With the advent and development of assisted reproductive technology (ART), more and more people affected by infertility have been able to obtain offspring successfully. Nevertheless, various adverse outcomes have been found to be associated with ART, and mechanisms behind them are still unclear. Therefore, in this study, we examine the differences between mouse pre-implantation embryos obtained via in vitro fertilization (IVF) and in vivo fertilization (IVO) at both transcriptional and epigenetic levels. We find remarkable H3K4me3 differences at blastocyst stage, which could be ascribed to the higher oxidative stress in IVF-derived blastocysts. Intriguingly, treatment with CPI-455, the inhibitor of KDM5 that catalyzes the demethylation of H3K4, successfully rescues the H3K4me3 signatures as well as transcription levels of several genes, facilitating embryo development in vitro and improving the pregnancy outcome. Consistently, CPI-455 supplementation also enhances the formation of high-quality human embryos, emphasizing the potential clinical application of CPI-455 in human ART.

Thyroid hormones (THs) are indispensable regulators of vertebrate embryogenesis, orchestrating signaling networks that direct cardiac morphogenesis. To investigate how disruption of this pathway impacts early development, fertilized Gallus domesticus eggs were exposed to amiodarone, a potent TH receptor (THR) antagonist and deiodinase inhibitor. Treated embryos displayed pronounced defects, including impaired heart looping, edema, increased apoptotic regions and sustained bradycardia during Hamburger-Hamilton stages 12 to 18. By day 10, histology revealed significant thinning of ventricular and atrial walls, with the compact ventricular layer reduced by ∼22 % while trabeculae were relatively preserved. These changes were accompanied by reduced acetylcholinesterase activity, indicating impaired neurocardiac regulation. Molecular analyses showed broad downregulation of WNT11, GATA4/5, TBX20, HAND2, BMP4, SHH, FGF8, MYOD, and MYOSIN, together with decreased PCNA and compensatory upregulation of GATA6. Interestingly, discrepancies between transcript and protein levels suggested post-transcriptional control under hypothyroid conditions. In silico promoter scanning identified thyroid hormone response elements within HAND2, GATA6, TBX5, PITX2, and BMP4, linking maternal TH signaling directly to lateral plate mesoderm gene networks. Flow cytometry and whole-mount immunolocalization confirmed reduced expression and altered localization of MYOD and MYOSIN, including loss of the normal heart-tube-restricted MYOD signal. Collectively, these findings establish that TH signaling networks coordinate structural, functional, and molecular programs essential for early cardiogenesis. Amiodarone-induced THR blockade recapitulates developmental hypothyroidism, providing mechanistic insight into how maternal TH deficiency or endocrine-disrupting exposures may contribute to congenital heart defects.

Cadmium (Cd) is a toxic heavy metal that is closely associated with the occurrence and progression of lung cancer. Our previous studies showed that Cd promoted lactate utilization and the expression of phosphoglycerate dehydrogenase (PHGDH), which is the key enzyme in serine biosynthesis. In this study, the role of PHGDH in Cd-induced lactate utilization was investigated. First, we found that PHGDH enhanced Monocarboxylate transporter 1 (MCT1) but not MCT4 in both A549 cells and tumor tissues formed by injection of siPHGDH-treated A549 cells in male BALB/c mice. Then, glutamine deprivation and transfection with siASCT2 (Alanine-Serine-Cysteine Transporter 2) revealed that glutamine was involved in Cd-induced Nrf2, PHGDH, glycolysis-related proteins, MCT1 and cell migration. Moreover, inhibition of Nrf2 with ML385 attenuated Cd-induced glutamine metabolism, PHGDH, MCT1, lactate production, and cell migration, while activation of Nrf2 with RTA-408 had the opposite effect. In addition, using RTA-408, ML385, glutamine addition and deprivation, we discovered that glutamine metabolism and Nrf2 interacted to enhance PHGDH and PHGDH-induced lactate utilization. Collectively, these findings suggest that PHGDH plays a crucial role in Cd-induced lactate utilization, and the mechanism underlies the interaction between glutamine and Nrf2. This study provides insights into the mechanism of Cd-related tumorigenesis and toxicity.

