Search Results (8,854)

Mumps virus (MuV) is a single-stranded, negative-sense RNA virus of the Family Paramyxoviridae. MuV is a highly contagious human pathogen that causes primarily mild symptoms, including hallmark swelling of the parotid glands. Severe cases can occur, leading to neurological complications, including deafness, meningitis, and encephalitis. The mumps vaccine, now included in combination with measles and rubella vaccines (MMR), was first made available in the 1960s. After its introduction, mumps incidence dropped dramatically to less than 500 cases annually in the US. However, even with long-standing vaccination programs, MuV continues to challenge the landscape of public health due to a resurgence of cases in the past several decades and a still present lack of approved antiviral drugs and treatments available for the disease. This review will explore the biology of MuV, focusing on how MuV replicates and interacts with the host immune system. Recent studies have also shed light on the role of protein phosphorylation in regulating viral RNA synthesis—particularly the dynamic interactions between the nucleoprotein (NP) and phosphoprotein (P)—offering new insights into how the virus controls its replication machinery both mechanistically and through utilizing host cell advantages. We also examine how the immune system responds to mumps infection and vaccination, and how those responses may vary across viral genotypes. Although the Jeryl Lynn vaccine strain has played a key role in controlling mumps for decades, outbreaks among vaccinated individuals have raised questions about the present vaccine’s efficacy against circulating and emerging genotypes and if novel strategies will be required to prevent future outbreaks. We review current epidemiological data, highlighting shifts in MuV transmission and genotype distribution, and discuss the need for updated or genotype-matched vaccines. By connecting molecular virology with real-world trends in disease spread and vaccine performance, this review aims to support ongoing efforts to strengthen mumps control strategies and inform the development of next-generation vaccines. Full article

Background: The family Cyprinidae is predominantly restricted to freshwater habitats, making the evolution of diadromy and seawater adaptation exceptionally rare within this group. Pseudaspius hakonensis, a rare anadromous cyprinid, and its strictly freshwater congener P. leptocephalus, provide an ideal comparative model to investigate the molecular mechanisms underlying salinity adaptation. This study aimed to elucidate the tissue-specific transcriptional reprogramming, identify candidate genes and key pathways, and explore their association with seawater acclimation in P. hakonensis. Methods: We performed comparative transcriptomic analyses of gill, liver, and kidney tissues from both species using RNA-Seq. Sequencing reads were aligned to a high-quality reference genome of P. hakonensis. Differential expression analysis was conducted using DESeq2, followed by functional enrichment analyses (GO and KEGG) to identify significant biological processes and pathways. Results: A total of 8784, 5965, and 5719 differentially expressed genes (DEGs) were identified in gill, kidney, and liver tissues, respectively, with the gill showing the highest differences. Functional enrichment revealed tissue-specific roles: gill DEGs were associated with protein synthesis and energy metabolism; kidney DEGs with transport and detoxification; and liver DEGs with metabolic regulation and stress signaling. Cross-tissue analysis highlighted three core pathways consistently enriched: MAPK signaling, ABC transporters, and glutathione metabolism. Key candidate genes, including DUSP10, SLC38A2, ATP8B1, GSTA4, and MGST1, were significantly upregulated in P. hakonensis. Conclusions: This first multi-tissue transcriptomic comparison of an anadromous and a freshwater cyprinid reveals pervasive, tissue-specific molecular reprogramming underlying seawater adaptation in P. hakonensis. The coordinated activation of MAPK signaling, glutathione metabolism, and transporter pathways suggests an integrated regulatory network for osmoregulation and stress resistance. These findings provide novel insights into the genetic basis of salinity adaptation in cyprinids and identify candidate genes for future functional validation. Full article

Osteoarthritis (OA) is the most common multifactorial joint disease characterized by progressive cartilage degradation and impaired tissue repair. Osteochondral defects represent a major clinical challenge within OA, as damage to cartilage and underlying bone can initiate degenerative changes and contribute to joint deterioration. The Wnt/β-catenin signaling pathway plays an important role in OA pathogenesis, and its dysregulation contributes to chondrocyte catabolism and cartilage loss. NOTUM, an extracellular Wnt inhibitor, has emerged as a potential therapeutic modulator capable of restoring signaling balance and promoting cartilage homeostasis. This study aimed to evaluate the efficacy of NOTUM compared with hyaluronic acid (HA), human adipose-derived mesenchymal stromal cells (hAd-MSCs), and Colchicine in a rabbit osteochondral defect model relevant to osteoarthritis. Twenty-seven New Zealand White rabbits underwent standardized femoral condyle injury and received single-dose treatments. Serum levels of cartilage biomarkers—Procollagen Type IIA N-terminal Propeptide (PIIANP) and Cartilage Oligomeric Matrix Protein (COMP)—were measured by ELISA at 4, 6, and 8 weeks post-surgery, and histological repair at week 12 was assessed using the modified O’Driscoll scoring system. NOTUM treatment significantly increased PIIANP and decreased COMP levels compared with HA, indicating enhanced cartilage synthesis and reduced degradation. Histological scores confirmed superior surface morphology and tissue composition in NOTUM-treated joints. These findings suggest that NOTUM performs a protective and regenerative effect through Wnt/β-catenin modulation, supporting the conclusion that it enhances osteochondral defect repair and motivating further studies of NOTUM as an OA therapy. Full article

