An increasing number of studies have shown that lncRNAs are crucial for the control of hormones and the regulation of various physiological processes in the human body, and deletion mutations in RNA ...are related to many human diseases. LncRNA- disease association prediction is very useful for understanding pathogenesis, diagnosis, and prevention of diseases, and is helpful for labelling relevant biological information. In this manuscript, we propose a computational model named bidirectional generative adversarial network (BiGAN), which consists of an encoder, a generator, and a discriminator to predict new lncRNA-disease associations. We construct features between lncRNA and disease pairs by utilizing the disease semantic similarity, lncRNA sequence similarity, and Gaussian interaction profile kernel similarities of lncRNAs and diseases. The BiGAN maps the latent features of similarity features to predict unverified association between lncRNAs and diseases. The computational results have proved that the BiGAN performs significantly better than other state-of-the-art approaches in cross-validation. We employed the proposed model to predict candidate lncRNAs for renal cancer and colon cancer. The results are promising. Case studies show that almost 70% of lncRNAs in the top 10 prediction lists are verified by recent biological research. The experimental results indicated that our proposed model had an accurate predictive ability for the association of lncRNA-disease pairs.
Fibroblast growth factor (FGF) belongs to a large family of growth factors. FGFs use paracrine or endocrine signaling to mediate a myriad of biological and pathophysiological process, including ...angiogenesis, wound healing, embryonic development, and metabolism regulation. FGF drugs for the treatment of burn and ulcer wounds are now available. The recent discovery of the crucial roles of the endocrine-acting FGF19 subfamily in maintaining homeostasis of bile acid, glucose, and phosphate further extended the activity profile of this family. Here, the applications of recombinant FGFs for the treatment of wounds, diabetes, hypophosphatemia, the development of FGF receptor inhibitors as anti-neoplastic drugs, and the achievements of basic research and applications of FGFs in China are reviewed.
Incredible accomplishments have been achieved in agricultural production in China, but many demanding challenges for ensuring food security and environmental sustainability remain. Field experiments ...were conducted from 2011-2013 at three different sites, including Honghu, Shayang, and Jingzhou in China, to determine the effects of fertilization on enhancing crop productivity and indigenous nutrient-supplying capacity (INuS) in a rice (Oryza sativa L.)-rapeseed (Brassica napus L.) rotation. Four mineral fertilizer treatments (NPK, NP, NK and PK) were applied in a randomized complete block design with three replicates. Crop yields were increased by 19-41% (rice) and 61-76% (rapeseed) during the two years of rice-rapeseed rotation under NPK fertilization compared to PK fertilization across the study sites. Yield responses to fertilization were ranked NPK > NP > NK > PK, illustrating that N deficiency was the most limiting condition in a rice-rapeseed rotation, followed by P and K deficiencies. The highest and lowest N, P and K accumulations were observed under NPK and PK fertilization, respectively. The INuS of the soil decreased to a significant extent and affected rice-rapeseed rotation productivity at each site under NP, NK, and PK fertilization when compared to NPK. Based on the study results, a balanced nutrient application using NPK fertilization is a key management strategy for enhancing rice-rapeseed productivity and environmental safety.
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•N-acetyl-l-cysteine-stabilized Ag nanoparticles are synthesized by a chemical reduction method.•The surface plasmon resonance intensity of the silver nanoparticles decreases with ...Fe3+ concentration.•The silver nanoparticles can be used for sensitive and selective detection of Fe3+ ions in water.•A new detection mechanism of oxidation–reduction reaction between Ag NPs and Fe3+ ions is proposed.
