Inflammatory bowel disease (IBD) represents a chronic relapsing disorder driven by a loss of homeostatic balance between the host immune system and the intestinal microbiota. Endogenous antimicrobial peptides (AMPs), produced primarily by epithelial and immune cells, function in concert with commensal microorganisms to preserve mucosal integrity and barrier function. Disruption of this antimicrobial equilibrium-through genetic susceptibility such as NOD2 mutations or environmental perturbations including antibiotic overuse-can impair antimicrobial defense, distort microbial composition, and initiate chronic inflammation. Recent investigations have revealed distinct alterations in AMP expression across IBD subtypes. In Crohn's disease, Paneth cell-derived α-defensins (HD5 and HD6) are markedly diminished in the ileal mucosa, whereas colonic, segmental IBD exhibits inadequate induction of β-defensins and LL-37. Conversely, in actively inflamed regions, certain AMPs such as human β-defensin-2 (HBD2) and lysozyme are strongly upregulated, reflecting a compensatory response to inflammatory cell infiltration and microbial invasion. Beyond host-derived peptides, broad-spectrum antibiotic exposure profoundly reshapes commensal communities, attenuates basal pattern-recognition receptor signaling, and secondarily perturbs AMP regulation-creating a feedback loop that amplifies dysbiosis. Here, we conceptualize these interactions as an integrated AMP-antibiotic-microbiota triad, in which endogenous antimicrobial regulation, exogenous antimicrobial pressure, and microbial ecological resilience dynamically co-determine mucosal stability. By positioning AMPs within this tripartite regulatory framework, this review delineates how antimicrobial imbalance arises across IBD subtypes, compares emerging therapeutic strategies-including AMP enhancement, microbiota-sparing antibiotic regimens, fecal microbiota transplantation, and metabolite-guided interventions-and highlights implications for precision recalibration of antimicrobial homeostasis in IBD.

OBJECTIVE:To investigate implant-supported prosthetic outcomes and influencing factors in alveolar bone atrophy. MATERIAL AND METHODS:One hundred and fifty patients with atrophy receiving implants (2021-2022) were followed for 2 years. Success (n = 97, 64.7%) and failure (n = 53, 35.3%) groups were compared using univariate analysis, followed by multivariate logistic regression to identify factors associated with overall failure and Cox regression to assess time to failure. RESULTS:Univariate analysis identified age, gender, smoking, implant length, and prosthesis type as significant (p < 0.05). Multivariate logistic regression showed short implant length (< 10 mm) as the sole independent risk factor for failure (OR = 4.418, p = 0.004); age ≥ 60 years (OR = 2.560, p = 0.094) and female gender (OR = 1.127, p = 0.807) were not significant. Multivariable Cox regression revealed age ≥ 60 years as a significant predictor of earlier failure (HR = 2.558, p = 0.010), while female gender and short implants were not (p > 0.05). Kaplan-Meier curves showed significant survival differences for age (p = 0.010), gender (p = 0.023), and implant length (p = 0.021). CONCLUSION:Short implant independently increases failure risk; age ≥ 60 years accelerates failure. Bone augmentation is preferred. Findings need validation.