Genetic profiles alone do not fully describe the development and evolution of prostate cancer (PCa), whereas epigenetic alterations are emerging as promising therapeutic targets. This review explores FDA-approved and experimental epigenetic strategies, including DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), histone methyltransferase inhibitors, bromodomain and extra-terminal domain inhibitors (BETi), non-coding RNA therapies, antisense oligonucleotides, and future prospects such as chromatin remodeling, DNA hydroxymethylation, and RNA methylation. Although DNMTis and HDACis have historically dominated clinical trials, mainly in hematologic cancers, the 2020 approval of an epigenetic therapy for a solid tumor marked an important breakthrough. Despite this, epigenetic drugs remain underexplored in PCa: among 2254 clinical studies of such agents, only 58 (2.57 %) included PCa patients. This disparity highlights an urgent need for novel therapeutic approaches beyond chemotherapy and androgen deprivation. By assessing current progress and outlining opportunities in drug repositioning and novel targets, this review underscores epigenetics as a critical frontier for advancing PCa treatment.

Oviduct glycoprotein 1 (OVGP1) is a key protein involved in oviductal functions. β-estradiol (E2) and progesterone (P4), oxytocin (OXT) and tumor necrosis factor-α (TNFα) modulate the equine oviduct function, through prostaglandin regulation. The objective was to evaluate OVGP1 expression within each equine oviduct segment (infundibulum, ampulla isthmus), throughout the estrous cycle. The in vitro effect of (i) E2, P4, OXT, TNFα; and (ii) spermatozoa, on oviduct OVGP1 transcription and secretion was studied. Gene transcription was assessed by real-time PCR; protein expression by western blot; and protein production by enzyme immunoassay. OVGP1 mRNA increased in the ampulla, in the early-luteal phase (P < 0.05). OVGP1 protein expression increased in the follicular phase, in all portions (P < 0.05). A temporal desynchronization between transcription and protein synthesis might maintain oviduct function. In ampulla explants, OXT and TNFα up-regulated OVGP1 transcripts in follicular phase; E2 in early-luteal phase; and P4 in mid-luteal phase (P < 0.05). OXT and TNFα effect on OVGP1 transcripts might be ascribed to prostaglandin modulation. Oviductal endogenous E2 in follicular phase, could prime E2 stimulation of OVGP1 transcripts in early-luteal phase. The stimulatory effect of P4 on OVGP1 transcripts may modulate early embryogenesis. OVGP1 in vitro production was not dependent of E2, P4, OXT or TNFα treatments. Sperm cells, either in direct or indirect contact with oviduct explants, up-regulated OVGP1 production, in the isthmus (P < 0.05). These data suggest that OVGP1 modulates sperm and mare's oviduct cross-talk and may play an important role in improving assisted reproductive technologies.

Epigenetic dysregulation is a significant factor contributing to cisplatin resistance in bladder cancer (BCa). Increasing studies indicated a synergistic effect of cisplatin and Entinostat, which is an FDA-approved histone deacetylases (HDAC) inhibitor, however, the underlying mechanisms of this effect remains unknown. Herein, the synergy of cisplatin and Entinostat was confirmed in BCa cells. Integrated RNA-seq and ATAC-seq analysis revealed that the combined regimen of cisplatin and Entinostat led to significant downregulation of platinum resistance and DNA damage repair-related pathways. We focused on the candidate gene dehydrogenase/reductase member 2 (DHRS2), and found that Entinostat counteracted cisplatin resistance via promoting histone H3K18 lactylation (H3K18la)-mediated DHRS2 upregulation and enhancing the nuclear translocation of DHRS2. DHRS2 downregulation promoted cisplatin resistance by upregulating aldo-keto reductase family 1 member C3 (AKR1C3), a key enzyme in androgen synthesis. Moreover, we validated a negative correlation between DHRS2 levels and AKR1C3 expression in clinical BCa samples. It was found that high DHRS2 and low AKR1C3 expression correlates with improved neoadjuvant chemotherapy (NAC) response. Furthermore, high DHRS2 predicts better survival specifically in male patients, indicating sex-specific androgen involvement. Overall, these findings elucidate the epigenetic mechanism underlying the cisplatin-sensitizing effect of Entinostat, and identifies the DHRS2-AKR1C3-androgen axis as a potential target, particularly for male patients.

