Text abstracts Lipid homeostasis is essential for organismal physiology, and its disruption contributes to metabolic disorders. Using an unbiased genetic modifier screen in Drosophila , we identified GAR1, a core component of the box H/ACA small nucleolar ribonucleoprotein complex, as a pivotal regulator of systemic lipid storage. We show that the H/ACA snoRNP complex is essential for maintaining lipid droplet morphology in adipose tissue and preventing ectopic fat accumulation. Moreover, null mutants of Gar1 or Dkc1 exhibit severe developmental defects, including reduced body size and larval lethality. RNA-seq analysis revealed that Gar1 dysfunction triggered widespread alternative splicing defects, specifically targeting key transcripts within the insulin signaling cascade, including chico , Pi3K92E , sgg , and Lip4 . Furthermore, knockdown of Gar1 impaired insulin signaling, as evidenced by the reduced membrane localization of the tGPH fluorescence. Genetic epistasis further positions GAR1 upstream of the lin-28 / foxo axis, as knocking down lin-28 or foxo fully rescues the lipometabolic defects in GAR1-deficient animals. These findings reveal a previously unrecognized link between the snoRNP machinery and metabolic process, establishing the box H/ACA complex as an important coordinator that integrates RNA processing with insulin-mediated nutrient sensing to ensure developmental and lipid homeostasis. Article summary Lipid metabolism is tightly controlled by multiple factors. To find new regulators, the authors performed a genetic screen and identified a small nucleolar protein GAR1 participate in fat storage and larval development. They demonstrated a critical role of box H/ACA snoRNP complex in modulating alternative splicing and balancing insulin cascade. Blocking two insulin-related genes reversed the lipid defects caused by Gar1 loss. These findings revealed the box H/ACA complex integrates RNA processing with insulin-mediated nutrient sensing to ensure developmental and lipid homeostasis, offering a perspective for understanding the metabolic regulation network.

The RXFP2 gene is a key regulator of horn morphology in sheep (Ovis aries Linnaeus), with a 1.78-kb insertion in its 3'-untranslated region (UTR) previously linked to the polled phenotype. However, horned individuals homozygous for this insertion (1.78 kb+/+) have been observed in typically polled breeds such as Hu sheep, suggesting additional regulatory mechanisms. In this study, a significant horn-associated quantitative trait locus (QTL) on chromosome 10 was identified through genome-wide association analysis which was consistent with a previous study. We found that the 1.78-kb insertion in the 3'-UTR of RXFP2 is associated with horn status across sheep breeds, and that elevated RXFP2 expression correlates with horn development even in 1.78 kb+/+ individuals, as revealed by expression analyses in multiple breeds. RNA-seq and hormonal profiling further demonstrated that the INSL3/RXFP2 signaling axis, particularly its interactions with hormones such as testosterone, plays a central role in horn morphogenesis. These results indicate that horn development is modulated not only by structural variations in RXFP2, but also through its transcriptional and hormonal regulation, providing new insights into the polygenic basis of horn formation and informing breeding strategies for polled sheep.

