Search Results (18,606)

Resveratrol (RES), a natural polyphenol with lipid metabolism-regulating properties, also demonstrates remarkable efficacy in strengthening intestinal barrier integrity. In order to elucidate the mechanism by which RES ameliorates intestinal damage and lipid metabolism disturbances in Megalobrama amblycephala under a high-fat (HF) diet, a conventional diet (CON), an HF diet (HF), or an HF diet supplemented with 0.6, 3, or 6 g/kg RES (HF + 0.06%, 0.3%, or 0.6% RES) was fed to fish. After 8 weeks, RES supplementation in the HF diet significantly improved the growth performance and alleviated hepatic lipid deposition. Microbiota profiling revealed RES improved intestinal barrier function by reducing α-diversity, Actinobacteria and Bosea abundances, and enriching Firmicutes abundance. RES also maintained the integrity of the intestinal physical barrier and inhibited the inflammatory response. MeRIP-seq analysis indicated that RES modulated intestinal mRNA m⁶A methylation by upregulating methyltransferase-like 3 (mettl3) and downregulating fat mass and obesity-associated gene (fto) and Alk B homolog 5 (alkbh5). Combined RNA-seq and MeRIP-seq data revealed that RES alleviated endoplasmic reticulum stress (ERS) by upregulating the m⁶A methylation and gene level of heat shock protein 70 (hsp70). Correlation analyses identified significant associations between intestinal microbiota composition and ERS, tight junction, and inflammation. In summary, RES ameliorates lipid dysregulation via a synergistic mechanism involving intestinal microbiota, m⁶A modification, ERS, barrier function, and inflammatory response. Full article

Type 2 diabetes (T2D) is a chronic metabolic disorder marked by insulin resistance and impaired glucose metabolism, with skeletal muscle being a major site of systemic glucose disposal. This review examines the bidirectional relationship between T2D and sarcopenia, and synthesizes current evidence on how skeletal muscle deterioration and insulin resistance interact to disrupt glucose homeostasis. We summarize molecular mechanisms by which physical exercise enhances glucose uptake via insulin-dependent and insulin-independent pathways, and review the ergogenic and metabolic effects of creatine monohydrate (CrM). We also evaluate studies combining CrM supplementation with resistance or aerobic training and their effects on glycaemic control, muscle mass and function. Overall, combined exercise and creatine supplementation show potential to improve glucose regulation and attenuate muscle loss in older adults and people with T2D. Available data indicate that CrM is well tolerated in healthy and clinical populations when used at recommended doses, with no consistent evidence of adverse renal or hepatic effects. Further large randomized trials are needed to define optimal dosing, training modalities and long-term benefits for metabolic outcomes. Full article

Salt stress severely constrains agricultural productivity in arid and semi-arid regions. This study evaluated exogenous proline as an osmoprotector in Physalis ixocarpa Brot. (Mexican husk tomato) under salinity. Germination screening identified 75 mM NaCl as a threshold stress level, reducing germination by 38.9% while maintaining seedling viability. Proline pretreatment (30-min imbibition) at 8 mM restored germination to 78% and fresh weight to control levels under salt stress. In vitro experiments revealed that 8 mM proline enhanced chlorophyll content above salt-stressed controls while reducing root length from 9.72 to 5.08 cm, indicating resource reallocation toward photosynthetic protection. Infrared spectroscopy showed characteristic polysaccharide shifts and bands potentially associated with proline incorporation. Gas chromatography–mass spectrometry metabolomics of stem–leaf extracts revealed salt-induced synthesis of nitrogenous osmolytes (such as long-chain amines) and carbohydrate reorganization from α-D-glucopyranoside to β-D-riboside. Proline treatment restored the original carbohydrate profile while generating pyrrolidine derivatives (2.83%), evidence of active proline metabolism. Phenolic antioxidants (e.g., catechol) present in controls were absent under both salt stress and proline treatment, suggesting that proline’s protective mechanism may operate through metabolic regulation of osmolyte pathways and membrane stabilization rather than inducing phenolic antioxidant synthesis. These findings demonstrate proline’s multifaceted protective mechanisms and support its potential application for enhancing salt tolerance in this crop. Full article

