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.

Through network pharmacology and molecular docking technology, combined with in vitro experiment verification, we explored the mechanism of action of Porana racemosa Roxb. (PRA) in the treatment of rheumatoid arthritis (RA), and provided a modern pharmacological basis for the treatment of RA by PRA. The potential target of chemical components in the analyzed moth rattan was predicted by Swiss Target Prediction database; OMIM, GeneCards, TTD and Disgenet databases were used to search the disease targets of RA; the protein interaction (PPI) network and medicine-composition-target network were constructed using STRING database and Cytoscape software; GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis were carried out using DAVID database, and molecular docking software was used to dock the potentially active ingredients of PRA and core targets; finally, MH7A cells were selected for cell viability, scratch healing and mRNA expression level analysis of key genes to explore the effects of PRA and their potentially active ingredients on the proliferation, migration and apoptosis of MH7A cells. In this study, a total of 628 potentially active ingredient targets, 1 890 RA targets and 235 intersection targets were identified. It was screened that the potentially active ingredients of RA treatment by PRA were ethylcaffeate, N-p-coumaroyltyramine, 9,12,15-octadecatrienoic acid, methyl ester and so on, and the core targets involved tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2) and so on. 1 200 GO entries and 166 KEGG pathway entries were obtained from the enrichment analysis; molecular docking results showed that N-p-coumaroyltyramine and ethylcaffeate had good binding activity with TNF, MMP9, cysteine-aspartate protease 3 (CASP3), PTGS2, B-cell lymphoma 2 (BCL2) proteins. In vitro experiments showed that PRA, ethylcaffeate and N-p-coumaroyltyramine could inhibit the proliferation, migration and invasion of MH7A cells, up-regulate the expression of apoptosis-related gene CASP3 mRNA, and down-regulate the expression of MMP9, PTGS2 and BCL2 mRNA, and it can also down-regulate the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) mRNA and PI3K and p-AKT proteins. This study preliminarily revealed that the treatment of RA by PRA may be related to proliferation, migration, invasion, apoptosis and regulation of PI3K/AKT signaling pathway.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

AIM: To explore the relationship between hyperopia reserve and ocular biometric parameters in 4-14 year-old Uyghur students from Hotan County, Xinjiang, and to provide scientific evidence for myopia prevention.METHODS: From September 1 to October 31, 2023, a stratified random cluster sampling method was used to select 3 264 students(3 264 eyes)from 6 schools in Hotan County. Participants underwent uncorrected distance visual acuity testing, cycloplegic refraction, and ocular biometric measurements. The correlation between spherical equivalent(SE)and ocular biometric parameters was analyzed by multiple linear regression.RESULTS: A total of 1 998 non-myopic students(1 998 eyes)were included in the study, with 1 354 students(67.77%)showing insufficient hyperopia reserve. The detection rate of insufficient hyperopia reserve decreased with age, from 94.12% at age 4 to 18.13% at age 14(P<0.001). Multiple linear regression analysis showed that in the group with sufficient hyperopia reserve, age, gender, uncorrected distance visual acuity, axial length(AL), and keratometry(K)explained 66.5% of the variance in SE; while in the group with insufficient hyperopia reserve, these factors explained only 28.0% of the SE variance.CONCLUSION: In non-myopic Uyghur students aged 4-14 in Hotan County, Xinjiang, the detection rate of insufficient hyperopia reserve was 67.77%. In the group with insufficient hyperopia reserve, age, gender, AL, and K explained only a small portion of the SE variance, suggesting that the refractive status of this population may be influenced by more complex factors.

