Search Results (304)

R-loops, three-stranded nucleic acid structures formed by an RNA-DNA hybrid, have emerged as important regulators of transcription and genome stability. Although advances in high-throughput sequencing have revealed widespread R-loop landscapes, platform-specific biases hinder the identification of conserved R-loops in specific cell types. Mouse embryonic stem cells, which are transcriptionally active, provide an ideal system for investigating the potential roles of stable R-loops in RNA biology. Here, we integrated 13 independent R-loop profiling datasets from four experimental platforms to define 27,950 Common R-loop regions in mouse embryonic stem cells and characterized their chromatin environment and associated biological functions. Common R-loop regions were reproducibly detected across methods and were preferentially localized to promoter-proximal and genic regions enriched in CpG islands. Genes associated with Common R-loops were highly and stably expressed, showing strong functional enrichment in RNA metabolic processes such as mRNA processing, RNA splicing, and ribonucleoprotein complex biogenesis. Chromatin state analysis revealed that Common R-loops are enriched in transcriptionally active and regulatory contexts. Sequence feature analysis further identified GC skew as a prominent signature of Common R-loops, particularly within transcribed chromatin states. Transcription factor motif analyses have identified distinct regulatory environments in Common R-loop regions, including pluripotency-associated OCT4-SOX2-TCF-NANOG motifs in enhancers, CTCF motifs in open chromatin, and YY1 motifs in promoters. Together, this study provides the first integrated analysis of conserved R-loop regions in mouse embryonic stem cells, revealing their preferential localization at regulatory loci linked to RNA metabolism and highlighting R-loops as structural and functional nodes in RNA biology. Full article

Carbon nanotubes (CNTs) represent promising nanoplatforms for drug delivery due to their high surface area, tunable surface chemistry, and unique physicochemical properties. This study investigated the effect of chemical functionalization on the dispersion, drug loading, release behavior, aerosolization, and preliminary in vitro cytotoxicity of CNT-based drug delivery systems, with a view toward potential intranasal applications. Pristine CNTs and CNTs functionalized with hydroxyl (–OH) and carboxyl (–COOH) groups were loaded with methylene blue as a model therapeutic compound. The nanosystems were characterized using Raman spectroscopy, UV–Vis analysis, aerosol deposition measurements, electrical mapping by conductive atomic force microscopy (C-AFM), and MTT cytotoxicity assays. Functionalization significantly enhanced CNT dispersion stability and drug release control, with COOH–CNTs exhibiting the most sustained release profile and improved cytocompatibility, maintaining cell viability above XX% at concentrations up to YY µg/mL. Aerosolization tests demonstrated stable droplet formation compatible with nasal delivery devices. Overall, this work provides a proof-of-concept physicochemical and technological assessment of functionalized CNTs as potential carriers for intranasal drug delivery, laying the groundwork for future in vivo validation. Full article

Reproductive traits are critical for improving productivity and profitability in the pig industry, and genome-wide association studies (GWASs) are a powerful tool in detecting genetic markers related to target traits. Genome imputation provides an effective approach to obtain a greater number of genetic markers from low-density sequencing data. China’s pig industry recently introduced an imputation panel and is now seeking to determine what types of data are required to meet breeding needs. In this study, we collected and analyzed two pig sequencing datasets, including Yorkshire pig (YY), Landrace pig (LL), and Duroc pig (DD), genotyped by either an SNP chip (n = 816) or genotyping-by-targeted sequencing (n = 314), and applied an imputation strategy before validation in a third dataset (n = 2401). The aim of this study was to identify SNPs associated with reproductive traits and compare imputation results of two different types of data to evaluate whether sample size or marker density more strongly impacts imputation-enabled GWAS performance. Through a GWAS, we identified 73 significant SNPs from imputed Chip data across seven reproductive traits, 94 SNPs from imputed GBTS data across three traits, and 34 SNPs from the combined dataset across seven traits. Seven of these SNPs passed validation and were associated with number born alive, number born healthy, and gestation length. Gestation length (GL) and number born alive (NBA) are the most noteworthy traits. LOXL2 and PTPRD are high-confidence candidate genes affecting GL and NBA, respectively. In addition to LOXL2, STC1, NKX2-6, HMGCLL1, MLIP, TINAG, FAM83B, GFRAL, HCRTR2, ENTPD4, MYH8, IER5L, and U5 are associated with GL. Moreover, in addition to PTPRD, KLHL32, U6, MMS22L, and FHL5 are associated with NBA. The results of this study indicate that sample size is of greater importance than marker density in imputation strategies and provide beneficial insights into genes affecting pigs’ reproductive traits. Full article

