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Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions1,2. Expansion of T follicular helper (TFH) and T peripheral helper (TPH) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE3,4. Human TFH and TPH cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs. 5,6), yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4+ T cell phenotypes in patients with SLE, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4+ T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ TPH/TFH cell differentiation and promote an IL-22+ phenotype. Type I interferon, a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ TPH/TFH cells on a polarization axis opposite from T helper 22 (TH22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states.

Abstract Background The relationship between vitamin D deficiency and Pseudomonas aeruginosa (P. aeruginosa) colonization in bronchiectasis patients is not well understood. Methods This study was conducted at Shanghai Pulmonary Hospital from June 2014 to May 2018. Serum 25-hydroxyvitamin D levels were measured in patients with bronchiectasis, and clinical data including sputum culture results were collected. To investigate the relationship between vitamin D levels and P. aeruginosa colonization, we conducted correlation analysis and logistic regression. Additionally, in vitro experiments with bone marrow-derived macrophages (BMDMs) infected with P. aeruginosa strain PAO1 were performed to further explore the influence of vitamin D on the bacterial infection and inflammatory response. Results Among the 195 patients with bronchiectasis, 83.1% (162/195) were vitamin D deficient. A significant negative correlation was observed between serum vitamin D levels and the BSI (Bronchiectasis Severity Index) score. Patients with vitamin D deficiency showed higher rates of P. aeruginosa colonization compared to those with adequate vitamin D levels. Female gender and vitamin D deficiency were identified as risk factors for P. aeruginosa colonization in patients with bronchiectasis. Additionally, serum interleukin (IL)-1β levels were significantly elevated in the vitamin D-deficiency group. In vitro experiments, 1,25-dihydroxyvitamin D [1,25D] was shown to inhibit PAO1 phagocytosis in BMDMs and to suppress IL-1β secretion. Conclusions Vitamin D deficiency was strongly associated with an increased risk of P. aeruginosa colonization in patients with bronchiectasis. Furthermore, vitamin D demonstrated protective effects by reducing P. aeruginosa survival in cells and modulating the inflammatory dysregulation induced by the bacterium.

Abstract Background Oral cancer is one of the most prevalent malignant neoplasms globally, with its microenvironment being extremely complicated and heterogeneous with regard to distribution of different types of cells, which creates a barrier against treatment. We integrated single-cell RNA sequencing, pseudotime analysis, and intercellular communication to identify subtypes, state transitions, and interactions in the development of oral cancer and their roles in tumor progression and immune response. Methods Principal component analysis (PCA) followed by dimensionality reduction techniques (UMAP and t-SNE) revealed multiple populations in the single-cell data from oral cancer. Analysis of gene expression patterns associated individual genes with distinct principal components that described features of cell subtypes or states in the oral cancer microenvironment. We also conducted gene set enrichment analysis (GSEA) and cell–cell communication network analysis to investigate the important signaling pathways as well as potential cell–cell communications. Results Gene expression patterns linked to oral cancer cell subtypes and states in this study included cell membrane, signal transduction and immune response in different biological processes. Pseudotime analysis showed differentiation trajectories and expression of essential differentiation genes were also altered. Cell–cell communication network analysis revealed that myeloid cells interacted heavily with myeloid cells and they also had strong interactions with endothelial cells. Analysis of the MIF signaling pathway network showed participation of various cell types in MIF signaling, suggesting its potential significance in the oral cancer microenvironment. Conclusion The intercellular communication complexity of TME in oral cancer is reported here with the first-ever single cell analysis and data providing new perspective regarding the heterogeneity of oral cancer.

Abstract Chenpi, or dried tangerine peel, is a traditional Chinese ingredient valued in medicine and edible for its digestive and respiratory benefits. The geographical origin of Chenpi is important, as it can impact its quality, active compounds and market value. This study develops a strategy to distinguish Chenpi samples on its origin. Thirty-nine samples from eight regions in Xinhui district (Guangdong, China) are analyzed by gas chromatography (GC) and mid-infrared (MIR) technique. Four machine learning methods are employed to establish discrimination models based on GC and MIR data, with two mid-level data fusion strategies to combine the data. The results show that data fusion significantly improves Chenpi origin discrimination. The K-nearest neighbors and artificial neural network models, using modified mid-level data fusion, provide the best performance, misclassified only one sample. Machine learning in combination with modified mid-level data fusion strategy provides effective classification of Chenpi samples from different geographical origins.

Abstract Objectives A predictive model was developed based on enhanced computed tomography (CT), laboratory test results, and pathological indicators to achieve the convenient and effective prediction of single lymph node metastasis (LNM) in gastric cancer. Methods Sixty-six consecutive patients (235 regional lymph nodes) with pathologically confirmed gastric cancer who underwent surgery at our hospital between December 2020 and November 2021 were retrospectively reviewed. They were randomly allocated to training (n = 38, number of lymph nodes = 119) and validation (n = 28, number of lymph nodes = 116) datasets. The clinical data, laboratory test results, enhanced CT characteristics, and pathological indicators from gastroscopy-guided needle biopsies were obtained. Multivariable logistic regression with generalised estimation equations (GEEs) was used to develop a predictive model for LNM in gastric cancer. The predictive performance of the model developed using the training and validation datasets was validated using receiver operating characteristic curves. Results Lymph node enhancement pattern, Ki67 level, and lymph node long-axis diameter were independent predictors of LNM in gastric cancer (p

In the emerging 5G and beyond 5G (B5G) era, the spotlight is sharply focused on the power amplifier, a critical component with stringent specification requirements that dictates the performance of the transmitter. The gallium nitride (GaN) device, with its superior inherent properties, is surfacing as a front-runner for power amplifier applications. The increasing demand for high frequency, high linearity, and cost-effective GaN power amplifiers is driven by anticipated traffic surges and the need for extensive 5G deployment. This paper offers a thorough review and future perspective on research developments in RF GaN device technology. It encompasses critical issues in advanced device and circuit technology, with a focus on high frequency, high linearity, cost-effective GaN-on-Si high electron mobility transistors (HEMTs), and compact modeling. This work aims to serve as a guide for the utilization of GaN HEMTs in 5G communication applications.

Abstract Tuberculosis (TB) remains a prominent global health challenge, with the World Health Organization documenting over 1 million annual fatalities. Despite the deployment of the Bacille Calmette-Guérin (BCG) vaccine and available therapeutic agents, the escalation of drug-resistant Mycobacterium tuberculosis strains underscores the pressing need for more efficacious vaccines and treatments. This review meticulously maps out the contemporary landscape of TB vaccine development, with a focus on antigen identification, clinical trial progress, and the obstacles and future trajectories in vaccine research. We spotlight innovative approaches, such as multi-antigen vaccines and mRNA technology platforms. Furthermore, the review delves into current TB therapeutics, particularly for multidrug-resistant tuberculosis (MDR-TB), exploring promising agents like bedaquiline (BDQ) and delamanid (DLM), as well as the potential of host-directed therapies. The hurdles in TB vaccine and therapeutic development encompass overcoming antigen diversity, enhancing vaccine effectiveness across diverse populations, and advancing novel vaccine platforms. Future initiatives emphasize combinatorial strategies, the development of anti-TB compounds targeting novel pathways, and personalized medicine for TB treatment and prevention. Despite notable advances, persistent challenges such as diagnostic failures and protracted treatment regimens continue to impede progress. This work aims to steer future research endeavors toward groundbreaking TB vaccines and therapeutic agents, providing crucial insights for enhancing TB prevention and treatment strategies.

