Search Results (7,338)

Climate change necessitates a deeper understanding of plant tolerance mechanisms to dual water stresses. This study investigated the distinct physiological and genetic responses of Longleaf Speedwell (Pseudolysimachion longifolium) to drought and waterlogging using RNA-Seq. Physiological data showed a rapid and comparable reduction in photosynthetic efficiency after one week and a reduction in biomass under both stresses after two weeks. However, transcriptomic analysis revealed fundamentally distinct strategies: Drought induced a massive transcriptional response characterized by the strong upregulation of defense and stress-tolerance pathways and the severe shutdown of growth-related metabolism. In contrast, waterlogging triggered a constrained hypoxic response, prioritizing energy conservation by downregulating synthesis processes and activating ethylene signaling. The reliability of the RNA-Seq data was confirmed by qRT-PCR, which also crucially identified Alcohol dehydrogenase (ADH), Ethylene Responsive Factor (ERF), and Peroxidase (POD) as common candidate genes highly induced under both drought and waterlogging conditions, suggesting a shared genetic module for general water stress tolerance. These findings provide valuable insights into the adaptation mechanisms of non-model plants to complex environmental changes. Full article

Homogalacturonan (HG) methylesterification is a key determinant of plant cell wall (CW) structure and function, shaping growth, morphogenesis, and responses to biotic and abiotic stresses. This review highlights recent advances in the regulation of homogalacturonan (HG) methylesterification, focusing on the coordinated roles of pectin methylesterases (PMEs), pectin methylesterase inhibitors (PMEIs), transcription factors (TFs), and hormonal signals. We examine how these regulators interact within the CW microenvironment to modulate elasticity, porosity, and remodeling dynamics. Insights from immunolocalization and biomechanical studies reveal the spatiotemporal patterning of HG de-esterification and its integration with developmental and stress-adaptive signaling. Beyond basic biology, HG methylesterification dynamics directly influence traits such as fruit firmness, pathogen resistance, and stress tolerance, positioning HG methylesterification-related genes as promising targets for molecular breeding and biotechnological interventions. By integrating mechanistic understanding with genomic and phenotypic selection approaches, breeders can precisely tailor CW properties to enhance crop resilience and quality. A comprehensive view of HG methylesterification—from enzymatic control to mechanical feedback—offers a conceptual and practical framework for guiding crop improvement and sustainable agricultural practices. Full article

Background: Bee pollen is a uniquely complete nutritional product that has shown promise in alleviating obesity. While existing research has largely focused on the role of gut microbiota in obesity, the mechanisms by which bee pollen influences bile acid (BA) metabolism via microbial regulation remain poorly understood. Methods: This study hypothesized that Schisandra chinensis bee pollen extract (SCPE) could mitigate high-fat diet (HFD)-induced obesity by regulating BA metabolism. Results: In a 12-week animal experiment, SCPE supplementation significantly reduced body weight gain, lipid accumulation, and adipocyte hypertrophy, while improving insulin sensitivity and relieving hepatic oxidative stress. These benefits were attributed to an increased relative abundance of bile salt hydrolase (BSH)-producing microbes, including Bacteroides, Lachnospiraceae NK4A136 group, and Akkermansia, which modulated BA metabolism by improving the expression of BA metabolism-related genes and reducing the concentrations of various types of BAs. Conclusions: These findings provide new insights into the mechanism by which SCPE alleviates obesity through the gut microbiota-BA axis and support the potential of bee pollen as a functional food for obesity management. Full article

