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.

Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.

ObjectiveTo explore the role and potential mechanism of circulating glutamate in enhancing insulin sensitivity by aerobic exercise. This research may provide a novel strategy for preventing metabolic diseases through precise exercise interventions. MethodsTo investigate the effects of elevated circulating glutamate on insulin sensitivity and its potential mechanisms, 18 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into 3 groups: a control group (C), a group receiving 500 mg/kg glutamate supplementation (M), and a group receiving 1 000 mg/kg glutamate supplementation (H). The intervention lasted for 12 weeks, with treatments administered 6 d per week. Following the intervention, an insulin tolerance test (ITT) and a glucose tolerance test (GTT) were conducted. Circulating glutamate levels were measured using a commercial kit, and the activity of the skeletal muscle InsR/IRS1/PI3K/AKT signaling pathway was analyzed via Western blot. To further investigate the role of circulating glutamate in enhancing insulin sensitivity through aerobic exercise, 30 male C57BL/6 mice were randomly assigned to 3 groups: a control group (CS), an exercise intervention group (ES), and an exercise combined with glutamate supplementation group (EG). The ES group underwent treadmill-based aerobic exercise, while the EG group received glutamate supplementation at a dosage of 1 000 mg/kg in addition to aerobic exercise. The intervention lasted for 10 weeks, with sessions occurring 6 d per week, and the same procedures were followed afterward. To further elucidate the mechanism by which glutamate modulates the InsR/IRS1/PI3K/AKT signaling pathway, C2C12 myotubes were initially subjected to graded glutamate treatment (0, 0.5, 1, 3, 5, 10 mmol/L) to determine the optimal concentration for cellular intervention. Subsequently, the cells were divided into 3 groups: a control group (C), a glutamate intervention group (G), and a glutamate combined with MK801 (an NMDA receptor antagonist) intervention group (GK). The G group was treated with 5 mmol/L glutamate, while the GK group received 50 μmol/L MK801 in addition to 5 mmol/L glutamate. After 24 h of intervention, the activity of the InsR/IRS1/PI3K/AKT signaling pathway was analyzed using Western blot. ResultsCompared to the mice in group C, the circulating glutamate levels, the area under curve (AUC) of ITT, and the AUC of GTT in the mice of group H were significantly increased. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle were significantly downregulated. Compared to the mice in group CS, the circulating glutamate levels, the AUC of ITT, and the AUC of GTT in the mice of group ES were significantly reduced. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle of group ES mice were significantly upregulated. There were no significant changes observed in the mice of group EG. Compared to the cells in group 0 mmol/L, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in cells of group 5 mmol/L were significantly downregulated. Compared to the cells in group C, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in the cells of group G were significantly downregulated. No significant changes were observed in the cells of group GK. ConclusionLong-term aerobic exercise can improve insulin sensitivity by lowering circulating levels of glutamate. This effect may be associated with the upregulation of the InsR/IRS1/AKT signaling pathway activity in skeletal muscle. Furthermore, glutamate can weaken the activity of the InsR/IRS1/PI3K/AKT signaling pathway in skeletal muscle, potentially by binding to NMDAR expressed in skeletal muscle.

Objective: To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies. Methods: A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE). Results: There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years. Conclusions The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.

Objective:To investigate the effects of psychological state on the setup errors of radiotherapy for breast cancer patients.Methods:A prospective cohort study was conducted. A total of 193 breast cancer patients in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from October 2022 to May 2023 were selected. Radiotherapy was performed after fixation with an integrated multi-functional device for the head, chest and abdomen. Psychological status of patients was assessed by using 9-item health questionnaire (PHQ-9) and generalized anxiety disorder 7 self-rating scale (GAD-7) before first radiotherapy, the 10th radiotherapy and the last radiotherapy. Based on the results of the questionnaires, patients were divided into psychological problem (anxiety or depression) group and non-psychological problem group. The general data and setup errors of radiotherapy in both groups were compared.Results:All the 193 patients were female, with a median age of 47 years. There were 53 patients in psychological problem group and they underwent a total of 507 image-guided procedures, with setup errors [ M ( Q1, Q3)] of 0.18 (0.07, 0.33), 0.20 (0.10, 0.33) and 0.19 (0.09, 0.30) in the left-right (X), superior-inferior (Y), and anterior-posterior (Z) directions, respectively; the remaining 140 patients in non-psychological problem group underwent 1 240 image-guided procedures, with setup errors [ M ( Q1, Q3)]of 0.17 (0.08, 0.30), 0.20 (0.10, 0.30) and 0.18 (0.09, 0.28) in the X, Y, and Z directions, respectively, and the differences were statistically significant ( Z values were -3.78, -2.00; P < 0.001, P = 0.046). Conclusions:Anxiety and depression have an influence on the setup errors of radiotherapy in patients with breast cancer. In the processs of radiotherapy for breast cancer, it is important to pay attention to the psychological status of patients.