Abstract Background CD109 is a glycosylphosphatidylinositol‑anchored glycoprotein implicated in tumor progression and physiological homeostasis. Although aberrant CD109 expression has been reported in multiple malignancies, its prognostic relevance across cancer types and its potential immunomodulatory roles remain incompletely characterized. Methods We performed an integrative pan-cancer analysis of CD109 using RNA sequencing data from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. CD109 expression, genetic alterations, survival associations, and immune infiltration patterns were systematically assessed. Single-cell RNA sequencing (scRNA-seq) data from non-small cell lung cancer (NSCLC) cohorts were analyzed to define cellular CD109 distribution. Functional validation was performed using siRNA-mediated CD109 knockdown in A549 lung adenocarcinoma cells, followed by macrophage co-culture experiments, flow cytometry, qPCR, ELISA, and migration assays. Results CD109 was markedly upregulated in 15 tumor types and showed heterogeneous prognostic associations across cancers. Elevated CD109 expression was associated predominantly with unfavorable survival in several tumor types, whereas opposite prognostic associations were observed in a subset of cancers. Bioinformatic analysis revealed that high CD109 expression was associated with an immunosuppressive tumor immune microenvironment, characterized by the enrichment of M2-like tumor-associated macrophages (TAMs) and activation of oncogenic signaling axes. Single-cell profiling showed that CD109 was predominantly expressed in malignant cells and a subset of M2 macrophages. Consistent with these clinical and computational insights, functional validation in an in vitro lung cancer model showed that CD109 knockdown in A549 cells significantly suppressed tumor migration and was associated with a shift in macrophage polarization away from a pro-tumorigenic M2 phenotype toward an anti-tumor M1 state. Conclusions Our study highlights CD109 as a context-dependent biomarker with tumor type specific prognostic relevance and links its expression to immunosuppressive features of the tumor immune microenvironment. These findings suggest that CD109 warrants further investigation as a potential therapeutic target, particularly in tumor contexts characterized by macrophage-associated immunosuppression, although the macrophage-related functional effects observed here were validated in a lung cancer model and require further investigation in additional tumor types.

Atherosclerosis, the pathological basis of cardiovascular diseases including coronary artery disease and ischemic stroke, is increasingly recognized as a chronic inflammatory disease. The contribution of nucleotide-binding oligomerization domain containing 2 (NOD2), a key pattern recognition receptor in immunity, to atherosclerosis remains poorly defined. This study investigated the role of NOD2 in platelet-mediated monocyte activation and evaluated the therapeutic potential of pharmacological NOD2 inhibition. NOD2 protein wasdecreased in platelets from atherosclerotic patients and mice, accompanied by elevated NOD2 expression in peripheral blood mononuclear cells. These alterations were not attributable to transcriptional regulation. Plasma exosomes from atherosclerotic patients contained increased NOD2 protein. Accordingly, platelet activation caused a reduction in NOD2 protein within platelets and the release of NOD2-enriched exosomes that increased NOD2 expression in THP-1 monocytes. NOD2 overexpression in THP-1 cells enhanced cell migration and proinflammatory response without affecting cell adhesion and differentiation, whereas treatment with the NOD2 receptor antagonist GSK669 attenuated both processes. Mechanistically, NOD2 upregulated LOX-1 and activated the RIP2/JNK/p38 axis during THP-1 differentiation. In hyperlipidemic ApoE-/- mice, platelet-derived exosomes carrying NOD2 exacerbated atherosclerosis, while intravenous administration of GSK669 attenuated atherosclerosis and showed efficacy comparable to aspirin in this mouse model. In conclusion, we uncover a previously unrecognized mechanism whereby platelet-to-monocyte transfer of NOD2 via exosomes drives monocyte inflammation and migration, exacerbating atherosclerosis. The anti-atherosclerotic effects of GSK669, a NOD2 receptor antagonist with previously reported antithrombotic efficacy comparable to aspirin and a favorable bleeding profile in mice, highlight NOD2 antagonism as a promising alternative therapeutic strategy against atherosclerosis.

Cerebral ischemia-reperfusion injury (CIRI) represents a critical pathological cascade that paradoxically exacerbates neurological damage following revascularization therapy for acute ischemic stroke (AIS). The pathogenesis of CIRI is intricately linked to dysregulated neuroinflammation, with microglia—the resident innate immune cells of the central nervous system—serving as central orchestrators of this response. Emerging evidence indicates that microglia undergo profound metabolic reprogramming encompassing glucose metabolism, the tricarboxylic acid (TCA) cycle, fatty acid metabolism, and NAD+ homeostasis, which fundamentally dictates their functional polarization and consequent neuroinflammatory outcomes. Rather than existing as discrete pro-inflammatory versus reparative phenotypes (classically referred to as M1/M2), microglia exhibit a continuum of activation states with distinct metabolic signatures that evolve dynamically across spatiotemporal dimensions following CIRI. Here, we systematically synthesize current knowledge on the core molecular mechanisms underlying microglial metabolic reprogramming, including the ACOD1/itaconate pathway, the glycolysis-OxPhos balance, and NAMPT-mediated NAD+ homeostasis. We critically examine the intricate crosstalk between these metabolic pathways and neuroinflammatory signaling cascades, revealing how metabolic checkpoints serve as integrative nodes that decode microenvironmental cues into functional outputs. Building on this mechanistic foundation, we evaluate emerging intervention strategies targeting metabolic reprogramming, stratified by intervention modality and translational readiness, with emphasis on agents in active clinical development. Finally, we identify prevailing challenges—including spatiotemporal heterogeneity, cell-specific targeting requirements, and clinical translation barriers—and outline future directions integrating single-cell omics, systems biology approaches, and advanced delivery systems. This comprehensive analysis aims to provide a refined conceptual framework and highlight promising therapeutic avenues for mitigating CIRI through strategic modulation of microglial immunometabolism.

