Mining functional gene modules by multi-view NMF of phenome-genome association.

Background: Mining functional gene modules from genomic data is an important step to detect gene members of pathways or other relations such as protein-protein interactions. This work explores the plausibility of detecting functional gene modules by factorizing gene-phenotype association matrix from the phenotype ontology data rather than the conventionally used gene expression data. Recently, the hierarchical structure of phenotype ontologies has not been sufficiently utilized in gene clustering while functionally related genes are consistently associated with phenotypes on the same path in phenotype ontologies.

Establishing superfine nanofibrils for robust polyelectrolyte artificial spider silk and powerful artificial muscles.

Spider silk exhibits an excellent combination of high strength and toughness, which originates from the hierarchical self-assembled structure of spidroin during fiber spinning. In this work, superfine nanofibrils are established in polyelectrolyte artificial spider silk by optimizing the flexibility of polymer chains, which exhibits combination of breaking strength and toughness ranging from 1.83 GPa and 238 MJ m to 0.

Ube2L6 Promotes M1 Macrophage Polarization in High-Fat Diet-Fed Obese Mice via ISGylation of STAT1 to Trigger STAT1 Activation.

Introduction: In obesity-related type 2 diabetes mellitus (T2DM), M1 macrophages aggravate chronic inflammation and insulin resistance. ISG15-conjugation enzyme E2L6 (Ube2L6) has been demonstrated as a promoter of obesity and insulin resistance. This study investigated the function and mechanism of Ube2L6 in M1 macrophage polarization in obesity.

A network analysis of anxiety and depression symptoms in Chinese disabled elderly.

Background: Mental health is an essential dimension of healthy aging. The number and severity of disabled elderly in China show an increasing tendency year by year. Due to their impaired ability of daily activities, reduced social participation and reduced self-care ability, they are more prone to depression and anxiety.

The interaction effect of transfusion history and previous stroke history on the risk of venous thromboembolism in stroke patients: a prospective cohort study.

Background: Blood transfusion and previous stroke history are two independent risk factors of venous thromboembolism (VTE) in stroke patients. Whether the potential interaction of transfusion history and previous stroke history is associated with a greater risk of VTE remains unclear. This study aims to explore whether the combination of transfusion history and previous stroke history increases the risk of VTE among Chinese stroke patients.

The Green Walnut Husks Induces Apoptosis of Colorectal Cancer through Regulating NLRC3/PI3K Pathway.

Background: Colorectal cancer (CRC) is the most common type of gastrointestinal tumor, but the available pharmacological treatment is insufficient. As a traditional Chinese medicine, the green walnut husks (QLY) exhibit anti-inflammatory, analgesic, anti-bacterial and anti-tumor effects. However, the effects and molecular mechanisms of QLY extracts on CRC were not yet made known.

Morphology modulation of artificial muscles by thermodynamic-twist coupling.

Human muscles can grow and change their length with body development; therefore, artificial muscles that modulate their morphology according to changing needs are needed. In this paper, we report a strategy to transform an artificial muscle into a new muscle with a different morphology by thermodynamic-twist coupling, and illustrate its structural evolution during actuation. The muscle length can be continuously modulated over a large temperature range, and actuation occurs by continuously changing the temperature.

A Protein-Like Nanogel for Spinning Hierarchically Structured Artificial Spider Silk.

Spider dragline silk is draw-spun from soluble, β-sheet-crosslinked spidroin in aqueous solution. This spider silk has an excellent combination of strength and toughness, which originates from the hierarchical structure containing β-sheet crosslinking points, spiral nanoassemblies, a rigid sheath, and a soft core. Inspired by the spidroin structure and spider spinning process, a soluble and crosslinked nanogel is prepared and crosslinked fibers are drew spun with spider-silk-like hierarchical structures containing cross-links, aligned nanoassemblies, and sheath-core structures.

[Preparation of brazilein from by high performance countercurrent chromatography].

Brazilein is among the main chemical constituents of . It has diverse pharmacological activities. Modern pharmacological studies have shown that the compound has antitumor, anti-inflammatory, antibacterial, antioxidant, immunomodulatory, and other pharmacological activities.

Development of a strategy for a quick process for separation of volatile compounds in counter-current chromatography: purification of cinnamaldehyde from by high performance counter-current chromatography.

It is a challenge for many researchers to separate volatile compounds. In this study, we introduce a rapid and efficient method of separating target compound from the twigs of by high performance counter-current chromatography. Under the bioassay guidance, the total extract exhibited a potential activity against NO production in RAW 264.

A novel pentacyclic triterpene from the canes of (Rubiaceae).

One novel pentacyclic triterpene, 24-dimethoxymethyl-3,6,19- trihydroxy -12-en-28-oic acid (), along with six known compounds -, were isolated from the canes of Roxb. Their structures were determined according to spectroscopic and spectrometric analysis. The anti-inflammatory activities of the isolated compounds (-) were scanned against NO production in LPS-activated RAW 264.

Baseline Frequency of Inflammatory Cxcl9-Expressing Tumor-Associated Macrophages Predicts Response to Avelumab Treatment.

The tumor microenvironment is rich with immune-suppressive macrophages that are associated with cancer progression and resistance to immune checkpoint therapy. Using pre-treatment tumor biopsies complemented with single-cell RNA sequencing (RNA-seq), we characterize intratumoral immune heterogeneity to unveil potential mechanisms of resistance to avelumab (anti-PD-L1). We identify a proinflammatory F480MHCIILy6C macrophage population that is associated with response rather than resistance to avelumab.

CD40 agonist-induced IL-12p40 potentiates hepatotoxicity.

Background: CD40 is a compelling target for cancer immunotherapy, however, attempts to successfully target this pathway have consistently been hampered by dose-limiting toxicity issues in the clinic that prevents the administration of efficacious doses.