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease often causing functional disability. Current therapies provide only temporary relief and can cause adverse effects that frequently result in pain and disability. Current pharmacological options offer only temporary symptom relief and may cause adverse effects. Piper sarmentosum (PS), a plant traditionally used for its medicinal properties, has demonstrated antioxidant and anti-inflammatory activities that may counteract OA-related degeneration. This study provides preliminary insight into the therapeutic potential of PS aqueous extract in human OA chondrocytes. Methods: Compounds in the PS aqueous extract were profiled using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Primary human OA chondrocytes (HOCs) were treated with 0.5, 2, and 4 µg/mL of PS aqueous extract for 72 h. Key OA-related parameters were assessed, including anabolic markers (sulfated glycosaminoglycan (sGAG), collagen type II (COL II), aggrecan core protein (ACP), SRY-box transcription factor 9 (SOX9)), catabolic markers (matrix metalloproteinase (MMP) 1, MMP13, cyclooxygenase 2 (COX2)), oxidative stress (nitric oxide (NO) production, inducible NO synthase (iNOS) expression), and inflammatory responses (interleukin (IL) 6). Gene expression was quantified using qPCR, and protein levels were evaluated using the colorimetric method, immunocytochemistry, and Western blot. Results: A total of 101 compounds were identified in the extract, including vitexin, pterostilbene, and glutathione—bioactives known for antioxidant, anti-inflammatory, and chondroprotective functions. PS-treated chondrocytes maintain healthy polygonal morphology. PS aqueous extract significantly enhanced anabolic gene expression (COL2A1, ACP, SOX9) and sGAG production, while concurrently suppressing COX2 expression and NO synthesis. Additionally, PS aqueous extract reduced COX2 and iNOS protein levels, indicating inhibition of the NO signaling pathway. Catabolic activity was attenuated, and inflammatory responses were partially reduced. Conclusions: PS aqueous extract exhibits promising chondroprotective, antioxidant, and anti-inflammatory effects in human OA chondrocytes, largely through the suppression of NO-mediated catabolic signaling. The presence of multiple bioactive compounds supports its mechanistic potential. These findings highlight PS aqueous extract as a potential therapeutic candidate for OA management. Further ex vivo and in vivo studies are warranted to validate its efficacy and clarify its mechanism in joint-tissue environments. Full article

Background: The anabolic window hypothesis suggests a limited post-exercise period for optimal nutrient uptake and utilization. Prior research indicates that miRNAs in extracellular vesicles (EVs) may regulate post-exercise adaptation by influencing protein synthesis. This study aimed to examine the effects of resistance exercise (RE) on physiological parameters and the expression and function of miRNAs transported in EVs. Methods: Twenty resistance-trained male participants (22 ± 2 years) completed a five-week RE program designed for hypertrophy. They consumed maltodextrin and whey protein based on assigned nutrient timing: immediately post-exercise (AE), three hours post-exercise (AE3), or no intake (CTRL). Body composition and knee extensor strength were assessed. Small EVs were isolated and then validated via three methods. Nanoparticle tracking analysis determined EV concentration and size, followed by pooled miRNA profiling and signaling pathway analysis. Results: Skeletal muscle mass significantly increased in AE (p = 0.001, g = 2) and AE3 (p = 0.028, g = 1), and it was higher in AE compared to CTRL (p = 0.013, η² = 0.41), while knee extensor strength improved only in AE (p = 0.032, g = 0.9). Body fat percentage significantly decreased in all groups, AE (p = 0.005, g = 1.5), AE3 (p = 0.024, g = 1), and CTRL (p = 0.005, g = 1.7). Vesicle concentration significantly increased in the AE group (p = 0.043, r = 0.7), while it decreased in the CTRL group (p = 0.046, r = 0.8). Distinct miRNA expression profiles emerged post-intervention: 20 miRNAs were upregulated in AE, while 13 in AE3 and 15 in CTRL were downregulated. Conclusions: Nutrient timing influences training adaptation but is not more critical than total macronutrient intake. Changes in EV-transported miRNAs may regulate anabolic processes via the PI3K-AKT-mTOR and FoxO pathways through PTEN regulation. Full article