Cardiovascular diseases (CVDs) remain a leading cause of mortality worldwide. According to the WHO, every year, there is an increase in the rate of death globally due to CVDs, stroke, and myocardial infarction. Several risk factors contribute to the development of CVDs, one of which is hypoxia, defined as a reduction in oxygen levels. This major stressor affects aerobic species and plays a crucial role in the development of cardiovascular disease. Research has uncovered the “hypoxia-inducible factors (HIFs) switch” and investigated the onset, progression, acute and chronic effects, and adaptations of hypoxia, particularly at high altitudes. The hypoxia signalling pathways are closely linked to natural rhythms such as the circadian rhythm and hibernation. In addition to genetic and evolutionary factors, epigenetics also plays an important role in postnatal cardiovascular responses to hypoxia. Oxidized LDL-C initiates atherosclerosis amidst oxidative stress, inflammation, endothelial dysfunction, and vascular remodelling in CVD pathogenesis. Anti-inflammatory and antioxidant biomarkers are needed to identify individuals at risk of cardiovascular events and enhance risk prediction. Among these, C-reactive protein (CRP) is a recognized marker of vascular inflammation in coronary arteries. Elevated pro-atherogenic oxidized LDL (oxLDL) expression serves as an antioxidant marker, predicting coronary heart disease in apparently healthy men. Natural antioxidants and anti-inflammatory molecules protect the heart by reducing oxidative stress, enhancing vasodilation, and improving endothelial function. For instance, the flavonoid quercetin exerts antioxidant and anti-inflammatory effects primarily by activating the Nrf2/HO-1 signaling pathway, thereby enhancing cellular antioxidant defense and reducing reactive oxygen species. Carotenoids, such as astaxanthin, exhibit potent antioxidant activity by scavenging free radicals and preserving mitochondrial integrity. The alkaloid berberine mediates cardiovascular benefits through activation of AMO-activated protein kinase (AMPK) and inhibition of nuclear factor kappa B [NF-kB] signalling, improving lipid metabolism and suppressing inflammatory cytokines. Emerging evidence highlights microRNAs (miRNAs) as potential regulators of oxidative stress via endothelial nitric oxide synthase (eNOS) and silent mating-type information regulation 2 homolog (SIRT1). While the exact mechanisms remain unclear, their benefits are likely to include antioxidant and anti-inflammatory effects, notably reducing the susceptibility of low-density lipoproteins to oxidation. Additionally, the interactions between organs under hypoxia signalling underscore the need for a comprehensive regulatory framework that can support the identification of therapeutic targets, advance clinical research, and enhance treatments, including FDA-approved drugs and those in clinical trials. Promising natural products, including polysaccharides, alkaloids, saponins, flavonoids, and peptides, as well as traditional Indian medicines, have demonstrated anti-hypoxic properties. Their mechanisms of action include increasing haemoglobin, glycogen, and ATP levels, reducing oxidative stress and lipid peroxidation, preserving mitochondrial function, and regulating genes related to apoptosis. These findings emphasise the importance of anti-hypoxia research for the development of effective therapies to combat this critical health problem. A recent approach to controlling CVDs involves the use of antioxidant and anti-inflammatory therapeutics through low-dose dietary supplementation. Despite their effectiveness at low doses, further research on ROS, antioxidants, and nutrition, supported by large multicentre trials, is needed to optimize this strategy. Full article

Phosphoenolpyruvate carboxylase (PEPC) is a crucial enzyme in plant photosynthesis and stress responses, yet its gene family remained uncharacterized in Zanthoxylum armatum. This study presents the first genome-wide identification and comprehensive analysis of the PEPC gene family in Z. armatum. A total of 12 ZaPEPC genes were identified and classified into plant-type (PTPC) and bacterial-type (BTPC) subfamilies based on phylogenetic analysis. These genes exhibited conserved protein domains but distinct gene structures, with evidence of gene duplication events contributing to family expansion. Promoter analysis revealed an abundance of stress- and hormone-responsive cis-elements, particularly those related to light, abscisic acid (ABA), and methyl jasmonate (MeJA). Expression profiling demonstrated that ZaPEPC genes display environment-specific expression patterns, with ZaPEPC7 and ZaPEPC11 showing significantly higher expression in high-altitude, high-light environments (Yunnan) compared to other regions (Shandong and Chongqing). Co-expression network analysis further indicated interactions between specific ZaPEPCs and stress-related transcription factors. These findings systematically reveal the molecular characteristics and potential roles of the ZaPEPC gene family in environmental adaptation, providing valuable genetic resources and a theoretical foundation for improving stress tolerance and photosynthetic efficiency in Z. armatum through molecular breeding. Full article

Preeclampsia (PE) is a complex hypertensive disorder of pregnancy characterized by new-onset hypertension and proteinuria after 20 weeks of gestation. It is classified into early-onset (EOPE, <34 weeks) and late-onset (LOPE, ≥34 weeks) subtypes, which differ in their pathophysiology, clinical course, and maternal and neonatal outcomes. EOPE arises from abnormal placentation with inadequate spiral artery remodeling and impaired uteroplacental perfusion, whereas LOPE is mainly related to maternal cardiovascular and metabolic predisposition. This review integrates current molecular, immunological, and hemodynamic evidence distinguishing EOPE from LOPE, emphasizing recent insights into angiogenic imbalance (VEGF, PlGF, sFlt-1), oxidative stress, and immune modulation. It also summarizes evolving diagnostic and prognostic biomarkers and evaluates emerging therapeutic approaches, including gene therapy targeting placental dysfunction. By comparing mechanistic pathways and clinical implications, this review highlights how gestational age–specific pathogenesis may inform risk stratification, early detection, and precision-based management of PE. Full article