Objective:To explore the value of non-invasive habitat imaging (HI) multi-parametric MRI (mpMRI) in predicting the risk of prostate cancer (PCa).Methods:In this cross-sectional study, 220 patients with PCa confirmed by radical prostatectomy (RP) who underwent multi-parametric MRI (mpMRI) scanning at Xijing Hospital, Air Force Military Medical University from January 2018 to May 2024 were retrospectively collected. Patients were divided into a training set (154 cases) and a test set (66 cases) by simple random sampling in a 7∶3 ratio. Based on mpMRI imaging, the apparent diffusion coefficient (ADC), perfusion fraction (f), and mean kurtosis (MK) of each voxel were integrated. The K-means clustering algorithm was used to divide the PCa target lesions into habitat subregions, generate habitat maps, and calculate the proportion of each habitat subregion in the entire lesion. According to the 2019 International Society of Urological Pathology (ISUP) guidelines, patients were categorized into a low-risk group (ISUP≤2, 65 cases) and a high-risk group (ISUP≥3, 155 cases). The RP specimens were matched with the habitat map to identify corresponding habitat subregions, and the ISUP grade of each subregion was individually evaluated to calculate the detection rate of high-risk PCa patients. The logistic regression analysis was applied to identify the independent risk factors associated with PCa risk, and the HI-clinical imaging model and clinical imaging model were constructed. The efficacy of the models was assessed using receiver operating characteristic curve.Results:Based on the optimal cluster number, the habitat was divided into three subregions. Habitat 1 had lower ADC and f values and higher MK values, while habitat 2 had the opposite characteristics, and habitat 3 was intermediate. The proportion of habitat 1 in the high-risk group was 28.8%, in the low-risk group was 8.9%. In the training set, the comparison of habitat subregions with pathological results showed that the detection rate of high-risk lesions was 66.9% (103/154) in habitat 1, 25.3% (39/154) in habitat 2, and 47.4% (73/154) in habitat 3. The logistic regression analysis indicated that the proportion of habitat 1 ( OR=3.03, 95% CI 1.77-5.18, P<0.001), prostate-specific antigen ( OR=1.66, 95% CI 1.04-2.66, P=0.034), and the prostate imaging reporting and data system score ( OR=1.65, 95% CI 1.00-2.70, P=0.048) as independent risk factors for high-risk PCa. In the training set, the area under the curve (AUC) for predicting PCa risk was 0.854 (95% CI 0.789-0.920) for the HI-clinical imaging model and 0.779 (95% CI 0.701-0.856) for the clinical imaging model. In the test set, the AUC values were 0.809 (95% CI 0.693-0.895) and 0.738 (95% CI 0.619-0.856), respectively. Conclusion:HI based on mpMRI can effectively predict the risk of PCa.

OBJECTIVE T o carry out the health economics evaluation and cost-benefit analysis of the type b Hae-mophilus influenzae(Hib)vaccination for the children who were hospitalized due to Hib infection so as to provide evidence for public health policies.METHODS The children who were diagnosed with Hib-related respiratory tract infections or meningitis and were hospitalized in respiratory medicine department,infection management depart-ment,emergency rooms and neurology department of Jiangxi Provincial Children's Hospital from Jan.1,2021 to Dec.31,2023 were recruited as the research subjects.Based on a 1∶1 matching condition,the matching variables included four items such as the same age for the admission to the hospital,same gender,same department and same grade of disease severity.The children for whom the primary immunization of Hib vaccination(including Hib monovalent vaccine and Hib-containing combination vaccine)were completed and the integrity of vaccination infor-mation could be checked out were assigned as the intervention group,while the children for whom the primary im-munization of Hib vaccination was not completed were chosen as the control group.The clinical data,vaccination data and the data such as length of hospital stay and hospitalization cost were collected from the children.The cost-benefit of the Hib vaccination among the children with Hib infection was observed.RESULTS A total of 622 hospi-talized children who were detected with Hib-positive respiratory tract infections or meningitis were enrolled in the study,and 73 children(20 children from infection management department,27 children from respiratory medi-cine department,26 children from emergency rooms)were finally included in the intervention group after matc-hing and multiple rounds of screening,73 children were chosen as the control group based on a 1∶1 matching con-dition.The male children accounted for 57.53％(42 cases)in both groups,and the female children accounted for 42.47％(31 cases)in both groups.With the respect to the length of hospital stay,it was 7.00(5.00,8.00)days in the intervention group,7.00(6.00,8.00)days in the control group(Z=-0.341,P=0.733).In terms of the hospitalization cost,it was 7 756.17(6 617.92,10 617.69)yuan in the intervention group,9 040.65(8 033.76,10 935.84)yuan in the control group(Z=-2.795,P=0.005).The cost of Hib vaccination was 343.03 yuan per capita in the intervention group,and the benefit-cost ratio(BCR)was 1∶3.74(343.03 yuan/1 284.48 yuan).CONCLUSIONS The Hib vaccination can save the hospitalization cost and has high cost effectiveness.It is sugges-ted that the Hib vaccination should be promoted and the coverage rate of Hib vaccination should be raised among the age-eligible children.