Objectives:To investigate the effects of nutritional risk stratification management on relapse control and quality of life (QoL) in patients with Inflammatory Bowel Disease (IBD), and to evaluate the clinical value of systematic nutritional intervention in the comprehensive management of IBD. Methods:This single-center retrospective cohort study analyzed 752 IBD patients (408 with ulcerative colitis and 344 with Crohn's disease) who were managed in the Department of Gastroenterology at the Affiliated Hospital of Nantong University between January 2024 and December 2024. Patients were classified into an intervention group if they were managed under an institutional nutritional risk stratification pathway, which included dietitian-led screening with NRS-2002 or MUST and individualized nutrition plans with scheduled reassessment. Patients who received conventional care without entering this structured pathway served as the comparison group. All data, including nutritional status, inflammatory markers, disease activity, relapse events, hospitalization outcomes, and quality of life (IBDQ), were obtained retrospectively from electronic medical records and follow-up databases. Time-to-relapse was analyzed with Cox regression, and changes in continuous outcomes were evaluated using linear mixed-effects models. Propensity score matching and inverse probability of treatment weighting were used to mitigate measured confounding. Results:In this observational analysis, significant improvements from baseline were observed in the intervention group for body weight, BMI, and laboratory nutritional indicators (all p < 0.001). Increases in albumin and prealbumin showed a significant negative correlation with the decrease in inflammatory markers (r = -0.42, p < 0.001). The median CRP level decreased from 15.2 to 9.6 mg/L (p < 0.001), and fecal calprotectin decreased from 298 to 184 μg/g (p < 0.001). Disease activity scores (HBI and Mayo) significantly decreased in both CD and UC patients (all p < 0.001). After a median follow-up of 9.8 months, the relapse rate was significantly lower in the intervention group (20.5%) compared to the control group (34.8%) (p < 0.001). Cox regression analysis indicated that nutritional management was independently associated with a reduced risk of relapse (adjusted HR = 0.61, 95% CI: 0.46-0.83, p = 0.001). Furthermore, the intervention group had significantly lower hospitalization rates (12.7% vs. 20.9%, p = 0.009) and shorter hospital stays (6 days vs. 8 days, p = 0.015). Regarding QoL, the total IBDQ score increased significantly in the intervention group (Δ = +13.5, p < 0.001), and the significant time × group interaction (p < 0.001) suggested sustained, cumulative improvement. Subgroup and sensitivity analyses yielded consistent results, supporting the robustness of this association (IPTW HR = 0.59, 95% CI: 0.44-0.81, p = 0.001). Conclusion:In this single-center retrospective cohort, exposure to nutritional risk stratification management was associated with better nutritional status, lower inflammatory markers and disease activity, reduced relapse and hospitalization rates, and improved quality of life in IBD patients. These findings support the hypothesis that integrating structured nutritional risk screening and individualized nutrition management into routine IBD care may be beneficial. However, given the observational design and potential residual confounding, the observed associations should not be interpreted as definitive causal effects, and prospective multicenter randomized studies are needed to confirm these results and guide clinical practice.

Background Osteoporosis is a common metabolic bone disease characterized by an imbalance in bone remodeling, which leads to elevated bone resorption due to enhanced osteoclastic activity. Current anti-resorptive therapies are limited by adverse effects and suboptimal efficacy. Coixol, a natural compound derived from the traditional edible plant Coix lacryma-jobi L., exhibits anti-inflammatory properties. However, its role in osteoporosis remains unclear. Methods The effects of coixol on osteoclast formation and function during receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis were examined in bone marrow-derived macrophages. Differentiation was evaluated using tartrate-resistant acid phosphatase staining and F-actin ring formation assays, whereas bone resorption activity was quantified using pit formation assays. The expression levels of osteoclast-associated markers (NFATc1, CTSK, and MMP9) and hypoxia-inducible factor 1-alpha (HIF-1α) were assessed using reverse transcription quantitative real-time polymerase chain reaction and western blot assays. In vivo efficacy in an ovariectomized mouse model was determined using micro-computed tomography and histomorphometric analyses. Results Coixol dose-dependently inhibited osteoclast differentiation, disrupted F-actin ring formation, and decreased bone resorption activity, and these activities were accompanied by the downregulation of key osteoclastogenic genes and proteins. Under normoxic conditions, coixol increased HIF-1α protein levels. In ovariectomized mice, coixol significantly attenuated bone loss, improved trabecular bone microstructure, and suppressed osteoclast activity. Conclusion Coixol likely inhibits osteoclast formation and bone resorption in vitro and in vivo by activating HIF-1α and suppressing nuclear factor-kappa B pathway signaling. These findings suggest that coixol, acting through an HIF-1α-mediated mechanism, could be a potential natural therapeutic agent for osteoporosis.

