To explore the effects of curcumol on ferroptosis and angiogenesis of hepatic sinusoidal endothelial cells, further elucidate the molecular mechanism of curcumol against liver fibrosis, and provide new ideas for the prevention and treatment of chronic liver disease.

Mitochondrial ribosome biogenesis depends on RNA helicases such as DDX28, a DEAD-box helicase that plays an essential role during early mitoribosome large-subunit assembly by interacting with 16S rRNA. Here, we demonstrate that the helicase core domain of DDX28 binds sequence and structure specifically to the H88_L stem-loop in 16S rRNA, with the RecA2 domain residue M431 as a key determinant for substrate selectivity. The N-terminal disordered region of DDX28 enhances nonspecific RNA binding but does not contribute to enzymatic activity. Furthermore, DDX28 deficiency disrupts mitochondrial translation, impairs OXPHOS complex assembly, and leads to metabolic dysfunction, including reduced membrane potential, elevated ROS, and suppressed glycolysis. Transcriptomic and metabolomic analyses reveal a compensatory upregulation of ribosome biogenesis genes alongside a dysregulation of the TCA cycle, oxidative phosphorylation, and lipid metabolism. Our integrated structural and functional study establishes DDX28 as an essential factor for mitoribosome assembly with potential links to mitochondrial disorders.

Chemically generated singlet oxygen via cycloreversion reaction of aromatic endoperoxides is poised to evolve into a highly promising therapeutic protocol. Singlet oxygen can also be produced endogenically, with a short half-life especially in biological media, and it acts locally, only when a threshold value is exceeded. Conserving the essence of photodynamic therapy, which is the delivery of singlet oxygen to tumors, two limiting issues of light penetration and low tumor oxygenation can be circumvented simultaneously by endoperoxide-delivered singlet oxygen. The endoperoxides are also amenable to derivatization for more specific targeting as well. In this work, pyridone-endoperoxides with mitochondria targeting triphenylphosphonium moieties were shown to target tumors and result in significant tumor suppression. The series of endoperoxides tested also confirms the importance of mitochondria targeting. In mouse tumor models, these compounds show no signs of systemic or organ level toxicity.

Rotator cuff tear (RCT) is a prevalent age-related condition whose underlying mechanisms remain poorly understood. This study employed spatial transcriptomics and multiplex immunofluorescence (mIF) to investigate gene expression and spatial heterogeneity in rotator cuff tissues from elderly RCT patients compared to age-matched controls, aiming to uncover key molecular pathways. Tendon samples were collected from RCT patients (n = 10) and controls (n = 10). Five from each group underwent spatial transcriptomic sequencing for differential gene expression, functional enrichment, and cell interaction analyzes. Results were validated with mIF on the remaining samples. Compared to controls, the RCT group showed 1261 downregulated and 2789 upregulated genes. Spatial analysis revealed distinct expression gradients: COMP and CHI3L1 were upregulated in the bone region, CHI3L1 and MT1X in the mid-tendon, and MT1X and FMOD in the tendon area-confirmed by mIF. Biological processes also varied regionally: cartilage development and extracellular matrix (ECM) organization were enriched in the bone, while ECM and collagen fibril organization dominated mid-tendon and tendon regions. The PI3K-AKT and ECM-receptor interaction pathways were central to these processes. Tenogenic progenitor-like cells (TPLCs) were significantly reduced in RCT (p < 0.0001), whereas mesenchymal cells increased in bone and mid-tendon areas (p < 0.001, p < 0.01), consistent with structural gradients. These findings suggest that elderly RCT may arise from chronic inflammation, ECM dysregulation, and failed regeneration. Spatial transcriptomics identified repair-related genes (COMP, CHI3L1, MT1X, FMOD) with region-specific expression, providing new insights into pathology and potential therapeutic targets.

