Salinity stress severely limits barley (Hordeum vulgare L.) growth and productivity. This study examined the effects of chitosan (Cs), selenium (Se), and chitosan-selenium nanoparticles (Cs-Se NPs) on salt tolerance of two barley cultivars, Mv Initium and Tectus, exposed to 0, 100, and 200 mM NaCl. Salinity reduced plant height, biomass, and chlorophyll content. Foliar application of Cs and especially Cs-Se NPs significantly improved these traits. Cs-Se NPs enhanced proline (PRO) accumulation and activities of ascorbate peroxidase (APX) and catalase (CAT) under salt stress in both cultivars, which supports improved ROS scavenging capacity. The significant upregulation of antioxidant enzyme genes (HvAPX, HvSOD, HvCAT) following Cs-Se NPs treatment under salinity strongly indicates enhanced reactive oxygen species (ROS) detoxification. Key ion homeostasis genes (HvSOS1, HvSOS3, HvNHX1 and HvHKT2) were also upregulated, supporting improved salt stress tolerance. Strong correlations were found between antioxidant activity, chlorophyll content, and growth. These findings suggest that Cs-Se NPs effectively boost barley's physiological and molecular defenses against salinity.

Leaf senescence after harvest limits the economic value of leafy cruciferous vegetables such as Chinese flowering cabbage (Brassica rapa ssp. parachinensis). Understanding the intricate gene regulatory networks that govern postharvest leaf senescence offers potential strategies to extend the shelf life of these vegetables. This study elucidated the regulatory networks modulating leaf senescence by utilizing time-series gene expression analysis on postharvest leaves of Chinese flowering cabbage treated with cytokinin analog 6-benzylaminopurine and abscisic acid (ABA). ABA treatment accelerated leaf senescence, including the dismantling of chloroplasts and mitochondria, whereas 6-benzylaminopurine treatment decelerated these processes. Subsequent RNA sequencing and integrated analyses led to the construction of transcriptional regulatory networks comprising 49 transcription factors potentially regulating senescence-related pathways, including reactive oxygen species (ROS) metabolism and chlorophyll degradation. Validation experiments on ROS metabolism confirmed that increased ROS accumulation paralleled the progression of leaf senescence, whereas ABA and 6-benzylaminopurine treatment resulted in opposing effects on ROS scavenging. Furthermore, exogenous ROS treatment promoted leaf senescence and the disassembly of chloroplasts and mitochondria, while ROS inhibitors delayed these processes. Further validation assays affirmed the expression patterns, transcription factor-binding capacities, and activation potentials of eight critical transcription factors and their possible target genes associated with ROS scavenging. Moreover, the role of two transcription factors (BrAGL42 and BrCRF11-2) in regulating postharvest leaf senescence and ROS scavenging ability was verified through transformation assays. Collectively, our findings shed light on the overarching transcription factor-mediated regulatory pathways in postharvest leaf senescence and indicate how cytokinin and ABA modulate this process antagonistically.

The microsporidium Vairimorpha (Nosema) ceranae is an emerging threat to honey bees (Apis mellifera), known to disrupt gut microbiota and suppress immune responses, potentially contributing to colony losses. Fungal extracts have recently gained interest as sources of bioactive compounds with antimicrobial and immunomodulatory potential. In this study, we explored the effects of different dietary supplements-sugar syrup, HiveAlive™, and a novel Ganoderma australe extract (GanoBee)-on gut bacterial composition and immune-related gene expression in honey bees subjected to experimental exposure to V. ceranae 1 x 104 spores per bee. The GanoBee diet altered the gut microbiota, notably reducing the relative abundance of Rhizobiaceae (Bartonella apis) and increasing Frischella compared to other treatments. While alpha diversity was not significantly affected by diet or exposure to V. ceranae, beta diversity differed significantly in bees fed with GanoBee. Additionally, the expression of the antimicrobial peptide genes abaecin and hymenoptaecin was elevated in both exposed and unexposed bees fed with GanoBee, depending on the sampling day. However, the establishment of V. ceranae infection appeared limited, likely due to low spore viability, and mortality in control bees was higher than expected. The low Vairimorpha ceranae infection levels observed in this study are likely attributable to reduced spore viability caused by storage conditions and/or suboptimal environmental conditions within the laboratory cages. Post hoc analyses indicated that the high viscosity of GanoBee-supplemented diets likely contributed to the elevated bee mortality observed, underscoring a critical limitation of the experimental design related to diet formulation and delivery method. These physical factors complicate the interpretation of treatment efficacy and highlight the importance of optimizing feeding protocols to avoid confounding effects. Despite these constraints, GanoBee demonstrated promising potential as a modulator of gut microbiota composition and immune-related gene expression, supporting the need for further research under improved and carefully controlled experimental conditions.

