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.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
3.Predictive value of cerebroplacental ratio,cerebro-uterine ratio combined with cystatin C for adverse pregnancy outcomes in preeclampsia fetuses
Huan LU ; Tian TIAN ; Xue-hui WU ; Chun-mei ZHOU ; Xin-yu WU ; Wei LI
Journal of Regional Anatomy and Operative Surgery 2025;34(9):827-831
Objective To investigate the predictive value of cerebroplacental ratio(CPR),cerebro-uterine ratio(CUR)combined with cystatin C(CysC)for adverse pregnancy outcomes in preeclampsia(PE)fetuses.Methods A retrospective analysis was conducted on the clinical data of 150 PE patients admitted to the department of obstetrics and gynecology of Nuclear Industry 416 Hospital from January 2019 to December 2024,and patients were divided into the adverse-outcome group and the favorable-outcome group according to pregnancy outcomes.The clinical data,CPR,CUR and CysC level were compared between the two groups.Multivariate Logistic regression was used to analyze the independent influencing factors of adverse pregnancy outcome in PE patients;then,receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive efficiency of each index on adverse pregnancy outcome.Results The adverse-outcome group had shorter/lower gestational age at diagnosis,estimated fetal body weight,CUR,and CPR,but higher body mass index and CysC level compared to those in the favorable-outcome group,with significant differences(P<0.05).Multivariate Logistic regression identified that the elevated CysC level,and decreased CUR and CPR were related influencing factors for adverse pregnancy outcome(P<0.05).ROC curve analysis demonstrated that CUR,CPR and CysC had strong predictive value for adverse pregnancy outcome,with the area under the curve(AUC)of 0.802(95%CI:0.729 to 0.863),0.834(95%CI:0.764 to 0.890),and 0.791(95%CI:0.717 to 0.853),respectively;the combined prediction of CUR,CPR and CysC had grater AUC of 0.909(95%CI:0.851 to 0.950)than the individual prediction of the above three indicators(P<0.05).Conclusion CUR,CPR and CysC are influencing factors of adverse pregnancy outcome in PE patients,and their combined detection demonstrates good predictive value for adverse pregnancy outcome in PE patients.
4.Subacute toxicity study of triethylenediammonium perchlorate ammonium complex salt in rats
Hui DENG ; Hongni LIU ; Huan LI ; Ting GAO ; Cunzhi LI ; Xiaoqiang LYU ; Zhiyong LIU ; Junhong GAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(9):693-697
Objective:To investigate the subacute toxicity and target organs of triethylenediammonium perchlorate ammonium complex salt (DAP-4) .Methods:In August 2024, 40 SPF-grade SD rats were selected, with 10 rats in each group, half male and half female. There were 45, 140, and 420 mg/kg DAP-4 groups and a control group. Rats in each dose DAP-4 group were orally administered the corresponding amount of DAP-4 solution, while the control group was given the same dose of 1% sodium carboxymethyl cellulose. SD rats were given intragastric administration once a day for 28 consecutive days. The behaviors, histopathological changes, and blood physiological and biochemical indicators of rats were detected at the corresponding time points respectively. One-way analysis of variance was used for the comparison of quantitative data between groups.Results:Compared with the control group, the body weight, food intake and food utilization rate of female and male rats in the 420 mg/kg DAP-4 group were significantly decreased ( P<0.05), while no abnormalities were observed in the other dose groups. Compared with the control group, the white blood cell count of female rats in the 420 mg/kg DAP-4 group decreased, while the hemoglobin and hematocrit decreased and the total serum protein increased of male rats ( P<0.05). Compared with the control group, fibrinogen was increased in both female and male rats in the 420 mg/kg DAP-4 group, and the thrombin time of female rats was shortened ( P<0.05). In each dose group, the livers of female and male rats showed varying degrees of vacuolar degeneration, and the renal tubules of female rats were swollen. Conclusion:420 mg/kg DAP-4 can cause damage to the liver and kidney of rats, and the maximal no effect level of DAP-4 for rats is 140 mg/kg.
5.Quality evaluation of Chuanxiong Chatiao Pills based on UPLC fingerprints,chemometrics and content determination
Zhuo XUE ; Hui-yong LI ; Huan CAO ; Xue-yan BI
Chinese Traditional Patent Medicine 2025;47(6):1773-1781
AIM To evaluate the quality of Chuanxiong Chatiao Pills.METHODS The UPLC fingerprints were established,after which hierarchical cluster analysis,principal component analysis,orthogonal partial least squares discriminant analysis were performed,the contents of cimifugin,ferulic acid,liquiritin,nodakenin,senkyunolide Ⅰ,5-O-methylvisamminol,rosmarinic acid,ammonium glycyrrhizinate,imperatorin and isoimperatorin were determined.RESULTS There were 18 common peaks in the fingerprints for 44 batches of samples with the similarities of 0.75-1.00.Various batches of samples were clustered into 2 catagories,3 principal components demonstrated the accumulative variance contribution rate of 87.1%,5 quality difference markers were screened.Ten constituents showed good linear relationships within their own ranges(r≥0.999 3),whose average recoveries were 90.22%-105.30%with the RSDs of 0.66%-1.98%,whose content ranges were 0.070-0.438,0.147-0.529,0.052-0.444,1.228-6.934,0.016-0.545,0.049-1.554,0.018-0.415,0.382-2.187,0.568-3.700,0.069-0.996 mg/g,respectively.CONCLUSION This accurate,reliable and specific method can provide scientific evidence for the quality control and standardization of Chuanxiong Chatiao Pills.