The establishment of dorsoventral polarity is a critical step in leaf morphogenesis, enabling the transition from radial primordia to flattened laminae. The MYB domain transcription factor ASYMMETRIC LEAVES1 (AS1) plays a central role in this process by regulating leaf polarity and developmental transitions, primarily through the repression of Class I KNOX genes. Here, four AS1 paralogs were identified in soybean (Glycine max), two of which showed collinearity with Arabidopsis thaliana and Medicago truncatula. The AS1 proteins of soybean and Arabidopsis exhibit high conservation, whereas the four GmAS1 genes in soybean display different tissue-specific expression patterns. Strikingly, each GmAS1 gene was able to fully rescue the defective phenotype of the Arabidopsis as1 mutant, indicating that GmAS1 genes are functionally conserved in leaf polarity regulation. Promoter analysis further indicated that GmAS1 genes are enriched in cis-acting elements related to light response, hormone regulation, development, and stress response, suggesting potential subfunctionalization among these paralogs. In conclusion, these findings demonstrate that GmAS1 genes are evolutionarily conserved in function but potentially diversified in regulation, providing new insights into their role in leaf polarity and stress adaptation. Full article

Background: Diabetic retinopathy (DR), a leading cause of blindness, lacks early biomarkers and mechanism-targeted therapies. While oxidative stress drives DR pathogenesis, the role of oxeiptosis—a reactive oxygen species-induced, caspase-independent cell death pathway—remains largely unexplored. Methods: We integrated transcriptomic profiling (GSE221521: 69 DR vs. 50 controls), two-sample Mendelian randomization (MR) using blood cis-eQTLs (GTEx) as instruments and DR GWAS (FinnGen R12) as outcome, machine learning-based feature selection (SVM-RFE and Boruta algorithms), and single-cell RNA sequencing (scRNA-seq) analysis (GSE165784). Functional enrichment, immune deconvolution (CIBERSORT), and diagnostic nomogram construction were performed. We validated the key genes using human retinal microvascular endothelial cells (hRMECs) treated with high glucose (30 mM). Results: Oxeiptosis scores were elevated in DR blood samples (p < 0.001). MR analysis identified five putative causal genes: CASP2 (OR = 1.067), PLEC (OR = 1.035) and FBN2 (OR = 1.016) as risk factors, and CYP27A1 (OR = 0.960) and GPD2 (OR = 0.958) as protective factors. SVM-RFE and Boruta algorithms confirmed CASP2 and PLEC as hub genes. A nomogram incorporating both genes achieved robust DR prediction (AUC = 0.811). Functional analysis associated these genes with innate immune activation and extracellular matrix reorganization. Single-cell transcriptomics revealed PLEC was markedly overexpressed in disease-relevant cells (fibroblasts, endothelial cells), whereas CASP2 exhibited a distinct pattern, with notable enrichment in retinal CD8+ T cells. Both genes were associated with a pro-inflammatory shift in the immune landscape. Their upregulation was validated in independent datasets and high-glucose-stressed retinal cells. Conclusions: This study establishes an integrated multi-omics framework implicating oxeiptosis-related pathways in DR and nominates CASP2 and PLEC as putatively causal, biologically relevant candidate biomarkers and potential therapeutic targets. Full article

Background: Skeletal muscle aging is characterized by impaired myogenic differentiation, disrupted circadian rhythms, elevated oxidative stress, and mitochondrial dysfunction. Rutin, a natural flavonoid with antioxidant properties, has been suggested to mitigate aging processes; however, its effects on circadian regulation and muscle homeostasis remain unclear. Methods: In vitro, differentiated C2C12 myotubes were treated with D-galactose (D-gal, 20 g/L) with or without rutin (20 μM). In vivo, C57BL/6 mice were supplemented with rutin (100 mg/kg b.w.) via oral gavage in a D-gal-induced aging mouse model (150 mg/kg b.w., i.p.). Results: D-gal induced cellular senescence, impaired myogenic differentiation, disrupted circadian oscillations, increased oxidative stress, and compromised mitochondrial function. Rutin treatment restored myotube formation, enhanced circadian rhythmicity of differentiation-related genes, and corrected the antiphase patterns of Per2 and Rorc. It also reduced reactive oxygen species and malondialdehyde levels; increased superoxide dismutase, catalase, and glutathione peroxidase activity; improved ATP production and membrane potential; and decreased mitochondrial oxidative aging, as confirmed by pMitoTimer imaging. Furthermore, rutin reinstated the rhythmic expression of oxidative phosphorylation proteins and Pgc1α. In vivo, rutin supplementation enhanced muscle performance (prolonged hanging time) and oxidative capacity, particularly at night (ZT14–ZT16), without altering muscle fiber-type distribution, and normalized circadian rhythmicity of core clock genes. Conclusions: Rutin attenuates D-gal-induced cellular senescence by modulating circadian rhythms, reducing oxidative stress, and improving mitochondrial function. Importantly, its in vivo effects on muscle performance and circadian regulation suggest that rutin is a promising therapeutic strategy to counteract skeletal muscle aging and sarcopenia. Full article

