Suppression of viral rebound by a Rev-dependent lentiviral particle in SIV-infected rhesus macaques.

Persistence of human immunodeficiency virus (HIV) reservoirs prevents viral eradication, and consequently HIV-infected patients require lifetime treatment with antiretroviral therapy (ART) [1-5]. Currently, there are no effective therapeutics to prevent HIV rebound upon ART cessation. Here we describe an HIV/SIV Rev-dependent lentiviral particle that can be administered to inhibit viral rebound [6-9].

Redox signalling regulates breast cancer metastasis via phenotypic and metabolic reprogramming due to p63 activation by HIF1α.

Background: Redox signaling caused by knockdown (KD) of Glutathione Peroxidase 2 (GPx2) in the PyMT mammary tumour model promotes metastasis via phenotypic and metabolic reprogramming. However, the tumour cell subpopulations and transcriptional regulators governing these processes remained unknown.

Methods: We used single-cell transcriptomics to decipher the tumour cell subpopulations stimulated by GPx2 KD in the PyMT mammary tumour and paired pulmonary metastases.

Risk source identification and diffusion trends of metal(loid)s in stream sediments from an abandoned arsenic-containing mine.

Stream sediments from mine area are a converging source of water and soil pollution. The risk and development trends of metal(loid)s pollution in sediments from an abandoned arsenic-containing mine were studied using modelling techniques. The results showed that the combined techniques of geographic information system (GIS), random forest (RF), and numerical simulation (NS) could identify risk sources and diffusion trends of metal(loid)s in mine sediments.

Pollution Risk Prediction for Cadmium in Soil from an Abandoned Mine Based on Random Forest Model.

It is highly uncertain as to the potential risk of toxic metal(loid)s in abandoned mine soil. In this study, random forest was used to predict the risk of cadmium pollution in the soils of an abandoned lead/zinc mine. The results showed that the random forest model is stable and precise for the pollution risk prediction of toxic metal(loid)s.

Impact of endometrial scratching on reproductive outcome in patients: A systematic review and meta-analysis.

Background: Endometrial scratching (ES) has demonstrated initial success in women with recurrent implantation failure, but the effect in women with 1 previous assisted reproductive technology (ART) failure is unknown. This meta-analysis aimed to evaluate the impact of ES as a treatment in clinical outcomes for women with at least 1 failed in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)/Intrauterine Insemination (IUI).

Methods: PubMed, Medline, Embase, Cochrane Library, Web of Science, CNKI, and EMCC databases were searched for randomized controlled trial studies utilizing endometrial scratching for infertility women with at least 1 failed assisted reproductive technology (ART) to collect pregnancy outcomes, including clinical pregnancy rate (CPR), embryo implantation rate (IR), miscarriage rate (MR), live birth rate (LBR), and multiple pregnancy rate (MPR).

Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer.

In search of redox mechanisms in breast cancer, we uncovered a striking role for glutathione peroxidase 2 (GPx2) in oncogenic signaling and patient survival. GPx2 loss stimulates malignant progression due to reactive oxygen species/hypoxia inducible factor-α (HIF1α)/VEGFA (vascular endothelial growth factor A) signaling, causing poor perfusion and hypoxia, which were reversed by GPx2 reexpression or HIF1α inhibition. Ingenuity Pathway Analysis revealed a link between GPx2 loss, tumor angiogenesis, metabolic modulation, and HIF1α signaling.

Stabilization mechanism of arsenic-sulfide slag by density functional theory calculation of arsenic-sulfide clusters.

Stabilization of arsenic sulfur slag (As‒S slag) is of high importance to prevent the release of deadly As pollutants into environment. However, the molecular understanding on the stability of As‒S slag is missing, which in turn restricts the development of robust approach to solve the challenge. In this work, we investigated the structure-stability relationship of As‒S slag with adopting various As‒S clusters as prototypes by density functional theory (DFT).

A small-molecule allosteric inhibitor of BAX protects against doxorubicin-induced cardiomyopathy.

Doxorubicin remains an essential component of many cancer regimens, but its use is limited by lethal cardiomyopathy, which has been difficult to target, owing to pleiotropic mechanisms leading to apoptotic and necrotic cardiac cell death. Here we show that BAX is rate-limiting in doxorubicin-induced cardiomyopathy and identify a small-molecule BAX inhibitor that blocks both apoptosis and necrosis to prevent this syndrome. By allosterically inhibiting BAX conformational activation, this compound blocks BAX translocation to mitochondria, thereby abrogating both forms of cell death.

p21CIP1 Promotes Mammary Cancer-Initiating Cells via Activation of Wnt/TCF1/CyclinD1 Signaling.

Cancer stem cells (CSC) generate and sustain tumors due to tumor-initiating potential, resulting in recurrence or metastasis. We showed that knockout of the cell-cycle inhibitor, p21CIP1, in the PyMT mammary tumor model inhibits metastasis; however the mechanism remained unknown. Here, we show a pivotal role for p21 in potentiating a cancer stem-like phenotype.

An Akt3 Splice Variant Lacking the Serine 472 Phosphorylation Site Promotes Apoptosis and Suppresses Mammary Tumorigenesis.

The Akt pathway is a well-known promoter of tumor malignancy. Akt3 is expressed as two alternatively spliced variants, one of which lacks the key regulatory serine 472 phosphorylation site. Whereas the function of full-length Akt3 isoform (Akt3/+S472) is well-characterized, that of Akt3/-S472 isoform remains unknown.

Genistein interferes with SDF-1- and HIV-mediated actin dynamics and inhibits HIV infection of resting CD4 T cells.

Background: Binding of HIV to the chemokine coreceptor CXCR4 mediates viral fusion and signal transduction that promotes actin dynamics critical for HIV infection of blood resting CD4 T cells. It has been suggested that this gp120-mediated actin activity resembles the chemotactic actin dynamics mediated by chemokines such as SDF-1. To determine whether inhibiting SDF-1-mediated chemotactic activity can also inhibit HIV infection, we screened several inhibitors known to reduce SDF-1-mediated chemotaxis of T cells.