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.

Objective To assess the stability of the molluscicidal activity of the fermentation broth supernatant of Bacillus indicus F19, so as to provide insights into development of novel molluscicides derived from this isolate. Methods Healthy Oncomelania hupensis snails free from Schistosoma japonicum infections and acclimated in the laboratory for 7 days were selected. The fermentation broth supernatant of B. indicus F19 was prepared. For each treatment condition, four experimental groups and one control group were established, with 10 mL of the fermentation broth supernatant each group. O. hupensis snails were exposed to different pH values (3, 6, 9 and 12), temperatures (40, 60, 80 °C and 100 °C), and ultraviolet (UV) exposure durations (1, 2, 3 h and 4 h). Then, the supernatant was diluted with dechlorinated water to concentrations of 50%, 10%, and 5% (v/v), and 10 mL of each dilution solution was added to three separate tubes, with an equal volume of dechlorinated water as a blank control. Twenty O. hupensis snails were transferred to each tube, immersed for 48 h and 72 h, and collected for viability assessment using the shell-tapping method. The mortality of O. hupensis snails was calculated and compared among dilution groups and the blank control group to evaluate the molluscicidal activity of the fermentation broth supernatant of B. indicus F19. Results There was a significant difference in the mortality of O. hupensis snails immersed in 5% fermentation broth supernatants of B. indicus F19 for 48 h at various pH levels (χ² = 11.556, P < 0.05), and the mortality reduced to 13.33% (8/60) in the experimental groups at a pH value of 12, which was significantly lower than in the blank control group [33.33% (20/60)] (χ² = 6.708, P < 0.05). There was a significant difference in the mortality of O. hupensis snails immersed in 10% fermentation broth supernatants of B. indicus F19 for 72 h at various pH levels (χ² = 31.691, P < 0.001), and the mortality reduced to 71.67% (43/60) and 65.00% (39/60) in the experimental group at pH values of 9 and 12, which was significantly lower than in the blank control group [100.00% (60/60)] (χ² = 8.571 and 12.110, both P values < 0.01). The mortality of O. hupensis snails both reduced to 23.33% (14/60) following immersion in 5% fermentation broth supernatants of B. indicus F19 heated in a water bath at 80 °C and 100 °C for 48 h, which was lower than that of unheated O. hupensis snails [33.33% (20/60)] and snails heated in a water bath at 40 °C [35.00% (21/60)] and 60 °C [33.33% (20/60)], and there was no significant difference in the mortality of O. hupensis snails among groups (χ² = 3.898, P > 0.05). The mortality of O. hupensis snails was 68.33% (41/60), 66.67% (40/60), 65.00% (39/60), and 68.33% (41/60) following immersion in fermentation broth supernatants heated in a water bath at 40, 60, 80 °C and 100 °C for 72 h, which was all lower than that of snails in the control group [71.70% (43/60)]; however, there was no significant difference seen in the snail mortality among groups (χ² = 0.674, P > 0.05). The mortality of O. hupensis snails was 73.33% (44/60), 71.67% (43/60), 71.67% (43/60), and 75.00% (45/60) following 48 h immersion in 10% fermentation broth supernatants of B. indicus F19 irradiated by UV for 1, 2, 3 h and 4 h, 33.33% (20/60), 31.67% (19/60), 35.00% (21/60), and 33.33% (20/60) following 48 h immersion in 10% fermentation broth supernatants of B. indicus F19 irradiated by UV for 1, 2, 3 h and 4 h, and 71.67% (43/60) and 33.33% (20/60) following 48 h immersion in 10% fermentation broth supernatants of B. indicus F19 without UV irradiation, and no significant differences were found among groups (χ² = 0.229 and 0.150, both P values > 0.05). In addition, the mortality of O. hupensis snails was 76.67% (46/60), 71.67% (43/60), 70.00% (42/60), and 76.67% (46/60) following 72 h immersion in 5% fermentation broth supernatants of B. indicus F19 irradiated by UV for 1, 2, 3 h and 4 h, and 71.67% (43/60) in the control group, and there was no significant difference in the snail mortality among groups (χ² = 1.193, P > 0.05). Conclusion The molluscicidal action of the fermentation broth supernatants of B. indicus F19 is tolerant to high temperature and UV irradiation; however, the activity is attenuated under alkaline conditions.

Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

Objective:To evaluate the clinical outcomes of total knee arthroplasty (TKA) assisted by 3D printing in the treatment of traumatic osteoarthritis secondary to severe knee deformity after old tibial plateau fracture.Methods:A retrospective study was conducted to analyze the clinical data of the 18 patients who had been treated for traumatic osteoarthritis secondary to severe knee deformity after old tibial plateau fracture at Department of Orthopaedics, The People's Hospital of Guizhou Province from March 2015 to June 2017. The cohort included 7 males and 11 females, with a mean age of (64.0±7.7) years. The left knee was affected in 12 cases and the right in 6 ones. The injury was caused by a traffic accident in 12 cases, by a fall from heights in 4 cases, and by a heavy object in 2 cases. The time from fracture to TKA was (5.9±2.8) years. All patients underwent TKA assisted by 3D printing after admission. Knee range of motion (ROM), Hospital for Special Surgery (HSS) knee score, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were compared between preoperation and postoperative 6 months. Complications during the follow-up period were also recorded.Results:All the 18 patients completed a 6-month follow-up. At 6 months after operation, the knee ROM increased significantly from preoperative 85.1°±2.9° to 125.3°±1.3°, the HSS knee score increased significantly from preoperative (39.6±1.4) points to (75.8±1.8) points, and the WOMAC score decreased significantly from preoperative (49.3±1.0) points to (8.3±0.7) points in the 18 patients ( P<0.05). One patient experienced poor wound healing 1 week after operation, and 3 patients developed low-lying patella postoperatively. No such complications as prosthesis loosening, infection, or joint stiffness were reported during the follow-up period. Conclusion:For patients with traumatic osteoarthritis secondary to severe deformity following old tibial plateau fracture, TKA assisted by 3D printing can significantly improve their knee ROM and restore their limb function, but lead to no serious complications.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

Objective:To investigate the anti-leukemic effects and resistance mechanisms of venetoclax in acute myeloid leukemia (AML). Genomic, transcriptomic, and clinical data from AML patients who underwent venetoclax drug sensitivity testing were downloaded from the Beat AML database. Correlation analysis was performed between these data and venetoclax sensitivity outcomes. Differentially expressed genes (DEGs) associated with venetoclax sensitivity were identified from transcriptomic data and subsequently validated using GEO database transcriptomic results and in vitro experiments (including Western blot). Functional enrichment analyses (KEGG and GSEA), transcription factor enrichment analysis (KnockTF), and data from public databases were employed to further investigate key genes and pathways influencing drug sensitivity.Results:After filtering the Beat AML cohort, data from 52 patient samples with available in vitro venetoclax sensitivity results were included for analysis. Patients with FLT3 mutations exhibited greater sensitivity to venetoclax compared to those with FLT3 wild-type. Correlation analysis between clinical information and drug sensitivity data indicated that higher peripheral blood tumor burden was associated with increased sensitivity to venetoclax. Transcriptomic analysis and in vitro experiments confirmed that venetoclax inhibits the FLT3-related signaling pathway, including downregulation of FLT3 expression and reduced phosphorylation of its downstream targets AKT and STAT5. KEGG pathway and KnockTF transcription factor enrichment analyses indicated that venetoclax resistance was associated with increased transcriptional activity of FOXM1 and STAT3. Moreover, high expression of FOXM1 and STAT3 correlated with shorter overall survival in patients.Conclusion:Venetoclax can inhibit the activation of FLT3-related signaling pathways. The activation of STAT3 and FOXM1 transcription factors is a potential key mechanism contributing to venetoclax resistance in AML.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.