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.

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.

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.

OBJECTIVE To explore the efficacy and safety of sofosbuvir-velpatasvir(SOF/VEL)combined with or without ribavirin(RBV)in treatment of the patients with genotype 3(GT3)chronic hepatitis C(CHC)and liver cirrhosis.METHODS Totally 230 patients with CT3 CHC and liver cirrhosis who were treated in Traditional Chi-nese Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Hetian Specialized Hospital of Infectious Diseases and Xinjiang Manasi County People's Hospital from Jun.2018 to Mar.2023 were recruited as the research sub-jects.The clinical curative effects were observed after the subjects were treated with single SOF-VEL or the com-bination with RBV for 12 to 24 weeks.The indexes including high-sensitivity hepatitis C RNA(HCV RNA),blood routine indexes,liver function indexes and noninvasive diagnosis indexes for liver fibrosis were observed,and the sustained virological response 12 weeks after the treatment(SVR12)was analyzed.RESULTS The mean age of the enrolled patients was(42.31±11.18)years old,the male patients accounted for 66.52％,and there were 137 cases of GT3a and 93 cases of GT3b 93,there were 183 cases of CHC,44 cases of compensated cirrhosis(CC)and 3 cases of decompensated cirrhosis(DCC).There were 189 cases of single HCV infection,33 cases of mixed infections of HCV and HIV,6 cases of mixed infections of HBV/HCV and 2 cases of triple infections of HBV/HCV/HIV.The overall SVR12 of the 230 patients was 99.57％,the SVR12 of the GT3a type patients was 100.00％,the GT3b type patients 98.92％.The SVR12 of the patients with CHC,CC and DCC were 99.45％,100.00％and 100.00％,respectively.The SVR12 of the patients with single HCV infection,HCV/HIV infec-tion,HBV/HCV infection and HBV/HCV/HIV were 99.47％,100.00％,100.00％and 100.00％,respective-ly.No patient quit the direct-acting antivirals(DAAs)treatment due to the drug-induced adverse reactions.1 pa-tient had relapse due to irregular administration of DAAs.CONCLUSION The virological response rate is high a-mong the patients with GT3 CHC and liver cirrhosis who are treated with single SOF/VEL or the combination with RBV,with the safety favorable.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

OBJECTIVE To summarize the clinical characteristics and diagnosis and treatment experiences in dealing with non-severe Chlamydia psittaci pneumonia.METHODS The clinical data were collected from 34 patients who were diagnosed with non-severe C.psittaci pneumonia through quantitative polymerase chain reactiong(qPCR)for sputum in fever clinic of the First Medical Center of Chinese PLA General Hospital from Mar.2023 to Mar.2024 and were retrospectively analyzed.The clinical characteristics and treatment outcomes were evaluated.RESULTS The average age of the patients was(44.82±13.74)years old,the ratio of male to female was 1∶1.83;all of the patients had fever;major symptoms were cough(70.59％),pharyngodynia(44.12％),and flu-like symptoms(41.18％);82.35％of the patients had the history of contact with poultry.The C-reactive pro-tein(CRP)level,interleukin-6(IL-6),systemic inflammatory response index(SIRI)and aggregate index of sys-temic inflammation(AISI)were higher among the patients aged no less than 44 years old than among the patients less than 44 years old(P＜0.05);the percentage of lymphocytes of the patients aged no less than 44 years old was lower than that of the patients aged less than 44 years old(P＜0.05).As for the imaging findings,73.53％of the patients had consolidation shadows,26.47％had ground-glass opacities,and 32.35％involved both lungs.All of the patients received quinolones or tetracyclines for treatment of 7-14 days and all symptoms relieved.CT reexami-nated 1 month after the treatment showed that 55.88％of the cases had complete absorption of pulmonary infec-tious lesions,and 35.29％had partial absorption.CONCLUSIONS The patients with non-severe Chlamydia psitta-ci pneumonia are characterized by the history of contact with poultry,fever complicated with respiratory tract symptoms,rise of inflammatory markers(more significant among patients of advanced age)and lower lobe con-solidation shadow/ground-glass opacities.Early identification and standardized treatment may facilitate the favora-ble treatment outcomes.