BackgroundImmune checkpoint inhibitor-related pneumonitis (CIP) is an important pulmonary toxicity in cancer immunotherapy. Its diagnostic assessment is difficult because symptoms and imaging overlap with infection, radiation pneumonitis, tumor progression, pre-existing interstitial lung disease, and other drug-induced lung injuries. Although publications on CIP have increased in recent years, research on diagnostic assessment remains insufficiently described.MethodsPublications on CIP and diagnostic assessment were retrieved from the Web of Science Core Collection (WoSCC) and PubMed. After screening, 628 WoSCC records were included as the main dataset for bibliometric analysis, and 74 PubMed records were used for supplementary clinical-topic assessment. Microsoft Excel, VOSviewer, CiteSpace, Bibliometrix, and SCImago Graphica were used to examine publication trends, country and institutional contributions, author collaboration, journal distribution, keyword co-occurrence, clustering, burst terms, and PubMed-based diagnostic topic classification.ResultsCIP research was sparse before 2015, increased after 2015, and accelerated after 2019, with the highest annual output observed in 2023. China published the highest number of papers, while the United States has the greatest citation impact. Institutional and author analysis identified active research groups mainly from China, the United States and Japan. Research is mainly published in oncology, immunology, thoracic medicine and respiratory journals. Keyword analysis shows a shift from melanoma, T cells and immune checkpoint inhibition towards clinically focused themes, including diagnosis, differential diagnosis, imaging features, bronchoalveolar lavage (BAL), biomarkers, risk factors and nomogram-based prediction. A supplementary PubMed analysis similarly highlights imaging features, BAL, bronchoscopy or pathological assessment, and risk prediction as the primary clinical diagnostic themes.ConclusionResearch into CIP has evolved from the recognition of immune-related pulmonary toxicity to diagnostic assessment, differential diagnosis and personalised risk assessment. Current diagnostic studies reflect the clinical challenge of distinguishing CIP from other pulmonary complications in patients receiving immunotherapy. Future research should focus on developing and validating standardised, multicenter diagnostic strategies linked to prognosis. Current research trends suggest that imaging findings, bronchoalveolar lavage fluid or histopathological assessment, biomarkers, baseline lung function, and predictive models may form key components of such strategies; however, their clinical utility requires validation through prospective studies.

Long noncoding RNAs (lncRNAs) play crucial roles in regulating chromatin dynamics and gene expression, and their dysregulation is closely linked to tumorigenesis. However, their specific functions in gastric cancer (GC) remain poorly understood. Here, we found that lncRNA solute carrier family 16 member 1 antisense RNA 1 (SLC16A1-AS1) was markedly overexpressed in GC through integrated RNA sequencing (RNA-seq) analysis and validation in clinical tissues. High SLC16A1-AS1 expression correlated with advanced cancer stage, greater invasion depth, and poorer patient prognosis. Functional assays showed that SLC16A1-AS1 overexpression promoted GC cell proliferation, whereas knockdown inhibited proliferation in vitro and in vivo. Mechanistically, SLC16A1-AS1 interacted with the 5-methylcytosine (m5C) methyltransferase NOL1/NOP2/ SUN (NSUN2), enhancing m5C modification of GRP78 mRNA, which stabilized the transcript and increased GRP78 protein levels. Rescue experiments demonstrated that GRP78 overexpression reversed the proliferation-inhibitory effect of SLC16A1-AS1 depletion. These findings reveal that SLC16A1-AS1 drives GC cell proliferation via NSUN2-mediated m5C modification of GRP78 mRNA, suggesting a potential target for GC diagnosis and therapy.

