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.

Atherosclerosis （AS） is the main pathological basis of cardiovascular diseases and seriously threatens human quality of life. Its prevention and treatment urgently need breakthroughs. The inflammatory response， which runs through the physiological and pathological evolution process of AS， is one of the important mechanisms for AS occurrence. Currently， the treatment methods for AS in Western medicine are relatively mature. However， they have adverse reactions such as abnormal liver and kidney function， drug tolerance， target vessel restenosis， and stent thrombosis， which remain the key bottleneck restricting clinical efficacy. Traditional Chinese medicine （TCM）， characterized by multiple components， multiple targets， and multi-pathway synergy， shows unique clinical application potential and efficacy advantages in the intervention of AS. This article reviewed the research progress of TCM in intervening in AS by regulating inflammatory-related signaling pathways， such as nuclear factor-κB （NF-κB）， Toll-like receptors （TLRs）， mitogen-activated protein kinase （MAPK）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）， in the past five years. It summarized the combined mechanism of action of TCM monomers， TCM pairs， and compound preparations in inhibiting the inflammatory cascade reaction through multiple targets， regulating lipid metabolism disorders， and improving vascular endothelial dysfunction and the imbalance of the microenvironment. It deepened the research on the molecular mechanism of TCM in anti-AS， so as to provide a scientific basis for the clinical transformation application and related theoretical research of TCM in anti-AS.

Atherosclerosis （AS） is the main pathological basis of cardiovascular diseases and seriously threatens human quality of life. Its prevention and treatment urgently need breakthroughs. The inflammatory response， which runs through the physiological and pathological evolution process of AS， is one of the important mechanisms for AS occurrence. Currently， the treatment methods for AS in Western medicine are relatively mature. However， they have adverse reactions such as abnormal liver and kidney function， drug tolerance， target vessel restenosis， and stent thrombosis， which remain the key bottleneck restricting clinical efficacy. Traditional Chinese medicine （TCM）， characterized by multiple components， multiple targets， and multi-pathway synergy， shows unique clinical application potential and efficacy advantages in the intervention of AS. This article reviewed the research progress of TCM in intervening in AS by regulating inflammatory-related signaling pathways， such as nuclear factor-κB （NF-κB）， Toll-like receptors （TLRs）， mitogen-activated protein kinase （MAPK）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）， in the past five years. It summarized the combined mechanism of action of TCM monomers， TCM pairs， and compound preparations in inhibiting the inflammatory cascade reaction through multiple targets， regulating lipid metabolism disorders， and improving vascular endothelial dysfunction and the imbalance of the microenvironment. It deepened the research on the molecular mechanism of TCM in anti-AS， so as to provide a scientific basis for the clinical transformation application and related theoretical research of TCM in anti-AS.