This systematic review critically evaluates and synthesizes current evidence on the efficacy of biostimulants in enhancing soybean seed yield and quality. A comprehensive literature search was conducted following the PRISMA approach using the Web of Science (WoS) database, focusing on peer-reviewed studies from 2014 to 2025 reporting on the effects of biostimulants applied alone or in combination with other agro-inputs on soybean performance. Over 500 publications were retrieved from the database, of which 72 were included in this review. Extracted data were used to calculate changes in yield (kg ha⁻¹), percentage yield increase (%), oil content (%), and protein concentration (%). Our synthesis demonstrated that the sole application of biostimulants, including seaweed extracts, humic acids, amino acids, and beneficial microbes (Bradyrhizobium, PGPR, AMF), consistently enhanced soybean yield by 4% to 65%, while their interaction with other agro-inputs was shown to be capable of increasing yield by more than 150% under abiotic stress conditions, indicating strong synergistic effects. These improvements are mediated through various physiological mechanisms such as enhanced nutrient uptake, improved root growth, increased photosynthetic efficiency, and elevated stress tolerance. Furthermore, biostimulant application positively affects seed quality, increasing oil and protein content by 0.4–5.5% and 0.5–7.3%, respectively, by optimizing source–sink relationships and metabolic pathways. Overall, the greatest benefits are frequently observed through synergistic combinations of biostimulants with one another or with reduced rates of mineral fertilizers, highlighting a promising pathway toward sustainable crop intensification in soybean systems. Full article

N6-methyladenosine (m6A), a predominant and reversible modification of mammalian RNA, plays a critical role in regulating growth, development, and metabolism. While methyltransferase-like 14 (METTL14) is an essential component of the m6A methyltransferase complex, its specific function in regulating milk fat metabolism in dairy goats remains unexplored. This study therefore aimed to elucidate the role of METTL14 in lipid metabolism within dairy goat mammary epithelial cells (GMECs). METTL14 overexpression significantly promoted the synthesis of TAG (Triacylglycerol) and TC (Total cholesterol), as well as lipid droplet accumulation in GMECs. Furthermore, METTL14 upregulated CCAAT enhancer binding protein beta (CEBPB) expression at both the mRNA and protein levels by directly inducing m6A modification on its transcripts. Finally, we confirmed that m6A modification occurs specifically at site 1662 of CEBPB mRNA, and the “Readers” YTH N6-methyladenosine RNA binding protein F1 and F3 (YTHDF1/3) were found responsible for the m6A site recognition and interpretation. This study demonstrated that METTL14 facilitates lipid synthesis and deposition in GMECs. Mechanistically, METTL14 installs the m6A modification at site 1662 of CEBPB transcripts. This m6A mark is specifically recognized by the readers YTHDF1 and YTHDF3, which promote the translation of CEBPB mRNA, thereby upregulating its expression. Full article

Biogenic nanoparticles have recently emerged as promising bacterial growth inhibitors, requiring low concentrations and not producing harmful byproducts. However, knowledge gaps remain regarding how different extraction techniques affect nanoparticle synthesis, thereby influencing their replicability and scalability across various applications. To address these knowledge gaps, this study compared six extracts derived from Moringa oleifera biomass for the synthesis of iron oxide nanoparticles. Multivariate statistical analyses correlated extraction methods with biomolecule content (polyphenols, flavonoids, carbohydrates, proteins), iron percentage, and E. coli growth inhibition. All extracts showed varying concentrations of biomolecules, and different extraction methods were preferable for specific components. Flavonoids were best extracted by salting-out, while infusion methods were better for obtaining carbohydrates. Higher percentages of iron (22.77%) were linked to the presence of polyphenols and flavonoids. Nanoparticles prepared using salting-out and infusion extraction from leaf biomass displayed the highest efficiency in inhibiting E. coli growth, up to a dilution factor of 4. The outcomes of this research study provide an in-depth understanding of the role of specific biomolecules in biogenic nanoparticle synthesis, confirming that both synthesis yield and application effectiveness depend on the extract preparation method. Full article

