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Ischemia/reperfusion injury (I/R) is the main causes of acute kidney injury (AKI), which is a global health concern. Evidence suggests that asiaticoside plays vital roles on anti-inflammatory and, anti-kidney fibrosis effects, and promotes tissue repair. However, the effects of asiaticoside on AKI caused by ischemia-reperfusion have not been well defined. Herein, we explored the protective effect of asiaticoside on renal ischemia-reperfusion injury (IRI) using in vivo and in vitro studies, and elucidated the potential mechanism of asiaticoside-mediated repair. Results showed that asiaticoside attenuated the levels of blood urea nitrogen (BUN) and serum creatinine (Scr) in the IRI model. Meanwhile, asiaticoside reduced the secretion of IL-6, IL-1β and TNF-α, but increased IL-10 secretion in a dose-dependent manner. Treating Raw264.7 cells with lipopolysaccharide (LPS) induced an inflammatory response, but the LPS-induced effects were attenuated after administering asiaticoside. Furthermore, asiaticoside significantly inhibited the expression of inducible Nitric Oxide Synthase (iNOS) and promoted the expression of Arginase1 induced by LPS, which are the polarization marker proteins. In conclusion, this study shows that asiaticoside possesses protective action in AKI after ischemia-reperfusion, due to the inhibition of inflammatory mediators and promoting transformation of macrophages from M1 type to M2 type.

As newly developed 2D materials, due to their advanced physical/chemical properties and potential applications in energy storage, electromagnetic interference shielding, electronics and photon-detectors, MXenes have attracted extensive attention in recent years. MXenes are synthesized by selectively etching the A element from MAX phases using hydrochloric acid and lithium fluoride, so hardly any pure structures of MXenes (

Lung cancer is one of the most common solid tumors worldwide and the leading cause of cancer-related deaths, causing a devastating impact on human health. The clinical prognosis of lung cancer is usually restricted by delayed diagnosis and resistance to anticancer therapies. MicroRNAs, a range of small endogenous noncoding RNAs 22 nucleotides in length, have emerged as one of the most important players in cancer initiation and progression in recent decades. Current evidence reveals pivotal roles of microRNAs in regulating cell proliferation, migration, invasion and metastasis in lung cancer. An increasing number of preclinical and clinical studies have also explored the potential of microRNAs as promising biomarkers and new therapeutic targets for lung cancer. The current review summarizes the most recent progress on the functional mechanisms of microRNAs involved in lung cancer development and progression and further discusses the clinical application of miRNAs as putative therapeutic targets for molecular diagnosis and prognostic prediction in lung cancer.

Realizing a densely packed waveguide antenna array is of great importance in light detection and ranging (LIDAR), owing to its suppressed grating lobes. In this work, a low-cross-talk half-wavelength pitch silicon waveguide array is proposed and experimentally demonstrated. It has a periodic arrangement of silicon strip nanophotonic waveguides, between which deep-subwavelength silicon strips are placed. Our experimental results show that this array’s cross talk suppression is nearly 20 dB and has a bandwidth covering a wavelength range from 1500 nm to 1560 nm. Our realization of a half-wavelength pitch waveguide array may offer a promising platform for studying integrated optical phased arrays for solid-state LIDAR with a very low grating lobe and thus potentially a large field of view.

The inflammatory response has been implicated in various cardiac and systemic diseases. Epigallocatechin-3-gallate (EGCG), the major polyphenol extracted from green tea, has various biological and pharmacological properties, such as anti-inflammation, anti-oxidative and anti-tumorigenesis. To some extent, the mechanism of EGCG in the inflammatory response that characterizes myocardial dysfunction is not fully understood. The present study aimed to investigate the inhibiting effect of EGCG on lipopolysaccharide (LPS)-induced inflammation in vitro. Treatment with LPS affected rat H9c2 cardiomyocytes and induced an inflammatory response. However, the LPS-induced effects were attenuated after treatment with EGCG. The present results demonstrated that EGCG treatment repressed several inflammatory mediators, such as vascular endothelial growth factor, chemokine ligand 5, chemokine ligand 2, intercellular adhesion molecule-1, matrix metalloproteinase-2, tumor necrosis factor-α and nitric oxide (induced by LPS), and the repressing effect of EGCG on inflammatory response was dose-dependent in the range of 6.25-100 µM. EGCG inhibited these marked inflammatory key signaling molecules by reducing the expression of phospho-nuclear factor-κB p65, -Akt, -ERK and -MAPK p38 while the total protein level of these signal proteins were not affected. In conclusion, the present findings suggested that EGCG possesses cardiomyocyte-protective action in reducing the LPS-induced inflammatory response due to the inhibition of the phosphorylation of Akt and ERK signaling molecules.

