Aims Epidemiological studies indicate a heightened risk of pancreatic adenocarcinoma (PAAD) in patients with type 2 diabetes mellitus (T2DM). This study investigates the molecular mechanisms underlying their comorbidity. Materials and methods Common DEGs between T2DM and PAAD were identified from GEO datasets. Functional and pathway enrichment analyses were performed via PPI, GO, and KEGG. Core genes were screened and their diagnostic value was validated by ROC curves. Immune infiltration and TF–mRNA–miRNA regulatory networks were constructed to explore disease mechanisms. Core gene expression and prognostic significance in PAAD were assessed using GEPIA2 and HPA. Potential therapeutics targeting core genes were predicted via the Therapeutic Target Database. Results A total of 35 DEGs were identified. GO analysis linked these genes to cell adhesion and extracellular matrix (ECM) components. KEGG enrichment highlighted ECM-receptor interaction as the top pathway. Key ECM-related molecules—ITGA3, FN1, LAMB3, ITGA2, and LAMC2—were upregulated in both T2DM and PAAD. Six potential therapeutic agents targeting ITGA2, LAMB3, and FN1 were identified. Conclusion Three genes and associated known drugs identified in this study may serve as potential targets for treating the coexistence of the two diseases.

Altered homotopic functional connectivity in primary angle-closure glaucoma (PACG) and their underlying molecular mechanisms remain poorly understood. In our study, we investigated voxel-mirrored homotopic connectivity (VMHC) alterations in patients with PACG and the molecular mechanisms of VMHC. In this study, we investigated alterations in VMHC among 47 patients with PACG and 45 matched healthy controls. We then integrated these spatial patterns with cortical transcriptomic data from the Allen Human Brain Atlas using partial least squares (PLS) regression to identify gene expression profiles associated with VMHC alterations. In this study, we identified widespread reductions in interhemispheric functional connectivity in patients with PACG using VMHC analysis. Multivariate spatial correlation with gene expression data revealed that VMHC alterations were significantly associated with a distinct transcriptional signature captured by the first PLS component. Functional enrichment of these genes indicated downregulation of pathways related to synaptic and metabolic maintenance, and upregulation of immune, stress, and chromatin regulatory processes. Cell-type analysis showed that astrocytes and endothelial cells were selectively enriched with VMHC-related genes, reflecting glial and vascular involvement. Moreover, spatial alignment with neurotransmitter receptor maps highlighted significant associations with serotonergic, dopaminergic, GABAergic, cholinergic, and opioidergic pathways, suggesting a neuromodulatory basis for VMHC disruption. Together, these findings suggest that interhemispheric dysconnectivity in PACG is not only a reflection of functional brain changes but is also grounded in molecular and cellular mechanisms. This integrative approach advances our understanding of PACG as a brain-wide neurodegenerative condition and offers new perspectives for targeting glial, vascular, and neuromodulatory pathways in future therapeutic interventions.

Engineering polyamidoamine dendrimer nanoparticles for targeted drug delivery to proximal tubular cells after renal ischemia/reperfusion injury.

Music enhances lipid nanoparticle brain delivery and mRNA transfection in brain cells.

Immune landscape and molecular regulators in renal interstitial fibrosis.

Radiation-responsive Salmonella mediate therapeutics precise delivery for synergistic tumor radio-immunotherapy.

mRNA nanomedicine reprograms the cell cycle to increase the effectiveness of targeted therapy for HER2-low breast cancers.

Fiber scaffolds augment aged bone regeneration by modulating energy metabolism, immunity and angiogenesis.

