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This article narrates and analyzes the author’s life experiences as a learner, teacher, and researcher of diverse languages across three contexts: mainland China, Hong Kong, and Norway. Deconstructing the influential episodes in the writer’s life trajectory, this autoethnography explores the author’s transformation from a monolingually-minded individual to a border-crossing, multilingually hearted scholar. The analysis is undertaken through the theoretical lens of language ideology and dominant language constellation (DLC) and epitomizes the profound influence of sociocultural structures on an individual’s identity search and development. Confronting the multilingual turn in education and echoing the call to centralize identity in language teaching, this self-study exemplifies autoethnography as an empowering method for an ideological shift from perceiving “language(s)-as-problem” to advocating “language(s)-as-resource.” The study also illustrates how the construct of DLC can be deployed as a tangible model of multilinguals’ ever-evolving linguistic identities.

Global concerns towards potentially toxic elements (PTEs) are steadily increasing due to the significant threats that PTEs pose to human health and environmental quality. This calls for immediate, effective and efficient remediation solutions. Earthworms, the 'ecosystem engineers', can modify and improve soil health and enhance plant productivity. Recently, considerable attention has been paid to the potential of earthworms, alone or combined with other soil organisms and/or soil amendments, to remediate PTEs contaminated soils. However, the use of earthworms in the remediation of PTEs contaminated soil (i.e., vermiremediation) has not been thoroughly reviewed to date. Therefore, this review discusses and provides comprehensive insights into the suitability of earthworms as potential candidates for bioremediation of PTEs contaminated soils and mitigating environmental and human health risks. Specifically, we reviewed and discussed: i) the occurrence and abundance of earthworms in PTEs contaminated soils; ii) the influence of PTEs on earthworm communities in contaminated soils; iii) factors affecting earthworm PTEs accumulation and elimination, and iv) the dynamics and fate of PTEs in earthworm amended soils. The technical feasibility, knowledge gaps, and practical challenges have been worked out and critically discussed. Therefore, this review could provide a reference and guidance for bio-restoration of PTEs contaminated soils and shall also help developing innovative and applicable solutions for controlling PTEs bioavailability for the remediation of contaminated soils and the mitigation of the environment and human risks.

In order to improve the analysis effect of legal issues of the crime of endangering public safety, this paper analyzes the legal issues of the crime of endangering public safety based on the actual mining algorithm and uses numerical methods to qualitatively study the evolution behavior across phase intervals. Moreover, this paper improves the algorithm based on the actual needs of legal mining. When solving the eigenvalues of the given Hamiltonian’s duration equation, the zero-energy solution can be found in the case of open boundaries. In addition, this paper applies the improved algorithm proposed in this paper to the mining of criminal law legal issues of crimes against public safety, assigns a dynamic IP to each process, and builds a model based on this. Through the above simulation research, it can be seen that the legal problem analysis model of the crime of endangering public safety based on the data mining algorithm proposed in this paper has a good legal data mining effect.

Oxidative stress-induced vascular endothelial cell (VEC) injury is a major mechanism in the initiation and development of atherosclerosis. Lunasin, a soybean-derived 43-aa peptide, has been previously shown to possess potent antioxidant and anti-inflammatory activities other than its established anticancer activities. This study investigated the effects of lunasin on protecting VECs from oxidative damage and inhibiting atherosclerotic plaque progression in apolipoprotein E-deficient (ApoE-/-) mice and explored its underlying mechanism. Biochemical and histologic analyses were performed by using EA.hy926 human VECs and a high-fat diet (HFD) ApoE-/- mouse atherosclerosis model. Our data indicated that lunasin attenuated H2O2-induced, mitochondria-dependent endothelial apoptosis via down-regulating Bax and up-regulating Bcl-2, inhibiting the mitochondrial depolarization, and reducing the release of cytochrome c, as well as decreasing the activation of caspase-9 and caspase-3 in vitro and in vivo. Mechanic studies showed that lunasin significantly up-regulated heme oxygenase-1 via the PI3K/Akt/nuclear factor erythroid 2-related factor 2/antioxidant response element pathway, and reduced H2O2-induced ROS production in VECs, thereby attenuating oxidant-induced endothelial injury and inhibiting atherosclerotic plaque progression in ApoE-/- mice. In conclusion, our in vitro and in vivo data suggest that lunasin protects VECs from oxidative damage by enhancing heme oxygenase-1 expression via activation of the PI3K/Akt/nuclear factor erythroid 2-related factor 2/antioxidant response element pathway and inhibiting mitochondria-dependent apoptosis, thereby effectively attenuating atherosclerosis in HFD-fed ApoE-/- mice. Lunasin may act as a potential therapeutic agent for the prevention and treatment of atherosclerosis.-Gu, L., Ye, P., Li, H., Wang, Y., Xu, Y., Tian, Q., Lei, G., Zhao, C., Gao, Z., Zhao, W., Tan, S. Lunasin attenuates oxidant-induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE-/- mice by up-regulating heme oxygenase-1 via PI3K/Akt/Nrf2/ARE pathway.

