1.The Structure and Function of The YopJ Family Effectors in The Bacterial Type III Secretion System
Ao-Ning LI ; Wen-Bo LI ; Yu-Ying LU ; Min-Hui ZHU ; Yu-Long QIN ; Yong ZHAO ; Zhao-Huan ZHANG
Progress in Biochemistry and Biophysics 2026;53(3):516-533
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.
2.Chemical constituents from the roots of Siraitia grosvenorii and their α-glucosidase inhibitory activities
Si-yu WEI ; Yu-lu WEI ; Feng-lai LU ; Wen-long LONG ; Xiao-hua JIANG
Chinese Traditional Patent Medicine 2025;47(4):1181-1188
AIM To study the chemical constituents from the roots of Siraitia grosvenorii(Swingle)C.Jeffrey and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract was isolated and purified by silica gel,MCI,ODS and HSCCC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The α-glucosidase inhibitory activities were evaluated by PNPG method,after which molecular docking was performed.RESULTS Twenty-one compounds were isolated and identified as vanillin(1),siraitic acid B(2),cucurbitacin B(3),salicylic acid(4),ferulic acid(5),p-hydroxybenzaldehyde(6),(+)-lariciresinol(7),(+)-isolariciresinol(8),liballinol(9),3-(hydroxyacetyl)indole(10),2E-4-hydroxy-nonenoic acid(11),vomifolilol(12),vanillic acid(13),indole-3-carboxylic acid(14),ω-hydroxypropioguaiacone(15),p-hydroxybenzoic acid(16),p-coumaric acid(17),dehydrodipinocarpine(18),secoisolariciresinol(19),sesquimarocanol A(20),threo-guaiacylglycerol-β-O-4-lariciresinol ether(21).IC50 values of compounds 4,10,18 and 21 were(0.42±0.060)-(0.89±0.037)mg/mL.CONCLUSION Compounds 4,10-12,15,16,18,and 21 are isolated from the roots of this plant for the first time.Compounds 4,10,18,21 have α-glucosidase inhibitory activities,and 18 has the strongest activity.
3.Shengmai Yin alleviates myocardial ischemia/reperfusion injury via inhibiting Calpains expression
Rong MIAO ; Jing-wen GUO ; Ming HUANG ; Hai-shuo REN ; Rui LIU ; Xiao-yu SUN ; Opoku Bonsu FRANCIS ; Qi-long WANG ; Shi-ming FANG ; Ling LENG
Chinese Pharmacological Bulletin 2025;41(8):1569-1577
Aim To investigate the protective effect of Shengmai Yin on myocardial ischemia/reperfusion in-jury(MI/RI)in vitro and in vivo and to unravel the underlying mechanism.Methods SD rats were divid-ed into the sham group,model group,and Shengmai Yin group(SM).Rat MI/RI model was established.Cardiac function,infarct area,pathological changes,cardiomyocyte apoptosis,macrophage infiltration,and serum cTnT and CK-MB levels were measured.The mRNA and protein expressions of Calpain-1 and Cal-pain-2 were assessed.The hypoxia/reoxygenation(H/R)model was constructed in H9c2 cells.The active ingredients of Shengmai Yin were screened using net-work pharmacology and verified by CCK-8.In the car-diomyocytes H/R model,Fluo-4 AM staining was used to detect the changes of Ca2+levels.Results Com-pared with model group,LVEF and LVFS of Shengmai Yin-treated rats increased,myocardial infarction area was reduced,while myocardial tissue injury was allevi-ated.Myocardial apoptosis rate and the number of macrophages were reduced.Similarly,cTnT and CK-MB levels decreased.In addition,the expression lev-els of Calpain-1 and Calpain-2 mRNA and protein de-creased in the SM treatment group.Under the H/R model,all the active ingredients of Shengmai decoction had protective effects on cardiomyocytes,and the treat-ment could reduce the level of Ca2+in cardiomyocytes.Conclusions Shengmai Yin has protective effects on MI/RI in rats.This effect may be related to the de-crease in Ca2+levels,as well as Calpain-1 and Calap-in-2 mRNA and protein expression.