The wnt gene family encodes a group of highly conserved secreted glycoproteins that play essential roles in vertebrate development, including tissue patterning, cell differentiation, and gonadal regulation. However, the genomic organization, evolutionary dynamics, and functional roles of Wnt signaling components in flatfish remain poorly understood. In this study, we performed a comprehensive genome-wide identification, evolutionary characterization, expression profiling, and functional analysis of wnt genes in Cynoglossus semilaevis, a flatfish species exhibiting ZW/ZZ sex determination and temperature-induced sex reversal. A total of 20 wnt genes were identified and classified into 13 subfamilies, displaying conserved structural organization and phylogenetic relationships consistent with other teleosts. Chromosomal mapping revealed lineage-specific WNT clusters, including a unique wnt3–wnt7b–wnt5b–wnt16 block, as well as syntenic associations with reproduction-related genes (e.g., adipor2, sema3a, nape-pld, erc2, lamb2), suggesting coordinated genomic regulation. Tissue transcriptome analysis demonstrated strong sex- and tissue-biased expression patterns, with wnt5a predominantly expressed in ovaries and wnt5b specifically upregulated in pseudo-male testes. Functional assays revealed that knockdown of wnt5a or wnt5b induced testis-specific genes (sox9b, tesk1) and suppressed ovarian markers (foxl2, cyp19a1a), indicating antagonistic regulatory roles in gonadal fate determination. Promoter analysis identified yy1a as a selective repressor of wnt5b, but not wnt5a, providing a mechanistic basis for paralog divergence. Furthermore, pull-down combined with LC–MS/MS analysis showed that WNT5b interacts with proteins enriched in ribosome biogenesis and ubiquitin-mediated proteolysis, suggesting a role in translational regulation and protein turnover during spermatogenesis. Together, these findings establish WNT5 signaling—particularly wnt5b—as a key driver of testicular development in C. semilaevis and provide new insights into the molecular mechanisms underlying sex differentiation and sex reversal in flatfish. Full article

Background: Malnutrition and sleep disturbances are common in childhood and are associated with neuropeptides that regulate appetite and circadian rhythms. Hypothalamic peptides such as orexin A, agouti-related protein (AgRP), proopiomelanocortin (POMC), and peptide YY (PYY) play important roles in energy balance and eating behavior; however, their specific functions in pediatric malnutrition remain unclear. This study aimed to determine the levels of these peptides in malnourished children and to examine their relationship with eating and sleep behaviors. Methods: This case–control, cross-sectional study included 99 children aged 5–15 years diagnosed with malnutrition and 85 age-matched healthy controls. Blood samples were collected from all participants, and peptide levels were measured using ELISA. Additionally, the Children’s Eating Behaviour Questionnaire (CEBQ) and the Children’s Sleep Habits Questionnaire (CSHQ) were administered to assess eating patterns and sleep behaviors. Statistical comparisons and hierarchical logistic regression analyses were performed. Results: Orexin A and PYY levels were significantly higher in malnourished children than in controls (p < 0.001). No significant group differences were found for AgRP and POMC, although AgRP tended to be lower and POMC higher in the malnutrition group. Regression analyses identified orexin A and PYY as significant predictors of malnutrition. Orexin A showed a positive correlation with emotional undereating. Sleep habits did not differ significantly between groups. Conclusions: Elevated orexin A and PYY levels may function as potential neuropeptidergic biomarkers of malnutrition. Their association with emotional eating highlights the psychobiological components of malnutrition. Further longitudinal studies are warranted to clarify causal mechanisms and support clinical translation. Full article

The cryptochromes (CRYs) perceive blue light to regulate various developmental and metabolic events. However, the role of CRYs in flavonoid biosynthesis and flower pigmentation in safflower (Carthamus tinctorius L.) remains unknown. In this study, we determined flower color diversity among 485 safflower genotypes using the integrated CIELAB color space parameters and cluster analysis. On this basis, distinct colors were categorized into four groups, namely white (WW), yellow (YY), orange–red (OR), and yellow–red (YR). A genome-wide association study (GWAS) via 933,444 high-quality SNPs showed CtCRY2 as a flower color variation gene. Subsequently, genomic analysis identified three genes of the CRY family, including CtCRY1.1, CtCRY1.2, and CtCRY2. In silico analysis, such as gene structure, phylogeny and cis-acting elements, suggested CtCRY1.1 as a key candidate in pigment biosynthesis and was, therefore, selected for functional validation. Overexpression of CtCRY1.1 in Arabidopsis accumulated a high flavonoid content, particularly upregulating the expression of CHS, FLS, and ANS, proving its role as a positive regulator of flavonoid biosynthesis in safflower. These findings provide insights into the molecular mechanisms underlying flower color regulation in safflower and highlight CtCRY1.1 as a new target to enhance pigment-related traits in plants. Full article