Programmed death-1 (PD-1) and its ligand PD-L1 play critical roles in immune checkpoint regulation. This study investigated the relationship between PD-1 and PD-L1 expression on peripheral blood lymphocytes and Non- Hodgkin Lymphoma progression.

Cerebral ischemia reperfusion injury (CIRI) poses a significant clinical and economic burden worldwide. Therefore, it is essential to identify key regulators that may improve stroke prognosis. Cystatin B (CSTB) is known to be involved in neuroprotection, inflammation modulation, and apoptosis regulation, but its specific function and mechanisms in CIRI remain unclear.

BACKGROUND: University students are at a critical stage of professional socialization, where intense competition in the job market exposes them to considerable employment challenges and pressure. These factors often lead to negative expectations regarding future career prospects and contribute to the development of employment anxiety. This study aimed to investigate the relationship between outdoor sports education and employment anxiety using a combined longitudinal and cross-sectional design. Specifically, the research examined both the long-term effects and immediate associations of this relationship, as well as the potential mediating roles of self-management and fear of failure. METHODS: A total of eight classes were selected and randomly allocated to either an intervention group (four classes) or a control group (four classes). The intervention group participated in a structured outdoor sports education program, while the control group engaged in conventional physical activities (e.g., basketball, aerobics). Employment anxiety was measured using the Future Employment Anxiety Scale, self-management was assessed with the Self-Management Questionnaire, and fear of failure was measured using the Performance Failure Appraisal Inventory. Data were analyzed using independent-samples t-tests, descriptive statistics, correlation analysis, and mediation analysis. Mediation effects were examined through Baron and Kenny’s causal steps approach, supplemented by 5,000 bootstrap iterations to assess the statistical significance of indirect effects. RESULTS: Following the intervention, students in the intervention group showed significantly lower levels of anxiety in the domains of Personal Ability, Career Replaceability, and Social Relations compared to the control group (p < .05). Conversely, they exhibited significantly higher scores across all four dimensions of self-management: Behavior Management, Emotion Management, Time Management, and Cognition Management (p < .05). Furthermore, the intervention group reported significantly lower scores on three dimensions of fear of failure—Fear of Experiencing Embarrassment, Fear of Devaluation by Others, and Fear of Others Losing Interest (p < .05). Regarding effect decomposition, outdoor sports education accounted for 28.1% of the total effect, reflecting a significant direct predictive role on employment anxiety. The indirect effect mediated by self-management contributed 26.3%, while that mediated by fear of failure explained 33.3% of the total effect. Additionally, the chain-mediated pathway involving both self-management and fear of failure accounted for 12.3% of the total effect. CONCLUSIONS: Outdoor sports education was associated with lower employment anxiety, enhanced self-management competencies, and reduced fear of failure among university students. Both self-management and fear of failure function as independent mediating factors in the link between outdoor sports education and employment anxiety. Furthermore, these two variables operate sequentially in a chain-mediation pathway, jointly accounting for a meaningful proportion of the overall effect. TRIAL REGISTRATION: ISRCTN Registry (ISRCTN14022322). Registered on 30 March 2026. Retrospectively registered.

Spotted steed (Hemibarbus maculatus Bleeker, 1871), a small and medium-sized benthic fish, is widely distributed between the Yangtze and Heilongjiang River basins and is considered to be one of the most widely distributed freshwater fish in East Asia. It is also an economically valuable aquaculture fish and has become a commercial freshwater aquaculture species in China. Here, a high-quality chromosome-level genome of spotted steed was produced by combining PacBio single molecule sequencing technique and high-throughput chromosome conformation capture technologies. Ultimately, the genome was assembled into 1098.66 Mb with a contig N50 of 33.57 Mb and a scaffold N50 of 40.40 Mb. We constructed a chromosome-level genome assembled with 25 chromosomes, whose total lengths accounted for 97.49%, and the assembled genome represents 95.64% completeness (BUSCO). We also identified 285.16 Mb (25.96%) of repetitive genome sequences and 23233 predicted genes. A total of 23021 genes were functionally annotated, representing 99.09% of the predicted genes. These results will provide valuable genomic resources for subsequent study of the genetic, evolutionary, and biological characteristics of spotted steed.