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

Aim To explore the relevant mechanisms of isoliquiritigenin(ISL)in inhibiting the proliferation and migration of vascular smooth muscle cells(VSMCs)by regulating the GRB2/ERK signaling pathway.Methods Human primary vascular smooth muscle cells(hVSMCs)were cultured,and stimulated with different concentrations of ISL and fixed concen-trations of growth factors PDGF-BB and EGF,respec-tively.Subsequently,the effect of overexpressing GRB2 on the efficacy of ISL was observed.CCK-8 assay was used to detect cell proliferation;BrdU assay was used to detect DNA synthesis;Western blot was used to de-tect the expression levels of OPN,ICAM-1,VCAM-1,GRB2,ERK1/2,and p-ERK1/2;wound healing assay was used to detect cell migration;transwell assay was used to detect cell invasion.Results Compared with the blank control group and the ISL 20 mg·L-1 group,the PDGF-BB group and the EGF group showed increased cell viability and DNA synthesis,decreased cell migration distance,and increased number of inva-sive cells.Additionally,the expression levels of GRB2 and p-ERK1/2 increased.Compared with the PDGF-BB 40 μg·L-1group or the EGF 10 mg·L-1 group,the ISL drug intervention group showed decreased cell viability and DNA synthesis,increased migration dis-tance of cells,decreased number of invasive cells,and decreased expression levels of GRB2 and p-ERK1/2.Compared with the ISL 20 mg·L-1+PDGF-BB and ISL 20 mg·L-1+EGF groups,the groups with ISL+PDGF-BB+pcDNA-GRB2 group and ISL+EGF+pcDNA-GRB2 group showed increased expression lev-els of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Compared with the ISL+PDGF-BB+pcDNA-GRB2 group and the ISL+EGF+pcDNA-GRB2 group,the pcDNA-GRB2+PDGF-BB group or the pcDNA-GRB2+EGF group showed increased expres-sion levels of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Conclusions Isoliquiritigenin inhibits the proliferation and migration of vascular smooth mus-cle cells by regulating the GRB2/ERK signaling path-way.

Objective To investigate the changes in metabolites detected by magnetic resonance spectroscopy(MRS)in the dorsal thalamus of patients with cervical spondylotic myelopathy(CSM)and to analyze their correlation with spinal cord injury based on diffusion tensor imaging(DTI).Methods A total of 93 patients with CSM(patient group)and 67 healthy volunteers(control group)were selected.DTI parameters of the spinal cord and MRS parameters of the thalamus were compared between the two groups.Correlation analysis were performed among clinical features,conventional imaging features,DTI parameters,and metabolites in CSM patients.Multifacto-rial linear regression equations for thalamic metabolites based on the aforementioned characteristics were established.Results The fractional anisotropy(FA)value was significantly lower in the patient group than in the control group(P=0.005,t=2.874).The N-acetyl aspartate/creatine(NAA/Cr)ratio(P<0.001,Z=-5.922),choline/Cr(Cho/Cr)ratio(P<0.001,Z=-6.857),and myo-inositol/Cr(MI/Cr)ratio(P<0.001,Z=-6.573)were significantly lower in the patient group than in the control group.The NAA/Cr ratio(r=0.444,P<0.001),Cho/Cr ratio(r=0.308,P=0.003),and MI/Cr ratio(r=-0.489,P<0.001)were corre-lated with the FA value in the patient group.There was a correlation between the NAA/Cr ratio and the duration(r=-0.365,P<0.001).Multifactorial linear regression equations for each metabolites in the thalamus:NAA/Cr=0.833+1.520×FA-0.007×duration;Cho/Cr=0.209+0.774×FA;MI/Cr=1.566-1.722×FA+0.008×modified Japanese Orthopaedic Association(mJOA)score;glu-tamate/Cr(Glx/Cr)=0.942+0.009×duration.Conclusion CSM patients exhibit metabolic alterations in the dorsal thalamus,which are linearly correlated with the degree of spinal cord injury.

