further reveal the significant contributions of each module to overall performance. Moreover, the inference efficiency and cost of LAFA are substantially lower than those of existing large language model-based methods, and it boasts strong scalability, being able to adapt to various language models.

Residual feed intake (RFI) is a metric that provides a more accurate measure of feed efficiency. The lower the RFI, the higher the feed efficiency. The changes in the host microbiome and metabolome contribute to the greater feed efficiency of low RFI (LRFI) animals. The aim of this study was to explore the differences in rumen microorganisms, rumen metabolites and plasma metabolites of Hu sheep with differing RFI through the microbiome and metabolome. A total of 80 Hu sheep were used. The experiment consisted of a 15-d pretrial period and a 128-d experimental period. The RFI in the experimental period was calculated for all sheep, and the sheep were screened into high RFI (HRFI, n = 8) and LRFI (n = 8) groups. The HRFI and LRFI sheep did not differ in their initial and final body weights, average daily gain and body measurements, but the dry matter intake of LRFI sheep was significantly decreased (28.4%, P

ABSTRACT Aims/Introduction To investigate risk factors for diabetic peripheral neuropathy (DPN) and to explore the connection between insulin‐like growth factor‐1 (IGF‐1) and DPN in individuals with type 2 diabetes. Materials and Methods A total of 790 patients with type 2 diabetes participated in a cross‐sectional study, divided into two groups: those with DPN (DPN) and those without DPN (non‐DPN). Blood samples were taken to measure IGF‐1 levels and other biochemical markers. Participants underwent nerve conduction studies and quantitative sensory testing. Results Patients with DPN exhibited significantly lower levels of IGF‐1 compared with non‐DPN patients (P 0.05), or the temperature detection threshold (P > 0.05). Multivariate regression analysis identified diabetes duration, HbA1c, and the low levels of IGF‐1 as independent risk factors (P

In order to solve the problem of poor performance of welded joints of steel and aluminum dissimilar materials, this study proposes the use of ceramic particle-reinforced aluminum alloy as an alternative to traditional aluminum alloy for welding, effectively overcoming this problem. In this paper, the laser welding of stainless steel/6061 aluminum alloy (SA) and stainless steel/TiC–TiB2 duplex nanoparticle-reinforced 6061 aluminum alloy (SRA) was realized. The effect of ceramic nanoparticles on the microstructure and mechanical properties of SRA joint was systematically studied, and the strengthening mechanism of nanoparticles was revealed. Under the same process parameters, the melting zone of SRA joint is larger and the intermetallic compound (IMCs) layer is narrower. Moreover, the grain size of the brittle Fe–Al compound phase in the IMCs layer is significantly reduced, which effectively inhibits the initiation of cracks at the steel/aluminum interface. The study shows that ceramic particles have a pinning effect on the dislocations, limiting the grain growth, reducing the thickness of the intermetallic compound layer, and decreasing the content of the brittle FeAl3 phase. Moreover, ceramic nanoparticles promote the formation of Mg2Si strengthened phase at the grain boundary, further hinder the dislocation movement and improve the strength of the joint. Under the welding power of 3400 W and welding speed of 31 mm/s, SRA joint achieves the maximum tensile shear of 1718 N, which is 15% higher than the strength of SA joint.

Prostaglandin E2 (PGE2) has been reported to be involved in reproduction as one of the most abundant and widely distributed prostaglandins in invertebrates. Regulating gonad development and gamete production in mollusks can greatly assist artificial breeding, which is believed to promote the commercial benefits of various mollusk species. In the present study, the contents of PGE2 in the gonads of abalone at different developmental stages (maturing stage, ripe stage, and spawning stage) and reproduction states (before and after spawning) were measured. A higher PGE2 level was found in the gonads of abalones at the ripe stage than other stages, and the highest PGE2 level was detected in the ovaries of female H. diversicolor in the UV-stimulated group. Then the effects of PGE2 injection on the spawning efficiency were explored, and the gamete emission rates of female and male abalone were significantly increased after PGE2 injection. Through qRT-PCR and in situ hybridization assay, higher expression levels and wide distribution of phospholipase A2 (PLA2), cyclooxygenase 2 (COX2), prostaglandin E synthases (PGES2), and prostaglandin E2 receptor 4 (EP4) in the gonads of H. diversicolor were observed after spawning. It is speculated that PGE2 may promote the reproductive cycle in both male and female H. diversicolor, although the regulation mechanism of PGE2 in female and male abalone might be different. The results will be useful for the application of PGE2 in the abalone aquaculture practices to increase the reproduction efficiency in future.