The fruit of Aronia melanocarpa (Michx.) Elliott is a berry with multiple properties and was included as a new raw food material by the National Health Commission of China (NHC) in September 2018. This study focused on the immune regulatory properties and underlying mechanism of polysaccharides extracted from Aronia melanocarpa fruit (AMFP) by undertaking an integrated analysis of multiple endogenous metabolic pathways. An improvement in AMFP in immunosuppressed model mice at three levels of immune organs, immune cells, and immune factors was determined. The immunomodulatory role of AMFP was assessed through measurement of metabolomic and lipidomic profilings by UPLC-Q-TOF/MS. A total of 53 differential endogenous metabolites in the urinary, serum, and lipid metabolomics were identified, followed by KEGG pathway enrichment. Furthermore, the underlying mechanisms were elucidated by an integrated analysis of multiple metabolomics and lipidomics. Primarily, we found regulation of immune-related metabolic pathways, including nicotinate and nicotinamide metabolism, sphingolipid metabolism, glycerophospholipid metabolism, purine metabolism, steroid hormone biosynthesis, and arachidonic acid metabolism. The results also demonstrated the mutual validation of key pathways and mechanisms. AMFP potentiated both humoral and cellular immunity responses and protected the immune system from oxidative damage. This research provides a reference and a basis for the development and application of AMFP in the field of health foods that regulate immunity.

Adult survivors of childhood cancer are at risk for neurocognitive impairment, emotional distress, and chronic pain, factors independently associated with substance use. However, interrelationships among these factors and their association with substance use remain poorly understood.

Acute pancreatitis (AP) is a common gastrointestinal condition characterized by inflammation of the pancreas. AP treatment is highly challenging due to the long hospital stays, higher medical expenses, and multiple complications. Traditional Chinese medicine has been used in China for thousands of years and is clinically proven to be a safe and effective treatment strategy for pancreatitis.

Vascular calcification, a common complication of metabolic diseases such as diabetes and obesity, is closely associated with chronic inflammation and contributes to cardiovascular morbidity. The adipokine visfatin, which is secreted by visceral fat, is a proinflammatory mediator linked to metabolic dysfunction. In this study, we investigated its role in vascular calcification. A murine model was established by vitamin D injection. Serum visfatin levels were significantly elevated in patients with higher coronary artery calcification scores and in calcified mice, accompanied by increased visfatin expression in visceral fat. Adipose tissue-specific overexpression of visfatin further exacerbated vitamin D-induced vascular calcification. In cultured vascular smooth muscle cells (VSMCs), visfatin increased osteogenic differentiation under calcification conditions. Mechanistically, visfatin directly bound to TLR4 to promote osteogenic transformation of VSMCs, whereas TLR4 knockout markedly attenuated visfatin- and calcification medium-induced aortic calcification both in vivo and in vitro. Furthermore, the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin alleviated vascular calcification and reduced serum visfatin levels in mice. Mechanistically, empagliflozin suppressed p38/NF-κB activation, inhibited NF-κB nuclear translocation, and reduced NF-κB binding to the visfatin promoter, thereby decreasing visfatin expression in adipocytes. Collectively, these findings identify visfatin as a proinflammatory adipose-derived regulator of vascular calcification via TLR4 and a potential therapeutic target for vascular calcification and related cardiovascular disorders.