Metabolic dysfunction-associated steatotic liver disease is associated with vitamin D deficiency, and platelets exhibit hyperactivity. Zhang et al provide novel insights into the mechanisms underlying platelet hyperreactivity and thrombotic risk in patients with metabolic dysfunction-associated steatotic liver disease, demonstrating that calcitriol activates the vitamin D receptor in megakaryocytes and platelets, leading to the downregulation of P2Y12 expression and the modulation of the cyclic adenosine monophosphate/protein kinase A and mitogen-activated protein kinase signaling pathways, thereby attenuating platelet activation.

Abstract INTRODUCTION: High-grade, locally advanced primary prostate cancer (PC) carries an increased risk of metastatic progression. The Androgen Receptor indifferent (ARi) phenotype is characterized by low PSA expression despite high expression of AR and has been noted in CRPC where it is considered to be induced by treatment. We sought to examine primary, treatment-naïve PC cases for evidence of ARi. METHODS: We applied digital pathology and multiplexed, single-cell resolution tissue staining techniques to a locally advanced PC patient cohort with 27 patients and computational RNA expression analysis to the TCGA prostate cancer dataset (TCGA-PRAD). Thus, we first quantify AR and PSA protein expression levels in cells and then identify tissue regions with >30% AR+ cells and <30% PSA+ cells as ARi cases. The PC regions we analyzed include seminal vesicle invasion (SV), lymph node metastasis (LN), extracapsular extension (ECE), perineural invasion (PNI), cribriform (CRIB), and non-cribriform (HGNC). For computational analysis of the TCGA bulk RNA sequencing data, we stratify patients according to high AR / low PSA (ARi-cohort) and high AR / high PSA (AR responsive, or ARr-cohort) and perform differential expression and gene set enrichment analysis accordingly. RESULTS: Pathologically, we identified ARi phenotype in one or more tissue samples from 5 out of 27 patients. ARi is more frequent in LN compared to SV; and within the prostate, HGNC exhibited more ARi than CRIB. Computational analysis of the TCGA-PRAD cohort (n=500) revealed that ARi patients, compared to AR-responsive patients, are enriched in epithelial-mesenchymal transition (EMT), stem-like, and ONECUT2-induced gene signatures. Moreover, we demonstrate that ARi phenotype is strongly associated with the Prostate Cancer Subtype 1 (PCS1) and PAM50 Basal subtype, consistent with the aggressiveness of the disease. CONCLUSION: We identified the ARi phenotype in two cohorts of primary PC patients using both tissue staining with single cell resolution and computational analysis of bulk RNA expression. We further characterized this phenotype using published gene signatures and determined its relationship to PCS and PAM50 subtypes. Furthermore, we propose that the presence of the ARi phenotype can be assessed quickly by clinical immunohistochemistry with AR and PSA antibodies followed by quantification of positive ARi cells (as defined by a high AR:PSA ratio). Moving forward, we will perform single cell RNA expression analysis on the cohort we performed tissue staining to further validate the presence and behavior of ARi phenotype in primary PC, expand into other cohorts, as well as evaluate treatment strategies likely to elicit a response in these cells according to their transcriptomic phenotypes. Citation Format: Tessa Tolson, Beatrice Knudsen, Wei Zhang, Mason Hovinga, Chance Walker, Galaxy Yang, Erika Egal, Yosep Chong, Michael Freeman, Yi Qiao. Identification and phenotypical evaluation of androgen receptor indifferent phenotype in treatment-naïve primary prostate cancer cases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4152.