Specialised skeletal blood-vessel subtypes have established the importance of angiogenesis-osteogenesis coupling in bone development, homeostasis and repair. Emerging evidence further indicates that bone-associated lymphatics contribute to interstitial fluid drainage, immune trafficking, inflammatory resolution, damage-associated molecular pattern clearance and regenerative signalling. However, how vascular and lymphatic compartments are coordinated in the skeletal microenvironment remains incompletely defined.In this review, we propose an evidence-graded working model of skeletal vascular-lymphatic dual circulation. We distinguish established observations from logical extensions and author-proposed analytical constructs. Current evidence is organised into shared upstream cues, blood-vessel-biased programmes, lymphatic identity and functional programmes, proposed coupling interfaces, and disease-integration modules. We discuss their context-dependent relevance across osteoporosis, glucocorticoid-associated skeletal injury, osteoarthritis, rheumatoid arthritis, bone metastasis, Gorham-Stout disease and heterotopic ossification.Finally, we evaluate therapeutic directions aimed at restoring pro-osteogenic vascular competence, lymphatic drainage and clearance, and vascular-lymphatic-immune coordination. This framework is intended to organise current evidence, define knowledge gaps and guide future validation rather than to assert a validated disease taxonomy or clinical stratification system. The translational potential of this article:This review offers an evidence-graded translational framework for skeletal repair and bone disease by integrating vascular niche competence, lymphatic drainage and clearance, osteoimmune regulation, and stromal repair. It highlights functional endpoints, including perfusion quality, lymphatic transport, inflammatory resolution, pathological osteoclastogenesis, and repair quality, that may improve preclinical study design and therapeutic evaluation. Vascular-skewed and lymphatic-skewed features are used as heuristic descriptors rather than diagnostic categories. After validation of skeletal vascular-lymphatic biomarkers, imaging tools, and functional endpoints, this framework may inform future stratification and network-informed combination therapy.

Background:Osteoporosis (OP) is a systemic disease featured by reduced bone mass, deteriorated microstructure and elevated fracture risk. Traditional therapies mainly target direct regulators of bone remodeling. Emerging evidence suggests a critical crosstalk between the skeletal and nervous systems. Traumatic brain injury (TBI) markedly accelerates fracture healing, which holds great potential for OP treatment, yet the underlying mechanism remains unclear. Methods:A mouse TBI plus femoral fracture model was established. Micro-CT, histomorphometry and transcriptome sequencing were performed. In vitro studies included qPCR, Western blot, ALP/Alizarin Red staining, co-culture, ELISA and tube formation assays. Ovariectomized (OVX) mice received tail vein injection of Gfrα2 overexpression plasmid or siRNA for in vivo validation. Results:TBI significantly accelerated fracture healing with elevated GFRα2 in callus BMSCs. GFRα2 promoted BMSC osteogenesis by maintaining iron homeostasis via Ferritin Heavy Chain 1 (FTH1) and enhanced angiogenesis by increasing VEGFD secretion. In OVX mice, GFRα2 overexpression markedly improved bone mineral density, trabecular microstructure, bone formation rate and intraosseous angiogenesis. Conclusions:GFRα2 serves as a key hub linking TBI to accelerated bone formation via dual effects on osteogenesis and angiogenesis. Targeting GFRα2 represents a promising therapeutic strategy against osteoporosis. The translational potential of this article:This study identifis GFRα2 as a key mediator linking traumatic brain injury-accelerated bone formation to osteogenesis and angiogenesis. Targeting GFRα2 effectively ameliorates bone loss in osteoporotic mice by restoring both bone formation and intraosseous vascularization. These findings establish a novel neuro-osteogenic regulatory axis and provide a promising molecular target for developing new therapeutic strategies to treat osteoporosis and improve fracture healing in clinical practice.