Objective To investigate the mechanism by which blue light irradiation-activated microglia mediate immune cell recruitment and exacerbate retinal damage,and to explore the role of microglial depletion in inhibiting immune infiltration and protecting the retina.Methods SPF-grade C57BL/6J mice were randomly divided into control group,blue light irradiation group,and PLX5622 pretreatment blue light irradiation group.A retinal injury model was established by continuous LED blue light irradiation for 2 days.In the PLX5622 pretreatment group,microglia were specifically depleted before blue light irradiation.After modeling,HE staining and OCT examination were used to examine retinal histomorphological changes;ERG examination was performed to evaluate retinal function;DHE staining and RT-qPCR were used to detect oxidative stress and inflammatory responses,and Iba1,CD68,CD11b immunofluorescence staining and flow cytometry were used to analyze microglial activation status and immune cell infiltration.Results After blue light irradiation,the retinal outer nuclear layer thickness was significantly reduced;ERG a-wave and b-wave amplitudes decreased;expression of oxidative stress-related genes Nrf2,Sod2,and HO-1 was upregulated;expression of inflammatory factors IL-1β,TNF-α,and ICAM-1 increased;the number of Iba1-positive microglia increased and migrated extensively to the outer nuclear layer;the proportion of CD68+cells and CD11b+immune cells was elevated;and activated microglia aggregated around blood vessels to mediate immune cell infiltration.After PLX5622 pretreatment to deplete microglia,immune cell infiltration was significantly reduced;inflammatory responses were alleviated;retinal structural damage was markedly improved,and visual function was protected.Conclusions Blue light irradiation activates microglia and promotes their migration to the injury area.Activated microglia mediate immune cell recruitment and infiltration,exacerbating retinal inflammatory damage.Microglial depletion can effectively inhibit immune infiltration,rescue retinal structure and function,and provide new therapeutic strategies for the prevention and treatment of blue light-related ocular diseases.

Aim To investigate the effect of Shenqi Dihuang decoction(SQDH)on henoch-schonlein pur-pura nephritis(HSPN)rats by regulating AMPK/Sirt1/Nrf2 mediated ferroptosis and the possible mech-anism.Methods Thirty SD rats were randomly divid-ed into a control group(Control),HSPN group,SQDH low-dose group(SQDH-L,5.4 g·kg-1),SQDH high-dose group(SQDH-H,21.6 g·kg-1),and SQDH high-dose+AMPK inhibitor group(SQDH-H+CC,20 mg·kg-1),with six rats in each group.Except for the control group,all other groups of rats were injected intraperitoneally with ovalbumin and complete Freund's adjuvant to establish HSPN rat models.After the successful construction of the model,each group of rats was orally administered with the cor-responding dosage or physiological saline once a day for five weeks.HE staining was used to observe the his-topathological changes in renal tissues;immunohisto-chemistry(IHC)was employed to detect the deposition of IgA and IgG in renal tissues;serum biochemical pa-rameters of renal function and urinary protein levels were measured;commercial assay kits were utilized to determine oxidative stress markers and Fe2+levels in renal tissues;Western blot analysis was performed to assess ferroptosis-related proteins and the protein ex-pression of the AMPK/Sirt1/Nrf2 signaling pathway in renal tissues.Results Compared with the control group,the HSPN group showed significant pathological damage in kidney tissue,with significantly increased scores,increased deposition of IgA and IgG in kidney tissue,decreased serum total protein(TP)and albu-min(ALB),and average increases in serum creatinine(Cre),urea nitrogen(BUN),and urinary protein levels(P＜0.05).The levels of MDA,ROS,Fe2+,and ACSL4 protein expression in the kidney tissue sig-nificantly increased,while SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein ex-pression significantly decreased(P＜0.05).Com-pared with the HSPN group,the pathological damage to renal tissue was reduced,IgA and IgG deposition in renal tissue decreased,TP and ALB decreased,Cre,BUN,and urinary protein levels were all reduced(P＜0.05),and the levels of MDA,ROS,Fe2+,and ACSL4 protein expression in renal tissue were signifi-cantly reduced in each dose group of SQDH rats.SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein expression significantly increased(P＜0.05).Compared with the SQDH-H group,the AMPK inhibitor CC could inhibit the AMPK/Sirt1/Nrf2 signaling pathway induced ferroptosis and reverse the protective effect of SQDH on renal injury in HSPN rats.Conclusions SQDH can improve renal injury in HSPN rats,and its mechanism may be related to the activation of AMPK/Sirt1/Nrf2 signaling pathway to in-hibit ferroptosis.

Objective:To investigate the predictive value of endothelial activation and stress index(EASIX)for the prognosis of patients with mantle cell lymphoma(MCL).Methods:A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023,had therapeutic indications and received standard treatment.Results:A total of 66 patients were included and divided into high EASIX group and low EASIX group,according to a cutoff value of 0.97 determined by the receiver operating characteristic(ROC)curve.Multivariate Cox regression analysis showed that prealbumin＜0.2 g/L,high EASIX,and ECOG PS score ≥2 were independent risk factors influencing overall survival(OS)in MCL patients.The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months,and the median progression-free survival was 8.8 and 26.0 months,respectively.The proportions of patients with ECOG PS score ≥2 and prealbumin＜0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.Conclusion:At the time of initial diagnosis,EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL.Furthermore,patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.