4.Investigation on ventilator use and management in secondary and tertiary medical institutions in Sichuan Province
Zheng-hua LIANG ; Si-mei WANG ; Qiu-yu LIU ; Jin-long XU ; Ze-fang LIU ; Dan WEN
Chinese Medical Equipment Journal 2025;46(3):75-80
Objective To investigate the current situation of the ventilator use and management in secondary and tertiary medical institutions in Sichuan Province to provide references for management and training of ventilator users.Methods A questionnaire survey involving in 235 nurses from 13 secondary and tertiary medical institutions in Sichuan Province was conducted in terms of general information of the respondents,pipeline connection and parameter setup of ventilators,cleaning,sterilization and maintenance of ventilators,identification and treatment of ventilator alarms and hospital-acquired infection prevention and control.Results The results showed 20.4%of the respondents were nurses from critical care departments,and 79.6%of the respondents underwent the training for using the ventilator in their department;91.9%of the respondents could conduct ventilator self-testing by connecting the simulated lungs after the ventilator was switched on;66.4%of the respondents indicated that the initial parameters of the ventilator were set by the doctor;60.9%of the respondents proved that the performance monitoring and routine maintenance of the ventilator were carried out by the nurse;63.4%of the respondents showed disposable lines were commonly used in the departments.There were 89.8%of the respondents said the daily sterilization and management of the ventilator were performed by the nurse;46.0%of the respondents expressed the external surface of the ventilator was disinfected mainly with gamma disinfectant wipes;44.7%of the respondents indicated the external surface of the ventilator was sterilized every day;48.5%of the respondents said the internal airway of the ventilator was disinfected;57.0%of the respondents proved the disinfection was conducted after the expiratory flow sensors were used by any patient.There were 74.5%of the respondents that had paid attention to the ventilator waveform,and by the ventilator waveform only 21.3%were correct in determining whether there was secretion or fluid in the circuit and 22.1%in clarifying whether there was air leakage in the circuit.There were 59.1%of the respondents indicated that the closed suction tube was replaced once every 24 h;71.1%of the respondents could perform airbag pressure monitoring by the special pressure gauge.Conclusion Most of the nurses from secondary and tertiary medical institutions in Sichuan Province can use ventilators correctly,who have problems in disinfection specifications,infection prevention and control or recognition of ventilation waveform.It's suggested the training be strengthened to enhance the clinical nursing staffs in ventilator management.[Chinese Medical Equipment Journal,2025,46(3):75-80]
5.Correlation between immune cells and cardiovascular diseases in patients with HIV/AIDS and the construction of a risk prediction model
Jiangying LONG ; Cuizhi LI ; Chunyan WEN ; Zhihua TANG ; Yu YUAN
Immunological Journal 2025;41(11):793-801
Objective To investigate the correlation between immune cells and the occurrence of cardiovascular disease(CVD)in patients with human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS),and to construct a risk prediction model.Methods A total of 280 HIV/AIDS patients treated from June 2024 to August 2025 were selected as the research subjects and divided into a training set(n=200)and a test set(n=80)at a ratio of 5:2.The patients in the training set were subdivided into a CVD subgroup(n=60)and a non-CVD subgroup(n=140)according to whether they developed CVD.The baseline characteristics and immune cells of the two groups were compared,and the longitudinal trajectory changes of immune cells in the CVD subgroup and the non-CVD subgroup were analyzed.LASSO regression analysis was used to screen the independent influencing factors of CVD,multivariate Logistic regression analysis was used to screen the independent risk factors for the occurrence of CVD,and a risk prediction nomogram model was constructed.The area under the receiver operating characteristic(ROC)curve(AUC),Hosmer-Lem show test,calibration curve,and decision curve were used to compare the risk prediction nomogram model with the general cardiovascular risk assessment model,to evaluate its discrimination,goodness-of-fit,and clinical utility.Results There were significant differences in the baseline characteristics and immune cells between the two groups(P<0.05).The longitudinal trajectory plots revealed that the CD4+count,CD8+count,and CD4+/CD8+level in the CVD group exhibited substantial fluctuations,while the trajectories of these parameters in the non-CVD group remained relatively stable.After LASSO regression analysis screened out 11 non-zero coefficient variables,multivariate logistic regression analysis showed that age,hypertension,total cholesterol,smoking,high-sensitivity C-reactive protein,CD4+count at the time of HIV diagnosis,CD8+count at the time of HIV diagnosis,and globulin were all independent influencing factors for the occurrence of CVD in HIV/AIDS patients(P<0.05).The AUC of the risk prediction nomogram model was 0.960 in the training set and 0.914 in the test set,indicating good discrimination of the model.The Hosmer-Lem show test and calibration curve showed good accuracy and consistency of the model,and the decision curve showed a high net benefit value,indicating good clinical utility.Conclusion The CVD risk in HIV/AIDS patients is jointly affected by immune dysfunction and traditional metabolic factors.The risk prediction nomogram model constructed significantly improves the accuracy of risk prediction of CVD and can provide a basis for early identification of high-risk patients and the formulation of individualized intervention strategies.
