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.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Objective To investigate the current status of work readiness and its influencing factors among patients returning to work after lung cancer surgery. Methods A retrospective study was conducted on young and middle-aged postoperative lung cancer patients who were treated at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to September 2023 and returned to their jobs. Data were collected through a general information questionnaire, readiness for return-to-work scale (RRTW), general self-efficacy scale (GSES), and simplified coping style questionnaire (SCSQ). Univariate and multivariate logistic regression analyses were used to explore the factors affecting the work readiness of patients returning to work. Results A total of 219 patients were included, with 59 males and 160 females aged 18-60 years. Among the postoperative lung cancer patients returning to work, 73.1% were in the active maintenance stage of return-to-work readiness with a RRTW score of (17.59±1.48) points, and 26.9% were in the uncertain maintenance stage with a RRTW score of (16.22±1.50) points. Multivariate logistic regression analysis showed that patients aged≤30 years (OR=52.381), employees of enterprises and institutions (OR=7.682), agricultural, pastoral, fishery, forestry laborers (OR=15.665), positive coping (OR=5.043), those with higher self-efficacy (OR=1.157) and engaged in physically demanding work (OR=2.449) had higher return-to-work readiness, while patients with≥2 children (OR=0.055), self-payment (OR=0.044), and those working more than 40 hours per week (OR=0.122) had lower return-to-work readiness. Conclusion The return-to-work readiness of young and middle-aged postoperative lung cancer patients needs to be improved, and occupation, job nature, main coping styles, general self-efficacy and other factors are associated with return-to-work readiness.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

Tissue repair requires the reconstruction of functional vascular networks to restore oxygen and nutrient delivery, eliminate metabolic waste, and maintain tissue homeostasis. Although biochemical factors such as growth factors and cytokines have been extensively studied in vascular regeneration, increasing evidence indicates that mechanical signals from the extracellular matrix (ECM) are equally important regulators of angiogenesis. Matrix stiffness, as a major biomechanical property of the tissue microenvironment, provides critical information that influences endothelial cell (EC) behavior and vascular remodeling through mechanotransduction. However, the biological effects of matrix stiffness are not universally defined as either pro- or anti-angiogenic, but are highly dependent on tissue context, cellular composition, disease progression, and the dynamic changes occurring during tissue repair. Therefore, understanding how matrix stiffness regulates vascular regeneration is essential for developing more precise strategies for tissue engineering and regenerative medicine. In this review, we summarize recent advances in the regulation of angiogenesis by matrix stiffness during tissue repair from multiple perspectives. First, we discuss the direct effects of matrix stiffness on EC behaviors, including differentiation, morphological remodeling, migration, proliferation, barrier maintenance, and vascular network formation. ECs sense mechanical alterations in the surrounding matrix through various mechanosensitive structures, including integrins, focal adhesion complexes, and mechanosensitive ion channels such as Piezo1 and TRPV proteins. These mechanical signals are subsequently transmitted through intracellular pathways involving FAK, RhoA/ROCK, MAPK, and Hippo-YAP/TAZ signaling, leading to cytoskeletal reorganization and transcriptional regulation. Through these mechanisms, matrix stiffness regulates endothelial functional states and determines the balance between regenerative vascular formation and pathological vascular remodeling. Beyond the direct regulation of ECs, we further highlight the importance of stiffness-mediated intercellular communication within the regenerative microenvironment. Matrix stiffness can regulate the behavior and secretory profiles of vascular-associated cells, including mesenchymal stem cells and macrophages, thereby indirectly affecting endothelial function through paracrine mechanisms. Changes in matrix mechanics influence the secretion of angiogenic factors, inflammatory cytokines, and extracellular vesicles from these cells, creating a mechanical regulation network that coordinates vascular regeneration. This perspective extends the traditional concept of matrix stiffness from a physical support structure to an active regulatory signal that integrates multiple cellular responses during tissue repair. Furthermore, we discuss the tissue-specific effects of matrix stiffness in vascular regeneration across different organs, including the aorta, lung, liver, and heart. Although excessive matrix stiffening is