Chronic psychological stress is a major cause of various psychiatric disorders, such as depression and anxiety; however, the pathophysiological features of these disorders remain largely unknown. Polysialic acid (PSA), a linear homopolymer of α2-8-linked sialic acid residues, binds to the neural cell adhesion molecule (NCAM) and is involved in cell-to-cell interactions during neural cell migration and neurite outgrowth. Decreased PSA and PSA-NCAM expression have been observed in the brains of patients with psychiatric disorders. Nevertheless, the relationship between psychological stress and PSA has not been clarified. Thus, we examined whether chronic social defeat stress (cSDS), a well-established psychosocial stress model in rodents, affects PSA levels in the male mouse brain. Male C57BL/6J mice were exposed to social defeat stress for 10 consecutive days, after which their whole brains were collected. PSA and NCAM protein levels in the hippocampus and prefrontal cortex were analyzed by western blotting. In addition, we measured the expression of genes involved in PSA metabolism by real-time quantitative PCR analysis. Exposure to cSDS decreased PSA and NCAM protein levels in the hippocampus, but not in the prefrontal cortex. We also found that the expression of genes involved in removing sialic acid from NCAM, such as neuraminidase 3 and 4, was significantly elevated in the hippocampus of mice exposed to cSDS. We provide evidence showing that psychosocial stress disrupts PSA metabolism in adult mice brains. These findings advance our understanding of the mechanisms underlying the onset of stress-related psychiatric disorders.

Exploring the nephroprotective effects of combined finerenone and exenatide therapy in diabetic nephropathy.

Exploring the context-dependent role of miR-744 as a prognostic, diagnostic, and therapeutic biomarker across different cancer types.

Abstract Objectives Gastric carcinoma (GC) remains a high-mortality malignancy that needs efficient ways for the prognosis and therapy of the disease. LncRNAs are biomolecules that participate in cancer progression by regulating gene expression. This study thus investigated the role of lncRNA LINC01711 in GC progression and the underlying mechanisms. Methods GC tumor and normal tissues were collected from 150 GC patients. qRT-PCR was used to test the expression of biomolecules. LncBook, Miranda, and starBase databases were employed to explore miRNAs that interact with LINC01711. The association between the biomolecules was validated via a dual luciferase reporter assay. Biological functions of biomolecules in GC cells were measured by the Cell Counting Kit-8 (CCK-8) and the transwell migration and invasion assays. Results This study found an upregulation of LINC01711 in GC tumor tissues compared to normal tissues. The upregulation of LINC01711 was an indicator of adverse clinical outcomes in GC patients. The miRNA that interacted with LINC01711 in GC was hsa-miR-140-3p. There was a negative correlation between the expression levels of LINC01711 and hsa-miR-140-3p in both GC tumor tissues and cells. LINC01711 promoted GC tumor cell proliferation, migration, and invasion by sponging hsa-miR-140-3p. Conclusions LINC01711 might be an ideal prognostic marker and treatment target for GC. The upregulation of LINC01711 was a negative prognostic indicator for GC patients. LINC01711 facilitated GC tumor cell activities related to GC progression by sponging hsa-miR-140-3p.

J13 imparts drought tolerance to A. thaliana by accelerating plant auxin-dependent, auxin-amino acid conjugation pathway. Plant mutants defective in this pathway do not respond favorably to the bacterium under drought. The precise roles of plant auxin signaling and metabolism in beneficial plant-microbial interaction, especially for abiotic stress tolerance, have not been clearly understood. In this study, we have used the drought-alleviating PGPR strain, Bacillus endophyticus J13 and investigated its impact on auxin signaling and homeostasis in Arabidopsis thaliana, under drought stress. While drought stress elevated the levels of free auxin in A. thaliana plants, J13 inoculation under drought stress lowered the auxin levels in the plants. However, the decreased auxin levels in the drought-stressed plants were accompanied by an increase in the expression of key auxin biosynthetic genes. To understand the reason for this discrepancy, we investigated the role of J13 in auxin conjugation in A. thaliana under drought stress, and observed that, J13 upregulated the transcript levels of genes involved in auxin-dependent auxin conjugation in the plants. A. thaliana mutants deficient in auxin-dependent auxin conjugation (GH3.3) and auxin signalling (axr2-1) did not respond favourably to J13 inoculation under drought conditions. Rather, these mutants exhibited enhanced susceptibility to drought conditions under J13 inoculation. To understand the underlying mechanism of this enhanced drought susceptibility in the mutants, we studied the impact of J13 on the expression of selected genes of salicylic acid-mediated immune signaling in the plants. These mutants exhibited J13-specific modulation in the expression of these genes. Our study thus establishes the importance of auxin-dependent auxin conjugation as a key mechanism of PGPR-mediated drought amelioration in plants.