Inflammatory bowel disease (IBD) is a chronic intestinal disorder with recurrent inflammation for which effective therapeutic options remain limited. Probiotics from the Bifidobacterium genus have potential beneficial effects on the prevention of IBD by improving intestinal barrier integrity and modulating immune responses. However, whether these effects are mediated by the regulation of gut metabolism remains largely unclear. This study was designed to explore the protective effect of an infant-derived Bifidobacterium animalis subsp. lactis 832 (B. lactis 832) on dextran sulfate sodium (DSS)-induced colitis in mice and its underlying mechanism. B. lactis 832 treatment significantly alleviated colitis severity (p < 0.05), as evidenced by reduced weight loss, disease activity index (DAI), and colonic injury, accompanied by significantly decreased pro-inflammatory cytokine expression and increased Il10 expression (p < 0.05). It also improved intestinal barrier integrity and modulated gut microbiota composition by reducing potentially pathogenic bacteria while enriching beneficial taxa. Surprisingly, metabolomic analysis revealed that B. lactis 832 intervention enhanced intestinal phospholipid metabolism, particularly increasing phosphatidylethanolamine (PE) and phosphatidylcholine (PC) levels. Notably, PE or PC supplementation recapitulated the protective effects against DSS-induced colitis (p < 0.05). These findings suggest that B. lactis 832 alleviates colitis through microbiota-associated metabolic regulation, highlighting a key role for phospholipid metabolism in mediating probiotic effects.

Patients with osteoporosis often lack optimal bone conditions necessary for successful dental implant osseointegration. Consequently, research has focused on improving peri-implant bone regeneration in compromised bone environments. Our previous findings demonstrated that ephrinB2-gene-modified dental stem cells enhanced osteogenic potential and promoted angiogenesis in umbilical vein endothelial cells within a co-culture system. Furthermore, the extracellular matrix (ECM) from these endothelial cells promoted the differentiation of odontogenic stem cells into endothelial cells. Based on these results, we proposed amplifying the biological effects of ephrinB2 to enhance synergistic cell-to-cell and cell-to-matrix interactions within the bone microenvironment. For this purpose, three-dimensional (3D) cell sheets were developed using ephrinB2-overexpressing canine periodontal ligament stem cells (cPDLSCs) co-cultured with endothelial progenitor cells (EPCs). The resulting ephrinB2-cPDLSCs/EPCs 3D cell sheet constructs were placed around dental implants before transplantation into osteoporotic canine mandibles. The impact of this intervention was rigorously evaluated by assessing bone formation and vascular regeneration around the implants. This study provides a solid experimental and theoretical foundation for enhancing dental implant therapies in osteoporotic patients.

Diabetic ulcers, a serious complication associated with diabetes, present a significant therapeutic challenge due to their recurrent and persistent chronic inflammation. A crucial factor contributing to this sustained inflammation is mast cell degranulation. This study examined the effects of the traditional Chinese herbal formula Zizhu ointment (ZZO) on mast cell degranulation in diabetic ulcers, as well as its underlying mechanisms in promoting wound healing. Analysis of clinical specimens revealed that ZZO significantly inhibited mast cell degranulation in diabetic ulcer wounds. In a diabetic mouse wound model, ZZO was observed to suppress mast cell degranulation, decrease the expression of TNF-α and MMP-9, and facilitate wound healing. Cellular experiments demonstrated that ZZO inhibited IgE/DNP cross-linking-mediated degranulation, calcium (Ca2+) influx, and the release of β-hexosaminidase, histamine (HIS), and TNF-α in both human HMC-1 and murine P815 mast cells. Furthermore, ZZO was found to block the IgE/DNP cross-linking-mediated activation of FcεRI-proximal signaling pathways (LYN/SYK/PLCγ) and inflammatory cascades (IKK/NFκB and MAPKs). We hypothesize that ZZO facilitates the healing of diabetic ulcers by stabilizing mast cells and inhibiting their degranulation, thereby reducing the release of inflammatory mediators and promoting wound repair.