Metabolic stress caused by lipid overload is a key driver of cellular dysfunction in aging and disease. Excess saturated fatty acids such as palmitate impair fatty acid oxidation (FAO), promote lipid accumulation, and increase reactive oxygen species (ROS), ultimately triggering premature senescence-like states. Senescence further amplifies vulnerability by worsening mitochondrial dysfunction, enhancing lipid imbalance, and sustaining pro-inflammatory signaling. Here, we investigated the role of the neuron-enriched RNA-binding protein HuD (ELAVL4) in protecting cells against lipotoxic stress. Using Neuro2a neuroblastoma cells, we found that HuD knockdown suppressed FAO, leading to increased lipid accumulation and elevated ROS following palmitate exposure. HuD-deficient cells also exhibited cytosolic mitochondrial DNA release, IRF phosphorylation, and upregulation of senescence markers. Mechanistically, RNA immunoprecipitation revealed that HuD binds directly to PPARα mRNA, sustaining its expression by competing with the PPARα-targeting microRNAs miR-9-5p and miR-22-3p. Loss of HuD reduced PPARα levels, thereby weakening the FAO capacity and sensitizing cells to palmitate-induced lipotoxic stress. These findings identify a previously unrecognized HuD–PPARα–FAO axis that restrains metabolic stress and senescence. By linking post-transcriptional regulation to lipid metabolism and inflammatory signaling, this work highlights stress-induced premature senescence as both an outcome and a propagator of metabolic dysfunction, providing insight into mechanisms of aging-related vulnerability.

BACKGROUND:Ablative fractional CO2 laser is effective for acne scar treatment but is often associated with side effects such as erythema and dyspigmentation, along with prolonged recovery time. AIMS:The study aimed to evaluate the post-procedure reparative effects of a combination of vitamin C, E, and ferulic acid (CE Ferulic) in Chinese patients with atrophic acne scars. METHODS:In this randomized, investigator-blinded, split-face, controlled trial, patients aged 18-50 with moderate-to-severe atrophic acne scars were randomly assigned to apply CE Ferulic to intervention-side face and normal saline (NS) to control-side face, immediately after ablative CO2 laser treatment for 14 days. Patients were further divided into once-daily and twice-daily application subgroups. During the 14-day follow-up, the wound healing (measured by scabbing stage on Day 7), erythema index (EI), melanin index (MI), skin hydration, and transepidermal water loss (TEWL) were evaluated. Direct assessment of scar improvement was not within the scope of this study. RESULTS:Sixty-four patients were included in the analysis. On Day 7, the intervention side showed a higher complete scab detachment rate than the control side (60.9% vs. 34.4%, p = 0.0026). EI and MI reduced significantly greater on the intervention side compared to the control side (Days 3, 7, and 14; p < 0.0001). On Day 14, the intervention side also demonstrated significantly better capability of maintaining skin hydration (p = 0.0367) and preventing TEWL (p = 0.0246) than the control side. CONCLUSIONS:This study found that CE Ferulic led to enhanced wound healing, reduced erythema and melanin levels, and improved skin hydration following laser treatment, suggesting its beneficial application in combination with laser treatment to accelerate skin recovery. TRIAL REGISTRATION:ChiCTR2300078214.

Arterial thrombotic diseases are leading causes of global morbidity and mortality, primarily driven by platelet hyperactivity. Qiliqiangxin capsules (QLQX), a traditional Chinese medicine approved in China for the treatment of heart failure, have exhibited potential benefits in reducing cardiovascular death. However, its direct effects on platelet activation and thrombosis remain unclear. Ex vivo platelet function assays demonstrated that oral QLQX inhibited agonist‑induced aggregation in platelet‑rich plasma (PRP) from chronic heart failure (CHF) patients and dose-dependently suppressed washed platelet aggregation in wild‑type mice. In parallel, QLQX administration attenuated platelet spreading and clot retraction in washed platelets from both patients with CHF and wild-type mice, and reduced ex vivo thrombus formation area in a microfluidic whole‑blood perfusion under arterial shear stress. Flow cytometry analysis revealed that QLQX did not affect the surface expression levels of the major platelet receptors, but reduced the activation of αIIbβ3 and P-selectin exposure induced by thrombin in mouse platelets. In vivo experiments demonstrated that QLQX treatment inhibited FeCl₃-induced thrombus formation in mesenteric arterioles, reduced collagen/epinephrine-induced pulmonary embolism, and mitigated microvascular thrombosis during myocardial ischemia-reperfusion (I/R) injury, without increasing bleeding in mice. RNA sequencing of platelets from QLQX- versus vehicle-treated mice identified differentially expressed genes enriched in the calcium signaling pathway, and functional assays demonstrated that QLQX inhibited agonist-induced platelet Ca²⁺ influx and PKC phosphorylation. QLQX inhibits platelet activation and thrombosis by targeting Ca²⁺ influx and PKC signaling, supporting its potential therapeutic value in preventing thrombotic complications.

