To investigate the response of the suppressor of the cytokine signaling (socs) gene family in rainbow trout following exposure to microplastics, this study conducted a bioinformatics analysis of the socs gene family using rainbow trout genome data, complemented by experiments involving microplastic exposure and gene expression detection.

Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neurodevelopmental disorders and birth defects. To explore the effects of PAE on gastrulation, we used an in vitro model with subchronic moderate (20 mM) and severe (70 mM) ethanol exposures during the differentiation of human embryonic stem cells into germ layer cells. We analyzed genome-wide gene expression (mRNA sequencing), DNA methylation (EPIC Illumina microarrays) and metabolome (non-targeted LC-MS) of the endodermal, mesodermal and ectodermal cells. The largest number of ethanol-induced alterations were observed in endodermal cells, whereas the most prominent changes were in ectodermal cells. Methionine metabolism and genes of the main signaling pathways involved in gastrulation and body patterning were affected by ethanol in all germ layers. Many of the altered genes, including BMP4, FGF8, SIX3 and LHX2, have previously been associated with PAE and phenotypes of FASD, like defects in heart and corpus callosum development as well as holoprosencephaly. Our findings support the early origin of alcohol-induced developmental disorders and strengthen the role of methionine cycle in the etiology of FASD.

Radiation therapy has revolutionized the treatment of primary or liver metastases in colorectal cancer (CRC). In colorectal cancer, conventional fractionation (1.8 ~ 2.0 Gy daily) is typically used for treatment. Nevertheless, there is a paucity of research investigating the potential implications of radiation therapy-induced alterations in the expression levels of regulatory genes on resistance to chemotherapy agents. Herein, we explored the mechanism by which conventional fractionation drives 5-fluorouracil (5-FU) resistance and metformin (Met) rescued 5-FU resistance in CRC.

Colorectal cancer (CRC) is emerged as a global problem with high mortality rate; hence, finding of alternative treatment approaches is essential. The purposes of this research are to assess the impact of chitosan nanoparticles conjugated with the cell free supernatant of Bifidobacterium bifidum (CTNP/B.b-sup) on genes associated with CRC signaling pathways.

Overexpressed AlaAT3 in Populus enhances ammonium tolerance by modulating carbohydrate metabolism, nitrogen metabolism, and antioxidant system-related metabolic processes. Alanine aminotransferase (AlaAT) is a critical enzyme involved in the nitrogen assimilation process in plant cells, catalyzing the reversible transfer of an amino group from alanine to α-ketoglutarate. This reaction is essential for maintaining metabolic homeostasis. Previous studies have suggested that AlaAT plays a role in alleviating ammonium toxicity in plants. To investigate this hypothesis, transgenic Populus × xiaohei plants overexpressing AlaAT3 were generated, and their phenotypic, physiological, and transcriptional traits were compared with those of wild-type (WT) plants. Under treatment with 3 mM NH4+ ammonium nitrogen, the transgenic plants exhibited significantly enhanced root biomass. Compared with WT plants, the transgenic lines demonstrated higher activities of GS, SOD, and CAT enzymes, while POD activity was notably reduced. Levels of soluble protein, free amino acids, sucrose, starch, soluble sugars, and proline were significantly elevated, whereas concentrations of O2-, and NH4+ were markedly reduced. Transcriptomic analysis revealed significant enrichment in glutathione metabolism, peroxisome, nitrogen metabolism, and starch and sucrose metabolism pathway in the transgenic plants, with corresponding genes displaying notable transcriptional changes. Regulatory network analysis identified key transcription factors, including WRKY53, DOF3.4, and DOF1.5, as potential regulators of ammonium toxicity resistance in these transgenic lines. These findings demonstrate that AlaAT3 overexpression enhances Populus × xiaohei tolerance to NH4+ by modulating glutathione metabolism, peroxisome, nitrogen metabolism, and starch and sucrose metabolism pathway. This study provides candidate genes and lays a strong foundation for future research into the mechanisms underlying NH4+ tolerance in Populus plants overexpressing AlaAT3.