We report here a facile colorimetric sensor based on the N-acetyl-l-cysteine (NALC)-stabilized Ag nanoparticles (NALC–Ag NPs) for detection of Fe3+ ions in aqueous solution. The Ag NPs with an average diameter of 6.55±1.0nm are successfully synthesized through a simple method using sodium borohydride as reducing agent and N-acetyl-l-cysteine as protecting ligand. The synthesized silver nanoparticles show a strong surface plasmon resonance (SPR) around 400nm and the SPR intensity decreases with the increasing of Fe3+ concentration in aqueous solution. Based on the linear relationship between SPR intensity and concentration of Fe3+ ions, the as-synthesized water-soluble silver nanoparticles can be used for the sensitive and selective detection of Fe3+ ions in water with a linear range from 80nM to 80μM and a detection limit of 80nM. On the basis of the experimental results, a new detection mechanism of oxidation–reduction reaction between Ag NPs and Fe3+ ions is proposed, which is different from previously reported mechanisms. Moreover, the NALC–Ag NPs could be applied to the detection of Fe3+ ions in real environmental water samples.
Obesity increases the risk for a number of diseases including cardiovascular diseases and type 2 diabetes. Excess saturated fatty acids (SFAs) in obesity play a significant role in cardiovascular ...diseases by activating innate immunity responses. However, the mechanisms by which SFAs activate the innate immune system are not fully known. Here we report that palmitic acid (PA), the most abundant circulating SFA, induces myocardial inflammatory injury through the Toll-like receptor 4 (TLR4) accessory protein MD2 in mouse and cell culture experimental models. Md2 knockout mice are protected against PA- and high-fat diet-induced myocardial injury. Studies of cell surface binding, cell-free protein-protein interactions and molecular docking simulations indicate that PA directly binds to MD2, supporting a mechanism by which PA activates TLR4 and downstream inflammatory responses. We conclude that PA is a crucial contributor to obesity-associated myocardial injury, which is likely regulated via its direct binding to MD2.
Endocrine fibroblast growth factors (eFGFs) control pathways that are crucial for maintaining metabolic homeostasis of lipids, glucose, energy, bile acids, and minerals. Unlike the heparin-binding ...paracrine FGFs, eFGFs require a unique Klotho family protein to form a productive triad complex, but the structural and mechanistical details of this complex have remained obscure since the beginning of the eFGF field. However, recent breakthroughs in resolving the 3D structures of eFGF signaling complexes have now unveiled the atomic details of multivalent interactions among eFGF, FGFR, and Klotho. We provide here a timely review on the architecture and the structure–function relationships of these complexes, and highlight how the structural knowledge opens a new door to structure-based drug design against a repertoire of eFGF-associated metabolic diseases.
eFGFs are key regulators of metabolic homeostasis of lipids, glucose, energy, bile acids, and minerals.
Alterations in the components of eFGF signaling complex underlie a myriad of metabolic diseases.
The recently resolved crystal structures of eFGF signaling complexes open a new door for structure-based drug design.
Klotho (or betaKlotho), through its pseudo-catalytic pocket and receptor-binding arm, serves as a scaffold to tether eFGF to FGFR.
With an FDA-approved FGF23-based drug in the market, several other eFGF analogs and FGFR–KL/KLB agonists are on the horizon for various metabolic diseases.
Spinal cord injury (SCI) possesses a significant health and economic burden worldwide. Traumatic SCI is a devastating condition that evolves through two successive stages. Throughout each of these ...stages, disturbances in ionic homeostasis, local oedema, ischaemia, focal haemorrhage, free radicals stress and inflammatory response were observed. Although there are no fully restorative cures available for SCI patients, various molecular, cellular and rehabilitative therapies, such as limiting local inflammation, preventing secondary cell death and enhancing the plasticity of local circuits in the spinal cord, were described. Current preclinical studies have showed that fibroblast growth factors (FGFs) alone or combination therapies utilizing cell transplantation and biomaterial scaffolds are proven effective for treating SCI in animal models. More importantly, some studies further demonstrated a paucity of clinical transfer usage to promote functional recovery of numerous patients with SCI. In this review, we focus on the therapeutic capacity and pitfalls of the FGF family and its clinical application for treating SCI, including the signalling component of the FGF pathway and the role in the central nervous system, the pathophysiology of SCI and the targets for FGF treatment. We also discuss the challenges and potential for the clinical translation of FGF‐based approaches into treatments for SCI.