Abstract Objective To evaluate the effects of different SARS-CoV-2 inactivation methods on the blood concentration of colistin sulfate. Methods A colistin sulfate reference substance, a quality control plasma sample, and a clinically measured sample were transferred and heated in a 56 °C water batch for 30 min or irradiated under an ultraviolet (UV) lamp for 60 min to examine the stability of the reference solution and quality control plasma sample. Statistical analysis was conducted for the concentration of the clinically measured sample before and after inactivation with the intraclass correlation coefficient (ICC) method, the Passing–Bablok regression, and the Bland–Altman analysis. Results The reference substance of colistin sulfate was unstable under UV inactivation. Under moist heat inactivation, the reference substance and quality control plasma sample of colistin sulfate were stable. The ICC of the concentration results of 27 clinical blood samples with and without moist heat inactivation was 0.995 (P

Abstract Background Leisure activity was associated with depression in older adults. However, the specific processes by which diet and cognition mediate the role of leisure activities and depression remain uncertain. The study aims to investigate the relationship between leisure activity and depression in older people and the underlying mechanisms involved, while constructing a comprehensive model that links these variables. Methods Data came from the 2018 Chinese Longitudinal Healthy Longevity Survey. Mini-Mental State Examination and CES-D-10 were used to assess cognition and depression, respectively. PROCESS macro was employed to assess the mediation effects of diet and cognition on the relationship between leisure activity and depression. Results Leisure activity was negatively associated with depression, with 35.90% of the total effect mediated through dietary diversity and cognitive function, of which 1.28% was from the chain-mediated effect of dietary diversity and cognition. In addition, 20.94% of the total effect mediated through a plant-based diet and cognitive function, of which 0.43% was from the chain-mediated effect of plant-based diet and cognition. Conclusions Leisure activities are linked to depression, with diet and cognition acting as chain-mediating factors. Public health experts recommend that older adults engage in leisure activities, ensure a broad spectrum of dietary intake, and prioritize the augmentation of plant-based diets as preventative strategies against depression.

本研究為聚焦「年輕公民與社會／生態正義」跨國研究案的臺灣個案研究，於某大學表演相關科系執行以環境與氣候變遷為主題的「特定場域劇場」戲劇課程。本研究問題有二：如何將批判教育學具體實踐於戲劇教育課程？如何透過聚焦氣候與環境正義的戲劇課程，激發學生的批判思考，並使其得到轉化？為回答上述問題，研究者以大學鄰近深受重工業汙染影響的社區作為本課程的「提問」，把學生認為「太過龐大」的氣候變遷議題聚焦於「減少工業碳排放、促進工業轉型」的在地工業汙染議題。其次，透過「批判的五感教育學」將身體感官置於學習中心，讓學生參與記者會與田野調查，感受社區居民生活與環境運動，使學生從過往囤積式教育的無感學習得到轉化，開始將所學與生活經驗及當地特定脈絡連結，對環境議題有感並形成批判知識。期末學生於特定場域劇場展現其對環境不正義的批判意識與劇場中的行動，進而理解採取在地行動減緩氣候變遷之重要。此即為本研究所稱從「無感」學習經驗到「五感」的環境意識啟蒙及批判教育學實踐。本研究最後提出全球氣候正義議題在地化對永續教育的重要性，並結合五感教育與批判教育學，以補充國內批判教育學的實踐研究。 This study forms part of the broader research project “Global Youth (Digital) Citizen-Artists and their Publics: Performing for Socio-Ecological Justice,” with a specific focus on the Taiwan case study. We conducted a sitespecific theatre class on the environment and climate change in a university’s performing arts department. The research addresses two questions: How can concepts of critical pedagogy be practically applied in theatre education? How can such a class, focused on climate and environmental justice, inspire students to engage in critical thinking and transformative action? To explore these questions, we selected a community near the university severely impacted by heavy industrial pollution as the focal point for this class. By examining the challenge of “reducing industrial carbon emissions and promoting industrial transformation,” we aimed to shift students’ perceptions of climate issues from abstract and overwhelming to concrete and locally relevant. Through “critical sensory pedagogy,” we placed sensory experience at the centre of learning. Students engaged with the lived realities of community residents and environmental movements through immersive activities such as press conferences and field trips. This experiential approach moved them beyond passive containers in banking education, empowering them to connect their academic learning with life experience and specific local historical and social contexts, fostering critical awareness of environmental issues. By the semester’s end, students demonstrated a deepened critical consciousness of environmental injustice, staging sitespecific theatre performances that emphasized the importance of local initiatives in addressing climate change. This process exemplifies what we describe as a shift from “indifference” to “environmental conscientization” through critical sensory pedagogy praxis. This paper highlights the importance of localising global climate justice in sustainable education and contributes to the limited practical research on critical pedagogy by integrating sensory pedagogy with critical pedagogy.

This study explores the challenges and strategies of home care models for older adults with disabilities in China. The following challenges have been identified: limited policy support and lack of effective connections between different systems, pressure on caregivers, underestimation of caregivers’ value, and inadequate service capacity of community institutions. Evidence-based suggestions to promote the development of home care models for older adults with disabilities include establishing a family caregiver compensation mechanism and psychological support system, strengthening community health centers from quantity to service capabilities for aging-in-place services, and promoting the integration of pension, disability, and health insurance systems.

Abstract Background Sarcopenia was recognized to be one of the common comorbidities in heart failure (HF). The sarcopenia index (SI), based on serum creatinine to cystatin C ratio, was developed as a simple tool to evaluate skeletal muscle mass but has not been well-studied in the correlation of left ventricular ejection fraction (LVEF). The aim of this study is to analyze the SI in patients with HF, especially patients with HF with preserved ejection fraction (HFpEF), and to develop a prediction model for HFpEF. Methods The training cohort included 229 hospitalized patients with HF and 73 healthy controls (HCs) from the Third Affiliated Hospital of Soochow University between December 2019 and February 2022. An additional 78 patients with HF hospitalized at the same hospital between March 2022 to June 2023 were considered as an external validation cohort. Binary logistic regression model was used to analyze the influence factors of HFpEF. A prediction model was constructed and optimized based on the least absolute shrinkage and selection operator (LASSO), displayed by Nomogram and verified internally by Bootstrap with 500 resamples. Results SI was significantly different between the HF and HC groups (67.95 ± 13.07 vs. 98.57 ± 31.51) and had a significant negative correlation with LVEF. Multivariate logistic regression demonstrated that SI (OR 0.948, 95% CI 0.914—0.983, P = 0.004) was independently associated with HFpEF. The area under the curve (AUC) for the nomogram constructed based on SI was 0.902. The calibration curve was approximately distributed along the reference line in Bootstrap and the decision curve analysis demonstrated significantly better net benefit in the model. The external validation proved the good predictive performance of the model. Conclusions Lower SI is an independent factor associated with hospitalized patients with HF, especially patients with HFpEF. A prediction nomogram based on SI has good predictive power for HFpEF. Trial registration The study was registered with the China Clinical Trials Centre Registry (registration number: ChiCTR2200063401).