Metabolic reprogramming is a hallmark feature of malignant tumors. These metabolic pathways are regulated in a cell‑autonomous manner by oncogenic signaling and transcriptional networks, and tracking their metabolic reprogramming is frequently used in the diagnosis, detection and treatment of cancer. There are currently promising therapeutic prospects for a variety of types targeting fixed core metabolic pathways in tumor metabolic reprogramming. Among these, inosine monophosphate (IMP) is an essential intermediate in purine nucleotide synthesis that demonstrates significant target potential. Nevertheless, further research is needed to elucidate the regulatory networks that control IMP metabolism in tumor cells. This review combines the latest insights into IMP metabolism into an interesting conceptual framework. This includes the supply of IMP precursor substrates (reprogramming of glucose metabolism, serine/one‑carbon metabolism, glutamine and mitochondrial metabolism), the dynamic regulation of important enzymes [phosphoribosyl pyrophosphate synthetase, phosphoribosyl pyrophosphate amidotransferase, IMP dehydrogenase (IMPDH)], purinosomes and signaling pathways (RAS‑ERK, PI3K/AKT‑mTORC1 and Hippo‑YAP) that ultimately regulate IMP synthesis in tumor cells. Additionally, it focused on downstream associations between IMPDH and the immune microenvironment, offering a fresh perspective for current research on tumor therapy targeting IMP metabolism.

Rheumatoid arthritis (RA) is an inflammatory, systematic and articular autoimmune disease characterized by progressive cartilage degradation and bone erosion, leading to irreversible joint deformity. Fibroblast growth factor receptor 1 (FGFR1) is a key mediator of RA‑associated bone loss. Within inflamed joints, FGFR1 expression is markedly upregulated in synovial fibroblasts, osteoclasts and chondrocytes. Ligand engagement drives receptor dimerization and kinase activation, activating PI3K/Akt, MAPK and STAT signaling cascades that amplify cytokine release, matrix metalloproteinase expression and osteoclastogenesis. These converging signals promote cartilage degradation and cortical bone erosion, fueling progressive deformity. Targeting FGFR1 markedly attenuates bone loss and disease severity in both murine and humanized models. The present review aimed to summarize the potential of FGFR1 as a tractable therapeutic node for RA bone destruction.

BACKGROUND:Sepsis-induced acute lung injury (SI-ALI) is a major cause of morbidity and mortality among septic patients. Recent evidence highlights the role of mitochondria-associated membranes (MAMs)-specialized contact sites between the endoplasmic reticulum (ER) and mitochondria-in regulating calcium signaling, lipid metabolism, energy homeostasis, and immune responses. Structural and functional alterations of MAMs are increasingly recognized as critical contributors to the pathogenesis of SI-ALI. OBJECTIVES:This review aims to summarize the structural and functional characteristics of MAMs, elucidate their alterations and immunoregulatory roles in sepsis-induced lung injury, and discuss potential therapeutic strategies targeting MAMs to mitigate pulmonary damage. METHODS:A comprehensive literature review was conducted using recent studies focused on the molecular structure, signaling mechanisms, and pathological changes of MAMs in sepsis and related inflammatory diseases. Emphasis was placed on calcium signaling, mitochondrial dysfunction, oxidative stress, and inflammasome activation. RESULTS:MAMs maintain close ER-mitochondria contacts (10-30 nm) through key proteins such as inositol 1,4,5-trisphosphate receptor (IP3R), glucose-regulated protein 75 (GRP75), voltage-dependent anion channel (VDAC), and mitofusin-2 (MFN2). During sepsis, oxidative stress and inflammatory cytokines disrupt these contacts, leading to impaired calcium transfer, mitochondrial dysfunction, and energy deficiency. Dysregulated MAMs promote NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, excessive reactive oxygen species (ROS) production, and mitochondrial DNA (mtDNA) release, thereby amplifying inflammatory cascades and immune cell apoptosis. Therapeutic strategies that restore MAM integrity-such as upregulating MFN2, activating ER autophagy, or modulating calcium transport proteins-have shown potential to attenuate lung injury by improving mitochondrial metabolism and reducing oxidative stress. CONCLUSIONS:MAMs play essential roles in maintaining intracellular homeostasis and immune balance. Their structural and functional disruption contributes significantly to the progression of SI-ALI. Targeting MAMs offers promising therapeutic opportunities for preventing and treating sepsis-induced lung injury, although further mechanistic and clinical studies are warranted to translate these findings into practice.

