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 evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies. Methods: A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE). Results: There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years. Conclusions The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

Objective:To investigate the effects of prognostic nutritional index (PNI) on the readmission rate, complication rate, mortality rate and survival of patients with liver cirrhosis.Methods:From January 1, 2020 to December 31, 2022, 395 hospitalized patients with liver cirrhosis at Tianmen Hospital Affiliated to Wuhan University of Science and Technology were retrospectively enrolled. The clinical data were collected from the patients at their first hospitalization (baseline period) and re-hospitalization during follow-up period. The 18-month follow-up was divided into 4 periods, including the first period (from the 0th to the 3rd month), the second one was from the 4th to the 6th month, the third one was from the 7th to the 12th month, and the fourth one was from the 13th to the 18th month of follow-up. The prognostic value of PNI for patients with liver cirrhosis was evaluated through the receiver operating characteristic curve (ROC) of the baseline PNI. The 395 patients were divided into the low PNI group and the high PNI group based on the optimal cut-off value of PNI on the ROC. Patients readmitted during each follow-up period were divided into the PNI improvement group (PNI at follow-up -PNI at baseline>0) and the PNI non-improvement group (PNI at follow-up-PNI at baseline ≤0). Independent sample t-test, one-way analysis of variance (ANOVA), Mann-Whitney U test, chi-square test or Fisher′s exact test were used for statistical analysis. Survival curves depicting the relationship between PNI and overall survival rate of patients with liver cirrhosis were constructed using the Kaplan-Meier method. Results:The ROC analysis indicated that the optimal cut-off value of PNI at baseline was 32.65, with an area under the curve of 0.639 (95% confidence interval: 0.541 to 0.738, P=0.011), with a sensitivity of 0.567 and a specificity of 0.701. There were 269 cases in the high PNI group and 126 cases in the low PNI group. The readmission rate, complication rate and mortality rate in the low PNI group were all higher than those in the high PNI group at the first and fourth follow-up periods (32.5% (41/126) vs. 22.3% (60/269), 31.7% (40/126) vs. 20.4% (55/269), 6.3% (8/126) vs. 1.1% (3/269), 25.0% (29/116) vs. 16.2% (42/260), 25.0% (29/116) vs. 15.4% (40/260), 6.0% (7/116) vs. 1.5% (4/260)), and the differences were statistically significant ( χ2=4.72, 6.00, 6.86, 4.10, 4.95, and 4.24; P=0.030, 0.014, 0.009, 0.043, 0.026, and 0.040). The mortality rates of the PNI improvement group at the first and fourth follow-up periods were both lower than those of the PNI non-improvement group (4.3% (2/47) vs. 16.7% (9/54), 0 (0/24) vs. 23.4% (11/47)), and the differences were statistically significant ( χ2=3.99, Fisher′s exact test; P=0.046 and 0.012). There were no statistically significant difference in the incidence of complications between the PNI improvement group and the PNI non-improvement group at each follow-up period (all P>0.05). The Kaplan-Meier survival curve demonstrated that the average survival time of the high PNI group was longer than that of the low PNI group (17.54 months (95% confidence interval: 17.26 to 17.83 months) vs. 16.74 months (95% confidence interval: 16.96 to 17.52 months), and the difference was statistically significant ( χ2=9.18, P<0.001). The survival rate of the high PNI group at the 18th month of follow-up period was higher than that of the low PNI group (95.2% (256/269) vs. 86.5% (109/126), and the difference was statistically significant ( χ2=9.17, P=0.002). Conclusions:PNI has certain predictive efficacy for the survival period of patients with liver cirrhosis. Low-level PNI may increase the readmission rate, complication rate, and mortality of patients with liver cirrhosis, and shorten the survival period, indicating poor prognosis.