Objective: To analyze the dental plaque microecological characteristics and the levels of salivary interleukin (IL)-5, IL-12, and IL-16 in school aged children with mixed dentition, providing a theoretical basis for the prevention and control of childhood dental caries. Methods: A total of 199 school aged children admitted aged 6-12 years to Tianjin Stomatological Hospital from January 2023 to January 2025 were selected. According to the decayed missing and filled teeth(DMFT) index, they were divided into high caries group ( n =68, DMFT index≥4), low caries group ( n =65, 1≤DMFT index≤3) and caries free group ( n =66, DMFT index=0). The microbial composition of dental plaque was analyzed by 16S rDNA high throughput sequencing. Salivary levels of IL-5, IL-12 and IL-16 were detected by enzymelinked immunosorbent assay kit. Pearson correlation test was used to analyze the correlation between levels of salivary IL-5, IL-12 and IL-16 and the DMFT index in children with caries. Results: Species richness and evenness (Shannon index) and uniformity (Shannonevenness index) in the high caries group were (3.28±0.64) and (0.61±0.13), respectively, which were lower than (3.66±0.52) and (0.74±0.15) in low caries group, and ( 3.60± 0.49) and (0.72±0.16) in caries free group ( F =9.08, 15.20, both P <0.05). The relative abundances of Firmicutes and Actinobacteria in the high caries group were higher than those in the low caries and caries free groups, while the relative abundances of Bacteroidetes, Fusobacteria, and Candidate phylum TM7 were lower than those in the low caries and caries free groups. The relative abundances of Streptococcus, Leptotrichia, Veillonella, Prevotella, and Actinomycesin in the high caries group were higher than those in the low caries and caries free groups, while the relative abundances of Capnocytophagaand Porphyromonas were lower ( F = 47.55- 1 969.24 , all P <0.05). The levels of salivary IL-5, IL-12, and IL-16 in the high caries group [(12.57±3.21, 28.73±6.79, 45.31 ±11.14)pg/mL] were higher than those in the low caries [(8.63±2.39, 18.16±4.62, 32.60±9.46)pg/mL] and caries free groups [(7.84±2.17, 14.94±3.83, 29.55±8.21)pg/mL] ( F =62.08, 141.23, 49.35, all P <0.05). Pearson correlation test results showed that salivary IL-5, IL-12, and IL-16 levels were positively correlated with the DMFT index in children with caries ( r = 0.73 , 0.68, 0.65, all P <0.05). Conclusions The microecological structure of dental plaque in school aged children with mixed dentition caries is significantly altered, the levels of pro inflammatory factors are significantly elevated, and these levels are positively correlated with the severity of caries.Oral microbial dysbiosis and local inflammatory responses may play a key role in the development and progression of dental caries.

ObjectiveTo construct a nomogram prediction model for non-valvular persistent atrial fibrillation （PeAF） patients with left ventricular hypertrophy （LVH） ， followed by prognostic analysis through follow-up. MethodsThis study retrospectively enrolled 949 patients with newly diagnosed and hospitalized non-valvular PeAF. Among them， 403 patients presented with LVH. The cohort was randomly stratified into a training set （n=665） and a validation set （n=284）. Univariate and multivariate Logistic regression analyses were employed to identify independent risk factors for PeAF complicated by LVH. A nomogram prediction model was subsequently constructed and evaluated for discriminative ability， calibration， and clinical utility using receiver operating characteristic （ROC） curve analysis， calibration plots， and decision curve analysis （DCA）. ResultsSeven independent risk factors were ultimately identified and included in the prediction model： female sex， hypertension， diabetes， red blood cell distribution width-SD （RDW-SD）， body mass index （BMI）， left atrial diameter （LAD）， and left ventricular ejection fraction （LVEF）. The area under the ROC curve （AUC） in the training set was 0.862 （95% CI： 0.834-0.890）， and in the validation set， it was 0.870 （95% CI： 0.829-0.911）， demonstrating excellent predictive performance. ConclusionIndependent risk factors for LVH in PeAF patients include female， hypertension， diabetes， RDW-SD， BMI， LAD， and LVEF. The prediction model built based on this can help early identification of PeAF patients with high risk of LVH. At the same time， the incidence of major adverse cardiovascular events （MACE） is higher in PeAF patients with LVH. Patients with atrial fibrillation combined with LVH may benefit from catheter ablation.

Currently, transcatheter intervention is the preferred treatment for patients with anatomically suitable atrial septal defects. However, the use of nickel-titanium alloy occluders in interventional procedures results in lifelong presence of the implant in the body, leading to complications such as metal allergies and arrhythmias in some patients. To overcome the short-term and long-term complications associated with the presence of metal, and to avoid radiation exposure and metal toxicity, this paper reports a case of successful transcatheter closure of atrial septal defect in a pediatric patient with metal allergies using fully biodegradable occluder under ultrasound guidance, achieving excellent results by interventional therapy.

Lung cancer exhibits the highest incidence and mortality rates among cancers globally,with a five-year overall survival rate alarmingly below 20％.Targeting autophagy,though a controversial therapeutic strategy,is extensively employed in clinical practice.Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy.Nevertheless,the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention.This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer.It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells.Notably,most autophagy-targeting drugs,primarily natural small molecules,have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer,as opposed to inhibiting protective autophagy.These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies,offering promising approaches to combat this disease.