Skeletal muscle regeneration is a highly coordinated physiological process. It relies on the intricate collaboration of a complex cellular ecosystem. This ecosystem includes muscle stem cells, immune cells, stromal cells, vascular cells, neural cells, and the extracellular matrix. Research has recently expanded beyond focusing solely on satellite cells. It now delves into the multi-level regulatory networks within this ecosystem. These networks encompass key signaling pathways, such as Wnt/β-catenin, TGF-β, Hippo/YAP, and AMPK. They also include epigenetic regulation, cellular metabolic reprogramming, and extracellular vesicle-mediated intercellular communication. However, under pathological conditions, this regenerative program is severely impaired. This leads to failed repair, fibrosis, and fatty infiltration, ultimately resulting in loss of muscle function. This review aims to systematically outline recent advances in the field of skeletal muscle regeneration. First, from the perspective of the “cellular ecosystem,” we will elaborate on the dynamic behaviors and regulatory mechanisms of various cell types during regeneration. Second, we will dissect the core mechanisms underlying regenerative failures in various pathological states. Third, we will comprehensively evaluate the most promising current intervention strategies. Finally, considering the limitations of current research, we will provide future perspectives. This review aims to systematically integrate existing knowledge and provide a clear roadmap for future research, ultimately offering a robust theoretical foundation and innovative insights for the development of clinical treatments targeting skeletal muscle regenerative disorders.

This study aimed to investigate the effect of ginseng glucosyl oleanolate (GGO) on non-small cell lung cancer (NSCLC) both in vitro and in vivo. GGO significantly inhibited the proliferation of A549 cells and tumor growth of A549-xenograft nude mice. Metabonomics analysis showed that GGO treatment changed the metabolites of glycolysis and tricarboxylic acid (TCA) cycle, which was consistent with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of transcriptomics. GGO inhibited the expression of glutaminase (GLS), decreased the content of glutamic acid and the carbon input of the TCA cycle, and finally significantly blocked the production of ATP. Meanwhile, GGO treatment decreased the levels of glutathione (GSH) and glutathione peroxidase (GPX), increased the accumulation of Fe2+ and malondialdehyde (MDA), downregulated solute carrier family 7 member 11 (SLC7A11) and GPX4 protein expression, which led to the redox imbalance and induced ferroptosis in A549 cells and tumor tissue. These findings provided compelling evidence that GGO may represent a potential new approach to treating NSCLC.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness characterized by an irreversible pathological process that creates an urgent need for novel molecular targets for effective prevention, diagnosis, and treatment. Estrogen sulfotransferase (SULT1E1), a phase II cytoplasmic enzyme, is downregulated in various cancers and inflammatory diseases. Although its role in other conditions has been explored, its function in COPD remains unclear. This study aimed to assess SULT1E1 expression and underlying mechanisms in COPD pathogenesis. We identified differentially expressed genes by analyzing four microarray datasets (GSE10006, GSE18385, GSE29133, and GSE37768) obtained from the gene expression omnibus database. Gene ontology and Kyoto encyclopedia of genes and genomes analyses were conducted, and protein-protein interaction networks were constructed. The SULT1E1 expression was validated in clinical samples from patients with COPD (n = 92) and healthy controls (n = 40) using serum enzyme-linked immunosorbent assay and PBMC RT-qPCR, with a correlation to lung function assessed. A rat model of COPD was used to evaluate SULT1E1 protein levels in lung tissue by Western blotting and immunohistochemistry. In vitro studies modulated SULT1E1 expression in BEAS-2B cells to assess effects on cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and AKT phosphorylation. Bioinformatic analyses revealed a significantly lower SULT1E1 expression in lung tissues of patients with COPD. Clinically, serum and PBMC SULT1E1 levels were significantly reduced in patients with COPD, exhibiting a positive correlation with lung function indicators, including FEV1% and FEV1/FVC (P < 0.001). These findings were further supported by a rat model of COPD, which demonstrated decreased SULT1E1 protein expression. In vitro studies indicated that SULT1E1 knockdown in BEAS-2B cells promoted proliferation and EMT, inhibited apoptosis, and increased AKT phosphorylation. Conversely, SULT1E1 overexpression led to opposing effects, inhibiting proliferation and EMT; however, it also promoted apoptosis and reduced AKT phosphorylation. Our findings demonstrate that low SULT1E1 expression is a key characteristic of COPD and correlates with disease severity. SULT1E1 appears to play a protective role by regulating AKT phosphorylation, thereby influencing cell proliferation, apoptosis, and EMT. These results identify SULT1E1 as a potential prognostic biomarker and a novel therapeutic target for COPD.

