Peaches are susceptible to chilling injury when exposed to low temperature conditions. ABA function as a regulator for chilling damage in peach fruit. In this research, we examined an ABA-induced receptor-like protein kinase, FERONIA, whose transcript levels showed significant up-regulation during ABA mitigation of chilling injury. This study found that ABA treatment promoted the sucrose metabolism-related enzymes activities and genes transcriptions, maintained higher sucrose content. Furthermore, molecular biology tests indicated that PpFERL increased the expression of PpSPS4, a regulator of sucrose mechanism during ABA alleviating chilling injury of peaches. When transiently over-expressed PpFERL in peach fruit, the sucrose content were increased, meanwhile the expression of PpSPS4 and the activity of SPS were be enhanced. Yeast two-hybrid and biomolecular fluorescence complementation analysis revealed that PpFERL directly interacts with PpSPS4. Our findings indicate that PpFERL interacts with and positively regulates PpSPS4, which is associated with changes in SPS activity and sucrose metabolism.

Mannheimia haemolytica (Mh) is an opportunistic pathogen that causes pneumonic infections in different ruminants. It is also part of the respiratory tract microbiome, but it descends into the lower respiratory tract under stress, causing shipping fever. The stress hormones epinephrine and norepinephrine have been suggested to induce Mh biofilm dispersion, but their roles in virulence have not been shown. In this study, the effects of these two hormones on Mh growth and on the expression of adhesins, proteases, and biofilm formation are evaluated. Physiological concentrations (1-5 ng/mL) of epinephrine and norepinephrine increase the growth of Mh and the expression of 42- and 75-kDa gelatin proteases, induce biofilm dispersion, and decrease biofilm protein and carbohydrate concentrations. At 50 or 500 ng/mL concentrations of epinephrine and norepinephrine, the expression of OmpA and OmpH adhesins and 42- and 100-kDa casein proteases increases. Bacterial adhesion to bovine monocytes or oral epithelial cells also increases, but antibodies against OmpH and OmpA diminish adhesion. Our results strongly suggest that epinephrine and norepinephrine modulate the expression of Mh virulence factors.

The effects of exposure to air pollution on epigenetic age acceleration remain unclear. This study investigated the associations between exposure to six air pollutants (PM2.5, PM10, CO, NO2, SO2, and O3) and DNA methylation age using multiple epigenetic clocks, including Horvath (353 CpGs), Best Linear Unbiased Predictor (BLUP, 319,607 CpGs), and Elastic Net (EN, 514 CpGs) among 2462 participants from the Taiwan Biobank. Both PM2.5 and PM10 exposure showed significant associations with all three epigenetic clocks. In multi-pollutant models combining PM2.5 with other pollutants, the associations remained significant. The weighted sum of all air pollutants showed significant associations with all three epigenetic clocks. Weight distribution analyses identified PM2.5 and PM10 as the predominant contributors across all clock models. These results underscore the importance of air pollution control as a key component of public health strategies aimed at promoting healthy aging.

This review systematically summarizes the research progress on the regulation of microRNAs (miRNAs) by traditional Chinese medicine (TCM) in the prevention and treatment of hepatocellular carcinoma (HCC). As one of the most prevalent and lethal malignancies worldwide, the efficacy of current therapeutic strategies for HCC remains limited due to tumor heterogeneity and drug resistance, necessitating the exploration of novel treatment approaches. TCM, with its multi-target regulatory advantages, has demonstrated unique potential in influencing HCC progression by modulating miRNA expression, thereby affecting tumor cell proliferation, apoptosis, and invasion. This review provides an in-depth discussion of the biological pathways involved in TCM-mediated miRNA regulation, including transmembrane transport, targeted modulation, and bio-carrier-mediated delivery mechanisms. The dual role of miRNAs in HCC as either tumor suppressors or oncogenes is extensively analyzed. Moreover, we highlight the key mechanisms by which TCM modulates miRNA expression, such as epigenetic regulation, signal transduction pathway intervention, and anti-inflammatory and immunoregulatory effects, ultimately influencing HCC progression. Additionally, the clinical significance of serum miRNAs in HCC diagnosis, prognosis assessment, and correlation with pathological characteristics is discussed. Finally, we explore the challenges and future directions in HBV-associated HCC treatment via miRNA modulation, providing new insights into HCC prevention and therapeutic strategies.

