Background The progression of metabolic dysfunction-associated steatohepatitis (MASH) involves chronic, irreversible inflammatory responses linked to intracellular organelle dysfunction. While endoplasmic reticulum (ER) stress and mitochondrial impairment are recognized as critical drivers, the precise molecular mechanisms governing inter-organelle communication in this disease context remain incompletely understood. Aim This study aimed to investigate the role of the ER transmembrane protein SEC62 in MASH pathogenesis. Specifically, it sought to determine whether SEC62 expression is altered in MASH, define its functional impact on disease phenotypes, and elucidate the mechanistic pathway through which it regulates mitochondrial homeostasis and inflammation. Results SEC62 was upregulated in both human and mouse MASH livers. Hepatocyte-specific SEC62 overexpression worsened hepatic steatosis, inflammation, and mitochondrial damage, whereas SEC62 knockout ameliorated these features. Mechanistically, SEC62 interacted directly with ATAD3B at the mitochondria-associated membranes (MAMs) interface, leading to the significant downregulation of ATAD3B expression. This SEC62-ATAD3B axis resulted in defective mitophagy, increased mitochondrial reactive oxygen species (ROS) production, and amplified inflammatory responses. Conclusion Our results demonstrate that SEC62 is a novel regulator of MAMs that drives MASH progression. By interacting with and suppressing ATAD3B, SEC62 disrupts mitochondrial quality control, leading to oxidative stress and inflammation. Together, these findings define a specific molecular mechanism of organelle interplay in MASH and position SEC62 as a potential therapeutic target for intervention.

INTRODUCTION:Ulcerative colitis (UC) is a chronic, relapsing-remitting immune-mediated disorder, in which aberrant inflammatory activation within the intestinal submucosa is regarded as a central driver of its pathogenesis. Indirubin (IND), a bisindole compound extracted from Indigo naturalis and an active component of Qingbai Decoction (QBD), exerts anti-inflammatory effects. However, the specific mechanisms by which IND mitigates dysregulated mucosal inflammation in UC remain unclear. OBJECTIVES:The primary aim of the present study was to elucidate the anti-inflammatory properties and underlying mechanisms of IND using experimental models of UC. METHODS:Cellular and animal colitis models were established to evaluate the anti-inflammatory effects of IND. To investigate the underlying mechanisms, we conducted proteomic sequencing, single-cell RNA sequencing, and immunofluorescence assays. Next, we assessed whether the anti-inflammatory effects of IND were dependent on macrophagy and the AGE-RAGE signaling pathway using specific pharmacological agonists and antagonists. Furthermore, the targeting and inhibitory effects of IND on the transcription factor Macrophage Antigen Recognition Receptor 1 (MAC1)-CCCTC-binding Factor (CTCF) were evaluated through molecular docking and dual-luciferase reporter assays. RESULTS:QBD exerted its anti-inflammatory effects in UC primarily by targeting the AGE-RAGE signaling pathway, with IND mediating this therapeutic action. Proteomic sequencing and mechanistic studies revealed that MAC1 and the receptor for advanced glycation end products (RAGE), both critical components of the AGE-RAGE pathway activation, were significantly upregulated during UC progression and exacerbated inflammatory responses. Crucially, IND attenuated intestinal submucosal inflammation and reduced mucosal permeability in colitis models in a macrophage-dependent manner. In vitro experiments further showed that IND inhibited inflammatory responses specifically through the AGE-RAGE signaling pathway. Moreover, IND suppressed CTCF-mediated transcriptional activation of MAC1, thereby inhibiting downstream inflammatory cascades in vivo. CONCLUSION:Collectively, these findings demonstrate that IND targets MAC1 to suppress AGE-RAGE signaling, thereby alleviating UC progression.