Abstract Background Epithelial ovarian cancer (EOC) is a lethal form of gynecological malignancy. Some EOC patients experience relapse after standard primary debulking surgery (PDS) and adjuvant chemotherapy (ACT). Identifying molecular residual disease (MRD) by circulating tumor DNA (ctDNA) detection can timely signal the potential for relapse. However, research on the usage of ctDNA for MRD detection in EOC is limited. Methods Fifty-one EOC patients who received standard PDS and ACT were included. Targeted sequencing based on a panel of 1021 cancer-related genes, along with further validation using Enrich-rare-mutation sequencing, was performed on tumor tissues acquired during PDS and on plasma samples collected before and after PDS/ACT to identify variants reflecting tumor signals. Results Post-surgery MRD was associated with relapse (Log-rank p = 0.0006) and was identified as an independent prognostic factor (HR, 3.4; 95% CI, 1.02–11.42; p = 0.047). The negative and positive predictive values were 0.83 and 0.62 respectively. Additionally, post-surgery MRD outperformed CA125 in predicting relapse, and integrating both parameters could provide more accurate risk stratification. Post-ACT MRD detection identified the patients with ctDNA clearance who were still at risk of relapse. Furthermore, baseline ctDNA detection could help determine patients who are not suitable for further tests after surgery. Conclusions Post-surgery MRD is superior to CA125 in predicting relapse in EOC. Patients exhibiting transient ctDNA clearance, as evaluated by post-ACT MRD, may require longitudinal monitoring. Baseline ctDNA detection could help determine whether post-surgery ctDNA monitoring should be performed.

Abstract Background Clinical reception training plays a crucial role in developing undergraduates’ clinical thinking and competence. The study aimed to evaluate the effectiveness of clinical reception training conducted by standard patients (SPs) and dental simulators among undergraduate students. Materials and methods In the first week of the internship, sixty-five 5th-year undergraduate students were divided into two groups: SP group, which received traditional theoretical training along with clinical reception training, and control group that only received traditional theoretical training. After 2 weeks and 8 weeks of training, all students were assessed with real patients by experienced prosthodontists using Mini-CEX assessment score sheets. Statistical analysis was performed using independent-samples T test or repeated-measures ANOVA (P

Hip fracture in the elderly is a major health problem. Multi-professional rehabilitation approaches were recommended; however, there were various multi-professional rehabilitation models; therefore, identifying the multi-professional rehabilitation model, especially for older persons after hip fracture surgery, is needed. The aim of this review study is to identify a multi-professional rehabilitation model among the elderly with hip fracture surgery. A literature search for relevant articles in PubMed, Scopus, Embase, and CINAHL was used. Studies that met the following criteria were included: Patients with hip fracture surgery, multi-professional rehabilitation, and randomized controlled trial study, measured physical outcome, published during 2018 to 2024, English full-text article. Finally, six articles met inclusion criteria. The multi-professional rehabilitation model among older persons after hip fracture surgery includes geriatric interdisciplinary home rehabilitation, multicomponent home-based rehabilitation, comprehensive geriatric care, fragility integrated rehabilitation, and comprehensive orthogeriatric care. In addition, hip fracture rehabilitation problems include fear of falling and comorbid and postoperative complications. The multi-professional rehabilitation model improved the quality of life of the older persons after hip fracture surgery. Multi-professionals’ rehabilitation model effectively improved physical performance among older persons after hip fracture surgery. Identifying multi-professional rehabilitation models with specific needs for older persons after hip fracture surgery are recommended in clinical practice.

Abstract Background Risk prediction models can identify individuals at high risk of chronic liver disease (CLD), but there is limited evidence on the performance of various models in diverse populations. We aimed to systematically review CLD prediction models, meta-analyze their performance, and externally validate them in 0.5 million Chinese adults in the China Kadoorie Biobank (CKB). Methods Models were identified through a systematic review and categorized by the target population and outcomes (hepatocellular carcinoma [HCC] and CLD). The performance of models to predict 10-year risk of CLD was assessed by discrimination (C-index) and calibration (observed vs predicted probabilies). Results The systematic review identified 57 articles and 114 models (28.4% undergone external validation), including 13 eligible for validation in CKB. Models with high discrimination (C-index ≥ 0.70) in CKB were as follows: (1) general population: Li-2018 and Wen 1–2012 for HCC, CLivD score (non-lab and lab) and dAAR for CLD; (2) hepatitis B virus (HBV) infected individuals: Cao-2021 for HCC and CAP-B for CLD. In CKB, all models tended to overestimate the risk (O:E ratio 0.55–0.94). In meta-analysis, we further identified models with high discrimination: (1) general population (C-index ≥ 0.70): Sinn-2020, Wen 2–2012, and Wen 3–2012 for HCC, and FIB-4 and Forns for CLD; (2) HBV infected individuals (C-index ≥ 0.80): RWS-HCC and REACH-B IIa for HCC and GAG-HCC for HCC and CLD. Conclusions Several models showed good discrimination and calibration in external validation, indicating their potential feasibility for risk stratification in population-based screening programs for CLD in Chinese adults.

Abstract Tissue regeneration is a complex process involving large changes in cell proliferation, fate determination, and differentiation. Mitochondrial dynamics and metabolism play a crucial role in development and wound repair, but their function in large-scale regeneration remains poorly understood. Planarians offer an excellent model to investigate this process due to their remarkable regenerative abilities. In this study, we examine mitochondrial dynamics during planarian regeneration. We find that knockdown of the mitochondrial fusion gene, opa1, impairs both tissue regeneration and stem cell pluripotency. Interestingly, the regeneration defects caused by opa1 knockdown are rescued by simultaneous knockdown of the mitochondrial fission gene, drp1, which partially restores mitochondrial dynamics. Furthermore, we discover that Mitolow stem cells exhibit an enrichment of pluripotency due to their fate choices at earlier stages. Transcriptomic analysis reveals the delicate mitonuclear balance in metabolism and mitochondrial proteins in regeneration, controlled by mitochondrial dynamics. These findings highlight the importance of maintaining mitochondrial dynamics in large-scale tissue regeneration and suggest the potential for manipulating these dynamics to enhance stem cell functionality and regenerative processes.