Prunus subgenus Cerasus contains numerous species with ornamental, edible, and medicinal value. However, limited genomic resources have constrained systematic analyses of structural variation and the genetic basis of key phenological traits in this group. Here, we assemble eight genomes from diverse Cerasus species. Together with 13 published genomes, we construct a pangenome of 21 accessions representing 17 species. Phenological observations reveal substantial variation in flowering time. Integrating comparative genomics, transcriptomics, and population genetic analyses highlight candidate regulators of flowering time. We find that AGAMOUS-LIKE 9 (AGL9) is strongly associated with flowering progression. Both ectopic expression and transient overexpression of PavAGL9 can accelerate post-dormancy flowering progression. We reveal that PavBPC6 binds the PavAGL9 promoter and represses its transcription, indicating a negative regulatory role. Furthermore, PavAGL9 interacts physically with PavSEP1 and PavPMADS2, suggesting synergistic roles in floral organ development. Our pangenome resource establishes a comprehensive genomic framework for Cerasus and provides insights into the regulation of flowering progression.

Repression of DNA damage repair by PARP inhibitors (PARPi) has shown great efficacy in cancer treatment. However, therapy resistance remains a significant clinical challenge.

The formation of foam cells (FCs) is the major contributor to the development of atherosclerosis (AS). Gynostemma pentaphyllum is widely used to treat AS and exhibits biological activity against FCs formation. Narcissoside (Nar) is an important component from G. pentaphyllum flavonoids. This study aimed to reveal the beneficial effect and underlying mechanism of Nar on inhibiting the formation of FCs in AS.

Cuproptosis, a copper-dependent cell death process induced by excessive copper, represents an emerging therapeutic strategy in oncology. However, tumor-specific molecular pathways regulating this process remain poorly defined. Here, we demonstrate that copper levels are elevated in lung adenocarcinoma (LUAD), and LUAD cell lines exhibit increased resistance to cuproptosis. Mechanistically, elevated copper stress promotes the expression of the desuccinylase SIRT5 while reducing global succinylation in LUAD cells. Furthermore, we found that SIRT5 is a critical mediator of cuproptosis through the desuccinylation modification on ferredoxin1 (FDX1) protein at Lys84. This modification triggers TRIM8-mediated ubiquitination, leading to FDX1 proteasomal degradation and enhanced cuproptosis resistance. These results reveal the important role of SIRT5 in LUAD cuproptosis resistance. Notably, combining the SIRT5 inhibitor MC3482 with the cuproptosis inducer Elesclomol-Cu synergistically suppresses tumor growth in vivo, suggesting a promising therapeutic strategy. These findings elucidate mechanisms underlying cuproptosis resistance and propose a novel treatment approach for LUAD.

The rumen epithelium of Tibetan sheep plays a critical role in energy metabolism and immune defense; however, its post-transcriptional regulatory mechanisms under high-altitude hypoxia stress remain unclear. In this study, we employed integrated mRNA and miRNA transcriptome sequencing to analyze the adaptive strategies of the rumen epithelium in Tibetan sheep at different altitudes. A total of 2183 differentially expressed genes (DEGs) and 135 differentially expressed miRNAs (DEmiRNAs) were identified. Functional enrichment analysis revealed that DEGs and their target genes were significantly enriched in immune-related pathways such as the NF-κB signaling pathway and cytokine-cytokine receptor interaction, as well as metabolic pathways including oxidative phosphorylation and branched-chain amino acid degradation. Integrated network analysis highlighted key regulatory pairs, including oar-miR-370-3p targeting PCK2 and IL1R2, and novel-miR-781 regulating PIK3R5, suggesting coordinated modulation between mitochondrial homeostasis and immune responses. Specifically, the upregulation of immune genes (CCL19, MADCAM1) and heat shock proteins at TS4500m indicates enhanced mucosal immunity and stress tolerance, while altered expression of metabolic genes reflects a shift in energy substrate utilization. These findings elucidate a complex mRNA-miRNA regulatory network that enables Tibetan sheep to maintain rumen epithelial integrity and energy balance under extreme high-altitude conditions, providing novel insights into the molecular basis of hypoxia adaptation in ruminants.