This study aimed to evaluate the global burden of inflammatory bowel disease (IBD) among women of reproductive age (15–49 years) from 1990 to 2021, analyze its association with socio-demographic index (SDI), and identify age-period-cohort (APC) effects to inform region-specific public health strategies. Using data from the Global Burden of Disease (GBD) 2021 study, we assessed age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (ASDR) across 204 countries. Statistical analyses included Pearson correlation to evaluate SDI associations, decomposition analysis to quantify burden drivers, and APC modeling to disentangle age, period, and cohort effects. In 2021, the global ASIR, ASPR, ASMR, and ASDR for IBD in women of reproductive age were 4.38, 45.90, 0.50, and 17.75 per 100,000, respectively. The health burden of IBD in women of reproductive age varies by region. Australasia has the highest ASIR and ASPR globally, while these metrics are lowest in Central Latin America. Western Europe exhibits the highest ASMR, whereas Oceania has the lowest. In terms of ASDR North America, with its higher income, bears the heaviest burden, while Oceania experiences the lightest. Furthermore, APC analysis revealed age-specific risks peaking at 45–49 years, and significant cohort effects in middle/low-SDI regions, where post-1977 birth cohorts showed elevated incidence. Period effects highlighted diverging trends: stable incidence in high-SDI regions vs. rising rates in mid-SDI regions due to urbanization and lifestyle shifts. The IBD burden among reproductive-aged women is rising disproportionately, shaped by SDI gradients and demographic transitions. High-SDI regions require strategies targeting aging populations and comorbidities, while low/middle-SDI regions need investments in early diagnosis and equitable care.

Aim: Hepatocellular carcinoma (HCC) remains a major challenge due to poor prognosis. This study investigates 3-methylcytidine (m3C) RNA methylation regulators to elucidate their roles in HCC and to develop a prognostic scoring system for clinical application. Methods: We integrated data from 486 HCC patients [The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets] and 16 pairs of clinical tissue samples. The expression, mutation profiles, and prognostic significance of 6 m3C regulators were analyzed. Functional assays, including cell proliferation and migration, were performed, alongside immune infiltration analysis using single-sample gene set enrichment analysis (ssGSEA). Finally, an m3C scoring system was constructed to evaluate prognostic potential. Results: Most m3C regulators (except METTL8) were upregulated in HCC tissues. Knockdown of METTL2, METTL6, ALKBH1, or ALKBH3, as well as overexpression of METTL8, inhibited HCC cell proliferation and migration. Two distinct m3C modification modes were identified, each associated with unique clinical features. The m3C score was positively correlated with longer overall survival in high-score patients and was associated with tumor mutation burden (TMB) and expression of PD-1 and CTLA4, suggesting its potential to predict immunotherapy response. Conclusion: This study highlights the genetic variation and prognostic relevance of m3C methylation regulators in HCC and introduces a novel scoring system for prognosis prediction, providing a potential tool to guide HCC treatment strategies.

Background and Aims: Acetaminophen (APAP)-induced liver injury (AILI) has an increasing incidence worldwide. However, the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently available. Methods: We performed a proteomic analysis of the AILI model and found basic transcription factor 3 like 4 (BTF3L4) was the only outlier transcription factor overexpressed in the AILI model in mice. BTF3L4 overexpression increased the degree of liver injury in the AILI model. Results: BTF3L4 exerts its pathogenic effect by inducing an inflammatory response and damaging mitochondrial function. Increased BTF3L4 expression increases the degree of apoptosis, reactive oxygen species generation, and oxidative stress, which induces cell death and liver injury. The damage of mitochondrial function by BTF3L4 triggers a cascade of events, including reactive oxygen species accumulation and oxidative stress. According to the available AILI data, BTF3L4 expression is positively associated with inflammation and may be a potential biomarker of AILI. Conclusions: Our results suggest that BTF3L4 is a pathogenic factor in AILI and may be a potential diagnostic maker for AILI.

