Systemic BCG administration induces transcription factor signature in CD4+ T cells that cooperates with IL-12 signaling to drive antiviral Th1 differentiation.

Objective: To investigate the molecular mechanism of toll-like receptor adaptor protein SARM1 in glaucomatous optic neuropathy. Methods: The experimental study was conducted from February 2024 to October 2025. A chronic ocular hypertension glaucoma model was established by injecting micro-magnetic beads into the anterior chamber of 8- to 10-week-old male Wistar rats. At 3 days, 1 week, and 2 weeks post-modeling, retinal and optic nerve tissues from 6 eyes of 6 rats were collected as the chronic ocular hypertension glaucoma model group, and 6 eyes from 6 wild-type rats that received an equal volume of saline via anterior chamber injection served as the control group. Intraocular pressure was measured using a TonoLab tonometer. Retinal whole-mounts were prepared and POU domain class 4 transcription factor 1 (POU4F1 or Brn3A) immunofluorescence staining was used to detect retinal ganglion cell loss. Western blotting was performed to detect the expression levels of SARM1 and SNPH in the rat retina and optic nerve. Immunofluorescence staining was used to examine their distribution in these tissues. Furthermore, CRISPR/Cas9 technology was used to knock down the expression of SARM1 and SNPH in mouse 661W retinal ganglion cells, respectively. Cells were collected 48 hours after transfection, and Western blotting was performed to detect the expression levels of SARM1 and SNPH. Normally distributed continuous data are presented as mean±SEM. Comparisons between two groups were performed using the Student's t-test, while comparisons among multiple groups were assessed by the one-way analysis of variance followed by the Tukey's multiple comparisons test. Results: Western blot analysis revealed that in the glaucoma model group, the relative expression level of SARM1 protein in the optic nerve at one week post-modeling (1.22±0.06) was significantly higher than that in the control group (1.03±0.01; P=0.027, q=4.38). In contrast, the expression level of SARM1 in the retina at three days post-modeling (0.79±0.02) was significantly lower than that in the control group (1.04±0.03; P<0.001, q=6.86). Concurrently, the expression level of SNPH at three days post-modeling (0.74±0.01) was lower than that in the control group (1.03±0.04; P=0.040, q=0.58), and its expression at one week post-modeling (1.19±0.10; P=0.002, q=4.36) was significantly higher than that at three days (0.74±0.01). Consistent with the Western blot results, immunofluorescence staining results showed that in the optic nerve of the glaucoma model group, the expression of SARM1 was significantly higher than that in the control group at one week post-modeling, while the expression of SNPH was lower than that in the control group at three days post-modeling. Both proteins partially co-localized with the neuronal marker β3-tubulin. Immunofluorescence staining also revealed co-localization of these two proteins within axons. Additionally, SARM1 co-localized with the mitochondrial marker protein TOM20. Western blot results from 661W cells showed that the knockdown of SARM1 expression (0.54±0.04) significantly reduced SNPH expression (0.54±0.05; P=0.003, q=7.98), whereas the knockdown of SNPH expression (0.39±0.06) did not markedly affect SARM1 levels (0.75±0.05; P=0.010, q=6.39). Conclusion: The elevated expression of SARM1 protein in the axons of the rat glaucoma model can promote retinal ganglion cell axonal pathology by localizing to axonal mitochondria and regulating SNPH expression.

SOX4 is a transcriptional activator for CTHRC1 in lung fibroblast activation.

Connexin32 inhibits renal tubulointerstitial fibrosis in diabetic kidney disease by regulating NOX4/MRTF-A positive feedback loop.

Antidepressant effect of psychedelic compounds and mechanisms underlying the G protein-coupled receptors activation psychedelics: Antidepressant action and GPCR signaling.

AtGATA11 activates AtBCCP2 transcription in Arabidopsis in response to NaHCO3 stress.

CREST regulates the Ca2+ signaling-mediated circadian transcriptional rhythms of the Per1 and Dbp promoters by coactivating with CLOCK/BMAL1.

Fruits and vegetables are key components of the human diet, valued for their unique textures and flavors. In recent years, numerous studies have demonstrated that individual transcription factors (TFs) can simultaneously regulate two biological processes; these TFs are defined as bifunctional TFs. However, systematic reviews on these bifunctional TFs in fruits and vegetables remain limited. This review systematically summarizes current knowledge on bifunctional TFs in fruits and vegetables, focusing on three themes: (i) molecular mechanisms (cis-element diversity, partner switching, posttranslational); (ii) network topology (hubs vs bottlenecks); and (iii) agronomic trade-offs. Meanwhile, the functional conservation and divergence of homologous TFs in different fruits and vegetables have also been investigated. In addition, we elaborate how key TF families, including MYB, bHLH, WRKY, ERF, and NAC, regulate diverse physiological processes in fruits and vegetables via dual mechanisms. We also identify several limitations in the existing literature, such as insufficient understanding of bifunctional regulatory mechanisms, incomplete identification of target genes, and inadequate exploration of crop applications.