Objective:To explored the application value of dynamic susceptibility contrast-perfusion weighted imaging(DSC-PWI)combined with amide proton transfer(APT)imaging in brian glioma grading.Methods:Retrospective analysis of clinical data of 100 patients with brian glioma admitted to The Second Affiliated Hospital of Xinjiang Medical University from January 2022 to September 2024.They were divided into a low-grade group(WHO grades Ⅰ-Ⅱ,n=62)and high-grade group(WHO grades Ⅲ-Ⅳ,n=38)according to the World Health Organization(WHO)grading system for tumors.All patients underwent DSC-PWI and APT imaging preoperative examinations.Apparent diffusion coefficien(ADC),cerebral blood volume(CBV),cerebral blood flow(CBF),mean transit time(MTT),time to peak(TTP),maximum APT value(APTmax),minimum APT value(APTmin),the average APT value of the whole lesion(APTwhole)were recorded.The general datas and ADC,CBV,CBF,MTT,TTP,APTmax,APTmin,APTwhole of two group were compared.The influencing factors of high-grade brian glioma were analysed by Multivariate logistic regression.The diagnostic value of high-grade brian glioma was analysed of DSC-PWI combined with APT imaging by receiver operating characteristic(ROC)curve.Results:There was no statistically significant difference in age,gender,lesion location,basilar artery occlusion,necrosis and growth pattern between the two groups(P＞0.05),there was a statistically significant difference in the maximum diameter of lesions ≥2 cm and cystic lesions(P＜0.05).The ADC of the high-gradel group was lower than that of the low-grade group,while APTmax,APTmin,APTwhole,CBF,CBV,MTT and TTP were all higher than those of the low-grade group(P＜0.05).Elevated APTmax,APTmin,CBV,MTT,and TTP were risk factors for high-grade brian glioma(P＜0.05),while elevated ADC was a protective factor(P＜0.05).The results of ROC analysis showed that,the area under the curve(AUC)values of APTmax,APTmin,ADC,CBV,MTT,and TTP for diagnostic high-grade brian glioma were 0.830,0.868,0.852,0.843,0.803 and 0.827(all P＜0.05).The results of ROC analysis showed that,the AUC values of the logistic model for diagnostic high-grade brian glioma was 0.993.Conclusion:Single detection of DSC-PWI and APT imaging parameters has high diagnostic value in brian glioma grading,and combined detection of APTmax,APTmin,ADC,CBV,MTT and TTP imaging parameters can further improve diagnostic accuracy.

Objective:To explored the application value of dynamic susceptibility contrast-perfusion weighted imaging(DSC-PWI)combined with amide proton transfer(APT)imaging in brian glioma grading.Methods:Retrospective analysis of clinical data of 100 patients with brian glioma admitted to The Second Affiliated Hospital of Xinjiang Medical University from January 2022 to September 2024.They were divided into a low-grade group(WHO grades Ⅰ-Ⅱ,n=62)and high-grade group(WHO grades Ⅲ-Ⅳ,n=38)according to the World Health Organization(WHO)grading system for tumors.All patients underwent DSC-PWI and APT imaging preoperative examinations.Apparent diffusion coefficien(ADC),cerebral blood volume(CBV),cerebral blood flow(CBF),mean transit time(MTT),time to peak(TTP),maximum APT value(APTmax),minimum APT value(APTmin),the average APT value of the whole lesion(APTwhole)were recorded.The general datas and ADC,CBV,CBF,MTT,TTP,APTmax,APTmin,APTwhole of two group were compared.The influencing factors of high-grade brian glioma were analysed by Multivariate logistic regression.The diagnostic value of high-grade brian glioma was analysed of DSC-PWI combined with APT imaging by receiver operating characteristic(ROC)curve.Results:There was no statistically significant difference in age,gender,lesion location,basilar artery occlusion,necrosis and growth pattern between the two groups(P＞0.05),there was a statistically significant difference in the maximum diameter of lesions ≥2 cm and cystic lesions(P＜0.05).The ADC of the high-gradel group was lower than that of the low-grade group,while APTmax,APTmin,APTwhole,CBF,CBV,MTT and TTP were all higher than those of the low-grade group(P＜0.05).Elevated APTmax,APTmin,CBV,MTT,and TTP were risk factors for high-grade brian glioma(P＜0.05),while elevated ADC was a protective factor(P＜0.05).The results of ROC analysis showed that,the area under the curve(AUC)values of APTmax,APTmin,ADC,CBV,MTT,and TTP for diagnostic high-grade brian glioma were 0.830,0.868,0.852,0.843,0.803 and 0.827(all P＜0.05).The results of ROC analysis showed that,the AUC values of the logistic model for diagnostic high-grade brian glioma was 0.993.Conclusion:Single detection of DSC-PWI and APT imaging parameters has high diagnostic value in brian glioma grading,and combined detection of APTmax,APTmin,ADC,CBV,MTT and TTP imaging parameters can further improve diagnostic accuracy.