ObjectiveTo assess the implementation of insurance-based compensation for adverse reactions following immunization in Wuxi City,Jiangsu Province.MethodsData on basic insurance and supplementary insurance for adverse reactions following immunization from 2020 to 2022 in Wuxi City was collected, and a descriptive epidemiological method was used to analyze the data.ResultsA total of 2 272 cases were compensated for adverse reactions following immunization,with a total compensation amount of 5.255 9 million yuan, and an average of 2.3 thousand yuan per case. Basic insurance accounted for 0.62% of the total cases and 10.72% of the total compensation amount, while supplementary insurance accounted for 99.43% of the total cases and 89.28% of the total compensation amount. Compensation amounts for disability and third-degree damage in basic insurance accounted for 63.18% and 88.71%, respectively, while fourth-degree and lower damage in supplementary insurance accounted for 96.52%. The compensation rate for supplementary insurance was higher than that for basic insurance. The highest number of compensated cases was in the 0‒ year age group, and vaccines included in the Expanded Program on Immunization (EPI) accounted for the majority of the cases and compensation amounts, with a percentage of 70.11% and 73.84%, respectively. For basic insurance, the largest number of compensated cases involved the Bacillus Calmette-Guérin (BCG) vaccine. For supplementary insurance, the top three compensated cases for EPI vaccines were the measles-mumps-rubella (MMR) vaccine, the hepatitis B (HepB) vaccine, and the acellular diphtheria-tetanus-pertussis (DTaP) vaccine. For non-EPI vaccines, the top three compensated cases were the 13 valent pneumococcal polysaccharide conjugate (PPCV13) vaccine, the acellular DPT-inactivated poliovirus-haemophilus influenzae type b combined vaccine (DPT-IPV/Hib), and enterovirus 71 (EV71) inactivated vaccine. In basic insurance, thrombocytopenic purpura and BCG local abscess both accounted for 21.43% of the cases, while in supplementary insurance, respiratory system diseases accounted for 77.47% of the cases. The time intervals from reporting to submission of compensation materials (

Soliton microcombs, which require the hosting cavity to operate in an anomalous dispersion regime, are essential to integrate photonic systems. In the past, soliton microcombs were generated on cavity whispering gallery modes (WGMs), and the anomalous dispersion requirement of the cavity made by normal dispersion material was achieved through structural dispersion engineering. This inevitably degrades the cavity optical quality factor (Q) and increases pump threshold power for soliton comb generation. To overcome the challenges, here, we report a soliton microcomb excited by cavity polygon modes. These modes display anomalous dispersion at near-infrared while optical Q factors exceeding 4×106 are maintained. Consequently, a soliton comb spanning from 1450 nm to 1620 nm with a record low pump power of 11 mW is demonstrated, a three-fold improvement compared to the state of the art on the same material platform.

In this study, the nano-TiC/AZ61 composites with different heterogeneous bimodal grain (HBG) structures and uniform structure are obtained by regulating the extrusion speed. The effect of HBG structure on the mechanical properties of the composites is investigated. The increasing ductility and toughening mechanism of HBG magnesium matrix composites are carefully discussed. When the extrusion speed increases from 0.75 mm/s to 2.5 mm/s or 3.5 mm/s, the microstructure transforms from uniform to HBG structure. Compared with Uniform-0.75 mm/s composite, Heterogeneous-3.5 mm/s composite achieves a 116.7% increase in ductility in the plastic deformation stage and almost no reduction in ultimate tensile strength. This is mainly because the lower plastic deformation inhomogeneity and higher strain hardening due to hetero-deformation induced (HDI) hardening. Moreover, Heterogeneous-3.5 mm/s composite achieves a 108.3% increase in toughness compared with the Uniform-0.75 mm/s composite. It is mainly because coarse grain (CG) bands can capture and blunt cracks, thereby increasing the energy dissipation for crack propagation and improving toughness. In addition, the CG band of the Heterogeneous-3.5 mm/s composite with larger grain size and lower dislocation density is more conducive to obtaining higher strain hardening and superior blunting crack capability. Thus, the increased ductility and toughness of the Heterogeneous-3.5 mm/s composite is more significant than that Heterogeneous-2.5 mm/s composite.