The demand for robust safety monitoring in underground coal mines is increasing, yet traditional methods face limitations in long-term stability due to inadequate energy supply and high maintenance requirements. To address the critical challenges of high computational demand and energy constraints in this resource-limited environment, this paper proposes MineVisual, a battery-free visual sensing scheme specifically designed for underground coal mines. The core of MineVisual is an optimized lightweight deep neural network employing depthwise separable convolution modules to enhance computational efficiency and reduce energy consumption. Crucially, we introduce an energy-aware dynamic pruning network (EADP-Net) ensuring a sustained inference accuracy and energy efficiency across fluctuating power conditions. The system integrates supercapacitor buffering and voltage regulation for stable operation under wind intermittency. Experimental validation demonstrates that MineVisual achieves high accuracy (e.g., 91.5% Top-1 on mine-specific tasks under high power) while significantly enhancing the energy efficiency (reducing inference energy to 6.89 mJ under low power) and robustness under varying wind speeds. This work provides an effective technical pathway for intelligent safety monitoring in complex underground environments and conclusively proves the feasibility of battery-free deep learning inference in extreme settings like coal mines. Full article

Cardiovascular diseases (CVDs) are a group of disorders in which inflammatory processes play a crucial role. Age-related chronic systemic inflammation is characterized by elevated levels of inflammatory mediators in the bloodstream. It can occur even in the absence of overt infection, contributing to endothelial dysfunction, vascular stiffness, and atherosclerosis. The regulation of vascular tissue homeostasis and inflammation is primarily mediated by tissue-resident macrophages (TRMs) and monocyte-derived macrophages. The proportion of monocyte-derived macrophages increases with age, contributing to vascular damage and accelerating CVD progression. In aging tissue, monocyte-derived macrophages exposed to various microenvironmental stimuli are predominantly polarized into the pro-inflammatory M1 phenotype. This polarization, in turn, triggers the release of pro-inflammatory cytokines (IL-1β, IL-6, and IL-18) and promotes the generation of oxidative stress molecules. In this review, we examine the role of macrophages in cardiovascular aging, their secretory phenotypes, and the impact of chronic low-grade inflammation on vascular integrity. We also propose reliable biomarkers of chronic cardiovascular inflammation that may aid in risk prediction, patient stratification, and the development of senotherapeutic interventions for cardiovascular disease. Full article

Curcumin has been extensively investigated as an anticancer agent, yet its clinical application remains constrained by low bioavailability, incomplete mechanistic understanding, and limited therapeutic optimization. In light of growing resistance to conventional chemotherapies and the demand for safer, multi-targeted agents, this review revisits curcumin with a contemporary lens. We critically evaluate the literature published since 2020, focusing on newly elucidated molecular mechanisms by which curcumin regulates tumor progression, including modulation of oncogenic signaling pathways (Wnt/β-catenin, PI3K/Akt/mTOR, JAK/STAT, and MAPK), induction of ferroptosis, and epigenetic reprogramming. A particular emphasis is placed on recent advances in nanoformulation strategies that enhance curcumin’s pharmacokinetic profile and target-specific delivery. Furthermore, the emerging paradigm of combination therapy is explored, where curcumin acts synergistically with chemotherapeutics and phytochemicals to overcome drug resistance and potentiate anticancer efficacy. This review identifies key knowledge gaps, such as inconsistent clinical translation and the underexplored interplay between nanocurcumin systems and immune modulation, outlining directions for future translational research. Full article

