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.Umbrella decision-making model for diagnosis and treatment of elderly lung cancer patients: Construction and practice
Lunxu LIU ; Jian ZHOU ; Xiang DING ; Nan CHEN ; Jianxin XUE ; Xuelei MA ; Ye WANG ; Weiya WANG ; Liqing PENG ; Xin YOU ; Minggang SU ; Xu CHENG ; Jiao WANG ; Ning GE ; Deying KANG ; Yuchen HUANG ; Jinghan WANG ; Yu TONG ; Yaoxi ZHANG ; Jirong YUE ; Hu LIAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):833-839
With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.
3.Study of adsorption of coated aldehyde oxy-starch on the indexes of renal failure
Qian WU ; Cai-fen WANG ; Ning-ning PENG ; Qin NIE ; Tian-fu LI ; Jian-yu LIU ; Xiang-yi SONG ; Jian LIU ; Su-ping WU ; Ji-wen ZHANG ; Li-xin SUN
Acta Pharmaceutica Sinica 2025;60(2):498-505
The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure
4.The effect of rutaecarpine on improving fatty liver and osteoporosis in MAFLD mice
Yu-hao ZHANG ; Yi-ning LI ; Xin-hai JIANG ; Wei-zhi WANG ; Shun-wang LI ; Ren SHENG ; Li-juan LEI ; Yu-yan ZHANG ; Jing-rui WANG ; Xin-wei WEI ; Yan-ni XU ; Yan LIN ; Lin TANG ; Shu-yi SI
Acta Pharmaceutica Sinica 2025;60(1):141-149
Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg-1) and a high dose (15 mg·kg-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D303)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.
5.Pelvic floor reconstruction with gluteus maximus myocutaneous flap in the treatment of perineal wound healing failure after pelvic exenteration
Yu TAO ; Yulu WANG ; Lie ZHU ; Zhiguo WANG ; Ning SU ; Jian ZHANG
Chinese Journal of Gastrointestinal Surgery 2025;28(1):81-85
Objective:To investigate the value of pelvic floor reconstruction with gluteus maximus myocutaneous flap in second-stage surgery for patients with failed perineal wound healing after pelvic exenteration (PE).Methods:This was a descriptive case series study. The clinical data of 24 patients with locally advanced (LARC) or recurrent (LRRC) rectal cancer who underwent PE and had long-term nonunion of postoperative perineal wounds were collected from the department of colorectal surgery of the Second Affiliated Hospital of Navy Medical University (Shanghai Changzheng Hospital) from January 2022 to January 2023. The specific operation methods of pelvic reconstruction by gluteus maximus myocutaneous flap are as follows: the necrotic tissue of the perineal wound was debrided and rinsed repeatedly, the gluteus maximus muscle was cut and separated from the gluteus superior and inferior arteries, the middle muscle pedicle was retained, part of the skin and muscle were separated from the medial margin, part of the epidermis was removed, the muscle and subcutaneous tissue at the medial margin of the flap were fixed to the medial edge of the wound, negative pressure suction tubes were placed above and below the wound cavity and in the muscle space on the right side, and the subcutaneous muscle and fat layer were sutured. The skin was sutured intersegmentally, and a negative pressure suction device was placed on the wound surface. After surgery, the patient should remain prone, and the drainage tube should be placed for at least 7 days. The drainage tube can be removed after 24-hour drainage is less than 30 ml. Perineal wound healing and complications related to gluteal major myocutaneous flap were observed.Result:The median reconstruction time of 24 patients was 180 (150 ~ 230) minutes, and the median intraoperative blood loss was 100 (30 ~ 200) ml. 91.7% (22/24) patients had successful healing of perineal wound within 30 d after operation. After a follow-up of 6 months, no complete or partial flap necrosis occurred. The incidence of complications related to gluteus maximus myocutaneous flap was 8.3% (2/24). One patient had flap infection and sinus tract, and one patient had flap sinus tract. All patients healed after debridement under local anesthesia.Conclusion:For LARC/LRRC patients with poor perineal wound healing after PE, pelvic floor reconstruction with gluteus maximus myocutaneous flap in second-stage operation is safe and feasible, and could successfully close the perineal wound, and has a low incidence of postoperative flap-related complications.