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system; however, its etiology remains unclear. Clarifying its pathogenesis is essential to improve the prognosis of patients with HCC. Studies have shown that the 3-methylcytidine (m3C) methylation regulator is closely related to the occurrence and development of tumors and has an excellent potential prognostic value. In the present study, 486 patients with HCC were collected from TCGA and GEO databases, and 16 patients with HCC and adjacent tissues in our hospital were collected. The expression level, mutation of six m3C regulators, and their relationship with the prognosis of patients were comprehensively analyzed, and an m3C scoring system was simultaneously constructed for quantifying m3C modifications. The expression of m3C regulators in HCC was generally different, and most were related to patient prognosis. We further determined two different m3C modification modes in HCC samples. We found differences in clinical characteristics and total survival times between different modification classifications, which further proved that patients with higher m3C scores had longer survival times and better clinical characteristics. This study explored the genetic variation and prognostic value of m3C methylation regulators in HCC and designed a scoring system to predict the prognosis of HCC, providing help for the treatment and prognosis of HCC patients.

ObjectiveSARS-CoV-2 transmission has become a serious worldwide public health concern. However, there is currently insufficient data to determine whether SARS-CoV-2 infection would affect opportunistic infections in inflammatory bowel disease (IBD) patients.MethodsA retrospective study included 451 IBD patients (294 UC and 157 CD). The IBD patients were divided into two groups: before SARS-CoV-2 infection and after SARS-CoV-2 infection, and outcomes were measured for these groups. The primary outcome was the presence and distribution of opportunistic infections. The secondary outcomes included factors associated with opportunistic infections, based on which a nomogram prediction model was developed and validated.ResultsAfter SARS-CoV-2 infection, the proportion of IBD patients with opportunistic infections by Clostridium difficile (21.31% vs. 14.01%, p = 0.044) and Epstein–Barr virus (13.93% vs. 4.35%, p = 0.001) was significantly higher compared to that before. Conversely, the proportion of patients with hepatitis B virus (3.69% vs. 10.14%, p = 0.006) and herpes simplex virus type I (1.23% vs. 4.35%, p = 0.04) infections was significantly lower after the infection. Additionally, pre-SARS-CoV-2 infection factors associated with opportunistic infections in IBD include duration of illness, red blood cell count, the presence of comorbid chronic illnesses, and alcohol consumption, while post-SARS-CoV-2 infection, the primary risk factors involve corticosteroid use, red blood cell count, protein level, and high-sensitivity C-reactive protein.ConclusionAfter the SARS-CoV-2 infection, there has been a shift in the occurrence of opportunistic infections among IBD patients. It might be attributed to the use of corticosteroids and also the strengthening of containment measures, heightened public health awareness, and widespread vaccination.

BACKGROUND:Epigenetic reprogramming has been reported to play a critical role in the progression of thyroid cancer. RNA methylation accounts for more than 60% of all RNA modifications, and N6-methyladenosine (m6A) is the most common modification of RNAs in higher organisms. The purpose of this study was to explore the related modification mode of m6A regulators construction and its evaluation on the clinical prognosis and therapeutic effect of thyroid cancer.METHODS:The levels of 23 m6A regulators in The Cancer Genome Atlas (TCGA) were analyzed. Differentially expressed genes (DEGs) and survival analysis were performed based on TCGA-THCA clinicopathological and follow-up information, and the mRNA levels of representative genes were verified using clinical thyroid cancer data. In order to detect the effects of m6A regulators and their DEGs, consensus cluster analysis was carried out, and the expression of different m6A scores in Tumor Mutation Burden (TMB) and immune double antibodies (PD-1 antibody and CTLA4 antibody) were evaluated to predict the correlation between m6A score and thyroid cancer tumor immunotherapy response.RESULTS:Different expression patterns of m6A regulatory factors were detected in thyroid cancer tumors and normal tissues, and several prognoses related m6A genes were obtained. Two different m6A modification patterns were determined by consensus cluster analysis. Two different subgroups were established by screening overlapping DEGs between two m6A clusters, with cluster A having the best prognosis. According to the m6A score extracted from DEGs, thyroid cancer patients can be divided into high and low score subgroups. Patients with lower m6A score have longer survival time and better clinical features. The relationship between m6A score and Tumor Mutation Burden (TMB) and its correlation with the expression of PD-1 antibody and CTLA4 antibody proved that m6A score could be used as a potential predictor of the efficacy of immunotherapy in thyroid cancer patients.CONCLUSIONS:We screened DEGs from cluster m6A and constructed a highly predictive model with prognostic value by dividing TCGA-THCA into two different clusters and performing m6A score analysis. This study will help clarify the overall impact of m6A modification patterns on thyroid cancer progression and formulate more effective immunotherapy strategies.

