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.

ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.

Background: As Taiwan’s population ages, falls among older adults have become a critical public health concern. However, limited data exist regarding temporal trends and injury patterns in fall-related emergency department (ED) visits. This study aimed to examine trends in fall-related ED visits and hospitalizations among older adults in Taiwan and to explore injury distributions by age group. Methods: We conducted a retrospective cohort study using data from the National Taiwan University Hospital between 2011 and 2017. Patients aged ≥65 years were compared with those aged 20–64 years. Fall-related visits were identified using chief complaints and the International Classification of Diseases 9th/10th revision (ICD-9/ICD-10) codes. Outcomes included hospitalization rates, length of stay, and 30-day mortality. Results: A total of 22,471 fall-related ED visits were analyzed. While visits among younger adults declined (annual growth rate, -1.34%), visits among older adults increased (2.37% annually), with the steepest rise in those aged ≥85 years. Hospitalization occurred in 27.1% of older adults, nearly double that of younger adults (14.4%). Older adults also had longer hospital stays and higher 30-day mortality rates, findings consistent even when restricted to lower limb fractures. Conclusion Fall-related ED visits and hospitalizations are rising disproportionately among Taiwan’s older population. Targeted prevention strategies and transitional care interventions are urgently needed to address the growing clinical and economic burden of falls in aging societies.

The global burden of hepatocellular carcinoma (HCC) has shifted from viral to nonviral etiologies.However, successful antiviral therapy does not fully eliminate the risk of HCC, underscoring the demand for more effective surveillance strategies. Current screening methods, such as semi-annual ultrasonography and the measurement of α-fetoprotein levels, offer suboptimal sensitivityfor early detection. A cost-effective, reliable surveillance approach remains an unmet need. The Barcelona Clinic Liver Cancer staging system provides a framework to guide HCC therapy; yet, some gray zone exists, particularly for patients with intermediate-stage disease. Although tyrosine kinase inhibitors and immunotherapies have transformed the therapeutic landscape, their efficacies vary among patients, highlighting the necessity for personalized treatment strategies.In response to these challenges, artificial intelligence (AI) approaches have emerged as transformative tools in healthcare. By processing complex, nonlinear relationships and uncovering hidden patterns in clinical data, AI methods offer capabilities beyond those of traditional statistical methods. Furthermore, AI-driven multi-omics analysis holds promise for identifying novel biomarkers, thereby advancing precision medicine for HCC patients. This review introduces the potential of AI applications in enhancing the diagnosis, treatment, and prognosis of HCC.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

ObjectiveTo prepare photosensitive nanodiscs loaded with rapamycin and evaluate their in vitro antitumor activity against ovarian cancer. MethodsNanodiscs were prepared by the thin-film hydration method， and their particle size， potential and morphology were characterized by dynamic light scattering and transmission electron microscopy. High performance liquid chromatography was established for the determination of rapamycin content， and the specificity， linearity， precision， repeatability， stability， and recovery rate of the method were verified. The singlet oxygen generation and light-controlled drug release properties of nanodiscs under near-infrared light were evaluated respectively by singlet oxygen detection probe and reverse dialysis method. The cytotoxicity of the nanodiscs against human ovarian cancer cells （OVCAR-8） was evaluated by detecting cell metabolic activity. Confocal microscopy and flow cytometry were used to investigate the cellular uptake and endocytosis mechanisms of the nanodiscs. ResultsThe nanodiscs exhibited a hydrodynamic diameter of （63.66±0.27） nm， a zeta potential of （-18.2 ± 2.4） mV， and demonstrated good stability. The results from transmission electron microscopy revealed that the nanodiscs exhibited spherical and short rod-like morphologies. The peak area of rapamycin showed good linearity in the concentration range of 0.2-40 μg/mL （R²=0.999 9）， and the relative standard deviations of precision， repeatability and recovery were all less than 5%. Under near-infrared light irradiation， the nanodiscs could effectively produce singlet oxygen. At the same time， the singlet oxygen generated could induce lipid membrane oxidation， which significantly promoted the responsive release of rapamycin （P<0.001）. Nanodiscs had no obvious cytotoxicity， but the cytotoxicity to ovarian cancer cells was significantly enhanced after near-infrared irradiation. Cellular uptake experiments confirmed that the nanodiscs mainly entered cells through clathrin-mediated， energy-dependent endocytosis （P<0.001）， with drug release triggered by light exposure. ConclusionRapamycin photosensitive nanodiscs were successfully prepared， which showed significant light-controlled release properties and enhanced anti-ovarian cancer activity in vitro.