Bone, the rigid tissue of the human skeleton, supports the body and safeguards internal organs, necessitating continuous bone remodeling for optimal function. Traditionally, osteoclasts (OCs), particularly mature osteoclasts (mOCs), have been considered solely responsible for bone resorption through their unique ability to adhere to bone surfaces and degrade both mineral and organic components. This process contributes to pathological bone loss in conditions including osteoporosis, osteoarthritis, and fracture healing, leading to most anti-osteoporosis therapies focus on inhibiting OCs. However, recent research has unveiled a new dimension to OC biology, revealing significant heterogeneity among OCs and the existence of non-bone resorbing OC subtypes within the osteoclast lineage with emerging functions. This review delves into the latest discoveries of cellular subtypes within this non-resorbing category and their roles in regulating bone homeostasis and pathological bone diseases. We also highlight the novel therapeutic potential of targeting non-bone resorbing OCs for bone loss diseases. Lastly, we explore the promising avenues and challenges in translating these findings into osteoporosis therapy, thus challenging the traditional paradigm that OCs are defined exclusively by their bone-resorbing capacity.

High-Pressure Nervous Syndrome (HPNS) refers to a series of neurological disturbances that occur during exposure to high hydrostatic pressure, characterized by cognitive and motor impairment manifestations. This review systematically summarizes the research progress on the pathophysiological mechanisms of HPNS. The main mechanism is the imbalance between inhibition of synaptic transmission and the increased excitability of neural networks, specifically involving voltage-gated sodium, potassium, calcium channels, and N-methyl-D-aspartate (NMDA) receptors. Most HPNS symptoms subside upon returning to normal pressure, making the study of its mechanisms challenging. HPNS remains a significant limiting factor for deep-sea diving, and to date, no effective drugs have been developed for human HPNS prevention. This review focuses on the pathophysiological mechanisms of HPNS, which is crucial for further understanding its mechanisms and extending the limits of human deep-sea diving.

Motion sickness is common in aerospace, aviation and maritime operations, and travel by vehicles or ships. Existing preventive and therapeutic drugs for motion sickness induce central nervous system (CNS)-related side effects; therefore, there is an urgent need to find new anti-motion sickness targets and to develop novel drugs with reduced adverse effects. In this study, we found that rotational stimulation significantly upregulated carbonic anhydrase 2 (CA2) expression in the inner ears of guinea pigs and mice. Pretreatment with acetazolamide (AZ), an inhibitor of carbonic anhydrase, effectively mitigated motion sickness-related behavioral symptoms in both species and inhibited increase in the inner ear endolymph volume induced by rotational stimulation. Further investigations revealed that AZ mediated its anti-motion sickness effects primarily through mechanisms involving the reduction of intracellular H+ concentrations in vestibular epithelial cells, inhibition of Na+-K+-ATPase activity, and modulation of intracellular Na+ and K+ homeostasis, thereby attenuating endolymph accumulation in the inner ear. This study demonstrated for the first time an involvement of the inner ear CA2 in the induction of motion sickness and an anti-motion sickness effect of its inhibitor AZ, providing a new strategy for developing anti-motion sickness drugs acting on the inner ear.

