The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP₆), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP₆-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective To explore the mechanism by which electroacupuncture improves ocular surface inflammation in dry eye mice.Methods 30 SPF-grade healthy male ICR mice were randomly divided into a blank group,a model group,a sham electroacupuncture group,a western medicine group and an electroacupuncture group,with 6 mice in each group.Mice in the blank group and other four groups were subcutaneously injected 200 μL of sterile physiological saline and 200 μL of scopolamine hydrobromide(0.5 mg dissolved in 0.2 mL of sterile physiological saline)at 8:00,11:00,14:00,and 17:00 every day for 35 consecutive days,respectively.From the 22nd day,mice in the sham electroacupunc-ture group were given blunt scalp acupuncture intervention at bilateral Jingming and Taiyang points,without subcutaneous penetration.In the western medicine group,fluorometholone eye drops were applied to both eyes of the mice at 8:00,13:00,and 18:00 daily,with 1 drop each time.Mice in the electroacupuncture group were given electroacupuncture in-tervention,with the same acupoint location and acupuncture time as the sham electroacupuncture group.The electroacu-puncture frequency was 2 Hz/20 Hz,the waves were sparse-dense and the intensity was 1 mA,once a day for 15 min.All groups were intervened for 14 days.The corneal fluorescein(FL)staining scores of mice in each group were detected be-fore modeling,after modeling,and after intervention.The corneal tissue morphology was observed under a light micro-scope.Immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR)were used to detect the protein and mRNA expression of high mobility group box 1(HMGB1)and receptor for advanced glyca-tion end products(RAGE)in the cornea,respectively.Results The FL scores of mice in model,sham electroacupunc-ture,western medicine,and electroacupuncture groups all significantly increased after modeling and intervention,com-pared with those before modeling(all P＜0.01).The FL scores of mice in electroacupuncture and western medicine groups significantly decreased after intervention,compared with those after modeling(both P＜0.01).Compared with the model group,electroacupuncture and western medicine groups showed a significant drop in FL score after intervention(both P＜0.01).HE staining showed that after intervention,mice in electroacupuncture and western medicine groups had a basically normal number of corneal epithelial layers,no obvious shedding of epithelial cells,and neatly arranged and slightly swollen collagen fibers in the stromal layer.The relative protein expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(allP＜0.01).The rela-tive protein expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).Conclusion Electroacupuncture mitigates corneal epithelial injury,reduces the expression of HMGB1 in the cor-neal tissue,inhibits the binding of HMGB1 and RAGE,and ultimately alleviates ocular surface inflammation responses of dry eye mice.

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective To explore the mechanism by which electroacupuncture improves ocular surface inflammation in dry eye mice.Methods 30 SPF-grade healthy male ICR mice were randomly divided into a blank group,a model group,a sham electroacupuncture group,a western medicine group and an electroacupuncture group,with 6 mice in each group.Mice in the blank group and other four groups were subcutaneously injected 200 μL of sterile physiological saline and 200 μL of scopolamine hydrobromide(0.5 mg dissolved in 0.2 mL of sterile physiological saline)at 8:00,11:00,14:00,and 17:00 every day for 35 consecutive days,respectively.From the 22nd day,mice in the sham electroacupunc-ture group were given blunt scalp acupuncture intervention at bilateral Jingming and Taiyang points,without subcutaneous penetration.In the western medicine group,fluorometholone eye drops were applied to both eyes of the mice at 8:00,13:00,and 18:00 daily,with 1 drop each time.Mice in the electroacupuncture group were given electroacupuncture in-tervention,with the same acupoint location and acupuncture time as the sham electroacupuncture group.The electroacu-puncture frequency was 2 Hz/20 Hz,the waves were sparse-dense and the intensity was 1 mA,once a day for 15 min.All groups were intervened for 14 days.The corneal fluorescein(FL)staining scores of mice in each group were detected be-fore modeling,after modeling,and after intervention.The corneal tissue morphology was observed under a light micro-scope.Immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR)were used to detect the protein and mRNA expression of high mobility group box 1(HMGB1)and receptor for advanced glyca-tion end products(RAGE)in the cornea,respectively.Results The FL scores of mice in model,sham electroacupunc-ture,western medicine,and electroacupuncture groups all significantly increased after modeling and intervention,com-pared with those before modeling(all P＜0.01).The FL scores of mice in electroacupuncture and western medicine groups significantly decreased after intervention,compared with those after modeling(both P＜0.01).Compared with the model group,electroacupuncture and western medicine groups showed a significant drop in FL score after intervention(both P＜0.01).HE staining showed that after intervention,mice in electroacupuncture and western medicine groups had a basically normal number of corneal epithelial layers,no obvious shedding of epithelial cells,and neatly arranged and slightly swollen collagen fibers in the stromal layer.The relative protein expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(allP＜0.01).The rela-tive protein expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).Conclusion Electroacupuncture mitigates corneal epithelial injury,reduces the expression of HMGB1 in the cor-neal tissue,inhibits the binding of HMGB1 and RAGE,and ultimately alleviates ocular surface inflammation responses of dry eye mice.

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

Objective To define the conceptual connotation of network dynamic collaboration capacity in medical surge response and construct its theoretical model.Methods A mixed concept analysis method was employed,integrating multidisciplinary literature and collecting empirical evidence through semi-structured expert interviews to extract the concept of network dynamic collaboration capacity in medical surge response.By integrating complex systems,network science,synergetics,and dynamic capability theory,and combining the interview results,the study used the analogy of flood control in hydraulic engineering to develop a"network-dynamic-collaboration"triangular capacity theoretical model.Results It reveals one antecedents(sudden external shocks have led to an abnormal and continuous surge in medical demand),six core attributes(information interconnection accessibility,dynamic resource adaptability,risk perception responsiveness,multi-party collaborative interactivity,service process adaptability elasticity,and learning iterative evolution),and four consequences(mitigation of crowding risk,protection of service continuity,minimization of crisis spillover,and enhancement of system resilience)for the network dynamic collaboration capacity in medical surge response.The theoretical model elucidates the coupling mechanisms among network structural resilience,dynamic regulation processes,and collaborative co-evolution in resisting medical surge.Conclusion The new concept and theoretical model proposed in this study deepen the understanding of medical surge response system mechanisms and offer a theoretical framework and practical guidance for strengthening the full-chain resilience of health emergency systems.

Objective To empirically analyze multiple pathways for enhancing medical surge response capacity and provide useful references for improving the resilience of health systems.Methods A comprehensive theoretical analysis framework for improving medical surge response capacity was constructed based on the 4S theory and collaborative governance theory.68 interview texts on medical surge response capacity conducted in July 2024 were selected as analysis samples.Using fuzzy-set Qualitative Comparative Analysis(fsQCA),7 conditional variables were selected from four dimensions:management system,information system,materials,and personnel to analyze their impact on medical surge response capacity.Results(1)A single conditional variable does not constitute a necessary condition for improving medical surge response capacity;(2)After the combination of conditions,8 specific configuration paths for capacity improvement were identified.Through systematic and comprehensive refinement,they were summarized into three modes of comprehensive configuration capacity improvement paths,namely:rapid response and collaborative operation mode,information empowerment and precise response mode,and resource conditions and resilience construction mode.Conclusion It is necessary to explore and construct systematic,combined,modularized and path-oriented capacity building strategies,refine the operational implementation paths for improving China's medical surge response capacity,target the linkage and configuration modes of different conditional variables,promote the formulation and implementation of modular construction schemes oriented by key capacity,and make efforts from multiple aspects to enhance the resilience of the health system.