变电站生产运行期间,高压电气设备属于变电站的基础设备,其运行质量直接影响着变电站生产安全、生产效率.高压电气试验仪器是在各类电力技术的支持下,通过电气试验评估高压电气设备的基本性能,使其满足变电站生产需求.因此,论文通过分析变电站高压电气试验仪器问题,明确了当前变电站设备管理的重点,随后提出了高压电气技术的改进思路,借此改善变电站的电气环境,使变电站能够安全、可靠地达成生产目标.

目前,我国的配电网智能化水平相对较低,造成配电运维人员工作效率低、杆塔位置不清晰等问题.基于此,设计一种基于集成传感器的"一键构图"功能装置,实现动态生成电网连接图、自动更新新旧杆塔信息、实时检测杆塔环境等,有效降低配电运维人员日常工作复杂度,提高现场巡视、隐患排查、到岗到位等工作效率,保障电网安全可靠运行.

针对10 kV配电网建设和运维中,传统的铜铝接线端子普遍存在规格型号单一、易锈蚀老化、安装烦琐、连接易松弛和绝缘防护性差等问题,研制了一种新型快速铜铝接线端子,根据不同规格导线采用偏心原理以内切圆方式分体设计,圆弧面上设有螺纹齿增加导线与导线槽接触的有效摩擦,同时采用软包胶技术,实现接线端子与塑胶一体成型,增加接线端子整体的抗摔、抗磨和耐腐蚀等性能.

目的 总结空军军医大学西京医院消化内科克罗恩病(CD)患者10年的用药趋势变化.方法 回顾性分析2010-2019年10年间,西京医院IBD中心确诊CD患者的临床一般信息资料、患者用药情况,其中将CD患者根据用药时间段分为2010-2014年组与2015-2019年组,分别分析两组CD患者的一般情况和用药趋势,再根据患者性别和年龄(≤40岁和＞40岁)进行亚组分析.结果 2015-2019年组与2010-2014年组分别纳入164和140例CD患者,2010-2014年组和2015-2019年组患者年龄和女性比例比较[(37.2±14.5)岁比(34.7±13.7)岁,30.0％(42/140)比40.9％(67/164)],差异均无统计学意义(P＞0.05).2015-2019年组免疫抑制剂和生物制剂使用率均高于2010-2014 年组[50.6％(83/164)比 32.1％(45/140)、52.4％(86/164)比 23.6％(33/140)],差异均有统计学意义(x2=10.566、x2=26.421,P＜0.001).2010-2014年组和2015-2019年组组内女性和男性CD患者的年龄、5-ASA(5-氨基水杨酸)类、激素、免疫抑制剂和生物制剂的使用率比较,差异均无统计学意义(P＞0.05).2015-2019年组组内≥40岁患者生物制剂使用率明显低于＜40岁组[34.0％(18/53)比61.3％(68/111)],差异具有统计学意义(P=0.001).结论 与2010-2014年相比,2015-2019年间,西京医院单中心CD患者数量基本保持稳定,CD患者的生物制剂和免疫抑制剂使用率明显增高;不同性别患者的用药情况基本一致.2015-2019年间,生物制剂使用率增加主要表现为年轻患者(＜40岁)使用率增加.

