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.

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 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

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 explore the role of diffusion tensor imaging (DTI) in monitoring prognosis after contralateral C7 nerve transfer in patients with central paralysis.Methods:The clinical data of a 56-year-old male patient with right limb motor impairment after cerebral infarction, admitted to the Department of Neurosurgery at Brain Hospital of Hunan Province in October 2023, were retrospectively analyzed. The patient had experienced right limb motor dysfunction for over 2 years following a cerebral infarction and was treated with contralateral C7 nerve transfer. Follow-ups were conducted at 2 and 6 months postoperatively. Motor function was assessed using the Fugl-Meyer Assessment (FMA) and Activities of Daily Living (ADL) scale, while changes in fractional anisotropy (FA) in the lesion area and corticospinal tract were monitored via DTI.Results:Postoperative follow-up of patient showed: (1) Significant improvement in motor function: ADL scores increased from 65 preoperatively to 75 (2 months postop) and 80 (6 months postop); FMA scores increased from 46 to 58 (2 months postop) and 61 (6 months postop). Muscle tension in the affected upper limb decreased markedly, and range of motion in the right shoulder joint improved. (2) Imaging improvements: DTI revealed an increase in FA values from 0.157 to 0.174 in the lesion area and from 0.52 to 0.53 in the corticospinal tract, indicating partial restoration of neural tract integrity.Conclusions:Contralateral C7 nerve transfer can effectively improve motor function in stroke patients. DTI technology provides an objective imaging basis for clinically assessing functional recovery by quantitatively evaluating changes in neural tract integrity, demonstrating significant value in guiding rehabilitation.

Objective To access the changes of thalamic metabolites before and 6 months after surgery in patients with cervical spondylotic myelopathy(CSM)using hydrogen proton magnetic resonance spectroscopy(1H-MRS)and to analyze its association with improvement in neurological function.Methods Forty-eight CSM patients(CSM group)who underwent cervical decompression surgery were included,and 33 healthy controls(HC)(HC group)were recruited.All subjects underwent bilateral thalamic 1H-MRS scans before the surgical procedure,and subsequently again 6 months later.Neurological function was assessed pre-operatively and post-operatively(6 months)in all patients with CSM using the modified Japanese Orthopaedic Association(mJOA)score.The changes of mJOA(△mJOA)were employed as an indicator of neurological improvement.The pre-and post-operative thalamic metabolites ratio of N-acetyl aspartate/creatine(NAA/Cr),choline/Cr(Cho/Cr),myo-inositol/Cr(mI/Cr),glutamate and glutamine/Cr(Glx/Cr)were compared in CSM patients and HC.A correlation analysis was conducted to determine the relationship between alterations in pre-and post-operative thalamic metabolites ratio(△NAA/Cr,△Cho/Cr,△mI/Cr,△Glx/Cr)and △mJOA.Results Compared to HC group,patients with CSM group showed significantly lower NAA/Cr(t=-4.988,P＜0.001;t=-3.562,P=0.001),Cho/Cr(t=-5.946,P＜0.001;t=-2.764,P=0.007)and mI/Cr(t=-3.988,P＜0.001;t=-2.079,P=0.041)before and 6 months after surgery.6 months post-operative NAA/Cr(t=-2.805,P=0.007)and mI/Cr(t=-3.285,P=0.003)were increased in CSM groups compared to pre-operative NAA/Cr and mI/Cr.In CSM group,△mI/Cr correlated significantly with △mJOA(r=0.478 2,P=0.000 6).Conclusion There are differences in thalamic metabolites in CSM patients before and after surgery.△mI/Cr is correlated with the improvement of neurological function,which can be used as an imaging parameter to evaluate the neurological function recovery in patients with CSM after surgery.

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 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.

Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

This study aims to elucidate the role and mechanism of clematichinenoside AR(CAR) in protecting bone marrow mesenchymal stem cells(BMSCs) from hypoxia-induced apoptosis. BMSCs were isolated by the bone fragment method and identified by flow cytometry. Cells were cultured under normal conditions(37℃, 5% CO_2) and hypoxic conditions(37℃, 90% N_2, 5% CO_2) and treated with CAR. The BMSCs were classified into eight groups: control(normal conditions), CAR(normal conditions + CAR), hypoxia 24 h, hypoxia 24 h + CAR, hypoxia 48 h, hypoxia 48 h + CAR, hypoxia 72 h, and hypoxia 72 h + CAR. The cell counting kit-8(CCK-8) assay and terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) were employed to measure cell proliferation and apoptosis, respectively. The number of mitochondria and mitochondrial membrane potential were measured by MitoTracker®Red CM-H2XRo staining and JC-1 staining, respectively. The level of reactive oxygen species(ROS) was measured with the DCFH-DA fluorescence probe. The protein levels of B-cell lymphoma-2 associated X protein(BAX), caspase-3, and optic atrophy 1(OPA1) were determined by Western blot. The results demonstrated that CAR significantly increased cell proliferation. Compared with the control group, the hypoxia groups showed increased apoptosis rates, reduced mitochondria, elevated ROS levels, decreased mitochondrial membrane potential, upregulated expression of BAX and caspase-3, and downregulated expression of OPA1. In comparison to the corresponding hypoxia groups, CAR intervention significantly decreased the apoptosis rate, increased mitochondria, reduced ROS levels, elevated mitochondrial membrane potential, downregulated the expression of BAX and caspase-3, and upregulated the expression of OPA1. Therefore, it can be concluded that CAR may exert an anti-apoptotic effect on BMSCs under hypoxic conditions by regulating OPA1 to maintain mitochondrial homeostasis.
Mesenchymal Stem Cells/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Animals ; Rats ; Cell Hypoxia/drug effects* ; Homeostasis/drug effects* ; Reactive Oxygen Species/metabolism* ; Rats, Sprague-Dawley ; Membrane Potential, Mitochondrial/drug effects* ; Saponins/pharmacology* ; Caspase 3/genetics* ; Male ; bcl-2-Associated X Protein/genetics* ; Bone Marrow Cells/metabolism* ; Cell Proliferation/drug effects* ; Protective Agents/pharmacology* ; Cells, Cultured