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.

ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

INTRODUCTION: In the early phase of the coronavirus disease 2019 (COVID-19) pandemic, children with COVID-19 in Singapore required hospital isolation. We aimed to explore the psychological experiences of children and their caregivers isolated in a tertiary university hospital due to COVID-19. METHODS: A prospective mixed-methods design was used to evaluate the psychological status of hospitalised family units with one or more children aged <18 years who had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patient medical records were reviewed for demographic and clinical information. Parents and children ≥7 years of age underwent a psychologist-administered telephone-based interview. Self-reported, age-appropriate instruments, Short Mood and Feelings Questionnaire, and Screen for Adult/Child Anxiety-Related Disorders, were used to assess anxiety and depression, respectively. Participants were also interviewed qualitatively. RESULTS: Fifteen family units were hospitalised between March 2020 and May 2020. Of these, 13 (73%) family units were recruited. The median age of the children and median hospitalisation duration were 57 months and 21 days, respectively. Median number of COVID-19 polymerase chain reaction swabs performed for each child was eight. All children had asymptomatic to mild SARS-CoV-2 disease. The criteria indicative of anxiety disorder were met by 40% of adults and 80% of children, while the criteria indicative of separation anxiety were met by 60% of parents and 100% of children. One child met the criteria indicative of depression. Uncertainty, separation, prolonged hospitalisation and frequent swabs caused significant reported anxiety. CONCLUSIONS Families, especially children, had heightened anxiety while in hospital isolation. Therefore, home-based recovery from COVID-19 and psychological support for children and their families, with focus on early recognition of anxiety disorders, are recommended. We support review of paediatric isolation policy as the pandemic evolves.
Humans ; COVID-19/epidemiology* ; Male ; Child ; Female ; Singapore/epidemiology* ; Anxiety/etiology* ; Prospective Studies ; Adolescent ; Hospitalization ; SARS-CoV-2 ; Adult ; Child, Preschool ; Pandemics ; Parents/psychology* ; Caregivers/psychology* ; Family/psychology* ; Depression ; Patient Isolation/psychology* ; Surveys and Questionnaires

Objective To explore the association and diagnostic performance of liver imaging reporting and data system(LI-RADS)CT signs with hepatocellular carcinoma(HCC)both in the LI-RADS target population and patients without LI-RADS-defined HCC risk factors.Methods A retrospective analysis was conducted on the data of 435 patients with 482 hepatic lesions confirmed by pathology.Of these,306 cases were assigned to the HCC group(327 HCC lesions),and other 129 cases were assigned to the non-HCC group(77 malignancies and 78 benign lesions).Receiver operating characteristic(ROC)curve analysis assessed the diagnostic performance of LI-RADS v2018 CT signs for HCC,and logistic regression analyses determined the association of CT signs with HCC.Results The asso-ciation of CT signs with all HCC lesions was statistically significant for non-peripheral washout[odds ratio(OR)15.1;95％ confi-dence interval(CI)5.6-40.4;P＜0.01]and non-rim arterial phase hyperenhancement(APHE)(OR 12.4;95％ CI 7.5-20.5;P＜0.01)higher than enhanced capsule(OR 9.9;95％ CI 2.8-34.8;P＜0.01;OR 2.4;95％ CI 1.4-3.8;P=0.01).The sensitivity,specificity,positive predictive value(PPV),and area under the curve(AUC)for diagnosing HCC were 85％,83％,91％,and 0.84,respectively for non-peripheral washout;82％,77％,88％ and 0.79,respectively for non-rim APHE;and 31％,98％,97％ and 0.65,respectively for enhanced capsule.Sensitivity(88％ vs 87％),specificity(83％ vs 82％),PPV(92％ vs 91％)and AUC(0.90 vs 0.87)were all slightly higher when non-peripheral washout,non-rim APHE,enhanced capsule,and ancillary features were combined for the diagnosis of HCC compared to combining the three major features.Enhanced capsule(OR 13.3;95％ CI 3.6-48.9;P＜0.01),blood products in mass(OR 20.3;95％ CI 2.4-171.4;P＜0.01),and mosaic appearance(OR 37.7;95％ CI 4.2-340.0;P＜0.01)were associations with HCC presenting with atypical imaging features and provided high specificity from 98％ to 99％.Conclusion In theLI-RADS target population and patients without LI-RADS-defined HCC risk factors,LI-RADS v2018 CT signs show excellent diag-nostic performance for HCC.Two ancillary features,blood products in mass and mosaic appearance,show good specificity for HCC with atypical imaging features.