Abstract This research explored the link between teacher-student relationships and learning engagement, considering perceived social support as a mediator and academic self-efficacy as a moderator. A total of 930 college students completed the Academic Self-Efficacy Scale, Teacher-Student Relationships Questionnaire, Multidimensional Scale of Perceived Social Support, and College Student Learning Engagement Questionnaire. Mediating and moderating effects were investigated using SPSS19.0 and one of its process plugins 3.5. The findings indicated (1) teacher-student relationships positively predicted learning engagement; (2) perceived social support mediated the link between teacher-student relationships and learning engagement; and (3) academic self-efficacy moderated the initial phase of the pathway to the mediating role of perceived social support. Moreover, the mediating effect was more significant at elevated academic self-efficacy levels. Establishing harmonious relationships between teachers and students, nurturing students’ confidence in their academic abilities , and expanding students’ access to social support were essential to boosting the educational involvement of college students. The study findings will help educators enhance college students’ engagement in learning and provide recommendations for educators to conduct educational and teaching activities.

Abstract Background Sarcopenia, the age‐related loss of muscle mass and function, brings multiple adverse outcomes including disability and death. Several sarcopenia consensuses have newly introduced the premorbid concept of possible sarcopenia and recommended early lifestyle interventions. Bidirectional transitions of premorbid states have been revealed in several chronic diseases yet not clarified in sarcopenia. This study aims to investigate the underlying transition patterns of sarcopenia states. Methods The study utilized three waves of data from a nationally representative survey, the China Health and Retirement Longitudinal Study (CHARLS), and included community‐dwelling individuals aged 60 years and older with at least two sarcopenia states assessments based on the Asian Working Group for Sarcopenia criteria 2019 (AWGS2019) between 2011 and 2015. The estimated transition intensity and probability between non‐sarcopenia, possible sarcopenia, sarcopenia, and death were investigated using multi‐stage Markov (MSM) models. Results The study comprised 4395 individuals (49.2% female, median age 67 years) with a total of 10 778 records of sarcopenia state assessment, and the mean follow‐up period was 3.29 years. A total of 24.5% of individuals with a current state of possible sarcopenia returned to non‐sarcopenia, 60.3% remained possible sarcopenia, 6.7% progressed to sarcopenia, and 8.5% died by the next follow‐up. The transition intensity of recovery to non‐sarcopenia (0.252, 95% CI 0.231–0.275) was 2.8 times greater than the deterioration to sarcopenia (0.090, 95% CI 0.080–0.100) for individuals with possible sarcopenia. For individuals with possible sarcopenia, the estimated probabilities of recovering to non‐sarcopenia, progressing to sarcopenia, and transitioning to death within a 1‐year observation were 0.181, 0.066, and 0.035, respectively. For individuals with sarcopenia, the estimated probabilities of recovering to non‐sarcopenia, recovering to possible sarcopenia, and transitioning to death within 1‐year observation were 0.016, 0.125, and 0.075, respectively. In covariables analysis, age, sex, body mass index, physical function impairment, smoking, hypertension, and diabetes are important factors influencing bidirectional transitions. Conclusions The findings highlight the bidirectional transitions of sarcopenia states among older adults and reveal a notable proportion of possible sarcopenia show potential for recovery in the natural course. Screening and intensifying interventions based on risk factors may facilitate a recovery transition.

Abstract Objective In the present study, we aimed to explore the association between left atrial appendage emptying velocity (LAAEV) measured by transesophageal echocardiography and atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) in patients with early persistent atrial fibrillation (PeAF). Methods We retrospectively analyzed patients with early PeAF who underwent their initial ablation procedure. The echocardiographic and clinical data of the enrolled patients were collected and recorded prior to the operation. Following adjustment for confounding factors, we investigated the relationship between the LAAEV and AF recurrence in patients with early PeAF after radiofrequency ablation. Results The proportions of AF recurrence in the low, medium, and high LAAEV groups were 48.8%, 16.0%, and 13.1%, respectively. After adjusting for potential confounding factors, we observed a gradual decrease in the risk of AF recurrence with increasing LAAEV (odds ratio: 0.882, 95% confidence interval: 0.842—0.924, p

Abstract Inflammatory bowel diseases (IBD) are a group of chronic, non-specific intestinal diseases that could comorbid with varieties of negative emotional constructs, including pain-related negative emotions and trait negative emotions; however, the link between brain functions and different dimensions of negative emotions remains largely unknown. Ninety-eight patients with IBD and forty-six healthy subjects were scanned using a 3.0-T functional magnetic resonance imaging scanner. The amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were used to assess resting-state brain activity. Partial least squares (PLS) correlation was employed to assess the relationship among abnormal brain activities, pain-related and trait negative emotions. Compared to controls, patients with IBD exhibited higher values of ALFF in the right anterior cingulate cortex (ACC), lower values of ALFF in the left postcentral gyrus, and higher values of DC in the bilateral ACC. Multivariate PLS correlation analysis revealed the brain scores of the ACC were correlated with pain-related negative emotions, the brain salience in the left postcentral gyrus was associated with the higher-order trait depression. These findings can enhance our comprehension of how pain-related negative emotion and trait negative emotion affect the brains of patients with IBD in distinct ways.

Abstract Adiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²). Genetically-predicted body mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-to-hip ratio (WHR) are significantly (FDR

BackgroundWith the events reporting on odors in drinking water, odorous substances in water have become a hot topic in water quality analysis. Due to the low concentration of the odor threshold and the complexity of the odor components in water, it is difficult to make accurate qualitative and quantitative analysis. So it is necessary to develop a highly sensitive and accurate qualitative and quantitative analysis method. ObjectiveTo establish a method for simultaneous determination of four odorous substances, including dimethyl disulfide, dimethyl trisulfide, 2-methylisoborneol, and geosmin in water by purge and trap-gas chromatography-tandem mass spectrometry. MethodsA certain amount of water sample was stored in the sample vial of a purge and trapinstrument. Through nitrogen purging, the odorous substances in water were purged out and enriched in the trap. Subsequently, the odorous substances were rapidly released at high temperatures after heating the trap, and then carried by carrier gas into gas chromatograph. After temperature programming, the substances were separated by an Agilent DB-624 capillary chromatographic column (30 m×0.25 mm, 1.4 μm) and determined by tandem mass spectrometry in multiple reaction monitoring modes, with internal standard method for quantification. The current project optimized purge time, sodium chloride concentration in water sample, desorption temperature, desorption time, and split ratio during the experimental process. Under the optimized experimental conditions, the standard curve, detection limit, and quantification limit were validated. Recovery tests with spiking concentrations of 5.0, 10.0, 30.0, 80.0 ng·L−1 and precision tests were conducted on water samples. Finally, the established method was applied to detect odorous substances in source water, finished water, and pipeline water in Deqing County of Huzhou City. ResultAfter the optimization, the purge time was 20 min, the desorption temperature was 280 ℃, the desorption time was 2 min, the split ratio was 10∶1, and no sodium chloride was added during the purge process. Under the optimized experimental conditions, the calibration curves for the four odorous substances showed an excellent linearity in the range of 1 to 100 ng·L−1 (R>0.999), with 0.3 ng·L−1 limit of detection and 1.0 ng·L−1 limit of quantitation. The average recoveries were from 85.5% to 102.4% and relative standard deviations (RSD) from 1.6% to 5.2%. After applying this method to detect local source water, finished water, and pipeline water, it was found that the positive rates of 2-methylisoborneo, and geosmin were relatively high, while the positive rates of dimethyl disulfide and dimethyl trisulfide were relatively low. Only one sample of source water tested positive for dimethyl disulfide, and all samples were negative for dimethyl trisulfide. ConclusionCombined with the superiority of purge and trap and tandem mass spectrometry, the method has the advantages of easy to perform, strong anti-interference ability, good accuracy and precision, which meet the limit requirements of the four odorous substances in the expanded indices and reference indices of Hygienic standards for drinking water (GB 5749-2022). It also provides technical support for water quality assessment and analysis of odorous substances.