6.Establishment and application of triplex TaqMan quantitative PCR for detection of blaNDM,mcr-1 and cfr
Wei YANG ; Haihang YU ; Yunmeng WANG ; Jue WANG ; Yu HAN ; Xiaoyue HU ; Zhiwei CHEN ; Junxia LU ; Ying GAO ; Ning ZHANG
Chinese Journal of Veterinary Science 2025;45(2):243-248,273
This study aims to simultaneously detect three antibiotic resistance genes(blaNDM,mcr-1 and cfr).A triplex fluorescence quantitative PCR method was established.Plasmids,primers and probes were designed and optimized.The method could specifically detect blaNDM,mcr-1 and cfr,but not other antibiotic resistance genes.The R2 of the standard curves of the three antibiotic re-sistance genes were all greater than 0.999,and the coefficients of variation were all lower than 1%.The lowest detection limits of the plasmids were 1 × 102 copies/μL.This method was used to de-tect 800 bacterial samples.The results showed that 32 samples contained mcr-1 gene,40 samples contained blaNDM gene,2 samples contained cfr gene,8 samples contained both mcr-1 and blaNDM genes.There were no samples carrying three antibiotic resistance genes detected.The results indica-ted that the triplex fluorescence quantitative PCR method established in this experiment had the advantages of high sensitivity,specificity and stability.It was suitable for rapid detection of blaNDM,mcr-1 and cfr antibiotic resistance genes in clinical practice.It provided a convenient and quick method basis for the detection of antibiotic resistance genes.
7.Altered patterns of interhemispheric functional connectivity in the cerebral cortex connected via the corpus callosum in Alzheimer's disease
Zheyu LI ; Yifan SHEN ; Renren LI ; Chenxi PAN ; Wei ZHANG ; Zhihao XU ; Qiurong YU ; Dazhi YIN ; Mingxia FAN ; Yunxia LI ; Ruipeng NING
Chinese Journal of Medical Physics 2025;42(11):1434-1444
Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.
8.Relationship between seminal plasma oxidation-reduction potential and sperm DNA fragmentation index,high DNA staining,and motility parameters
Xingchi LIU ; Qian ZHANG ; Liyan LI ; Xiaochuan GUAN ; Ning ZHANG ; Yuexin YU
Journal of China Medical University 2025;54(1):56-60
Objective To investigate the correlation between seminal plasma oxidation-reduction potential(ORP)and normalized ORP(nORP)with sperm DNA fragmentation index(DFI),high DNA staining(HDS),and motility parameters,and to explore whether these parameters can be used as biomarkers for evaluating male fertility potential.Methods A total of 309 men who attended the andrology clinic at the Department of Reproductive Medicine,General Hospital of Northern Theater Command,between October 2023 and December 2023,were selected in this study.We analyzed the correlation between seminal plasma ORP and nORP and parameters such as DFI using the electrode method,HDS,age,days of abstinence,semen volume,total sperm count,sperm concentration,sperm motility(forward motile sperm count,forward motile sperm percentage,non-forward sperm count,non-forward sperm percentage,immotile sperm count,immotile sperm percentage,and sperm motility rate),and motility indices(curvilinear velocity[VCL],straight-line velocity[VSL],average velocity[VAP],linear index[LIN],straightness index[STR],and wobble coefficient[WOB]).The nORP results were divided into three groups and analyzed in relation to each of the parameters mentioned above.A generalized linear regression model was used to assess the relationship between nORP and HDS,with smooth curve fitting performed to visualize this relationship.Results Pearson and Spearman correlation analyses revealed that both ORP and nORP were positively correlated with semen volume,percentage of immotile sperm,and DFI,but negatively correlated with forward motile sperm count,percentage of forward motile sperm,sperm motility rate,VSL,and VAP(P<0.05).Additionally,ORP was positively correlated with abstinence days and immotile sperm count(P<0.05)and negatively correlated with LIN,STR,and WOB(P<0.05).However,nORP was positively correlated with HDS(P<0.05),and negatively correlated with total sperm count,sperm concentration,non-forward sperm count,non-forward sperm percentage,immotile sperm count,and VCL(P<0.05).The nORP group showed significant differences in semen volume,total sperm count,sperm concentration,forward motile sperm count,forward motile sperm percentage,non-forward sperm count,non-forward sperm percentage,immotile sperm count,immotile sperm percentage,sperm motility rate,VCL,VSL,VAP,DFI,and HDS(P<0.05).A smooth curve fitting of nORP and HDS,adjusted for age and abstinence days,demonstrated a linear upward trend in nORP as HDS increased.Conclusion Both ORP and nORP are associated with sperm DFI and key motility parameters.Moreover,nORP is closely related to HDS,which reflects sperm maturity,offering a more comprehensive indicator of semen quality.Thus,nORP can be utilized as a biomarker for assessing male fertility potential.