Cardiac hypertrophy is an important risk factor for heart failure and is often accompanied by contractile dysfunction. While hypertrophic growth contributes to disease progression, the underlying molecular mechanisms remain incompletely understood. A proposed contributor is a metabolic shift toward glucose uptake, suggesting that kinases regulating this process, such as protein kinase D1 (PKD1) and downstream target phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ), might be effective targets to mitigate cardiac hypertrophy-induced contractile dysfunction. We investigated whether PI4KIIIβ inhibition downregulates enhanced glucose uptake in hypertrophic cardiomyocytes and thereby treats cardiac hypertrophy-induced contractile dysfunction. Hypertrophy was induced in cultured adult rat cardiomyocytes and human stem cell-derived cardiomyocytes using either phenylephrine (PE) or adenoviral PKD1 overexpression. PE-induced hypertrophy was associated with increased mRNA expression of BNP, activation of hypertrophic signaling, morphological alterations, enhanced protein synthesis and glucose uptake, and impaired contractile function. Treatment with the PI4KIIIβ inhibitor MI14 prevented and reversed PE-stimulated glucose uptake and contractile dysfunction, while hypertrophic signaling, cell size, and protein synthesis remained unaffected. Similar effects on glucose uptake were observed in the PKD1 overexpression model. These findings suggest that targeting myocardial substrate metabolism via the PI4KIIIβ pathway, rather than hypertrophic growth itself, could be a promising strategy to treat hypertrophy-induced contractile dysfunction. Full article

The present study aimed to evaluate the effects of fermented compound Chinese herbal medicine (FCHM, Vaccaria segetali, Tetrapanax papyriferus, Ligusticum chuanxiong Hort and Rhaponticum uniflorum) on the reproductive performance of Ningxiang sows. A total of 30 Ningxiang sows were randomly assigned to the control group (CON), CHM group, and FCHM group. The results indicated that dietary CHMs and FCHM supplementation significantly increased (p < 0.05) the milk production, feed intake, reproductive performance protein content, and lactose content in the milk of sows and significantly decreased (p < 0.05) the number of somatic cells in colostrum and in the number of low-birthweight piglets. Dietary FCHM supplementation significantly increased (p < 0.05) the number of healthy piglets, birth litter weight, colostrum fat content, and feed intake. Moreover, malondialdehyde, porcine interleukin-1α, and porcine interleukin-6 in sow serum were decreased (p < 0.05), and the activity of superoxide dismutase, total antioxidant capacity, immunoglobulin, prolactin and progesterone levels (p < 0.05) were increased, with FCHM supplementation. The colostrum metabolomics analyses showed that FCHM significantly enriched the oxytocin signaling pathway, calcium signaling pathway, and pathways associated with milk composition synthesis. In conclusion, supplementing with FCHM improved the reproductive performance and milk metabolic biomarkers of sows and may serve as an effective feed additive to improve productivity. Full article

The bovine mammary gland, the exclusive site of milk synthesis, is a structurally specialized tissue that houses distinct cellular subsets, yet it remains highly susceptible to major mastitis pathogens, including Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli. Infection disrupts redox homeostasis, leading to excessive accumulation of reactive oxygen species (ROS) and rapid activation of antioxidant pathways. In this study, we integrated 16S DNA sequencing, histopathology (hematoxylin and eosin), and immunohistochemistry to map the mastitis-associated microbiota and visualize oxidative-damage foci in mammary tissues challenged by Staphylococcus aureus, Streptococcus agalactiae, or Escherichia coli. Quantitative reverse transcription polymerase chain reaction and Western blot analyses were subsequently performed on the same samples to measure the kinetic response of six oxidative-stress-related signalling nodes: adenosine 5′-monophosphate-activated protein kinase, cytochrome P450 1A1, heme oxygenase 1, nitric oxide synthase, mammalian target of rapamycin, and superoxide dismutase. By correlating the temporal expression patterns of these genes/proteins with ROS accumulation and histological severity, this study delineates the molecular cascade linking oxidative imbalance to mastitis pathology, providing data-driven targets for future preventive and therapeutic strategies. Full article