While the relationship between miRNAs and malignant melanoma is well-established, the role of miR-425-5p in melanoma remains underexplored. This study investigated the molecular mechanisms underlying miR-425-5p-mediated regulation of malignant melanoma proliferation and metastasis, with emphasis on its interaction with scavenger receptor class A member 5 (SCARA5). The impact of SCARA5 and miR-425-5p on melanoma cell proliferation and metastatic potential was assessed using CCK-8, clonogenic, scratch, and Transwell assays. Western blotting was employed to quantify apoptosis markers, epithelial-mesenchymal transition (EMT)-related proteins, and components of the Akt signaling pathway. Bioinformatics and dual-luciferase reporter assays validated the direct interaction between miR-425-5p and SCARA5. In vivo, a subcutaneous tumor model in nude mice was used to evaluate tumor growth, and TUNEL staining was performed to assess apoptosis. Tandem Mass Tag (TMT) proteomics was applied to comprehensively identify downstream pathways modulated by miR-425-5p. Silencing SCARA5 in A375 and A2058 cells downregulated the expression of caspase-3 and E-cadherin levels while elevating Bcl-2, p-AKT, N-cadherin, β-catenin, and ZEB1 levels. Conversely, SCARA5 overexpression reversed these effects. Dual-luciferase assays confirmed that miR-425-5p could directly target SCARA5. Inhibition of miR-425-5p expression increased SCARA5 expression and suppressed proliferation/metastasis, whereas miR-425-5p mimics reduced SCARA5 expression and enhanced malignancy. In the in vivo model, SCARA5 overexpression significantly inhibited tumor growth, while the administration of miR-425-5p agonists promoted it. Proteomics further revealed that miR-425-5p could suppress the PPARγ pathway and activate the AKT signaling pathway. Our findings demonstrate that miR-425-5p promotes melanoma progression by downregulating SCARA5, thereby inhibiting apoptosis, activating AKT phosphorylation, and inducing EMT. These findings identify the miR-425-5p/SCARA5 axis as a potential therapeutic target for melanoma.

MAFB is a large Maf family bZIP transcription factor involved in myeloid differentiation, macrophage-state regulation, inflammatory control, and tissue adaptation. Accumulating evidence indicates that MAFB biology is highly context dependent rather than uniformly anti-inflammatory, pro-inflammatory, protective, or pathogenic. In macrophages and related myeloid cells, MAFB has been linked to inflammasome regulation, lipid-mediator switching, efferocytosis, tissue repair, and cell-state transitions. Across diseases, its interpretation depends on cellular source, disease stage, tissue niche, perturbation evidence, and human validation. In sterile inflammatory or repair-associated contexts, MAFB may support inflammatory restraint and resolution-associated programs, whereas in tuberculosis, tumor-associated macrophages, selected malignant cells, and Mendelian renal-skeletal disorders, MAFB-related findings reflect distinct evidence categories and levels of translational maturity. Clinically, current evidence does not support MAFB as a universal biomarker or broadly actionable therapeutic target. Instead, any translational value of MAFB requires interpretation within defined cell types, disease stages, tissue niches, and evidence categories. This review distinguishes direct mechanistic evidence, human genetic or Mendelian causal evidence, animal disease-model evidence, in vitro perturbation data, human tissue, single-cell or spatial association, and author-derived conceptual synthesis. We propose that MAFB is best viewed as a context-dependent immune-regulatory factor whose clinical relevance remains disease- and cell-state-specific and, in many settings, hypothesis-generating. This review highlights evidence boundaries, translational readiness, and priorities for cell-state-specific validation of MAFB biology.