Objective:To investigate the effects of prognostic nutritional index (PNI) on the readmission rate, complication rate, mortality rate and survival of patients with liver cirrhosis.Methods:From January 1, 2020 to December 31, 2022, 395 hospitalized patients with liver cirrhosis at Tianmen Hospital Affiliated to Wuhan University of Science and Technology were retrospectively enrolled. The clinical data were collected from the patients at their first hospitalization (baseline period) and re-hospitalization during follow-up period. The 18-month follow-up was divided into 4 periods, including the first period (from the 0th to the 3rd month), the second one was from the 4th to the 6th month, the third one was from the 7th to the 12th month, and the fourth one was from the 13th to the 18th month of follow-up. The prognostic value of PNI for patients with liver cirrhosis was evaluated through the receiver operating characteristic curve (ROC) of the baseline PNI. The 395 patients were divided into the low PNI group and the high PNI group based on the optimal cut-off value of PNI on the ROC. Patients readmitted during each follow-up period were divided into the PNI improvement group (PNI at follow-up -PNI at baseline>0) and the PNI non-improvement group (PNI at follow-up-PNI at baseline ≤0). Independent sample t-test, one-way analysis of variance (ANOVA), Mann-Whitney U test, chi-square test or Fisher′s exact test were used for statistical analysis. Survival curves depicting the relationship between PNI and overall survival rate of patients with liver cirrhosis were constructed using the Kaplan-Meier method. Results:The ROC analysis indicated that the optimal cut-off value of PNI at baseline was 32.65, with an area under the curve of 0.639 (95% confidence interval: 0.541 to 0.738, P=0.011), with a sensitivity of 0.567 and a specificity of 0.701. There were 269 cases in the high PNI group and 126 cases in the low PNI group. The readmission rate, complication rate and mortality rate in the low PNI group were all higher than those in the high PNI group at the first and fourth follow-up periods (32.5% (41/126) vs. 22.3% (60/269), 31.7% (40/126) vs. 20.4% (55/269), 6.3% (8/126) vs. 1.1% (3/269), 25.0% (29/116) vs. 16.2% (42/260), 25.0% (29/116) vs. 15.4% (40/260), 6.0% (7/116) vs. 1.5% (4/260)), and the differences were statistically significant ( χ2=4.72, 6.00, 6.86, 4.10, 4.95, and 4.24; P=0.030, 0.014, 0.009, 0.043, 0.026, and 0.040). The mortality rates of the PNI improvement group at the first and fourth follow-up periods were both lower than those of the PNI non-improvement group (4.3% (2/47) vs. 16.7% (9/54), 0 (0/24) vs. 23.4% (11/47)), and the differences were statistically significant ( χ2=3.99, Fisher′s exact test; P=0.046 and 0.012). There were no statistically significant difference in the incidence of complications between the PNI improvement group and the PNI non-improvement group at each follow-up period (all P>0.05). The Kaplan-Meier survival curve demonstrated that the average survival time of the high PNI group was longer than that of the low PNI group (17.54 months (95% confidence interval: 17.26 to 17.83 months) vs. 16.74 months (95% confidence interval: 16.96 to 17.52 months), and the difference was statistically significant ( χ2=9.18, P<0.001). The survival rate of the high PNI group at the 18th month of follow-up period was higher than that of the low PNI group (95.2% (256/269) vs. 86.5% (109/126), and the difference was statistically significant ( χ2=9.17, P=0.002). Conclusions:PNI has certain predictive efficacy for the survival period of patients with liver cirrhosis. Low-level PNI may increase the readmission rate, complication rate, and mortality of patients with liver cirrhosis, and shorten the survival period, indicating poor prognosis.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*