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in plant immune responses, yet their roles in rice resistance against Magnaporthe oryzae (M. oryzae) remain inadequately explored. In this study, we integrated translatome data with conventional genome annotations to construct an optimized protein-coding dataset. Subsequently, we developed a robust pipeline (“RiceLncRNA”) for the accurate identification of rice lncRNAs. Using strand-specific RNA-sequencing (ssRNA-seq) data from the resistant (IR25), susceptible (LTH), and Nipponbare (NPB) varieties under M. oryzae infection, we identified 9003 high-confidence lncRNAs, significantly improving identification accuracy over traditional methods. Among the differentially expressed lncRNAs (DELs), those unique to IR25 were enriched in the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan, which suggests that they are associated with the production of salicylic acid (SA) and auxin (IAA) precursors, which may be involved in defense responses. Conversely, DELs specific to LTH primarily clustered within carbon metabolism pathways, indicating a metabolic reprogramming mechanism. Notably, 21 DELs responded concurrently in both IR25 and LTH at 12 h and 24 h post-inoculation, indicating a synergistic regulation of jasmonic acid (JA) and ethylene (ET) signaling while partially suppressing IAA pathways. Weighted gene co-expression network analysis (WGCNA) and competing endogenous RNA (ceRNA) network analysis revealed that key lncRNAs (e.g., LncRNA.9497.1) may function as miRNA “sponges”, potentially influencing the expression of receptor-like kinases (RLKs), resistance (R) proteins, and hormone signaling pathways. The reliability of these findings was confirmed through qRT-PCR and cloning experiments. In summary, our study provides an optimized rice lncRNA annotation framework and reveals the mechanism by which lncRNAs enhance rice blast resistance through the regulation of hormone signaling pathways. These findings offer an important molecular basis for rice disease-resistant breeding. Full article

Background: DNA methylation, as an epigenetic modification, is crucial in the regulatory mechanism of salt resistance in plants. Methods: To gain deeper insight into the relationship between DNA methylation and mRNA exons in halophytes and their potential roles in regulating salt tolerance, this study employed whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing data to analyze the leaves of the halophyte Paspalum vaginatum, widely distributed in tropical regions. Results: The findings revealed that the methylation level of 5-methylcytosine (5mC) in the genomic elements of P. vaginatum increased with prolonged salt treatment under salt stress conditions. This observation suggested that the methylation level plays a pivotal role in the salt stress response of P. vaginatum. Notably, under salt stress, the number of variants at the mRNA exon level was significantly higher than that at the DNA level. Furthermore, comparative analysis revealed sequence variants within exonic regions of mature mRNA transcripts for several genes in salt-treated samples relative to pre-stress controls, and these changes were found to be enriched in several salt-tolerance pathways, including unsaturated fatty acid metabolism and ascorbic acid metabolism, among others. Further analysis demonstrated that the occurrence of these variants changed concomitantly with the dynamic changes in CG methylation levels in the gene body of some salt-tolerant genes. Therefore, it was speculated that mRNA exon variations probably promoted the elevation of CG 5mC methylation levels at the DNA level under salt stress conditions, further enabling the plant to adapt to the salt-stress environment. Conclusions: These findings offer preliminary insights into the relationship between DNA methylation and mRNA exon variations in P. vaginatum under salt stress, providing valuable information and avenues for further investigation into the regulatory role of mRNA in DNA methylation. Full article

Purinergic P2X7 receptors are involved in cellular processes such as inflammation, proliferation, and tissue remodeling, although their significance in human skin physiology remains poorly understood. In this study, we demonstrated strong P2X7 receptor immunoreactivity in the basal and granular layers of the epidermis. Cutaneous expression of P2X7 receptors was further confirmed at the level of specific mRNA and protein in cultured primary human keratinocytes and dermal fibroblasts. To reveal a possible role of these receptors in regulation of keratinocyte and fibroblast function, the cells were treated with a P2X7 agonist BzATP, or its selective antagonist A438079. Cell proliferation and viability were assessed using an immunofluorescence-based cell counter, and cell migration was evaluated by wound healing assay. P2X7 stimulation with BzATP significantly inhibited keratinocyte proliferation and migration, while P2X7 inhibition with A438079 significantly enhanced keratinocyte migration. In contrast, fibroblasts displayed minimal response to either treatment. These findings indicate that P2X7 regulates keratinocyte growth, and purinergic signaling may play a role in the skin. Our data also suggest that selective P2X7 inhibition may support re-epithelialization under conditions associated with impaired wound healing. Full article