Purpose. Peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in the control of lipid homeostasis. Here, we investigated the effects of CP775146, a new selective PPARα agonist, on lipid metabolism in diet-induced obese mice and its possible mechanism. Methods. C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity and then received CP775146 via intraperitoneal injection for 3 days. The content/morphology of the liver, serum lipid, and liver function was measured. The expression of genes related to lipolysis and synthesis in liver was detected by quantitative real-time PCR (qRT-PCR). Results. The safe dose of CP775146 was Acadl), acyl-CoA oxidase 1 (Acox-1), carnitine palmitoyltransferase-1 (CPT-1), and enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh)) was upregulated in CP775146-treated mice. Furthermore, CP775146 induced the expression of thermogenesis genes (cell death-inducing DFFA-like effector a (Cidea), uncoupling protein 1 (Ucp1)) and lipolysis genes (hormone-sensitive lipase (Hsl), adipose tissue triglyceride lipase (Atgl)) in epididymal white adipose tissue (eWAT), activating browning and thermogenesis. Conclusion. CP775146 efficiently alleviates obesity-induced liver damage, prevents lipid accumulation by activating the liver fatty acid β-oxidation pathway, and regulates the expression of genes that control brown fat-like pathway in eWAT.

Introduction Long noncoding RNAs (lncRNAs) play critical regulatory roles in metabolic disorder. Whereas, the regulatory role of lncRNAs in mitochondrial function of white adipose tissue (WAT) is unknown. Materials and Methods We investigated the role of Blnc1 in metabolic homeostasis and mitochondrial function of C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks, followed by multi-point injection of adenovirus carrying Blnc1 into epididymal fat (eWAT). In vitro, mitochondrial biogenesis and function were analyzed in 3T3-L1 pre-adipocytes with Blnc1 overexpression or knockdown. Mechanically, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) were used to highlight the molecular mechanism of Blnc1 in pre-adipocytes. Results Gross eWAT weight was significantly decreased and insulin resistance was improved in HFD-Ad-Blnc1 mice. Mitochondrial biosynthesis was induced by Blnc1 in eWAT, as evidenced by an increased mitochondrial DNA and enhanced Mito-tracker staining. The expression of mitochondria-related genes was increased in eWAT, hepatic fatty acid oxidation was upregulated, and lipid deposition was reduced in HFD-Ad-Blnc1 mice. Knockdown of Blnc1 in 3T3-L1 pre-adipocytes resulted in mitochondrial dysfunction. The mechanistic investigation indicated that Blnc1 stimulated the transcription of Pgc1β via decoying hnRNPA1. Conclusion Therefore, eWAT-specific overexpression of Blnc1 improves hepatic steatosis and systemic insulin sensitivity, likely by enhancing mitochondrial biogenesis and function.

Background Ischemia–reperfusion injury (IRI)-induced acute kidney injury (AKI) can repair itself completely. However, most moderate and severe patients undergoing IRI-AKI progress to chronic kidney disease due to incomplete repair. The present study is aimed to investigate the role of bone marrow mesenchymal stem cell-derived exosomes (MSC-Exo) with indoleamine 2,3-dioxygenase (IDO) overexpression on incomplete repair in mice after IRI. Methods IRI mice was established by clamping the unilateral renal pedicles and challenged with MSC-Exo. Blood biochemical indexes and inflammation factors contents were measured by ELISA assay. Histopathological examinations were monitored by HE, Masson, Immunohistochemical and TUNEL staining. Immunofluorescence, flow cytometry and immunoblotting were used to detect the polarization of macrophages, respectively. Results As compared to sham operation mice, IRI mice showed high contents of serum BUN and Scr, and more severe damaged kidney tissues on days 1 and 3, which all gradually declined over time, showing the lowest level on day 7 after injury. Once treated with MSCs-Exo that could directly transfer to kidney tubular cells, the restoration of kidney functions significantly accelerated by contrast to IRI mice, and the promotive effects were more obvious in IDO-overexpressed MSCs-Exo (MSCs-Exo-IDO)-treated IRI mice. Furthermore, MSCs-Exo-IDO administration also accelerated renal tubular cells proliferation, restrained tubular cells apoptosis, fibrosis and inflammation factor secretions during self-repair process compared to IRI mice, whose effects were higher than MSCs-Exo-NC-challenged IRI mice and IDO overexpressing plasmid-injected IRI mice. Mechanistically, MSCs-Exo-NC and MSCs-Exo-IDO exposure promoted the polarization from M1 macrophage to M2 macrophage, leading to more anti-inflammatory factors production, and subsequently altered the inflammatory microenvironment of renal tubular cells, which facilitated the self-repair process in mice after IRI. Conclusion MSCs-derived exosome accelerated renal self-repair in IRI mice by activating M2 macrophages polarization, which effects were amplified by IDO overexpression in MSCs. Potentially, genetically modified MSCs-Exo is an effective approach to improve renal self-repair in IRI-AKI mice.