BackgroundRecent research has made significant progress in elucidating gastrointestinal complications following acute cerebral infarction (ACI), which includes disorders in intestinal motility and dysbiosis of the gut microbiota. Nevertheless, the role of the gut (which is acknowledged as being the largest immune organ) in the immunoreactive effects of polydopamine nanoparticles (PDA) on acute ischemic stroke remains inadequately understood. In addition to its function in nutrient absorption, the gut acts as a protective barrier against microbes. Systemic immune responses, which are triggered by the disruption of gut barrier integrity, are considered as one of the mechanisms underlying acute ischemic stroke, with the gut-brain axis (GBA) playing a pivotal role in this process.MethodsIn this study, we used a PDA intervention in an ACI model to investigate ACI-like behavior, intestinal barrier function, central and peripheral inflammation, and hippocampal neuron excitability, thus aiming to elucidate the mechanisms through which PDA improves ACI via the GBA.ResultsOur findings indicated that as ACI mice experienced dysbiosis of the gut microbiota and intestinal barrier damage, the levels of proinflammatory factors in the serum and brain significantly increased. Additionally, the activation of astrocytes in the hippocampal region and neuronal apoptosis were observed in ACI mice. Importantly, our study is the first to provide evidence demonstrating that PDA effectively suppresses the neuroimmune interactions of the gut-brain axis and significantly improves intestinal epithelial barrier integrity.ConclusionWe hope that our discoveries will serve as a foundation for further explorations of the therapeutic mechanisms of PDA in ACI, particularly in elucidating the protective roles of gut microbiota and intestinal barrier function, as well as in the development of more targeted clinical interventions for ACI.

The shoot apex of Populus alba primarily comprises the shoot apical meristem, axillary meristem, leaf primordium, and young leaves, all of which exhibit high division potential. The single-cell RNA sequencing of the apical buds of P. alba can provide deeper insights into the processes of cell proliferation and differentiation, including the key genes and signaling pathways that regulate these processes. Scanning electron microscopy was used to examine the structure of the shoot apex, followed by single-cell sequencing analysis. A total of 29,011 cells were obtained from two biological replicates. Dimensionality reduction and clustering identified 17 distinct cell clusters. Pseudotime analysis revealed that shoot apex meristem cells and mesophyll cells emerged first, followed by the differentiation and maturation of vascular and intercalary meristem cells over time. Trichome differentiation occurred last, whereas epidermal cell differentiation persisted throughout development. At the single-cell level, auxin signaling pathway genes potentially involved in leaf tissue development were identified, along with an analysis of the expression specificity of CYC and CDK genes across mesophyll, epidermis, vascular, and shoot apex meristem tissues. These findings facilitate the elucidation of the molecular regulatory mechanisms by which CYC and CDK genes influence leaf development in P. alba.

In the realm of isolated direct-current microgrids with varying distributed energy storage unit capacities, a new energy equalization strategy is proposed. This method involves an innovative approach that integrates an improved state-of-charge equalization control integrated with a sigmoid function to adaptively adjust the droop coefficient, aiming to accelerate the state-of-charge equalization rate. Furthermore, a virtual voltage drop equalization control is designed to dynamically adjust the output current of each distributed energy storage unit through a simple proportional–integral controller. This eliminates the influence of line impedance on accurate current distribution, improving overall accuracy. Additionally, a dynamic consistency algorithm is employed to gather average information about the distributed energy storage system, reducing communication line pressure as local nodes only exchange information with neighboring nodes. Integrating the aforementioned modules, the strategy proposed in this paper achieves rapid state-of-charge equalization, precise distribution of output current, and stable maintenance of the bus voltage. Finally, rigorous analysis of experimental results under various operating conditions verifies the feasibility and effectiveness of this control strategy by using the RT-LAB.

BackgroundPolygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain.Methods and findingsWe constructed 80 PRSs for the 13 most common cancers using seven schemes and evaluated these PRSs in 100,219 participants from the China Kadoorie Biobank (CKB). The optimal PRSs with the highest discriminatory ability were used to define genetic risk, and their site-specific and cross-cancer associations were assessed. We modeled 10-year absolute risk trajectories for each cancer across risk strata defined by PRSs and modifiable risk scores and quantified the explained relative risk (ERR) of PRSs with modifiable risk factors for different cancers. More than 60% (50/80) of the PRSs demonstrated significant associations with the corresponding cancer outcomes. Optimal PRSs for nine common cancers were identified, with each standard deviation increase significantly associated with corresponding cancer risk (hazard ratios (HRs) ranging from 1.20 to 1.76). Compared with participants at low genetic risk and reduced modifiable risk scores, those with high genetic risk and elevated modifiable risk scores had the highest risk of incident cancer, with HRs ranging from 1.97 (95% confidence interval (CI): 1.11-3.48 for cervical cancer, P = 0.020) to 8.26 (95% CI: 1.92-35.46 for prostate cancer, P = 0.005). We observed nine significant cross-cancer associations for PRSs and found the integration of PRSs significantly increased the prediction accuracy for most cancers. The PRSs contributed 2.6%-20.3%, while modifiable risk factors explained 2.3%-16.7% of the ERR in the Chinese population.ConclusionsThe integration of existing evidence has facilitated the development of PRSs associated with nine common cancer risks in the Chinese population, potentially improving clinical risk assessment.

