Shixiong Deng

Immune non-responder after highly active antiretroviral therapy (HAART) is the main cause of opportunistic infections and high mortality in AIDS patients, but the mechanism underlying immune reconstitution failure is poorly understood. Here, we performed scRNA-seq, and scATAC-seq analysis of peripheral blood mononuclear cells (PBMCs) derived from immune non-responder (INR) and responder (IR) HIV-1-infected subjects. We found low expression of mucosal-associated invariant T (MAIT) cells in INRs, which exhibited transcriptional profiles associated with impaired mitochondrial function and apoptosis signaling. Single-cell assays for transposase-accessible chromatin (scATAC-seq) and flow cytometry revealed diminished mitochondrial fitness in MAIT cells from INRs, and MAIT had low expression of transcription factor A for mitochondria (TFAM) and peroxisomal proliferator-activated receptor alpha (PPARA). These findings demonstrate that restoring mitochondrial function could modulate the immune dysfunction characteristic of MAIT against bacterial co-infections in INRs subjects.

The authors report a self-oriented beacon liquid crystal (LC) biosensor for kanamycin (Kana) detection with gold nanoparticle (AuNPs) signal enhancement. In this study, an assay was proposed for Kana detection using the aptamer as a self-oriented beacon. Without an additional orientation agent, the Kana aptamer was used as a self-oriented beacon both as an orientation agent for the LCs and as a signal recognition probe for biological molecules. Gold nanoparticles are blended with desired concentrations of the target molecules, which can greatly improve the performance of the biosensor. In the presence of Kana, AuNPs–Kana–aptamer conjugates will form on the sensing interface of the biosensor, which can remarkably destroy the orientated arrangement of the LCs, resulting in changes in the corresponding polarized images of the LCs. The limit of Kana detection is as low as 0.1 pmol L⁻¹. It is important to note that the self-oriented beacons are immobilized on the assembled film of the glass slides for the specific recognition of Kana, simultaneously allowing the homeotropic orientation of the LCs. This study also provides a mechanism for the self-orientation beacon and liquid crystal biosensing.

Ischemic stroke is one of the leading causes of global mortality and disability. It is a multi-factorial disease involving multiple factors, and gene dysregulation is considered as the major molecular mechanisms underlying disease progression. Angiogenesis can promote collateral circulation, which helps the restoration of blood supply in the ischemic area and reduces ischemic necrosis following ischemic injury. Aberrant expression of long non-coding RNAs (lncRNAs) in ischemic stroke is associated with various biological functions of endothelial cells and serves essential roles on the angiogenesis of ischemic stroke. The key roles of lncRNAs on angiogenesis suggest their potential as novel therapeutic targets for future diagnosis and treatment. This review elucidates the detailed regulatory functions of lncRNAs on angiogenesis following ischemic stroke through numerous mechanisms, such as interaction with target microRNAs, downstream signaling pathways and target molecules.

The development of probes for the testing of the carcinogenic pollutant 2,4,6‐trinitrophenol (TNP) is of great importance for environmental protection and human health. In this paper, a new rapid and sensitive fluorescence detection method based on carbon dots (CDs) was designed for the detection of TNP. The CDs were synthesized by simple pyrolysis using citric acid as raw material and characterized by various advanced techniques. The addition of TNP caused a significant turn off in the fluorescence of the CDs. The fluorescence quench intensity and TNP concentration exhibited a good linear correlation in the range of 0–80 μM with a minimum detection limit of 0.48 μM and a related coefficient of 0.994. The analytical method was applied to the determination of trace TNP in river water and tap water with recoveries in the range of 98%–110% and relative standard deviations less than 5%. Importantly, carbon dots functionalized papers (CDFPs) were prepared using the synthesized CDs and successfully applied to the determination of TNP in aqueous solutions, demonstrating the promising application of the method.

In this article, we make a theoretical and in silico study for uncovering and evaluating biomarkers in colon and rectal cancer (CRC) by the dynamic network biomarker (DNB) theory. We propose a strategy to employ the theoretical concept of UICC TNM classification in CRC. To reveal the critical transition of CRC, the DNB algorithm was implemented to analyze the genome-wide dynamic network through temporal gene expression data. The relationship between gene sets and clinical features was evaluated by weighted gene co-expression network analysis. The results show that MYC was significantly associated with tumor amplification, tumor immune cells, and survival times. The candidate tumor suppressor genes were ZBTB16, MAL, LIFR, and SLIT2. Protein–protein interaction (PPI) analysis shows that these candidate tumor suppressor genes were significant in immune cells. Data from the Human Protein Atlas showed that a high expression of these candidate tumor suppressor genes was associated with favorable prognosis in TNM stages I–IV. In conclusion, this work provides significant and novel information regarding the TNM stage, cause, and consequences of elevated MYC expression in CRC. MYC expression levels had significant negative correlations with tumor suppressor genes and immune cells.

The authors report on a method for the determination of ractopamine (RAC) via liquid crystal (LC) optical imaging and gold nanoparticle-induced signal enhancement. The gold nanoparticles (AuNPs) were blended with the desired concentrations of RAC, and this is found to strongly improve the performance of the assay. The RAC aptamers were immobilized on the self-assembled film of a glass slide for specific recognition of RAC. This causes a homeotropic re-orientation of the LCs. Notably, the aptamers need not be immobilized on the nanoparticles like in other methods. The addition of RAC causes the formation of an AuNP-RAC-aptamer conjugate on the sensing interface. This disrupts the orientation of LCs and results in a change of the polarized images of the LCs. The method has a detection limit as low as 1 pM of RAC.

Prostate cancer (PCa) is a malignancy cause of cancer deaths and frequently diagnosed in male. This study aimed to identify tumor suppressor genes, hub genes and their pathways by combined bioinformatics analysis. A combined analysis method was used for two types of microarray datasets (DNA methylation and gene expression profiles) from the Gene Expression Omnibus (GEO). Differentially methylated genes (DMGs) were identified by the R package minfi and differentially expressed genes (DEGs) were screened out via the R package limma. A total of 4451 DMGs and 1509 DEGs, identified with nine overlaps between DMGs, DEGs and tumor suppressor genes, were screened for candidate tumor suppressor genes. All these nine candidate tumor suppressor genes were validated by TCGA (The Cancer Genome Atlas) database and Oncomine database. And then, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed by DAVID (Database for Annotation, Visualization and Integrated Discovery) database. Protein–protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. At last, Kaplan–Meier analysis was performed to validate these genes. The candidate tumor suppressor genes were IKZF1, PPM1A, FBP1, SMCHD1, ALPL, CASP5, PYHIN1, DAPK1 and CASP8. By validation in TCGA database, PPM1A, DAPK1, FBP1, PYHIN1, ALPL and SMCHD1 were significant. The hub genes were FGFR1, FGF13 and CCND1. These hub genes were identified from the PPI network, and sub-networks revealed by these genes were involved in significant pathways. In summary, the study indicated that the combined analysis for identifying target genes with PCa by bioinformatics tools promote our understanding of the molecular mechanisms and underlying the development of PCa. And the hub genes might serve as molecular targets and diagnostic biomarkers for precise diagnosis and treatment of PCa.