Objective: Diabetic foot (DF) is one of the common serious complications of diabetes, which is an important cause of death and disability, and is associated with diabetic vascular disease and diabetic neuropathy. The purpose of this study was to assess the incidence and risk factors for diabetic foot among a diabetic population. Methods: The study was a retrospective cohort review. The population studied was 348 male examinees of type 2 diabetes mellitus (DM), in which age-matched equal examinees (174 patients each) were with diabetic foot (DF Group) and with no indication of diabetic foot (non-DF group), hospitalized in the same year at The First Hospital of Jiaxing, China. Medical records were reviewed to collect clinical profile, including duration of disease, smoking, previous diabetic foot incidence, and medication (such as metformin). Categorical data between groups were analyzed using chi-square test (χ2). Unconditional logistic regression analysis was used for multi-factor analysis to identify the risk factors of diabetic foot. Results: Comparing the baseline data of DF Group and non-DF Group, age, course of disease, LDL-C and use of metformin showed no significant difference (P >0.05). The results of the logistic regression analysis showed that smoking history (OR=1.88, P=0.020), previous diabetic foot history (OR=2.290, P=0.016), Hcy (OR=1.194, p≤0.001) were independent risk factors for diabetic foot disease, and HgB (OR =0.984, P=0.021) was the protective factor of diabetic foot disease in male subjects. Age (OR=0.985, P=0.304), course of disease (OR=1.048, P=0.233), history of metformin use (OR=0.851, P=0.509), HbA1c (OR=1.302, P=0.059), LDL-C (OR=0.936, P=0.698), Creatinine (OR =1.010, P=0.326), and ALB (OR =0.943, P=0.084) were not significantly correlated with diabetic foot disease. Conclusions: Smoking, previous diabetic foot history, and homocysteine are independent risk factors for diabetic foot disease. HgB is the protective factor of diabetic foot disease in male patients.

Background Skeletal muscle is essential for glucose and lipid metabolism. Growing evidence reveals the importance of long non-coding RNAs (LncRNAs) in metabolism. This study aimed to investigate the function of LncRNA H19 (H19) in lipid metabolism of skeletal muscle and its potential mechanisms. Methods Glucose tolerance, serum insulin and lipid content in serum and skeletal muscle were determined in control and H19-overexpressed db/db mice. Lipid metabolism was evaluated in H19-overexpressed or H19-silencing muscle cells by detecting lipid contents and mitochondria related functions. The underlying mechanisms were explored by RNA pull-down, mass spectrometry and RNA immunoprecipitation (RIP). Results H19 was downregulated in skeletal muscle of db/db mice. H19 overexpression in db/db mice inhibited lipid ectopic deposition in skeletal muscle, meanwhile improved glucose intolerance and insulin resistance as compared with control db/db mice treated with ad-GFP. Furthermore, overexpression of H19 reversed FFA-induced lipid accumulation and increased cellular respiration in muscle cells, while H19 knockdown exhibited opposite effects in muscle cells. Mechanistically, H19 interacted with heterogeneous nuclear ribonucleoprotein (hnRNPA1) which was validated by RNA pulldown and RIP analysis, which increased translation of fatty acid oxidation closely related genes PGC1a and CPT1b. Conclusion Our data suggest that overexpression of H19 ameliorates insulin resistance by reducing ectopic lipid accumulation in skeletal muscle. The possible underlying mechanisms are that overexpression of lncRNAH19 promotes fatty acids oxidation via targeting of hnRNPA1.

