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Exercise can improve people’s physical health and strengthen their body bones. But the physique of college students is generally too poor. The enhancement of College Students’ physique cannot be completed in a day. This study aims to explore the best sports nutrition intervention scheme for strengthening college students’ physique from the construction of sports nutrition dynamic intervention mechanism, so as to provide theoretical reference for public physical education teaching and students’ independent exercise. In this study, 100 full-time associate students in our university were selected as the research objects. Before the experiment, the subjects’ body shape, body function, and physical quality were tested. Based on the random mathematical method, the full-time associate students were randomly divided into four groups: control group, exercise intervention group, nutrition intervention group, and sports nutrition intervention group, with 25 people in each group. After the experiment, the body shape, body function, and physical quality of the four groups were tested. The results show that exercise and nutrition intervention have little effect on college students’ height, but have great influence on body mass index, vital capacity and 800 meter running. Especially after the experiment, the vital capacity of the exercise group and the sports nutrition group increased by nearly 250 ml and 500 ml, respectively, and the 800 m running time increased by nearly 10 s and 18 s, respectively. Strengthening exercise and increasing nutritional intake can effectively improve the institutional health of college students.

With the rapid development of the Internet, malicious domain names pose more and more serious threats to many fields, such as network security and social security, and there have been many research results on malicious domain detection. This article proposes a malicious domain name detection model based on improved deep learning, which can combine the advantages of three different network models, convolutional neural network (CNN), temporal convolutional network (TCN), and long short-term memory network (LSTM) in malicious domain name detection, to obtain a better detection effect than that of the original single or two models. Experiments show that the effect of the improved deep learning model proposed in this article is better than that of the combined model of CNN and LSTM or the combined model of CNN and TCN, and the accuracy and regression rates reached 99.76% and 98.81%, respectively.

Long non‐coding RNA (lncRNA) lnc‐ISG20 has been found aberrantly up‐regulated in the glomerular in the patients with diabetic nephropathy (DN). We aimed to elucidate the function and regulatory mechanism of lncRNA lnc‐ISG20 on DN‐induced renal fibrosis. Expression patterns of lnc‐ISG20 in kidney tissues of DN patients were determined by RT‐qPCR. Mouse models of DN were constructed, while MCs were cultured under normal glucose (NG)/high glucose (HG) conditions. The expression patterns of fibrosis marker proteins collagen IV, fibronectin and TGF‐β1 were measured with Western blot assay. In addition, the relationship among lnc‐ISG20, miR‐486‐5p, NFAT5 and AKT were analysed using dual‐luciferase reporter assay and RNA immunoprecipitation. The effect of lnc‐ISG20 and miR‐486/NFAT5/p‐AKT axis on DN‐associated renal fibrosis was also verified by means of rescue experiments. The expression levels of lnc‐ISG20 were increased in DN patients, DN mouse kidney tissues and HG‐treated MCs. Lnc‐ISG20 silencing alleviated HG‐induced fibrosis in MCs and delayed renal fibrosis in DN mice. Mechanistically, miR‐486‐5p was found to be a downstream miRNA of lnc‐ISG20, while miR‐486‐5p inhibited the expression of NFAT5 by binding to its 3'UTR. NFAT5 overexpression aggravated HG‐induced fibrosis by stimulating AKT phosphorylation. However, NFAT5 silencing reversed the promotion of in vitro and in vivo fibrosis caused by lnc‐ISG20 overexpression. Our collective findings indicate that lnc‐ISG20 promotes the renal fibrosis process in DN by activating AKT through the miR‐486‐5p/NFAT5 axis. High‐expression levels of lnc‐ISG20 may be a useful indicator for DN.

Scanning ion conductance microscopy (SICM) is a powerful and versatile technique that allows an increasingly wide range of interfacial properties and processes to be studied. SICM employs a nanopipette tip that contains electrolyte solution and a quasi-reference counter electrode (QRCE), to which a potential is applied with respect to a QRCE in a bathing solution, in which the tip is placed. The work herein considers the potential-controlled delivery of uncharged electroactive molecules (solute) from an SICM tip to a working electrode substrate to determine the effect of the substrate on electroosmotic flow (EOF). Specifically, the local delivery of hydroquinone from the tip to a carbon fiber ultramicroelectrode (CF UME) provides a means of quantifying the rate of mass transport from the nanopipette and mapping electroactivity via the CF UME current response for hydroquinone oxidation to benzoquinone. EOF, and therefore species delivery, has a particularly strong dependence on the charge of the substrate surface at close nanopipette-substrate surface separations, with implications for retaining neutral solute within the tip predelivery and for the delivery process itself, both controlled via the applied tip potential. Finite element method (FEM) simulations of mass transport and reactivity are used to explain the experimental observations and identify the nature of EOF, including unusual flow patterns under certain conditions. The combination of experimental results with FEM simulations provides new insights on mass transport in SICM that will enhance quantitative applications and enable new possibilities for the use of nanopipettes for local delivery.

Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine‐derived stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA‐16‐5p (miR‐16‐5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR‐16‐5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual‐luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR‐16‐5p and promote VEGFA in human podocytes (HPDCs). miR‐16‐5p in hUSCs was transferred through the exosome pathway to HG‐treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR‐16‐5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG‐induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR‐16‐5p were injected into diabetic rats via tail vein, followed by qualification of miR‐16‐5p and observation on the changes of podocytes, which revealed that overexpressed miR‐16‐5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR‐16‐5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.

Scanning ion conductance microscopy (SICM) is becoming a powerful multifunctional tool for probing and analyzing surfaces and interfaces. This work outlines methodology for the quantitative controlled delivery of ionic redox-active molecules from a nanopipette to a substrate electrode, with a high degree of spatial and temporal precision. Through control of the SICM bias applied between a quasi-reference counter electrode (QRCE) in the SICM nanopipette probe and a similar electrode in bulk solution, it is shown that ionic redox species can be held inside the nanopipette, and then pulse-delivered to a defined region of a substrate positioned beneath the nanopipette. A self-referencing hopping mode imaging protocol is implemented, where reagent is released in bulk solution (reference measurement) and near the substrate surface at each pixel in an image, with the tip and substrate currents measured throughout. Analysis of the tip and substrate current data provides an improved understanding of mass transport and nanoscale delivery in SICM and a new means of synchronously mapping electrode reactivity, surface topography, and charge. Experiments on Ru(NH3)63+ reduction to Ru(NH3)62+ and dopamine oxidation in aqueous solution at a carbon fiber ultramicroelectrode (UME), used as the substrate, illustrate these aspects. Finite element method (FEM) modeling provides quantitative understanding of molecular delivery in SICM. The approach outlined constitutes a new methodology for electrode mapping and provides improved insights on the use of SICM for controlled delivery to interfaces generally.

Transmembrane protein 88 (TMEM88) belongs to a member of the TMEM family, and was reported to be involved in fibrogenesis. However, the biological role of TMEM88 in renal fibrosis has not been elucidated. Therefore, the objective of this study was to investigate the effect of TMEM88 on cell proliferation and extracellular matrix (ECM) accumulation in a TGF-β1-induced human renal proximal tubular epithelial cell line (HK2). Our results showed that TMEM88 was downregulated in renal fibrotic tissues and TGF-β1-treated HK2 cells. In addition, TMEM88 overexpression inhibited TGF-β1-induced cell proliferation and migration in HK2 cells. Furthermore, TMEM88 overexpression reduced the production of α-SMA, collagen I, and collagen III in TGF-β1-stimulated HK2 cells. Mechanistically, TMEM88 overexpression suppressed the phosphorylation status of Smad2 and Smad3 in TGF-β1-stimulated HK2 cells. In conclusion, data from our experiments demonstrate that TMEM88 plays a pivotal role in the pathological process of renal fibrosis. TMEM88 inhibited fibrosis in renal proximal tubular epithelial cells by suppressing the TGF-β1/Smad signaling pathway.

Forkhead box O 6 (FOXO6), a FOX transcription factor, has been found to be involved in diabetes mellitus and related complications. However, the role of FOXO6 in diabetic nephropathy (DN) has not been fully understood. In the present study, we evaluated the functions of FOXO6 in high glucose (HG)-induced glomerular mesangial cells (MCs). The results showed that FOXO6 expression was significantly elevated in MCs after HG stimulation. Knockdown of FOXO6 by transfection with small interfering RNA (siRNA) targeting FOXO6 (siRNA-FOXO6) suppressed cell proliferation in MCs. The productions of extracellular matrix (ECM) components including collagen IV (Col IV) and fibronectin (FN) were markedly decreased after FOXO6 knockdown in MCs. Furthermore, knockdown of FOXO6 inhibited HG-induced activation of p38 MAPK signaling pathway in MCs. Collectively, these findings suggested that knockdown of FOXO6 inhibited cell proliferation and ECM accumulation in HG-induced MCs via inhibiting p38 MAPK signaling pathway. FOXO6 might be a beneficial therapeutic target for the prevention and treatment of DN.

Two novel Gram-strain-negative and rod-shaped bacteria, designated strain G1T and G2T, were isolated from sediment samples collected from the coast of Xiamen, PR China. The cells were motile by a single polar flagellum. Growth of strain G1T occurred at 10–40 °C (optimum, 30 °C), at pH 6.0–9.0 (optimum, pH 7.5) and with 5–1530 mM NaCl (optimum, 510 mM), while the temperature, pH and NaCl concentration ranges for G2T were 4–45 °C (optimum, 28 °C), pH 5.5–8.0 (optimum, pH 6.5) and 85–1530 mM NaCl (optimum, 340 mM). The two isolates were obligate chemolithoautotrophs capable of using thiosulfate, sulfide, elemental sulphur or tetrathionate as an energy source. Strain G1T used molecular oxygen or nitrite as an electron acceptor, while strain G2T used molecular oxygen as the sole electron acceptor. The dominant fatty acids of G1T and G2T were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16 : 0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The DNA G+C content of G1T and G2T were 45.1 and 48.3 mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain G1T and G2T were members of the genus Thiomicrorhabdus , and most closely related to Thiomicrorhabdus hydrogeniphila MAS2T (96.0 %) and Thiomicrorhabdus indica 13-15AT (95.4 %), respectively. The 16S rRNA gene sequence similarity between strains G1T and G2T was 95.8 %. Based on the phylogenetic, genomic and phenotypic data presented here, the isolate strains represent novel species of the genus Thiomicrorhabdus , for which the names Thiomicrorhabdus sediminis sp. nov. (type strain G1T=MCCC 1A14511T=KCTC 15841T) and Thiomicrorhabdus xiamenensis sp. nov. (type strain G2T=MCCC 1A14512T=KCTC 15842T) are proposed.

