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.

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

OBJECTIVES: To study the clinical and genetic characteristics of osteopetrosis (OPT) in children. METHODS: A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized. RESULTS: Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (P<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the CLCN7 gene (53%), 6 in the TCIRG1 gene (40%), and 1 in the TNFRSF11A gene (7%). Three novel CLCN7 variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with TCIRG1 variants exhibited MOP clinical phenotypes. Of the seven patients with CLCN7 variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP. CONCLUSIONS Clinical phenotypes of OPT in children are heterogeneous, predominantly involving CLCN7 and TCIRG1 gene variants, with a correlation between clinical phenotypes and genotypes.
Humans ; Osteopetrosis/genetics* ; Male ; Female ; Infant ; Child, Preschool ; Retrospective Studies ; Vacuolar Proton-Translocating ATPases/genetics* ; Child ; Chloride Channels/genetics* ; Mutation ; Receptor Activator of Nuclear Factor-kappa B

Objective:The aim of this study is to analyse the clinical characteristics of Special clinical types of lung cancer nodules with "small tumors and big metastases" .Methods:From Jan. 2019 to Nov. 2024, patients with stage T1 solid lung cancer who were pathologically confirmed in the First Affiliated Hospital of Chongqing Medical University were prospectively collected and divided into lung cancer nodule with metastasis group (study group) and stage Ia lung cancer group (control group). The differences in clinical, imaging, pathological and molecular features between the two groups were compared, and the differences in the distribution of metastases in the study group and in patients with or without bone metastasis were analyzed.Results:A total of 827 patients with an average age of 62.65±11.01 years were included, including 425 in the study group and 402 in the control group. The proportion of males, number of smokers, nodule size and EGFR mutation rate in the study group were significantly higher than those in the control group (all P<0.05). Stage IV patients accounted for 63.76% in the study group, among which bone metastasis patients accounted for the highest proportion (51.66%), and alkaline phosphatase, calcium and phosphorus were significantly increased. Conclusions:Patients with smoking, male and solid lung cancer nodules are more likely to have "small tumor and large metastasis", and bone metastasis is the most common distant metastatic site. The increase of alkaline phosphatase, calcium and phosphorus is helpful for early identification of bone metastases.

Objective To investigate the application effect of three-dimensional CT-assisted pedicle measurement in elderly patients undergoing percutaneous vertebroplasty(PVP).Methods A total of 80 osteoporotic patients with L1 vertebral compression fracture who were treated in People's Hospital of Qujiang District in Shaoguan from March 2021 to March 2023 were selected as the study subjects.Three-dimensional CT-assisted pedicle measurement was performed before surgery,including L1 axial effective angle,axial effective pedicle transverse,oblique sagittal effective angle,oblique sagittal effective longitudinal diameter,and pedicle transverse diameter,and their differences between different genders were analyzed.Four patients with an effective pedicle diameter of less than 3 mm were included into the bilateral group,and the rest of the patients were divided into the unilateral group(received unilateral-approach PVP)and the bilateral group(received bilateral-approach PVP)according to the random number table method.The perioperative conditions of patients in the two groups were collected.The follow-up was performed for six months after surgery,and the visual analogue scale(VAS)score and Oswestry dysfunction index(ODI)score of patients between the two groups were compared before surgery,1 month after surgery and 6 months after surgery.X-ray examinations were performed before and after surgery to evaluate the recovery of Cobb angle and cement leakage.Results No significant difference was observed in axial universal effective angle or universal oblique sagittal effective angles between genders(P>0.05).The male patients showed greater axial lateral effective angle,axial lateral effective pedicle transverse,axial universal effective pedicle transverse,lateral oblique sagittal effective angle,lateral oblique sagittal effective longitudinal diameter,universal oblique sagittal effective longitudinal diameter,and pedicle transverse as compared to female patients,with statistically significant differences(P<0.05).The intraoperative fluoroscopy times and bone cement injection volume of patients in the unilateral group were less/lower than those in the bilateral group,with statistically significant differences(P<0.05).There was no significant difference in the operation time of patients between the two groups(P>0.05).During the follow-up period,3 patients were lost to follow-up in the unilateral group and 4 patients in the bilateral group.One patient in the unilateral group had cement leakage.There were no significant differences in the VAS scores,ODI scores before surgery and 1 month after surgery or Cobb angles before and after surgery between the two groups(P>0.05).The VAS and ODI scores of patients in the unilateral group 6 months after surgery were significantly higher than those in the bilateral group,with statistically significant differences(P<0.05).Conclusion In the treatment of osteoporotic vertebral compression fractures,three-dimensional CT-assisted pedicle measurement before PVP can help to achieve accurate puncture,and improve the safety and effectiveness of the surgery.

