Aedes albopictus is an important vector of Dengue virus (DENV) and it has quickly invaded the tropical and temperate environments worldwide. A few studies have shown that, microRNAs (miRNAs) regulate mosquito defense against pathogens. However, there is no systematic analysis of the impact of DENV infection on miRNA expression in Ae. albopictus. We conducted this study to investigate the miRNA expression of Ae. albopictus upon DENV-2 infection using Illumina RNA sequencing. A total of 103 known and 5 novel candidate miRNAs were identified in DENV-2 infected and non-infected adult female Ae. albopictus. Comparative analysis indicated that 52 miRNAs were significantly down-regulated and 18 were up-regulated significantly after infection. Furthermore, RT-qPCR validated the expression patterns of eleven of these differentially expressed miRNAs. Targets prediction and functional analysis of these regulated miRNAs suggested that miR-34-5p and miR-87 might be involved in the anti-pathogen and immune responses. This is the first systematic study on the impact of DENV infection on miRNA expression in Ae. albopictus. Complex changes in miRNA expression suggest a potential role of miRNAs in antiviral responses by regulating immune-related genes. This investigation provides information concerning DENV-induced miRNAs and offers clues for identifying potential candidates for vector based antiviral strategies.

Podocyte injury is the primary cause of glomerular injury in diabetic nephropathy (DN). Advanced oxidation protein products (AOPPs), the triggers and markers of oxidative stress in DN, have been linked to podocyte damage. However, the underlying mechanism is not yet clear. Here, we investigated the potential role of FOXO3a, a key transcription factor in the response to stress, in mediating AOPPs‐induced podocyte injury. We found that FOXO3a expression was increased in the glomeruli of kidney biopsies from patients with DN and it was positively correlated with proteinuria. The serum from patients with DN significantly increased FOXO3a and its downstream genes FasL and Bim, thereby inducing the high level of cleaved caspase3 and the loss of nephrin and podocin expressions in podocytes. Blockade of AOPPs signaling by a neutralizing antibody against the receptor of advanced glycation end products (αRAGE) abolished the effect of DN serum on podocytes, confirming the pathogenic role of AOPPs in DN serum. Downregulation of FOXO3a decreased AOPPs‐induced podocyte apoptosis and restored the levels of podocyte markers nephrin and podocin, and upregulation of FOXO3a exacerbated these changes in podocytes after AOPPs treatment. Furthermore, FOXO3a specifically activated proapoptotic genes in podocytes only in the presence of AOPPs. Mechanistically, AOPPs increased the FOXO3a protein levels by inhibiting their autophagic degradation in a ROS/mTOR‐dependent manner. Moreover AOPPs activated the accumulated FOXO3a by maintaining FOXO3a in the nucleus, and this process was dependent on ROS‐mediated AKT signaling deactivation. These studies suggest that FOXO3a plays a critical role in mediating AOPPs‐induced podocyte injury and reveal a new mechanistic linkage of oxidative stress, FOXO3a activation and podocyte injury in DN.

Diabetic retinopathy (DR) remains a leading cause of vision impairment worldwide, with limited therapeutic options and early detection methods. This study aims to identify novel biomarkers for DR to address the critical need for therapeutic targets. We employed a multi-omics strategy combining scRNA-seq analysis of DR-related immune cell populations with bidirectional MR integrating quantitative trait loci (eQTL)/protein quantitative trait loci (pQTL) data to establish HLA-A's causal role in DR. Clinical validation utilized Chinese cohort peripheral blood samples (n = 81), complemented by molecular docking and cellular experiments testing resveratrol's modulation of HLA-A under metabolic stress conditions. Bidirectional Mendelian randomization identified HLA-A as a causal risk factor for DR, with consistent evidence from both expression quantitative trait loci (eqtl: OR = 1.121, 95% CI [1.057, 1.19], p = 1.584 × 10^-4. pqtl: OR = 1.136, 95% CI [1.095, 1.178], p = 1.05 × 10^-11). Sensitivity analyses showed no evidence of horizontal pleiotropy (p = 0.234) or heterogeneity (p = 0.199). Shared causal variants (PP.H4 > 0.8) emerged from Bayesian colocalization. Clinically, peripheral blood HLA-A mRNA levels were significantly increased in DR patients (HbA1c ≥ 7.5%). Critically, in glucolipotoxic conditions, HLA-A knockdown suppressed pro-inflammatory cytokines in THP-1 cells, while glucolipotoxicity potently upregulated HLA-A expression, which was dose-dependently inhibited by resveratrol. This multi-omics study establishes HLA-A as a novel causal factor in DR pathogenesis and reveals resveratrol's potential therapeutic value through HLA-A modulation, providing new insights for targeted intervention strategies.