Fibrotic diseases contribute to nearly half of all deaths in industrialized countries, yet effective early detection strategies remain lacking, particularly in low-resource settings. This study aimed to quantify the global burden of fibrosis-related diseases using updated global burden of disease (GBD) 2021 data across 204 countries and territories and establish a cost-effective diagnostic approach targeting vestigial-like family member 3 (VGLL3), a fibrosis-associated transcriptional co-regulator. Our analysis revealed that from 1990 to 2021, fibrosis-related disability-adjusted life years (DALYs) and mortality increased by 16.71% and 4.83%, respectively, with neoplasms and chronic obstructive pulmonary disease (COPD) being the main contributors. We also found a growing burden disproportionately concentrated in low socio-demographic index (SDI) regions. To address the diagnostic gap, we developed a novel immunoassay targeting VGLL3, an intrinsically disordered transcriptional co-regulator implicated in early fibrotic remodeling. The assay demonstrated a detection range of 27.01–2512.36 nM and a limit of detection of 12.55 nM. Immunohistochemical validation in a mouse myocardial infarction model confirmed the antibody’s specificity in fibrotic tissues. This work highlights widening global health disparities in fibrosis burden and introduces a cost-effective, scalable diagnostic strategy for early fibrosis detection, particularly suitable for resource-limited settings. Full article

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial cardiovascular disorder characterized by diastolic dysfunction, systemic inflammation, and myocardial fibrosis. Emerging evidence indicates that macrophage polarization imbalance plays a central role in HFpEF pathogenesis. Traditional Chinese medicine (TCM) has demonstrated therapeutic potential in modulating macrophage activity through pathways such as NO/cGMP/PKG, TGF-β/Smads, and PI3K/Akt, thereby exerting anti-inflammatory, antifibrotic, and antioxidant effects. In this review, we conducted a literature search in PubMed, Google Scholar, Web of Science, and CNKI for studies published up to May 2025, using the terms “HFpEF”, “Traditional Chinese Medicine”, and “macrophage”. A total of 19 relevant studies were included. We highlight representative TCM metabolites and TCM formulas, such as resveratrol, Qishen Yiqi Pill, Shenfu Injection, etc. And we summarize their mechanisms in regulating M1/M2 macrophage polarization. Finally, we identify current challenges, including limited HFpEF-specific models and insufficient mechanistic validation, and propose directions for future research. Full article

RNA modifications regulate diverse aspects of transcripts’ function and stability. Among these, N1-methyladenine (m¹A) is a reversible mark primarily installed by the TRMT6/TRMT61A methyltransferase on tRNA, though it is also found on other RNA types. m¹A has been implicated in protecting mRNAs during acute protein misfolding stress. However, the role of m¹A under chronic proteotoxic conditions, such as intracellular amyloid aggregation, remains poorly understood. To address this gap, we examined the effects of reduced N1-adenine methylation in human cells undergoing amyloidogenesis. Suppression of the methyltransferase TRMT61A or overexpression of the m¹A-specific demethylase ALKBH3 enhanced amyloid aggregation. A deficiency of N1-adenine methylation also impaired the expression of a reporter mRNA-encoded protein, highlighting the protective role of m¹A in safeguarding transcript functionality. Proteomic analysis of amyloid aggregates from TRMT61A-deficient cells revealed increased co-aggregation of bystander proteins, particularly those with known RNA-binding activity. At the same time, the aggregates from methylation-deficient cells contained elevated levels of mRNAs. Collectively, our findings support a role for m¹A in preventing RNA entanglement within aggregates and limiting RNA-mediated propagation of protein co-aggregation. Full article

