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.

[摘 要] 目的：探究半乳糖凝集素-9（Gal-9）对胰腺癌细胞的侵袭与迁移功能的促进作用及其机制。方法：基于公开单细胞转录组数据分析胰腺癌中免疫检查点分子的表达谱，结合Western blotting和ELISA验证Gal-9在胰腺癌细胞及临床相关模型中的表达与分泌特征。建立C57BL/6小鼠胰腺原位移植瘤模型，通过免疫组化、免疫荧光染色和流式细胞术分析Gal-9对肿瘤细胞增殖及其对瘤内CD8+ T细胞浸润与功能状态的影响。Gal-9重组蛋白及肿瘤细胞条件培养基（CM）处理肿瘤相关成纤维细胞（CAF），Western blotting、RT-qPCR和免疫荧光检测CAF中Ⅰ型胶原表达变化。免疫共沉淀、免疫荧光染色和Western blotting分析Gal-9与CD44的相互作用及JAK2/STAT3通路相关蛋白的表达。构建过表达Gal-9胰腺癌细胞与CAF共移植的裸鼠皮下荷瘤模型，结合天狼星红和马松染色评估小鼠肿瘤组织中胶原沉积情况。脱细胞外基质法提取CAF中沉积的细胞外基质（ECM）蛋白；通过细胞划痕、Transwell迁移及侵袭实验，检测CAF来源Ⅰ型胶原对胰腺癌细胞侵袭、迁移功能的影响，并通过siRNA干扰Gal-9表达进行功能反向验证。结果：与经典免疫检查点分子PD-L1和CTLA-4相比，Gal-9在胰腺癌中显著高表达（P < 0.000 1）。体内实验表明，Gal-9促进肿瘤生长（P < 0.001），上调Ki-67表达，同时减少肿瘤内CD8⁺ T细胞浸润并诱导肿瘤组织中TIM-3⁺细胞比例升高，Granzyme B、IFN-γ及TNF-α表达下降（P < 0.05）。体外实验显示，外源性Gal-9及肿瘤细胞来源的CM均可上调CAF中Ⅰ型胶原表达（P < 0.001）。机制研究表明，在CAF中抗Gal-9抗体免疫沉淀复合物中检测到CD44，且JAK2/STAT3蛋白表达水平增加。CAF来源的Ⅰ型胶原处理胰腺癌细胞后，肿瘤细胞的迁移和侵袭数量增加。相反，肿瘤细胞中敲低Gal-9表达后，CAF来源Ⅰ型胶原水平下降，同时肿瘤细胞侵袭和迁移数量下降。结论：胰腺癌来源的Gal-9具有双重作用：一方面，通过促进肿瘤细胞增殖和诱导CD8+ T细胞耗竭促进肿瘤进展；另一方面，通过结合CAF上的CD44受体，激活JAK2/STAT3信号通路，刺激CAF合成并分泌Ⅰ型胶原，进而增强胰腺癌细胞的侵袭迁移能力。

AIM:A mouse model of acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF)was estab-lished.METHODS:One hundred and twenty male C57BL/6 mice were randomly divided into a negative control group,an IPF group,and an acute exacerbation of interstitial fibrosis(AE-IPF)group.The IPF group received a low dose(3 mg/kg)of bleomycin(BLM)by endotracheal drip on days 0,14,and 28.The AE-IPF group received a high dose(5 mg/kg)of BLM by endotracheal drip on day 56.The control group received an equal volume of saline at different time points.The AE-IPF group was injected with a high dose(5 mg/kg)of BLM via tracheal drip on day 56 on top of the initial IPF induction,while the control group received equal amounts of saline at different time points.Experiments were con-ducted on the 57th,59th,63rd,and 70th days after the initial modeling.Mice were observed for general conditions,CT imaging changes,HE,and Masson staining to assess the degree of alveolitis and fibrosis in lung tissues.Lung function,hydroxyproline(HYP)content in lung tissues,and interleukin-6(IL-6)content in bronchoalveolar lavage fluid(BALF)were also measured.RESULTS:Mice in the AE-IPF group exhibited wheezing,shortness of breath,dyspnea,and weight loss.CT imaging revealed that IPF group mice showed patchy,subpleural reticular fuzzy shadows with irregular thickening of interlobular septa and intralobular linear shadows,along with tractional bronchiectasis.In the AE-IPF group,new ground-glass shadows and solid shadows appeared in addition to the IPF features.AE-IPF group mice demon-strated decreased lung function,elevated lung index,and acute pulmonary edema.HE and Masson staining of AE-IPF group mice showed consistent pathological manifestations of AE-IPF.HYP content in lung tissues,total cell count in BALF,and IL-6 concentration were significantly higher in the AE-IPF group compared to the control group(P<0.05).CONCLUSION:The use of multiple tracheal drip administrations of bleomycin successfully established an AE-IPF ani-mal model in mice.The 63rd day of the experiment was identified as the optimal observation point,as it exhibited the most significant pathological features and clinical symptoms.This model provides ideal conditions for studying AE-IPF patho-genesis and evaluating therapeutic efficacy.