Low frequency oscillation occurs frequently in the smart grid, which threatens the security and stability of the physical system. Wide-area damping controller (WADC), which belongs to cyber system, can effectively suppress inter-area low frequency oscillations and improve the small signal stability of the closed-loop cyber-physical system (CPS). However, with the introduction of global signals, time delays of communication are inevitable. Considering that, this paper deduces the general mathematics expression among electromagnetic torque coefficients, WADC control parameters and time delays, which makes it possible to analyse the influence mechanism of time delay on small signal stability. Based on these analysis, on the one hand, the time-delay small signal stability region is established to evaluate the operation state of closed-loop CPS, on the other hand, if small signal stability is not achieved due to the measured time delays, optimisation scheme is proposed to carry out WADC control parameters coordination to optimise small signal stability of the closed-loop system. Finally, taking two time delays as example, this study verifies the effectiveness and advantages of the proposed method by comparing the closed-loop system performance considering two time delays with the cases of considering singe time delay and without time delay.

Transforming growth factor-β1 (TGF-β1)-induced epithelial to mesenchymal transition (EMT) and renal fibrosis plays critical role in the development and progression of diabetic nephropathy (DN). Our study aimed to determine the detailed roles of miR-133b & miR-199b on TGF-β1-induced EMT & renal fibrosis in DN and its underlying mechanism. The expressions of miR-133b & miR-199b in OLETF rats, LETO rats & TGF-β1-treated human proximal tubule cell line (HK-2) were examined by qRT-PCR. Inhibition of miR-133b or miR-199b was realized in cells by transfection of lentivirus containing miR-133b inhibit or miR-199b inhibitor. The expression levels of collagen I (COL I), fibronectin (FN), α-smooth muscle actin (α-SMA), E-cadherin & sirtuin 1 (SIRT1) were detected by western blot and immunohistochemistry. Masson staining was conducted to estimate the degree of renal fibrosis. The interaction between SIRT1 and miR-133b, miR-199b was explored by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. miR-133b and miR-199b were highly expressed in the renal cortex of diabetic OLETF rats and TGF-β1-treated HK-2 cells. EMT and renal fibrosis were induced in diabetic OLETF rats and TGF-β1-treated HK-2 cells. Inhibition of miR-133b and miR-199b attenuated EMT and renal fibrosis in diabetic OLETF rats and TGF-β1-treated HK-2 cells. In addition, SIRT1 was identified as a target of miR-133b & miR-199b in HK-2 cells. SIRT1 knockdown dramatically reversed the suppression on TGF-β1-induced EMT and renal fibrosis in HK-2 cells mediated by anti-miR-133b or anti-miR-199. Inhibition of miR-133b & miR-199b attenuated TGF-β1-induced EMT & renal fibrosis by upregulating SIRT1 shows that using different miRNAs is a potential strategy for the future treatment of DN.

Acute kidney injury (AKI) is a sudden decay in renal function leading to increasing morbidity and mortality. miR-182 has been reported to be actively involved in kidney diseases. However, the function and molecular mechanism of miR-182 in AKI still need to be elucidated. The levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urine Kim-1 in I/R-induced rat AKI model were detected by a Beckman Autoanalyzer. miR-182 and transcription factor 7-like-2 (TCF7L2) mRNA expression were measured by qRT-PCR. Flow cytometry and caspase-3 colorimetry analysis were performed to determine NRK-52E cell apoptosis. Bioinformatics and dual-luciferase reporter were used to identify the interaction between miR-182 and TCF7L2. miR-182 expression was increased in both I/R-induced rat models and hypoxia-treated NRK-52E cells, and miR-182 overexpression stimulated the apoptosis of hypoxia-induced NRK-52E cells. Dual-luciferase analysis disclosed that TCF7L2 was a target of miR-182. TCF7L2 suppressed hypoxia-induced apoptosis in NRK-52E cells, and the inhibitory effect of TCF7L2 on cell apoptosis could be reversed with miR-182 restoration. Moreover, the activity of Wnt/β-catenin signaling pathway was promoted following overexpression of TCF7L2 in NRK-52E cells with hypoxia treatment, and this effect was greatly attenuated by the increased miR-182 expression. Finally, in vivo experiment also validated the alleviation of miR-182 inhibitor on I/R-induced kidney injury and apoptosis via regulating TCF7L2/ Wnt/β-catenin pathway. miR-182 exacerbated AKI involving the targeting and regulation of TCF7L2/Wnt/β-catenin signaling, unveiling a novel regulatory pathway in ischemia-reperfusion injury and elucidating a potential biomarker for AKI treatment.