Colorectal cancer (CRC) is among the most prevalent malignancies. However, the regulatory networks involved in tumor occurrence and development are still poorly understood. Human endogenous retroviruses (HERVs), a class of transposable elements, have been implicated in the development and progression of various human cancers. This study presents the first comprehensive locus-specific profiling of the expression of HERV gene transcripts in rectal cancer, revealing significantly dysregulated HERVs. Analysis of data from three Gene Expression Omnibus data sets revealed 25 upregulated HERVs and 7 downregulated HERVs. Dysregulation of HERV6196, a type of HERVH, was validated through reverse transcription quantitative PCR and droplet digital PCR in cells and tissues. Additionally, HERV6196 promoted the proliferation, inhibited the apoptosis, enhanced the colony formation ability, and enhanced the migration capability of rectal cancer cells. Moreover, HERV6196 functioned as an enhancer, promoting the expression of neighboring genes and the development of CRC. In summary, the present results revealed that HERV6196 is involved in the pathogenesis of rectal cancer, indicating the potential contribution of dysregulated HERVs to the development and progression of CRC through gene expression modulation.IMPORTANCEThe role of human endogenous retroviruses (HERVs) in colorectal cancer (CRC) remains insufficiently understood. The present study revealed aberrant expression of HERV gene transcripts in cancerous tissues compared with non-cancerous tissues. HERV6196 contributes to CRC progression by regulating the expression of neighboring genes. These findings suggest that HERVs may serve as enhancers and regulate oncogenic gene expression, providing new insights for rewiring transcriptional regulatory networks in CRC pathogenesis.

Transposable elements (TEs) play an important role in shaping gene transcription regulatory networks and driving genome evolution. However, there is still little understanding for TE polymorphisms at the species level of rapeseed and their impacts on gene expression and phenotypic formation. This study systematically identified 8268255 TEs from 14 rapeseed genomes and constructed the first rapeseed pan-TE map and then obtained TE insertion polymorphisms (TIP) in 2311 oilseed rape accessions (Brassica napus). Integrative analysis of transcriptome data suggests TEs modulate transcription by diverse cis-regulatory mechanisms and 67% TEs related to nearby gene promote transcription. TE-GWAS identified 1427 TEs in 80 loci associated with 15 traits. Further multi-omics analysis identified a TE insertion in BnaA03.FLCb. suppresses its transcription and ultimately results in early flowering. Besides, one CACTA-like insertion in BnaA09.CYP78A9 reveals the regulatory mechanism how TE-derived cis-regulatory elements promote gene expression to regulate silique length. These results provide a TIP map at the species level and demonstrate that TEs play an important role in transcription regulatory and breeding improvement in rapeseed.

Introduction The long non-coding RNA ZFHX4-AS1 is a recently identified transcript with an unknown role in glioma. Here, we demonstrate that ZFHX4-AS1 and its neighboring protein-coding gene, ZFHX4, are both significantly upregulated in glioma, and their high expression correlates with poor patient prognosis. Methods We integrated pan-cancer and glioma transcriptomic datasets from TCGA to assess ZFHX4-AS1 and ZFHX4 expression patterns and their prognostic relevance. We analyzed the expression of ZFHX4-AS1 and its neighboring gene ZFHX4 in human glioma tissues and correlated it with patient prognosis. Functional assays, including cell proliferation, migration, and invasion tests, were conducted in vitro , and tumor growth was assessed in vivo . Additional mechanistic assays—including RNA-FISH, subcellular fractionation, and co-immunoprecipitation—were performed to determine the localization and molecular interactions of ZFHX4-AS1. The mechanistic interactions between ZFHX4-AS1, ZFHX4, SOX2, and the JAK-STAT pathway were investigated using gene expression analysis, protein-protein interaction studies, and signaling pathway activation assays. Results Functionally, both ZFHX4-AS1 and ZFHX4 promote glioma cell proliferation, migration, and invasion in vitro and tumor growth in vivo . Mechanistically, ZFHX4-AS1 acts in cis to positively regulate the expression of ZFHX4. Crucially, we identified the stemness factor SOX2 as a key functional partner of ZFHX4. ZFHX4 and SOX2 physically interact and form a positive feedback loop, where each protein promotes the other’s expression. This regulatory circuit serves to amplify the oncogenic signal, robustly driving the malignant phenotype. Finally, we demonstrate that this signaling axis converges on the activation of the JAK-STAT pathway. Discussion In conclusion, our study significantly expands upon the understanding of the ZFHX4-AS1 pathway in glioma. We demonstrate that ZFHX4-AS1 initiates an oncogenic signal which is powerfully amplified by a previously unidentified ZFHX4/SOX2 positive feedback loop. We further establish that this entire axis ultimately converges on the activation of the JAK-STAT pathway. This detailed ZFHX4-AS1/ZFHX4/SOX2/JAK-STAT axis represents a promising set of therapeutic targets for glioma treatment.