BackgroundAdvanced triple-negative breast cancer (TNBC) presents significant therapeutic challenges, particularly in Asian populations, which exhibit distinct biological and genetic characteristics. Immunotherapy combined with chemotherapy has emerged as a promising approach; however, its efficacy compared to chemotherapy alone remains under investigation. This meta-analysis aims to evaluate the clinical outcomes of PD-1/PD-L1 inhibitors combined with chemotherapy (PIC) versus chemotherapy alone in the treatment of advanced TNBC in Asian patients.MethodsA systematic literature search was performed across six databases for phase 3 randomized controlled trials (RCTs). Only studies comparing the outcomes of PIC versus chemotherapy alone in patients with advanced TNBC, including subgroup analyses of Asian populations, were included. Data were pooled to assess overall survival (OS), progression-free survival (PFS), responses, and safety profiles.ResultsA total of 1041 patients from five phase 3 RCTs were included in the final analysis. Compared to chemotherapy alone, PIC therapy significantly improved PFS (hazard ratio [HR]: 0.74 [0.62, 0.88], P = 0.0008). No significant difference was observed in OS (HR: 0.78 [0.55, 1.12], P = 0.18), although a slight trend favoring PIC therapy was noted. Among PD-L1-positive patients, both OS (HR: 0.62 [0.44, 0.86], P = 0.005) and PFS (HR: 0.66 [0.50, 0.86], P = 0.003) were significantly improved in the PIC group. The PIC group also exhibited a substantially higher OS rate at 12–36 months and a higher PFS rate at 6–30 months. However, the incidence of immune-related AEs (irAEs) (risk ratio [RR]: 1.69 [1.33, 2.15], P < 0.0001) and grade 3–5 irAEs (RR: 3.11 [1.59, 6.10], P = 0.001) was significantly higher in the PIC group. The most common irAEs in the PIC group were hypothyroidism (14.40%), dermatitis (10.00%), and infusion reactions (8.85%). Both treatment groups exhibited similar response rates and treatment-related AEs (TRAEs).ConclusionsIn Asian patients with advanced TNBC, PIC significantly improved survival compared to chemotherapy alone. Although the combination therapy was associated with a higher incidence of irAEs, its clinical benefits support its use as a viable treatment option for this population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024622428.

ABSTRACT Background There is limited evidence about the association of muscle mass, strength and quality with respiratory disease, especially in Chinese populations. We aimed to comprehensively examine such associations and identify better metrics with more clinical and public health relevance. Methods We conducted a prospective cohort study based on data from the second resurvey of the China Kadoorie Biobank (CKB) study in participants with no prevalent respiratory disease or cancer. Arm muscle quality was calculated as the ratio of grip strength to arm muscle mass. Low muscle mass, grip strength and arm muscle quality were defined as the sex‐specific lowest quintiles of corresponding variables. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for respiratory disease. Results In total, 17 510 participants aged 38–88 (65.4% women; mean age 57.8 ± 9.6) were enrolled in 2013–2014 and followed up until 31 December 2018. During a median follow‐up of 4.82 years, 1346 participants developed respiratory disease. After adjustment for sociodemographic characteristics, lifestyle factors and medical histories, the elevated HR of respiratory disease was 1.31 (1.14–1.51) for low grip strength and 1.25 (1.09–1.44) for low arm muscle quality. Grip strength and arm muscle quality exhibited a linearly inverse association between respiratory disease (p = 0.137 and 0.102), with each standard deviation (SD) decrease in grip strength and arm muscle quality associated with a 22% (95% CI: 11%–34%) and 14% (95% CI: 7%–22%) increased risk of respiratory disease. No association was found for low total muscle mass index and low appendicular muscle mass index. Conclusion Low grip strength and arm muscle quality are associated with increased risks of respiratory disease, and they are better muscle‐related metrics for identifying adults at high risk of respiratory disease. Chinese adults may need to maintain normal muscle mass, strength and quality to achieve better respiratory health, but this needs to be validated in appropriately designed clinical trials.

Abstract Background The integrity of brain function is at stake due to cerebral ischemia‐reperfusion injury (CIRI), which encompasses mitochondrial dysfunction, autophagy, and neuroinflammation. The role of E2F1 in mediating these processes in microglia during CIRI remains unclear. Methods A CIRI mouse model was utilized for single‐cell RNA transcriptome sequencing of brain tissues. The research comprised diverse gene expression, gene ontology (GO), and the enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Experimental techniques included oxygen‐glucose deprivation (OGD/R) cell models, RT‐qPCR, Western Blot, ChIP assays, and microglia‐neuron co‐cultures. Results A significant aspect highlighted in the study was the involvement of CDK5 in the induction of mitochondrial abnormalities associated with CIRI. Upregulation of E2F1 and CDK5 in post‐CIRI microglia was observed. E2F1 facilitated CDK5 transcription, leading to DRP1 phosphorylation, exacerbating neurotoxic effects. Silencing E2F1 improved neurobehavioral outcomes in CIRI mice. Conclusions Activation of E2F1‐mediated CDK5 drives mitochondrial division while inhibiting mitophagy in microglia, triggering inflammation, neuronal apoptosis, and exacerbating CIRI damage. Targeting this pathway could offer novel therapeutic strategies for mitigating CIRI‐induced brain injury. Key points Identification of the E2F1/CDK5/DRP1 Axis in CIRI This study reveals that the E2F1 transcription factor upregulates CDK5 expression, which in turn phosphorylates DRP1, promoting excessive mitochondrial fission and inhibiting mitophagy in microglia. This mechanism plays a critical role in cerebral ischemia‐reperfusion injury (CIRI). Mitochondrial Dysfunction and Neuroinflammation The activation of DRP1 leads to mitochondrial fragmentation and excessive ROS accumulation, triggering microglial activation and inflammatory responses, exacerbating neuronal apoptosis and brain injury in CIRI. Therapeutic Potential of E2F1 Silencing Knockdown of E2F1 in microglia effectively reduces mitochondrial damage, restores mitophagy, suppresses inflammation, and improves neurological outcomes in a CIRI mouse model, highlighting a promising therapeutic target for ischemic stroke intervention.

Abstract The prediction of high‐energy radiation belt electrons is vital for preventing their damage to satellites. Previous machine learning models mostly predict the fluxes of high‐energy electrons (hundreds of keV to MeV) in the outer radiation belt and slot region (L > 2.6). Here, we trained a double‐layer long short‐term memory (LSTM) neural network model and successfully predicted the spatial and temporal variations of the 108–749 keV electrons in the inner radiation belt (L ∼ 1.2–2.2) and slot region (L ∼ 2.2–3.2). Under different solar or geomagnetic conditions, the prediction efficiency of the present model maintains 0.6–0.99 in the inner belt and slot region, and its prediction error is less than 0.48. The high‐resolution (∼11 s) LSTM model could predict the rapid injection events of high‐energy electrons within several minutes in the radiation belts.

