Exogenous IAA applying within 32 days after herbaceous peony bud germination induces a 6-h transient stem change: first bending then upright. This process correlates with the degradation of cell wall substances like cellulose and pectin. Herbaceous peony (Paeonia lactiflora) holds a growing presence in the cut flower market. A vital criterion for selecting cut herbaceous peonies is the uprightness of their stems, which is largely determined by cell wall materials (CWMs). Our previous study indicated that applying indole-3-acetic acid (IAA) during the development process could enhance the stem straightness of herbaceous peonies at the flowering stage. Interestingly, in certain development phases, after IAA application, the stems were observed to first bend and then regain an upright position within hours (transient changes), yet the underlying mechanism remains unclear. This study aimed to identify the stages during which these transient changes occur and elucidate the role of CWMs in terms of their contents, enzyme activities, metabolites, and gene expression. The results showed that IAA-induced transient changes were most prevalent in the first three stages. The accumulated cellulose, pectin, and lignin in the IAA-treated group were consumed as the stem regained their upright position. Cinnamyl-alcohol dehydrogenase, β-glucosidase, and pectin methylesterase played key degradation roles. Combined metabolome and transcriptome analyses revealed that differential metabolites and differentially expressed genes were enriched in pathways such as glycolysis/gluconeogenesis, xylan biosynthesis process, secondary cell wall biogenesis, and lignin catabolism. The cellulose synthesis gene CESA2, decomposition gene CEL5, and pectin decomposition gene At1g48100 deserved further investigation. This study provides support for clarifying the mechanism by which IAA regulates stem uprightness of P. lactiflora and serves as a reference for selection and cultivation of herbaceous peony cut flowers.

Expression of many bacterial genes is regulated by cis- and trans-acting elements in their 5' upstream regions (URs). Cis-acting regulatory elements in URs include upstream ORFs (uORFs), short ORFs that sense translation stress that manifests as ribosomes stalling at specific codons within the uORF. Here, we show that the transcript encoding the Escherichia coli TopAI-YjhQ toxin-antitoxin system is regulated by a uORF that we name 'toiL'. We propose that in the absence of translation stress, a secondary structure in the UR represses translation of the topAI transcript by occluding the ribosome-binding site. Translation repression of topAI leads to premature Rho-dependent transcription termination within the topAI ORF. At least five different classes of ribosome-targeting antibiotics relieve repression of topAI. Our data suggest that these antibiotics function by stalling ribosomes at different positions within toiL, thereby altering the RNA secondary structure around the topAI ribosome-binding site. Thus, toiL is a multipurpose uORF that can respond to a wide variety of translation stresses.

Pancreatic cancer (PC) has a poor prognosis and limited response to therapies. Combinatorial approaches, such as natural product-based therapies, can enhance anticancer efficacy while minimizing side effects. This study evaluated M. sativa's anticancer properties and its potential as adjunctive therapy with Gemcitabine (GEM) to sensitize PANC-1 cells to chemotherapy.

Omaveloxolone is a synthetic oleanane triterpene with considerable antitumor activity. It induces human glioblastoma (GBM) cell death in vitro and in vivo, but the underlying mechanism remains to be determined. In this study, GBM cell lines (GBM8401 and U-87 MG cells) were exposed to different concentrations of omaveloxolone (0, 600, 800 and 1000 nM). A cell viability assay was conducted using the PrestoBlue Cell Viability Reagent. Three-dimensional microscopy revealed changes in cell morphology. Cell cycle, apoptosis and mitochondrial membrane potential were tested using flow cytometry. The expression levels of cell cycle-related proteins and genes were determined through Western blotting and next-generation sequencing, respectively. The results indicated that omaveloxolone had significant selective cytotoxicity against human GBM cells and suppressed the migration and invasion of these cancer cells. It also caused cell cycle arrest through the downregulation of cell cycle-related genes, including cell division cycle 20 homologue (CDC20), as revealed by next-generation sequencing. In a xenograft tumour model, omaveloxolone decreased tumour volume and CDC20 expression. Taken together, these findings suggest that omaveloxolone is a potential drug candidate for GBM treatment by promoting GBM cell death through the downregulation of CDC20 expression.