Mammalian sperm has a high metabolic activity and primarily relies on glycolysis and mitochondrial oxidative phosphorylation for energy supply. It has been reported that imiquimod (R837), a specific ligand of TLR7 protein, reduces the motility of sperm. However, the specific molecular mechanism by which TLR7 modulates boar sperm is unclear. In this study, the effect of R837, a Toll-like receptor 7 (TLR7) agonist, on boar sperm motility was investigated. Sperm samples were incubated with varying concentrations of R837 (0 to 0.8 µM) at different time points (30, 60, and 90 min). Findings reveal for the first time that TLR7 protein, a key component of the immune system’s Toll-like receptors, is predominantly localized in the middle section of the boar sperm tail, with a smaller concentration observed in the neck. Also, immunofluorescence (IF) revealed that approximately half of the boar sperm sample expressed TLR7. Furthermore, the TLR7 agonist influenced glycolytic hexokinase activity and mitochondrial function via the PI3K-GSK3β signaling pathway. It also selectively inhibited motility in the lower-layer sperm, while motility in the upper-layer sperm remained unaffected. Additionally, this study determined that incubation conditions for boar sperm with 0.2 μM R837 at 37 °C for 60 min yielded the most pronounced inhibition of forward motility in the lower layer of sperm, without compromising the integrity of the acrosome or plasma membrane. The present study reveals the crucial role of R837 in boar sperm motility and highlights TLR7 as an important protein that regulates boar sperm energy metabolism. Full article

Background/Objectives: Epithelioid Hemangioendothelioma (EHE) is an ultra-rare, metastatic vascular sarcoma with limited therapeutic options. The hallmark of EHE is a chromosomal translocation that produces the WWTR1-CAMTA1 gene fusion, encoding the aberrant transcriptional regulator TAZ-CAMTA1. Given its central role in the EHE initiation and progression, TAZ-CAMTA1 represents a compelling therapeutic target. Methods and Results: In this study, we identified AMP-activated protein kinase (AMPK) as one of several proteins capable of repressing the TAZ-CAMTA1 transcriptional activity in NIH3T3 and HEK293 cell lines. The pharmacologic activation of AMPK inhibited the proliferation of EHE cell lines without inducing apoptosis; however, in contrast to the NIH3T3 and HEK293 models, AMPK activation in EHE cells unexpectedly increased the TAZ-CAMTA1 expression and activity. Notably, elevated TAZ-CAMTA1 expression was also associated with reduced EHE cell growth, suggesting that the induction of TAZ-CAMTA1 may be one mechanism by which AMPK suppresses EHE growth. Additionally, we found that AMPK inhibits mTOR activity and that direct mTOR inhibition also suppresses EHE cell growth. Conclusions: Together, these findings demonstrate that AMPK activation impairs EHE viability through dual mechanisms: by promoting TAZ-CAMTA1 expression and by inhibiting mTOR signaling. This work highlights AMPK as a potential therapeutic target in EHE and supports the growing body of evidence favoring mTOR inhibitors as promising treatments for this rare cancer. Full article

Extra-osseous calcification refers to the pathological deposition of calcium salts in soft tissues. Its most recognized forms affect the cardiovascular system, leading to vascular and heart valve calcifications. This process is active and regulated, involving the phenotype transition of resident cells into osteo/chondrogenic lineage. Chronic kidney disease (CKD) patients frequently suffer from vascular and other soft tissue calcification. OsteoSense dyes are fluorescent imaging agents developed to visualize calcium deposits during bone formation. In addition to its application in bone physiology, it has been used to detect vascular smooth muscle cell calcification in vitro and to evaluate calcification ex vivo. Here, we investigated CKD-associated soft tissue calcification by applying OsteoSense in vivo. CKD was induced by a diet containing adenine and elevated phosphate. OsteoSense (80 nmol/kg body weight) was injected intravenously through the retro-orbital venous sinus 18 h before the measurement on an IVIS Spectrum In Vivo Imaging System. OsteoSense staining detected calcium deposition in the aorta, kidney, heart, lung, and liver in CKD mice. On the other hand, no calcification occurred in the brain, eye, or spleen. OsteoSense positivity in the calcified soft tissues in CKD mice was associated with increased mRNA levels of osteo/chondrogenic transcription factors. Our findings demonstrate that OsteoSense is a sensitive and effective tool for detecting soft tissue calcification in vivo, and may be particularly valuable for studies of CKD-related ectopic calcification. Full article