Protocatechuic acid (PCA), a phenolic compound of anthocyanins, was reported to possess various pharmacologic properties, including anti-oxidant, anti-inflammatory, anti-apoptosis, anti-diabetic and anti-tumor activities. However, the role of PCA in diabetic nephropathy remains elusive. The present study was conducted to evaluate the effects of PCA on extracellular matrix (ECM) accumulation in high glucose (HG)-induced human mesangial cells (MCs) and explore the possible mechanism. Our results demonstrated that PCA obviously inhibited HG-induced proliferation of MCs in a dose-dependent manner. In addition, PCA effectively reduced the protein expression levels of type IV collagen, laminin and fibronectin induced by HG, as well as decreased the levels of ROS and MDA in HG-stimulated MCs. Mechanistic studies showed that PCA efficiently down-regulated the phosphorylation level of p38 MAPK in HG-stimulated MCs. Taken together, our present study demonstrated that PCA protects MCs against HG damage might via inhibition of the p38 MAPK signaling pathway. Thus, PCA might be a beneficial agent for the prevention and treatment of diabetic nephropathy.

Scoparone, a major constituent of Artemisia capillaries, has a variety of biological properties including anticoagulant, hepatoprotective, anti-tumor, anti-fibrosis, anti-inflammatory, antioxidant, and antidiabetic activities. However, the renoprotective effect of scoparone under diabetic conditions remains elusive. Thus, the present study was undertaken to examine the role of scoparone in high glucose-induced mesangial cell proliferation and extracellular matrix (ECM) accumulation and elucidate the possible mechanism of action of scoparone. Our results demonstrated that treatment with scoparone significantly inhibited the proliferation of mesangial cells under high glucose conditions. In addition, scoparone reversed high glucose-induced fibronectin and collagen IV expression in mesangial cells, as well as suppressed reactive oxygen species production and NOX2/4 expression in high glucose-exposed mesangial cells. Mechanistic studies revealed that scoparone prevented the activation of ERK1/2 signaling pathway in high glucose-exposed mesangial cells, and an ERK inhibitor (U0126) protected mesangial cells treated with high glucose. Taken together, these results demonstrated that scoparone protects mesangial cells against high glucose damage in part through the inactivation of ERK signaling pathway. These findings suggest that scoparone may represent a potential drug for the treatment of diabetic nephropathy.

Scanning ion conductance microscopy (SICM) is a nanopipette-based scanning probe microscopy technique that utilizes the ionic current flowing between an electrode inserted inside a nanopipette probe containing electrolyte solution and a second electrode placed in a bulk electrolyte bath, to provide information on a substrate of interest. For most applications to date, the composition and concentration of the electrolyte inside and outside the nanopipette is identical, but it is shown herein that it can be very beneficial to lift this restriction. In particular, an ionic concentration gradient at the end of the nanopipette, generates an ionic current with a greatly reduced electric field strength, with particular benefits for live cell imaging. This differential concentration mode of SICM (ΔC-SICM) also enhances surface charge measurements and provides a new way to carry out reaction mapping measurements at surfaces using the tip for simultaneous delivery and sensing of the reaction rate. Comprehensive finite element method (FEM) modeling has been undertaken to enhance understanding of SICM as an electrochemical cell and to enable the interpretation and optimization of experiments. It is shown that electroosmotic flow (EOF) has much more influence on the nanopipette response in the ΔC-SICM configuration compared to standard SICM modes. The general model presented advances previous treatments, and it provides a framework for quantitative SICM studies.

BACKGROUND Resistin-like molecule beta (RELM-β) has been reported to be associated with diabetic nephropathy (DN). However, the role of RELM-β in DN is poorly understood. This study was conducted to delineate the underlying mechanisms of action and to investigate the role of RELM-β in the primitive development of DN via MAPK signaling pathways. MATERIAL AND METHODS Lentivirus-mediated vectors and RNAi technology were used to establish the model of RELM-β up-regulated and down-regulated expression in human mesangial cells (HMCs). The proliferation of HMCs was detected through CCK-8 method. The cell cycle and cell proliferation of HMCs was detected through flow cytometry. The MAPKs pathway protein activity was detected through Western blotting. RESULTS The HMCs with up-regulated and down-regulated expression of RELM-β increased or decreased significantly at 2-3 days. The HMCs with high glucose intervention reversed the proliferation inhibition. The HMCs with exogenous glucose or RELM-β protein intervention partially reversed the cell cycle inhibition. Among the MAPKs pathway, the phosphorylation activity of p38MAPK and JNK increased or decreased and ERK1/2 did not change in the overexpression or inhibition of RELM-β. The p38 MAPK pathway inhibitor SB202190 significantly inhibited the proliferation of HMCs caused by overexpression of RELM-β. Up-regulated expression of RELM-b induced the phosphorylation of p38 MAPK, JNK in HMCs and promoted HMCs proliferation and participated in early DN through the MAPKs pathway. CONCLUSIONS The results provide evidence that RELM-b is a potential molecular target for the treatment of DN.