Cadmium is one of the most toxic heavy metal pollutants in the world, seriously affecting crop growth and human health. 2,4-Epibrassinolide (BRs) has been proven to promote plant growth, enhance abiotic stress resistance and improve crop quality and yield. In this study, adzuki bean (V. angularis) cultivar 'Zhen Zhuhong' was grown hydroponically in 1/2 Hoagland nutrient solution with 0, 1, and 2 mg L-1 cadmium chloride (CdCl2), and then treated with 0 or 1 μM BR at the V1 stage. Compared with Cd stress, ascorbic acid content, peroxidase (POD, EC 1.11.1.7), catalase (CAT, EC 1.11.1.6) and superoxide dismutase (SOD, EC1.15.1.1) activities in adzuki Cd-stressed bean roots under BR treatment were increased by 30.63%, 41.83%, 51.49%, and 29.48%, which alleviated intracellular ROS accumulation and DNA oxidative damage. In addition, proline content and free amino acid content in BR-treated adzuki bean seedling roots under Cd stress increased by 30.37% and 35.96%, which was conducive to maintaining cell membrane homeostasis and improving root activity. RNA-seq and real-time quantitative reverse transcription PCR analyses revealed that BR treatment regulates the absorption, transport, and accumulation processes of Cd2+ in adzuki bean seedling roots, reducing the nonspecific accumulation of Cd2+ within cells and alleviating the toxic effects of Cd on root cells. BR treatment enhances the DNA damage repair in the roots of adzuki beans under Cd stress by reducing the extent of DNA oxidative damage, and effectively promoting the transition of cells from the G1 phase to the S phase.

Common carp is one of the most economically important freshwater fish species globally. Ammonia exposure, a frequent challenge in aquaculture, can lead to significant economic losses. This study investigated the impact of un-ionized ammonia (UIA) exposure on the expression profiles of three key genes in common carp fry: interleukin-1 beta (IL-1β), corticotropin-releasing hormone (CRH), and leptin a1 (Lep-a1). These genes are crucial indicators of immune response, stress regulation, and appetite control, respectively. Fish were exposed to 0.7 mg/L of UIA, and gene expression was analysed in liver and gill tissues at five time points (12 h, 2-, 4-, 7-, and 14-days of exposure) using quantitative real-time PCR (RT-qPCR).

Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematopoietic malignancy, necessitating the exploration of innovative therapeutic approaches. Targeting epigenetic mechanisms has emerged as a promising avenue for cancer treatment. EP300 belongs to the KAT3 family of histone/non-histone lysine acetyltransferases, regulating gene expression by acetylating H3K27. However, the role of EP300 and its potential as a targeted therapy in DLBCL remains unknown.

The prevalence of depression in women is approximately twice that in men. Differences in androgens levels between men and women, due to gonadal differences, may be associated with the development of depression, although the underlying mechanisms are not well understood.

Chromium (Cr) contamination poses food safety and environmental challenges, yet the early-stage physiological and molecular responses to Cr(III) stress remain unclear. Citrus and tomato are economically important crops representing woody and herbaceous species, making them valuable models for studying heavy metal toxicity in plants. This study investigates the impact of Cr (III) exposure on citrus and tomato seedlings, with a focus on physiological phenotypes and transcriptional response. Citrus seed germination declines with increasing Cr(III) concentrations, while low Cr(III) levels promote tomato germination, with inhibition occurring above 1 g/L. Under hydroponic conditions, Cr (III) severely hampers root and leaf growth in both citrus and tomato plants, accompanied by decreased net photosynthetic rate. Using a GFP-based confocal microscopy system, we observed reduced fluorescence intensity within three days of Cr(III) exposure (100 mg/L and 500 mg/L), indicating early cellular damage. Biochemical assays revealed oxidative stress, marked by increased H2O2, malondialdehyde (MDA), and antioxidant enzyme activity. Additionally, low Cr (III) concentrations could result in the death of various microorganisms, including Escherichia coli, Agrobacterium rhizogenes, and Agrobacterium tumefaciens. Transcriptomic analysis identified differentially expressed genes related to "MAPK signaling pathway" and "Plant hormone signal transduction pathway". Transcription of many transcription factors, such as bHLH, WRKY, and MYB, also underwent significant changes.

Long-term exposure to arsenic (As), which is a ubiquitous environmental contaminant, significantly enhances the risk of multiple cancers, including bladder and lung cancers. In recent years, the important roles of circular RNAs (circRNAs) in tumorigenesis and development have attracted widespread attention. However, the specific molecular mechanisms by which circRNAs promote bladder cancer development following exposure to arsenic remain incompletely understood. This study is the first to demonstrate that circPDE3B is significantly upregulated in a cell model of transformation triggered by arsenic and that it promotes this transformation process. Our study elucidated the biological function of circPDE3B in vitro, in SV-HUC-1 cells, showing that it accelerates the malignant transformation from arsenic via increasing cell proliferation and inhibiting apoptosis. Furthermore, we delineated a novel molecular mechanism whereby circPDE3B directly binds to NF-κB and STAT3, inhibiting their ubiquitination and increasing their stability. This, in turn, affects downstream HIF-1α expression, promoting the malignant transformation of SV-HUC-1 cells and eventually resulting in bladder carcinogenesis. Our research reveals the critical regulatory role of circPDE3B in the arsenic-triggered malignant transformation within SV-HUC-1 cells. This study offers broader perspectives on the molecular mechanisms driving bladder cancer progression, while also identifying potential targets for early diagnosis and treatment of bladder tumour.