电力生产中,10 kV配电室及开闭所高、低开关柜开关的运行、储能、分合闸等状态,通常是通过指示灯的亮、灭来表明.但因指示灯长期工作在封闭环境内,容易老化损坏.而常规指示灯更换方式步骤多、耗时长,并存在误碰造成的设备故障,甚至人员触电等风险.针对传统指示灯更换方式存在的问题,本文提出了一种新型拆卸式指示灯,效仿灯泡原理,将灯芯和底座采用分体式设计,通过拔插灯芯或底座即可实现损坏指示灯的更换,更换方便、操作便捷、安全可靠,且能够有效地缩短检修时间,提高工作效率.

N6-methyladenosine (m6A) methylation plays an important role in the occurrence and development of tumors. This study aimed to explore the effects of m6A methylation regulatory genes on rectosigmoid cancer (RSC). RNA-seq data and related clinical information in The Cancer Genome Atlas database were analyzed. The Wilcoxon test was used to analyze the different expression levels of m6A methylation regulatory genes between the tumor and normal samples. Least absolute shrinkage and selection operator Cox regression analysis was used to construct a risk prognosis model between the m6A methylation regulatory genes and RSC. The median risk score was used to classify RSC patients into high and low-risk groups. Kaplan-Meier survival analysis and receiver operating characteristic curves were used to evaluate the sensitivity and specificity of the prediction model. The expression of m6A methylation regulation genes was different between the tumor and normal samples, 6 genes were overexpressed in tumor and 2 genes were down-regulated. Four m6A methylation regulatory genes, YTHDF3, KIAA1429, ALKBH5 and METTL3, were screened by least absolute shrinkage and selection operator Cox regression analysis. The overall survival of high-risk group was significantly lower than that of low-risk group (P = 4.681 x 10(-4)). The area under the curve value in the receiver operating characteristic curve was 0.935, indicating that the prediction model was effective. Univariate and multivariate Cox regression were used to test the effectiveness of the model. m6A methylation regulators YTHDF3, KIAA1429, ALKBH5, and METTL3 can be used to construct predictive models to predict overall survival in different clinical subgroups of RSC patients.

Perceptions and attitudes of patients with inflammatory bowel disease (IBD) about pregnancy may influence their fertility planning and disease progression. We aimed to compare Chinese IBD patients and gastroenterologists’ cognitive differences and biases about IBD pregnancy. A web-based cross-sectional survey was conducted at the IBD centers in China nationwide. Gastroenterologists and IBD patients were invited to participate in this study. The questionnaire included three sections on demographics, patient disease status, physicians’, and patients’ knowledge of IBD pregnancy management. Analyze cognitive congruence and differences between physicians and patients. A total of 794 participants from 63 IBD centers participated in this study. Gastroenterologists and IBD patients have large cognitive differences in three key domains of IBD pregnancy. Firstly, less IBD patients thought they would have normal children compared with physicians (39.1% vs.70.8%, p < 0.001). Secondly, even less IBD patients thought they would take imaging examinations (22.8% vs. 72.4%, p < 0.001) or endoscopy (19.9% vs. 71.4%, p < 0.001). Thirdly, incorrect attitude about the vaccination for patients compared with that of physicians (16.6% vs. 46.5%, p < 0.001). However, even among gastroenterologists, they are also not well educated in terms of the effects of pregnancy on IBD, the mode of delivery, medication, and emergency surgery during pregnancy. Not only IBD patients are lack of knowledge, gastroenterologists are not fully educated about pregnancy in some aspects. Enough education to physicians, and communication for IBD patients about pregnancy is necessary to improve the management of IBD pregnancy in China. ChiECRCT20210478