Chromatin remodeling factors are involved in the inflammatory responses, contributing to tissue damage and multi-organ dysfunction in COVID-19 patients. However, the underlying mechanisms remain unclear. In this study, high-dimensional analyses of single-cell RNA sequencing and single-cell ATAC sequencing data revealed increased chromatin accessibility at the promoters or enhancers of the pro-inflammatory cytokine tissue inhibitor of metalloproteinase-1 (TIMP1), as well as altered gene transcription profiles in monocytes from COVID-19 patients. Motif enrichment and positive regulators analyses identified SMARCC1, the core subunit of the chromatin remodeling complex, and the transcription factor JUND as positive regulators to co-modulate TIMP1 expression. In-vitro experiments, co-immunoprecipitation and chromatin immunoprecipitation (ChIP)-qPCR, and others, demonstrated the collaboration of SMARCC1 and JUND. Increased 7α,25-dihydroxycholesterol (7α,25-OHC) enhanced SMARCC1-JUND interactions to co-regulate TIMP1 expression. Further investigation indicated that 7α,25-OHC promoted the expression of SMARCC1 and its co-localization with H3K27ac, which involved in the expression of TIMP1 and inflammatory responses. Our study highlights the critical roles of SMARCC1 and JUND in COVID-19 inflammation, and offers the potential targets for the prevention and treatment of COVID-19.

The SWI/SNF (switch/sucrose non-fermentable) related BAF (BRG1/BRM-related factor) chromatin remodeling complex subunit ATPase 4 (SMARCA4) is a gene with a high mutation frequency in the SWI/SNF complex. It plays a role as an ATP-dependent catalytic subunit, participates in remodeling chromatin structure and regulation of gene expression, and is closely related to the poor prognosis of malignant tumors. It is imperative to conduct a comprehensive investigation into the distinctive biological functions and mechanisms by which SMARCA4 contributes to cancer development and to devise targeted therapeutic strategies. Despite numerous studies associating SMARCA4 with the regulation of essential genes, ferroptosis, autophagy, lipid metabolism, and oxidative stress, the precise mechanisms of SMARCA4 in tumors remain unclear. Patients with SMARCA4 mutations exhibit a poor prognosis and demonstrate limited responsiveness to surgery, targeted therapies, immunotherapy, and chemotherapies. Thus, SMARCA4 emerges as a promising biomarker and therapeutic target. However, the development of more effective precision therapy tools remains an urgent unmet need. The unique molecular characteristics of SMARCA4 pose significant challenges for targeted drug development. Notably, the discovery of inhibitors targeting SMARCA4 synthetic lethal partners and associated pathways has marked a breakthrough in this field. Monotherapies directed against SMARCA4 face several limitations, including drug resistance, suboptimal objective response rates, and dose-limiting toxicities. Consequently, the exploration of combinatorial therapeutic strategies for SMARCA4 deficiency populations represents a critical direction for future clinical translation.

Glioblastoma (GBM), Isocitrate Dehydrogenase-wildtype (IDH-WT) represents the most prevalent and clinically aggressive subtype of adult diffuse gliomas, typically associated with poor prognosis. Temozolomide (TMZ) remains the first-line chemotherapeutic agent for GBM; however, the emergence of TMZ resistance represents a major therapeutic obstacle in clinical practice. This study identifies placenta-specific 8 (PLAC8) as a novel mediator of TMZ resistance in IDH-WT GBM. Elevated PLAC8 expression was strongly correlated with poorer survival rates, higher tumor grades in glioma, establishing it as an independent prognostic factor. Notably, consistent upregulation of PLAC8 was observed in both TMZ-resistant GBM cells and TMZ-treated patients, suggesting its potential as a biomarker for TMZ resistance. Mechanistic studies revealed that PLAC8 regulates TMZ sensitivity in GBM cells through the AKT-mTOR signaling pathway. Additionally, integrated bioinformatics and clinical analyses demonstrated that PLAC8 expression positively correlates with immune cell infiltration while promoting an immunosuppressive tumor microenvironment and modulating immunotherapy-related biomarkers, suggesting its potential as a predictive biomarker for immunotherapy response. In conclusion, PLAC8 represents a promising biomarker and therapeutic target for overcoming TMZ resistance and guiding immunotherapy in GBM. This study provides valuable insights for the development of personalized treatment strategies aimed at improving patient outcomes.