Objective To investigate the therapeutic effect of Ziwuliuzhu acupuncture in a rat model of insomnia and its regulatory effect on the glutamic acid(Glu)/γ-aminobutyric acid(GABA)-glutamine(Gln)metabolic loop.Methods Forty male SD rats were randomly assigned to control group,model group,Najia group and Nazi group(n=10).In the latter 3 groups,rat models of insomnia were established by intraperitoneal injections of p-chlorophenylalanine and verified using a sodium pentobarbital-induced sleep test.After modeling,the rats in Najia and Nazi groups received acupuncture for 7 days at specifically chosen sets of acupoints based on the Ziwuliuzhu rationale in traditional Chinese medicine.Pathological changes in the hypothalamic tissue of the rats were examined with HE staining,and the levels of Glu and GABA in the hypothalamus were determined with high-performance liquid chromatography(HPLC)-mass spectrometry(MS)/MS.Immunohistochemistry was used to detect the expressions of GABAA receptors(GABAARs)in the hypothalamus,and the expression levels of glutamate decarboxylase(GAD65/67)and glutamine synthetase(GS)were determined with Western blotting.Results Compared with the model group,the rats in Najia and Nazi groups exhibited decreased Glu levels and GABAA receptor expression and increased GABA levels with a decreased Glu/GABA ratio in the hypothalamus.Ziwuliuzhu acupuncture significantly increased the protein expressions of GAD65 and GAD67 and lowered the expression of GS in the hypothalamus in the rat models of insomnia.Conclusion Ziwuliuzhu acupuncture produces sedative and hypnotic effects in rat models of insomnia possibly by regulating Glu and GABA-Gln metabolism to restore the excitatory/inhibitory balance between Glu and GABA.

Alzheimer's disease(AD)is an age-related neurodegenerative disease with an increasing incidence worldwide.A large number of studies have shown that the incidence rates of hearing loss is high in patients with mild cognitive impairment and Alzheimer's disease,and may be a risk factor for the occurrence and development of cognitive impairment.There is an interaction between the two,but the causal mechanism is still unclear.Early screening and management of hearing impairment may play an important role in the early diagnosis,symptom im-provement and disease progression of Alzheimer's disease.This paper reviews relevant clinical and basic research to discuss the correlation between hearing loss and Alzheimer's disease,and the possible causal mechanism between them.

Objective To investigate the effect of sodium glucose cotransporter 2 inhibitor(SGLT2i)on cardiac function in T2DM rats with heart failure(HF)by regulating the silencing signaling protein 1/mitochondrial uncoupling protein 2(SIRT1/UCP2)signaling pathway.Methods Forty SD rats were randomly divided into normal control(NC)group,T2DM combined with HF(T2DM-HF)group,SGLT2i group,and SGLT2i+SIRT1 inhibitor(EX527)(SGLT2i+EX527)group.Fasting blood glucose(FBG),cardiac function,and oxidative stress indicators were tested in each group.The pathological morphological changes of myocardial tissue were evaluated by HE and Masson staining,and the expression of SIRT1 and UCP2 proteins in myocardial tissue was evaluated by Western blot.Results Compared with NC group,the T2DM-HF,SGLT2i,and SGLT2i+EX527 groups showed a decrease in body weight(P<0.05)and an increase in cardiac mass index(P<0.05).Compared with T2DM-HF group,the SGLT2i group showed decreased protein expression of FBG,LVESD,LVEDD,LVEDP,MDA,and UCP2(P<0.05),while increased protein expression of LVFS,LVEF,LVSP,±dp/dtmax,SOD,and SIRT1(P<0.05).Compared with SGLT2i group,the SGLT2i+EX527 group showed an increase in FBG,LVESD,LVEDD,LVEDP,MDA,and UCP2 opal levels,while LVFS,LVEF,LVSP,±dp/dtmax,SOD,and SIRT1 opal levels decreased(P<0.05).Conclusions SGLT2i can improve the cardiac function in T2DM rats combined with HF,enhance antioxidant capacity,and exert a protective effect on cardiac function.Its mechanism of action may be related to the regulation of SIRT1/UCP2 signaling pathway.