Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

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.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

AIM To investigate the protective effects of Shuangyi Qushi Tongluo Capsules(Shuangyi Capsules)on Dexamethasone(Dex)induced osteoporosis in mice.METHODS The C57BL/6J mice were randomly divided into the control group,the model group,the Xianling Gubao Capsules group(1.5 g/kg),and the low-dose,moderate-dose,and high-dose Shuangyi Capsules groups(0.6,1.2,and 2.4 g/kg).The mouse model of osteoporosis was induced by 8-week intraperitoneal injection of Dex sodium phosphate injection(5 mg/kg).The mice had their femur osteogenesis observed with hematoxylin and eosin(HE)staining and tartrate-resistant acid phosphatase(TRAP)staining;their serum alkaline phosphatase(ALP)and osteocalcin(BGP)activities detected by ELISA;their femoral mRNA expressions of Col-Ⅰ,OCN,and OPN detected by RT-qPCR;and their femoral protein expressions of OPG and RANKL detected by Western blot.Upon the MC3T3-E1 cells exposed to Dex and Shuangyi Capsules,their viability was evaluated by CCK-8 assay;their mineralization determined by alkaline phosphatase staining and alizarin red staining(ARS);and their intracellular ROS level detected using DCFH-DA probe.RESULTS Compared with the model group,Shuangyi Capsules groups demonstrated improved fracture of femoral trabeculae and reduced number of osteoclasts;increased serum ALP and BGP activities(P＜0.05,P＜0.01);increased femoral expressions of Col-Ⅰ mRNA and OPG protein(P＜0.05,P＜0.01);and decreased RANKL protein expression(P＜0.05).Compared with the MC3T3-E1 cells stimulated by Dex,those underwent further treatment of Shuangyi Capsules demonstrated increased cell viability and ALP activity(P＜0.05,P＜0.01);increased mineralization and calcium nodule formation;increased expressions of Col-Ⅰ,OCN,OPN mRNA and OPG protein(P＜0.05,P＜0.01);decreased RANKL protein expression(P＜0.05,P＜0.01);and reduced ROS levels.CONCLUSION Shuangyi Capsules ameliorate Dex-induced osteoporosis in mice by suppressing osteoclast overactivation,enhancing osteoblast activity,and stimulating bone formation through modulation of Col-Ⅰ,OCN,OPN mRNA and OPG/RANKL protein levels.

Aim To investigate the high expression of LINC00626 in colorectal cancer,and explore the effects of LINC00626 on the proliferation,apoptosis,and drug sensitivity of colorectal cancer SW480 cells,as well as its underlying mechanisms.Methods Flu-orescence in situ hybridization(FISH)was used to de-tect the expression levels of LINC00626 in 38 colorec-tal cancer tissues and their corresponding adjacent nor-mal tissues.The JASPAR database was utilized to pre-dict co-expressed genes and their possible binding sites.Cell transfection technology was employed to knockdown LINC00626.Western blot and qRT-PCR techniques were used to verify the transfection efficien-cy.CCK-8 assay,cell apoptosis and necrosis staining,and Western blot were used to detect the changes in the proliferation,apoptosis,drug sensitivity,and ap-optotic proteins of SW480 cells,respectively.Results The FISH results indicated that LINC00626 was highly expressed in colorectal cancer tissues(P＜0.05).The expression of LINC00626 was not associat-ed with the age or gender of patients,but was related to the TNM stage and the presence of lymph node me-tastasis($ P＜0.05 $).The results of CCK-8 assay and cell apoptosis and necrosis staining showed that af-ter knockdown of LINC00626,the proliferation ability of SW480 cells decreased,the apoptosis level in-creased,and the drug resistance decreased(P＜0.05).Western blot results showed that with the de-crease in the expression level of LINC00626,the ex-pression of caspase-3 protein decreased,the expression of cleaved caspase-3 protein increased,and the expres-sion of Bcl-2 protein decreased(P＜0.05).Conclu-sions LINC00626 is highly expressed in colorectal cancer and is associated with the TNM stage and the presence of lymph node metastasis.LINC00626 can af-fect the proliferation,apoptosis,and drug sensitivity of SW480 cells and alter the expression of apoptotic pro-teins.