Bacillus amyloliquefaciens exhibits significant efficacy in the production of alkaline protease. Identifying the factors that trigger alkaline protease overproduction during the fermentation process provides valuable insights for enhancing the performance of alkaline protease-producing strains. Transcriptomic analysis revealed that quorum sensing (QS) plays a crucial role in regulating alkaline protease production. Fermentation experiments demonstrated that the addition of exogenous surfactin, a key QS signaling molecule, enhanced alkaline protease production. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis indicated that the positive effects of surfactin are associated with carbon catabolite repression (CCR), QS, and the regulation of global nitrogen metabolism. Based on these findings, rational genetic modifications, including the deletion of the rapF and kinC genes, were performed, led to a 91.1 % increase in alkaline protease production and a 15 h reduction in fermentation time. This study not only provides insights into the molecular mechanisms of surfactin-mediated alkaline protease overproduction but also offers valuable strategies for improving the industrial performance of alkaline protease-producing strains.

The use of bisphenol A has been restricted due to its toxicity. However, the impact of its substitute, bisphenol Z (BPZ), on Leydig cell function remains uncertain. We aimed to examine the associations between BPZ exposure and the disruption of Leydig cell function via upregulating Mettl3 and inducing oxidative stress. To address this, in vivo, male adult Sprague-Dawley rats received BPZ (0, 1, 10, or 100 mg/kg/d orally) for 7 days, and in vitro, purified Leydig cells were treated with BPZ (0-20 μM, 24 h). Leydig cell morphology and function were assessed. The results showed that BPZ did not alter Leydig cell quantity but notably decreased serum testosterone levels. Furthermore, it significantly downregulated the expression levels of genes and proteins (SCARB1, STAR, CYP17A1, HSD17B3, and INSL3) in Leydig cells. Concurrently, BPZ treatment led to diminished expression of antioxidant genes (Gpx1 and Cat), an upregulation in m6A related gene (Mettl3) subsequent to the enrichment of RNA methylation fragments in the testis. In vitro analysis of primary Leydig cells demonstrated that BPZ heightened oxidative stress and diminished testosterone production. In conclusion, BPZ reduces rat testosterone by downregulating steroidogenic genes (Star, Scarb1, Cyp17a1, and Hsd17b3) via METTL3-m6A-Camkk2 pathway, impairing Leydig cell function.

Endocrine disrupting compounds such as bisphenol A (BPA) negatively affect oocyte maturation and embryo development, while promoting epigenetic changes in miRNAs (miRs), including that of miR-21. miR-21 is an integral miR involved in various developmental processes, such as oocyte maturation, granulosa cells function and embryo development. Connexin (Cx) gap junction proteins play an important role in the communication among granulosa cells and cumulus cells and are impacted by bisphenols and linked to specific miRs. We hypothesize that miR-21 downregulation and BPA exposure affect Cxs mRNA and downstream miRNAs expression. Oocyte maturation was unaffected by miR-21 downregulation, but was significantly decreased (p = 0.0059) following BPA exposure. Also, BPA significantly increased Cx 43 mRNA levels when miR-21 is knocked-down in cumulus cells (p = 0.0476). miR-378a, a target of Cx 43 and 37, increased due to BPA and combination treatment in denuded oocytes (p = 0.0349) and cumulus cells (p = 0.0177). miR-96, a Cx 26 target, displayed a significant decrease in all samples following BPA exposure, in a miR-21 independent manner (p < 0.05). These data strengthen previous evidence of a strict relationship among BPA, miR-21 and especially Cx 43 and miR-378a. Further investigations are worthy in elucidating these interactions and their response to BPA exposure during early development.