Opisthorchis viverrini, Southeast Asian liver fluke, is a parasitic flatworm that has been widely spread in Asia and is a major risk factor for bile duct cancer - cholangiocarcinoma (CCA). Over 12 million people are at risk of opisthorchiasis, and the associated CCA is known to have claimed around 20,000 deaths per year in Thailand alone, with the number projected to be underestimated elsewhere. There is an opportunity to develop more efficient drug targets and diagnostic biomarkers, and these are urgently needed. Despite previous studies on gene expression analysis and reference genome, the knowledge on the biological processes of O. viverrini during its development remains largely unclear. Our study employed RNA-sequencing transcriptomics of O. viverrini developmental stages within hamsters from the juvenile stage (14-day post-infection), the adult stage of acute infection (42 days), and the adult stage of chronic infection (180 days). Differential gene expression and functional analyses were performed, and genes with stable expression (GSEs) were identified based on the transcript per million (TPM) normalization method and coefficient of variation. Our results show that key genes in juveniles were mostly associated with proteolysis, energy metabolism, signal transduction, and development. Significantly up-regulated genes in adult O. viverrini were associated with parasitic reproductive systems and parasitism. A total of 2,011 GSEs were identified, with 27 genes being highly expressed, and 628 genes showing no orthologues in the human reference genome. From this novel dataset, we illustrated insight into parasite biology, which revealed key molecular processes during intra-mammalian infection, and provided the candidate targets for biomarkers, drugs, and vaccine development. This valuable information will contribute to opisthorchiasis diagnostics and prevention in endemic countries and provide leads for future characterization of essential genes across liver fluke species.

Human germline gene expression is normally constrained to the germ cells, responsible for the production of sperm and oocytes. Cancer-germline (CG) genes, a subset of germline genes involved in testis development, are frequently aberrantly activated in cancer cells. The present study investigates the broader hypothesis that epigenetic modifications, specifically DNA methylation, can modulate the expression profiles of several CG genes in cancer and germ cells. Breast cancer (BC), normal breast (NB), and chronic myelogenous leukemia (CML) cell lines were treated with the DNA methyltransferase inhibitor (DNMTi) 5-aza-2'-deoxycytidine for three days. The effects of this treatment on the transcriptional activation of CG genes (SYCP1, ADAD1, SYCE1, PRSS54, DMRTC2, and TEX101) were then evaluated. We comprehensively analyzed differential methylation, survival analysis (Kaplan-Meier), correlation (Spearman's), and pathway enrichment analysis (GO/KEGG) of CG genes (SYCP1, ADAD1, SYCE1, PRSS54, DMRTC2, and TEX101) in BC and leukemia. Treatment with 5-aza-2'-deoxycytidine upregulated CG genes in BC cells but downregulated them in leukemia cells, highlighting tissue-specific epigenetic responses. Differential methylation analysis revealed cancer-specific patterns: ADAD1 was hypermethylated in both malignancies, while PRSS54 was hypomethylated in leukemia. Survival analysis linked SYCE1 and PRSS54 to prolonged survival in BC, whereas TEX101 and SYCP1 correlated with poorer outcomes. Functional enrichment identified ADAD1 and SYCP1 as key players in BC and leukemia pathways, respectively. Meta-analysis validated SYCP1 as a robust biomarker with consistent effect sizes across datasets. Methylation-expression correlations were stronger in tumors, with SYCE1 and DMRTC2 showing inverse relationships in leukemia. These findings demonstrate that the expression of a subset of CG genes is responsive to modulation by hypomethylating drugs in a tissue-specific manner, highlighting their promise as candidates for future investigation in cancer immunotherapy.

Polycystic Ovary Syndrome (PCOS) is a common endocrine and metabolic disorder characterized by chronic inflammation, insulin resistance, and hormonal imbalances, often leading to infertility and metabolic dysfunction. Metformin, an insulin-sensitizing agent, has shown potential to improve these conditions. This study investigated the impact of metformin on inflammasome-regulating microRNAs (miR-9, miR-223, miR-132) and related genes (IL-1β, IL-18, caspase-1, NLRP3) in obese and non-obese PCOS patients compared to healthy controls.