Aim To explore the relevant mechanisms of isoliquiritigenin(ISL)in inhibiting the proliferation and migration of vascular smooth muscle cells(VSMCs)by regulating the GRB2/ERK signaling pathway.Methods Human primary vascular smooth muscle cells(hVSMCs)were cultured,and stimulated with different concentrations of ISL and fixed concen-trations of growth factors PDGF-BB and EGF,respec-tively.Subsequently,the effect of overexpressing GRB2 on the efficacy of ISL was observed.CCK-8 assay was used to detect cell proliferation;BrdU assay was used to detect DNA synthesis;Western blot was used to de-tect the expression levels of OPN,ICAM-1,VCAM-1,GRB2,ERK1/2,and p-ERK1/2;wound healing assay was used to detect cell migration;transwell assay was used to detect cell invasion.Results Compared with the blank control group and the ISL 20 mg·L-1 group,the PDGF-BB group and the EGF group showed increased cell viability and DNA synthesis,decreased cell migration distance,and increased number of inva-sive cells.Additionally,the expression levels of GRB2 and p-ERK1/2 increased.Compared with the PDGF-BB 40 μg·L-1group or the EGF 10 mg·L-1 group,the ISL drug intervention group showed decreased cell viability and DNA synthesis,increased migration dis-tance of cells,decreased number of invasive cells,and decreased expression levels of GRB2 and p-ERK1/2.Compared with the ISL 20 mg·L-1+PDGF-BB and ISL 20 mg·L-1+EGF groups,the groups with ISL+PDGF-BB+pcDNA-GRB2 group and ISL+EGF+pcDNA-GRB2 group showed increased expression lev-els of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Compared with the ISL+PDGF-BB+pcDNA-GRB2 group and the ISL+EGF+pcDNA-GRB2 group,the pcDNA-GRB2+PDGF-BB group or the pcDNA-GRB2+EGF group showed increased expres-sion levels of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Conclusions Isoliquiritigenin inhibits the proliferation and migration of vascular smooth mus-cle cells by regulating the GRB2/ERK signaling path-way.

Aim To explore the biological mechanism of ligustilide in the prevention and treatment of osteo-porosis by regulating H-type blood vessels,combined with animal experiments for verification,based on net-work pharmacology and molecular docking technology Methods The possible mechanism of ligustilide regu-lating H-type blood vessels to prevent osteoporosis was predicted by network pharmacology.Molecular docking technology was used to verify the binding ability of the core target EGFR to ligustilide.The rat model of osteo-porosis was established and divided into the sham group,model group,ligustilide high,medium and low dose(80,40,20 mg·kg-1)groups.The pathological changes of femur were observed by HE staining.The expressions of CD31,EMCN,OSX+and RUNX2+pro-tein in tibial metaphysis were detected by immunofluo-rescence.The expression of p-EGFR,p-PI3K and p-Akt protein was detected by Western blot.Results The results of network pharmacology showed that a total of 20 intersection targets were obtained.EGFR,PTGS2,ESR1 and ICAM1 were core targets,and mo-lecular docking showed that EGFR had a strong bind-ing ability with ligustilide.The signaling pathways of ligustilide in the prevention and treatment of osteoporo-sis by regulating the expression of H-type blood vessels were mainly enriched in PI3K-Akt,TNF,etc.Com-pared with the model group,ligustilide could signifi-cantly increase the number of trabecular bone and im-prove the destruction of bone microstructure.The ex-pression of CD31,EMCN,OSX+and RUNX2+signifi-cantly increased(P＜0.01,P＜0.05),the formation of H-type blood vessels were promoted,and the expres-sion of p-EGFR,p-PI3K and p-Akt significantly in-creased(P＜0.01,P＜0.05).Conclusions Ligusti-lide can increase the expression of H-type blood vessels in bone tissue of osteoporosis model rats,reduce the damage of bone trabecula and improve bone micro-structure effectively.EGFR-mediated PI3K/Akt signa-ling pathway may be the key way to exert its biological effects.