Background: Cerium oxide nanoparticles (nanoceria) have attracted growing attention as promising anticancer agents due to their unique redox properties. Their selective cytotoxicity in cancer cells is thought to be mediated primarily through disruption of redox homeostasis. However, the precise molecular mechanisms underlying their action in breast cancer remain unclear. To address this gap, the present study investigates the dose-dependent cytotoxic, oxidative, and mitochondrial effects of nanoceria in MCF7 breast cancer cells, with mechanistic insights gained through gene expression and proteomic analyses. Methods: MCF7 breast cancer cells were treated with nanoceria (200 µg/mL and 400 µg/mL). Cytotoxicity, ROS levels, and mitochondrial membrane potential were assessed via MTT, DCFDA staining, and MitoTracker, respectively. Gene expression and label-free LC-MS/MS proteomics were used to evaluate molecular and pathway-level changes. Results: Nanoceria exhibited dose-dependent cytotoxicity, significantly reducing MCF7 cell viability to 61 ± 1.5% (p < 0.01) and 57 ± 1.8% (p < 0.01) at 200 µg/mL and 400 µg/mL, respectively, compared with the control. ROS levels increased 1.4-fold (p < 0.01) and 1.5-fold (p < 0.0001), accompanied by a decreased mitochondrial membrane potential by 11% (p < 0.01) and 25% (p < 0.05), indicating oxidative stress and mitochondrial dysfunction. Gene expression analysis supported activation of apoptotic pathways demonstrated by upregulation of BNIP3, the BAX/BCL-2 ratio (p < 0.05), and disruption of mitochondrial homeostasis. Proteomic profiling revealed dose-specific alterations in >150 proteins (fold change ≥ 1.5, p < 0.05) related to redox balance, mitochondrial function, apoptosis, and cell cycle regulation. Conclusions: Nanoceria induces dose-dependent oxidative stress and mitochondrial dysfunction in MCF7 breast cancer cells, triggering apoptotic pathways and widespread alterations in protein expression. These results offer valuable mechanistic insights into nanoceria’s selective anticancer activity and highlight its potential as a promising therapeutic agent for breast cancer. Full article

The viable bacterial count is a crucial quality indicator for lactic acid bacteria (LAB) starters and fermented foods. Metabolic activity is an integral component of stress tolerance pathways. Lacticaseibacillus rhamnosus exhibits enhanced heat and oxidative stress tolerance in tryptone-free media. To investigate the stress tolerance mechanisms from a metabolic perspective, the heat and oxidative stress tolerance and transcriptomic changes in L. rhamnosus hsryfm 1301 and its ccpA deficient strain (ΔccpA) were analyzed under different nitrogen source conditions. Slower growth, decreased heat stress tolerance, and enhanced oxidative stress tolerance were observed in ΔccpA in MRS. Compared to the wild-type strain, 260 genes were upregulated and 55 genes were downregulated in ΔccpA, mainly including carbon source transport and metabolism genes, but no typical stress tolerance genes. The regulation of pfk, pyk, dnaK, and groEL was different from that in other lactic acid bacteria. The pathways related to acetate production were regulated solely by ccpA deletion, while dnaK, groEL, and de novo pyrimidine synthesis genes were only regulated by tryptone. Fatty acid and purine synthesis genes and glmS were co-regulated by ccpA and tryptone. The deletion of ccpA eliminated the nitrogen source-induced oxidative stress tolerance changes. It was found that ccpA in L. rhamnosus can affect both carbon and nitrogen source metabolism, altering stress tolerance. Full article

Ryanodine receptor 1-related myopathies (RYR1-RM) are caused by RYR1 gene variants and comprise a wide spectrum of histopathological manifestations. Here, we focus on patients carrying RYR1 variants and muscle histopathology consistent with central core disease (CCD) or multi-minicore disease (MmD). RNA-sequencing analyses of skeletal muscle biopsies obtained from both CCD and MmD patients and from healthy controls were performed to better understand the molecular pathways activated by RYR1 variants. Our analyses revealed that, beyond the well-established role of RYR1 in calcium homeostasis, broader cellular pathways are implicated. In CCD, differentially expressed genes were enriched for pathways related to oxidative stress response, SMAD signalling, and apoptosis, consistent with the role of intracellular calcium dysregulation in promoting mitochondrial dysfunction and cell death. In contrast, MmD patients exhibited enrichment of pathways related to immune activation. This was corroborated by the upregulation of GTPase-regulating genes and the down-regulation of transcriptional repressors such as ZFP36 and ATN1. When considering all RYR1-RM patients collectively, Wnt signalling, immune-related pathways, and oxidative phosphorylation emerged as shared enriched pathways, indicating possible convergent mechanisms across histopathological phenotypes. Our study suggests that complex gene regulation driven by RYR1 variants may be a unifying feature in CCD and MmD, offering new insight into potential therapeutic targets. Full article