Pluripotent stem cells (PSCs) isolated
from embryonic stem cells (ESCs), induced PSC (iPSC) and also post-implantation epiblast-derived stem cells (EpiSCs) are known for their two unique ...characteristics: the ability to give rise to all somatic lineages and the self-renewal capacity. Numerous intrinsic signaling pathways contribute to the maintenance of the pluripotency state of stem cells by tightly controlling key transcriptional regulators of stemness including sex determining region Y box 2 (Sox-2), octamer-binding transcription factor (Oct)3/4, krueppel-like factor 4 (Klf-4), Nanog, and c-Myc. Signaling by fibroblast growth factor (FGF) is of critical importance in regulating stem cells pluripotency. The FGF family is comprised of 22 ligands that interact with four FGF receptors (FGFRs). FGF/FGFR signaling governs fundamental cellular processes such as cell survival, proliferation, migration, differentiation, embryonic development, organogenesis, tissue repair/regeneration, and metabolism. FGF signaling is mediated by the activation of RAS - mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT, Phospholipase C Gamma (PLCγ), and signal transducers and activators of transcription (STAT), which intersects and synergizes with other signaling pathways such as Wnt, retinoic acid (RA) and transforming growth factor (TGF)-β signaling. In the current review, we summarize the role of FGF signaling in the maintenance of pluripotency state of stem cells through regulation of key transcriptional factors.
In recent years, metal–organic frameworks (MOFs) have been extensively investigated for diverse heterogeneous catalysis due to their diversity of structures and outstanding physical and chemical ...properties. Currently, most related work focuses on employing MOFs as porous substrate materials to fabricate confined nanoparticle or heteroatom-doped electrocatalysts which have to be annealed at high temperature before application. However, the annealing process would destroy the structure completely and lose the intrinsic active sites in MOFs framework. Herein, a simple solvothermal process is used to synthesize a series of Fe/Ni bimetallic MOFs. The as-prepared MOFs are applied directly as highly efficient oxygen evolution reaction (OER) electrocatalysts with no post-annealing treatment. The bimetallic FeNi-MOFs show higher OER activity than single metal MOFs and commercial precious RuO2 catalysts. With the optimized FeNi-MOF as the catalyst, the OER current densities of 50 and 100 mA/cm2 can be achieved at the overpotentials of only 270 and 287 mV, respectively. Meanwhile, a small Tafel slope of 49 mV/dec was obtained. Moreover, this catalyst shows high electrochemical stability in strong basic solution. This work demonstrates that through structural optimization, bimetallic and multimetallic MOFs may have promising potentials as advanced catalysts for electrochemical energy conversion.
: Autophagy in Schwann cells (SCs) is crucial for myelin debris degradation and clearance following peripheral nerve injury (PNI). Nerve growth factor (NGF) plays an important role in reconstructing ...peripheral nerve fibers and promoting axonal regeneration. However, it remains unclear if NGF effect in enhancing nerve regeneration is mediated through autophagic clearance of myelin debris in SCs.
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, free NGF solution plus with/without pharmacological inhibitors were administered to a rat sciatic nerve crush injury model.
, the primary Schwann cells (SCs) and its cell line were cultured in normal medium containing NGF, their capable of swallowing or clearing degenerated myelin was evaluated through supplement of homogenized myelin fractions.
: Administration of exogenous NGF could activate autophagy in dedifferentiated SCs, accelerate myelin debris clearance and phagocytosis, as well as promote axon and myelin regeneration at early stage of PNI. These NGF effects were effectively blocked by autophagy inhibitors. In addition, inhibition of the p75 kD neurotrophin receptor (p75
) signal or inactivation of the AMP-activated protein kinase (AMPK) also inhibited the NGF effect as well.
: NGF effect on promoting early nerve regeneration is closely associated with its accelerating autophagic clearance of myelin debris in SCs, which probably regulated by the p75
/AMPK/mTOR axis. Our studies thus provide strong support that NGF may serve as a powerful pharmacological therapy for peripheral nerve injuries.
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