Liver fibrosis is a global health issue with limited treatments. While apigenin has demonstrated potential in alleviating liver fibrosis, its mechanisms remain unclear. This study employed an integrated proteotranscriptomic approach to elucidate the molecular mechanisms underlying apigenin's protective effects against CCl4-induced liver fibrosis. Liver tissues from mice with CCl4-induced fibrosis treated with different doses of apigenin (10, 20, and 40 mg/kg) were analyzed using transcriptomics and proteomics. Results demonstrated dose-dependent antifibrotic effects of apigenin. Notably, numerous genes and proteins were inversely regulated by CCl4 and apigenin, with generally low and variable mRNA-protein abundance correlations. We identified 82 biological processes or molecular functions that were inversely regulated by CCl4 and high-dose apigenin at both mRNA and protein levels. Among the 48 key proteins (KPs) involved, 11 and 14 KPs correlated with liver fibrosis in mouse and human data sets, respectively. Six KPs maintained consistent correlations with fibrosis severity across both species, highlighting their potential as both biomarkers for fibrosis progression and translational targets. These findings underscore apigenin's therapeutic potential and emphasize the importance of multiomics approaches in understanding complex diseases like liver fibrosis. This study also provides valuable insights for developing improved therapeutic strategies and diagnostic tools for liver fibrosis.

Akkermansia muciniphila is a beneficial gut bacterium because of its improving metabolic effect. However, it is not fully understood how A. muciniphila interacts with host substances to inhabit the human gut. To examine the effect of deoxycholate (DCA) produced by the combination of host and gut bacteria, which enhances the growth of A. muciniphila, on the metabolic changes of A. muciniphila using transcriptome and proteome analyses. Transcriptome analysis showed that carbohydrate metabolism, including glycosyl hydrolase activity and glycosyl bond activity, was significantly upregulated. Notably, transcriptome and proteome analyses demonstrated that the γ-aminobutyric acid (GABA) production pathway, which is related to acid or osmotic stress responses, was upregulated in the presence of DCA. Our results demonstrated that carbohydrate metabolism and GABA production were altered in response to DCA. Therefore, DCA may be a key intestinal substance for the physiological regulation and persistence of A. muciniphila in the gut. This study provides valuable insights into understanding the interaction between host and gut bacterium to persist in the gut.

Cervical cancer is the leading type of primary malignancy in the uterus, causing significant morbidity and mortality, particularly in developing countries. Traditional treatments often result in severe side effects and recurrence, highlighting the need for safer alternatives. This study investigates the anticancer potential of Tetraselmis suecica, a green microalga known for its bioactive compounds.

Our study unravels a complex multi-layered molecular response of peanut roots to salinity, where reprograming of gene-expression is partly executed by changes in methylome via RdDM pathway and exerted through transcription factors. Peanut (Arachis hypogaea L.) is a major oilseed crop of global importance, whose production is severely impacted by salinity. Here, we have explored the transcriptional response of peanut roots to salinity stress using deep sequencing. Further, we have unravelled the salinity-induced changes in peanut root methylome. When peanut seedlings were grown under high-salt conditions for 7 days, their root and shoot growth was significantly impaired. A large-scale transcriptional reprogramming was recorded where 1926 genes were down- and 3260 genes were up-regulated due to salt stress in peanut roots. The molecular response of peanut root comprised several layers of regulators, which included the genes related to ion transport, osmolyte accumulation, signal transduction, and salt stress-responsive genes. Several negative regulators are also differentially expressed in peanut roots, which may contribute to its susceptibility. This response is regulated by a large number of transcription factors (TFs) and epigenetically by changes in DNA methylation. The DNA methylation changes in roots were highly complex and context dependent when exposed to salt stress. An inverse relationship between the changes in gene expression and methylation status was partially observed for several important gene sets and TFs. A treatment with 5'-azacytidine recovered the inhibitory impact of salt stress in peanut roots. Thus, a complex multilayered molecular response to salinity in peanut roots was observed. A part of this response may be modulated by the reprogramming of RNA-directed DNA methylation pathway. This investigation also serves as a resource for future gene-mining and methylation studies for improving peanut resistance to salt stress.

