Uncovering receptor-ligand interactions using a high-avidity CRISPR activation screening platform.

The majority of clinically approved drugs target proteins that are secreted or cell surface bound. However, further advances in this area have been hindered by the challenging nature of receptor deorphanization, as there are still many secreted and cell-bound proteins with unknown binding partners. Here, we developed an advanced screening platform that combines CRISPR-CAS9 guide-mediated gene activation (CRISPRa) and high-avidity bead-based selection.

Engineering CD276/B7-H3-targeted antibody-drug conjugates with enhanced cancer-eradicating capability.

CD276/B7-H3 represents a promising target for cancer therapy based on widespread overexpression in both cancer cells and tumor-associated stroma. In previous preclinical studies, CD276 antibody-drug conjugates (ADCs) exploiting a talirine-type pyrrolobenzodiazepine (PBD) payload showed potent activity against various solid tumors but with a narrow therapeutic index and dosing regimen higher than that tolerated in clinical trials using other antibody-talirine conjugates. Here, we describe the development of a modified talirine PBD-based fully human CD276 ADC, called m276-SL-PBD, that is cross-species (human/mouse) reactive and can eradicate large 500-1,000-mm triple-negative breast cancer xenografts at doses 10- to 40-fold lower than the maximum tolerated dose.

The role of HIRA-dependent H3.3 deposition and its modifications in the somatic hypermutation of immunoglobulin variable regions.

The H3.3 histone variant and its chaperone HIRA are involved in active transcription, but their detailed roles in regulating somatic hypermutation (SHM) of immunoglobulin variable regions in human B cells are not yet fully understood. In this study, we show that the knockout (KO) of HIRA significantly decreased SHM and changed the mutation pattern of the variable region of the immunoglobulin heavy chain (IgH) in the human Ramos B cell line without changing the levels of activation-induced deaminase and other major proteins known to be involved in SHM.

A Bayesian model based computational analysis of the relationship between bisulfite accessible single-stranded DNA in chromatin and somatic hypermutation of immunoglobulin genes.

The B cells in our body generate protective antibodies by introducing somatic hypermutations (SHM) into the variable region of immunoglobulin genes (IgVs). The mutations are generated by activation induced deaminase (AID) that converts cytosine to uracil in single stranded DNA (ssDNA) generated during transcription. Attempts have been made to correlate SHM with ssDNA using bisulfite to chemically convert cytosines that are accessible in the intact chromatin of mutating B cells.

Role of Dot1L and H3K79 methylation in regulating somatic hypermutation of immunoglobulin genes.

Somatic hypermutation (SHM) and class-switch recombination (CSR) of the immunoglobulin (Ig) genes allow B cells to make antibodies that protect us against a wide variety of pathogens. SHM is mediated by activation-induced deaminase (AID), occurs at a million times higher frequency than other mutations in the mammalian genome, and is largely restricted to the variable (V) and switch (S) regions of Ig genes. Using the Ramos human Burkitt's lymphoma cell line, we find that H3K79me2/3 and its methyltransferase Dot1L are more abundant on the V region than on the constant (C) region, which does not undergo mutation.

[The Effect of 4 2 Polymorphism on Initial Warfarin Dose in Patients with Heart Valve Replacement].

Objective: To study the effect of cytochrome P-4504F2 ( 4 2) gene polymorphism on the initial dose of warfarin in patients after mechanical heart valve replacement.

Methods: We collected 350 patients receiving warfarin after mechanical heart valve replacement from January 2013 to December 2015 in our hospital. According to the international standardized ratio (INR) ≥2 at the initial stage after surgery, the patients were divided into two groups: INR≥2 group and INR<2 group.

Long non-coding RNA HOTAIR functions as a competitive endogenous RNA to regulate PRAF2 expression by sponging miR-326 in cutaneous squamous cell carcinoma.

Background: LncRNAs may exert a regulatory effect in tumorigenesis. Although the expression of lncRNA has been confirmed to be notably elevated in the tissues of CSCC, its biological mechanism in CSCC is still unknown.