Ionic aluminum (Al) forms in acidic soils and inhibits plant growth, even at low concentrations. Rose myrtle (Rhodomyrtus tomentosa), a shrub native to tropical and subtropical regions, thrives in acidic-Al soils. Here, we found that mild concentrations of Al promote rose myrtle growth. Transcriptomic disturbances induced by low or high Al stress were predominantly nonoverlapping in the species. Mild Al stress (0.1 mM Al3+) enhanced rose myrtle root elongation through the upregulation of xyloglucan metabolism, nutrient uptake and utilization, and auxin transport. In contrast, high Al stress (1 mM Al3+) activated detoxification pathways, including the secretion of organic acid and glutathione metabolism. Members of the aluminum-activated malate transporter (ALMT) family, particularly the conserved RtALMT11 and variable RtALMT18, play a pivotal role in Al tolerance. Heterologous expression of RtALMT11 and RtALMT18 complemented the Al-sensitive phenotype of almt1-KO Arabidopsis (Arabidopsis thaliana). High Al3+ induced the expression of RtALMT11, mediating the synthesis of callose, which may serve as a physical barrier to mitigate Al penetration and facilitate vacuolar Al sequestration. RtALMT18 pre-emptively regulated internal defense in the stele independently of aluminum load, while also functioning as a proton/malate transporter. Beyond enhancing Al tolerance, RtALMT18 promoted the growth of transgenic Arabidopsis and poplar (Populus alba  ×  Populus glandulosa, "84K"). The functional divergence within the ALMT family reveals distinct roles in promoting the growth of rose myrtle under low Al conditions and during the high-Al detoxification process. These findings uncover Al's dual role as both a growth promoter and stress inducer, offering insights for developing Al-tolerant crops and rehabilitating acidic soils.

Aberrant paracrine cytokine signaling and dysregulated signal transduction are critical drivers of tumor progression and therapeutic resistance in aggressive cancers such as non-small cell lung cancer and triple-negative breast cancer. This study aimed to explore a dual-targeting strategy using mebendazole, a repurposed anti-parasitic agent known to disrupt microtubules, in combination with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor. The objective was to assess the combinatorial impact on cell viability and key regulatory pathways involved in inflammation, mitotic control, and nuclear transport.

Chronic alcohol drinking increases susceptibility to cognitive impairment; however, the underlying mechanisms remain unclear. In this study, we investigated the effects of chronic alcohol drinking on working and recognition memory in a Marchigian Sardinian alcohol-preferring (msP) rat line. Due to interest in insulin-based medications for alcohol use disorder, we examined insulin/insulin-like growth factor 1 (IGF-1) genes in the prelimbic (PL) and infralimbic (IL) medial prefrontal cortex, a region linked to alcohol dependence and cognition. Male and female msPs received access to alcohol (20% v/v) and water (H2O) using a group-housed 2 bottle-choice drinking paradigm for several weeks, while controls received H2O only. After five weeks, the radial arm maze and novel object recognition tasks evaluated working and recognition memory. At the end of the study, genes encoding for insulin/IGF-1, their receptors, and downstream effectors were assessed in the PL, IL and hippocampus CA1 (CA1), three main regions involved in working and recognition memory processing. Genes regulating brain plasticity were also assessed. Females consumed more alcohol than males. Chronic alcohol exposure selectively impaired recognition memory in males, while working memory remained unaffected in both sexes. Chronic alcohol exposure altered transcription of insulin/IGF-1 signaling components. In females, chronic alcohol reduced Ins transcript levels in the IL, while increasing Insr expression in the PL, but not in the CA1. In males, chronic alcohol reduced Igf1r transcript levels in the IL, but not PL or CA1. Across both sexes and all regions, chronic alcohol decreased Irs2, a downstream effector of insulin/IGF-1, transcript levels. Lastly, we observed some alterations in genes linked to memory and plasticity including Bdnf, TrkB, Psd95, and Pkmζ. Together, these findings suggest that chronic alcohol drinking impairs recognition memory in males, while broadly disrupting metabolic and plasticity-associated genes in the mPFC and CA1.