UHRF1 (ubiquitin-like with PHD and RING finger domains 1) is a multi-domain epigenetic regulator that integrates DNA methylation, histone modification, and ubiquitin signaling. Its overexpression is consistently observed across diverse cancers, where it silences tumor suppressor genes, stabilizes oncogenic proteins, and rewires metabolic and stress pathways, thereby driving tumor progression and therapy resistance. Targeting UHRF1 offers a domain-specific and context-dependent strategy distinct from global demethylation, reducing off-target toxicity and providing a refined therapeutic window. Natural compounds such as flavonoids, berberine, and thymoquinone, as well as synthetic inhibitors of reader domains, proteasomal degraders, and RNA-based approaches, have demonstrated potential to disrupt UHRF1 function. UHRF1 inhibition may also synergize with DNMT or HDAC inhibitors, immune checkpoint blockade, and ferroptosis inducers. Current evidence supports UHRF1 as both a biomarker and a promising druggable target for next-generation epigenetic cancer therapies.

The mitochondrial gene ORF188 enhances salt stress tolerance in rapeseed by boosting ATP synthesis, thereby fueling antioxidant defense systems and maintaining cellular homeostasis. Soil salinity severely impairs crop productivity by inducing osmotic stress, ionic toxicity, and oxidative damage. An energy deficit, arising from impaired mitochondrial ATP production under stress, represents a critical bottleneck that compromises the plant's antioxidant capacity. Here, we report that the mitochondrial gene ORF188, a homolog of the ATP synthase F0 subunit, significantly enhances salt stress tolerance in rapeseed. ORF188-overexpressing lines exhibited superior growth and reduced oxidative damage under salt stress, which was underpinned by constitutively elevated ATP synthase activity and cellular ATP levels. This energy surplus enhanced the antioxidant system, maintained favorable Na+/K+ ratio and orchestrated a homeostasis-oriented stress transcriptome. Crucially, treatment with the ATP synthase inhibitor Oligomycin A abolished both the salt-tolerant phenotype and the associated transcriptional reprogramming, thereby confirming the essential role of enhanced ATP synthesis. Our findings demonstrate that ORF188 as a key genetic determinant of salt stress tolerance via ATP-dependent antioxidant activation, and representing a promising target for breeding salt-resilient crops.

ANAC032 directly bind to the promoter regions of XTH31 and XTH33 and repress their expression, and loss-of-function xth31 mutant plants exhibited increased sensitivity to Ni stress, with phenotypes similar to those of NAC32-overexpressing plants.