Chemotherapy remains one of the principal treatment strategies in cancer treatment, is widely used but often limited by the development of chemoresistance and adverse side effects. This study aimed to develop highly effective chemotherapeutic agents with minimal or no adverse effects, specifically focusing on synthesizing a diisothiocyanatozinc(II) complex, [Zn(LCX)(NCS)₂], and evaluating its antineoplastic efficacy and host toxicity. The compound's in vitro anticancer activity was assessed against MCF7 cells using cell growth inhibition, apoptotic morphological observation, and gene expression analysis. In vivo antitumor properties of the compound were assayed in Swiss albino mice bearing EAC cells by monitoring key parameters such as tumor burden, survival rate, tumor cell proliferation, and hematological profiles. Toxicity was evaluated through biochemical, hematological, and histological assessments in mice. The compound demonstrated dose-dependent growth (11-85%) inhibition at 20-500µg/mL doses against MCF7 cells. Compound-treated cells showed apoptotic body formation under fluorescent and phase-contrast microscopes. Notably, mRNA expressions of proapoptotic genes such as p53, Bax, PARP1, Caspase-3, -8, -9, etc., were upregulated while anti-apoptotic genes such as Bcl2 were downregulated in compound-treated cells. Also, the compound showed 83% and 86% inhibition of tumor cell proliferation at doses of 100 and 200µg/kg/day, respectively, compared to the control group of EAC-bearing mice (p < 0.001). Mice treated with 200µg/kg/day showed a 60.3% increase in mean survival time compared to untreated controls (p < 0.001). Hematological parameters (RBC, WBC, hemoglobin), which were significantly reduced in EAC-bearing control mice, were restored to near-normal levels in treated mice. Transient alterations in hematological and biochemical parameters (serum glucose, cholesterol, creatinine, SGOT, SGPT) were observed during treatment; however, they normalized post-treatment, indicating minimal host toxicity. The compound also demonstrated a low LC50 value (7.734µg/mL) in the brine shrimp lethality bioassay, further confirming its pharmacological potential. The [Zn(LCX)(NCS)₂] complex demonstrated potent anticancer activity, followed by induction of apoptosis with minor host toxicity, positioning it as a viable option for advancement as an efficient chemotherapeutic agent. However, more research and clinical studies with animal and human models are needed to further develop the compound as a chemotherapeutic agent.

This study aims to evaluate the cytotoxic effects of methanol (AOME) and ethyl acetate (AOEE) extracts obtained from the flowers of Althaea officinalis L., which is known for its high antioxidant capacity, on prostate cancer cell lines (LNCaP and PC3), as well as their inhibitory effects on cell migration and invasion, and their influence on pro-apoptotic gene expression. Cell viability was assessed using the MTT assay, while cell migration and invasion were analyzed using the scratch assay. Changes in pro-apoptotic gene expression were evaluated by real-time PCR (RT-qPCR), as determined at the IC₅₀ concentrations obtained from cytotoxicity tests. The results showed that AOME and AOEE induced dose-dependent cytotoxicity in both cell lines. The IC₅₀ values were found to be 1.1×10⁻³ μg/mL (AOME) and 11×10⁻⁵ μg/mL (AOEE) for PC3 cells, and 0.21×10⁻³ μg/mL (AOME) and 0.45×10⁻³ μg/mL (AOEE) for LNCaP cells. Scratch assay analyses demonstrated that both extracts significantly inhibited cell migration and invasion compared to the control group. Additionally, RT-qPCR analyses revealed that pro-apoptotic gene expression was significantly increased, and anti-apoptotic gene expression was significantly decreased in treated cells (p