TP53 mutation-driven gene expression programs define oncogenic phenotypes. While extensive studies have concentrated on the transcriptome and proteome, post-transcriptional processes, particularly translational variation, remain underexplored. This study presents a comprehensive analysis of the transcriptomics, translatiomics, and proteomics dynamics in the ovarian cancer cell line SKOV3, with a focus on the effects of p53 missense mutations (R175H, R273H, and Y220C) on gene dosage fluctuations. Despite clear transcriptional differences between wild-type and mutant p53, we find that extensive translational and post-translational buffering processes attenuate these discrepancies, yielding comparatively stable protein abundances. Moreover, we delineate that the relative contributions of transcription output, translation engagement, and protein stability collectively shape the final protein abundance in the context of p53 mutations. Clinical proteomic analysis of platinum-resistant ovarian cancer tissues reveals tumor-specific factors and acquired resistance pathways linked to p53 mutations. Our findings elucidate the multilayered regulatory landscape of p53 mutations and identify potential risk factors for platinum resistance associated with these mutations.

Under bedaquiline (BDQ) pressure, a temporary persistence period (24-96 h) has been observed, during which H37Rv undergoes metabolic rerouting. However, little is known of transcriptomic changes in BDQ-resistant Mycobacterium tuberculosis (Mtb) isolates during this period. We explored transcriptomic adaptations occurring under inhibitory concentrations of BDQ to delineate pathways supporting drug tolerance and contributing to BDQ resistance. We report overexpression of genes involved in the biosynthesis of L-arginine and L-cysteine in our study isolates. Among stress response genes, genes from the suf operon, involved in Fe-S biogenesis, were upregulated in the study isolates. Differentially expressed amino acid gene clusters likely indicate an under-recognized metabolic pathway contributing to BDQ persistence in the study clinical isolates. Furthermore, Fe-S stress response activated under BDQ pressure may be of particular interest as a mechanism broadly used by Mtb in mitigating different environmental stresses. We propose that these pathways should be explored further as potential drug targets.

Two-component signaling systems (TCSSs) serve as primary signal transduction pathways in bacteria, regulating essential processes including growth, physiology, and virulence, making them attractive drug targets. In Mycobacterium tuberculosis (M. tb), the PhoPR system plays a critical role in pathogenesis, with the PhoR histidine kinase (HK) functioning at the intersection of cognate and noncognate signaling networks. Using PhoR as a prototypical HK, we hypothesized that targeting this system would compromise M. tb's adaptive capacity. We developed and optimized a high-throughput screen of pharmacologically active small-molecule libraries to identify PhoR autophosphorylation inhibitors. Selected compounds were evaluated using kinase assays, protein interaction analyses, molecular docking studies, and growth inhibition using Mycobacterium bovis BCG. Screening identified 11 potential inhibitors, with tamoxifen (TAM) demonstrating the most potent activity. TAM inhibited PhoR autophosphorylation at micromolar concentrations both in vitro and in vivo. Mechanistic studies revealed that TAM competitively binds to the ATP-binding pocket of PhoR with a dissociation constant (Kd) of 108.5 ± 44 nM. Although maximum inhibition was found with PhoR, additional screening of HKs revealed MtrB as another low-affinity target of TAM (Kd = 412 ± 83 nM). Treatment with TAM significantly inhibited M. bovis BCG growth in culture and suppressed PhoPR-regulated acid-responsive gene expression. Our findings establish PhoR HK as a promising antimycobacterial drug target and demonstrate the potential for repurposing the clinically approved anticancer drug TAM as an anti-tuberculosis therapeutic with TCS-targeting effects. This work provides proof of concept for targeting bacterial TCSSs and supports further development of TAM derivatives for tuberculosis treatment.IMPORTANCETwo-component signaling systems are essential for bacterial growth, metabolism, and survival, making them ideal candidates for selective antimicrobial therapy. Tamoxifen (TAM), a well-known anticancer drug, has recently been shown to exhibit antimicrobial activity and is emerging as a potential anti-tuberculosis (TB) agent. In this study, we report for the first time that TAM inhibits Mycobacterium tuberculosis histidine kinases, PhoR and MtrB, implicated in virulence. Using a combination of biochemical and computational biology techniques, we demonstrate that TAM competes with ATP for PhoR binding and impairs its autophosphorylation activity, thereby disrupting downstream regulation of gene expression. Dissociation kinetics revealed that in comparison to PhoR, TAM bound MtrB with a lower affinity. These findings establish PhoR as a novel drug target, highlight a plausible mechanism of TAM's antimycobacterial action, and, more importantly, support its repurposing as a promising therapeutic candidate against TB.