1,5-Pentanediamine (PDA) is an important monomer for the synthesis of nylon materials. However, its microbial production from glucose is severely limited by product cytotoxicity, which slows the metabolism of both precursor lysine and glucose uptake. To overcome this limitation, a PDA-responsive dynamic regulatory switch (PDRS) was constructed using the transcriptional repressor CgmR and the P_cgmA promoter. By replacing promoters and ribosome-binding sites, the response window of the PDRS was optimized to a PDA concentration range of 38.9–87 g/L. Based on this system, the PDRS was employed to enhance lysine biosynthesis and glucose uptake. Following fermentation optimization, the optimal strain Corynebacterium glutamicum YY3.6 produced 105.5 g/L PDA within 36 h, achieving a PDA productivity of 2.93 g/L/h and a yield of 0.36 g/g glucose. Collectively, these results provide an effective strategy for the microbial production of PDA from glucose. Full article

The article presents a blockchain-based architecture for decentralized electricity trading that tokenizes energy delivery rights and cash-flows. Energy Attribute Certificates (EACs) are implemented as NFTs, while buy/sell orders are encoded as ERC-1155 tokens whose tokenId packs a time slot and price, enabling precise matching across hours. A clearing smart contract (Matcher) burns filled orders, mints an NFT option, and issues two ERC-20 assets: PT, the right to consume kWh within a specified interval, and YT, the producer’s claim on revenue. We propose a simple, linearly increasing discounted buyback for YT within the slot and introduce an aggregating token, IndexYT, which accumulates YTs across slots, redeems them at par at maturity, and gradually builds on-chain reserves—turning IndexYT into a liquid, yield-bearing instrument. We outline the PT/YY lifecycle, oracle-driven policy controls for DSO (e.g., transfer/splitting constraints), and discuss transparency, resilience, and capital efficiency. The contribution is a Pendle-inspired split of electricity into Principal/Yield tokens combined with a time-stamped on-chain order book and IndexYT, forming a programmable market for short-term delivery rights and yield derivatives with deterministic settlement. Full article

Desertification poses a severe challenge in China. Although long-term sand control measures have proven effective, the extensive and challenging nature of sandy land necessitates systematic research to identify optimal sand control measures for soil amelioration, thereby promoting ecological restoration in sandy areas. This study focused on the Gonghe Basin to assess the effectiveness of four 24-year afforestation treatments—Salix cheilophila + Populus simonii, S. cheilophila, P. simonii (YY), and Caragana korshinskii—compared to untreated mobile dunes. Surface soils (0–10 cm and 10–20 cm) were analyzed for physicochemical properties, enzyme activities, and bacterial community structure using Illumina high-throughput sequencing and PICRUSt2 functional prediction. All afforestation treatments significantly improved soil quality, increasing fine particle content, moisture, nutrients, enzyme activity, and microbial richness and diversity, especially in the topsoil. Bulk density and pH were notably reduced. Among the treatments, YY demonstrated the most substantial improvements. pH emerged as the primary factor influencing bacterial community structure, with enzyme activities also playing a significant role. Metabolism was the dominant functional category across all sites, while YY enhanced environmental information processing functions in the topsoil. Secondary functions showed high redundancy across treatments. These findings confirm that afforestation can effectively rehabilitate degraded alpine sandy soils, with the YY treatment offering the greatest benefits. The study provides a scientific basis for optimizing sand control measures and supports broader ecological restoration efforts in similar environments worldwide. Full article