frequently associated with fibrosis and vascular dysfunction, the consequences of mechanical changes vary considerably among tissues. Moderate stiffness alterations may support endothelial activation and vascular stabilization in certain regenerative contexts, whereas persistent pathological stiffening can promote inflammation, endothelial dysfunction, and impaired vascular repair. These findings emphasize that the biological meaning of “soft” and “stiff” microenvironments should be interpreted according to specific tissue and experimental conditions rather than as universal mechanical classifications. Finally, we summarize current challenges and future perspectives in this field. A major limitation is the lack of standardized mechanical characterization among different studies, as stiffness measurements are influenced by material properties, testing methods, and experimental conditions, limiting direct comparison across research systems. Moreover, most existing models fail to fully reproduce the dynamic and viscoelastic properties of native ECM during tissue regeneration. Future studies should combine advanced biomaterials with standardized mechanical analysis, organoid models, and multi-omics approaches to establish more accurate mechanical regulatory maps. Overall, this review proposes that matrix stiffness is not merely a structural feature of tissues, but an active biological signal that regulates vascular regeneration through coordinated mechanotransduction and multicellular interactions. A deeper understanding of stiffness-mediated vascular regulation will provide new theoretical insights and therapeutic opportunities for improving tissue repair outcomes.

Objective To investigate the correlation and lag effect between atmospheric particulate matter and the risk of hospitalization for chronic kidney disease(CKD).Methods The daily hospitalization data for CKD in 9 hospitals in Urumqi from Jan.1,2019,to Dec.31,2020,and the air pollution and meteorological data during the same period were collected.The relationship between PM2.5 and PM10 concentrations and CKD incidence was analyzed after controlling for long-term trends,meteorological factors,and potential confounding factors such as the"day of the week effect"by using the generalized additive model(GAM).The effects of single-day lag of 0-7 d(lag0-lag7)and cumulative lag of 0-7 d(lag01-lag07)were analyzed,and subgroup analyses were conducted for gender,age,and season.On the basis of the single pollutant model,other pollutants were included(at most 2 pollutants were included at a time),and a double pollutant model was constructed to evaluate the stability of the model.Results For every 10 μg/m3 increase in PM2.5 concentration,the highest risk of CKD hospitalization occured when lagged alone at lag2(relative risk[RR]=1.014,95％confidence interval[CI]1.006-1.023)and lagged cumulatively at lag04(RR=1.018,95％CI 1.007-1.029).For every 10 μg/m3 increase in PM10 concentration,the risk of CKD hospitalization was highest when lagged alone at lag0 and lagged cumulatively at lag07(RR=1.012,95％CI 1.007-1.017;RR=1.024,95％CI 1.016-1.032).In gender stratification,for every 10 μg/m3 increase in PM2.5 concentration,the cumulative lag at lag04 indicated that males had the highest risk of CKD hospitalization(RR=1.023,95％CI 1.008-1.038);for every 10 μg/m3 increase in PM10 concentration,the highest risk of CKD hospitalization was observed in males when lagged alone at lag0(RR=1.013,95％CI 1.006-1.020),and in females when lagged alone at lag1(RR=1.013,95％CI 1.006-1.020).In age stratification,for every 10 μg/m3 increase in PM2.5 concentration,the risk of CKD hospitalization was highest in people 65 years old with single-day lag at lag3 and cumulative lag at lag04(RR=1.016,95％CI 1.007-1.026;RR=1.022,95％CI 1.010-1.035);for every 10 μg/m3 increase in PM10 concentration,the cumulative lag at lag07 indicated that individuals aged＜65 years old and ≥65 years old had the highest risk of CKD hospitalization(RR=1.027,95％CI 1.017-1.037;RR=1.015,95％CI 1.001-1.028).In seasonal stratification,for every 10 μg/m3 increase in PM2.5 concentration during the cold season,the risk of CKD hospitalization was highest when lagged alone at lag3 and lagged cumulatively at lag07(RR=1.020,95％CI 1.011-1.029;RR=1.025,95％CI 1.011-1.038).For every 10 μg/m3 increase in PM10 concentration during the cold season,the risk of CKD hospitalization was highest when lagged alone at lag2(RR=1.013,95％CI 1.007-1.019).For every 10 μg/m3 increase in PM10 concentration during the warm season,the risk of CKD hospitalization was highest when lagged alone at lag7(RR=1.015,95％CI 1.006-1.024).In the dual pollutant model,the effects of PM2.5 adjusting PM10,SO2,O3 and CO,and PM10 adjusting NO2,SO2,O3,and CO on the risk of CKD hospitalization were still significant(P＜0.05).Conclusion The increase in atmospheric particulate matter concentrations of PM2.5 and PM10 can lead to an increased risk of CKD,and there is a lag effect.Men,people under the age of 65 years old,and those in cold seasons(heating periods)are more sensitive to exposure to PM2.5 and PM10.

