Rapid and accurate multi-phenotype imputation for millions of individuals.

Deep phenotyping can enhance the power of genetic analysis, including genome-wide association studies (GWAS), but the occurrence of missing phenotypes compromises the potential of such resources. Although many phenotypic imputation methods have been developed, the accurate imputation of millions of individuals remains challenging. In the present study, we have developed a multi-phenotype imputation method based on mixed fast random forest (PIXANT) by leveraging efficient machine learning (ML)-based algorithms.

Two new sesquiterpene eudesmanolides from the Raeusch.

Two new sesquiterpene eudesmanolides, 5-hydroxy-eudesman-7(11)-en-8(12)-olide (), and 5-hydroxy-7(11)-en-8-oxo-eudesmane (), along with six known sesquiterpene eudesmanolides, were isolated from the leaves and twigs of Raeusch. The structures of these compounds were established basis on NMR and MS spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated.

Tanreqing Injection Inhibits Activation of NLRP3 Inflammasome in Macrophages Infected with Influenza A Virus by Promoting Mitophagy.

Objective: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway.

Methods: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway.

PI3K/AKT mediated De novo fatty acid synthesis regulates RIG-1/MDA-5-dependent type I IFN responses in BVDV-infected CD8T cells.

Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8T lymphocytes obtained from healthy cattle with BVDV in vitro.

Functional analysis of differentially expressed circular RNAs in sheep subcutaneous fat.

Background: Circular RNAs (circRNAs), as important non-coding RNAs (ncRNAs), are involved in many biological activities. However, the exact chemical mechanism behind fat accumulation is unknown. In this paper, we obtained the expression profiles of circRNAs using high-throughput sequencing and investigated their differential expression in subcutaneous fat tissue of Duolang and Small Tail Han sheep.

Establishment and verification of a digital PCR assay for the detection of expression in quantitative analysis of circulating tumor cell.

The objective of this study was to establish and verify a digital PCR assay for the detection of gene expression, and to use it to detect circulating tumor cells (CTC) by taking advantages of its ultra-high sensitivity and absolute quantitation. Firstly, the primers and probes were designed according to the mRNA sequence of gene, and housekeeping gene was used as the internal control. The best candidate was screened by human breast cancer MCF7 cells and healthy human leukocytes from 13 sets of primer and probes and verified by direct sequencing.

Heterogenization of Salen Metal Molecular Catalysts in Covalent Organic Frameworks for Photocatalytic Hydrogen Evolution.

Integrating a molecular catalyst with a light harvester into a photocatalyst is an effective strategy for solar light conversion. However, it is challenging to establish a crystallized framework with well-organized connections that favour charge separation and transfer. Herein, we report the heterogenization of a Salen metal complex molecular catalyst into a rigid covalent organic framework (COF) through covalent linkage with the light-harvesting unit of pyrene for photocatalytic hydrogen evolution.

A Virtual Reality Platform for Context-Dependent Cognitive Research in Rodents.

Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.

Genome-Wide Analysis of microRNAs Identifies the Lipid Metabolism Pathway to Be a Defining Factor in Adipose Tissue From Different Sheep.

microRNAs are a class of important non-coding RNAs, which can participate in the regulation of biological processes. In recent years, miRNA has been widely studied not only in humans and mice, but also in animal husbandry. However, compared with other livestock and poultry breeds, the study of miRNA in subcutaneous adipose tissue of sheep is not comprehensive.

CK-3, A Novel Methsulfonyl Pyridine Derivative, Suppresses Hepatocellular Carcinoma Proliferation and Invasion by Blocking the PI3K/AKT/mTOR and MAPK/ERK Pathways.

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis that highly expresses phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (ERK). The PI3K/AKT/mTOR and MAPK/ERK signaling pathways play a crucial role in HCC tumor formation, cell cycle, apoptosis and survival. However, no effective targeted therapies against these pathways is available, mainly due to the extensive and complex negative feedback loops between them.

[Professor -' clinical experiences of "syndrome differentiation and Chinese herbal plaster application" based on meridian and theories].

Focusing on the limits of the plaster application of Chinese herbal medicine in clinical practice, i.e. limit in the region exerted, inadequate meridian effect, more attention to the exterior rather than the interior and limit in the application of differentiation, professor - proposes his clinical experiences in the plaster application of Chinese herbal medicine based on meridian and differentiation, including: The Chinese herbal plaster application alone meridian course guided by meridian differentiation.

Diagnosis and treatment of pure arterial malformation: Three case reports and literature review.

Rationale: The incidence of pure arterial malformations is relatively low, and few cases have been reported. Only 2 cases with pure arterial malformation have been reported to receive surgery or endovascular treatment.

Patient Concerns: We report 3 cases and review the relevant literatures.

Novel ADAM-17 inhibitor ZLDI-8 inhibits the proliferation and metastasis of chemo-resistant non-small-cell lung cancer by reversing Notch and epithelial mesenchymal transition in vitro and in vivo.

