PSMD1 and PSMD2 regulate HepG2 cell proliferation and apoptosis via modulating cellular lipid droplet metabolism.

Background: Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC). The lipid-rich environment enhances the proliferation and metastasis abilities of tumor cells. Previous studies showed the effect of the ubiquitin-proteasome system (UPS) on tumor cell proliferation.

The antimicrobial peptides and their potential clinical applications.

Nowadays, the bacterial drug resistance leads to serious healthy problem worldwide due to the long-term use and the abuse of traditional antibiotics result in drug resistance of bacteria. Finding a new antibiotic is becoming more and more difficult. Antimicrobial peptides (AMPs) are the host defense peptides with most of them being the cationic (positively charged) and amphiphilic (hydrophilic and hydrophobic) α-helical peptide molecules.

Deletion of miR-126a Promotes Hepatic Aging and Inflammation in a Mouse Model of Cholestasis.

MicroRNAs (miRNAs) act as regulators of aging at the tissue or organism level or as regulators of cellular senescence. Targeted deletion of miR-126 in mice causes partial embryonic lethality, but its biological function in the liver is still largely unknown. Here, we deleted miR-126a, using the CRISPR/Cas9 system in vitro and in vivo.

Structural and Functional Insights into Host Death Domains Inactivation by the Bacterial Arginine GlcNAcyltransferase Effector.

Enteropathogenic E. coli NleB and related type III effectors catalyze arginine GlcNAcylation of death domain (DD) proteins to block host defense, but the underlying mechanism is unknown. Here we solve crystal structures of NleB alone and in complex with FADD-DD, UDP, and Mn as well as NleB-GlcNAcylated DDs of TRADD and RIPK1.

A Frizzled-Like Cysteine-Rich Domain in Glypican-3 Mediates Wnt Binding and Regulates Hepatocellular Carcinoma Tumor Growth in Mice.

Wnt signaling is one of the key regulators of hepatocellular carcinoma (HCC) tumor progression. In addition to the classical receptor frizzled (FZD), various coreceptors including heparan sulfate proteoglycans (HSPGs) are involved in Wnt activation. Glypican-3 (GPC3) is an HSPG that is overexpressed in HCC and functions as a Wnt coreceptor that modulates HCC cell proliferation.

Designing a Green Fluorogenic Protease Reporter by Flipping a Beta Strand of GFP for Imaging Apoptosis in Animals.

A family of proteases called caspases mediate apoptosis signaling in animals. We report a GFP-based fluorogenic protease reporter, dubbed "FlipGFP", by flipping a beta strand of the GFP. Upon protease activation and cleavage, the beta strand is restored, leading to reconstitution of the GFP and fluorescence.

Differences in neurotropism and neurotoxicity among retrograde viral tracers.

Background: Neurotropic virus-based tracers have been extensively applied in mapping and manipulation of neural circuits. However, their neurotropic and neurotoxic properties remain to be fully characterized.

Methods: Through neural circuit tracing, we systematically compared the neurotropism discrepancy among different multi-trans-synaptic and mono-synaptic retrograde viral tracers including pseudorabies virus (PRV), rabies virus (RV), and the newly engineered retro adeno-associated virus (rAAV2-retro) tracers.

Expression of RNA-binding protein Rbfox1l demarcates a restricted population of dorsal telencephalic neurons within the adult zebrafish brain.

Rbfox RNA-binding proteins are expressed in the adult mammalian brain and are required for proper brain development and function. Studies in mice and humans have implicated Rbfox1/RBFOX1 in autism, neuronal excitation and epilepsy, and Rbfox2/RBFOX2 in cerebellar development. The zebrafish has emerged as a prominent model system for brain study, possessing neuroanatomical conservation with mammals and an extensive capacity for adult neurogenesis and plasticity.

Dissecting Molecular and Circuit Mechanisms for Inhibition and Delayed Response of ASI Neurons during Nociceptive Stimulus.

The mechanisms by which off-response neurons stay quiescent during stimulation are largely unknown. Here, we dissect underlying molecular and circuit mechanisms for the inhibition of off-response ASI neurons during nociceptive Cu stimulation. ASIs are inhibited in parallel by sensory neurons ASER, ADFs, and ASHs.

A Streptococcus suis Live Vaccine Suppresses Streptococcal Toxic Shock-Like Syndrome and Provides Sequence Type-Independent Protection.

Background: Streptococcus suis is an encapsulated zoonotic pathogen. Increasing antimicrobial resistance invokes the need for effective vaccines. Despite many attempts to develop an effective vaccine, none is currently available.