Members of the genus Streptomyces are major producers of a wide variety of secondary metabolites that serve as bioactive compounds. Many secondary metabolites are produced in response to environmental signals such as biotic and abiotic stresses. In this study, we identified salt supplementation as one of the stimuli activating secondary metabolism in the model Streptomyces species, Streptomyces coelicolor. Comparative metabolomics revealed overproduction of several known secondary metabolites, most notably undecylprodigiosin and coelimycin P1, in addition to their biosynthetic intermediates and derivatives, as well as many unknown metabolites. Transcriptomic analysis revealed activation of diverse biological processes including cation uptake, compatible solute production, and the phosphate limitation stress response through conserved and species-specific mechanisms, presumably to overcome the increased salinity. This response leads to activation of a variety of regulatory and metabolic pathways required for production of secondary metabolites including activation of conserved metabolic pathways for energy and substrate supply and species-specific secondary metabolite biosynthetic gene clusters. Furthermore, several promoter sequences contributing to upregulation of secondary metabolism induced by salt supplementation were identified. Overall, our data show how S. coelicolor copes with the increased salinity and tailors the cellular metabolism toward secondary metabolism in a conserved and species-specific manner.IMPORTANCEPrecise control of cellular metabolism is critical to ensure directing cellular resources toward metabolic pathways required for the environment. Many Streptomyces species activate production of secondary metabolites upon exposure to environmental stimuli. This study reveals dynamic reprogramming of cellular metabolism in Streptomyces coelicolor under increased salinity, which induces production of various secondary metabolites. Notably, this model biological system redirects cellular resources toward various metabolic pathways required for proper activation of secondary metabolite biosynthesis, including precursor and energy supply and posttranslational modification of biosynthetic enzymes. Interestingly, some pathways are activated by phosphate limitation stress, presumably caused as a result of increased salinity. Certain aspects of this metabolic reprogramming are likely common in many Streptomyces species and may be controlled by rather complex regulatory pathways. Overall, this study unveils how Streptomyces species tailor the cellular metabolism toward secondary metabolism and paves the way for understanding metabolic regulation.

Aluminum (Al³⁺) toxicity is a major limitation to plant productivity in acidic soils, disrupting cellular homeostasis, redox balance, and nutrient uptake. Brassinosteroids are key regulators of plant stress signaling, yet their role in Al³⁺ tolerance remains insufficiently understood. Here, we investigated the signaling functions of 24-epibrassinolide (24-EBL) in mediating aluminum stress responses in Nicotiana tabacum grown under soilless culture conditions. Exogenous 24-EBL significantly alleviated Al³⁺-induced photosynthetic inhibition, as reflected by increased transpiration rate (Tr), stomatal conductance (Gs), net photosynthetic rate (Pn), electron transport rate (ETR), and effective quantum yield of PSII (ΦPSII). Enhanced non-photochemical quenching (NPQ) indicated improved dissipation of excess excitation energy, suggesting photoprotective regulation. At the molecular level, 24-EBL treatment upregulated the antioxidant defense genes CAT1, NtPOD1, and NtSOD3, leading to increased enzymatic activities and reduced reactive oxygen species (ROS) accumulation, thereby preserving membrane stability. Notably, 24-EBL modulated metal detoxification pathways by inducing the expression of the phytochelatin-related genes Pr8 and Pr2, along with Al-ATPase transporters associated with vacuolar sequestration. This was accompanied by altered ion homeostasis, where enhanced Ca²⁺ and K⁺ uptake antagonized Al³⁺ accumulation and restricted its translocation to shoots. The marked upregulation of calmodulin (CaM) suggests that Ca²⁺-dependent signaling plays a central role in 24-EBL-mediated aluminum tolerance. Correlation analysis revealed strong associations between CaM expression, photosynthetic efficiency, antioxidant capacity, and metal detoxification markers. Together, these findings indicate that 24-EBL enhances aluminum tolerance in tobacco through a coordinated signaling network involving Ca²⁺-mediated signal transduction, redox regulation, and metal homeostasis. This study highlights brassinosteroid-calcium crosstalk as a key regulatory module in plant adaptation to aluminum stress.

This study aimed to examine the impact of riboflavin (RF) on tumor necrosis factor-alpha (TNF-α), caspase-3 (Cas-3) expression, and Sirtuin1 (SIRT1)/protein 53 (p53)/Bcl-2-associated X protein (Bax)/B-cell lymphoma gene-2 (Bcl-2) gene expressions in the diatrizoate (DTZ)-induced experimental nephropathy model.

Approximately 30% of epilepsy patients still develop drug resistance after standard antiepileptic treatment. Therefore, there is an urgent need to identify new drug targets to improve seizure control. Previous studies have shown that NCX1 can regulate the intracellular Ca2+ levels in astrocytes and neurons, which are closely associated with epilepsy. MCC-135 has shown potential as an antiseizure medication due to its ability to downregulate NCX and reduce intracellular calcium overload; however, its role and mechanism in epilepsy remain unclear.