Venous thromboembolism (VTE) remains a leading contributor to maternal morbidity and mortality during pregnancy and the immediate postpartum period. Although pregnancy is recognized as a hypercoagulable state, the molecular mechanisms underlying this prothrombotic shift remain incompletely characterized. In this study, lactoferrin was identified as an enhancer of coagulation factor XIa (FXIa) activity. Elevated plasma concentrations of lactoferrin were observed in pregnant women and found to be estrogen dependent, mediated through estrogen response elements (EREs) within the lactoferrin gene promoter. In murine models, pregnancy-induced thrombotic pathology was ameliorated by either genetic knockout of lactoferrin or pharmacological blockade using HS9, a peptide that selectively inhibits lactoferrin-mediated potentiation of FXIa. Notably, HS9 (1 mg/kg) exhibited a substantially reduced hemorrhagic profile compared with low-molecular-weight heparin. These findings identify lactoferrin as a physiological modulator of gestational hypercoagulability and implicate it as a potential therapeutic target for pregnancy-associated VTE, with the capacity to reduce thrombotic risk while preserving hemostatic integrity.

Paclitaxel (PTX), a commonly utilized chemotherapy drug, is linked to peripheral neuropathy, which limits dosing and significantly affects patients' quality of life. C-terminal binding protein 1 (CtBP1) is a transcriptional coregulator that participates in epigenetic gene regulation, but its role in PTX-induced neuropathic pain remains unclear. In this study, the role of CtBP1 in PTX-induced neuropathic pain is examined, with a focus on its epigenetic regulation in the dorsal root ganglia (DRGs). PTX administration markedly increased CtBP1 protein levels in DRG neurons, which coincided with the development and continuation of mechanical allodynia and thermal hyperalgesia in rat models. Our findings also revealed that CtBP1 interacts with the histone demethylase LSD1-a regulator of H3K9me2-at ErbB2 promoter sites in DRG neurons. PTX treatment increased CtBP1 protein levels, which subsequently induced LSD1 expression and decreased H3K9me2 protein levels at the ErbB2 promoter, indicating epigenetic activation of ErbB2 signaling in DRG neurons implicated in neuropathic pain. Reducing either CtBP1 or LSD1 expression reversed ErbB2 upregulation and attenuated PTX-induced pain sensitivity. These results suggest that the CtBP1-LSD1 complex epigenetically increases ErbB2 expression in DRG neurons, contributing to PTX-induced neuropathy. Targeting the CtBP1-LSD1 pathway could represent a promising therapeutic strategy for the treatment of chemotherapy-induced neuropathic pain.

Temozolomide (TMZ) resistance is an urgent problem in the treatment of glioma. circNEIL3 is related to the malignant progression of glioma. Nevertheless, the function of circNEIL3 in TMZ resistance is still unclear. In this study, we found that circNEIL3 is overexpressed in glioma tissues and cells and is related to TMZ resistance. Cell experiments and mouse experiments have shown that inhibiting the expression of circNEIL3 can enhance the sensitivity of glioma cells to TMZ. RNA immunoprecipitation and other molecular experiments demonstrated that circNEIL3 and the RNA-binding protein U2 small nuclear RNA auxiliary factor 2 (U2AF2) interact with each other and partially colocalize in cells. SPI1 was highly expressed in glioma, more significantly in TMZ-resistant tissues, and correlated with circNEIL3 expression. Furthermore, we discovered that U2AF2 interacts with SPI1 mRNA as well, and circNEIL3 and U2AF2 together regulate the expression and mRNA stability of SPI1. More importantly, SPI1 silencing inhibited the malignant progression of cells and partially reversed the effects of circNEIL3 on glioma cell proliferation and apoptosis. In conclusion, circNEIL3 stabilizes SPI1 mRNA expression by binding to U2AF2, thereby promoting glioma progression and TMZ resistance.