Acquired drug-resistant non-small cell lung cancer (NSCLC) has strong proliferation ability and is prone to epithelial-mesenchymal transition (EMT) and subsequent metastasis. Notch pathway mediates cell survival and EMT and is involved in the induction of multidrug resistance (MDR). ZLDI-8 is an inhibitor of Notch activating/cleaving enzyme ADAM-17 we found before.

In Silico Analyses for Key Genes and Molecular Genetic Mechanism in Epilepsy and Alzheimer's Disease.

Background: Epilepsy and Alzheimer's disease are common neuropathies with a complex pathogenesis. Both of them have some correlations in etiology, pathogenesis, pathological changes, clinical manifestations and treatment.

Objective: This study investigated the key genes and molecular genetic mechanism in epilepsy and Alzheimer's disease by bioinformatics analysis.

Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.

CD4 T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR.

Sterol O-acyltransferase 1 deficiency improves defective insulin signaling in the brains of mice fed a high-fat diet.

Insulin resistance induced by a high-fat diet (HFD) is related to metabolic diseases, and sterol O-acyltransferase 1 (SOAT1) is a key enzyme for the biosynthesis of cholesteryl ester. In the present study, wild-type (WT) mice and SOAT1-knockout (KO) mice with a C57BL6 background fed a HFD were used to explore the role of SOAT1 in the hypothalamus. The results show that the WT mice exhibited a significant increase in body weight as well as hepatic histologic changes; they also had a lower glucose and insulin tolerance than the WT mice fed a normal diet.

Massive rare desmoplastic fibroma of the ilium and ischium in a young adult: A case report.

Rationale: Desmoplastic fibroma (DF) is a rare, locally invasive but benign bone tumor. It represents one of the rarest bone diseases, with an incidence of only 0.11% of all primary bone tumors.

Frequent CpG island methylation: a risk factor in the progression of traditional serrated adenoma of the colorectum.

Background: Traditional serrated adenoma (TSA) features a unique serrated configuration because it involves two cell types: tall and short columnar cells. The serrated neoplasia pathway is related to the carcinogenesis of colorectal cancer. CpG island methylator phenotype-high (CIMP-high) is a unique genetic alteration in this pathway.

The Content of Statistical Requirements for Authors in Biomedical Research Journals.

Background: Robust statistical designing, sound statistical analysis, and standardized presentation are important to enhance the quality and transparency of biomedical research. This systematic review was conducted to summarize the statistical reporting requirements introduced by biomedical research journals with an impact factor of 10 or above so that researchers are able to give statistical issues' serious considerations not only at the stage of data analysis but also at the stage of methodological design.

Methods: Detailed statistical instructions for authors were downloaded from the homepage of each of the included journals or obtained from the editors directly via email.

BCR-ABL-specific CD4 T-helper cells promote the priming of antigen-specific cytotoxic T cells via dendritic cells.

The advent of tyrosine kinase inhibitor (TKI) therapy markedly improved the outcome of patients with chronic-phase chronic myeloid leukemia (CML). However, the poor prognosis of patients with advanced-phase CML and the lifelong dependency on TKIs are remaining challenges; therefore, an effective therapeutic has been sought. The BCR-ABL p210 fusion protein's junction region represents a leukemia-specific neoantigen and is thus an attractive target for antigen-specific T-cell immunotherapy.

Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells.

Vα24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer. Conversely, reduced iNKT cell numbers and function have been observed in many patients with cancer.

Generation of mouse pluripotent stem cell-derived proliferating myeloid cells as an unlimited source of functional antigen-presenting cells.

The use of dendritic cells (DC) to prime tumor-associated antigen-specific T-cell responses provides a promising approach to cancer immunotherapy. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can differentiate into functional DCs, thus providing an unlimited source of DCs. However, the previously established methods of generating practical volumes of DCs from pluripotent stem cells (PSC) require a large number of PSCs at the start of the differentiation culture.

Protective effects of daphnetin on sodium taurocholate‑induced severe acute pancreatitis in rats.

Severe acute pancreatitis (SAP) is the sudden onset of pancreatic inflammation, which is characterized by edema, acinar cell necrosis, hemorrhage and severe inflammation of the pancreas and is associated with a high mortality rate. Daphnetin has been shown to alleviate organ injury in a variety of preclinical animal models of coagulation disorders. The aim of the present study was to investigate the protective effects of daphnetin on severe acute pancreatitis in a rat model.

Repeated exposure of mouse dermal fibroblasts at a sub-cytotoxic dose of UVB leads to premature senescence: a robust model of cellular photoaging.

Background: Photoaging skin is due to accumulative effect of UV irradiation that mainly imposes its damage on dermal fibroblasts. To mimic the specific cellular responses invoked by long term effect of UVB, it is preferable to develop a photo-damaged model in vitro based on repeated UVB exposure instead of a single exposure.

Objective: To develop a photo-damaged model of fibroblasts by repeated UVB exposure allowing for investigation of molecular mechanism underlying premature senescence and testing of potential anti-photoaging compounds.