Fused silica with surface structures has potential applications in microfluidic, aerospace and other fields. To fabricate structures with high dimensional accuracy and surface quality is of paramount importance. However, it is indeed a challenge to strike a balance between accuracy and efficiency at the same time. Here, a temporally shaped femtosecond laser Bessel-beam-assisted etching method with dual-control of incubation effect is proposed to achieve this balance. Instead of layer-by-layer ablation continuously with Gaussian pulses, silica is modified discretely by double pulse Bessel beam with one single layer. During the modification process, incubation effect is dual-controlled in single shot process and spatial scanning process to generate even modified region efficiently. Then, the modified region is etched to form designed structures such as microholes, grooves, etc. The proposed method exhibits high efficiency for fabrication of surface structures in fused silica.

Two large-scale snow and rain weather processes occurred in china from February 1-4, 2024 (Process 1, hereinafter), and February 19-24, 2024 (Process 2, hereinafter). During these two weather processes, the impact of freezing rain was extensive, the intensity of the disaster was severe, and the duration was long, which was rare in history. This study utilized multi-source observational data and ERA5 reanalysis data to focus on analyzing the environmental conditions and temperature layer characteristics of these two freezing rain events. The results indicate: (1) During both weather events, the 500 hPa weather patterns and influencing systems were quite similar, which were stably sustained, providing favorable conditions for widespread snow, rain, and freezing weather. However, there were differences in the low-level temperature configuration and the speed of movement. In Process 1, due to the slower movement of the cold air, the distribution of freezing rain was more concentrated. The initial southwest jet stream in Process 2 was stronger and positioned further north compared to Process 1, leading to the occurrence of freezing rain further northward. However, in the later stages, the rapid southward movement of strong cold air caused a fast-moving rain, snow, and ice, and thus a larger impacting range of the freezing rain. (2) In both processes, the mid-level warm layer was mainly located between 700 hPa and 850 hPa, while the low-level cold layer was mainly located below 900 hPa. The positions were lower than the classic conceptual model of a warm layer at 700 hPa and a cold layer at 850 hPa, which could easily lead to misjudgment of the weather situations and types. (3) Using the area method, the strength of the mid-level warm layer and the low-level cold layer was calculated separately for both processes. The results show that the strength of the warm and cold layers in Process 1 was weaker than in Process 2. In addition, the freezing rain in both processes mainly occurred in areas where the strength of the mid-level warm layer and the low-level cold layer were close.

The prevalence of sarcopenia in type 1 diabetes is higher than that in type 2 diabetes and non-diabetes patients. Screening, diagnosis and intervention of sarcopenia in type 1 diabetes patients as early as possible is of great significance for improving the life quality of these patients. The occurrence of sarcopenia in type 1 diabetes mellitus may be closely related to the decline of skeletal muscle function caused by the decrease of insulin-like growth factor-1, activation of inflammatory factors, mitochondrial dysfunction, and accumulation of advanced glycation end-products. At present, the mechanism of the occurrence and development of sarcopenia induced by type 1 diabetes is not completely clear, and the relevant new drug treatment lacks data support. Further in-depth research may bring a new direction for the prevention and treatment of sarcopenia in type 1 diabetes patients.

Abstract Objective The ultrasonographic characteristics of lymph node metastasis in breast cancer patients were retrospectively analyzed, and a predictive nomogram model was constructed to provide an imaging basis for better clinical evaluation. Methods B-mode ultrasound was used to retrospectively analyze the imaging characteristics of regional lymph nodes and tumors. Pathological examination confirmed the presence of lymph node metastasis in breast cancer patients. Univariable and multivariable logistic regression analyses were performed to analyze the risk factors for lymph node metastasis. LASSO regression analysis was performed to screen noninvasive indicators, and a nomogram prediction model was constructed for breast cancer patients with lymph node metastasis. Results A total of 187 breast cancer patients were enrolled, including 74 patients with lymph node metastasis in the positive group and 113 patients without lymph node metastasis in the negative group. Multivariate analysis revealed that pathological type (OR = 4.58, 95% CI: 1.44–14.6, p = 0.01), tumor diameter (OR = 1.37, 95% CI: 1.07–1.74, p = 0.012), spiculated margins (OR = 7.92, 95% CI: 3.03–20.67, p

