A Pilot Randomised Double-Blind Study of the Tolerability and efficacy of repetitive Transcranial Magnetic Stimulation on Persistent Post-Concussion Syndrome.

This study investigates the effect of Repetitive Transcranial Magnetic Stimulation (rTMS) on persistent post-concussion syndrome (PCS). The study design was a randomized (coin toss), placebo controlled, and double-blind study. Thirty-seven participants with PCS were assessed for eligibility; 22 were randomised and 18 completed the study requirements.

pH-Operated Triplex DNA Device on MoS Nanosheets.

We report a triplex-based DNA device coupled with molybdenum disulfide (MoS) nanosheets for use as a pH-sensing platform. The device transitions from a duplex state at pH 8 to a triplex state at pH 5. The interaction of the device with MoS nanosheets in the two states is read out as a fluorescence signal from a pH-insensitive dye attached to the device.

Single-Cell RNA Profiling of Glomerular Cells Shows Dynamic Changes in Experimental Diabetic Kidney Disease.

Background: Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into cell-specific gene expression profiles in normal kidneys. However, in diseased kidneys, understanding of changes in specific cells, particularly glomerular cells, remains limited.

Methods: To elucidate the glomerular cell-specific gene expression changes in diabetic kidney disease, we performed scRNA-seq analysis of isolated glomerular cells from streptozotocin-induced diabetic endothelial nitric oxide synthase (eNOS)-deficient (eNOS) mice and control eNOS mice.

Analysis of the Antigenic Properties of Membrane Proteins of Mycobacterium tuberculosis.

Tuberculosis (TB) is a continuing major threat to global health and a leading cause of death, particularly in developing countries. In this study, we aimed to identify a specific and sensitive diagnostic biomarker and develop a vaccine to prevent this disease. We investigated membrane proteins to reveal biomarkers in serum and peripheral blood mononuclear cells (PBMCs) obtained from TB patients.

Expression of Glutamate Receptor Subtype 3 Is Epigenetically Regulated in Podocytes under Diabetic Conditions.

Background: Recent studies suggest a role of epigenetics in the pathogenesis of diabetic kidney disease. However, epigenetic changes occurring specifically in kidney cells is poorly understood.

Methods: To examine the epigenetic regulation of genes in podocytes under diabetic conditions, we performed DNA methylation and transcriptomic profiling in podocytes exposed to high glucose conditions.

MALDI-TOF Characterization of Protein Expression Mutation During Morphological Changes of Bacteria Under the Impact of Antibiotics.

Antimicrobial resistance (AMR) is one of the most serious problems affecting public health and safety. When treated by antibiotics, bacteria usually experience changes in morphology that can lead to the development of AMR. In this work, we propose a strategy to study mutation in protein expression during morphological changes of bacteria under the impact of antibiotics.

Pressure-Regulated Gene Expression and Enzymatic Activity of the Two Periplasmic Nitrate Reductases in the Deep-Sea Bacterium WP3.

species are widely distributed in marine environments, from the shallow coasts to the deepest sea bottom. Most species possess two isoforms of periplasmic nitrate reductases (NAP-α and NAP-β) and are able to generate energy through nitrate reduction. However, the contributions of the two NAP systems to bacterial deep-sea adaptation remain unclear.

miRBaseConverter: an R/Bioconductor package for converting and retrieving miRNA name, accession, sequence and family information in different versions of miRBase.

Background: miRBase is the primary repository for published miRNA sequence and annotation data, and serves as the "go-to" place for miRNA research. However, the definition and annotation of miRNAs have been changed significantly across different versions of miRBase. The changes cause inconsistency in miRNA related data between different databases and articles published at different times.

Estimating heterogeneous treatment effect by balancing heterogeneity and fitness.

Background: Estimating heterogeneous treatment effect is a fundamental problem in biological and medical applications. Recently, several recursive partitioning methods have been proposed to identify the subgroups that respond differently towards a treatment, and they rely on a fitness criterion to minimize the error between the estimated treatment effects and the unobservable ground truths.

Results: In this paper, we propose that a heterogeneity criterion, which maximizes the differences of treatment effects among the subgroups, also needs to be considered.

Blueberry Malvidin-3-galactoside Suppresses Hepatocellular Carcinoma by Regulating Apoptosis, Proliferation, and Metastasis Pathways In Vivo and In Vitro.

