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

Objective To explore the effectiveness of the generative large language model MedGo in nursing decision-making for elderly patients with multimorbidity. Methods A quasi-randomized controlled trial study was conducted involving 6 junior nurses, 6 senior nurses and the MedGo model from January 1, 2025 to March 31, 2025 at the Emergency Internal Medicine Ward of Shanghai East Hospital Affiliated to Tongji University. Clinical data of 120 elderly patients with multimorbidity were analyzed to compare the performance of the three groups in four tasks (nursing diagnosis assessment, nursing intervention formulation, complication identification, and complication prevention) from three evaluation dimensions: decision-making time consumption, decision accuracy, and decision-making quality. Results In terms of decision-making time, the senior nurse group completed all four tasks faster than the junior nurse group (P＜0.01), and the MedGo group completed all four tasks faster than the junior nurse group (P＜0.001) and the senior nurse group (P＜0.001). In terms of decision-making accuracy, senior nurse group scored higher than junior nurse group in all four tasks (P＜0.001), while the MedGo group outperformed the senior nurse group only in complication identification (P＜0.001). In terms of decision-making quality, the MedGo group scored higher than junior nurse group (P＜0.001) and senior nurse group (P＜0.001) in all four tasks. Conclusions The MedGo model demonstrates advantages of high efficiency, accuracy, and quality in nursing decision-making for elderly patients with multimorbidity; senior nurses outperform junior nurses in decision-making, providing diverse references for clinical nursing decision-making.

Objective: To investigate the cross sectional association between bedroom nocturnal light exposure and objectively measured sleep parameters in college students, so as to provide evidence for promoting sleep health. Methods: From September to October 2019, a convenience sampling method was used to recruit 365 healthy college students from two universities in Hefei, establishing a cohort. Bedroom nocturnal light exposure was measured at the individual level for two consecutive days using a portable illuminometer (TES-1339R; Taishi Corp, Taiwan, China). Sleep parameters were objectively measured over seven consecutive days using wrist worn accelerometers (ActiGraph GT3X-BT, Pensacola, FL). Multiple linear regression models were employed to examine the association between nocturnal light exposure and sleep parameters. Results: Compared to the low nocturnal light exposure (<3 lx) group, the high exposure (≥3 lx) group exhibited significantly lower sleep efficiency[(93.5± 2.7 )%,(92.2±2.9)%, t =3.93], longer wake after sleep onset (WASO)[(24.7±90.3)(29.2±11.2)min, t =-3.66], higher movement index(11.0±3.6, 12.2± 3.8, t =-2.80), and higher sleep fragmentation index(20.5±6.5,23.0±7.0, t =-3.24) (all P <0.01). After adjusting for covariates,multiple linear regression showed that,compared to the low nocturnal light exposure group, the high exposure group had reduced sleep efficiency ( β =-1.15, 95% CI =-1.78 to -0.52), increased WASO [ β (95% CI )=3.94(1.55- 6.33 )], higher movement index[ β (95% CI )=1.05(0.20-1.89)], and elevated sleep fragmentation index[ β (95% CI )=2.35(0.81-3.88)](all P <0.05). Conclusions Light exposure at night negatively impacts college students sleep. Optimizing bedroom lighting management may improve sleep quality in adolescents.

Objective: To investigate the impact of intergenerational parent-child separation (PCS) on allergic diseases among rural preschool children, providing theoretical guidance for developing targeted public health interventions. Methods: From March to June 2024, 10 kindergartens were selected from Nanling, Wuhu City, Anhui Province. A total of 2 279 children aged 3-6 years and their parents/primary caregivers participated in the survey by a combination of convenience sampling and cluster sampling method. Children s fathers and mothers reported the experiences of PCS during their childhood. The children s PCS experiences and allergies were reported by their primary caregivers. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to supplement the allergies (allergic asthma, allergic rhinitis and atopic dermatitis). Analysis of variance (ANOVA) and Chi square tests were used to compare differences between children in different PCS groups. Logistic regression models assessed the association between PCS and the risk of allergic diseases in preschool children. Results: Among the preschoolers enrolled, the prevalence of allergic diseases in only parent-child separation group in childhood, only child separation group, and the intergenerational continuity of PCS groups were significantly higher than those of the none separation group (38.0%, 41.8%, 48.1%,30.4%; χ 2=40.45, P < 0.01 ). After adjusting for covariates including child age, sex and body mass index, Logistic regression model revealed that compared to children in the group without PCS, those in the only parent-child separation in childhood( OR =1.43, 95% CI =1.06-1.94), only child separation ( OR =1.82, 95% CI =1.22-2.71), and intergenerational continuity of PCS ( OR =2.33, 95% CI =1.68-3.24) exhibited higher allergic disease risk (all P <0.05). Conclusions Intergenerational continuity of PCS is related to the increased risk of allergies in preschool children. The multigenerational accumulation of adverse effects from PCS underscores the importance of breaking the cycle of disadvantage across generations.

Tooth loss is a common oral problem, and cognitive decline is a primary manifestation of neurodegenerative diseases in the elderly. Both conditions affect their daily living abilities and quality of life. Studies have shown that tooth loss may negatively impact cognitive function through physiological mechanisms such as neural pathways and inflammatory factors, and social, psychological and behavioral factors are identified as important modifiable elements for preventing cognitive decline. This review examined literature about tooth loss and cognitive decline in the elderly, and explored the potential pathways of social, psychological and behavioral factors between these two conditions. The findings indicated that tooth loss may increase the risk of cognitive decline through reduced social participation, social isolation and limited social capital, increased chronic stress, depression and negative aging attitudes, as well as altered physical activity patterns, sleep duration and diets. For the elderly with tooth loss, targeted preventive and intervention measures addressing social, psychological and behavioral aspects can be implemented to prevent and delay cognitive decline, thereby improving their quality of life.

Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Nanoparticles/chemistry* ; Animals ; Nanomedicine/methods* ; Drug Delivery Systems/methods* ; Drug Carriers/chemistry* ; Radiotherapy/methods*

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.