Abstract Background Automated test assembly (ATA) represents a modern methodology that employs data science optimization on computer platforms to automatically create test form, thereby significantly improving the efficiency and accuracy of test assembly procedures. In the realm of medical education, large-scale high-stakes assessments often necessitate lengthy tests, leading to elevated costs in various dimensions (such as examinee fatigue and expenses associated with item development). This study aims to augment the design of the medical education assessments by leveraging modern ATA approaches. Methods To achieve the objective, a four-step process employing psychometric methodologies was used to calibrate and analyze the item pool of the Standardized Competence Test for Clinical Medicine Undergraduates (SCTCMU), a nationwide summative test comprising 300 multiple-choice questions (MCQ) in China. Subsequently, two modern ATA approaches were employed to determine the optimal item combination, accounting for both statistical and content requirements specified in the test blueprint. The qualities of the assembled test form, generated using modern ATA approaches, underwent meticulous evaluation. Results Through an exploration of the psychometric properties of the SCTCMU as a foundational step, the evaluation revealed commendable quality in the item properties. Furthermore, the evaluation of the quality of assembled test form using modern ATA approaches indicated the ability to ascertain the optimal test length within the predefined measurement precision. Specifically, this investigation demonstrates that the application of modern ATA approaches can substantially reduce the test length of assembled test form, while simultaneously maintaining the required statistical and content standards specified in the test blueprint. Conclusions This study harnessed modern ATA approaches to facilitate the automatic construction of test form, thereby significantly enhancing the efficiency and precision of test assembly procedures. The utilization of modern ATA approaches offers medical educators a valuable tool to enhance the efficiency and cost-effectiveness of medical education assessment.

Abstract Respiratory diseases are a growing concern in public health because of their potential to endanger the global community. Cell death contributes critically to the pathophysiology of respiratory diseases. Recent evidence indicates that necroptosis, a unique form of programmed cell death (PCD), plays a vital role in the molecular mechanisms underlying respiratory diseases, distinguishing it from apoptosis and conventional necrosis. Necroptosis is a type of inflammatory cell death governed by receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like protein (MLKL), resulting in the release of intracellular contents and inflammatory factors capable of initiating an inflammatory response in adjacent tissues. These necroinflammatory conditions can result in significant organ dysfunction and long-lasting tissue damage within the lungs. Despite evidence linking necroptosis to various respiratory diseases, there are currently no specific alternative treatments that target this mechanism. This review provides a comprehensive overview of the most recent advancements in understanding the significance and mechanisms of necroptosis. Specifically, this review emphasizes the intricate association between necroptosis and respiratory diseases, highlighting the potential use of necroptosis as an innovative therapeutic approach for treating these conditions.

The power grid CO2 emission factor is a critical parameter for accurately calculating indirect emissions from the electricity consumption side, serving as a core indicator for precisely quantifying the CO2 emission pathways at the consumption side. This study explores the temporal and spatial characteristics of the province-level power-grid CO2 emission factors from 2020 to 2035 and compares them with official-source factors. Moreover, it integrates historical direct-emission data to accurately quantify the importance of indirect emissions from the electricity consumption side. Additionally, it predicts the province-level indirect emissions and emission pathways under different scenarios from 2020 to 2035, quantifying the impacts of power grid CO2 emission factors with distinct temporal and spatial accuracies on provincial emission pathways. The results indicate that: (1) from 2020 to 2035, the power grid CO2 emission factors of all provinces are expected to exhibit sustained decreasing trends, and there are disparities between the existing publicly available power-grid CO2 emission factors and provincial levels in the study. (2) From 2010 to 2020, the indirect emissions from electricity consumption and their proportions in net electricity-importing provinces had gradually increased, with Beijing, Shanghai, and Zhejiang province having the largest proportions. (3) Under Scenarios 1 (constant power-grid CO2 emission factors on the national level) and 3 (constant power-grid CO2 emission factors on the provincial level), the indirect emissions from electricity consumption and total emissions of all provinces will be significantly higher than the estimated results in Scenarios 2 (dynamic power-grid CO2 emission factor on the national level) and 4 (dynamic power-grid CO2 emission factor on the provincial level). The estimation results of Scenarios 1 and 2 are projected to differ significantly from those of Scenarios 3 and 4. For provinces with large proportions of indirect emissions from electricity consumption, such as Beijing, Shanghai, and Guangdong, selecting power grid CO2 emission factors with different spatial accuracies is expected to have noticeable impacts on their total emissions, further leading to shifts in their peaking years. The research results can provide a reference for supporting the planning of carbon peaking pathways in various provinces and reducing the uncertainty in indirect emission forecasts.