Objective:Special clinical types of lung cancer nodules with " small tumors and big metastases" are seriously harmful to human health, but their clinical characteristics are rarely reported. The aim of this study is to analyse the clinical characteristics of these lung cancer nodules.Methods:From Jan. 2019 to Nov. 2024, patients with stage T1 solid lung cancer who were pathologically confirmed in the First Affiliated Hospital of Chongqing Medical University were prospectively collected and divided into lung cancer nodule with metastasis group (study group) and stage Ia lung cancer group (control group). The differences in clinical, imaging, pathological and molecular features between the two groups were compared, and the differences in the distribution of metastases in the study group and in patients with or without bone metastasis were analyzed.Results:A total of 827 patients with an average age of 62.65±11.01 years were included, including 425 in the study group and 402 in the control group. The proportion of males, number of smokers, nodule size and EGFR mutation rate in the study group were significantly higher than those in the control group (all P<0.05). Stage IV patients accounted for 63.76% in the study group, among which bone metastasis patients accounted for the highest proportion (51.66%), and alkaline phosphatase, calcium and phosphorus were significantly increased. Conclusions:Patients with smoking, male and solid lung cancer nodules are more likely to have " small tumor and large metastasis", and bone metastasis is the most common distant metastatic site. The increase of alkaline phosphatase, calcium and phosphorus is helpful for early identification of bone metastases.

Objective:To investigate the expression and clinical significance of Prohibitin 2(PHB2)in the kidney tissue of patients with Diabetic Kidney Disease(DKD).Methods:From March 2015 to May 2024,samples were collected from 16 patients diagnosed with diabetic nephropathy through renal biopsy,who met the inclusion criteria(referred to as the DKD group).Additionally,20 patients with renal tumors undergoing nephrectomy,who had partially normal kidney tissue,were selected to serve as the control group(NC group).The pathological changes of the two groups of samples were evaluated by HE and PAS staining.Immunohistochemistry was utilized to analyze the differences in PHB2 protein expression between the two groups.Pearson or Spearman correlation methods were applied for statistical analysis.Results:PHB2 was expressed in renal tubules,and its expression level in the diabetic kidney disease(DKD)group was significantly lower than that in the normal control(NC)group(P＜0.05).Additionally,the expression level of PHB2 in diabetic nephropathy was found to be negatively correlated with glycated hemoglobin,serum creatinine,cystatin C,and blood urea nitrogen(P＜0.05).In contrast,there was a positive correlation between PHB2 expression and the estimated glomerular filtration rate(eGFR)(P＜0.05).Therefore,PHB2 expression serves as a negative correlation factor for serum creatinine,cystatin C,and blood urea nitrogen,while being a positive correlation factor for eGFR.Conclusions:In patients with diabetic nephropathy,the expression of PHB2 in renal tissue significantly decreases.This reduction in PHB2 levels closely correlates with glucose metabolism and renal function.Low levels of PHB2 may worsen glucose metabolism disorders,renal function damage,and proteinuria.Therefore,PHB2 serves as a potential biomarker for assessing prognosis and offers new insights into the treatment of diabetic kidney disease.