Bacteria have been known to thrive in challenging environmental niches through diverse phenomena. Swarming is one such favourable adaptations that could help bacteria survive extreme conditions. Therefore, targeting swarming is crucial for improving our understanding of bacterial motility and preventing related infections. Bacillus cereus, which causes food poisoning, has been shown to perform swarming, and salts like NaCl can act as a food preservative to control bacterial growth. To explore the possible alterations in the swarming of Bacillus cereus in the presence of salt, the present study encompasses the effect of NaCl on the swarming characteristics of a natural bacterial isolate, Bacillus cereus MHS, with a hyperswarming phenotype. Here we report that increased NaCl in growth media could induce a reduction in swarming motility and pattern of MHS on Luria agar plates. This observed reduction in swarming was found to be associated with reduced flagellation and a reduction in the abundance of bacterial nanotubes. Gene expression studies supported the phenotypic and ultrastructure observations as the expressions of bfla and ymdB genes, involved in formations of flagella and nanotubes, respectively, were found to be reduced in the swarming MHS cells in the presence of increased NaCl. It was also observed that the salt-induced reduction in swarming of MHS is associated with the reduced expression of the quorum sensing regulator gene plcR. This study first time reports the bacterial nanotubes in a Bacillus cereus strain indicating a possible link between the bacterial nanotube formation and hyperswarming phenotype in Bacillus cereus MHS.

This study aimed to investigate the target genes of active components in Dingxiang Guanshitong (DGST) and evaluate their significance in the prognosis of esophageal cancer (EC) through integrated approaches, including network pharmacology, molecular docking, prognostic analysis, and in vitro experiments. EC-related data were obtained from TCGA database, while SymMap and TCMSP databases were utilized to identify DGST's bioactive components and their targets. A comprehensive network was constructed to map component-target-pathway interactions. Bioinformatics analysis revealed 113 key signaling pathways and 424 differentially expressed targets associated with DGST and EC. Univariate Cox regression analysis identified 21 target genes significantly correlated with overall survival (OS) in EC patients, among which six exhibited pharmacological activity. Molecular docking confirmed strong binding affinities between DGST's active components and critical targets. In vitro experiments demonstrated that DGST suppressed migration, invasion, and proliferation of TE-1 and EC-109 cell lines while promoting apoptosis. Furthermore, DGST significantly upregulated the protein and mRNA expression of the prognostic factor NFKBIA, while downregulating GPER1, HK2, MAOB, TNFRSF10B, and ECE1. This study is the first to elucidate the molecular mechanisms underlying DGST's anti-EC effects. DGST exerts its anti-cancer activity by targeting prognosis-related genes and modulating the expression of critical molecular markers, thereby inhibiting EC progression and improving therapeutic outcomes. These findings provide a robust scientific foundation for the clinical application of DGST and further exploration of its mechanistic basis.

Localized ablative immunotherapy (LAIT), a combination of photothermal therapy (PTT) and the immunostimulant glycated chitosan (GC), has demonstrated therapeutic efficacy in cancer treatment. However, its impact on the tumor microenvironment (TME), particularly on tumor-infiltrating natural killer (TINK) cells, remains to be fully elucidated. Using single-cell RNA sequencing (scRNAseq), we analyzed the transcriptional and functional modulations of TINK cells by LAIT in a mouse breast cancer model. Additionally, we investigated immune checkpoint inhibitor (ICI)-induced changes in NK cells across multiple cancer types and evaluated the clinical relevance of these transcriptional changes using The Cancer Genome Atlas (TCGA) database. ScRNAseq revealed five NK cell subtypes, with LAIT increasing the proportion of interferon-enriched NK cells and enhancing NK cell differentiation and cytotoxicity. Functional analyses demonstrated that LAIT upregulated activation, cytotoxic, and interferon pathway genes while downregulating immune-suppressive genes, effects largely driven by GC. Comparative analysis showed significant transcriptional overlap between ICI and LAIT, highlighting shared pathways in NK cell-mediated cytotoxicity and chemokine signaling. Prognostic models constructed from ICI- and LAIT-induced gene signatures effectively stratified breast cancer patients by survival risk, with LAIT-induced genes showing the highest predictive performance. Furthermore, higher NK cell proportions and the expression of key prognostic genes, such as PSME2, IGKC, and KLRB1, were associated with improved overall survival. LAIT and ICIs enhance NK cell-mediated antitumor responses via distinct yet complementary mechanisms, emphasizing their potential for synergistic use. These findings provide novel insights into NK cell modulation within the TME and support the development of combinatorial immunotherapy strategies.