BACKGROUND:Postmenopausal osteoporosis is primarily driven by estrogen deficiency-associated osteoclast hyperactivation, resulting in excessive bone resorption and progressive deterioration of bone microarchitecture. Although current anti-resorptive therapies are clinically effective, their long-term application remains limited by adverse effects. PURPOSE:This study aimed to evaluate the anti-osteoporotic effects of Gengnianshou Formula (GNS), identify its pharmacologically relevant absorbed constituents, and investigate the molecular mechanisms underlying its regulation of osteoclast differentiation under estrogen-deficient conditions. METHODS:An ovariectomized (OVX) rat model was used to evaluate the anti-osteoporotic effects of GNS in vivo. Bone microarchitecture and osteoclast activity were assessed using micro-CT, histological staining, ELISA, and western blotting. Serum and fecal metabolite profiling was performed by UPLC-MS/MS to identify exposure-related compounds. Candidate compounds were screened in RAW264.7 osteoclast differentiation models. Public transcriptomic datasets (GSE230665 and GSE246769) were integrated to identify key regulatory genes associated with osteoclastogenesis. CRISPR/Cas9-mediated knockout, molecular docking, microscale thermophoresis (MST), qPCR, immunofluorescence, and western blot analyses were performed for mechanistic validation. RESULTS:GNS significantly improved trabecular bone microarchitecture and reduced osteoclast activity in OVX rats. Exposure profiling identified adenosine, phellodendrine, and jatrorrhizine as prototype compounds in both serum and feces, whereas (+)-magnoflorine (MAG) was detected as a prototype in feces and as a demethylated metabolite in serum, indicating pharmacologically relevant MAG-related exposure. Functional screening identified (+)-MAG as the most potent inhibitor of osteoclast differentiation in vitro. Integrated transcriptomic analyses revealed that CCDC88A was an early-response gene associated with osteoporosis progression and osteoclast differentiation. CCDC88A deficiency attenuated osteoclastogenesis and altered CCDC88A-associated signaling responses. Moreover, molecular docking and MST analyses supported a direct interaction between (+)-MAG and CCDC88A, while CCDC88A depletion abolished the additional inhibitory effects of (+)-MAG on osteoclast differentiation. CONCLUSION:GNS effectively alleviated estrogen deficiency-associated bone loss by suppressing osteoclast activation. (+)-MAG was identified as an exposure-related bioactive constituent, and its anti-osteoclast effects were mediated through a CCDC88A-dependent regulatory mechanism. These findings provide new insights into osteoclast regulation and highlight GNS-derived compounds as potential therapeutic candidates for postmenopausal osteoporosis.

We extracted turmeric volatile oil (TVO) from turmeric using supercritical CO₂ extraction for potential allergic rhinitis (AR) therapy. The volatile components of TVO were analyzed using gas chromatography mass spectrometry and gas chromatography-ion migration spectrometry. The pharmacological effects of TVO on ovalbumin (OVA)-induced AR in mice were evaluated through pathological markers, microbiomics, metabolomics, and proteomics. An inflammatory model using human mast cells (HMCs) was established to assess whether TVO could mitigate inflammation. TVO effectively alleviated AR symptoms in OVA-sensitized mice and reduced inflammation in lipopolysaccharide- and interferon-γ-treated HMCs. TVO suppressed the inflammatory cytokine production, restored the nasal microbiota composition, and regulated serum metabolic profiles. Proteomic analysis using four-dimensional data-independent acquisition indicated that the mitogen-activated protein kinase (MAPK) and transcription factor nuclear factor-κB (NF-κB) signaling pathways are involved in TVO’s anti-inflammatory mechanism. Accordingly, TVO inhibited the activation of MAPK and NF-κB pathways in the OVA mouse model and the inflammatory HMCs model. Jun N-terminal kinase and Relb were identified as key mediators in the therapeutic action of TVO, with Relb knockdown enhancing its anti-inflammatory effect, suggesting that TVO has potential as a therapeutic agent for alleviating AR.