Phosphorus is an essential macronutrient for plant growth and development. Under phosphate (Pi) starvation conditions, plants activate a series of adaptive responses, among which reactive oxygen species (ROS) accumulation in root tissues represents a notable yet poorly characterized phenomenon. This study investigated the regulatory role of hydrogen peroxide (H2O2) in rice adaptation to Pi deficiency through pharmacological intervention using potassium iodide (KI), a specific H2O2 scavenger. Physiological analysis revealed that root-specific H2O2 depletion via KI treatment significantly impaired both Pi uptake and root growth under Pi-deficient conditions. Transcriptomic profiling demonstrated that H2O2 elimination substantially modulated the expression of 196 Pi starvation-responsive genes, particularly those involved in SPX-mediated phosphate sensing, extracellular acid phosphatases (APase) biosynthesis, high-affinity phosphate transporters, lipid metabolism enzymes, and redox homeostasis maintenance. Subsequent biochemical validation confirmed that both KI and diphenyleneiodonium (DPI) treatments suppressed Pi-starvation-induced APase activity and compromised Pi uptake ability. Notably, comparative analysis with the phr1/2/3 triple mutant revealed a 24% overlap in differentially expressed genes between H2O2 and PHR-deficient plants, with 90% of shared genes exhibiting congruent expression patterns. These findings collectively establish that H2O2 serves as a pivotal signaling mediator in the Pi starvation regulatory network, orchestrating metabolic reprogramming and developmental adaptation to Pi stress in rice.

Lung cancer is one of the malignant tumors with the highest morbidity and mortality in China. Despite the use of some targeted therapies in lung cancer treatment, the prognosis remains suboptimal, highlighting the urgent need for new, effective drugs to enhance outcomes. Ticagrelor, a marketed anti-platelet drug, has been reported to have anti-tumor effects. This study primarily investigates the inhibitory effect of Ticagrelor on lung adenocarcinoma in both in vivo and in vitro models, as well as its molecular mechanisms. Firstly, the effects of ticagrelor on the proliferation (CCK-8 and Edu staining), migration (scratch test), and invasion (Transwell chamber) of lung adenocarcinoma cells were evaluated using a variety of lung adenocarcinoma cell models. Secondly, the efficacy of ticagrelor on lung adenocarcinoma in vivo was evaluated by A549, H1975 tumor-bearing mouse models. Finally, transcriptomic sequencing (RNA-Seq) and immunohistochemistry were used to explore the molecular mechanism of the intervention effect of ticagrelor on lung cancer. Ticagrelor significantly inhibits the proliferation, migration and invasion of various lung cancer cells in vitro, and markedly suppressed tumor growth in A549 and NCI-H1975 CDX model in vivo. The pathological results showed that the number of tumor cells in the intervention group was significantly reduced, with large area necrosis, and the expression of Ki-67 in the intervention group was significantly decreased by immunohistochemistry. RNA-seq sequencing results from NCI-H1975 xenograft showed that several integrin-related pathways were down-regulated in the Ticagrelor treatment group, along with a significant reduction in spleen tyrosine kinase (SYK), a pivotal protein related to integrin signaling. Furthermore, we demonstrated that ticagrelor inhibits lung adenocarcinoma by down-regulating SYK and regulating PI3K/AKT pathway using WB. Ticagrelor has obvious inhibitory effect on a variety of lung adenocarcinoma cell lines and cell line transplanted tumors, and its antitumor effect may be related to the inhibition of SYK signaling pathway and PI3K/AKT pathway.