Prediabetes, also known as impaired glucose tolerance (IGT), is a common metabolic disorder and is often considered a risk factor for the development of diabetes. Metformin (MET) is a widely used medication for the treatment of diabetes and has the potential to improve insulin sensitivity and blood sugar control. This work aimed to investigate the impact of MET treatment on serum miRNA expression in IGT patients and explore the quantitative changes in miRNA after MET treatment.

Thiamine, also known as vitamin B1, serves as an inducer that strengthens plants and elicits defense responses to enhance resistance against pathogens. Currently, the antiviral mechanism of thiamine remains unclear. Here, we used maize chlorotic mottle virus (MCMV) as a model to elucidate the antiviral mechanism of thiamine. We found that thiamine application improved maize resistance to the MCMV. Transcriptome sequencing indicated that MCMV infection influenced the expression of thiamine synthesis pathway-related genes. Besides, MCMV P31 interacted with the key thiamine synthesis factor, ZmTHIC in cytoplasm, and blocked ZmTHIC entering into chloroplast. Using the cucumber mosaic virus (CMV) induced gene silencing system, we silenced ZmTHIC in maize, resulting in higher accumulation of MCMV compared to the control plants. LC-MS analysis revealed that both ZmTHIC silencing and MCMV infection reduced the thiamine content in maize. Thiamine treatment prior to MCMV infection enhanced plant defense responses by activating the MAPK pathway and promoting lignin synthesis in plant cell walls, ultimately inhibiting MCMV infection. Taking together, our results suggest that thiamine induced the synthesis of lignin and MAPK pathway to enhance the systemic immunity, promoting antiviral defense in maize. MCMV P31 hijacked ZmTHIC and prevented it from entering the chloroplasts, thereby inhibiting the synthesis of thiamine to dampen the synthesis of lignin and MAPK pathway to dampen the plant immunity. This research provides new insights into the antiviral mechanism of thiamine.

Nasopharyngeal carcinoma (NPC) is a unique cancer type originating from the nasopharynx. To investigate novel strategies for improving prognosis and reducing the adverse effects of current treatments, this study examined the efficacy of hellebrigenin. Hellebrigenin demonstrated selective cytotoxicity against NPC-BM and NPC-039 cell lines without harming normal nasopharyngeal cells. Treatment with hellebrigenin resulted in G2/M cell cycle arrest in both NPC cell lines. The apoptotic phenomena induced by hellebrigenin included chromatin condensation, increased apoptotic cells and altered mitochondrial membrane potential. Proteomics analysis and the bioinformatic data identified coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) as a candidate oncogene in NPC. Moreover, the combination of CHCHD2 siRNA, CHCHD2 plasmid and hellebrigenin pointed out that CHCHD2 could be a critical mediator of hellebrigenin-induced apoptosis. The combined treatment of hellebrigenin with mitogen-activated protein kinase inhibitors revealed the involvement of the extracellular signal-regulated kinases and c-Jun N-terminal kinases pathways in hellebrigenin-induced apoptosis in NPC cells. In vivo studies demonstrated that hellebrigenin suppressed the tumour volume without affecting body weight, accompanied by the downregulation of Ki67 and CHCHD2 expression. In conclusion, this study provides evidence that hellebrigenin induces NPC apoptosis through regulating CHCHD2 both in vitro and in vivo.