Prenatal alcohol exposure (PAE) has a strongly documented effect on the structure and function of brain vasculature including effects on brain microvascular endothelial cell (BMVEC) behavior, impacting appropriate angiogenesis in development. We previously demonstrated that the effects of PAE on BMVEC behavior are partially mediated by the upregulation of miR-150-5p, a negative regulator of angiogenesis. Here, we characterize transcriptional mechanisms by which alcohol exposure results in upregulated miR-150-5p in BMVECs. We provide evidence for increased transcription of the miR-150 gene with alcohol exposure; specifically, we show elevated pri-miR-150 abundance, an altered miR-150 promoter methylation landscape, and overall increased miR-150 promoter activity. The alterations to the methylation landscape prompted investigation of enzymes responsible for DNA methylation dynamics, and we show altered expression of DNA methyltransferase (Dnmt) genes and Tet methylcytosine dioxygenase 1 (Tet1). We also illuminate alterations to the activation of a wide array of transcription factors throughout the nucleus as well as altered association between transcription factors and the miR-150 promoter. Overall, we uncover a novel mechanism of gene expression dysregulation by alcohol exposure in BMVECs through differential transcription factor binding as a result of altered DNA methylation mediated primarily by elevated Tet1.NEW & NOTEWORTHY Elevation of miR-150-5p in the brain vasculature during prenatal alcohol exposure occurs partially through increased transcription. This increase in transcription is mediated by the upregulation of Tet1; the elevated TET1 protein partially demethylates the miR-150 promoter into a 5hmC-rich sequence. Consequently, transcription factor binding to the promoter sequence is altered, resulting in increased miR-150 transcription.

PmTCP18, a class I TCP transcription factor from Prunus mume, regulates plant height and branching when ectopically expressed in poplar.

CD8+ T lymphocytes differentiate from effector to memory cells after antigen clearance, with prolonged IL-2 production characterizing functional cytotoxic T lymphocytes (CTLs). To identify transcription factors associated with sustained IL-2 production, we compared influenza virus-specific and cytomegalovirus-specific CTLs, identifying Basic Leucine Zipper ATF-Like Transcription Factor 3 (BATF3) as a key candidate. BATF3 overexpression significantly enhanced cell proliferation in both virus-specific CTLs and CD19 chimeric antigen receptor T (CAR-T) cells while reducing cytokine production. Among AP-1 transcription factor family members, BATF and BATF3 demonstrated similar functions during effector phase expansion, but BATF3 exhibited distinct roles in promoting memory cell formation. ATAC-seq analysis revealed that BATF3 overexpression dynamically regulates chromatin accessibility, affecting diverse cellular processes including cytoskeletal organization, metabolic pathways, and survival signaling. BATF and BATF3 showed comparable kinetics until peak expansion, but BATF3 specifically facilitated the transition from effector to memory phase, up-regulating memory-associated genes while down-regulating exhaustion markers. These findings establish BATF3 as a master regulator of CD8+ T-cell fate determination through chromatin remodeling, offering therapeutic targets for enhancing CAR-T cell persistence in immunotherapy.

Krüppel‑like factor (KLF) 5 has garnered increasing interest in cancer research, as a zinc finger transcription factor integral to the regulation of cellular growth and division through gene transcription control. Initially investigated for its role in transcriptional regulation during normal tissue development, KLF5 was subsequently identified as a driver of cancer progression upon aberrant activation of its transcriptional activity. This functional dichotomy in transcriptional regulation has considerably enhanced the current understanding of the significance of KLF5 in human cancer. The dysregulation of such critical transcription factors has been shown to be closely linked with gynecological tumors, including cervical, ovarian and endometrial cancer. However, the specific regulatory mechanisms by which KLF5 influences the initiation and progression of gynecological tumors remains to be elucidated. The present review highlights the role of the KLF5 transcriptional regulatory network in the pathogenesis of gynecological tumors and its potential as a therapeutic target.

Regulatory mechanisms of secondary metabolite biosynthesis in medicinal plants under drought: advances and perspectives.

Molecular and functional characterization of the ovarian development associated transcription factor ZGLP1 in the marine fish four-eyed sleeper (Bostrychus sinensis)

Multi-Stage transcriptomic dissection identifies key molecular determinants of chicken follicular development.

Alopecia areata (AA) is an autoimmune disorder characterized by hair loss due to immune-mediated destruction of hair follicles. The polygenic nature of AA, influenced by genetic and environmental factors, complicates its pathogenesis. Advances in bioinformatics have facilitated understanding of AA's genetic basis, providing insights into key molecular pathways and regulatory mechanisms. This study utilized the GEO database (dataset GSE111061) to analyze differentially expressed genes (DEGs) between healthy controls and AA patients. Functional enrichment and protein-protein interaction (PPI) network analyzes identified hub genes, transcription factors (TFs), and miRNAs. Tools such as STRING, Cytoscape, and KEGG were employed to uncover key interactions and pathways. An aggregate of 5134 DEGs was discovered, with 2576 elevated genes constituting a PPI network. Key pathways included chemokine signaling and cytokine-cytokine receptor interactions. Ten hub genes (e.g., CCL5, CCR7, and CXCL9) and top TFs (ZNF683, FOXP3, and TBX21) were identified. Additionally, 49 miRNAs were predicted to regulate AA-related genes. This work focuses on critical molecular regulators involved in AA pathogenesis, such as TFs and miRNAs. These findings suggest possible treatment targets and shed light on the molecular mechanisms of AA.