Acute lymphoblastic leukemia (ALL) has high relapse rates, requiring new therapies. Quercetin, a natural flavonoid, exhibits anti-cancer potential, but its mechanisms in ALL, particularly involving miRNAs, are unclear. This study explores quercetin's effects and its role in regulating the miR-367/KLF4/JNK axis. Using ALL cell lines and xenograft models, quercetin's efficacy was assessed. It inhibited tumor growth in mice and induced apoptosis and autophagy in vitro. Mechanistically, quercetin downregulated miR-367, leading to upregulation of KLF4, which subsequently suppressed JNK signaling to promote cell death. In vivo results confirmed that quercetin suppresses ALL progression via this pathway. These findings identify quercetin as a potent anti-leukemic agent targeting the miR-367/KLF4/JNK axis to induce cell death. This reveals a novel regulatory pathway in ALL and highlights quercetin's potential as a miRNA-based therapy.

Introduction: Lung cancer is a highly lethal disease characterized by a significant mortality rate. Cisplatin, a common drug used for lung cancer treatment, frequently develops resistance over time. Therefore, overcoming cisplatin resistance is crucial in the effective management of lung cancer. The ubiquitin-proteasome system (UPS) serves as a vital regulatory mechanism for maintaining protein homeostasis within cells. Recent studies have shown that manipulating deubiquitinating enzymes (DUBs) can overcome cisplatin resistance. This study aims to investigate the expression levels of DUBs under cisplatin treatment. Methods: Multiplex RT-PCR analysis was performed to identify potential biomarkers by comparing the differential expression patterns of DUBs, and their expression levels were analyzed by RT-qPCR. In addition, their protein expression levels were determined by western blot analysis. The bioinformatics tools including TCGA database and GEPIA website were used to validate potential as prognostic markers in lung cancer. Results: Multiplex RT-PCR analysis was performed to identify potential biomarkers by comparing the differential expression patterns of DUB genes. Multiplex RT-PCR showed distinct mRNA expression profiles of several DUB genes, including USP35, USP36, USP37, USP47, USP49, and OTUD6B in A549 lung cancer cells following exposure to cisplatin. In addition, RT-qPCR analysis revealed the downregulation of USP35, USP36, USP37, USP47, USP49, and OTUD6B, juxtaposed with the upregulation of USP47 under cisplatin treatment. Substantiating these findings, western blotting analysis confirmed the protein expression levels of USP35, USP36, USP37, USP47, USP49, and OTUD6B in cisplatin-treated lung cancer cells, mirroring the mRNA trends observed in non-treated counterparts except for OTUD6B. Bioinformatics analysis demonstrates that these DUBs except USP47 are upregulated and overall survival analysis indicates that lower expression of these DUBs, except USP37 and USP49, is correlated with improved overall survival in lung cancer patients. Conclusion: These findings strongly suggest that DUBs may play a crucial role in overcoming cisplatin resistance and improving the treatment efficacy for lung cancer.