6.Establishment and validation of a predictive model for increased drainage volume after open transforaminal lumbar interbody fusion
Yin HU ; Hai-long YU ; Hong-wen GU ; Kang-en HAN ; Shi-lei TANG ; Yuan-hang ZHAO ; Zhi-hao ZHANG ; Jun-chao LI ; Le XING ; Hong-wei WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(11):981-986
Objective To analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.
7.Quality inspection of ultrasound soft tissue cutting hemostatic equipment
Jing HUANG ; Qi-di SUN ; Ao-wen DUAN ; Li XU ; Heng-yu LONG ; Hai-jiang ZHU ; He-hua ZHANG
Chinese Medical Equipment Journal 2025;46(10):49-53
Objective To carry out quality inspection of the ultrasound soft tissue cutting hemostatic equipment to ensure its safety and effectiveness.Methods Five brands of ultrasound soft tissue cutting hemostatic equipment were selected and noted as test equipment A,test equipment B,test equipment C,test equipment D and test equipment E,which underwent quality inspection in terms of tip main amplitude,tip lateral amplitude,tip vibration frequency,excitation frequency,static electrical power and contact current based on YY/T 0644-2008 Ultrasonics-surgical systems—Measurement and declaration of the basic output characteristics,YY/T 1750-2020 Ultrasonic surgical equipmetn for soft tissue excision and hemostasia and GB 9706.1-2020 Medical electrical equipment—Part 1:General requirements for basic safety and essential performance.Results The test data of the five brands in terms of tip main amplitude,tip lateral amplitude,tip vibration frequency,excitation frequency,static electrical power and contact current met the technical requirements of YY/T 0644-2008,YY/T 1750-2020,GB 9706.1-2020.Conclusion The quality inspection of the ultrasound soft tissue cutting hemostatic equipment contributes to enhancing the accuracy and stability of the equipment and decreasing the risk during its clinical application.[Chinese Medical Equipment Journal,2025,46(10):49-53]
8.Diagnostic Value of Total Bilirubin to Albumin Ratio Combined with Alpha-Fetoprotein and Abnormal Prothrombin Induced by Vitamin K Absence-Ⅱ for Hepatocellular Carcinoma
Yong LI ; Shou-lin YANG ; Lu-fa WU ; Tao LONG ; Hong-yu LI ; Wen-liang XIE
Progress in Modern Biomedicine 2025;25(10):1734-1742
Objective:To explore the diagnostic value of total bilirubin to albumin ratio(B/A ratio)combined with alpha-fetoprotein(AFP)and abnormal prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)for hepatocellular carcinoma(HCC).Methods:35 HCC patients(HCC group),35 cirrhosis patients(cirrhosis group),35 HCC patients post-transcatheter arterial chemoembolization(TACE)(TACE postoperative group),and 35 healthy volunteers(healthy control group)were selected in our hospital from October 2023 to October 2024.The serum B/A ratio,AFP,and PIVKA-Ⅱ levles were measured and compared across the groups.The correlations between serum B/A ratio,AFP,and PIVKA-Ⅱ in the HCC group were analyzed.The B/A ratio,AFP,PIVKA-Ⅱ were compared across different clinical and pathological features in HCC patients.The serum B/A ratio,AFP,and PIVKA-Ⅱ levels were compared pre and post operation in the HCC group.The diagnostic value of B/A ratio,AFP,PIVKA-Ⅱ alone and in combination for HCC were analyzed by receiver operating characteristic(ROC)curves.Results:The serum B/A ratio,AFP,and PIVKA-Ⅱ levels in HCC group and TACE postoperative group were significantly higher than those in the cirrhosis group and healthy control group,and the HCC group was higher than that in the TACE postoperative group(P<0.05).Pearson correlation analysis results showed that,B/A ratio in the HCC group was positively correlated with AFP(r=0.352,P=0.001),B/A ratio was positively correlated with