Objective:To investigate the expression and clinical significance of Prohibitin 2(PHB2)in the kidney tissue of patients with Diabetic Kidney Disease(DKD).Methods:From March 2015 to May 2024,samples were collected from 16 patients diagnosed with diabetic nephropathy through renal biopsy,who met the inclusion criteria(referred to as the DKD group).Additionally,20 patients with renal tumors undergoing nephrectomy,who had partially normal kidney tissue,were selected to serve as the control group(NC group).The pathological changes of the two groups of samples were evaluated by HE and PAS staining.Immunohistochemistry was utilized to analyze the differences in PHB2 protein expression between the two groups.Pearson or Spearman correlation methods were applied for statistical analysis.Results:PHB2 was expressed in renal tubules,and its expression level in the diabetic kidney disease(DKD)group was significantly lower than that in the normal control(NC)group(P＜0.05).Additionally,the expression level of PHB2 in diabetic nephropathy was found to be negatively correlated with glycated hemoglobin,serum creatinine,cystatin C,and blood urea nitrogen(P＜0.05).In contrast,there was a positive correlation between PHB2 expression and the estimated glomerular filtration rate(eGFR)(P＜0.05).Therefore,PHB2 expression serves as a negative correlation factor for serum creatinine,cystatin C,and blood urea nitrogen,while being a positive correlation factor for eGFR.Conclusions:In patients with diabetic nephropathy,the expression of PHB2 in renal tissue significantly decreases.This reduction in PHB2 levels closely correlates with glucose metabolism and renal function.Low levels of PHB2 may worsen glucose metabolism disorders,renal function damage,and proteinuria.Therefore,PHB2 serves as a potential biomarker for assessing prognosis and offers new insights into the treatment of diabetic kidney disease.

Objective:The aim of this study is to analyse the clinical characteristics of Special clinical types of lung cancer nodules with "small tumors and big metastases" .Methods:From Jan. 2019 to Nov. 2024, patients with stage T1 solid lung cancer who were pathologically confirmed in the First Affiliated Hospital of Chongqing Medical University were prospectively collected and divided into lung cancer nodule with metastasis group (study group) and stage Ia lung cancer group (control group). The differences in clinical, imaging, pathological and molecular features between the two groups were compared, and the differences in the distribution of metastases in the study group and in patients with or without bone metastasis were analyzed.Results:A total of 827 patients with an average age of 62.65±11.01 years were included, including 425 in the study group and 402 in the control group. The proportion of males, number of smokers, nodule size and EGFR mutation rate in the study group were significantly higher than those in the control group (all P<0.05). Stage IV patients accounted for 63.76% in the study group, among which bone metastasis patients accounted for the highest proportion (51.66%), and alkaline phosphatase, calcium and phosphorus were significantly increased. Conclusions:Patients with smoking, male and solid lung cancer nodules are more likely to have "small tumor and large metastasis", and bone metastasis is the most common distant metastatic site. The increase of alkaline phosphatase, calcium and phosphorus is helpful for early identification of bone metastases.

Iron is an essential trace element for the human body and is critical for vital cellular processes,such as DNA synthesis,respiration,and oxygen transport.The body maintains iron homeostasis through a coordinated balance of absorption,utilization,storage,and distribution.Both iron deficiency and excess can lead to pathologies,with the latter triggering lipid peroxidation and DNA mutations via the Fenton reaction,potentially causing iron-induced cell death in severe cases.Although iron overload can inflict severe damage on multiple organs,including the brain,liver,spleen,heart,ovaries,and kidneys,the mechanisms that regulate iron homeostasis in response to overload are not fully understood.Various animal models have been developed to help elucidate these mechanisms,each reflecting different aspects of iron overload relevant to human diseases,and selection of the most appropriate animal model is needed for the accurate simulation of the pathological and physiological states associated with human iron overload-related diseases.This review synthesizes recent literature on animal models pertinent to iron overload,to offer insights to support the development and analysis of models for diseases related to iron overload.