Objective:To explore the prognostic model for construction and preliminary evaluation of tumor invasion of im-mune cells after hemithyroidectomy in patients with thyroid cancer.Methods:The gene expression profiles and follow-up parameters of 152 patients with thyroid cancer after hemithyroidectomy from November 2020 to November 2022 were selected from The Cancer Genome Atlas(TCGA);ssGSEA was used to quantify immune cell infiltration in tumor tissues.LASSO was used to screen for key pre-dictors to verify the relationship between prognosis and different infiltrating immune cells.A prognostic risk score model was constructed using appropriate immune cells,and thyroid cancer patients were stratified into high-and low-risk groups.Kaplan-Meier survival curves were used for validation.Nomogram models were developed based on the risk model to predict survival rates and treatment inef-ficiency in thyroid cancer patients.Model accuracy was verified using ROC curve and AUC value.Calibration curves were employed to compare predicted and observed outcomes,and clinical decision curves were used to assess model reliability.Results:Immune cell in-filtration data were quantified by ssGSEA to obtain 22 infiltrating immune cells,including activated mast cells,naive B cells,unacti-vated mast cells,plasma cells,CD8+T cells,γδT cells,naive CD4+T cells,activated memory CD4+T cells,Treg cells,follicular helper T cells,memory B cells,activated NK cells,unactivated NK cells,unactivated memory CD4+T cells,M0 macrophages,monocytes,M1 macrophages,neutrophils,unactivated dendritic cells,activated dendritic cells,M2 macrophages and eosinophils.Six immune cells were selected as predictors,M0 macrophages,M2 macrophages,activated dendritic cells,unactivated mast cells,CD8+T cells,and monocytes.Risk scores calculated from these six immune cells were positively correlated with poor prognosis in high-risk patients.Kaplan-Meier analysis showed significantly longer overall survival in the low-risk group compared to the high-risk group(Log-Rank χ2=4.524,P=0.024).The total score of the prognostic nomogram model was 425,and the mortality risk was 79.12%;the treatment efficacy nomogram model had a total score of 406 points,corresponding to a 77.97%risk of treatment failure.Model validation results were reliable.Conclusion:The nomogram model of immune cells infiltration in thyroid cancer patients suggest that immune cell infiltration can be used as an important indicator to predict therapeutic efficacy and prognostic outcome in thyroid cancer patients.

Objective:To investigate the clinical efficacy of trimetazidine,dopamine combined with furosemide in eld-erly patients with rheumatic heart disease(RHD)and chronic heart failure(CHF)and its effect on the levels of me-teorin-like protein(Metrnl),soluble triggering receptor expressed on myeloid cells-1(sTREM-1)and syndecan-1.Methods:This randomized controlled study enrolled 106 elderly patients with RHD and CHF who were hospi-talized in the First People's Hospital of Xianyang between March 2022 and December 2023.Patients were divided in-to control group(n=53,routine treatment)and intervention group(n=53,additional trimetazidine,dopamine and furosemide combined treatment),and treated for 1 week.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd),6-min walking distance(6MWD),Minnesota living with heart failure questionnaire(MLHFQ)score,serum levels of B-type natriuretic peptide(BNP),Metrnl,sTREM-1 and syndecan-1,and incidence of adverse reactions during treatment were compared between the two groups.Binary Logistic regression was used to analyze the association be-tween influencing factors and therapeutic effect.Results:The total effective rate of intervention group was signifi-cantly higher than that of control group(96.23％vs.83.02％,P=0.026).Compared to patients in the control group after treatment,those in the intervention group had significantly lower LVEDd[(45.27±5.95)mm vs.(50.11±4.47)mm],LVESd[(34.85±4.19)mm vs.(40.93±4.77)mm],MLHFQ score[(34.51±4.47)points vs.(45.62±5.08)points],levels of BNP[(95.29±8.31)pg/ml vs.(145.39±25.71)pg/ml],sTREM-1](43.59±4.21)pg/ml vs.(50.61±5.48)pg/ml]and syndecan-1[(7.01±1.88)μg/L vs.(11.02±2.36)μg/L],and significantly higher LVEF[(58.14±4.02)％vs.(50.61±6.15)％],6MWD[(433.48±45.74)m vs.(386.51±31.25)m]and Metrnl level[(205.08±27.45)ng/L vs.(188.52±22.37)ng/L](P＜0.001 all).Bi-nary Logistic regression analysis showed that the combination of trimetazidine,dopamine and furosemide was an in-dependent protective factor for the efficacy of elderly patients with RHD and CHF(OR=0.096,95％CI:0.011～0.837,P=0.034).There was no significant difference in the total incidence of adverse reactions between interven-tion group and control group(13.20％vs.11.32％,P=0.767).Conclusion:The combination of trimetazidine,do-pamine and furosemide could significantly improve cardiac function and exercise tolerance,reduce serum sTREM-1 and syndecan-1 levels,and increase Metrnl level with good safety in elderly patients with RHD and CHF.