Most cancer cells rely on aerobic glycolysis to support uncontrolled proliferation and evade apoptosis and switch to glutamine metabolism to survive under hypoxic conditions. In hepatocellular carcinoma (HCC), the Wnt/β-catenin pathway acts as a critical driver of metabolic reprogramming and stemness, primarily by enhancing aerobic glycolysis and altering the tumour microenvironment. The Wnt/β-catenin pathway induces activation of enzymes required for glucose metabolism and regulates the expression of glutamate transporter and glutamine synthetase. The objective of this study is to examine the mechanism by which riluzole inhibits HCC growth and induces autophagy. The results indicate that riluzole inhibits cell viability and colony formation of HCC cells and cancer stem cells (CSCs) and induces apoptosis, while sparing human normal hepatocytes. Riluzole induces autophagic cell death by inducing Beclin1 and Atg5. Riluzole inhibits β-catenin, Wnt3a, Wnt5a, Axin1, TCF, LEF and GSK3β expression, and TCF/LEF activity in HCC cells. Inhibition of the Wnt-β-catenin/TCF-LEF pathway by riluzole suppresses the expression of Cyclin D1, Axin2, cMyc, MCT1 and DNMT1. Riluzole inhibits the expression of Glut1 and Glut3, PDK1, LDHA and PKM2, glucose uptake and NAD+ levels. Furthermore, riluzole inhibits glutamate release, which reduces the antioxidant glutathione, leading to increased reactive oxygen species (ROS). Riluzole disrupts mitochondrial homeostasis by increasing Bax/Bcl-2 ratio, resulting in a drop of mitochondrial membrane potential. In conclusion, riluzole inhibits HCC growth by regulating glucose and glutamine metabolism and inducing autophagic cell death, thereby highlighting its therapeutic potential for HCC treatment.

Transient overexpression assays and RNA sequencing (RNA-seq) showed that the transcription factor HmPIF1 enhances lead (Pb) tolerance in Hydrangea by improving antioxidant capacity and altering transporter protein expression. Lead (Pb) soil contamination has caused serious ecological and environmental issues. Hydrangea represents a promising candidate species for phytoremediation, whereas research on its Pb-tolerant genes remains relatively limited. This study aimed to explore the Pb tolerance function of HmPIF1 at the physiological and transcriptional levels. Results showed that Pb stress significantly upregulated the expression of HmPIF1. Subcellular localization and transcriptional autoactivation assays demonstrated that HmPIF1 is a nuclear-localized transcription factor without transcriptional autoactivation activity. Transient overexpression experiments confirmed that eight substances, including glutathione reductase, superoxide dismutase, and total protein, were key physiological factors for HmPIF1-enhanced Pb tolerance in Hydrangea leaves, while transcriptomic analysis identified "photosynthesis" and "glutathione metabolism" as likely the core regulatory pathways. Furthermore, HmPIF1 overexpression promoted Pb accumulation in leaves, accompanied by differential expression of ion transporter proteins. Taken together, HmPIF1 positively regulates plant Pb tolerance and enhances Pb uptake in leaves, which may be achieved through multiple regulatory pathways including photosynthesis, antioxidation and ion transporter-mediated processes. These findings provide a theoretical basis for subsequent related research.

Spinocerebellar ataxia type 8 (SCA8) is a member of a group of dominantly inherited, debilitating neurological diseases caused by CAG•CTG expansions for which there are no effective treatments. RAN translation, which was discovered in SCA8, has previously been shown to occur across CAG and CUG expansion transcripts, making treatments for SCA8 potentially relevant to a broad group of diseases, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA12, Huntington's disease, and myotonic dystrophy type 1. In addition, CUG and CAG expansion transcripts have been reported to cause RNA gain-of-function effects. Using SCA8 BAC transgenic mice as a model for CAG•CTG expansion diseases, we now show that metformin improves ambulatory performance using rotarod, DigiGait, and open-field testing. At the molecular level, metformin-treated mice show reduced RAN protein levels and improved splicing, without altering sense or antisense RNA levels. Metformin-treated mice also show decreased neuroinflammation, with reduced astrogliosis and fewer activated microglia. These data provide strong preclinical support for testing metformin in clinical trials for SCA8 and potentially the broader group of CAG•CTG repeat expansion disorders.