IntroductionKlebsiella pneumoniae is a Gram-negative bacterium and the third most commonly isolated microorganism in blood cultures from septic patients. Despite extensive research, the mechanisms underlying K. pneumoniae-induced sepsis and its pathogenesis remain unclear. Acute respiratory failure is a leading cause of mortality in systemic K. pneumoniae infections, highlighting the need to better understand the host immune response and bacterial clearance mechanisms.MethodTo investigate the impact of K. pneumoniae infection on organ function and immune response, we utilized a systemic infection model through intraperitoneal injection in mice. Bacterial loads in key organs were quantified, and lung injury was assessed. Survival analysis was performed in wild-type (WT) and gene deficient mice. Mitochondrial damage and reactive oxygen species (ROS) production, as well as cytokine levels were measured in macrophages isolated from these mice to evaluate their contribution to bacterial clearance capacity.ResultsOur findings demonstrate that K. pneumoniae systemic infection results in severe lung injury and significant bacterial accumulation in multiple organs, with the highest burden in the lungs. Deficiency of caspase-11 or NLRP3 led to prolonged survival, a reduction in pulmonary bacterial load, increased blood oxygen levels, and decreased IL-6 levels in the lungs compared to WT controls. Furthermore, caspase-11- and NLRP3-deficient macrophages exhibited elevated mitochondrial ROS production in response to K. pneumoniae, which correlated with more effective bacterial clearance.DiscussionThese results suggest that caspase-11 and NLRP3 contribute to K. pneumoniae-induced sepsis by impairing mitochondrial function and reducing ROS production in macrophages, thereby compromising bacterial clearance. The observed reduction in lung injury and increased survival in caspase-11- and NLRP3-deficient mice indicate that targeting these pathways may offer potential therapeutic strategies to improve host defense against systemic K. pneumoniae infection.

Background: Bile duct carcinoma (BTC) is an uncommon malignant tumor of the gastrointestinal tract. Management is limited after the progress of first-line treatment. Immune checkpoint inhibitors (ICIs) have been proven popular in solid tumors. Immunotherapy plus chemotherapy has been a standard scheme in the management of multiple types of cancer. However, their efficacy and safety still need further exploration in patients who diagnosed BTC. This research mainly discusses the efficacy of immunotherapy in the second-line use of cholangiocarcinoma. Methods: In total, 126 individuals with BTC diagnosis from 2014 to 2024, who were treated with first-line or neoadjuvant treatment but were evaluated for progression or intolerance, were retrospectively included. All patients received standard chemotherapy, 57 received ICIs in combination with targeted therapy or not, and 69 did not. Patients were divided into simple chemotherapy (SC) and CT. Differences in efficacy, adverse events, progression-free survival (PFS), overall survival (OS), progressive disease (PD), and efficacy of multiple factors and efficacy were analyzed. The primary endpoint is defined as OS. The secondary endpoint is defined as PFS, objective response rate (ORR), disease control rate (DCR), and treatment-related adverse reactions (TRAEs). Results: The PFS and OS of 4.68 and 30.26 months for ICIs with or without targeted therapy were proven statistically significant ( P = .0012; P

ObjectiveTo analyze the prevalence of myopia among children and adolescents in Chengdu from 2021 to 2023, providing insights for myopia prevention and control.MethodsThis study was a school-based cross-sectional study in children and adolescents aged 3–18 years in Hi-tech District of Chengdu City. All the students underwent comprehensive ocular measurement, including uncorrected binocular visual acuity (VA), spherical equivalent error (SER) with noncycloplegic autorefraction, corneal radius (CR), and axial length (AL).ResultsOver the three-year study period from 2021 to 2023, the overall prevalence of myopia was 38.15%, with annual rates of 38.74% in 2021, 38.67% in 2022, and 37.03% in 2023. The prevalence and severity of myopia increased significantly with age (P

ObjectiveTo explore the developmental trajectory of sleep disturbance in geriatric oncology inpatients and assess the impact of locomotive syndrome (LS) on this trajectory.MethodsThis longitudinal study enrolled 284 geriatric oncology inpatients through convenience sampling from August 2023 to February 2024 at the Oncology Center of the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China. Sleep quality was monitored for seven days following admission (T0-T6) using a wrist motion analyzer. The developmental trajectory of sleep disturbance was analyzed using the latent category growth model (LCGM). Patients were categorized into the LS group (n=177) and the non-LS group (n=107) based on the 25-question Geriatric Locomotive Function Scale (GLFS-25). Comparisons were made between the two groups regarding the distribution of sleep disturbance trajectories.ResultsThree potential categories for the development trajectory of sleep disturbance in inpatients were identified: non-sleep disturbance, sleep disturbance improvement, and sleep disturbance persistence. The lowest sleep quality was observed on the second day after admission (T2). In the non-LS group, 40 cases (37.4%) experienced no sleep disturbance, 45 cases (42.1%) showed improvement, and 22 cases (20.6%) showed persistence of sleep disturbance. In the LS group, 32 cases (18.1%) experienced no sleep disturbance, 50 cases (28.2%) showed improvement, and 95 cases (53.7%) exhibited persistent sleep disturbance. Significant differences were found in the trajectory distribution of sleep disturbance between the two groups (P

The Tibetan Plateau (TP) is a hotspot for early human history research, however, there is no evidence of prehistoric human activity on the southern TP during the Last Glacial Maximum (LGM). Thus, it remains unclear how the cold climate affected human activities and whether humans could survive such extremes on the Tibetan Plateau. Here, we present eight AMS 14C dates obtained from charcoal at a newly discovered blade site-Pengbuwuqing (PBWQ) in the Yarlung Zangbo River Valley basin, southern TP. We have also identified ochre at Paleolithic sites on the TP for the first time. Our chronological data indicate the human occupation of the Yarlung Tsangpo River basin during MIS2 (cal 29.2–27.0 kyr B.P), (cal 25.03–24.37 kyr B.P), and (cal 23.7–23.1 kyr B.P). This site represents the first evidence of human activity during the LGM in the southern TP valley and indicates that the southern TP river valley could have served as a refugium enabling prehistoric humans to survive the cold LGM on the TP.

PurposeThe Chinese Visceral Adiposity Index (CVAI), a measure of visceral adiposity dysfunction, is used to assess visceral fat (VFA) malfunction. This research was performed to evaluate the relationship between CVAI and serum uric acid levels in type 2 diabetes mellitus (T2DM) patients.MethodsA total of 2268 patients with T2DM were enrolled in this study. We collected the general clinical information of patients, measured the basic anthropometric indicators, tested glycolipid metabolism and biochemical indicators, and measured the visceral and subcutaneous fat area with bioelectrical impedance technology. According to the quartiles of the CVAI, the T2DM patients were classified into four groups: group A (CVAI ≤ 94.43), group B (94.43