The long DNA concatemers have been well developed to fabricate various biosensing platforms for the signal amplification. Herein, this signal amplification strategy was firstly used for an ultrasensitive scanning electrochemical microscopy (SECM)-based DNA biosensing platform. This platform was constructed through the hybridization of target DNA (TD) with thiol-tethered DNA capture probes (CP), immobilized on the gold substrate surface, and biotinylated DNA signal probes (SP), which formed then the long DNA concatemers through the continuous self-assembly with alternating DNA auxiliary probes (AP). The streptavidin-horseradish peroxidase (HRP) was linked to the long DNA concatemers through biotin-streptavidin interaction. In the HRP-catalyzed reaction, hydroquinone (H 2 Q) was oxidized to benzoquinone (BQ) with H 2 O 2 at the modified substrate surface where sequence-specific hybridization had occurred, and the BQ generated could be monitored by a SECM tip. This platform exhibited a low detection limit of 0.18 aM estimated by the 3σ rule. Combined with DNA microarrays, four kinds of TDs (100 fM) as the models were detected simultaneously by using this proposed strategy, which also demonstrated sufficient selectivity to distinguish specific DNA sequences and good reproducibility. This method opens a promising direction to improve the SECM sensitivity for high-throughput DNA detection.

Low frequency oscillation occurs frequently in power systems. Wide-area damping controller (WADC) based on Wide-Area Measurement System (WAMS) can effectively suppress inter-area low frequency oscillations. However, with the introduction of global signals, time delays are inevitable. Electromagnetic torque analysis method(ETA) can establish the analytic relation between electromagnetic torque coefficients and control parameters of power component, which is facilitative to analyze small signal stability. Considering that WADC has inherent characteristics of multiple time delays, based on the ETA for equivalent two-machine system, this paper deduces the general mathematics expression among electromagnetic torque coefficients, WADC parameters and time delays. The influence mechanism of time delay on electromagnetic torque coefficients and small signal stability is further analyzed. Based on these analysis, performance of damping control of WADC can be improved, on one hand, time-delay small signal stability region is established under fixed WADC parameters, on the other hand, if small signal stability is not achieved under the given WADC parameters due to set of the time delays, optimization scheme is proposed to carry out parameters coordination according to the measured time delays. Finally, taking two time delays as an example, the paper verifies the effectiveness of the proposed method by comparing the system dynamic performance considering two time delays with the system only considering single time delay and the system without time delay in a two-area four-machine power system.

Remote signal transmission time delays are the major factors affecting damping performance of wide-area damping controller (WADC), and it even deteriorates small signal stability of large-scale power system. Traditional time delay damping controller based on linear matrix inequalities (LMI) has relatively large conservatism and complexity. Conventional time delay compensation controller suffers large amount of simulations and there is no general formulation to determine control parameters. In this paper, the design method of wide-area time-delay damping controller based on parametric Lyapunov theory is derived. The explicit expression of the controller parameter value associated with the time delay is determined. The controller is determined according to the system stability original definition (The system energy function is finite and positive and its first derivative is negative), which avoids complex matrix inequalities cyclic solution and reduces the conservatism of the controller. Moreover, it can directly give simple and explicit control law and specific control parameters, which enable this method to adjust its parameters online according to the exact time delay obtained by GPS. Case study is undertaken based on the New England ten-machine 39-bus power system. Compared with the free weight matrix controller, which is a kind of LMI-based design strategy with excellent performance, the effectiveness and superiority of the proposed design method for WADC are verified.

Inflammatory response is important for the development and progression of diabetic nephropathy (DN). Artesunate (ART), an antimalarial drug, possesses anti-inflammatory effect and exhibits protective effect on chronic kidney diseases. However, the effect of ART on DN is unknown. The aim of the present study was to evaluate the effect and the molecular mechanism of ART on DN in an in vitro model. The rat mesangial cell line, HBZY-1, was induced by high glucose (HG; 30 mM d -glucose) in the presence or absence of ART (15 and 30 μg/ml) and incubated for 24 h. We found that HG induced the proliferation of HBZY-1 cells, while treatment with ART inhibited the cell proliferation. Treatment with ART inhibited HG-induced inflammatory cytokines production and expression of extracellular matrix (ECM). Besides, HG induced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and inhibited the superoxide dismutase (SOD) activity of HBZY-1 cells, and the effects were attenuated by ART treatment. ART decreased HG-induced the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), nuclear factor κB (NF-κB) p-p65, and nod-like receptor protein 3 (NLRP3). Inhibition of the TLR4/NF-κB pathway suppressed NLRP3 inflammasome in HBZY-1 cells. In conclusion, ART exhibited protective effect on HG-induced HBZY-1 cells by inhibiting the inflammatory response, oxidative stress and ECM accumulation. The TLR4/NF-κB/NLRP3 inflammasome pathway was involved in the protective effect of ART. The results suggested that ART might be a potential therapy agent for the DN treatment.

