The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP₆), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP₆-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.

Background The global prevalence of obesity is on the rise and is closely associated with various chronic non-communicable diseases such as cardiovascular diseases and diabetes. There is a relative lack of long-term dynamic studies on compound obesity among occupational populations. Objective To explore the changing trends of compound obesity among different occupational groups aged 18–59 years in nine provinces (autonomous regions, municipalities) of China from 1993 to 2018, and to provide a scientific basis for formulating targeted weight management strategies for occupational populations. Methods A total of 34519 employed adults aged 18–59 years from nine waves of the China Health and Nutrition Survey in1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, and 2018 were included. Obesity types were determined according to the Chinese Adult Weight Management Guidelines. The Joinpoint regression model was used to calculate the average annual percentage change (AAPC) and annual percentage change (APC) of compound obesity rates. Results From 1993 to 2018, the age-standardized compound obesity rate among the occupational population aged 18–59 years showed an upward trend (AAPC=6.24%, 95%CI: 5.09%, 7.41%, P<0.05). The AAPCs (95%CI) for age-standardized compound obesity rates among agricultural workers, blue-collar workers, other occupational groups, service workers, and white-collar workers were 9.55% (7.51%, 11.64%), 6.18% (4.70%, 7.69%), 5.53% (2.27%, 8.90%), 4.07% (2.40%, 5.77%), and 3.89% (2.16%, 5.65%), respectively, with statistically significant differences (P<0.05). Among males, the AAPCs (95%CI) for age-standardized compound obesity rates among agricultural workers, blue-collar workers, other occupational groups, service workers, and white-collar workers were 11.52% (7.71%, 15.47%), 7.28% (6.18%, 8.40%), 5.92% (2.28%, 9.69%), 5.56% (2.11%, 9.12%), and 4.22% (2.33%, 6.15%), respectively, with statistically significant differences (P<0.05). Among females, the AAPCs (95%CI) for age-standardized compound obesity rates among agricultural workers, blue-collar workers, and white-collar workers were 7.45% (6.22%, 8.69%), 3.72% (0.84%, 6.67%), and 2.41% (0.17%, 4.70%), respectively, with statistically significant differences (P<0.05). A turning point was observed in the compound obesity rate among female white-collar workers in 2006, with an APC (95%CI) of 9.69% (5.24%, 14.33%) from 2006 to 2008, showing a statistically significant difference (P<0.05), while no significant trend was found from 1993 to 2006 (P>0.05). No significant trends were observed in the age-standardized compound obesity rates among females in other occupational groups and service workers (P>0.05). Conclusion The compound obesity rate among China's occupational population is increasing rapidly, with the growth rate among agricultural workers being particularly prominent. In 2018, male white-collar workers and female agricultural workers exhibit relatively high compound obesity rates, warranting focused attention. Although the overall growth rate among service workers is slower, the expanding workforce in this sector indicates that obesity remains a serious issue. Targeted occupational health and weight management interventions are needed in the future.

Hepatic alveolar echinococcosis is a highly invasive zoonotic parasitic disease with poor prognosis. Surgical intervention serves as the pivotal approach to achieve radical cure and improve the prognosis of hepatic alveolar echinococcosis patients. In recent years, with the popularization of the concept of precision surgery and the development of the multidisciplinary diagnosis and treatment model, the surgical treatment strategies for hepatic alveolar echinococcosis have been continuously enriched, and the selection of surgical procedures has become increasingly diversified. Although key surgical techniques such as radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation have achieved remarkable progress in clinical application, many insurmountable challenges still remain. Therefore, by sorting out the latest evidence-based advances in the field of surgical treatment for hepatic alveolar echinococcosis, this article focuses on discussing the application status and bottlenecks of radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation in hepatic alveolar echinococcosis, aiming to provide a reference for the clinical treatment of hepatic alveolar echinococcosis.

ObjectiveTo analyze the epidemiological and etiological characteristics of a cluster of human metapneumovirus (HMPV) infection in a kindergarten in Gongshu District of Hangzhou City in May 2024, and to provide reference for the prevention and control of similar outbreaks. MethodsAn on-site investigation was conducted using an epidemiological case investigation form. Throat swab specimens collected from cases were screened for 13 respiratory pathogens using real-time fluorescent polymerase chain reaction (PCR). For HMPV nucleic acid positive specimens, the F gene of HMPV was used as the target gene for amplification and sequencing. The sequencing results were then compared with sequences in GenBank database to determine the virus subtypes and perform phylogenetic analyses. ResultsThe outbreak occurred in a kindergarter junior class with a total of 28 preschoolers and 3 teachers and childcare workers. A total of 11 cases (10 preschoolers and 1 teacher) were identified, including 8 male cases and 3 female cases. Clinical manifestations included fever in all 11 cases (100.00%), cough in 8 cases (72.72%), catarrhal symptoms in 4 cases (36.36%), and headache in 3 cases (27.27%). All symptoms were mild, and no severe cases were observed. A total of 11 throat swab samples were collected. Real-time fluorescent PCR test results showed that 3 samples were positive for HMPV nucleic acid, 2 samples were positive for both HMPV and Streptococcus pneumoniae, and 1 sample was positive for both HMPV and rhinovirus. The sequences of the 6 HMPV nucleic acid positive specimens were amplified and analyzed using specific primers, and all were determined to be HMPV subtype A2b. The F gene fragment sequence showed the highest similarity to PV081665.1/Brazil/2024 (99.65%), and also exhibited high similarity to PP683455.1/Indonesia/2021 (99.48%), PV016275.1/Beijing/2024 (99.31%), and PV052230.1/USA/2024 (99.13%). ConclusionThis cluster of acute respiratory tract infection was caused by HMPV subtype A2b, with co-infection of rhinovirus and Streptococcus pneumoniae. The F gene fragment sequences of the HMPV in this outbreak were highly homologous to those of the A2b strains isolated from Brazil, Beijing, Indonesia, and the the United States.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

BACKGROUND: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

This study developed a core outcome set(COS) for traditional Chinese medicine(TCM) interventions in diabetic peripheral neuropathy(DPN), standardizing evaluation metrics for TCM efficacy and providing a new framework for DPN treatment and management. A systematic search was conducted across databases, including CNKI, Wanfang, and PubMed, targeting clinical trial literature published between January 1, 2013, and January 1, 2023. The search focused on extracting outcome indicators and measurement tools used in TCM treatments for DPN. Retrospective data collection was performed from January 2018 to June 2023, involving 200 DPN patients hospitalized at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Additionally, semi-structured interviews were conducted with inpatients, outpatients, their families, and nursing staff to further refine and enhance the list of outcome indicators. After two rounds of Delphi questionnaire survey and consensus meeting, a consensus was reached. The study initially retrieved 3 421 publications, of which 170 met the inclusion criteria after review. These publications, combined with retrospective analysis and semi-structured interviews, supplemented the list of indicators. After two rounds of Delphi surveys, experts agreed on 24 indicators and 6 measurement tools. The final COS determined by expert consensus meeting included 5 domains and 13 outcome indicators: neurological function signs, quality of life, TCM syndrome score, nerve conduction velocity, current perception threshold test, fasting blood glucose, 2 h postprandial blood glucose, glycated hemoglobin, complete blood count, urinalysis, liver function test, kidney function test, and electrocardiogram.
Humans ; Diabetic Neuropathies/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Male ; Female