Objective To investigate the perioperative management of antithrombotic drugs in patients undergoing non-cardiac surgery.Methods Patients on long-term antithrombotic drugs who underwent non-cardiac surgery in our hospital were included.Through interviews with patients and physicians,perioperative antithrombotic medication regimens were reviewed and compared with the"Multidisciplinary Expert Consensus on Perioperative Management of Antithrombotic Therapy"to evaluate compliance with consensus and analyze influencing factors.Results A total of 372 patients were included in the analysis.Among them,355 patients were on long-term antiplatelet therapy alone,and 17 were on long-term oral anticoagulantion.364(97.8％)discontinued antithrombotic medications prior to surgery.109 patients(29.3％)received low molecular weight heparin(LMWH)bridging therapy.Among the 355 patients on antiplatelet therapy,108(30.4％)had discontinuation durations consistent with the consensus recommendations,while 186(52.4％)discontinued medications for longer periods.Postoperatively,the average hospital stay for antiplatelet therapy patients was 6.64 days,with only 37(10.4％)resuming therapy during hospitalization.The average hospital stay for patients on anticoagulants was 9.94 days,with only 2(11.8％)resuming therapy during hospitalization.Regarding perioperative risk assessment,only 40(10.8％)of patients underwent additional internal medical evaluation for thromboembolic risk after medication discontinuation,with the remainder assessed soly by surgeons.Coronary heart disease was an independent risk factor associated with internal medical evaluation(OR 2.851,95％CI 1.160-7.011,P=0.022).For bleeding risk assessment,surgeons evaluations aligned with the consensus in 68.0％of cases,but surgeons tended to underestimate risk compared to the consensus.Conclusions In this single-center study,perioperative antithrombotic management showed low compliance with expert consensus,characterized by prolonged preoperative medication discontinuation,high rates of LMWH bridging,and low postoperative in-hospital resumption of therapy.A robust multidisciplinary collaboration system should be established to enhance comprehensive patient assessment.

AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P＜0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P＜0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P＜0.05),which was higher than that in the latter produced by manufacturer B(P＜0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P＞0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.

OBJECTIVE To explore the efficacy and safety of sofosbuvir-velpatasvir(SOF/VEL)combined with or without ribavirin(RBV)in treatment of the patients with genotype 3(GT3)chronic hepatitis C(CHC)and liver cirrhosis.METHODS Totally 230 patients with CT3 CHC and liver cirrhosis who were treated in Traditional Chi-nese Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Hetian Specialized Hospital of Infectious Diseases and Xinjiang Manasi County People's Hospital from Jun.2018 to Mar.2023 were recruited as the research sub-jects.The clinical curative effects were observed after the subjects were treated with single SOF-VEL or the com-bination with RBV for 12 to 24 weeks.The indexes including high-sensitivity hepatitis C RNA(HCV RNA),blood routine indexes,liver function indexes and noninvasive diagnosis indexes for liver fibrosis were observed,and the sustained virological response 12 weeks after the treatment(SVR12)was analyzed.RESULTS The mean age of the enrolled patients was(42.31±11.18)years old,the male patients accounted for 66.52％,and there were 137 cases of GT3a and 93 cases of GT3b 93,there were 183 cases of CHC,44 cases of compensated cirrhosis(CC)and 3 cases of decompensated cirrhosis(DCC).There were 189 cases of single HCV infection,33 cases of mixed infections of HCV and HIV,6 cases of mixed infections of HBV/HCV and 2 cases of triple infections of HBV/HCV/HIV.The overall SVR12 of the 230 patients was 99.57％,the SVR12 of the GT3a type patients was 100.00％,the GT3b type patients 98.92％.The SVR12 of the patients with CHC,CC and DCC were 99.45％,100.00％and 100.00％,respectively.The SVR12 of the patients with single HCV infection,HCV/HIV infec-tion,HBV/HCV infection and HBV/HCV/HIV were 99.47％,100.00％,100.00％and 100.00％,respective-ly.No patient quit the direct-acting antivirals(DAAs)treatment due to the drug-induced adverse reactions.1 pa-tient had relapse due to irregular administration of DAAs.CONCLUSION The virological response rate is high a-mong the patients with GT3 CHC and liver cirrhosis who are treated with single SOF/VEL or the combination with RBV,with the safety favorable.