Methods: expression level in CSCC cell lines was monitored via qRT-PCR.

Tumor stroma-targeted antibody-drug conjugate triggers localized anticancer drug release.

Although nonmalignant stromal cells facilitate tumor growth and can occupy up to 90% of a solid tumor mass, better strategies to exploit these cells for improved cancer therapy are needed. Here, we describe a potent MMAE-linked antibody-drug conjugate (ADC) targeting tumor endothelial marker 8 (TEM8, also known as ANTXR1), a highly conserved transmembrane receptor broadly overexpressed on cancer-associated fibroblasts, endothelium, and pericytes. Anti-TEM8 ADC elicited potent anticancer activity through an unexpected killing mechanism we term DAaRTS (drug activation and release through stroma), whereby the tumor microenvironment localizes active drug at the tumor site.

Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells.

Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggested by the extraordinary high frequency of mutation, insertion, and deletion in the broadly neutralizing HIV antibodies. Since HIV does not infect B cells, the molecular mechanisms of this genomic instability remain to be fully defined.

AANL (Agrocybe aegerita lectin 2) is a new facile tool to probe for O-GlcNAcylation.

O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm. O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization. However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research.

Deregulation of miR-183 promotes melanoma development via lncRNA MALAT1 regulation and ITGB1 signal activation.

Dysregulation of miR-183 has been recently elucidated in several carcinomas. However, the expression patterns and mechanisms of miR-183 involved in malignant melanoma remain unidentified. Here, we found down-regulation of miR-183 in melanoma tissues and cells.

Clinical study of Shengxuening tablet combined with rHuEPO for the treatment of renal anemia of maintenance hemodialysis patients.

The aim of the present study was to investigate the clinical effects of Shengxuening tablet (silkworm excrement) combined with recombinant human erythropoietin (rHuEPO) for the treatment of renal anemia of maintenance hemodialysis (MHD) patients. Seventy-two MHD patients with renal anemia were included in the study and randomly divided into the control (n=34) and observation (n=38) groups. Patients in the control group were treated by hypodermic injection of 100-150 U/(kg·w) rHuEPO and patients in the observation group were treated by rHuEPO + 1.

Autophagy Inhibits Apoptosis Induced by agrocybe aegerita Lectin in Hepatocellular Carcinoma.

Background: Lectins are carbohydrate-binding proteins that exhibit remarkable antitumor activities by inducing apoptotic or autophagic cell death. However, the relationship between apoptosis and autophagy induced by lectins has rarely been reported. Agrocybe aegerita lectin (AAL), a lectin isolated from the fungus Agrocybe aegerita, exerts antitumor activity through apoptosis.

Identification of GlcNAcylated alpha-1-antichymotrypsin as an early biomarker in human non-small-cell lung cancer by quantitative proteomic analysis with two lectins.

Background: Non-small-cell lung cancer (NSCLC) is the main type of lung cancer with high mortality rates in worldwide. There is a need to identify better biomarkers to detect NSCLC at an early stage as this will improve therapeutic effect and patient survival rates.

Methods: Two lectins (AAL/AAGL and AAL2/AANL), which specifically bind to tumour-related glycan antigens, were first used to enrich serum glycoproteins from the serum of early NSCLC patients, benign lung diseases subjects and healthy individuals.

Conversion of cycloalk-2-enones into 2-methylcycloalkane-1,3-diones--assessment of various Tamao-Fleming procedures and mechanistic insight into the use of the Me3SiMe2Si unit.

Conjugate addition of Me3SiMe2SiLi to cycloalk-2-en-1-ones, ketalization, Tamao-Fleming oxidation (Bu4NF, then H2O2, KHCO3), TPAP oxidation and acid hydrolysis generates 2-methyl cycloalkane-1,3-diones. Ketalization is needed in order to prevent addition of Me3Si(-) to the carbonyl. The pentamethyldisilanyl group has advantages over other silicon units that are used in Tamao-Fleming procedures.