Chemotherapy remains the frontline treatment strategy for triple-negative breast cancer (TNBC). However, the aggressive nature of TNBC, due to metabolic reprogramming, is often associated with chemoresistance, which limits treatment efficacy. Herein, we investigated the impact of altered lipid homeostasis, in particular, the fatty acid β-oxidation (FAO) pathway, during doxorubicin (Dox)-induced chemoresistance and its effect on drug retention and efficacy in TNBC cells. Results indicate that Dox-induced chemoresistance in MDA-MB-231 cells and an in vivo Dox-resistance breast cancer model in SCID mice are associated with a marked upregulation of FAO. Intriguingly, the basal levels of carnitine palmitoyltransferase 1 (CPT1; a rate-limiting enzyme of FAO), CD36, (a fatty acid translocase), FAO-related gene transcript levels, and acetyl-CoA production were significantly elevated with increased degree of Dox resistance. These changes were paralleled by enhanced uptake of fatty acids and their oxidation. Dox-resistance in TNBC cells was associated with enhanced mitochondrial respiration, possibly due to increased activities of complex I and IV. Conversely, inhibition of CPT1 by etomoxir caused increased intracellular Dox retention, leading to Dox-induced cytotoxicity and attenuating the invasiveness of TNBC cells. Importantly, FAO-derived ATP levels, compared to glucose-derived ATP, seem to enhance the invasiveness of Dox-resistant cells. Mechanistically, Dox-resistance potentiated FAO via CREB activation, which in turn led to the enhancement of the PGC1α/PPARα/CD36-CPT1 axis. Taken together, Dox-resistance reprograms cellular metabolism towards FAO regulatory circuit sustaining the mitochondrial bioenergetics, promoting drug efflux, and accentuating breast cancer progression. Based on these findings, it is possible that FAO inhibitors effectively combat drug-induced TNBC chemoresistance.

Soft rot is a major disease restricting the production of colored calla lily, with severe impacts on their ornamental, commercial, and market value, caused by infection with Pectobacterium carotovorum. This study investigated the involvement of long noncoding RNAs (lncRNAs) in the soft rot response of colored calla lily leaves. Transcriptome sequencing of infected leaves identified 35,175 potential lncRNAs. Differential expression analysis revealed significant upregulation or downregulation of numerous lncRNAs following infection, indicating their potential involvement in the plant's immune response to P. carotovorum. Among these, LNC86472 was identified as a differentially expressed lncRNA that functions as a potential endogenous target mimic (eTM) for miR166a. Meanwhile, miR166a directly targets homeodomain-leucine zipper 15 (HB15) transcripts, which activates immune responses and restricts pathogen invasion. Functional studies involving the transient expression and silencing of LNC86472 and HB15 in colored calla lily leaves demonstrated that overexpression resulted in enlarged lesion sizes and compromised plant immune responses, while silencing them led to the opposite effect. Notably, infection-induced increases in jasmonic acid levels were associated with the downregulation of LNC86472. Further analysis showed that MYC2 directly binds to the LNC86472 promoter to repress its expression. These results suggest that jasmonic acid (JA)-mediated downregulation of LNC86472 releases miR166a, thereby facilitating miR166a-mediated cleavage of HB15 transcripts. This study provides new insights into the role of lncRNAs in the soft rot infection process of colored calla lily.

Sea barley (Hordeum marinum), a wild barley relative, exhibits superior salt tolerance. Although we previously assembled the de novo genome of sea barley accession H559, salt-tolerant mechanisms across marinum accessions remain poorly characterized. Here, we compared transcriptomic and metabolomic responses to salt stress between two sea barley accessions: salt-tolerant H512 and salt-sensitive H111. After 14 d of 300 mM NaCl treatment, H512 showed strong salt tolerance, reflected by larger biomass accumulation and shoot K+/Na+ ratio than H111. RNA-seq analysis identified 3298 and 3770 differentially expressed genes (DEGs) in roots of H512 and H111, respectively, as well as 372 and 341 differentially expressed metabolites (DEMs) by LC-MS technique. Notably, gene expressions related to ion transporters (e.g. NHX1 and GORK1), Ca2+ signaling (e.g. GLR1 and CML40) and transcription factors (e.g. WRKY22, bZIP1, ARF5, DREB1A, GT2 and bZIP2) were differentially expressed in H512 than those in H111. Multi-omics analysis revealed that H512 was more energy-saving by down-regulating expression of ATP synthesis-related genes and up-regulating ATP hydrolysis-related genes. H512 also enhanced antioxidant activity by elevating levels of dehydrin, caffeic acid, cinnamaldehyde, taraxacoside and rhamnazin. Our findings illustrated key candidate genes and metabolites governing ion homeostasis, oxidative defense, and energy metabolism in sea barley, which may provide novel insights for improving salt tolerance in crops.