Progestin and AdipoQ Receptor 3 (PAQR3), a member of the PAQR family, was involved in multiple biological processes, including tumorigenesis, cholesterol homeostasis, autophagy, obesity, insulin sensitivity and energy metabolism. However, the role of PAQR3 in diabetic nephropathy is still unclear. Therefore, in this study, we investigated the effects of PAQR3 on cell proliferation and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) cultured under high glucose (HG), and explored the underlying mechanism. Our results demonstrated that HG significantly up-regulated the expression of PAQR3 in human MCs. In addition, knockdown of PAQR3 efficiently suppressed MC proliferation and ECM production in HG-stimulated MCs. Furthermore, knockdown of PAQR3 markedly reversed HG-induced PI3K/AKT activation in MCs. In summary, our present study demonstrated that knockdown of PAQR3 suppressed HG-induced the proliferation and ECM accumulation in human MCs, via inhibiting the PI3K/AKT signaling pathway. Thus, PAQR3 may be a potential therapeutic target for the treatment of diabetic nephropathy.

The aim of this study was to investigate the clinical significance of regulatory T cells (Tregs) and its subsets in immunoglobulin A nephropathy (IgAN) patients. Peripheral blood samples of 20 IgAN patients and 20 healthy individuals of similar ages were analyzed. Levels of Tregs and its subsets, namely nTregs and iTregs, were analyzed using flow cytometry. The number of Tregs in IgAN patients was significantly lower than that in the healthy controls. While significant reduction in iTregs primarily contributed to this effect (P0.01), nTreg levels did not significantly change (P0.05). The levels of serum IL-17, IL-10 and TGF-β were detected by ELISA method. The levels of IL-10 and TGF-β in IgAN patients were lower (P0.05), whereas those of IL-17 in the IgAN group were higher (P0.05) than those in the controls. In conclusion, the change in Tregs count in the peripheral blood of IgAN patients is mainly caused by the reduction in iTregs, suggesting a substantial role in the prognosis and treatment of IgAN.

In this study, we examined the effects of Tripterygium wilfordii glycosides (TWGs) on Th17 and regulatory T cells (Tregs) in an immunoglobulin A nephropathy (IgAN) rat model. IgAN model rats were randomly divided into the model group, TWG treatment group, and prednisone group. Normal rats were included as controls. There were 6 rats in each group. The urine protein levels and the number of red blood cells in urine were analyzed at 24 h. IgA deposition in renal tissue was detected by fluorescence microscopy. The concentration of interleukin-17 in serum was detected by an enzyme-linked immunosorbent assay and the number of Tregs in blood was analyzed by flow cytometry. TWGs and prednisone significantly reduced urine protein levels and urine red blood cells at 24 h in IgAN model rats (P0.01), but prednisone had a greater effect than did TWGs (P0.05). TWGs and prednisone reduced IgA deposition in renal tissue, but prednisone had a greater effect than TWGs. T. wilfordii glycosides and prednisone significantly decreased the serum IL-17 level in an IgAN rat model and increased the number of Tregs in the blood (P0.01). There was no significant difference between prednisone and TWGs (P0.05). In conclusion, TWGs had therapeutic effects on IgAN model rats and may regulate the immune balance of Th17 and Tregs.

NLRC5, the largest member of the Nucleotide-binding domain and leucine-rich repeat (NLR) protein family, is recently proven to be a critical modulator in fibrogenesis. However, the role of NLRC5 in renal fibrosis remains unknown. In the present study, we investigated the effects of NLRC5 on transforming growth factor β1 (TGF-β1)-stimulated rat renal fibroblasts in vitro. Our results showed that the expression of NLRC5 was also obviously upregulated in renal fibrosis tissues and TGF-β1-treated NRK-49F cells. Knockdown of NLRC5 inhibited the proliferation of NRK-49F cells induced by TGF-β1, as well as suppressed the accumulation of extracellular matrix (ECM) in NRK-49F cells induced by TGF-β1. Furthermore, knockdown of NLRC5 inhibited the expression of phosphorylated Smad3 in TGF-β1-treated NRK-49F cells. In conclusion, our results show that knockdown of NLRC5 inhibits renal fibroblast activation via modulating TGF-β1/Smad signaling pathway. Therefore, NLRC5 may act as a key mediator in renal fibroblast activation and fibrogenesis.

Objective To explore the effects of AMP-activated protein kinase (AMPK) over-expression on the proliferation, matrix synthesis and inflammatory cytokine production in glomerular mesangial cells from pristane-induced systemic lupus erythematosus (SLE) mice. Methods C57BL/6 mice were randomly divided into control group and model group. The SLE mouse model was established by the treatment with pristane. The levels of autoantibodies were detected by ELISA. The primary glomerular mesangial cells were isolated from the mice of the control and model groups. The primary glomerular mesangial cells of the model mice were divided into model subgroup, empty vector subgroup and over-expression subgroup. The pEGFP-C1-vector and pEGFP-C1-MPK were transferred into the cells of the empty vector and over-expression subgroups, respectively. The expression of AMPK was tested by Western blotting. After AMPK was successfully over-expressed, cell apoptosis was detected by flow cytometry. The expressions of AMPK, cyclin D1, proliferating cell nuclear antigen (PCNA), P21, P27, fibronectin (FN), collagen IV (Col4), interleukin 6 (IL-6) and interleukin 1β (IL-1β) were measured by Western blotting. Results The levels of serum dsDNA IgG, dsDNA IgM, Sm IgG, Sm IgM significantly increased in the model group compared with the control group, indicating that the mouse model used in this study successfully imitated the pathological process of SLE. In addition, over-expression of AMPK promoted the apoptosis of mesangial cells from the SLE mice. Moreover, the expressions of cyclin D1, PCNA, P21, FN, Col4, IL-6 and IL-1β were markedly depressed, whereas the level of P27 protein was raised in these cells after AMPK over-expression. Conclusion AMPK over-expression can inhibit the cell proliferation, matrix synthesis and inflammatory response of mesangial cells in pristane-induced SLE mice.