Objective To develop a static progressive ankle stretcher for the treatment of functional disorders caused by scar contracture of the Achilles tendon after burn,and to evaluate its application effect.Methods The static progressive ankle stretcher was composed of a plantar support section and a calf support section,which was mainly made of a 3.2 mm-thick medical low-temperature thermoplastic plate,a commercially available 1 mm-diameter steel wire rope,grooved wheels,ice fishing reels with a diameter of about 50 mm,curved folding hinges and a locking threader with a hole diameter of about 1.5 mm.Totally 49 patients with scar contracture after deep Ⅱ to Ⅲ-degree burns of the Achilles tendon admitted to some hospital from March 2021 to January 2023 were prospectively selected and divided into a conventional rehabilitation group(25 cases)and a combined rehabilitation group(24 cases)using a randomized numerical table method.The patients in the conventional rehabilitation group underwent routine scar care such as anti-scarring medication application at home,scar massage,resistance training,joint loosening training in the hospital and compression therapy with the customized compression stockings/pants at the rest of the time,the patients in the combined rehabilitation group were treated with the static progressive ankle stretcher besides the measures taken for the conventional group.The two groups were compared in terms of scarring,ankle function and active dorsiflexion mobility of the ankle joint before and 12 weeks after the treatment,balance and walking ability 4 weeks and 12 weeks after the treatment,adverse events during the treatment and patient satisfaction 12 weeks after the treatment.SPSS 23.0 statistical software was used for data analysis.Results In terms of scarring condition,ankle function and active dorsiflexion mobility of the ankle joint all the patients were improved 12 weeks after the treatment,and the ones in the combined rehabilitation group behaved better than the ones in the conventional group,with the differences being statistically significant(P<0.05).The balance and walking ability 12 weeks after the treatment was better than that 4 weeks after the treatment in the two groups,and the combined rehabilitation group gained advantages over the conventional group in balance and walking ability,with the difference being statistically significant(P<0.05).During the treatment no adverse events due to the static progressive ankle stretcher were found,such as muscle tissue strain,scarred skin rupture,instrument friction and pressure injury.The combined rehabilitation group had higher patient satisfaction than the conventional group 12 weeks after the treatment,with the differences being statistically significant(P<0.05).Conclusion The static progressive ankle stretcher combined with the conventional rehabilitation treatment contributes to improving contracture scar conditions and joint mobility at the Achilles tendon area of the post-burn patients,which helps accelerate the recovery of ankle function after burns and enhance the balance and walking ability of the patients.[Chinese Medical Equipment Journal,2025,46(10):54-59]

Objective To observe the impact of brain-computer interface(BCI)robot combined with task-oriented training(TOT)on hand function and activities of daily living in stroke patients.Methods A total of 40 patients with subacute stroke who were hospitalized in the Department of Rehabilitation Medicine of Anhui No.2 Province People's Hospital from December 2022 to December 2024 were prospectively and consecutively included in this study.The stroke patients were randomly assigned to the experimental group and the control group using the random number table method,with 20 cases in each group.Baseline data were collected from all patients,including gender,age,personal history(smoking,drinking),past medical history(hypertension,diabetes),stroke type(hemorrhagic stroke,ischemic stroke),hemiplegia side(left,right),disease course,stroke location(basal ganglia,internal capsule),and admission assessment indicators(including kinesthetic and visual imagery questionnaire[KVIQ-20]score,mini-mental state examination[MMSE]score and National Institutes of Health stroke scale[NIHSS]score).Both groups of patients received conventional rehabilitation training and TOT.The experimental group then underwent BCI robot training combined with TOT on this basis.Both groups received treatments for 4 weeks,and the upper limb and hand functions of all patients were evaluated using the Fugl-Meyer upper extremity function assessment scale(FMA-UE),the wrist-hand part of the FMA-UE scale(FMA-WH),the Wolf motor function test(WMFT),and the modified Ashworth scale(MAS)before and after the treatment;the hand function related part(feeding[10 score],bathing[5 score],dressing[10 score],grooming[5 score],and toilet using[10 score])of modified Barthel index(MBI)was used to assess the patients'hand dexterity to perform daily activities.Results(1)No statistically significant differences were found in the baseline data between the two groups of patients(all P＞0.05).(2)Before treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(18.75±7.38),(2.95±1.54),(26.90±8.69),(1.10±0.66),and(15.45±1.82)respectively,while those in the control group were(15.90±5.39),(2.25±1.12),(24.15±6.78),(1.25±0.60),and(15.65±3.12)respectively.There were no statistically significant differences in the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI between the two groups before treatment(all P＞0.05).After 4 weeks of treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(27.10±7.76),(5.75±2.97),(40.85±10.19),(0.73±0.57),and(21.15±2.66)respectively,while those in the control group were(21.25±5.29),(4.00±1.49),(31.85±7.60),(0.73±0.64),and(17.40±3.14)respectively.The time main effects(Ftime values were 925.061,138.138,624.635 and 405.986 respectively,all P＜0.01),group main effects(Fgroup values were 4.460,4.562,5.011 and 4.411 respectively,all P＜0.05),and the interaction effects of time and group(Ftime×group values were 44.358,7.356,52.506 and 114.128 respectively,all P＜0.05)of FMA-UE,FMA-WH,WMFT and hand function related score of MBI scores were all significant.The time main effect of MAS scores was significant(Ftime value was 59.478,P＜0.01),while the group main effect(Fgroup value was 0.162,P＞0.05),the interaction effects of time and group(Ftime×group value was 1.652,P＞0.05)were not significant.Conclusion The combined task-oriented training with BCI robots can improve the upper limb and hand functions of stroke patients,enhance their ability to perform daily activities,and the effect is superior to that of single task-oriented training.