Objective To explore the roles of transfer RNA-derived small RNAs(tsRNAs)in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma.Methods The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center.The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas(TCGA)database(TCGA-LUAD).The target genes were predicted based on TRFtarget2.0 and tRFTar databases.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed based on DAVID and KOBA KEGG online websites.The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal(UALCAN)database.In vitro cell proliferation,migration,and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.Results Compared with the normal tissues,tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues(log2FC=4.28,FDR＜0.05).High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival(HR=1.565,95％CI=1.142-2.145,P=0.005).And its overexpression promoted cell proliferation and migration(P＜0.001),and invasion(P=0.009)of A549 cells,and up-regulated COL1A1(P=0.002)and VCAN(P=0.022)significantly in the tRF-19-69M8LOJX overexpression cell model.Conclusion tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues.And its high expression is closely associated with poor prognosis.The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.

Objective To analyze the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP)in a hospital in Hainan Province,explore the differences in the distribution of resistance genes and virulence factors between hypervirulent CRKP(hv-CRKP)and non-hv-CRKP,analyze the clinical significance,and provide basis for optimizing treatment and prevention strategies.Methods CRKP strains isolated from a hospi-tal in Hainan Province from July 2023 to June 2024 were collected retrospectively.Their resistance phenotypes were detected by antimicrobial susceptibility testing.Carbapenemase genes(KPC-2,NDM-1,IPM)and virulence factors(rmpA/rmpA2,iucA,iroB,etc.)were detected by polymerase chain reaction(PCR).Department source,speci-men distribution,and resistance-virulence characteristics were analyzed.Results A total of 76 strains of CRKP were isolated,with an overall isolation rate of 7.7％(76/985).The strains were mainly distributed in the intensive care unit(ICU)(28.9％)and neurosurgery ICU(23.6％),with the highest proportion of strains isolated from re-spiratory tract specimens(60.5％).The resistance genes were mainly KPC-2(72.4％)and NDM-1(21.1％),and the virulence factors mrkD(type Ⅲ pili,85.5％)and fim H(type Ⅰ pili,84.2％)were commonly presented.Among 76 strains of CRKP,39 strains(51.3％)met the criteria for hv-CRKP and all carried KPC-2 gene(100％).The detection rates of resistance genes and virulence factors rmpA2(97.4％),iucA(100％),and iroB(89.7％)were all higher than those of non-hv-CRKP strains(KPC-2,43.2％;rmpA2,0;iucA,8.1％;iroB,13.5％).The main characteristics of hv-CRKP was the combination of KPC-2 resistance gene and rmpA2+iucA+iutA+iroB virulence factors(64.1％).Antimicrobial resistance phenotype of hv-CRKP was different from non-hv-CRKP.hv-CRKP presented higher susceptibility rates to aminoglycosides and compound sulfamethoxazole than non-hv-CRKP.Conclusion The proportion of hv-CRKP and non-hv-CRKP strains in this hospital is comparable.hv-CRKP is characterized by carrying the KPC-2 resistance gene in combination with rmpA2+iucA+iutA+iroB virulence factors,and the proportion of strains carrying multiple virulence factors is higher than that of non-hv-CRKP.Both are generally resistant to β-lactams and quinolones.hv-CRKP has lower resistance rates to aminoglycosides and com-pound sulfamethoxazole than non-hv-CRKP.Its advantage of aminoglycoside susceptibility provides a new treatment option.It is recommended to guide differential medication through molecular typing and strengthen infection control measures in ICU to curb the spread of antimicrobial-resistant bacteria.