BACKGROUND:Long non-coding RNA(LncRNA)plays an important role in nervous system development and neurological diseases.Previous studies by the research team have demonstrated that human umbilical cord mesenchymal stem cells overexpressing erythropoietin(EPO-MSCs)under ischemic and hypoxic conditions have better neuroprotective functions and significantly activate the expression of LncRNA XIST.Research suggests that XIST is related to the pathogenesis of hypoxic-ischemic encephalopathy,but the role and mechanism of its regulation by EPO-MSCs in protecting ischemic-hypoxic neurons remain unclear.OBJECTIVE:To explore the new mechanism by which LncRNA XIST,in response to EPO-MSC signaling,affects the apoptosis of ischemic-hypoxic SH-SY5Y cells.METHODS:(1)SH-SY5Y cell lines with knockdown of LncRNA XIST(sh-XIST)and negative control(NC-XIST)were constructed through lentiviral transfection.Oxygen-glucose deprivation was used to induce ischemic-hypoxic injury in the cells.Transwell chambers were used to create a non-contact co-culture system with EPO-MSCs,sh-XIST,and NC-XIST ischemic-hypoxic SH-SY5Y cells.Cell proliferation ability was detected using the CCK-8 assay.Cell migration ability was assessed using the scratch assay,and cell apoptosis was measured by flow cytometry.(2)RNA-seq bioinformatics analysis was performed to screen for differentially expressed genes and pathways between sh-XIST and NC-XIST cell lines.Dual-luciferase experiments were used to verify the relationship between miR-124-3p and the target genes XIST and GRIN1.qRT-PCR was conducted to validate the expression levels of downstream miR-124-3p and GRIN1 genes.(3)miR-124-3p inhibitors and mimics were added to verify phenotypic changes in SH-SY5Y cells after ischemic-hypoxic injury and co-culture with EPO-MSCs.RESULTS AND CONCLUSION:(1)Compared with the NC-XIST group,SH-SY5Y cells in the sh-XIST group showed reduced proliferation and migration abilities and increased apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs.(2)Dual-luciferase experiments showed that miR-124-3p interacted with the target gene XIST.SH-SY5Y cells transfected with miR-124-3p mimics and co-cultured with EPO-MSCs showed decreased apoptosis after ischemic-hypoxic injury,while SH-SY5Y cells transfected with miR-124-3p inhibitors showed increased apoptosis after co-culture with EPO-MSCs.(3)Transcriptomic sequencing and bioinformatics analysis of sh-XIST revealed significant downregulation of the neuroactive ligand-receptor pathway and the key receptor gene GRIN1 for central nervous system development.(4)Dual-luciferase experiments showed that miR-124-3p interacted with GRIN1.GRIN1 expression was significantly downregulated in the sh-XIST group after ischemic-hypoxic injury compared with the NC-XIST group.These findings indicate that LncRNA XIST promotes GRIN1 expression by upregulating miR-124-3p,thereby reducing cell apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs and enhancing proliferation and migration.sh-XIST can block this protective function.

Purpose To explore the predictive value of intravoxel incoherent motion quantitative parameters and pathological grading for the survival prognosis of patients with hepatocellular carcinoma(HCC)after surgery.Materials and Methods A retrospective analysis was performed on 65 patients with HCC who had complete imaging data and underwent radical surgery at the Fourth Hospital of Hebei Medical University from October 2018 to November 2019.All patients were followed up for a 5-year survival period.The receiver operating characteristic curve was used to determine the optimal cut-off values for intravoxel incoherent motion quantitative parameters,including standard apparent diffusion coefficient(sADC),diffusion coefficient(D),pseudo-diffusion coefficient(D*)and perfusion fraction(F).Univariate and multivariate Cox regression analyses were performed to select independent predictive factors affecting the overall survival time of HCC patients after surgery.Results Univariate Cox regression analysis showed that pathological grading(HR=1.588,95%CI 0.936-2.692,P=0.086),microscopic vascular invasion(HR=2.512,95%CI 1.308-4.823,P=0.006),neutrophil-to-lymphocyte ratio(HR=1.752,95%CI 1.000-3.068,P=0.050),sADC(HR=0.433,95%CI 0.235-0.796,P=0.007),D(HR=0.262,95%CI 0.121-0.565,P<0.001)and F(HR=2.268,95%CI 1.259-4.087,P=0.006)were all prognostic factors.Multivariate Cox regression analysis showed that pathological grade(grade Ⅲ and Ⅳ)was the independent risk factor for the survival prognosis of patients after HCC surgery(HR=1.748,95%CI 1.003-3.045,P=0.049);the D value>0.916×10-3 mm2/s was the independent protective factor for their survival prognosis(HR=0.249,95%CI 0.113-0.550,P<0.001).Conclusion The pathological grade(Ⅲ/Ⅳ)as an independent risk factor and higher D values as a protective factor are the independent predictors of survival and prognosis of patients with HCC after surgery,and the combination of the two can provide a reference for clinical prognosis assessment.