Metabolic syndrome (MetS) is a complex of interrelated risk factors including central adiposity, raised blood pressure, hyperglycemia, elevated triglyceride levels and low high-density lipoprotein. Association studies have reported several genetic variants in Sirt1 gene and Nrf2 gene (Sirt1 rs7895833 A>G, Sirt1 rs2273773 C>T and Nrf2 rs6721961 C>A ) with contributions to T2DM susceptibility as well as some glycemic and metabolic traits. However, little is known about contributions of these three single nucleotide polymorphisms (SNPs) to above phenotypes in Chinese. Our study recruited 141 individuals with MetS and 549 individuals without MetS to investigate association between three SNPs of Sirt1, Nrf2 gene and MetS risk in a Chinese Han population using PCR-CTPP method. The result showed that the AA genotype of Sirt1 rs7895833was 2.41 times higher in MetS group than those of AG genotype（P=0.038）and 1.94 times higher than those of GG genotype（P=0.016）. he serum level of low-density lipoprotein cholesterol and HOMA-IR were significantly higher (P

Curcumin has various physiological functions such as anti-oxidation, anti-cancer and prevention of Alzheimer's disease, but its poor water solubility and unstable physicochemical property limits the development and application of curcumin. The nano delivery carriers for curcumin prepared by nanotechnology can effectively solve these problems above. This paper summarized the research reports and literatures at home and abroad in recent years, categorized the nanocarriers of curcumin and analysed the definitions, preparation methods, properties and features, advantages and disadvantages of nano-emulsion, solid lipid particles, liposome, cyclodextrin inclusion compound respectively. In addition, this paper predicted application prospects of curcumin in the fields of food and medicine and provided references for the comprehensive development and utilization of curcumin.

Podocyte injury plays a key role in the occurrence and development of kidney diseases. Decreased autophagic activity in podocyte is closely related to its injury and the occurrence of proteinuria. Liver X receptors (LXRs), as metabolic nuclear receptors, participate in multiple pathophysiological processes and express in several tissues, including podocytes. Although the functional roles of LXRs in the liver, adipose tissue and intestine are well established; however, the effect of LXRs on podocytes function remains unclear. In this study, we used mouse podocytes cell line to investigate the effects of LXR activation on podocytes autophagy level and related signaling pathway by performing Western blotting, RT-PCR, GFP-mRFP-LC3 transfection, and immunofluorescence staining. Then, we tested this effect in STZ-induced diabetic mice. Transmission electron microscopy and immunohistochemistry were employed to explore the effects of LXR activation on podocytes function and autophagic activity. We found that LXR activation could inhibit autophagic flux through blocking the formation of autophagosome in podocytes in vitro which was possibly achieved by affecting AMPK, mTOR, and SIRT1 signaling pathways. Furthermore, LXR activation in vivo induced autophagy suppression in glomeruli, leading to aggravated podocyte injury. In summary, our findings indicated that activation of LXRs induced autophagy suppression, which in turn contributed to the podocyte injury.

Background Traumatic aortic arch rupture with pseudoaneurysm is a rare high fatal injury. Thoracic endovascular aortic repair(TEVAR) is widely used in the treatment of aortic diseases. However a unified traumatic aortic injury risk stratification tool still lacks. The patients’ disease assessment and operation method still rely on the doctors’ subjective anticipation of disease and surgical results. Case presentation A 31-year-old male presented with chest pain and hoarseness of recent onset. Imageological examination showed aortic rupture with mediastinal pseudoaneurysm in Zone 1. Debranching + TEVAR hybrid operation was considered: Using artificial blood vessels rebuild the arch branches, the covered stent was placed in aortic arch for endovascular repair via femoral artery. The follow-up was good in postoperative 7d, 1 year and > 2 years. Conclusion The traumatic aortic arch rupture with pseudoaneurysm treated by Debranching+TEVAR hybrid operation is feasible. The short-term and medium-term follow-up results are satisfactory. For traumatic aortic arch injury, hybrid operation is recommended to reduce the risk of cardiopulmonary bypass and deep hypothermia circulatory arrest under no open operation conditions or emergency situation.