Finding the molecular targets involved in the severity and drug resistance of Colorectal cancer (CRC) and applying targeted treatments against them is a promising approach. In this study, some candidate oncogenes related to disease severity and mortality were identified by extracting bioinformatics data, and the effect of Fe3O4@Glu-Cinnamon NPs on the survival of CRC cells (SW480) and the expression of these oncogenes was investigated. The NPs were characterized by FT-IR, XRD, DLS and zeta potential measurement, TEM and SEM imaging, EDS-mapping and VSM analysis. Cytotoxicity of the NPs was evaluated by the MTT assay and a flow cytometry analysis was done to investigate cell apoptosis/necrosis levels and cell cycle analysis of cancer cells. The Fe3O4@Glu-Cinnamon NPs with spherical morphology were correctly synthesized, containing no elemental impurities, with a size range of 26.8-60.2 nm, DLS of 213 nm, zeta potential of -15.4mV and maximum magnetization level of 20.33emu/g. Treatment of cancer cells with the NPs elevated primary and late apoptosis and cell necrosis levels to 20.85, 16.83 and 9.56% and treated cells were mainly arrested at the S and G2/M phases. The expression level of the oncogenes associated with mortality, SNAI1, THBS2 and INHBA reduced to 0.74, 0.66 and 0.7 folds, respectively. The magnetic properties of Fe3O4 NPs enable their potential use in targeted drug delivery, allowing for site-specific accumulation within tumors. This could minimize systemic toxicity while enhancing treatment efficacy.

The rise of drug-resistant fungal species, such as Candida auris, poses a serious threat to global health, with mortality rates exceeding 40% and resistance rates surpassing 90%. The limited arsenal of effective antifungal agents underscores the urgent need for novel strategies. Here, we systematically evaluate the role of histone H3 post-translational modifications in C. auris drug resistance, focusing on acetylation mediated by Gcn5 and Rtt109, and methylation mediated by Set1, Set2, and Dot1. Mutants deficient in these enzymes exhibit varying degrees of antifungal drug sensitivity. Notably, we discover that GCN5 depletion and the subsequent loss of histone H3 acetylation downregulates key genes involved in ergosterol biosynthesis and drug efflux, resulting in increased susceptibility to azoles and polyenes. Additionally, Gcn5 regulates cell wall integrity and echinocandin resistance through the calcineurin signaling pathway and transcription factor Cas5. In infection models using Galleria mellonella and immunocompromised mice, GCN5 deletion significantly reduces the virulence of C. auris. Furthermore, the Gcn5 inhibitor CPTH2 synergizes with caspofungin in vitro and in vivo without notable toxicity. These findings highlight the critical role of Gcn5 in the resistance and pathogenicity of C. auris, positioning it as a promising therapeutic target for combating invasive fungal infections.

Seed aging or deterioration can affect germination rate, vigor, and viability. Allium mongolicum seeds stored for different years were used to obtain germination indicators, physiological indicators, and proteomic and transcriptomic sequencing in seeds treated with spermidine (Spd). The germination ability of A. mongolicum seeds increased and then decreased with the extension of storage life. The germination rate was only about 40% after 6 years. Relative conductivity, malondialdehyde (MDA), and hydrogen peroxide (H2O2) content first decreased and then increased, while catalase activity (CAT), peroxidase activity (POD), superoxide dismutase activity (SOD), Ascorbate peroxidase activity (APX), and respiratory rate first increased and then decreased. Spd increased the seed germination rate, CAT, POD, SOD, and APX activity. However, it significantly reduced MDA, H2O2 content, and relative conductivity. Differentially expressed proteins were concentrated in energy metabolism pathways. Ten proteins related to the aging of A. mongolicum seeds were identified. The gene expression trend was basically consistent with the proteomic assay results. Energy metabolism is a key pathway in the aging of A. mongolicum seeds. Regulating the expression of genes involved in energy metabolism pathway can effectively alleviate A. mongolicum seed aging. The results enriched the molecular mechanism of the seed storability of A. mongolicum, providing theoretical bases for molecular marker-assisted breeding of its storability traits.