The global migratory pest, Spodoptera frugiperda, has garnered widespread attention due to the serious damage it inflicts on agricultural productivity, particularly in maize. Thymol is a phytochemical that exhibits functional diversification in plant defense, encompassing antibacterial activities and insect pest management. However, the impact of thymol on S. frugiperda is still undetermined. This study examined the growth inhibition and mortality induction in S. frugiperda larvae after thymol exposure. The detrimental effects of 2.0 and 4.0 mg/g thymol treatments on the growth and development of S. frugiperda were also examined. RNA-Seq was used to investigate the probable toxicological mechanism of thymol on S. frugiperda, resulting in the identification of 1754 and 1022 DEGs impacted by 2.0 and 4.0 mg/g thymol treatments, respectively. The DEGs associated with chitin metabolism and cuticle synthesis, hormone biosynthesis, and protein and fat digestion were subjected to additional analysis. Our findings demonstrate the efficacy of thymol in controlling S. frugiperda and lay the groundwork for understanding the molecular toxicological mechanisms of thymol on larvae. Full article

Human zinc finger Ran-binding protein 3 (ZRANB3) is crucial for DNA damage tolerance (DDT), as it prevents excessive damage, restores fork progression, and ultimately maintains genome stability. This unique and ancient architecture mainly exerts its function during replication fork reversal (RFR) and within the p53/Polι axis; thus, ZRANB3 is considered a tumour suppressor. However, possible additional roles in DNA synthesis and cell metabolism have been proposed. In tumour cells, ZRANB3 gene expression is deregulated, a condition that is frequently associated with poor survival and adverse clinical outcomes. ZRANB3 can be altered by functional mutations, gene copy number alterations, and a combination of the two. Although its mRNA levels typically correlate with p53 expression, this correlation breaks down in the context of p53 mutations and high proliferative activity. This comprehensive review integrates the currently available yet fragmented literature on ZRANB3, both at the gene and protein levels, examines its regulation in cancer development, and discusses the evidence supporting its role as a tumour suppressor and prognostic biomarker. Full article

As an important economic aquatic product in China, the farming method of Eriocheir sinensis significantly impacts its quality and physiological metabolism. In this study, the effects of lake (LK) farm and pond (PD) farm on the gene expression profiles and metabolic pathways in E. sinensis were evaluated by integrating transcriptomic and metabolomic analyses. A total of 812 differentially expressed genes (DEGs) were identified in the hepatopancreas of crabs. The DEGs were mainly enriched in nutrient reservoir activity, regulation of response to oxidative stress, and lipid transporter activity. In addition, LC-MS analysis identified 410 significantly differential metabolites, and KEGG pathway enrichment showed that these metabolites were mainly enriched in the MAPK signaling pathway, HIF-1 signaling pathway, and glycerolipid metabolism. Integrated transcriptomic and metabolomic analyses revealed that the AMPK signaling pathway, cytochrome P450-mediated xenobiotic metabolism, glycerophospholipid metabolism, and the apoptosis signaling pathway collectively exert a significant influence on the growth performance of crabs. Collectively, our findings demonstrated that the crabs in the LK group exhibit enhanced antioxidant and detoxification capacities, concomitant with reduced protein synthesis and energy metabolism, and underwent increased apoptotic events. The finding of this study will provide valuable and novel insight into crab farming practices in different aquaculture environments, providing theoretical foundations for optimizing ecological aquaculture models in Datong Lakes’ crab farms. Specifically, combined supplementation with natural feed organisms and mechanical aeration may effectively mitigate benthic hypoxia and nutritional deficits, thereby promoting sustainable production in the lake-based culture of crabs. Full article

Due to the neuroprotective and antioxidant properties, phenylethanoid glycosides (PhGs) are valuable plant-derived compounds. Traditional extraction methods are constrained by low yields and limited resources, prompting the integration of synthetic biology and enzyme engineering technologies for sustainable production. This review summarizes the advances in the microbial synthesis of PhGs, emphasizing the elucidation of biosynthetic pathways, enzyme engineering modifications of glycosyltransferases and acyltransferases, and strategies for optimizing microbial cell factories in Escherichia coli and Saccharomyces cerevisiae. Significant advancements encompass the efficient synthesis of verbascoside and echinacoside in S. cerevisiae, as well as the comprehensive elucidation of the echinacoside biosynthetic pathway in Cistanche spp., including the identification of key steps catalyzed by a rhamnosyltransferase, a CYP450 hydroxylase, and a terminal glucosyltransferase that enable pathway reconstruction in S. cerevisiae. We conduct a systematic analysis of methods to address the biosynthetic bottlenecks via protein engineering, including rational design and directed evolution, as well as the metabolic engineering strategies such as precursor enhancement and cofactor recycling. Additionally, we investigate the synthesis of non-natural PhG analogues and the prospective integration with AI-assisted design, emphasizing the significant potential of microbial systems in overcoming the supply challenges for medicine-food homologous ingredients. Full article