Anthocyanin, a natural antioxidant, is reported to have cytotoxicity against cancer cells; however, the mechanism remains unclear. The aim of the present study was to investigate the mechanism by which malvidin-3-galactoside (M3G), the prominent anthocyanin in blueberry, suppresses the development of hepatocellular carcinoma. In vitro, M3G suppressed the proliferation, polarization, migration, and invasion activities of HepG2 cells by regulating the protein expression of cyclin D1, cyclin B, cyclin E, caspase-3, cleaved caspase-3, Bax, p-JNK, and p-p38, activating phosphatase and tensin homologue deleted on chromosome 10 (PTEN), accompanied by a decrease in the p-AKT level, and lowering the protein expression levels of MMP-2 and MMP-9.

C5aR1 regulates T follicular helper differentiation and chronic graft-versus-host disease bronchiolitis obliterans.

CD4+ follicular helper T (Tfh) cells are specialized providers of T cell help to B cells and can function as pathogenic mediators of murine antibody-dependent chronic graft-versus-host disease (GvHD). Using a parent→F1 model of lupus-like chronic GvHD, in which Tfh cell and germinal center (GC) B cell differentiation occurs over 14 days, we demonstrate that absence of CD4+ T cell-expressed C5a receptor 1 (C5ar1) or pharmacological C5aR1 blockade abrogated generation/expansion of Tfh cells, GC B cells, and autoantibodies. In a Tfh cell-dependent model of chronic GvHD manifested by bronchiolitis obliterans syndrome (BOS), C5aR1 antagonism initiated in mice with established disease ameliorated BOS and abolished the associated differentiation of Tfh and GC B cells.

Aging of Antiviral CD8 Memory T Cells Fosters Increased Survival, Metabolic Adaptations, and Lymphoid Tissue Homing.

Aging of established antiviral T cell memory can foster a series of progressive adaptations that paradoxically improve rather than compromise protective CD8 T cell immunity. We now provide evidence that this gradual evolution, the pace of which is contingent on the precise context of the primary response, also impinges on the molecular mechanisms that regulate CD8 memory T cell (T) homeostasis. Over time, CD8 T generated in the wake of an acute infection with the natural murine pathogen lymphocytic choriomeningitis virus become more resistant to apoptosis and acquire enhanced cytokine responsiveness without adjusting their homeostatic proliferation rates; concurrent metabolic adaptations promote increased CD8 T quiescence and fitness but also impart the reacquisition of a partial effector-like metabolic profile; and a gradual redistribution of aging CD8 T from blood and nonlymphoid tissues to lymphatic organs results in CD8 T accumulations in bone marrow, splenic white pulp, and, particularly, lymph nodes.

Ellagic acid ameliorates learning and memory impairment in APP/PS1 transgenic mice via inhibition of β-amyloid production and tau hyperphosphorylation.

β-amyloid (Aβ) aggregation and tau hyperphosphorylation are considered to be the primary pathological hallmarks of Alzheimer's disease (AD). Targeted inhibition of these pathological processes may provide effective treatments for AD. Accumulating evidence has demonstrated that ellagic acid (EA) exerts neuroprotective effects in several diseases.

Method for Quantification of Ribonucleotides and Deoxyribonucleotides in Human Cells Using (Trimethylsilyl)diazomethane Derivatization Followed by Liquid Chromatography-Tandem Mass Spectrometry.

Investigation into intracellular ribonucleotides (RNs) and deoxyribonucleotides (dRNs) is important for studies of the mechanism of many biological processes, such as RNA and DNA synthesis and DNA repair, as well as metabolic and therapeutic efficacy of nucleoside analogues. However, current methods are still unsatisfactory for determination of nucleotides in complex matrixes. Here we describe a novel method for the determination of RN and dRN pools in cells based on fast derivatization with (trimethylsilyl)diazomethane (TMSD) followed by quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Pseudopterosin A ameliorates ischaemia-induced brain injury by acting on Akt signalling pathway.

Introduction: Brain injury caused by ischaemic stroke is a major cause of disability and death throughout the world. The present study evaluates the neuroprotective effect of pseudopterosin A (PtA) against ischaemia-induced brain injury.

Material And Methods: Ischaemia was induced by pMCAO model, and rats were separated in to three groups.

Three-Dimensional Printing of a Complex Aortic Anomaly.