[EFFECTS OF INTERMITTENT IRRIGATION OF INSULIN SOLUTION COMBINED WITH CONTINUOUS DRAINAGE OF VACUUM SEALING DRAINAGE IN CHRONIC DIABETIC LOWER LIMB ULCERS].

Objective: To investigate the effects of intermittent irrigation of insulin solution combined with continuous drainage of vacuum sealing drainage (VSD) in chronic diabetic lower limb ulcers.

Methods: Between January 2012 and December 2014, 45 patients with diabetic lower limb ulcer were treated with VSD (group A, n=15), with VSD combining irrigation of normal saline (group B, n=15), and with VSD combining irrigation of insulin solution (group C, n=15) after debridement. There was no significant difference in gender, age, course of ulcers, area and depth of wound, glycosylated hemoglobin, and Wagner grade among 3 groups (P>0.

A novel protein with anti-metastasis activity on 4T1 carcinoma from medicinal fungus Cordyceps militaris.

Cordyceps militaris is a famous fungus used in traditional Chinese medicine for nearly one thousand years. And its fruiting body is known to possess anticancer and immunomodulatory activities. This study describes the isolation, characterization, and test of antitumor activity of a C.

Fibrous hamartoma of infancy: a clinical pathological analysis of seventeen cases.

To discuss the clinical and pathological features, differential diagnosis and prognosis of fibrous hamartoma of infancy (FHI), seventeen FHI specimens were analyzed with H&E staining and strepavidin peroxidase (SP) immunohistochemistry to detect distinguishing tissue markers. The long-term outcomes of select cases were also obtained. Among the 17 patients (13 males, 4 females, average age 16 months), FHI manifested as a subcutaneous painless mass, primarily on the back of the neck, the upper arms and buttocks.

Proteome exploration to provide a resource for the investigation of Ganoderma lucidum.

Ganoderma lucidum is a basidiomycete white rot fungus that has been used for medicinal purposes worldwide. Although information concerning its genome and transcriptome has recently been reported, relatively little information is available for G. lucidum at the proteomic level.

Genome analysis of medicinal Ganoderma spp. with plant-pathogenic and saprotrophic life-styles.

Ganoderma is a fungal genus belonging to the Ganodermataceae family and Polyporales order. Plant-pathogenic species in this genus can cause severe diseases (stem, butt, and root rot) in economically important trees and perennial crops, especially in tropical countries. Ganoderma species are white rot fungi and have ecological importance in the breakdown of woody plants for nutrient mobilization.

Inhibition of hepatitis B virus gene expression and replication by hepatocyte nuclear factor 6.

Unlabelled: Hepatitis B virus (HBV), a small enveloped DNA virus, chronically infects more than 350 million people worldwide and causes liver diseases from hepatitis to cirrhosis and liver cancer. Here, we report that hepatocyte nuclear factor 6 (HNF6), a liver-enriched transcription factor, can inhibit HBV gene expression and DNA replication. Overexpression of HNF6 inhibited, while knockdown of HNF6 expression enhanced, HBV gene expression and replication in hepatoma cells.

CeCaFDB: a curated database for the documentation, visualization and comparative analysis of central carbon metabolic flux distributions explored by 13C-fluxomics.

The Central Carbon Metabolic Flux Database (CeCaFDB, available at http://www.cecafdb.org) is a manually curated, multipurpose and open-access database for the documentation, visualization and comparative analysis of the quantitative flux results of central carbon metabolism among microbes and animal cells.

Lethal protein in mass consumption edible mushroom Agrocybe aegerita linked to strong hepatic toxicity.

Edible mushrooms are well-known for their health and nutritional benefits, however, undesirable effects have been reported in animals fed with these types of edible mushrooms (Nieminen et al., 2009). For health and safety reason, it is necessary to evaluate the toxicity of edible mushrooms, especially those that have been artificially cultured in recent decades.

Transcriptome and proteome exploration to provide a resource for the study of Agrocybe aegerita.

Background: Agrocybe aegerita, the black poplar mushroom, has been highly valued as a functional food for its medicinal and nutritional benefits. Several bioactive extracts from A. aegerita have been found to exhibit antitumor and antioxidant activities.