9.Protective effect of Liraglutide inrats with diabetic kidney disease by regulating nuclear factor E2-related factor 2/glutathione peroxidase 4 ferroptosis signaling pathway
Dong LIANG ; Qianyu LIN ; Min YANG ; Mengjie LI ; Wenhua XING ; Ning YU ; Yunqi LIU ; Xiaomin ZHANG
Chinese Journal of Diabetes 2025;33(4):299-303
Objective To investigate the protective effect of Liraglutide in rats with diabetic kidney disease(DKD)by regulating the nuclear factor E2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)ferroptosis signaling pathway.Methods Twelve male Sprague-Dawley(SD)rats were randomly divided into normal control(NC)group,DKD group,and Liraglutide treatment(Lir)group,with 4 rats in each group.The 24 hUAlb,TC,TG,LDL-C,serum creatinine(Scr),BUN,ferrous ion(Fe2+),the activity of glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected in each group.Hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and periodic acid-silver methenamine-Masson(PASM-Masson)staining were used to observe the pathological changes of the kidneys.Immunofluorescence was performed to detect the localization and expression of reactive oxygen species(ROS)in the renal tissue.The protein expressions of Nrf2 and GPX4 were detected by Western blot.Results Compared with the NC group,the levels of 24 hUAlb,Scr,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were increased(P<0.05 or P<0.01),while the expressions of GSH-Px,Nrf2,and GPX4 proteins were decreased in the DKD group(P<0.01).Compared with the DKD group,the levels of 24 hUAlb,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were decreased(P<0.05 or P<0.01),and the expressions of GSH-Px,Nrf2,and GPX4 proteins were increased in the Lir group(P<0.01).Conclusions Liraglutide may exert a protective effect in DKD by upregulating the Nrf2/GPX4 signaling pathway and inhibiting ferroptosis.
10.Research on dry and wet durability of reusable surgical gowns
Ze-chen LIN ; Min WAN ; Yu-peng SUN ; Hui-jie SUN ; Jian-jun SUN ; Qing ZHANG ; Bo ZHANG ; An-ning LI ; Fu-xin DU
Chinese Medical Equipment Journal 2025;46(6):28-33
Objective To explore the changes of durability properties of reusable surgical gowns when used in dry and wet conditions.Methods Reusable surgical gowns made of single-layer polyester fiber or 3-layer composite material were selected as test samples,and a Martindale abrasion and pilling tester was used as the basic test platform and modified to form fixtures suitable for the wet state environment.The reusable surgical gowns underwent abrasion experiments in wet and dry conditions to observe the changes in their fiber structure,and were subjected to water penetration resistance and swelling strength tests.Results Visually the reusable surgical gowns had few changes of the microscopic textile fiber structure in dry and wet conditions,and the gowns made of single-layer polyster fiber gained advantages over the outer layers of those of 3-layer composite material in abrasion resistance with the same friction cycles.In dry and wet conditions,the hydrostatic pressure values of the gowns of single-layer polyster fiber gradually decreased with the increase of the degree of abrasion,which were always lower than those of the gowns of 3-layer composite material;the swelling strength of the gowns of single-layer polyster fiber was always greater than that of the gowns of 3-layer composite material,which decreased with the deterioration of the wear more significantly than that of the gowns of 3-layer composite material.Conclusion The reusable surgical gowns made of single-layer polyester fiber or 3-layer composite material have few differences in durability and protective properties at the early stages of ablation in dry and wet conditions.The durability of the gowns decreases as the degree of wear increases,while the trend of the decrease is slowing down until the fabric breaks down and completely loses its barrier effect.[Chinese Medical Equipment Journal,2025,46(6):28-33]

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