Basic leucine zipper (bZIP) transcription factors play pivotal roles in plant secondary metabolism, influencing the production of bioactive compounds that determine the medicinal value of plants. Despite their significance, a comprehensive genomic overview of bZIPs in non-model medicinal species remains limited. Here, we present the first genome-wide identification and characterization of the bZIP family in Lycium ruthenicum Murr. (black wolfberry), revealing 63 members grouped into 13 subfamilies. These genes showed conserved bZIP domains, distinct exon–intron architectures, and promoter cis-elements related to light, hormones and stress responses. Family expansion occurred through tandem (LrbZIP6-LrbZIP9 cluster) and segmental duplications under purifying selection (Ka/Ks < 1). Collinearity analysis revealed closer relationships with Solanaceae species than Arabidopsis thaliana, with LrbZIP10 and LrbZIP11 as conserved orthologs. Expression profiling identified tissue-specific patterns: LrbZIP17 showed broad expression while LrbZIP14 was fruit-specific. qRT-PCR confirmed floral-preferential (LrbZIP1, LrbZIP10, LrbZIP15, LrbZIP17, LrbZIP50) and root-specific (LrbZIP54, LrbZIP55) expression. The co-occurrence of light/hormone-responsive elements and high LrbZIP expression in anthocyanin-rich tissues suggests their regulatory roles in bioactive compound biosynthesis. This study provides foundational genomic resources for understanding L. ruthenicum bZIP evolution and identifies candidate genes for molecular breeding to enhance medicinal compound production. Full article

Background/Objectives: Copper-based wood preservatives are widely used to protect timber from fungal decay; however, the emergence of copper-tolerant fungi reduces their long-term effectiveness. This study aimed to elucidate the molecular mechanisms underlying copper resistance in Saccharomyces cerevisiae through adaptive evolution and transcriptomic profiling. Methods: A copper-resistant mutant was developed via stepwise exposure to CuSO₄·5H₂O, and its gene expression profile was compared to the wild-type strain under copper stress and non-stress conditions using Affymetrix GeneChip Yeast Genome 2.0 arrays. Results: Differential expression analysis revealed upregulation of key genes involved in copper transport (ATX1 and CTR1), the oxidative stress response (RCK1 and SOD1), and metal ion detoxification (FRE3 and SLF1). Functional enrichment analysis highlighted the significant activation of pathways related to protein folding, mitochondrial function, and transcriptional regulation. Conclusions: These findings provide insights into the adaptive strategies employed by S. cerevisiae to tolerate copper stress and suggest potential gene targets for the development of more effective wood preservatives capable of mitigating fungal resistance. Full article

Background: Cisplatin (CP) use is associated with testicular toxicity. Cuproptosis-related genes are associated with dysfunctional spermatogenesis. Additionally, the HMGB1/NF-κB axis has been involved in cuproptosis-mediated inflammation. The aim of the current study was to investigate the effect of CP toxicity on the HMGB1/NF-κB axis and cuproptosis in the rat testis. The effect of thymol was also explored. Methods: Four groups of male Wistar rats were used: control, thymol (60 mg/kg P.O. daily for 2 weeks), CP (8 mg/kg i.p single injection), and CP+thymol. Results: CP induced a significant decrease in serum testosterone and LH. CP-induced oxidative stress was evident by the modulation of oxidative stress markers. The expressions of IL-8, NF-κB, and HMGB1 were induced by CP treatment, accompanied by increased expression of cuproptosis genes, including SLC31A1, FDX1, and DLAT. On the other hand, thymol antagonized CP testicular injury. Thymol’s effect was associated with reduced expressions of IL-8, NF-κB, HMGB1, and cuproptosis markers. Conclusions: Collectively, this study provides evidence of the possible potential role of the HMGB1/NF-κB axis and cuproptosis in CP-induced testicular injury and illustrates the protective effects of thymol against testicular damage, which are attributed, at least in part, to blunting HMGB1 and cuproptosis-related genes expression. Full article