Isolation, Characterization, and Application of Bacteriophage LPSE1 Against in Ready to Eat (RTE) Foods.

infection is an important foodborne consumer health concern that can be mitigated during food processing. Bacteriophage therapy imparts many advantages over conventional chemical preservatives including pathogen specificity, natural derivation, potency, and providing a high degree of safety. The objective of this study aimed to isolate and characterize a phage that effectively control food contamination.

Digestion-ligation-only Hi-C is an efficient and cost-effective method for chromosome conformation capture.

Chromosome conformation capture (3C) technologies can be used to investigate 3D genomic structures. However, high background noise, high costs, and a lack of straightforward noise evaluation in current methods impede the advancement of 3D genomic research. Here we developed a simple digestion-ligation-only Hi-C (DLO Hi-C) technology to explore the 3D landscape of the genome.

Steric shielding protected and acidity-activated pop-up of ligand for tumor enhanced photodynamic therapy.

Tumor targeted drug delivery in vivo remains a significant challenge in tumor therapy. In this article, we fabricated a steric shielding protected/tumor acidity-activated chimeric peptide for tumor targeted photodynamic therapy. This amphiphilic chimeric peptide could form spherical nanoparticles at neutrally physiological environment with the shielding of biotin molecule (tumor target ligand).

A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer.

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls).

Functional peptide-based nanoparticles for photodynamic therapy.

Photodynamic therapy as a non-invasive approach has obtained great research attention during the last decade. However, photodynamic therapy still suffers from low tumor selectivity and therapeutic inefficacy due to the unspecific distribution of photosensitizers in normal tissues/cells. To overcome these hurdles, functional peptides have been introduced in photodynamic therapy systems due to their advantages of functional diversity, bioactivity, high biocompatibility and biodegradability.

Alleviation of Toxicity Caused by Overactivation of Pparα through Pparα-Inducible miR-181a2.

Widely varied compounds, including certain plasticizers, hypolipidemic drugs (e.g., ciprofibrate, fenofibrate, WY-14643, and clofibrate), agrochemicals, and environmental pollutants, are peroxisome proliferators (PPs).

Development and application of a recombination-based library versus library high- throughput yeast two-hybrid (RLL-Y2H) screening system.

Protein-protein interaction (PPI) network maintains proper function of all organisms. Simple high-throughput technologies are desperately needed to delineate the landscape of PPI networks. While recent state-of-the-art yeast two-hybrid (Y2H) systems improved screening efficiency, either individual colony isolation, library preparation arrays, gene barcoding or massive sequencing are still required.

In vivo cough suppressive activity of pectic polysaccharide with arabinogalactan type II side chains of Piper nigrum fruits and its synergistic effect with piperine.

Piper nigrum L. fruits are not only a prized spice, but also highly valued therapeutic agent that heals many ailments including asthma, cold and respiratory problems. Herein, we have investigated structural features and in vivo antitussive activity of three fractions isolated from Piper nigrum fruits.

Mortality along the continuum of HIV care in Rwanda: a model-based analysis.

Background: HIV is the leading cause of death among adults in sub-Saharan Africa. However, mortality along the HIV care continuum is poorly described. We combine demographic, epidemiologic, and health services data to estimate where are people with HIV dying along Rwanda's care continuum.

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART).

Analysis of reference interval and age-related changes in serum biochemistry and hematology in the specific pathogen free miniature pig.

We analyzed 72 items related to serum biochemistry and hematology in 85 specific pathogen-free (SPF) Seoul National University (SNU) miniature pigs aged 1- to 36-months which originated from a Minnesota miniature pig. Almost all examined items were similar between male and female pigs. However, some items such as Cr level, B/C ratio, C.

Microarray techniques for more rapid protein quantification: use of single spot multiplex analysis and a vibration reaction unit.

Protein microarray technology is a powerful, popular tool for the high-throughput analysis of protein interactions. One important use for protein microarray technology is protein quantification by immunoassay, which was originally based on enzyme linked immunosorbent assay (ELISA) methods. Recently, new research and diagnostic applications have created a need for a rapid and easily applied high-throughput protein quantification method.

Vibratory reaction unit for the rapid analysis of proteins and glycochains.

A protein digestion system using immobilized enzymes for protein identification and glycochain analyses has been developed, and a vibration reaction unit for micro-scale sample convection on an enzyme-immobilized solid surface was constructed. BSA as a model substrate was digested by this unit, and was successfully identified by mass spectrometry (MS) analyses. Compared to the conventional liquid-phase digestion, the reaction unit increased the number of matched peptides from 9 to 26, protein score from 455 to 1247, and sequence coverage from 21% to 48%.