Objective:To investigate the dynamic changes of cellular miRNA expression profiles in EBV latently infected Raji cells upon reactivation with Phorbol ester (TPA).Methods:Total RNA was extracted using TRIzol reagent from Raji cells treated with TPA at different time points (0 h, 24 h, 48 h). Small RNA libraries were constructed and sequenced on an Illumina SE50 platform. Differentially expressed miRNAs were identified, and their target genes were predicted and functionally annotated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out through online tools. Additionally, miRanda and RNAhybrid software were used to predict cellular miRNAs targeting the EBV genome. Real-time RT-qPCR was employed to validate the expression levels of differentially expressed novel miRNAs.Results:High-throughput sequencing identified 1 301 celluar miRNAs, comprising 1 189 known and 112 novel miRNAs. A total of 264 known differentially expressed cellular miRNAs and 13 novel miRNAs were identified through high-throughput miRNA sequencing. Secondary structure prediction revealed that the novel miRNAs exhibited typical pre-miRNA hairpin structures. Stem-loop quantitative real-time PCR (RT-qPCR) validation of Novel_miR_183 and Novel_miR_242 did not exhibit a statistically significant difference ( F=1.407, P=0.370 7 for Novel_miR_183; F=1.277, P=0.397 0 for Novel_miR_242) between the TPA-stimulated and untreated groups. Target gene prediction analysis revealed that the differentially expressed cellular miRNAs were involved in various important biological processes and signaling pathways. Furthermore, 1 189 known cellular miRNAs and 108 novel miRNAs were predicted to target the EBV genome. Conclusions:Treatment of Raji cells with TPA stimulation successfully reactivated Raji cells and significantly altered their miRNA expression patterns. Differentially expressed miRNAs were identified, suggesting that these miRNAs probably play crucial roles in regulating EBV infection and replication by directly targeting the EBV genome.

Objective:To evaluate the efficacy of dexmedetomidine-scalp nerve block (SNB) combined with general anesthesia in the patients with acute traumatic brain injury (TBI) undergoing craniotomy.Methods:In this randomized controlled trial, 74 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex with acute TBI, aged 30-78 yr, with body mass index of 18-30 kg/m 2, underwent craniotomy for hematoma evacuation combined with decompressive craniectomy at the Traditional Chinese Medicine Hospital of Kunshan from January to December 2024, of the Glasgow Coma Scale score 8-12, were selected and divided into 2 groups ( n=37 each) using a random number table method: dexmedetomidine combined with ultrasound-guided SNB group (DS group) and ultrasound-guided SNB group (S group). Before anesthesia, dexmedetomidine was infused as a loading dose of 1 μg/kg over 10 min followed by an infusion of 0.3 μg·kg -1·h -1 until the end of operation. Ultrasound-guided SNB was performed after completion of intubation in both groups. The consumption of intraoperative fentanyl, propofol and remifentanil and the usage of vasoactive drugs were recorded. Before surgery (T 0), at 1 h after the start of surgery (T 1) and at the end of surgery (T 2), blood samples from the jugular bulbar and radial artery were collected, the jugular venous oxygen saturation was recorded, the arteriovenous oxygen content and cerebral oxygen uptake rate were calculated, and the occurrence of postoperative complications was also recorded. Results:Compared with group S, the consumption of fentanyl, propofol and remifentanil was significantly reduced, the usage rate of vasoactive drugs was decreased, the arteriovenous oxygen content and cerebral oxygen uptake rate were decreased at T 1 and T 2, the jugular venous oxygen saturation was increased, and the incidence of postoperative agitation was decreased in group DS ( P<0.05). Conclusions:Dexmedetomidine-SNB combined with general anesthesia can optimize the analgesic effect, improve cerebral oxygen supply and demand, reduce the occurrence of postoperative agitation when used in patients with acute TBI undergoing craniotomy.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People