Objective:To investigate the risk factors for recurrence after modified Chevron osteotomy for hallux valgus.Methods:A total of 86 patients (102 feet) with hallux valgus who underwent modified Chevron operation in Beijing Jishuitan Hospital from December 2018 to February 2021 were retrospectively analyzed. There were 12 males (14 feet) and 74 females (88 feet), aged 50±15 years (range, 18-74 years). There were 36 cases on the right side, 34 on the left side, and 16 on the bilateral side. 4 feet were treated with Chevron osteotomy, 74 feet with modified McBride's osteotomy, 61 feet with Weil osteotomy, 24 feet with Akin osteotomy, and 23 feet with gastrocnemius aponeurotic release. At the last follow-up, hallux valgus angle (HVA) ≤15° was defined as the non-recurrence group after hallux valgus operation, and HVA>15° was defined as the recurrence group after hallux valgus operation. Compare the age, gender, preoperative HVA, the first and second intermetatarsal angles (IMA) before and after operation, the metatarsus adductus angles (MAA) before and after operation, the Meary angles before and after operation, the distal metatarsal articular angles (DMAA) before and after operation, the American Orthopaedic Foot and Ankle Society (AOFAS) forefoot scores before and after operation, and the rotation of the first metatarsal head between the two groups of patients. Include the indicators with statistically significant differences in the binary variable logistic regression analysis to screen for the risk factors of recurrence after modified Chevron operation for hallux valgus.Results:All patients successfully completed the operation and were followed up for 30.3±16.4 months (range, 12-52 months). Postoperative recurrence occurred in 21 feet, and the recurrence rate was 20.6% (21/102). The HVA at the last follow-up was 8.48°±4.52° in the non-recurrence group and 20.68°±3.61° in the recurrence group. In the non-recurrence group, the AOFAS ankle-hindfoot score increased from 60.31±16.62 points preoperatively to 86.89±12.79 points postoperatively ( t=-13.644, P<0.001). In the recurrent group, the AOFAS ankle-hindfoot score increased from 61.71±15.68 points preoperatively to 84.33±18.84 points postoperatively ( t=-6.082, P<0.001). The proportion of patients with preoperative Meary angle> 4° in the non-recurrence group was 52% (10/21), which was lower than 79% (64/81) in the recurrence group, and the difference was statistically significant (χ 2=6.077, P=0.014). The proportion of patients with square type of metatarsal rotation (type A) in the recurrence group was 58%(47/81), which was higher than 33%(7/21) in the non-recurrence group, and the difference was statistically significant (χ 2=4.081, P=0.043). There was no significant difference in gender, age, preoperative HVA, pre- and post-operative IMA, pre- and post-operative DMAA, pre- and post-operative MAA, or preoperative metatarsal rotation type between the two groups ( P>0.05). The results of the logistic regression analysis showed that a preoperative Meary angle ≤ 4° ( OR=3.299, P=0.024) and a non-type A metatarsal rotation pattern after operation ( OR=4.183, P=0.041) were independent risk factors for recurrence after modified Chevron operation for hallux valgus. Conclusion:Hallux valgus patients with a preoperative Meary angle ≤4° and non-type A metatarsal rotation after operation have an increased risk of recurrence following modified Chevron operation.

OBJECTIVE: To investigate the effect of inverted-Y urethral function-preserving holmium laser enucleation of the prostate (HoLEP) on stress urinary incontinence after surgery in patients with BPH. METHODS: We retrospectively analyzed the clinical data on 109 cases of BPH treated in our hospital from June 2022 to May 2023 by traditional HoLEP with preservation of the apical prostatic urethral valve (group A, n = 52) or inverted-Y urethral function-preserving HoLEP (group B, n = 57). We recorded the intra- and post-operative parameters, evaluated the urinary incontinence status and post-void symptoms according to the International Continence Society standards, and analyzed the effect of inverted-Y versus traditional HoLEP in improving the postoperative urinary incontinence of the patients. RESULTS: The incidence rate of stress urinary incontinence after catheter removal was significantly lower in group B than in A (10.52% vs 26.92%, P = 0.027), and so was it at 2 weeks after surgery (1.75% vs 11.54%, P = 0.037), and at 1 month postoperatively (0% vs 7.69%, P = 0.033). CONCLUSION For the treatment of BPH, inverted-Y urethral function-preserving HoLEP is superior to traditional HoLEP with preservation of the apical prostatic urethral valve in improving stress urinary incontinence after surgery.
Humans ; Male ; Retrospective Studies ; Lasers, Solid-State/therapeutic use* ; Prostatic Hyperplasia/surgery* ; Urethra/surgery* ; Postoperative Complications/prevention & control* ; Urinary Incontinence, Stress/etiology* ; Prostatectomy/adverse effects* ; Aged ; Urinary Incontinence ; Prostate/surgery*