Train control system is the core equipment to ensure the safety of railway operation. The conventional train control fails to consider the hybrid features of the system. In this paper, a hybrid modeling method for the positive safety of RBC sub-system in CTCS-3 train control system is proposed. Firstly, the paper analyzes the hybrid behaviors of the train control system, and presents a formal description of the positive safe function. Secondly, based on the integration of SCADE and Simulink, a hybrid modeling method is proposed. Finally, the simulation results show that the designed positive safe functions can effectively improve the safety and performance for train control.

Train control system is designed for ensuring the safety of trains in rail operation, and route safety is a key problem of train control. Due to its safety-critical nature and complicated circumstance, train control system is a typical large-scale and complex system. To address the serious challenge of route safety verification in the system development, this paper proposes a novel method by integrating the function model and the fail-safe fault model of train control. According to the fail-safe principle of railway signaling, with the help of Scade formalism, route safety properties are expressed into a fault tree. The two models are investigated for compatibility and, interlinkage constrains are discussed. Then integration rules are defined to combine the fault tree model and the function model into one lumping model, on which the safety verification is performed using Fault Tree Analysis (FTA). To illustrate how to apply the approach, examples are carried out on a part of WuGuang high-speed railway line in China. The results show that the proposed method has a good performance and meets the critical requirements of route safety verification for train control system.

Honokiol (HNK), an important bioactive compound purified from Magnolia officinalis Cortex, has been demonstrated to have manifold beneficial anti-oxidative, anti-inflammatory, anti-bacterial and antitumor pharmacological effects. In the present study, the association of HNK in the signaling mechanism associated with hydrogen peroxide (H2O2)-induced apoptosis of cultured mouse podocytes was investigated. HNK did not cause significant changes in podocyte viability when its concentration remained below 20 µM. MTS assay and flow cytometry confirmed that H2O2 significantly enhanced the rates of apoptosis while produce significant reduction in viability of podocytes. Following 24 h of pre-treatment with different concentrations of HNK, the viability of adherent podocytes increased and apoptosis significantly decreased in a dose-dependent manner below 20 µM. Reverse transcription-polymerase chain reaction and western blot results indicated that HNK significantly decreased the expression of mRNA and cleaved protein of caspase-3 and caspase-9 in podocytes pre-treated with H2O2. Furthermore, phosphorylation of the signaling molecules protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) 1/2 appeared to increase following HNK treatment. In conclusion, HNK largely eliminated the role of promoting podocyte apoptosis in an oxidative stress environment, which was a protective factor on podocytes cultured with H2O2. The anti-oxidative stress mechanisms of HNK are partly due to suppressing the expression of caspase-3 and caspase-9 and upregulating phosphorylated-Akt and -Erk 1/2.

Suzhou is experiencing a dynamic human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) epidemic. While serology based surveillance systems have reported the spread of HIV/AIDS, detailed tracking of its molecular epidemiology and transmission in populations remains mostly undetermined. Here, we conducted a molecular epidemiology study involving 261 HIV-1-positive serum samples collected in Suzhou from 2009 to 2014 and systematically analyzed the dynamic characteristics of virus genetic variation. Sequencing data showed that the predominant HIV-1 subtype was CRF01_AE (52.1%), followed by CRF07_BC (30.3%), CRF08_BC (8.4%), and B (8.0%). The genotype distance of the B-subtype strain was great and its degree of variation was high. Interestingly, a cluster of eight members was found in the phylogenetic tree of CRF01_AE samples from men who have sex with men (MSM). Although the main transmission route of HIV-1 circulating in Suzhou appeared to be sexual transmission, maternal vertical transmission was also observed in this study. These data provide the basis for a rational and effective prevention and control strategy to prevent further spread of HIV-1 in Suzhou.

Graphene possesses exceptional electronic, optical, thermal, and mechanical properties which make it an outstanding material for next-generation energy, electronics, and thermal management applications. Although there is a strong drive towards fabricating supersized single-crystal domains, recent advances in large-scale production of monolayer graphene sheets via chemical vapor deposition typically result in polycrystalline graphene whose properties can be drastically affected by the presence of grain boundaries. In this discussion, we present a study of the effect of strain on the thermal transport across grain boundaries in graphene using molecular dynamics simulations. The thermal boundary conductance is found to decrease significantly under biaxial tension as expected. In contrast, under biaxial compression, the thermal boundary conductance is strongly affected by the dimensions of the graphene monolayer, increasing with strain for specimen with length-to-width ratio of 20. This rather unexpected size-dependence under biaxial compression is found to be a result of geometric instabilities.