Objective The anti-tumor effects of 3-O-alpha-D-furanoribosyl-damar-24-ene-3 beta, 6 alpha, 12 beta, 20S-tetraol (RPPT) in vitro were explored in the present study.Methods This study initially employed the CCK-8 proliferation inhibition assay to systematically evaluate RPPT's anticancer activity against three distinct tumor cell lineages and its cytotoxic effects on primary normal cell lines. Subsequently, multiparameter flow cytometry was utilized to characterize RPPT's functional attributes, quantitatively analyzing its apoptotic induction efficacy and dose-dependent cell cycle arrest patterns. Furthermore, Transwell migration assays were conducted to determine the derivative's capacity to inhibit tumor cell motility.Results In vitro cytotoxicity assays demonstrate that RPPT exhibits significantly enhanced selective cytotoxic activity against tumor cell lines compared to its natural precursor compound protopanaxatriol. Under same concentration conditions, this derivative demonstrates equivalent biological efficacy to the reference compound Rg3, characterized by dose-dependent inhibitory characteristics. The experimental data reveal that RPPT effectively suppresses tumor cell proliferation through concentration-dependent mechanisms, while maintaining no statistically significant cytotoxic effects on normal cell lines within the tested concentration ranges. Subsequent flow cytometry analysis revealed that RPPT suppress the cell cycle progression by blocking cell entry into the G0/G1 phase, and promoting cell apoptosis. Furthermore, Western blot analysis showed that RPPT could regulate the modulated the equilibrium between anti-apoptotic Bcl-2 and pro-apoptotic Bax, coupled with Caspase-9 activation, indicating that RPPT might facilitate tumor cells apoptosis by activating the apoptotic signaling pathway. Moreover, RPPT could efficiently inhibit the invasion and metastasis.Conclusions In summary, the studies showed that the new derivative RPPT has a strong growth inhibition effect on tumor cells, which expands new sources for subsequent development of potential anti-tumor drugs with more efficacy.

BACKGROUND:Postoperative ileus (POI) is a common complication after abdominal operation, which is characterized by delayed gastrointestinal motility that can lead to prolonged hospitalization. Previous studies have demonstrated that gut microbiota and macrophages are involved in POI pathogenesis, but the underlying mechanism and the role of probiotics in it are still unclear. This work investigated the prophylactic effect of Lactobacillus reuteri (L. reuteri) DSM 17938 administration on POI mice. METHODS:Mice were supplemented with antibiotics or L. reuteri DSM 17938 for two weeks before intestinal manipulation surgery. One day after surgery, the small intestine transit rate was evaluated. Samples were collected to determine the intestinal macrophages, histology, cytokines, gut microbiota, and fecal metabolome. KEY RESULT:Results showed that gut microbiota alteration contributed to POI. L. reuteri DSM 17938 increased intestinal motility of POI mice, maintained the proportion of intestinal CX3CR1+ macrophage, reduced M1 macrophage, and modulated macrophage-associated cytokines. Additionally, L. reuteri DSM 17938 slightly alleviated gut metabolic disorders but had an effect on a portion of metabolites of fecal tryptophan metabolism, modulated gut microbiota composition and function, and specifically suppressed bacterial invasion of epithelial cells and the expansion of Escherichia coli, which had a negative correlation with the small intestine transit rate in POI mice. CONCLUSIONS AND INFERENCES:Our findings indicate that L. reuteri DSM 17938 is a promising probiotic for the prevention of POI, but it still needs further clinical validation.