Saccharomyces cerevisiae's ability to withstand formic acid, the most impactful weak acid on yeast growth and fermentation commonly encountered in lignocellulosic bioethanol, is decisive towards industrial applications. Nevertheless, the mechanisms of formic acid resistance inS. cerevisiaeremain poorly understood. This study explored the transcriptional and metabolic responses of three strains - two resistant (YI30 and CESPLG05), and the sensitive DSM 70449 - to 4.0 g/L formic acid for defining the first model of formic acid resistance in S. cerevisiae. Resistance was linked to the upregulation of SAT4, a regulator of TRK1, a putative formic acid transporter, and FDH1, which detoxifies formic acid. Upregulation of GPD2 and GPP2 highlighted an adaptive glycerol metabolism that supported osmotic stress adaptation and intracellular NAD+ regeneration. Notably, resistant strains showed significantly lower external glycerol concentrations, indicating a finely tuned glycerol pathway. S. cerevisiae strains YI30 and CESPLG05 demonstrated superior ethanol production, producing 23.64 and 22.65 g/L, respectively, from 50 g/L of glucose. Remarkably, this was accomplished in the presence of 4.0 g/L formic acid, reaching 93 and 89 % of the theoretical, respectively. This study provides novel insights into formic acid resistance in S. cerevisiae, offering potential genes candidates for engineering yeast strains for highly tolerant formic acid phenotypes towards their applications in lignocellulosic bioethanol.

Radiotherapy is a very common treatment method for various cancers; however, it is not effective for patients with radioresistance. Accordingly, the discovery of drugs for patients with radioresistance cancer is critical. This study used a Food and Drug Administration (FDA)-approved drug library to identify candidate drugs for the treatment of radioresistant colorectal cancer (CRC). This approach to drug development benefits from its low cost and time requirements and can lead to rapid clinical translation.

TaGF14g enhances drought and salt tolerance by reducing ROS levels and increasing osmoprotectants content through the activation of stress-related genes and ABA signaling. Drought and high salinity severely constrain plant growth. The 14-3-3 proteins, a family of phosphopeptide-binding proteins, play pivotal roles in various signaling pathways. However, their functional mechanisms underlying drought and salt stress adaptation remain poorly understood, particularly in crop plant wheat (Triticum aestivum L.). Here, we identified a wheat 14-3-3 protein, TaGF14g, which positively modulates drought and salt tolerance. Spatiotemporal expression profiling revealed that TaGF14g is expressed in a variety of organs and tissues. Moreover, the expression of TaGF14g was significantly upregulated in response to treatments with polyethylene glycol 6000 (simulating drought), NaCl (simulating salt stress), and abscisic acid (ABA). Ectopic expression of TaGF14g exhibited improved abiotic stress resilience in transgenic tobacco (Nicotiana tabacum L.), with seedlings developing longer roots under drought and high-salinity conditions compared to control plants. Physiological analysis further showed that overexpression of TaGF14g in tobacco enhanced the activity and transcriptional levels of antioxidant enzymes, thereby improving reactive oxygen species (ROS) scavenging capacity and alleviating oxidative damage to plants. Meanwhile, TaGF14g overexpression improved drought stress tolerance by improving water retention and the accumulation of osmolytes. Under salt stress, transgenic lines showed improved tolerance through the upregulation of genes related to ion transporters. Furthermore, TaGF14b increased ABA sensitivity in transgenic tobacco and induced stress-responsive gene expression under stress conditions. Our findings demonstrate that TaGF14g confers drought and salt stress resilience by modulating physiological processes and ABA signaling pathways, thus positioning it as a promising candidate for developing stress-resistant crop varieties.