Antiretroviral therapy (ART) adherence behavior is heterogeneous among adolescents and young adults (AYAs) with HIV and influenced by individual and interpersonal psychosocial factors. The primary objective of this study is to characterize ART adherence phenotypes and psychosocial symptom clusters, as related to ART adherence and HIV viral load suppression. This analysis included 60 AYAs with HIV enrolled in an ART adherence support clinical trial. Self-reported ART adherence at baseline, 12-weeks, and 24-weeks was used to define four ART adherence phenotypes: consistently high adherence (YY), early-only adherence (YN), late-only adherence (NY), and consistently low adherence (NN). Symptom clusters were empirically derived from baseline psychosocial measures, including adherence self-efficacy, ART knowledge, HIV stigma, psychological distress (depression, anxiety, trauma), and social support. Linear mixed-effects models were used to examine psychosocial symptom outcomes at three timepoints (baseline, 12-weeks, and 24-weeks) and across groups with different adherence or viral load phenotypes. Using hierarchical clustering, four distinct clusters were identified, underscoring heterogeneity of psychosocial symptoms and patterns of ART and viral suppression. Findings from this analysis are among the first known characterizations of ART adherence phenotypes and psychosocial symptom clusters among AYAs with HIV. Heterogeneity in clusters underscores the need to examine other factors, such as resilience, not captured in the present study. Overall, these study findings contribute to improved understanding of the multi-level psychosocial influences of ART adherence and viral load suppression. Full article

The current known data on the involvement of the peptidergic systems in breast cancer progression is overwhelmingly vast. Peptidergic systems are useful tools for imaging, diagnosis, prognosis and treatment of breast cancer. These systems play a crucial role in both basic and clinical breast cancer research by enabling the exploration of novel molecular mechanisms, signaling pathways, and the development of effective drug design strategies. Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1–7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin). This indicates that peptides, as well as peptide receptor agonists and antagonists, may serve as antitumor agents due to their diverse actions against breast cancer development, including the inhibition of cell proliferation, migration and invasion, induction of apoptosis, and anti-angiogenesis. Multiple strategies have been developed to combat breast cancer, including peptide receptor silencing; antibodies conjugated to specific signaling proteins; antibodies targeting specific peptide receptors or oncogenic peptides; and the use of peptides or peptide receptor agonists/antagonists loaded with antitumor cargo. Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9–39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review. Peptidergic systems have tremendous anti-breast-cancer clinical potential which must be exploited and developed. Taken together, the available data highlight the enormous promise of translational research into breast cancer and peptidergic systems for the development of effective treatments. A full understanding of the roles played by the peptidergic systems in breast cancer will serve to improve diagnosis and treatment. Full article

Kisspeptin is a neuropeptide recognised for a pivotal role within the reproductive system, but potentially important endocrine metabolic effects are less well understood. We examined effects of twice-daily intraperitoneal administration of saline vehicle or kisspeptin-10 (25 nmol/kg), for 21 days, on glucose homeostasis, energy balance, circulating hormones as well as the morphology-function of enteroendocrine and islet cells in high-fat diet (HFD) fed female mice, with normal diet (ND) mice as an additional control group. Kisspeptin-10 decreased body weight, blood glucose and energy intake to ND levels. HFD increased circulating follicle-stimulating hormone (FSH) levels, which were further enhanced by kisspeptin-10 along with luteinising hormone (LH) concentrations. Neither HFD nor kisspeptin-10 affected progesterone or corticosterone. In the ileum, kisspeptin-10 decreased crypt depth and restored villi length to ND control levels, as well as increasing the proportion of glucose-dependent insulinotropic polypeptide (GIP) positive cells when compared to HFD mice and glucagon-like peptide-1 (GLP-1) positive cells compared to ND mice. Peptide YY (PYY) immunoreactivity was unaltered by HFD or kisspeptin-10. Plasma GIP was unchanged but circulating GLP-1 and PYY were reduced to ND levels. Within the pancreas, total islet, beta- and alpha-cell areas were similar in all mice, but kisspeptin-10 intervention restored relative insulin area to ND levels. Glucagon radius, an indicator of peripherally located alpha-cells, was reduced in HFD mice but normalised by kisspeptin-10 alongside elevated glucagon-islet area. Notably, beta-cell proliferation was increased by kisspeptin-10 with no alteration in beta-cell apoptosis. Overall, we reveal a previously uncharacterised diverse metabolic role for kisspeptin in directly modulating the gut–pancreatic axis. Full article

Type 2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance, progressive β-cell dysfunction, and persistent hyperglycemia. While GLP-1 receptor agonists have revolutionized the management of T2D by improving glycemic control and reducing body weight, their insulinotropic effects increase the workload on pancreatic β-cells, which may hasten β-cell decline in certain individuals. Peptide YY (PYY), a gut-derived hormone secreted alongside glucagon-like peptide-1 (GLP-1) from L-cells, presents a unique and complementary therapeutic approach. In contrast to GLP-1, PYY does not directly induce insulin release but confers metabolic advantages by suppressing appetite through Y2 receptor pathways, enhancing insulin sensitivity via peripheral Y1/Y4 receptors, and slowing gastric emptying to minimize postprandial glucose surges. Notably, recent research suggests PYY supports the preservation and restoration of pancreatic islets by improving their structure and function without increasing the secretory demand. PYY levels are substantially increased after bariatric surgery, where it plays a pivotal role in weight-loss-independent improvements in glycemic regulation and islet hormone dynamics. These attributes position PYY as a strong candidate for use in combination with GLP-1 analogs, especially in individuals with advanced β-cell impairment or those who respond inadequately to GLP-1 monotherapy. This review discusses PYY’s physiological functions, mechanistic actions, and therapeutic opportunities in T2D, highlighting its potential as a valuable adjunct or alternative in gut-hormone-oriented treatment strategies. Full article

