- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Renal and related cancers
- RNA Interference and Gene Delivery
- Neurobiology and Insect Physiology Research
- Nuclear reactor physics and engineering
- Epigenetics and DNA Methylation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer-related molecular mechanisms research
- Drug Transport and Resistance Mechanisms
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Animal Genetics and Reproduction
- Wastewater Treatment and Nitrogen Removal
- Pharmacological Effects and Toxicity Studies
- Phytochemical Studies and Bioactivities
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Natural product bioactivities and synthesis
- Pancreatic function and diabetes
- Metabolism and Genetic Disorders
- Diabetes Treatment and Management
- Aquaculture disease management and microbiota
- Marine and fisheries research
Kunming Children's Hospital
2024-2025
Guangdong Ocean University
2008-2025
Chinese University of Hong Kong
2015-2024
Argonne National Laboratory
2015-2024
Chinese University of Hong Kong, Shenzhen
2013-2024
Ruikang Affiliated Hospital of Guangxi Medical University
2024
Chinese Academy of Sciences
2018-2024
Shanxi Medical University
2024
Wenzhou Medical University
2015-2024
Guangxi University of Chinese Medicine
2024
Elucidating the key signal transduction pathways essential for both antipsychotic efficacy and side-effect profiles is developing safer more effective therapies. Recent work has highlighted noncanonical modes of dopamine D 2 receptor (D R) signaling via β-arrestins as being important therapeutic actions antimanic agents. We thus sought to create unique R agonists that display bias β-arrestin–ergic signaling. Through a robust diversity-oriented modification scaffold represented by...
CRISPR/Cas9-induced site-specific DNA double-strand breaks (DSBs) can be repaired by homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathways. Extensive efforts have been made to knock-in exogenous a selected genomic locus in human cells; which, however, has focused on HDR-based strategies and was proven inefficient. Here, we report that NHEJ pathway mediates efficient rejoining of genome plasmids following DSBs, promotes high-efficiency integration various cell types....
Antarctic krill (Euphausia superba) is Earth’s most abundant wild animal, and its enormous biomass vital to the Southern Ocean ecosystem. Here, we report a 48.01-Gb chromosome-level genome, whose large genome size appears have resulted from inter-genic transposable element expansions. Our assembly reveals molecular architecture of circadian clock uncovers expanded gene families associated with molting energy metabolism, providing insights into adaptations cold highly seasonal environment....
Antibody-mediated activation of fibroblast growth factor receptor 1 reverses the diabetic phenotype in mice, likely by affecting brown adipose tissues.
Although it is known that OCT4–NANOG are required for maintenance of pluripotent cells in vitro, the upstream signals regulate this circuit during early development vivo have not been identified. Here we demonstrate, first time, signal transducers and activators transcription 3 (STAT3)-dependent regulation circuitry necessary to maintain inner cell mass (ICM), source vitro-derived embryonic stem (ESCs). We show STAT3 highly expressed mouse oocytes becomes phosphorylated translocates nucleus...
The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 factors (TF) offered a powerful precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating stringently silenced pluripotency Oct4 (Pou5f1) mouse human somatic cells. First, with number TALEs sgRNAs targeting various regions promoters, found that most efficient TALE-VP64s...
Hepatocellular carcinomas (HCC) exhibit distinct promoter hypermethylation patterns, but the epigenetic regulation and function of transcriptional enhancers remain unclear. Here, our affinity- bisulfite-based whole-genome sequencing analyses reveal global enhancer hypomethylation in human HCCs. Integrative epigenomic characterization further pinpoints a recurrent hypomethylated CCAAT/enhancer-binding protein-beta (C/EBPβ) which correlates with C/EBPβ over-expression poorer prognosis...
Abstract Pyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents. While the molecular mechanisms its insecticidal action are known, basis pyrethrum repellency remains a mystery. In this study, we find that principal components pyrethrum, pyrethrins, minor component, (E)-β-farnesene (EBF), each activate specific type olfactory receptor neurons Aedes aegypti mosquitoes. We identify Ae. odorant 31 (AaOr31) as cognate Or for EBF...
Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both pancreas liver glucokinase, postprandial in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, efficacy safety of dorzagliatin as an add-on to metformin were assessed T2D who had inadequate glycemic control using alone. Eligible (n = 767)...
Macrophage death in advanced atherosclerotic lesions leads to lesional necrosis and likely promotes plaque instability, a precursor of acute vascular events. Macrophages accumulate large amounts unesterified cholesterol, which is potent inducer macrophage apoptosis. We have shown recently that induction apoptosis cultured macrophages requires cholesterol trafficking the endoplasmic reticulum (ER). Moreover, from mice with heterozygous mutation cholesterol-trafficking protein Npc1 selective...
In advanced atherosclerosis, macrophage foam cells progressively accumulate large amounts of unesterified or "free" cholesterol (FC), a process that is thought to contribute cell death and lesional necrosis. The cellular consequences early FC accumulation, including those lead further are poorly understood. this context, we show phospholipid efflux mediated by ABCA1, which initially induced in the cholesterol-loaded macrophage, was inhibited ∼80% pre-toxic FC-loaded macrophages. Cholesterol...
Treatment with the antidepressant nefazodone has been associated clinical idiosyncratic hepatotoxicty. Using membranes expressing human bile salt export pump (BSEP), sandwich hepatocytes, and intact rats, we compared its marketed analogs, buspirone trazodone. We found that caused a strong inhibition of BSEP (IC50 = 9 μM), taurocholate efflux in hepatocytes 14 transient increase rat serum acids 1 h after oral drug administration. Buspirone or trazodone had no effect on biliary transport...
Glucokinase is a key regulator of glucose homeostasis, and small molecule allosteric activators this enzyme represent promising opportunity for the treatment type 2 diabetes. Systemically acting glucokinase (liver pancreas) have been reported to be efficacious but in many cases present hypoglycaemia risk due activation at low levels pancreas, leading inappropriately excessive insulin secretion. It was therefore postulated that liver selective activator may offer effective glycemic control...