This study reveals a role of rapid-adaptive transcriptional dynamics in AML chemotherapy resistance, highlighting master TFs as key regulators. These insights offer a pharmacologically accessible approach to potentially alleviate the major clinical problem of chemotherapy resistance.

Salicylic acid (SA)-mediated defense responses are crucial for plant immunity, yet transcription factors (TFs) that coordinate SA biosynthesis with immune activation remain incompletely characterized. Here, a basic leucine zipper (bZIP) TF, bZIP54, was identified as a positive regulator in response to Pseudomonas syringae pv. tomato (Pst) DC3000. Consistent with this, bZIP54 regulated SA accumulation and a suite of SA-related defense genes following Pst DC3000 infection. Mechanistically, bZIP54 directly bound to a G-box-like motif in the SARD1 promoter, activating its expression-an interaction that was further enhanced by SA. Genetic analysis demonstrated that SARD1 operates downstream of bZIP54 to confer resistance to Pst DC3000. Additionally, bZIP54 also contributed to defense against the fungal pathogen Sclerotinia sclerotiorum, indicating a broader role in plant immunity. Together, these findings revealed a bZIP54-SARD1 regulatory module thus providing insights into the transcriptional networks governing disease resistance in Arabidopsis.

Appendiceal cancer (AC) is a rare malignancy that often presents at advanced stages with significant histological variability influencing clinical outcomes. Precise genomic profiling is essential for accurate diagnosis and personalized patient management. This study interrogated DNA from appendiceal tumor tissue, buffy coat cells, and the cell-free DNA component of plasma using a 523-gene panel for comprehensive genomic profiling (CGP) to identify cancer-related genetic mutations in tumor and blood, evaluate tumor mutation burden, and determine genetic markers associated with histologic grade. A total of 73 patients provided blood samples comprising cell-free DNA (cfDNA) and germline buffy coat cells (bcDNA) for analysis compared with tumor tissues available from 56 of these patients. Concordance of mutations between matched tumor tissue and plasma samples (n = 51) was assessed and tumor-specific and germline variants were classified using OncoKB™ clinical criteria to delineate oncogenic and therapeutically actionable variants [level 1 mutations with U.S. Food and Drug Administration (FDA)-approved therapy]. Additionally, cfDNA concentrations were tested for association with clinical and pathologic features and oncologic outcome including disease-specific (DSS) and progression-free (PFS) survival. Circulating tumor DNA (ctDNA) from plasma cell-free DNA demonstrated high concordance with tumor genomic profiling, reaching 98.4% concordance [median, interquartile range (IQR) 13.5, 21.5] overall and 85.7% (IQR 64.6, 100) for therapeutically actionable level 1 mutations. Prevalent appendiceal tumor-specific mutations included KRAS proto-oncogene, GTPase (KRAS) (41%), GNAS complex locus (GNAS) (30%), tumor protein p53 (TP53) (30%), and SMAD family member 4 (SMAD4) (29%). Tumor-specific TP53, SMAD4, and spectrin alpha, erythrocytic 1 (SPTA1) mutations strongly correlated with intermediate and high-grade histology, whereas GNAS mutations predominated in low-grade tumors. Germline analysis identified coding mutations shared among this patient cohort in notch receptor 4 (NOTCH4) (55%) and BRCA1 associated RING domain 1 (BARD1) (48%) genes, with zinc finger homeobox 3 (ZFHX3) (29%) and adhesion G protein-coupled receptor A2 (ADGRA2), DNA polymerase epsilon (POLE), and transcription factor 3 (TCF3) mutations (all = 23%) specifically enriched in intermediate and high-grade AC. Both histological grade and cfDNA stratified by concentration tertiles independently predicted progression-free and disease-specific survival. Plasma samples exhibited consistently lower variant allele frequencies than solid tumors, limiting sensitivity for discovery of novel mutations exclusively from plasma. This study supports integrating comprehensive ctDNA assays into standard diagnostic and treatment pathways for AC using large gene panels. TP53, SMAD4, SPTA1, and GNAS mutations serve as prospective tumor-specific molecular classifiers for histological grade, while germline variants in NOTCH4 and BARD1 may further influence disease biology, with ZFHX3, ADGRA2, POLE, and TCF3 affecting grade stratification. Overall cfDNA concentration may serve as a potential prognostic biomarker in AC.

Nrf2 modulates cytosolic and mitochondrial calcium signal.