Ginseng (Panax ginseng C.A. Meyer) is a natural immune modulator with a long history of application. Ginsenosides, especially rare ginsenosides, as main bioactive components, have received extensive attention for modulating immune response in cancers. This study aimed to investigate the anti-tumor immune effect of the new rare ginseng glucosyl oleanolate (GGO) transformed from ginsenoside Ro in cervical cancer. GGO effectively induced cervical cancer cell apoptosis, inhibited epithelial mesenchymal transformation (EMT) and tumor growth in dose manner. GGO inhibited immune escape, increased the infiltration of immune cells cluster of differentiation 4 (CD4) T cells and cluster of differentiation 8 (CD8) T cells and the secretion of cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-u03B1), interferon gamma (IFN-u03B3) by activating the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) signaling pathway. In addition, GGO enhanced short-chain fatty acids (SCFAs) metabolism and intestinal immune barrier function by modulating the composition of gut microbiota through specific bacterial populations, including Lactobacillus, Bacteroides, Clostridium, Blautia, among others, and these influences also contributed to its anti-tumor immune effect. The results of this study offered encouraging indications that GGO might serve as a natural functional food ingredient with the potential to prevent and treat cervical cancer.

Hyperbaric oxygen (HBO) shows neuroprotective potential in cerebral ischemia-reperfusion (CIR) injury, but its variable efficacy suggests that the underlying cellular mechanisms remain incompletely defined. We previously showed that HBO suppresses microglial NLRP3 inflammasome activation after CIR injury in a reactive oxygen species (ROS)-dependent manner; yet, how ROS couples to this effect remains unclear. Since mitochondria regulate ROS and inflammasome signaling, we investigated whether HBO modulates microglial mitochondrial dynamics in CIR injury. In adult male ICR mice (n = 71, 8-12 weeks) subjected to 60 min middle cerebral artery occlusion followed by 24 h reperfusion, HBO improved neurological function, reduced infarct area, and decreased ASC-positive microglia/macrophages. In lipopolysaccharide/nigericin-stimulated primary microglia, HBO suppressed IL-1β release, reduced mitochondrial fragmentation, preserved mitochondrial membrane potential, maintained mitofusin 2 (MFN2) protein level, and reduced DRP1 Ser616 phosphorylation without altering total DRP1 or FIS1 expression. MitoTEMPOL abolished HBO-mediated protection against mitochondrial fragmentation, MFN2 reduction, and DRP1 Ser616 phosphorylation in vitro. Edaravone, when combined with HBO, attenuated HBO-mediated neuroprotection and counteracted HBO-induced regulation of MFN2 and DRP1 Ser616 phosphorylation in vivo. These findings support ROS-dependent remodeling of microglial mitochondrial dynamics as a mechanism contributing to HBO-mediated suppression of inflammasome-associated inflammation after CIR injury.

Background: Chronic cor pulmonale (CCP) represents a considerable health burden globally, especially in community settings where resources for management are frequently constrained. Objective: This study aims to establish an internet-based integrated healthcare and prevention self-management intervention model for community-dwelling patients with CCP (pulmonary heart disease) and to evaluate its effectiveness in improving disease management and health outcomes. Methods: Patients diagnosed with CCP within a community setting were enrolled. According to the management strategies they actually received, they were categorized into an intervention group and a control group. The intervention group received an internet-based integrated healthcare and prevention self-management intervention, while the control group received conventional management. The duration of the intervention was six months. Changes in the dyspnea index, oxygen saturation, quality of life scores, and readmission rates were measured before and after the intervention. Statistical analysis was conducted using SPSS version 21.0. Results: Compared to the control group, the intervention group exhibited significant improvements in the dyspnea index, oxygen saturation, and quality of life scores (P< 0.05), as well as a significant reduction in readmission rates (P< 0.05). Conclusion: The internet-based integrated healthcare and prevention self-management intervention model demonstrated significant effectiveness in enhancing self-management capacity and overall health status among community-dwelling patients with CCP.