To compare the patient-level diagnostic accuracy of PSMA-PET with multiparametric magnetic resonance imaging (mpMRI), computed tomography (CT), and bone scintigraphy (BS) for initial T, N, and M staging of newly diagnosed intermediate- to high-risk prostate cancer using paired studies. We searched PubMed, Embase, Web of Science, and Scopus from inception to December 1, 2025, for paired studies in which the same patients underwent PSMA-PET and conventional imaging, with histopathology or predefined composite criteria as the reference standard. Risk of bias was assessed with QUADAS-2 and QUADAS-C. Pooled sensitivity and specificity with 95

Objective Sepsis-induced myocardial injury is a serious complication of sepsis associated with high mortality rates; however, the underlying mechanisms of the pathological process are still incompletely elucidated. This study investigated the function of microRNA-132-3p (miR-132-3p) in sepsis-induced myocardial injury.Methods: miR-132-3p expression profiles, myocardial injury markers, proinflammatory cytokines, and inflammation-related proteins in serum, myocardial tissues, and H9C2 cardiomyocytes were assessed utilizing a suite of techniques, including ELISA, Western blot, and qRT-PCR analysis, after establishing sepsis-triggered myocardial injury models via lipopolysaccharide (LPS) stimulation. Flow cytometry assessed cardiomyocyte apoptosis, and dual luciferase reporter assays confirmed the targeting interaction between miR-132-3p and MyD88. Results In LPS-induced sepsis models, the level of miR-132-3p was significantly reduced, while the content of myocardial injury markers, proinflammatory cytokines, and inflammatory signaling proteins was markedly upregulated compared with control groups. pearson correlation analysis revealed a correlation between miR - 132 - 3p level and MyD88. Overexpression of miR-132-3p alleviated cardiomyopathies in vivo, inhibited cardiomyocyte apoptosis induced by LPS in vitro, Inhibited inflammatory cardiomyocyte cell factors induced by LPS. Mechanically, miR-132-3p targeted the 3′-untranslated region (3′-UTR) of MyD88 directly and remarkably decreased the MyD88 expression along with the MyD88/NF-κB inflammatory signal pathway. Conclusions The findings demonstrate that miR-132-3p, through inhibiting MyD88/NF-κB pathway activation, alleviates sepsis-induced myocardial injury. This mechanistic insight into the role of miR-132-3p may identify novel therapeutic strategies for sepsis-related cardiac dysfunction.

Endometrial cancer (EC) is characterized by metabolic reprogramming, with cholesterol biosynthesis playing a critical role. However, the upstream transcriptional regulation of this process requires further elucidation. In this study, we identified POU2F1 as a key oncogenic transcription factor that drives cholesterol biosynthesis and tumor progression in EC. Integrative bioinformatics and clinical analyses revealed that POU2F1 is upregulated in EC and predicts poor prognosis. Mechanistically, POU2F1 directly activates DHCR24 and ELOVL2 transcription, thereby promoting DHCR24-mediated cholesterol biosynthesis and ELOVL2-associated lipid metabolic remodeling in EC. Functional assays demonstrated that POU2F1 promotes proliferation, migration, invasion, and xenograft growth in a DHCR24/ELOVL2-dependent manner. Clinically, POU2F1 expression was positively correlated with DHCR24 and ELOVL2 levels and served as an independent prognostic factor. Together, these findings establish the POU2F1-DHCR24/ELOVL2 axis as a critical driver of cholesterol-associated lipid metabolic reprogramming and cancer progression in EC, highlighting a potential therapeutic target for metabolic intervention.

Ginseng, a high - value food and medicinal ingredient, is influenced by origin. Prior studies used spectroscopy for component analysis, but model optimization, band application, and field use remain challenging. This study presents a novel method using hyperspectral imaging to create a dual - function non - destructive model. It can measure ginsenoside (RS) and polysaccharide (RP) contents simultaneously and identify the geographic origin. The integrated methodology includes two parts. First, it uses component - specific algorithms for quantitative prediction. ELM performs well in RS prediction in VNIR band (R2 = 0.86), and GA - optimized back - propagation neural network is excellent in RP prediction (R2 = 0.85). Second, it classifies the origin. It can use second - order derivative preprocessing with particle swarm optimization (accuracy = 0.91 in VNIR) or standalone processing (accuracy = 0.91 in short - wave infrared). The developed four - dimensional optimization framework ("component - band - model - feature") shows VNIR's detection advantages for both components and improves feature selection stability by 30 % through GA iterative voting. Therefore, these findings establish an efficient, nondestructive ginseng quality - control tool enabling food producers to verify composition and origin during raw material screening and production standardization.