Objective:To investigate the differences in dosimetric parameters for target volumes and organs at risk (OARs), radiation doses to reconstructed tissues, and beam-on time in radiotherapy among helical tomotherapy (HT), volumetric modulated arc therapy (VMAT), and fixed-field intensity-modulated radiotherapy (F_IMRT) following immediate breast reconstruction for breast cancer, thereby providing a reference for the selection of clinical radiotherapy techniques.Methods:This study retrospectively investigated 15 breast cancer patients who underwent radiotherapy following modified radical mastectomy and immediate breast reconstruction at the Liuzhou Worker′s Hospital from August 2018 to July 2023. During target volume delineation, precautions were taken to avoid the reconstructed tissues, which were delineated separately. Customized HT, VMAT, and F_IMRT treatment plans were designed for each patient. The plans were categorized into the HT, VMAT, and F_IMRT groups based on different radiotherapy techniques employed. They were comparatively analyzed through one-way analysis of variance (ANOVA), with multiple comparisons further conducted in the case of significant differences.Results:Statistical analyses reveal significant differences in various parameters of target volumes among the three groups of plans ( F = 38.73, 14.95, 37.01, 48.05, 35.55, 22.56, 34.30, P < 0.05). Pairwise comparisons indicate that the maximum dose ( D2%), minimum dose ( D98%), mean dose ( Dmean), and the proportion of high-dose volumes within the target volume ( V107%and V110%) in both the HT and VMAT groups were significantly better than those in the F_IMRT group. The HT group demonstrated the optimal conformity index (CI), while the VMAT group displayed the superior homogeneity index (HI) compared to the other two groups. In terms of OAR, the V20 of the ipsilateral lung was the lowest in the HT group ( F = 14.31, P < 0.05) and the highest in the F_IMRT group ( F = 14.31, P < 0.05). However, the V5 and Dmean for both the ipsilateral and contralateral lungs in the HT group significantly surpassed those of the other groups ( F = 39.16, 31.91, P < 0.05). The mean dose Dmean ( F = 5.57, P < 0.05) of the contralateral breast was significantly reduced in the VMAT group compared to the other two groups. No statistically significant differences were observed for other OARs, including the heart, spinal cord PRV, thyroid, and humeral head ( P > 0.05). The radiation doses to reconstructed tissues ( Dmax, V53.5, Dmean) ascended in the order of HT, VMAT, and F_IMRT groups ( F = 17.69, 17.53, 15.11, P < 0.05). The HT and F_IMRT groups showed similar beam-on times ( P > 0.05), both exceeding that of the VMAT group by several folds ( F = 28.72, P < 0.05). Conclusions:The comparative analysis indicates that the three radiotherapy techniques exhibit distinct advantages and limitations, with F_IMRT demonstrating the least comprehensive advantage. HT can enhance the conformity of target volumes while reducing the overall radiation doses to reconstructed tissues and the crucial indicator V20 in the ipsilateral lung. VMAT demonstrates the highest treatment efficiency, yielding improved dose uniformity in the target volume and reduced radiation doses to the contralateral breast. It is advisable to prioritize HT or VMAT based on actual clinical conditions.