Background and aims Sec62 is a membrane protein of the endoplasmic reticulum that facilitates protein transport. Its role in cancer is increasingly recognised, but remains largely unknown. We investigated the functional role of Sec62 in gastric cancer (GC) and its underlying mechanism. Methods Bioinformatics, tissue microarray, immunohistochemistry (IHC), western blotting (WB), quantitative polymerase chain reaction (qPCR), and immunofluorescence were used to examine the expression of target genes. Transwell, scratch healing assays, and xenograft models were used to evaluate cell migration and invasion. Transmission electron microscopy and mRFP-GFP-LC3 double-labeled adenoviruses were used to monitor autophagy. Co-immunoprecipitation (CO-IP) was performed to evaluate the binding activity between the proteins. Results Sec62 expression was upregulated in GC, and Sec62 upregulation was an independent predictor of poor prognosis. Sec62 overexpression promoted GC cell migration and invasion both in vitro and in vivo. Sec62 promoted migration and invasion by affecting TIMP-1 and MMP2/9 balance. Moreover, Sec62 could activate autophagy by upregulating PERK/ATF4 expression and binding to LC3II with concomitant FIP200/Beclin-1/Atg5 activation. Furthermore, autophagy blockage impaired the promotive effects of Sec62 on GC cell migration and invasion, whereas autophagy activation rescued the inhibitory effect of Sec62 knockdown on GC metastasis. Notably, Sec62 inhibition combined with autophagy blockage exerted a synergetic anti-metastatic effect in vitro and in vivo. Conclusion Sec62 promotes GC metastasis by activating autophagy and subsequently regulating TIMP-1 and MMP2/9 balance. The activation of autophagy by Sec62 may involve the unfolded protein response (UPR)-related PERK/ATF4 pathway and binding of LC3II during UPR recovery involving FIP200/Beclin-1/Atg5 upregulation. Specifically, the dual inhibition of Sec62 and autophagy may provide a promising therapeutic strategy for GC metastasis.

The purpose of clinical medications is to treat the disease, reduce patients′ symptoms and improve their condition. However, in recent years, paradoxical reactions that cause the opposite or aggravate the disease during clinical medication are not uncommon, and the gastrointestinal tract is one of the common organs involved in such events. This article reviews the events and potential mechanisms of inflammatory bowel disease induced or aggravated by drugs, so that clinicians can better understand such contradictory events and choose more appropriate treatment options for patients.

BackgroundPatients with ulcerative colitis (UC) are at an increased risk of developing Clostridioides difficile infection (CDI), which in turn leads to poor outcomes. The gut microbial structure and metabolites in patients with UC and CDI have been scarcely studied. We hypothesized that CDI changes the gut microbiota and metabolites of patients with UC.Materials and MethodsThis study included 89 patients: 30 healthy controls (HC group), 29 with UC alone (UCN group), and 30 with UC and CDI (UCP group). None of the participants has been exposed to antibiotic treatments during the 3 months before stool collection. Stool samples were analyzed using 16S rRNA gene sequencing of the V3–V4 region and gas chromatography tandem time-of-flight mass spectrometry.ResultsThe UCN group displayed lower diversity and richness in gut microbiota and a higher relative abundance of the phylum Proteobacteria than the HC group. There were no significant differences between the UCN and UCP groups in the α-diversity indices. The UCP group contained a higher relative abundance of the genera Clostridium sensu stricto, Clostridium XI, Aggregatibacter, and Haemophilus, and a lower relative abundance of genera Clostridium XIVb and Citrobacter than the UCN group. In the UCP group, the increased metabolites included putrescine, maltose, 4-hydroxybenzoic acid, 4-hydroxybutyrate, and aminomalonic acid. Spearman’s correlation analysis revealed that these increased metabolites negatively correlated with Clostridium XlVb and positively correlated with the four enriched genera. However, the correlations between hemoglobin and metabolites were contrary to the correlations between erythrocyte sedimentation rate and high-sensitivity C-reactive protein and metabolites.ConclusionOur study identified 11 differential genera and 16 perturbed metabolites in patients with UC and CDI compared to those with UC alone. These findings may guide the design of research on potential mechanisms and specific treatments for CDI in patients with UC.