PIVKA-Ⅱ(r=0.327,P=0.003),and AFP was positively correlated with PIVKA-Ⅱ(r=0.285,P=0.008).Higher TNM stage,larger tumor diameter,presence of vascular invasion,and lower differentiation degree of HCC patients,who had higher B/A ratio,AFP,and PIVKA-Ⅱ levels(P<0.05).Serum B/A ratio,AFP,and PIVKA-Ⅱ levels in the HCC group post operation were significantly lower than those in pre operation(P<0.05).ROC curve analysis results showed that,when B/A ratio,AFP,and PIVKA-Ⅱ were detected separately,the area under the curve(AUC)was 0.785,0.756,and 0.802,respectively.The AUC for joint detection was 0.925.The AUC in combination was greater than that of individual detection of each indicator.Conclusion:The combination of B/A ratio,AFP,and PIVKA-Ⅱ testing significantly improves the diagnostic efficiency for HCC,which is worthy of clinical application.
9.Comparative study of single-criteria and multi-criteria optimization modes for cervical cancer VMAT radiotherapy plans by Raystation planning system
Gang LI ; Yu-song LONG ; Jun-wen TAN ; Xian-tao HE ; Yong-fu FENG ; Zhan-yu WANG
Chinese Medical Equipment Journal 2025;46(9):39-44
Objective To carry out cervical cancer VMAT radiotherapy planning respectively with the single-criteria optimization(SCO)and multi-criteria optimization(MCO)modes of Raystation 4.7 planning system,and to provide references for selecting optimization mode clinically by comparing and analyzing the dosimetric parameters such as target dose distribution,exposure dose to organ at risk(OAR),monitor unit and beam-on time.Methods Ten cervical cancer patients who attended some hospital from February to December 2022 were retrospectively selected,and some VMAT plans were designed for them with the SCO mode of Raystation 4.7 planning system and then enrolled into a SCO group;other VMAT plans were redesigned with the MCO mode under the premise the setup conditions such as machine model and shot field angle were unchanged,and divided into a MCO group.The two groups were compared in terms of maximum dose(D2%),minimum dose(D98%),homogeneity index(HI)and conformity index(CI)of the planning target volume(PTV),beam-on time,monitor unit and exposure doses to OARs including bladder V50 Gy,V40 Gy and V30 Gy,rectum V50 Gy,V40 Gy and V30 Gy,small intestine V50 Gy,V40 Gy and V30 Gy and left and right femur V50 Gy,V40 Gy and V30 Gy.SPSS 22.0 software was used for statistical analysis.Results Both the two groups met clinical requirements.There were no significant differences between the two groups in D98%,CI,small intestine V50 Gy and left and right femur V40 Gy(P>0.05).The MCO group had the values of HI,D2%,V50 Gy,V40 Gy and V30 Gy,rectum V50 Gy,V40 Gy and V30 Gy,small intestine V40 Gy and V30 Gy and left and right femur V30 Gy lower than those of the SCO group,with the differences being statistically significant(P<0.05).The SCO group had less monitor units and shorter beam-on time when compared with the MCO group,with the differences being statistically siginificant(P<0.05).Conclusion When compared with the SCO mode-based VMAT plans,the MCO mode-based VMAT plans significantly decrease the exposure doses and volume to rectum,bladder and small intestine and raise the PTV homogeneity,while lower the treatment efficiency to some extent by increased monitor units and prolonged beam-on time.[Chinese Medical Equipment Journal,2025,46(9):39-44]
10.Liraglutide may alleviate acetaminophen-induced liver injury by enhancing autophagy
Guo-jing XING ; Wen-bin LI ; Long-long LUO ; Li-fei WANG ; Yuan DENG ; Zhen WANG ; Zhao-jie ZHANG ; Xiao-hui YU ; Jiu-cong ZHANG
Chinese Pharmacological Bulletin 2025;41(10):1867-1875
Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.

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