Super-enhancers (SEs) are key DNA cis-regulatory elements that play a central role in regulating tissue/cell-specific gene expression, thereby maintaining cellular identity and function. SEdb 3.0 (http://www.licpathway.net/sedb) provides an extensively updated resource of SEs and their regulatory annotations across multiple species. The current version of SEdb now curates 3 478 186 SEs from 5387 H3K27ac ChIP-seq samples across four species. Compared to SEdb 2.0, it has achieved a two-fold expansion in human and mouse SE entries while newly incorporating Arabidopsis thaliana and maize data, significantly enhancing both the database's scale and its utility in plant research. Furthermore, abundant (epi)genomic features have been added, such as enhancer RNAs (eRNAs), binding sites of transcription co-factors (TcoFs), and chromatin regulators (CRs). The inclusion of eRNAs provides insights into SE transcriptional activity. Mapping TcoF binding sites highlights their roles in mediating enhancer-promoter looping and stabilizing transcriptional complexes at SEs. The integration of CRs uncovers how SEs are associated with histone modifications and chromatin remodeling, which are critical for maintaining an open chromatin state. Collectively, these annotations not only reveal the diverse mechanisms by which SEs exert regulatory functions but also enable more detailed investigations into their biological significance and functional roles. Meanwhile, existing annotations have been substantially expanded, such as an approximately five-fold increase in transcription factor (TF) ChIP-seq data, a 2.3-fold rise in TF motifs, and a roughly 1.8-fold growth in SE-associated eQTL-gene regulatory pairs. SEdb 3.0 introduces two advanced inference strategies for associating genes with SEs. Moreover, two newly developed analysis tools are provided in SEdb 3.0, including SE blast alignment analysis and SE-driven core TF enrichment analysis. In summary, SEdb 3.0 represents a significant upgrade over SEdb 2.0, with a substantial expansion in SE coverage across multiple species, alongside enhanced functional annotations encompassing SE upstream/downstream regulatory information, thereby offering a more comprehensive and user-friendly platform for exploring the biological roles of SEs.

Acute lymphoblastic leukemia (ALL) driven by KMT2A rearrangements (KMT2A-r) is an aggressive hematologic malignancy with poor prognosis and a high incidence in infants. While KMT2A fusion proteins drive leukemogenesis through transcriptional dysregulation, recent discoveries have highlighted the pivotal role of non-coding RNAs (ncRNAs) in shaping the molecular and epigenetic landscape of this disease. These key regulators of gene expression influence chromatin dynamics, transcriptional activation, and post-transcriptional control. Circular RNAs (circRNAs) contribute to genome instability and facilitate chromosomal translocations, while some fusion-derived circRNAs (f-circRNAs) sustain oncogenic signaling and promote chemoresistance. Long non-coding RNAs (lncRNAs) orchestrate transcriptional programs that maintain leukemic stem cell properties and reinforce aberrant self-renewal pathways. MicroRNAs (miRNAs) modulate critical oncogenic networks by regulating KMT2A fusion transcripts and downstream effectors, thereby impacting drug resistance, apoptosis, and proliferation. Meanwhile, enhancer RNAs (eRNAs) fine-tune transcriptional activity and epigenetic regulation, influencing KMT2A target gene expression and chromatin accessibility. Collectively, these ncRNAs integrate into the complex regulatory circuits of KMT2A-r ALL, revealing their potential as biomarkers for disease classification, risk stratification, and treatment response prediction. Understanding their interplay with KMT2A fusion proteins not only provides new insights into leukemogenesis but also highlights promising opportunities for therapeutic intervention and precision medicine in this high-risk leukemia subtype.