Heavy metal contamination severely impacts global food safety because of its toxicity, bioaccumulation, and nonbiodegradability. Recently developed nanotechnology strategies, including the use of greenly synthesized nanoparticles, offer environmentally safe solutions. An experiment on wheat investigated how biogenic calcium phosphate nanoparticles (CaPNPs) can improve the cellular defense against manganese toxicity. Cultivated wheat plants were irrigated with 300 μM MnSO4 and treated with foliar spraying of biogenic CaPNPs, which were green synthesized using Jania rubens extract, at concentrations of 25, 75, and 150 mg L-1. The 21-day-old seedlings manifested manganese (Mn) poisoning, represented by a reduction in plant height as well as weight, photosynthetic pigments, and nonenzymatic antioxidants, in addition to an escalation in the oxidative stress indicators represented by reactive oxygen species (H2O2) and lipid peroxidation (LPO). Furthermore, an increase in the pool of antioxidant compounds as well as antioxidant enzymes, minerals, in addition to the total antioxidant capacity, was clearly promoted by CaPNP application, especially at 75 mg L-1, which was consistent with the control. Consequently, CaPNPs caused a significant reduction in Mn, H2O2, MDA, and their oxidative damage. Additionally, 75 mg L-1 CaPNPs stimulated the expression of anti-oxidative stress responsive genes, catalase (CAT) and superoxide dismutase (SOD), in addition to betaine aldehyde dehydrogenase (BADH) and mitogen-activated protein kinases (MAPKs). Therefore, the use of biogenic 75 mg L-1 CaPNPs as an eco-friendly nanofertilizer plays a crucial role in plants growing in Mn-contaminated soil by promoting their growth characteristics, counterbalancing oxidative damage, and provoking the activity of the antioxidant defense machinery.

Bromodomain-containing protein 9 (BRD9) is an epigenetic reader component of the non-canonical BAF (BRG1/BRM-Associated Factors) chromatin remodeling complex, involved in the regulation of transcription. The ncBAF complex differs from the other two complexes, the canonical BAF and PBAF, as it contains unique subunits encoded by genes including BRD9, GLTSCR1 (Glioma Tumor Suppressor Candidate Region 1), and GLTSCR1L (GLTSCR1-Like). In recent years, BRD9 has emerged as a promising therapeutic target in several diseases.

Iron (Fe) deficiency causes anemia in humans and yield losses in crops. Increasing Fe concentration in plants would be beneficial for agriculture and global health. The allelochemical L-3-(3,4-dihydroxyphenyl)alanine (L-DOPA) can promote Fe accumulation, and its potential use for Fe biofortification was investigated. L-DOPA was exogenously supplied to Arabidopsis thaliana, and the expression of Fe deficiency genes was measured in shoots and roots of the ima8x and bhlh121 mutants defective in Fe deficiency response. L-DOPA and Fe were quantified, and Fe was imaged in leaves. L-DOPA triggers a transient and intense increase in the expression of Fe deficiency genes, leading to Fe accumulation in shoots. The transcription of Fe deficiency genes was also induced in shoots, indicating that L-DOPA affected Fe perception by leaves. Surprisingly, while L-DOPA accumulated in roots, it remained undetectable in shoots. The increased expression of the upstream Fe deficiency genes upon L-DOPA exposure did not require functional URI/bHLH121 nor IMA genes and also occurred in rice. L-DOPA stimulated the transcriptional response to Fe deficiency through a mechanism independent of the well-known network of BASIC HELIX-LOOP-HELIX transcription factors that regulate Fe homeostasis. This process involved a root-borne signal that activated the shoot response to Fe deficiency in Fe-overloaded plants.

The tamoxifen-inducible Cre-loxP system is an indispensable experimental tool in life sciences for inducing spatiotemporally controlled genetic recombination in the target tissues of living animals. The use of this technology is expected to increase in taste research. However, the direct effects of tamoxifen on taste buds remain largely unexplored. Here, we demonstrate that tamoxifen reduces cell supply to the taste buds in a dose-dependent manner. RNA sequencing of the circumvallate epithelium revealed that tamoxifen induced a transcriptional shift from proliferation to differentiation. The genes regulating the cell cycle were downregulated, whereas genes promoting the differentiation of epithelial cells and keratinocytes were upregulated. Within taste buds, Shh was downregulated in immature precursor cells, whereas cell type-specific genes were broadly upregulated in mature taste bud cells. Notably, transcription factors driving taste cell type differentiation, such as Pou2f3, Ascl1, and Nkx2-2, were induced, suggesting that tamoxifen activates transcription to promote the differentiation of all cell types in taste buds, rather than activating particular signaling pathways in specific cell types. These findings indicate that tamoxifen rapidly triggers a transcriptional switch from proliferation to differentiation in the circumvallate taste epithelium, highlighting a potential confounding effect in taste research that employs tamoxifen administration.