Objective To explore the molecular mechanism by which curcumin enhances the anti-tuberculosis function of macrophages through immune metabolic regulation mediated by liver X receptor α(LXRα)/ABCA1.Methods A model was established by infecting THP-1-derived macrophages with attenuated strain of Mycobacterium bovis(M.bovis).The control group,curcumin group,M.pavis group,M.pavis+LXRα agonist(T0901317)group,M.pavis+LXRα inhibitor(GSK2033)group,M.pavis+curcumin group,M.pavis+curcumin+GSK2033 group and M.pavis+curcumin+T0901317 group were set up.The protein and gene expressions of LXRα/ABCA1 were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The accumulation of lipid droplets was analyzed by Oil Red O staining and micro-assay.The lipid content of the supernatant was determined by a biochemical analyzer,and cell proliferation was assessed by the MTT method.Bacterial clearance capacity was evaluated by measuring intracellular bacterial load.Results Curcumin significantly upregulated the protein and gene expression of LXRα/ABCA1 in M.Bovis-infected macrophages,reduced intracellular lipid accumulation and promoted lipid efflux,while enhancing cell proliferation and reducing intracellular bacterial load(P<0.05,P<0.01).LXRα inhibitors could reverse the effect of curcumin,while agonists synergistically enhanced its effect.Correlation analysis showed that the expression of LXRα/ABCA1 in cells was negatively correlated with the intracellular bacterial load,while the lipid level was positively correlated with the intracellular bacterial load(P<0.01).Conclusion Curcumin activates the LXRα/ABCA1 pathway,coordinates the metabolic remodeling of macrophages and the enhancement of immune function,and forms a synergistic effect against tuberculosis,providing an experimental basis for the development of a novel host-directed treatment strategy for tuberculosis based on immune-metabolic regulation.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.

Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

Heatstroke,especially in high-temperature and high-humidity environments,is a life-threatening acute heat-injury disease that seriously endangers human health.Timely and effective on-site treatment is crucial for patients'survival and prognosis.Early recognition,rapid assessment,and on-site cooling are the core of pre-hospital treatment of heatstroke.Currently,there is a lack of standardized application procedures for pre-hospital emergency care of heatstroke.Therefore,the"Expert Consensus on Pre-hospital Emergency Management of Heatstroke(2024 edition)"was initiated by the Expert Group on Heatstroke Prevention of the People's Liberation Army and developed in collaboration with experts from local pre-hospital emergency care,emergency departments,and intensive care units.This consensus focuses on heatstroke prevention,on-site and ambulance-based treatment,and early emergency room interventions,and puts forward 10 evidence-based recommendations,aiming to provide a reference for scientific and standardized pre-hospital emergency care of heatstroke.

Objective To analyze the differences of brain activity between first-episode untreated depressive patients with and without suicidal ideation(SI),and its correlations with clinical characteristics.Methods A total of 40 major depressive disorder(MDD)patients with SI(MDD+SI group),40 patients without SI MDD(MDD+NSI group),and 40 healthy controls(HC)(HC group)were enrolled.The 17-item Hamilton depression scale(HAMD-17)and Beck scale for suicide ideation(BSI)were used to assess the severity of depression and SI,respectively.MRI data were collected.The values of fractional amplitude of low-frequency fluctuation(fALFF)were calculated.Results(1)Compared with the HC group,the MDD+NSI group showed decreases in the fALFF val-ues of the default network and attention network.The fALFF values of the attention network in the MDD+SI group showed decreases.Compared with the MDD+NSI group,the MDD+SI group showed decreases in the fALFF values of the attention network.(2)The fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.55;P<0.001)in the MDD+NSI group,while the fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.53;P<0.001)and the total score of BSI(r=-0.51;P<0.001)in the MDD+SI group.(3)The optimal critical value of fALFF value in left middle frontal gyrus for predicting SI occurrence in MDD patients was-0.039,area under the curve(AUC)was 0.76,sensitivity was 0.63,and specificity was 0.80.Conclusion The decreased local activity intensity in the left middle frontal gyrus of the brain might be the central mechanism for the occurrence of SI in MDD patients.In addition,the left middle frontal gyrus might have certain value in identifying SI and predicting the severity of SI.