DNA methylation alterations, including hypermethylation and silencing of tumor suppressor genes, contribute to cancer formation and progression. The FDA-approved nucleoside analogs azacytidine and decitabine are effective demethylating agents for hematologic malignancies but their general use has been limited by their toxicity and ineffectiveness against solid tumors. GSK-3484862, a dicyanopyridine-containing, DNMT1-selective inhibitor and degrader, offers a promising lead for developing novel demethylating therapeutics. Here, we demonstrate that GSK-3484862 treatment upregulates DNMT3B expression in lung cancer cell lines (A549 and NCI-H1299). Disrupting DNMT3B in NCI-H1299 sensitizes these cells to GSK-3484862, enhancing its inhibitory effects on cell viability and growth. GSK-3484862 treatment induces demethylation at DNMT3B regulatory elements including a candidate enhancer located ∼10 kb upstream of the DNMT3B transcription start site, as well as at the promoter of TERT (telomerase reverse transcriptase), a potential activator of DNMT3B expression. These demethylation events correlate with upregulation of DNMT3B expression. These findings suggest that combining inhibitors targeting DNMT1, the maintenance methyltransferase, with those targeting DNMT3A/3B, the de novo methyltransferases, or using pan-DNMT inhibitors, could enhance anticancer efficacy and reduce resistance.

Ischemic stroke (IS) is one of the most sinister diseases and the second leading cause of death in the world. Eugenol (EUG) is a natural and biologically active component that can be extracted from various plants. Studies have found that EUG can alleviate middle cerebral artery occlusion and reperfusion (MCAO/R) injury in mice, but the specific mechanism remains vague. Tripartite motif protein 59 (TRIM59) is a member of TRIM protein family, a group of E3 ubiquitin ligases. In this article, we conducted both in vivo and in vitro experiments to determine the effect of EUG on ischemia-reperfusion injury and to explore the underlying mechanisms by manipulating the expression of TRIM59. Results showed that EUG alleviates acute injury and promotes functional repair of mouse IS by enhancing the phagocytosis of microglia through up-regulating the TRIM59, activating the STAT3 pathway and promoting the expression of CD11b.

A cutting-edge smart nano-hybrid technology, offering potential benefits for plants, has recently been developed to address the pervasive issue of heavy metal pollution. This study explored the potential of this technology in mitigating chromium (Cr) stress in rapeseed using a nano-based system that integrates 100 μM hydrogen sulphide (H2S) and 50 μM manganese nanoparticles (Mn-NPs). This strategy reveals Cr-stress tolerance mechanisms through physiological assessments and transcriptome data analysis. The results demonstrated that Cr stress substantially inhibited rapeseed growth while increasing oxidative damage markers (MDA and ROS levels). Conversely, Mn-NP and H2S co-treatment significantly mitigated these effects, as shown by: (1) restored growth metrics, (2) improved photosynthetic performance and membrane integrity, (3) optimized Mn/H2S homeostasis, and (4) reduced tissue Cr accumulation. The reduction in Cr content was attributed to enhanced Cr-detoxification mechanisms, driven by the upregulation of enzymatic antioxidant activities, like superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase. Transcriptomic profiling revealed marked upregulation of genes involved in core metabolic processes, including photosynthetic pathways, carbon assimilation, secondary metabolite biosynthesis, inositol/phosphatidylinositol signalling systems, and stress-response networks. Under Cr stress, Mn-NP and H2S co-treated rapeseed plants displayed enhanced tolerance, highlighting the crucial role of these signalling agents in activating Cr-defence mechanisms. Our findings demonstrate that the integration of nanotechnology and gasotransmitter signalling molecule H2S presents a novel strategy for enhancing heavy metal tolerance and plant productivity in contaminated soils.

Kujigamberol, a dinorlabdane compound isolated from Kuji amber, exerts multiple biological effects, including anti-allergic and anti-inflammatory activities. The present study demonstrated that kujigamberol inhibited cytokine production by T cells. In response to a phorbol 12-myristate 13-acetate (PMA) and ionomycin (IM) stimulation, kujigamberol suppressed interferon-γ (IFN-γ) and interleukin-2 (IL-2) mRNA expression in murine T-cell lymphoma BW5147 cells stably transfected with the T-box transcription factor eomesodermin. IL-4 and Fas ligand mRNA expression was also inhibited by kujigamberol. In the murine cytotoxic T-cell line CTLL-2, kujigamberol more strongly decreased IFN-γ mRNA expression induced by IM alone than that induced by the combination of PMA and IM. A luciferase reporter assay showed that kujigamberol preferentially reduced nuclear factor of activated T cell (NFAT)-dependent transcription in human embryonic kidney 293T cells. Unlike the calcineurin inhibitor FK506, kujigamberol did not markedly affect NFATc2 protein levels in BW5147 cells but interfered with the binding of NFATc2 to the IFN-γ and IL-2 promoters. These results indicate that kujigamberol inhibited IFN-γ and IL-2 mRNA expression by preventing the binding of NFATc2 to their promoters; therefore, it has potential as an immunosuppressive agent.