Complex congenital aortic anomalies include diverse types of malformations that may be clinically asymptomatic or present with respiratory or esophageal symptoms. These anomalies may be associated with other congenital heart diseases. It is hard to identify the accurate anatomic vessel location from two-dimensional imaging data, such as computed tomography.

Epigenetic regulation of RCAN1 expression in kidney disease and its role in podocyte injury.

Mounting evidence suggests that epigenetic modification is important in kidney disease pathogenesis. To determine whether epigenetic regulation is involved in HIV-induced kidney injury, we performed genome-wide methylation profiling and transcriptomic profiling of human primary podocytes infected with HIV-1. Comparison of DNA methylation and RNA sequencing profiles identified several genes that were hypomethylated with corresponding upregulated RNA expression in HIV-infected podocytes.

SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts.

Background: We previously showed that the presence of a CKD-associated locus in SHROOM3 in a donor kidney results in increased expression of SHROOM3 (an F-actin-binding protein important for epithelial morphogenesis, via rho-kinase [ROCK] binding); this facilitates TGF-b signaling and allograft fibrosis. However, other evidence suggests Shroom3 may have a protective role in glomerular development.

Methods: We used human data, Shroom3 knockdown podocytes, and inducible shRNA-mediated knockdown mice to study the role of Shroom3 in adult glomeruli.

Changing Geographic Distribution of Japanese Encephalitis Virus Genotypes, 1935-2017.

Japanese encephalitis virus (JEV) is a representative virus of the JEV serogroup in genus Flavivirus, family Flaviviridae. JEV is a mosquito-borne virus that causes Japanese encephalitis (JE), one of the most severe viral encephalitis diseases in the world. JEV is divided into five genotypes (G1-G5), and each genotype has its own distribution pattern.

Efficient Genome Editing of AMB-1 by CRISPR-Cas9 System for Analyzing Magnetotactic Behavior.

Magnetotactic bacteria (MTB) are a diverse group of microorganisms capable of using geomagnetic fields for navigation. This magnetotactic behavior can help microorganisms move toward favorable habitats for optimal growth and reproduction. A comprehensive understanding of the magnetotactic mechanism at molecular levels requires highly efficient genomic editing tools, which remain underdeveloped in MTB.

Detection of novel germline mutations in six breast cancer predisposition genes by targeted next-generation sequencing.

In this study, a customized amplicon-based target sequencing panel was designed to enrich the whole exon regions of six genes associated with the risk of breast cancer. Targeted next-generation sequencing (NGS) was performed for 146 breast cancer patients (BC), 71 healthy women with a family history of breast cancer (high risk), and 55 healthy women without a family history of cancer (control). Sixteen possible disease-causing mutations on four genes were identified in 20 samples.

Simulated altitude exercise training damages small intestinal mucosa barrier in the rats.

This study investigated the effect of simulated altitude training on the changes of small intestinal mucosa barrier, bacterial overgrowth and inflammatory response in the small intestine of rat. Male 8-week-old Sprague-Dawley rats were randomly divided into four groups: normal oxygen sedentary group (n=30), normal oxygen exercise group (n=30), low oxygen sedentary group (n=30) and low oxygen exercise group (n=30). Exercise training was on a treadmill for 1 hr per day on days 3, 6, and 9 in the hypoxia condition.

Spatially constrained tandem bromodomain inhibition bolsters sustained repression of BRD4 transcriptional activity for TNBC cell growth.

The importance of BET protein BRD4 in gene transcription is well recognized through the study of chemical modulation of its characteristic tandem bromodomain (BrD) binding to lysine-acetylated histones and transcription factors. However, while monovalent inhibition of BRD4 by BET BrD inhibitors such as JQ1 blocks growth of hematopoietic cancers, it is much less effective generally in solid tumors. Here, we report a thienodiazepine-based bivalent BrD inhibitor, MS645, that affords spatially constrained tandem BrD inhibition and consequently sustained repression of BRD4 transcriptional activity in blocking proliferation of solid-tumor cells including a panel of triple-negative breast cancer (TNBC) cells.

Design, synthesis and evaluation of novel bivalent β-carboline derivatives as multifunctional agents for the treatment of Alzheimer's disease.

To develop potent multi-target ligands against Alzheimer's disease (AD), a series of novel bivalent β-carboline derivatives were designed, synthesized, and evaluated. In vitro studies revealed these compounds exhibited good multifunctional activities. In particular, compounds 8f and 8g showed the good selectivity potency on BuChE inhibition (IC = 1.