AIM To investigate the protective effects of Shuangyi Qushi Tongluo Capsules(Shuangyi Capsules)on Dexamethasone(Dex)induced osteoporosis in mice.METHODS The C57BL/6J mice were randomly divided into the control group,the model group,the Xianling Gubao Capsules group(1.5 g/kg),and the low-dose,moderate-dose,and high-dose Shuangyi Capsules groups(0.6,1.2,and 2.4 g/kg).The mouse model of osteoporosis was induced by 8-week intraperitoneal injection of Dex sodium phosphate injection(5 mg/kg).The mice had their femur osteogenesis observed with hematoxylin and eosin(HE)staining and tartrate-resistant acid phosphatase(TRAP)staining;their serum alkaline phosphatase(ALP)and osteocalcin(BGP)activities detected by ELISA;their femoral mRNA expressions of Col-Ⅰ,OCN,and OPN detected by RT-qPCR;and their femoral protein expressions of OPG and RANKL detected by Western blot.Upon the MC3T3-E1 cells exposed to Dex and Shuangyi Capsules,their viability was evaluated by CCK-8 assay;their mineralization determined by alkaline phosphatase staining and alizarin red staining(ARS);and their intracellular ROS level detected using DCFH-DA probe.RESULTS Compared with the model group,Shuangyi Capsules groups demonstrated improved fracture of femoral trabeculae and reduced number of osteoclasts;increased serum ALP and BGP activities(P＜0.05,P＜0.01);increased femoral expressions of Col-Ⅰ mRNA and OPG protein(P＜0.05,P＜0.01);and decreased RANKL protein expression(P＜0.05).Compared with the MC3T3-E1 cells stimulated by Dex,those underwent further treatment of Shuangyi Capsules demonstrated increased cell viability and ALP activity(P＜0.05,P＜0.01);increased mineralization and calcium nodule formation;increased expressions of Col-Ⅰ,OCN,OPN mRNA and OPG protein(P＜0.05,P＜0.01);decreased RANKL protein expression(P＜0.05,P＜0.01);and reduced ROS levels.CONCLUSION Shuangyi Capsules ameliorate Dex-induced osteoporosis in mice by suppressing osteoclast overactivation,enhancing osteoblast activity,and stimulating bone formation through modulation of Col-Ⅰ,OCN,OPN mRNA and OPG/RANKL protein levels.

Objective To explore the changes of durability properties of reusable surgical gowns when used in dry and wet conditions.Methods Reusable surgical gowns made of single-layer polyester fiber or 3-layer composite material were selected as test samples,and a Martindale abrasion and pilling tester was used as the basic test platform and modified to form fixtures suitable for the wet state environment.The reusable surgical gowns underwent abrasion experiments in wet and dry conditions to observe the changes in their fiber structure,and were subjected to water penetration resistance and swelling strength tests.Results Visually the reusable surgical gowns had few changes of the microscopic textile fiber structure in dry and wet conditions,and the gowns made of single-layer polyster fiber gained advantages over the outer layers of those of 3-layer composite material in abrasion resistance with the same friction cycles.In dry and wet conditions,the hydrostatic pressure values of the gowns of single-layer polyster fiber gradually decreased with the increase of the degree of abrasion,which were always lower than those of the gowns of 3-layer composite material;the swelling strength of the gowns of single-layer polyster fiber was always greater than that of the gowns of 3-layer composite material,which decreased with the deterioration of the wear more significantly than that of the gowns of 3-layer composite material.Conclusion The reusable surgical gowns made of single-layer polyester fiber or 3-layer composite material have few differences in durability and protective properties at the early stages of ablation in dry and wet conditions.The durability of the gowns decreases as the degree of wear increases,while the trend of the decrease is slowing down until the fabric breaks down and completely loses its barrier effect.[Chinese Medical Equipment Journal,2025,46(6):28-33]