6.Research progress of the prevention, care, and treatment services along the HIV/AIDS care cascade
Hui XIANG ; Wei MA ; Fangfang CHEN ; Huan LIU ; Houlin TANG
Chinese Journal of Epidemiology 2025;46(8):1506-1512
Since the 1980 s, AIDS has been a significant global public health threat. With the "95-95-95" targets for HIV/AIDS prevention and control, the HIV/AIDS "prevention, testing, and treatment" care cascade covering the entire process has become a core strategy. The present study examines combs the connotation and development of the HIV/AIDS care cascade, exploring application throughout the entire process and at each linkage. It analyzes extension value in key populations and HIV co-infected other infectious diseases, identifies obstacles in practice, and proposes strategies to help optimize, innovate, and precisely target HIV/AIDS prevention and control in China.
7.Research on the Application Value of Dynamic Susceptibility Contrast-Perfusion Weighted Imaging Combined with Amide Proton Transfer Imaging in Brian Glioma Grading
Huan CHEN ; Lu HAO ; KALIBUNUR·MAHEMUTI ; Ming-hui ZHU ; Yu-tong ZHU
Progress in Modern Biomedicine 2025;25(17):2811-2819
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.
8.Experimental study of magnetic tracer technique in the localization of pulmonary nodules in dogs
Huan-chen SHA ; Miao-miao ZHANG ; Jia-hui WAN ; Qiu-ye ZHONG ; Rui-min GONG ; Yi LYU ; Xiao-peng YAN
Journal of Regional Anatomy and Operative Surgery 2025;34(10):841-845
Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.
9.Effects of robust optimization parameters on radiation dose in proton radiotherapy for localized prostate cancer
Hui ZHOU ; Yibin ZHANG ; Jiayi CHEN ; Yujie WANG ; Huan LI ; Cheng XU
Chinese Journal of Medical Physics 2025;42(5):561-565,570
The effects of different robust optimization parameters on the doses to organs-at-risk(OAR)and the clinical target volume(CTV)in proton therapy plans for localized prostate cancer are explored for identifying the optimal robust optimization parameters.A retrospective analysis is conducted on 10 cases in which proton plans with a total dose of 76 Gy delivered in 38 fractions are designed.In robust optimization,uncertainties of 3.5%in range and setup errors of 3,5 and 7 mm are considered.After being grouped by setup errors,3 groups of plans are obtained.The effects of setup errors on the doses to CTV and OAR are analyzed,and the robustness of the CTV dose is assessed,including the worst-case values of dosimetric parameters and the passing rates under different scenarios.The results show that as the setup error increased,the doses to OAR tended to rise.Compared with the 3 mm plan group,the 5 mm and 7 mm plan groups experience increases of 1.99%and 5.15%in rectal V70,3.71%and 10.01%in rectal V45,0.93%and 2.55%in bladder V70,and 1.71%and 5.27%in bladder V45,respectively;similar patterns are observed for the doses to sigmoid colon and bulbous urethra,and the differences are statistically significant(P<0.05).In robustness analysis,the CTV D99 in the 5 mm and 7 mm plan groups increases by 0.68 Gy and 0.95 Gy as compared with the 3 mm plan group,with passing rates improving by 7.2%and 9.6%,respectively(passing criterion:D95 receives at least 100%of the prescribed dose),with significant differences(P<0.05).Considering both OAR dose and CTV robustness,the setup error of 5 mm is found to be a reasonable choice for robust optimization in proton therapy plans for localized prostate cancer,as it can effectively balance the enhancement of CTV dose robustness with the control of dose escalation to OAR.
10.Nanoplastics and microplastics impair spatial memory ability in mice by inhibiting autophagy
Huimei LIANG ; Jiarui PAN ; Xueer LIN ; Minyi ZHAO ; Huan ZENG ; Yuqiang CHEN ; Hou-hui SONG ; Wei WANG ; Jinghua ZHAO
Chinese Journal of Veterinary Science 2025;45(10):2246-2255
Approximately 300 million tons of plastic are produced globally each year,which has a serious impact on human health,marine life and the livestock industry.Microplastics have also been detected in meat and milk samples.Research has shown that nanoplastics(NP)(<1 μm)and mi-croplastics(MP)(1 μm-5 mm)can affect the digestive,immune and reproductive systems of ani-mals.This experiment aims to investigate whether NP and MP regulate autophagy and damage the nervous system and spatial memory of animals.This experiment was divided into control group,nanoplastic group(PS-NP group,0.1 μm)and microplastic group(PS-MP group,1 μm),with 20 mice in each group.The mice were given 0.5 mL of PS-NP and PS-MP every day for 35 consecutive days,followed by neck amputation and brain analysis.The results showed that NPs and MPs of dif-ferent diameters caused varying degrees of damage to the brains of mice.In the behavioral tests of new object recognition,barnes maze and Y-shaped maze spatial memory,compared with the control group,the PS-NP group and PS-MP group showed a significant decrease in spatial memory ability of mice.HE staining results showed that neuronal cells in the PS-NP and PS-MP groups of mice exhibited shrinkage,decreased cell volume and deepened staining.The number of Nissl bodies de-creased,leading to dissolution and disappearance.RT-PCR and Western blot results showed that compared with the control group,the expression of glutamate receptors NR1,NR2A and NR2B in-creased in mice administered NP and MP orally,while the expression of autophagy related proteins Parkin,LC3B and Beclin1 was inhibited.In summary,this study suggests that nanoplastics and mi-croplastics stimulate glutamate receptors in mice by inhibiting the autophagy pathway,leading to impaired spatial memory.


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