Bisphenols are widely used industrial chemicals with endocrine-disrupting properties, and their potential association with carcinogenesis has drawn considerable attention. Cervical cancer, as a prevalent gynecological malignancy, has a pathogenesis that is not yet fully understood, particularly regarding the influence of environmental factors. In this study, we systematically investigated the molecular effects of bisphenols on cervical cancer using multi-dimensional bioinformatics approaches. WGCNA analysis identified key modules closely associated with the disease, which were integrated with predicted bisphenols targets to screen for core genes, including AR, CDC25C, CDK2, and KIF11. Functional enrichment analysis suggested that bisphenols may disrupt cell cycle regulation, the G2/M checkpoint, and p53-mediated tumor suppressor pathways. Molecular docking and 100-ns molecular dynamics simulations indicated that various bisphenols can stably bind to core target proteins, with binding patterns influenced by halogenation or aromatic substitutions. Gene expression and immunohistochemical analyses showed that CDC25C, CDK2, and KIF11 were significantly upregulated in cervical cancer tissues, whereas AR was predominantly expressed in normal epithelium. Immune infiltration analysis further suggested that CDC25C, CDK2, and KIF11 may modulate the infiltration of B cells, CD8⁺ T cells, and macrophages, implying that bisphenols-induced molecular perturbations could impact the tumor microenvironment. This study provides a reference for further exploration of the links between environmental exposures and cervical cancer development and lays a foundation for mechanistic investigations.

Salt stress is a major abiotic factor limiting plant growth and productivity. One of the primary consequences of salinity is the enhanced production of reactive oxygen species (ROS). This study investigates the role of glycolate oxidase (GOX), a key enzyme in photorespiration and a source of ROS, in the salinity response of Arabidopsis thaliana. We used two GOX T-DNA insertion mutants, gox1 and gox2, alongside wild-type (WT) plants, grown hydroponically under control conditions or exposed to 100 mM NaCl for 24 h. Results showed that shoot and root fresh weight did not differ significantly between genotypes and after 24 h of NaCl treatment. In addition, both mutants, particularly gox2, accumulated less Na+ and Cl- in shoots and roots than WT. This result was supported by ion flux analysis in roots. This fact was associated with the upregulation of key ion transporters: NHX1 (Na+compartmentalization), SOS1 (Na+ exclusion), and KUP11 and HAK5 (K+ uptake). Additionally, gox2 showed differential regulation of nitrate/Cl- transporters, with downregulation of NPF2.4, SLAH1, and SLAH3 and upregulation of NPF2.5 and NPF7.2. Furthermore, gox2 exhibited reduced oxidative damage and increased peroxidase activity under salt stress. These findings suggest that GOX2 expression may regulate plant resilience to salinity by improving ion homeostasis and antioxidative responses.

Nanobiotechnology offers sustainable strategies to enhance plant resistance by activating innate immune responses. This study evaluates the effect of chitosan nanoparticles (CNPs) on transcriptional activation of defense-associated genes in Arabidopsis thaliana.

Celastrus paniculatus (CP) is a traditional medicinal plant widely used in Ayurveda and Southeast Asian medicine for enhancing memory and treating cognitive dysfunction. Although CP has been reported to exhibit antioxidant, anti-inflammatory, and neuroprotective effects, its direct impact on activity-dependent synaptic plasticity remains insufficiently characterized. This study is aimed at investigating the effects of CP seed extract on memory performance and synaptic plasticity in a rat model, with a particular focus on AMPA receptor modulation and associated synaptic proteins. Five-week-old male Sprague-Dawley rats were randomly assigned to five groups: control, CP (80 mg/kg), donepezil (1.5 mg/kg), scopolamine (1 mg/kg), and scopolamine followed by CP. Treatments were administered daily for 14 days. Spatial memory performance was assessed using the Morris water maze. Following behavioral testing, hippocampal tissue was collected for immunohistochemical analysis of Arc protein and Western blotting of pSer831-GluA1, Arc, and PSD-95. CP-treated rats exhibited significantly reduced escape latency and increased time in the target quadrant, with outcomes comparable to those of donepezil-treated rats. In scopolamine-pretreated rats, CP administration reversed memory deficits by enhancing platform crossings and reducing escape latency. Molecular analysis revealed that CP significantly upregulated hippocampal expression of pSer831-GluA1, Arc, and PSD-95, indicating enhanced AMPA receptor trafficking and synaptic integrity. CP seed extract enhances spatial memory and synaptic plasticity by modulating critical molecular components of the glutamatergic synapse. These findings suggest that CP may support memory performance in both baseline conditions and in animals with scopolamine-induced deficits.

