A microfluidic ratiometric electrochemical aptasensor for highly sensitive and selective detection of 3,3',4,4'-tetrachlorobiphenyl.

This study proposes a strategy using a microfluidic ratiometric electrochemical aptasensor to detect PCB77 with excellent sensitivity and specificity. This sensing platform combines a microfluidic chip, a wireless integrated circuit system for aptamer-based electrochemical detection, and a mobile phone control terminal for parameter configuration, identification, observation, and wireless data transfer. The sensing method utilizes a cDNA (MB-COOH-cDNA-SH) that is labelled with the redox probe Methylene Blue (MB) at the 5' end and has a thiol group at the 3' end. Additionally, it utilizes a single strand PCB aptamer that has been modified with ferrocenes at the 3' end (aptamer-Fc). Through gold-thiol binding, the labelled probe of MB-COOH-cDNA-SH was self-assembled onto the surface of an Au/Nb2CTx/GO modified electrode. On exposure to aptamer-Fc, it will hybridize with MB-COOH-cDNA-SH to form a stable double-stranded structure on the electrode surface. When PCB77 is present, aptamer-Fc binds specifically to the target, enabling the double-stranded DNA to unwind. Such variation caused changes in the differential pulse voltammetry (DPV) peak currents of both MB and Fc. A substantial improvement is observed in the ratio between the two DPV peaks. Under the optimum experimental conditions, this assay has a response that covers the 0.0001 to 1000 ng mL-1 PCB77 concentration range, and the detection limit is 1.56 × 10-5 ng mL-1. The integration of a ratiometric electrochemical aptasensor with designed microfluidic and integrated devices in this work is an innovative and promising approach that offers an efficient platform for on-site applications.

m7G-related gene NUDT4 as a novel biomarker promoting cancer cell proliferation in lung adenocarcinoma.

Background: Lung cancer is the leading cause of mortality in cancer patients. N7-methylguanosine (m7G) modification as a translational regulation pattern has been reported to participate in multiple types of cancer progression, but little is known in lung cancer. This study attempts to explore the role of m7G-related proteins in genetic and epigenetic variations in lung adenocarcinoma, and its relationship with clinical prognosis, immune infiltration, and immunotherapy. Methods: Sequencing data were obtained from the Genomic Data Commons (GDC) Data Portal and Gene Expression Omnibus (GEO) databases. Consensus clustering was utilized to distinguish m7G clusters, and responses to immunotherapy were also evaluated. Moreover, univariate and multivariate Cox and Least absolute shrinkage and selection operator LASSO Cox regression analyses were used to screen independent prognostic factors and generated risk scores for constructing a survival prediction model. Multiple cell types such as epithelial cells and immune cells were identified to verify the bulk RNA results. Short hairpin RNA (shRNA) Tet-on plasmids, Clustered Regularly Interspaced Short Palindromic Repeats CRISPR/Cas9 for knockout plasmids, and nucleoside diphosphate linked to moiety X-type motif 4 (NUDT4) overexpression plasmids were constructed to inhibit or promote tumor cell NUDT4 expression, then RT-qPCR, Cell Counting Kit-8 CCK8 proliferation assay, and Transwell assay were used to observe tumor cell biological functions. Results: Fifteen m7G-related genes were highly expressed in tumor samples, and 12 genes were associated with poor prognosis. m7G cluster-B had lower immune infiltration level, worse survival, and samples that predicted poor responses to immunotherapy. The multivariate Cox model showed that NUDT4 and WDR4 (WD repeat domain 4) were independent risk factors. Single-cell m7G gene set variation analysis (GSVA) scores also had a negative correlation tendency with immune infiltration level and T-cell Programmed Death-1 PD-1 expression, but the statistics were not significant. Knocking down and knocking out the NUDT4 expression significantly inhibited cell proliferation capability in A549 and H1299 cells. In contrast, overexpressing NUDT4 promoted tumor cell proliferation. However, there was no difference in migration capability in the knockdown, knockout, or overexpression groups. Conclusions: Our study revealed that m7G modification-related proteins are closely related to the tumor microenvironment, immune cell infiltration, responses to immunotherapy, and patients' prognosis in lung adenocarcinoma and could be useful biomarkers for the identification of patients who could benefit from immunotherapy. The m7G modification protein NUDT4 may be a novel biomarker in promoting the progression of lung cancer.

Recent Advances of Nanotechnology-Facilitated Bacteria-Based Drug and Gene Delivery Systems for Cancer Treatment.

Cancer is one of the most devastating and ubiquitous human diseases. Conventional therapies like chemotherapy and radiotherapy are the most widely used cancer treatments. Despite the notable therapeutic improvements that these measures achieve, disappointing therapeutic outcome and cancer reoccurrence commonly following these therapies demonstrate the need for better alternatives. Among them, bacterial therapy has proven to be effective in its intrinsic cancer targeting ability and various therapeutic mechanisms that can be further bolstered by nanotechnology. In this review, we will discuss recent advances of nanotechnology-facilitated bacteria-based drug and gene delivery systems in cancer treatment. Therapeutic mechanisms of these hybrid nanoformulations are highlighted to provide an up-to-date understanding of this emerging field.

Recent Advances of Cell Membrane Coated Nanoparticles in Treating Cardiovascular Disorders.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, causing approximately 17.9 million deaths annually, an estimated 31% of all deaths, according to the WHO. CVDs are essentially rooted in atherosclerosis and are clinically classified into coronary heart disease, stroke and peripheral vascular disorders. Current clinical interventions include early diagnosis, the insertion of stents, and long-term preventive therapy. However, clinical diagnostic and therapeutic tools are subject to a number of limitations including, but not limited to, potential toxicity induced by contrast agents and unexpected bleeding caused by anti-platelet drugs. Nanomedicine has achieved great advancements in biomedical area. Among them, cell membrane coated nanoparticles, denoted as CMCNPs, have acquired enormous expectations due to their biomimetic properties. Such membrane coating technology not only helps avoid immune clearance, but also endows nanoparticles with diverse cellular and functional mimicry. In this review, we will describe the superiorities of CMCNPs in treating cardiovascular diseases and their potentials in optimizing current clinical managements.