Summary: Background: Existing studies have not provided robust evidence about the CVD risk of non-smoking patients with restrictive spirometric pattern (RSP) or airflow obstruction (AFO), and how the risk is modified by body shape. We aimed to bridge the gap. Methods: We used never-smokers' data from the China Kadoorie Biobank (CKB) and performed Cox models by sex (278,953 females and 50,845 males). Spirometry was used to assess the baseline spirometric pattern. CVD outcomes were captured through multiple sources. Findings: Females’ results were presented primarily, though males' results were similar. During a median 12-year (maximum 14.5 years) follow-up, both RSP and AFO patients had increased risks of acute myocardial infarction (AMI), other ischaemic heart disease (other IHD), heart failure, pulmonary heart disease, arrhythmia, and intracerebral haemorrhage (ICH). RSP was also associated with ischaemic stroke (IS). The HRs (95% CIs) for AFO in females ranged from 1.29 (1.15–1.45) for ICH to 8.84 (7.79–10.03) for pulmonary heart disease, while those for RSP ranged from 1.11 (1.08–1.15) for IS to 3.17 (2.80–3.59) for pulmonary heart disease. These risks increased with the severity of AFO and reduced FVC. RSP/AFO was more strongly associated with other IHD, heart failure, and pulmonary heart disease in underweight females than in normal and obese counterparts, respectively. Interpretation: With the confounding of smoking fully controlled, both RSP and AFO were associated with higher risks of various CVD outcomes, which further increased with the severity of AFO and reduced FVC. These associations were even stronger in underweight individuals. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Ministry of Science and Technology of the People's Republic of China, Kadoorie Charitable Foundation, UK Wellcome Trust, UK Medical Research Council, Cancer Research UK, and British Heart Foundation.

Background: Acute variceal bleeding (AVB), a life-threatening complication of liver cirrhosis, can be effectively treated by endoscopy, but there is a risk of early rebleeding after endoscopic variceal treatment (EVT). Thrombocytopenia is the most common hemostatic abnormality in liver cirrhosis. However, it is still unclear about whether thrombocytopenia increases the failure of EVT in cirrhotic patients with AVB. Objectives: We investigated the association between thrombocytopenia and the failure of EVT in cirrhotic patients with AVB. Design: International multicenter, retrospective study. Methods: Overall, 2467 cirrhotic patients with acute gastrointestinal bleeding who were enrolled into an international multicenter study between September 30, 2020 and June 30, 2023 were retrospectively screened. Thrombocytopenia was defined as platelet count below 150 × 10 9 /L and further classified as mild (100 × 10 9 /L–150 × 10 9 /L), moderate (50 × 10 9 /L–100 × 10 9 /L), and severe (

Pyroptosis is a form of proinflammatory cell death characterized by inflammasome activation, pore formation, and the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-18 upon cell rupture. Nuclear factor-κB (NF-κB), a prototypical pro-inflammatory transcription factor, plays a critical role in immune system regulation. Recent research highlights the multifaceted roles of NF-κB signaling in pyroptosis. Various immunologically relevant ligands and their receptors can activate the NF-κB pathway to promote pyroptosis, with Toll-like receptors (TLRs), IL-1 receptors (IL-1Rs), and TNF receptors (TNFRs) being the most prominent. NF-κB regulates the transcription of key components of inflammasomes involved in pyroptosis, particularly the NLRP3 inflammasome. Recent studies also indicate that NF-κB modulates the activation of NLRC4 and AIM2 inflammasomes through distinct pathways in diverse inflammatory conditions, such as acute lung injury and neuroinflammation. Additionally, the NF-κB pathway mediates the production of inflammatory cytokines, including IL-1β, IL-33, and TNF-α, which further regulate pyroptosis. This review examines recent advances in understanding the role of the NF-κB signaling pathway in regulating pyroptosis during infection and inflammation.

Background Overexpression of tear matrix metalloproteinases-9 (MMP-9) on the ocular surface tissues has been reported to result in ocular surface damage. MMP-9 levels in tears have been listed as one of many tools for confirming dry eye disease (DED).Objective This investigation aimed to compare MMP-9 levels and ocular surface parameters in diabetic patients with and without DED.Design A cross-sectional study.Setting He Eye Specialist Hospital, Shenyang, China.Participants This study recruited 144 right eyes of 144 diabetic patients between November and December of 2023, and 110 patients with similar propensity scores were included in the analyses.Main outcome measures Non-invasive breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperaemia (redness score (RS)), corneoconjunctival staining (CS), corneal sensitivity and Ocular Surface Disease Index (OSDI) questionnaire were evaluated. MMP-9 was measured using an immunochromatography assay.Results In total, 55 patients (55 eyes) were grouped as diabetic dry eye (DDE) and 55 patients (55 eyes) as diabetic non-dry eye (DNDE). The mean MMP-9 concentrations were higher in patients with DDE than DNDE (70.63±52.06 ng/mL vs 33.98±33.93 ng/mL; p52.5 ng/mL, with 58.2% sensitivity and 78.2% specificity.Conclusions MMP-9 concentration was higher in patients with DDE than DNDE. The MMP-9 test is a potential diagnostic tool for DDE. It may help follow-up diabetic patients with DED and guide clinicians in deciding on anti-inflammatory treatments for these patients.

Abstract Background The AGEs levels in tissues of diabetics and elderly tend to be higher than in normal individuals. This study aims to determine the effects of AGEs on Achilles tendon repair. Materials and methods Thirty-six male eight-week-old Sprague Dawley rats were selected in this study. The rats were randomly divided into two experimental groups and a control group after the transection of the Achilles tendon. During the tendon repair, the experimental groups were injected around the Achilles tendon with 350mmol/L (low dose group) and 1000mmol/L (high dose group) D-ribose 0.2 ml respectively to increase the AGEs level, while in the control group were given the same amount of PBS. The injections were given twice a week for six weeks. Collagen-I, TNF-α, and IL-6 expression in the healed Achilles tendon was assessed. Additionally, macroscopic, pathological, and biomechanical evaluations of Achilles tendon repair were conducted. Results The repaired Achilles tendons in the high dose group showed severe swelling and distinctive adhesions. The histological score went up with the increase of the AGEs in the Achilles tendon (p

Abstract Researchers and policymakers hold diverse opinions about the impact of globalization on environmental degradation. Over the past three decades, increased economic, social, and political interconnections have fueled this debate. However, prior studies have largely overlooked these facets of globalization concerning environmental implications, particularly carbon emissions in developing countries. We contribute to this discourse by examining how various aspects of globalization (economic, social, and political) and two specific measures, de facto and de jure trade, influenced carbon emissions in four selected South Asian countries from 1996 to 2019. The results obtained through feasible generalized least squares (FGLS) reveal that economic globalization increases carbon emissions while social and political globalization reduces them. These results further confirm that, in South Asia, the pollution haven hypothesis is associated only with economic globalization. In contrast, social and political globalization support the world polity theory, indicating potential for positive change. The results also show that both de facto and de jure measures of disaggregated globalization equally influence carbon emissions, suggesting a significant impact from policy interventions. For future environmental sustainability, the governments of these nations should intensify their efforts to strengthen social and political globalization. Meanwhile, the adverse effects of economic globalization can be mitigated by reducing reliance on fossil fuels and providing financial assistance to businesses to encourage the use of renewable energy and modern technology in production.

Abstract Background There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. Methods The China Kadoorie Biobank cohort was followed up from the 2004–08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively. Results Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all P trend

Abstract Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004–2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (P interaction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.