Chronic endometritis (CE) is a persistent inflammatory condition associated with adverse pregnancy outcomes. Although impaired endometrial angiogenesis is thought to contribute to its pathogenesis, the underlying molecular mechanisms remain incompletely understood. This study aimed to investigate whether sphingolipid metabolism plays a role in the vascular dysfunction of CE patients.

Targeting CDKs has emerged as a significant strategy in cancer drug development. While CDK4/6 inhibitors have proven effective in several cancers, CDK2 and CDK9 inhibitors are under clinical trials. In biliary tract cancer (BTC), CDK2 and CDK9 expression levels are elevated compared to normal tissue. CDK9, a transcriptional CDK, regulates RNAPII, promoting the transcription of oncogenes, such as MCL1. Aberrant CDK activation contributes to cancer progression and apoptosis evasion in BTC. Notably, MCL1 is frequently amplified in intrahepatic cholangiocarcinoma (16-21%), supporting the therapeutic potential of CDK2 and CDK9. However, targeting CDK2/9 in BTC has not yet been explored. This study aimed to evaluate CDK2/9 inhibition and develop possible biomarker strategies in BTC.

Oxidative stress (OS) is a harmful threat during early preimplantation that compromises embryonic development. Ascorbic acid and cysteine were found to have significant contributions in various physiological processes, including embryonic development and mitigating various stressors, by acting as antioxidants and regulating gene expression. This study evaluated the mitigating impact of ascorbic acid and cysteine addition on OS during in vitro culture (IVC) and subsequent early embryonic developmental stages of the dromedary camel. The ovaries were sourced from a nearby slaughterhouse; only high-quality oocytes were used for in vitro embryo production (IVP). Produced zygotes were in vitro cultured with ascorbic acid, cysteine, or both under a high oxygen level (20%). This study included four experimental groups: an untreated group without antioxidant i.e., control (T1), the 2nd group supplemented with 150 µg/mL ascorbic acid (T2), the 3rd group supplemented with 100 µM cysteine (T3), and the 4th group (T4) enriched with a combination of both antioxidants (150 µg/mL ascorbic acid and 100 µM cysteine). Embryo development was monitored throughout different preimplantation stages. Real-time PCR was used to assess the relative abundance of various genes, including genes that are related to oxidative stress (catalase (CAT), superoxide dismutase (SOD), and thioredoxin (TXN)), apoptosis related genes (B-cell lymphoma 2 (BCL2), and tumor suppressor protein (p53)), and metabolic related gene (glucose transporter 1 (GLUT-1)).

It has been shown that 24-epibrassinolide (EBR), an active by-product of brassinolide biosynthesis, can stimulate different plant metabolic processes, including photosynthesis and protein and nucleic acid biosynthesis. EBR plays an important role in plant growth and development, especially in regulating the synthesis of secondary metabolites. The flavonoid-rich thorns of Gleditsia sinensis are used as a traditional Chinese medicine. Little is known about the molecular mechanism of flavonoid synthesis changes under EBR treatment. To elucidate the underlying molecular mechanism, we conducted comparative transcriptome analysis of plants treated with four different EBR concentrations (0, 0.5, 1.0, 1.5 mg/L) using RNA-Seq.

Plant growth depends on the integration of environmental signals and nutrient availability. Under stress conditions, growth is often attenuated to prioritise defense, creating a trade-off between growth and stress responses. Autophagy, a conserved degradation and recycling mechanism in eukaryotes, plays a central role in maintaining cellular homeostasis during stress. Enhancing autophagy has been shown to improve growth, yield, and stress tolerance in plants, yet the molecular triggers that initiate this process are not fully understood.

Hepatocellular carcinoma (HCC) poses a significant global health burden with limited therapeutic efficacy. Chinese herbal medicines (CHMs) offer multi-target potential, yet their systematic screening and mechanistic elucidation remain challenging. We established a high-throughput multi-omics platform integrating transcriptomics, proteomics, and deep learning (autoencoder and multiple kernel learning) to screen 187 medicinal plants. Five CHMs candidates were identified and shown to modulate hub genes (e.g., AKR1B10, HMGCR, THBS1) and key pathways (TNF/IL-17/MAPK, apoptosis, ferroptosis). Proteomic validation and functional assays confirmed their roles in suppressing proliferation, migration, and inducing apoptosis in HCC cells. This study provides a robust, data-driven pipeline for natural anti-HCC drug discovery, linking specific hub genes to CHM efficacy and offering novel insights into precision ethnopharmacology.