The link between glutaminolysis and osteoarthritis (OA) has only recently begun to be elucidated. Here, we report the association of obesity- and injury-induced cartilage damage with impaired glutaminolysis in chondrocytes. Defective glutaminolysis triggered the onset and progression of OA, with enhanced catabolism and decreased anabolism. Supplementation of α-ketoglutarate (αKG), a key component in glutaminolysis and an epigenetic factor, effectively protected cartilage against degradation in vivo via a TCA cycle- and HIF-1α-independent manner. Mechanistically, OA pathogenic factors increased H3K27me3 deposition on promoters of key glutaminolysis genes, including Slc1a5 and Gls1, leading to impaired glutaminolysis. Conversely, αKG facilitated Kdm6b-dependent H3K27me3 demethylation of not only glutaminolysis genes to rescue Gln metabolism but also Ube2o to reverse OA. Elevated Ube2o expression led to TRAF6 ubiquitination and subsequent inhibition of NF-κB signaling, thereby reversing the pathological reprogramming of glycolysis and oxidative phosphorylation and protecting against cartilage destruction. Collectively, these results demonstrated that OA pathogenic factors impair glutaminolysis through epigenetic regulation, which further exacerbate OA. Moreover, αKG restores metabolic homeostasis and alleviates OA through H3K27me3 demethylation.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau pathology, synaptic dysfunction, and neuroinflammation, which collectively drive progressive memory loss, cognitive decline, and behavioral changes. Increasing evidence implicates epigenetic dysregulation as a key contributor to these pathological processes by altering gene expression programs. Serotonergic psychedelics, which primarily act as agonists of the serotonin 2 A receptor (5-HT₂AR), have recently attracted attention for their ability to robustly promote neuroplasticity and induce sustained transcriptional changes in the brain. Preclinical studies indicate that these compounds can modulate epigenetic mechanisms, including histone modifications and DNA methylation (DNAm). This review examines the emerging intersection between psychedelic-induced epigenetic modulation and AD pathology, and proposes that targeted engagement of 5-HT₂Ars may help counteract epigenetic abnormalities that contribute to AD pathogenesis.

Small cell lung cancer (SCLC) is known for its rapid growth and early metastasis, and SCLC patients are highly susceptible to chemoresistance. Studies have shown that the combination of ferroptosis induction and TRX pathway inhibition can significantly inhibit SCLC tumor growth, but the molecular mechanisms underlying ferroptosis in SCLC are poorly understood. In this study, we explored the regulatory role of the ALDH1L2-related metabolic pathway in SCLC chemoresistance by machine learning. We found that ALDH1L2 expression is a poor prognostic factor for SCLC patients and that high ALDH1L2 expression can negatively regulate the level of cellular lipid peroxidation and inhibit ferroptosis, thereby promoting SCLC chemoresistance. Mechanistically, ALDH1L2 interacts with the TRX2-PRDX3 antioxidant network to reduce the levels of hyperoxidized PRDX3 and oxidized PRDX3 dimers in the plasma membrane under cisplatin-induced stress and decrease cellular susceptibility to ferroptosis, thus promoting SCLC chemoresistance. In addition, we found that thiostrepton, a PRDX3 inhibitor, can synergize with chemotherapy to suppress tumor growth in SCLC, suggesting that thiostrepton might be a promising new tool for overcoming SCLC chemoresistance.