The present study aimed to explore the roles of microRNA-21 (miR‑21) and the transforming growth factor-β (TGF-β)/Smad signaling pathway in the development of peritoneal fibrosis (PF). First, dialysis effluents from 30 patients with PF were collected, and after the establishment of a mouse model of PF, hematoxylin and eosin (HE) and Masson's staining were used to observe peritoneal tissues, inflammatory cells and blood vessels. High glucose was used to stimulate human peritoneal mesothelial cell lines and these stimulated cells were then transfected with miR‑21 inhibitor. Immunofluorescence microscopy was applied for the observation of the transfected cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR‑21, and RT-qPCR and western blot analysis were used to detect the mRNA and protein expression of Zonula occludens-1 (ZO-1), TGF-β, Smad, vimentin and connective-tissue growth factor (CTGF). The mRNA and protein expression levels TGF-β, Smad-3, vimentin and CTGF were elevated, while ZO-1 mRNA and protein expression was decreased with the prolonged duration of dialysis treatment in the patients with PF. The experiments using the mouse model of PF revealed that the peritoneal connective tissue was thickened, while the numbers of inflammatory cells and blood vessels were increased. The expression levels of miR‑21, and the mRNA and protein expression levels of TGF-β, Smad-3, vimentin and CTGF were increased over time, whereas the mRNA and protein expression levels ZO-1 constantly decreased in the mice in the experimental group. Moreoever, the expression of miR‑21 positively correlated with the expression levels of TGF-β, Smad-3, vimentin and CTGF, while it negatively correlated with the expression of ZO-1. The results of HE and Masson's staining revealed that miR‑21 expression was associated with the degree of PF. These findings thus indicate that miR‑21 promotes the progression of PF through the activation of the TGF-β/Smad signaling pathway.

Occurrence of oscillation phenomena on generalized frequency band caused by renewable energy generation (REG), which connects to power grid in the way of power electronic convertors, is analyzed. The eigenvalue analysis method is adopted to assess stability of a voltage source control inverter-fed ac system based on state space model. In detail, for the inverter, a comprehensive model covering power controller, outer voltage loop and inner current loop is established. Then combining inverter model with network and load model to establish overall state space model. By studying the characteristics of the eigenvalues distribution, useful information on the nature and extent of the generalized frequency oscillation can be found. Moreover, participation analysis is presented to evaluate the contributions of state variables to these oscillation modes. The root locus results validate the theoretical analyses.

Diabetic nephropathy (DN) is a metabolic disease characterized by mesangial cell proliferation and extracellular matrix (ECM) accumulation. Salidroside (SAL) is the major ingredient in Rhodiola rosea and possesses beneficial effects on DN. This study aimed to evaluate the effect of SAL on high glucose (HG)-induced oxidative stress and ECM accumulation and the underlying mechanism. Rat glomerular mesangial cells HBZY-1 were induced by high glucose (HG) in the presence or absence of SAL. Cell proliferation was measured by CCK-8 assay. The reactive oxygen species (ROS) level, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected to evaluate oxidative stress. The expression levels of ECM proteins including fibronectin (FN) and type IV collagen (Coll IV) were detected by qRT-PCR and western blot analysis. The expressions of thioredoxin-interacting protein (TXNIP), nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 were assessed by western blot. Si-TXNIP or si-NC was transfected into HBZY-1 cells to inhibit TXNIP-NLRP3 inflammasome pathway. The results showed that SAL treatment alleviated HG-induced cell proliferation. SAL reduced the levels of ROS and MDA, and induced the SOD activity. Besides, the mRNA and protein expressions of FN and Coll IV were decreased by SAL. The expression levels of TXNIP, NLRP3, ASC, and caspase-1 were reduced in the SAL treated cells. In addition, TXNIP knockdown inhibited TXNIP-NLRP3 inflammasome activation and suppressed HG-induced cell proliferation, oxidative stress, and ECM accumulation. In conclusion, SAL alleviated HG-induced oxidative stress and ECM accumulation in rat glomerular mesangial cells by the TXNIP-NLRP3 inflammasome pathway.