Occult hepatitis B virus(HBV)infection(OBI)represents a potential reservoir for HBV transmission,capable of spreading through routes such as blood transfusion.Additionally,OBI can con-tribute to the chronic progression of hepatitis B-related diseases,sustaining a state of chronic HBV infec-tion.In individuals with compromised immune function or undergoing immunosuppressive therapy,OBI may lead to HBV re-activation,potentially triggering severe liver conditions such as acute hepatitis or liv-er failure.As a result,OBI poses a significant public health challenge,profoundly impacting the health and well-being of affected populations and complicating HBV infection control efforts in China.Clinically diagnosing OBI remains challenging,but its hallmark is serum hepatitis B surface antigen negative and the presence of HBV covalently closed circular DNA(cccDNA)in the liver.With the increasing focus on achieving functional cure for chronic hepatitis B,both domestic and international guidelines have re-fined functional cure.Notably,these guidelines acknowledge that cccDNA may persist in the liver tissue of individuals who have achieved functional cure,suggesting resemblance of an occult infection state.Here,we provide a comprehensive overview of OBI,including its definition,classification,public health implications,underlying mechanisms,and clinical reactivation.By updating the understanding of OBI,we aim to raise awareness among clinicians and public health professionals regarding the significance of OBI in the current context and encourage greater attention to this population.

Objective To investigate the effect of salvianolic acid B(Sal B)on high glucose(HG)induced necrotic apoptosis of retinal pigment epithelial cells(RPE)by regulating the receptor-interacting protein kinase 1(RIP1)/RIP3/mixed lineage kinase domain like protein(MLKL)signaling pathway.Methods RPE cells ARPE-19 were used as the research object and separated into control(Con)group,HG group,L-Sal B group,M-Sal B group,H-Sal B group,pcDNA3.1-NC group,and pcDNA3.1-RIP1 group.The qRT-PCR method was applied to detect the expression of RIP1,RIP3,and MLKL in ARPE-19 cells in each group.CCK8 was applied to detect ARPE-19 cell survival rate.Flow cytometry was applied to detect cell apoptosis.DCFH-DA fluorescent probe was applied to detect reactive oxygen species(ROS)level.ELISA was applied to detect the expression of tumor necrosis factor-α(TNF-α),interleukin(IL-1β),and IL-6.Western blot was applied to detect the expression of RIP1,RIP3,and MLKL proteins.Results The cell survival rate was lower in the HG group than in the Con group(P<0.05).The cell apoptosis rate,the proportion of ROS-positive cells,TNF-α,IL-1β,IL-6,and the mRNA and protein expressions of RIP1,RIP3,and MLKL were higher in the HG group than in the Con group(P<0.05).The cell survival rates were higher,while the cell apoptosis rates,the proportion of ROS-positive cells,TNF-α,IL-1β,IL-6,and the mRNA and protein expressions of RIP1,RIP3,and MLKL were lower in the L-Sal B,M-Sal B,and H-Sal B groups than in the HG group(P<0.05).The cell survival rates increased successively(P<0.05),while the cell apoptosis rates,the proportion of ROS-positive cells,TNF-α,IL-1β,IL-6,and the mRNA and protein expressions of RIP1,RIP3,and MLKL decreased successively in the L-Sal B,M-Sal B,and H-Sal B groups(P<0.05).The cell survival rate was lower(P<0.05),while the cell apoptosis rate,the proportion of ROS-positive cells,TNF-α,IL-1β,IL-6,and the mRNA and protein expressions of RIP1,RIP3,and MLKL were higher in the pcDNA3.1-RIP1 group than in the H-Sal B and pcDNA3.1-NC groups(P<0.05).Conclusions Sal B may inhibit the necrotic apoptosis of RPE cells induced by HG by suppressing the RIP1/RIP3/MLKL signaling pathway.