Methods: Here, using cytokine and cytokine receptor depletion strategies in conjunction with a potent CD40 agonist, we investigated mechanisms underlying the two primary sources of CD40 agonist-associated toxicity, hepatotoxicity and cytokine release syndrome (CRS).

Results: We demonstrate that CD40 agonist -induced hepatotoxicity and CRS are mechanistically independent.

The Prevention and Inhibition Effect of Anthocyanins on Colorectal Cancer.

Background: Anthocyanins are a type of flavonoids that are natural water soluble glycosidic pigments with efficacious anti-cancer effects, which have good biological activity against many cancers including colorectal cancer (CRC). However, the exact molecular mechanism used by anthocyanins against cancer is unclear; it is also unclear what a reasonable dosage might be for their use against colorectal cancer.

Methods: Western blotting, immunohistochemistry, MTT assay, xenograft model, and hematoxylin-eosin (HE) staining were used to perform the experiments.

Artificial spider silk from ion-doped and twisted core-sheath hydrogel fibres.

Spider silks show unique combinations of strength, toughness, extensibility, and energy absorption. To date, it has been difficult to obtain spider silk-like mechanical properties using non-protein approaches. Here, we report on an artificial spider silk produced by the water-evaporation-induced self-assembly of hydrogel fibre made from polyacrylic acid and silica nanoparticles.

Torsional refrigeration by twisted, coiled, and supercoiled fibers.

Higher-efficiency, lower-cost refrigeration is needed for both large- and small-scale cooling. Refrigerators using entropy changes during cycles of stretching or hydrostatic compression of a solid are possible alternatives to the vapor-compression fridges found in homes. We show that high cooling results from twist changes for twisted, coiled, or supercoiled fibers, including those of natural rubber, nickel titanium, and polyethylene fishing line.

Prognostic Significance of Blood Transfusion in Elderly Patients with Primary Diffuse Large B-Cell Lymphoma.

The current study sought to evaluate whether blood transfusions affect survival of elderly patients with primary diffuse large B-cell lymphoma (DLBCL). A total of 104 patients aged 60 years and over were enrolled and divided into two groups: 24 patients who received transfusions and 80 patients who did not. Statistical analyses showed significant differences in LDH levels, platelet (Plt) counts, and hemoglobin (Hb) and albumin (Alb) levels between the two groups.

Alveolar macrophages are critical for broadly-reactive antibody-mediated protection against influenza A virus in mice.

The aim of candidate universal influenza vaccines is to provide broad protection against influenza A and B viruses. Studies have demonstrated that broadly reactive antibodies require Fc-Fc gamma receptor interactions for optimal protection; however, the innate effector cells responsible for mediating this protection remain largely unknown. Here, we examine the roles of alveolar macrophages, natural killer cells, and neutrophils in antibody-mediated protection.

Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies.

Influenza viruses exhibit a remarkable ability to adapt and evade the host immune response. One way is through antigenic changes that occur on the surface glycoproteins of the virus. The generation of escape variants is a powerful method in elucidating how viruses escape immune detection and in identifying critical residues required for antibody binding.

Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands Work Additively via MyD88 To Induce Protective Antiviral Immunity in Mice.

We previously demonstrated that the combination of synthetic small-molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity that is protective against influenza viruses in homologous, heterologous, and heterosubtypic murine challenge models. Combining the TLR4 and TLR7 ligands balances Th1 and Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function via their known receptors, with negligible off-target effects, to induce protective immunity.

Epitope specificity plays a critical role in regulating antibody-dependent cell-mediated cytotoxicity against influenza A virus.

The generation of strain-specific neutralizing antibodies against influenza A virus is known to confer potent protection against homologous infections. The majority of these antibodies bind to the hemagglutinin (HA) head domain and function by blocking the receptor binding site, preventing infection of host cells. Recently, elicitation of broadly neutralizing antibodies which target the conserved HA stalk domain has become a promising "universal" influenza virus vaccine strategy.

Broadly Neutralizing Hemagglutinin Stalk-Specific Antibodies Induce Potent Phagocytosis of Immune Complexes by Neutrophils in an Fc-Dependent Manner.

Unlabelled: Broadly neutralizing antibodies that recognize the conserved hemagglutinin (HA) stalk have emerged as exciting new biotherapeutic tools to combat seasonal and pandemic influenza viruses. Our general understanding of the mechanisms by which stalk-specific antibodies achieve protection is rapidly evolving. It has recently been demonstrated that broadly neutralizing HA stalk-specific IgG antibodies require Fc-Fcγ receptor (FcγR) interactions for optimal protection in vivo Here we examine the neutrophil effector functions induced by stalk-specific antibodies.

Optimal activation of Fc-mediated effector functions by influenza virus hemagglutinin antibodies requires two points of contact.

Influenza virus strain-specific monoclonal antibodies (mAbs) provide protection independent of Fc gamma receptor (FcγR) engagement. In contrast, optimal in vivo protection achieved by broadly reactive mAbs requires Fc-FcγR engagement. Most strain-specific mAbs target the head domain of the viral hemagglutinin (HA), whereas broadly reactive mAbs typically recognize epitopes within the HA stalk.

Autoimmune Variant PTPN22 C1858T Is Associated With Impaired Responses to Influenza Vaccination.

High-affinity-antibody production, T-cell activation, and interferon upregulation all contribute to protective immunity that occurs in humans following influenza immunization. Hematopoietic cell-specific PTPN22 encodes lymphoid phosphatase (Lyp), which regulates lymphocyte antigen receptor and pattern recognition receptor (PRR) signaling. A PTPN22 variant, R620W (LypW), predisposes to autoimmune and infectious diseases and confers altered signaling through antigen receptors and PRRs.