A good understanding of the effects of different afforestation measures in alpine sandy land on the physicochemical properties, enzymatic activities, and bacterial community structure of such crusts enables elucidation of the succession patterns of biological soil crusts and provides a theoretical basis for precise optimization of desertification control programs in alpine sandy land. In the present study, four afforestation measures—Salix cheilophila+ Populus simonii (WLYY00), S. cheilophila (WL), P. simonii (YY), and Caragana korshinskii (NT00) plantations—were adopted. The physicochemical properties and enzymatic activities of bare sand, algae crust, and moss crust in the four afforested sites were analyzed using Illumina high-throughput sequencing and PICRUSt2 functional prediction to investigate the bacterial community structure and function. Results indicated the following: (1) Water content, nutrient content, enzymatic activities, and bacterial community richness and diversity increased stepwise with succession from the bare sand stage to algae crust and to moss crust. The enhancement effect of YY on the above indicators and fine particle content was most prominent. (2) The primary environmental factors affecting bacterial community structure in algae and moss crusts were adequate phosphorus and organic matter, respectively, and the correlations between the activities of the four enzymes and the bacterial community structure are also quite close. (3) Functional prediction indicated that metabolism was the main primary function of biological soil crusts at the various sample sites. YY maintained the balance of primary functions and provided precise support for the physiological characteristics and ecological needs of different crust types in the secondary functions. In conclusion, among the four types of afforestation measures with a restoration period of 24 years, YY provided a greater advantage in improving the nutrient content, bacterial community structure, and functional potentials of biological soil crusts. The results of this study can serve as a scientific reference for screening of afforestation measures and protecting and utilizing biological soil crusts during the ecological restoration of alpine sandy lands in the present study area and other regions. Full article

MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology and cardiovascular disease. miR-106b-5p, a member of the miR-106b-25 cluster, has been widely studied for its oncogenic activity in various malignancies. However, its role as a direct molecular driver of anthracycline-induced cardiotoxicity has only recently been uncovered. This finding highlights new therapeutic possibilities at the intersection of oncology and cardiovascular medicine. This review outlines the dual role of miR-106b-5p as a key modulator in both tumor progression and chemotherapy-induced cardiac dysfunction. miR-106b-5p is upregulated in numerous cancers—including breast, prostate, lung, gastric, colorectal, hepatocellular, and esophageal—and promotes tumorigenesis via suppression of tumor suppressors such as PTEN, BTG3, p21, and SMAD7, leading to activation of oncogenic pathways like PI3K/AKT and TGF-β. Importantly, we present the first evidence that miR-106b-5p is significantly upregulated in the myocardium in response to doxorubicin treatment, where it drives left ventricular dysfunction by targeting PR55α, a key regulator of PP2A activity. This pathway results in cytoplasmic HDAC4 accumulation, aberrant activation of the YY1 transcription factor, and upregulation of sST2, a biomarker linked to adverse cardiac remodeling and poor prognosis. In response, we developed AM106, a novel locked nucleic acid antagomir that silences miR-106 b-5p. Preclinical studies demonstrate that AM106 restores PR55α/PP2A activity, reduces sST2 expression, and prevents structural and functional cardiac damage without compromising anti-tumor efficacy. In parallel, artificial intelligence (AI) tools could be leveraged in the future—based on established AI applications in miRNA cancer research—to accelerate the identification of miR-106b-5p-related biomarkers and guide personalized therapy selection. Our findings position miR-106b-5p as a previously unrecognized molecular bridge between cancer and doxorubicin-induced cardiotoxicity. The development of the AM106 antagomir represents a promising approach with potential clinical applicability in cardio-oncology, offering dual benefits: tumor control and cardioprotection. Coupling this innovation with AI-driven analysis of patient data may enable precision risk stratification, early intervention, and improved outcomes. miR-106b-5p thus emerges as a central therapeutic target and biomarker candidate for transforming the clinical management of cancer patients at risk for heart failure. Full article