An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19.

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19.

Impact of a Gold Nanocolloid Electrolyte on LiO Morphology and Performance of a Lithium-Oxygen Battery.

Aprotic lithium-oxygen batteries currently suffer from poor cyclic stability and low achievable energy density. Herein, gold nanoparticles capped with mercaptosuccinic acid are dispersed in 1.0 M LiClO/dimethyl sulfoxide (DMSO) as a novel electrolyte for lithium-oxygen batteries.

The L1 cell adhesion molecule affects protein kinase D1 activity in the cerebral cortex in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by deposition of β-amyloid protein (Aβ), neurofibrillary tangles and cognitive deficits resulting from neuronal cell death. In search for the molecular underpinnings of the disease, we were interested in the relationship between Aβ, L1 cell adhesion molecule and protein kinase D1 (PKD1), which are not only implicated in neural development and functional maintenance in the adult, but are also neuroprotective under pathological conditions. Based on our observations that L1 and phosphorylated, i.

The solute carrier transporters and the brain: Physiological and pharmacological implications.

Solute carriers (SLCs) are the largest family of transmembrane transporters that determine the exchange of various substances, including nutrients, ions, metabolites, and drugs across biological membranes. To date, the presence of about 287 SLC genes have been identified in the brain, among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain disorders. Although increasing interest in SLCs have focused on drug development, SLCs are currently still under-explored as drug targets, especially in the brain.

L1CAM Beneficially Inhibits Histone Deacetylase 2 Expression under Conditions of Alzheimer's Disease.

Background: Cognitive capacities in Alzheimer's Disease (AD) are impaired by an epigenetic blockade mediated by histone deacetylase 2 (HDAC2), which prevents the transcription of genes that are important for synaptic plasticity.

Objective: Investigation of the functional relationship between cell adhesion molecule L1 and HDAC2 in AD.

Methods: Cultures of dissociated cortical and hippocampal neurons from wild-type or L1-deficient mice were treated with Aβ1-42 for 24 h.

Glioma malignancy is linked to interdependent and inverse AMOG and L1 adhesion molecule expression.

Background: Gliomas account for the majority of primary human brain tumors and remain a challenging neoplasm for cure due to limited therapeutic options. Cell adhesion molecules play pivotal roles in the growth and progression of glial tumors. Roles of the adhesion molecules on glia (AMOG) and L1CAM (L1) in glioma cells have been shown to correlate with tumorigenesis: Increased expression of L1 and decreased expression of AMOG correlate with degree of malignancy.

Identification and characterization of synthetic chondroitin-4-sulfate binding peptides in neuronal functions.

Chondroitin sulfate proteoglycans (CSPGs), up-regulated in and around the glial scar after mammalian spinal cord injury, have been suggested to be key inhibitory molecules for functional recovery by impeding axonal regrowth/sprouting and synaptic rearrangements. CSPG-mediated inhibition is mainly associated with the glycosaminoglycan chains of CSPGs, and chondroitin-4-sulfate (C4S) is the predominant sulfated structure that regulates axonal guidance and growth in the adult nervous system. With the aim to find molecules that neutralize the inhibitory functions of C4S, we screened a phage display library for peptides binding to C4S.

CHL1 Is Expressed and Functions as a Malignancy Promoter in Glioma Cells.

The cell adhesion molecule with homology to L1CAM (close homolog of L1) (CHL1) is a member of the cell adhesion molecule L1 (L1CAM) gene family. Although CHL1 expression and function have been reported in several tumors, the roles of CHL1 in the development of glioma remain unclear. In the present study, we investigated the effects of CHL1 on proliferation indexes and activation of Akt1 and Erk signaling by siRNA in U-87 MG human glioblastoma and human U251 and SHG-44 glioma cells.

Trimebutine, a small molecule mimetic agonist of adhesion molecule L1, contributes to functional recovery after spinal cord injury in mice.

Curing spinal cord injury (SCI) in mammals is a daunting task because of the lack of permissive mechanisms and strong inhibitory responses at and around the lesion. The neural cell adhesion molecule L1CAM (L1) has been shown to favor axonal regrowth and enhance neuronal survival and synaptic plasticity but delivery of full-length L1 or its extracellular domain could encounter difficulties in translation to therapy in humans. We have, therefore, identified several small organic compounds that bind to L1 and stimulate neuronal survival, neuronal migration and neurite outgrowth in an L1-dependent manner.

Neuregulin-1 protects mouse cerebellum against oxidative stress and neuroinflammation.

Cerebellum undergoes degenerative changes in neurodegenerative diseases. Two main factors including oxidative stress and neuroinflammation mediate neurodegeneration. Neuregulin-1 (Nrg1) has been implicated in many neurodegenerative diseases, while the underlying mechanisms are unknown.

Neuregulin-1 (Nrg1) signaling has a preventive role and is altered in the frontal cortex under the pathological conditions of Alzheimer's disease.

Alzheimer's disease (AD), one of the neurodegenerative disorders that may develop in the elderly, is characterized by the deposition of β‑amyloid protein (Aβ) and extensive neuronal cell death in the brain. Neuregulin‑1 (Nrg1)‑mediated intercellular and intracellular communication via binding to ErbB receptors regulates a diverse set of biological processes involved in the development of the nervous system. In the present study, a linear correlation was identified between Nrg1 and phosphorylated ErbB (pNeu and pErbB4) receptors in a human cortical tissue microarray.

Differential changes in Neuregulin-1 signaling in major brain regions in a lipopolysaccharide-induced neuroinflammation mouse model.

Neuregulin 1 (Nrg1) is involved in multiple biological processes in the nervous system. The present study investigated changes in Nrg1 signaling in the major brain regions of mice subjected to lipopolysaccharide (LPS)-induced neuroinflammation. At 24 h post‑intraperitoneal injection of LPS, mouse brain tissues, including tissues from the cortex, striatum, hippocampus and hypothalamus, were collected.

L1.2, the zebrafish paralog of L1.1 and ortholog of the mammalian cell adhesion molecule L1 contributes to spinal cord regeneration in adult zebrafish.

Purpose: The aim of the study was to investigate the functional role of L1.2, the zebrafish paralog of L1.1 and ortholog of mammalian L1CAM in adult zebrafish spinal cord regeneration after injury.

China's postgraduate education practices and its academic impact on publishing: is it proportional?

Though postgraduate education started before the founding of new China in 1949, it was not until the implementation of the policy reform and the opening-up in 1978 that China's postgraduate productivity began to take off. Since the introduction of Regulations of the People's Republic of China on Academic Degrees in 1981, the number of graduate students enrolled each year has increased 50 times since 1978. China is now the second largest producer of publications indexed by the database of Science Citation Index (SCI) (Web of Science™, Thomson Reuters), which reflects great strides being made in the postgraduate education.

L1 modulates PKD1 phosphorylation in cerebellar granule neurons.

The neural cell adhesion molecule L1 (L1CAM) is crucial for the development of the nervous system, with an essential role in regulating multiple cellular activities. Protein kinase D1 (PKD1) serves as a key kinase given its diverse array of functions within the cell. Here, we investigated various aspects of the functional relationship between L1 and phosphorylated PKD1 (pPKD1) in cerebellar granule neurons.