C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs family, was involved in fibrosis. However, the biological function of CTRP6 in renal fibrosis remains elusive. This study aimed to examine the role of CTRP6 in renal fibrosis and explore the possible mechanism. Our results demonstrated that the expression of CTRP6 was significantly downregulated in renal fibrotic tissues and TGF-β1-treated NRK-49F cells. In addition, overexpression of CTRP6 inhibited the proliferation, migration, and ECM expression in TGF-β1-treated NRK-49F cells. Furthermore, overexpression of CTRP6 attenuated TGF-β-induced phosphorylation of ERK1/2 in NRK-49F cells. The ERK1/2 inhibitor U0126 enhanced the inhibitory effects of CTRP6 overexpression on cell proliferation, migration and ECM expression in TGF-β1-stimulated NRK-49F cells. In conclusion, we have demonstrated that CTRP6 suppressed ECM expression in renal fibroblasts induced by TGF-β1 through the ERK signaling pathway. Therefore, CTRP6 may be a potential therapeutic target for the treatment of renal fibrosis.

Background Ginkgetin aglycone (GA), a novel Ginkgo biloba extract (GBE) by acid hydrolysis and recrystallization, is characterized by higher liposolubility and antioxidation than classical GBEs. There is no study depicting the functional role of GA in acute kidney injury (AKI). Here, we firstly reported the protective effect of GA on lipopolysaccharide (LPS)-induced AKI and its underlying mechanism. Methods ELISA analysis was applied to measure plasma level of TNF-α and IL-6, and NF-κB activity in kidney homogenate. Renal function analysis was performed by detecting serum concentration of Kim-1 and urine level of BUN. Cell apoptosis in kidney tissues was detected by TUNEL assay and caspase-3 activity assay. qRT-PCR was conducted to determine mRNA expression of TNF-α, IL-6 and IκBα. Western blot was carried out to confirm expression of p-IκBα, SIRT1, and iNOS. Results GA administration protected mice from LPS-induced AKI by attenuating inflammatory response, renal injury, as well as tubular apoptosis both in vivo. GA suppressed inflammatory response induced by LPS in HK-2 cells. Moreover, GA upregulated SIRT1 expression and blocked the NF-κB signaling pathway in LPS-induced AKT in vivo and vitro. Furthermore, suppression of SIRT1 abated the inhibitory effect of GA on LPS-induced inflammatory response and renal injury. Conclusions GA prevented LPS-induced AKI by activating SIRT1 via inhibiting the NF-κB signaling pathway, providing new insights into the function and molecular mechanism of GA in AKI. Therefore, GA may be a promising therapeutic agent for the treatment of septic AKI.

Remote signal transmission time delays are the major factors to affect the performance of wide-area damping controller (WADC) and even deteriorate stability of large-scale power system. If the physical structure and the mathematical model of the system are different, the method of mathematically dealing with time delay is not the same. From the perspective of mathematical application engineering, there are two main ways to deal with the communication time delay: linear matrix inequalities (LMI) theory and conventional time-delay predictive compensation theory. Traditional time delay damping controller based on linear matrix inequalities (LMI) suffers relatively large conservatism and complexity. Traditional time delay damping controller based on time delay compensation has no clear relation between the control parameter and the time delay. On the other hand, the saturation of actuator leads to the deterioration of control performance and even threat system stability. The existing methods for saturation are negative feedback anti-saturation after the actuator is saturated, which is an afterwards control and it is difficult to well eliminate the influence of saturation. In this paper, a novel design strategy for wide-area time-delay damping controller based on parametric Lyapunov theory is derived. The explicit expression of the controller parameter value associated with the time delay is determined. This strategy can deal with arbitrary large time-vary delay theoretically and have extremely low controller dimension, which makes it have potential capability to be applied in large-scale inter-connected power systems. The control strategy is determined according to the system stability original definition (The system energy function is finite and positive and its first derivative is negative), which avoids complex matrix inequalities cyclic solution and reduces the conservatism of the controller. Moreover, it can directly give simple and explicit control law and specific control parameters, which enable this method to adjust its parameters online according to the exact time delay obtained by GPS. In the design process, the saturation characteristics of the actuator are taken into account in the linearization model of the closed-loop system. This makes it very adaptable to actuator saturation, so that the proposed design strategy can ensure the small signal stability of the closed-loop system considering time delays and actuator saturation. Case study is undertaken based on a New England ten-machine 39-bus power system, which stands for a large scale power system to verify the feasibility and effectiveness of the proposed design strategy. Compared with the free weight matrix damping controller (FWMC), which is a kind of LMI-based design strategy with excellent performance, the advantages and superiority of the proposed control strategy are verified. The proposed design strategy based on state feedback and output feedback has better control performance than FWMC.Remote signal transmission time delays are the major factors to affect the performance of wide-area damping controller (WADC) and even deteriorate stability of large-scale power system. If the physical structure and the mathematical model of the system are different, the method of mathematically dealing with time delay is not the same. From the perspective of mathematical application engineering, there are two main ways to deal with the communication time delay: linear matrix inequalities (LMI) theory and conventional time-delay predictive compensation theory. Traditional time delay damping controller based on linear matrix inequalities (LMI) suffers relatively large conservatism and complexity. Traditional time delay damping controller based on time delay compensation has no clear relation between the control parameter and the time delay. On the other hand, the saturation of actuator leads to the deterioration of control performance and even threat system stability. The existing methods for saturation ar...