It is of great significance to explore the remediation pattern in actual heavy metal (HM) contaminated sites. The field trial was carried out to research the remediation effect of biochar near a lead-zinc smelter in Feng County, China, under the rotation condition of different crops. This kind of cultivation mode is very representative in northern of China. And the pattern of production and restoration is suitable for scarce land resources and large food demand in China. The changes of soil physiochemical properties with the biochar addition, crop growth and the accumulated HMs by crops were focused on. The results showed the biochar application was excellent in improving soil nutrient elements and crop growth. The contents of TK were more obvious than those of TN and TP, with an increase of 2.6%-28.2% compared with the controls (without the addition of biochar). The yield of first season crops, i.e., soybean and corn, increased by 30%-42% and 34%-61%, respectively, and the second season crops, i.e., rape and wheat, with the increment of 25%-41% and 9%-29%, respectively. The availability forms of Cd and Pb decreased by 1.07-10.0% and 2.92-8.35%, respectively. While the improvement on the status of the HMs accumulated by crops was disappointing. The contents of HMs accumulated by crops increased to varying degrees (e.g., Pb and Zn in root, Cu and Pb in grain, and Cd in stems and leaves). Moreover, the concentrations of HMs in seeds of crops were higher than the limited levels given by the Chinese directive. Considering the results of the study and food safety, it is suggested to change the nature of the land around the smelter into woodland or construction land to prohibit the cultivation of food crops in this area.

It is of great significance to explore the remediation pattern in heavy metal (HM) contaminated soil under the actual farming mode. This field trial was carried out under the rotation condition s (soybean-rape, corn-wheat) lasting for a 2-crop season near a lead-zinc smelter, exploring the effect of biochar on the physical and chemical properties of rhizosphere soil, crop yield, total and different forms of HMs in soil, and the HM accumulation by crops. No significant change in pH in soil was observed, as did the EC values with a low dose of biochar added. The contents of TK increased by 0.87% ~ 28.2% with the biochar addition compared with the controls. The effect of high-dose biochar on increasing the nutrient elements in soil was obvious. Additionally, the contents of soil total humic carbon(THC) increased significantly ( P < 0.05) by 3.7% ~ 72.7%. The yield of first season crops (soybean and corn) increased by 30% ~ 42% and 34% ~ 61% respectively, as did the second season crops of rape (25% ~ 41%) and wheat (9% ~ 29%). Furthermore, the reduction in the availability form (F1+F2) of Cd and Pb was 1.07-10.0% and 2.92-8.35%, respectively, while there was a tendency of Zn to increase. The biochar addition led to significant differences in the soil total contents of HMs. The contents of HMs accumulated by crops increased, although biochar significantly ( P < 0.05) decreased the total contents of Pb and Zn in soil.The Cd, Pb and Zn accumulation in stems and leaves of crops was higher than that in roots. This study helped clarify the sustainable effect of biochar on the bioavailability of HMs under rotation conditionsand could be used to guide the remediation of contaminated soil in actual mining areas.

Skeletal muscle weight loss is accompanied by small fiber size and low protein content. Alpha-ketoglutarate (AKG) participates in protein and nitrogen metabolism. The effect of AKG on skeletal muscle hypertrophy has not yet been tested, and its underlying mechanism is yet to be determined. In this study, we demonstrated that AKG (2%) increased the gastrocnemius muscle weight and fiber diameter in mice. Our in vitro study also confirmed that AKG dose increased protein synthesis in C2C12 myotubes, which could be effectively blocked by the antagonists of Akt and mTOR. The effects of AKG on skeletal muscle protein synthesis were independent of glutamate, its metabolite. We tested the expression of GPR91 and GPR99. The result demonstrated that C2C12 cells expressed GPR91, which could be upregulated by AKG. GPR91 knockdown abolished the effect of AKG on protein synthesis but failed to inhibit protein degradation. These findings demonstrated that AKG promoted skeletal muscle hypertrophy via Akt/mTOR signaling pathway. In addition, GPR91 might be partially attributed to AKG-induced skeletal muscle protein synthesis.

The conversion of skeletal muscle fiber from fast twitch to slow‐twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber‐type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss‐of‐function models generated by phospholipase Cβ antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius‐specific knockdown, we found that the effects of succinate on skeletal muscle fiber‐type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate‐based compounds in both athletic and sedentary populations.

The structure and function of green-space system is an eternal subject of landscape architecture, especially due to limited land and a need for the coordinated development of PLEs (production, living, and ecological spaces). To make planning more scientific, this paper explored green-space structure planning via multidimensional perspectives and methods using a case study of Zhengzhou. The paper applies theories (from landscape architecture and landscape ecology) and technologies (like remote sensing, GIS&mdash, geographic information system, graph theory, and aerography) from different disciplines to analyze current green-space structure and relevant physical factors to identify and exemplify different green-space planning strategies. Overall, our analysis reveals that multiple green-space structures should be considered together and that planners and designers should have multidisciplinary knowledge. For specific strategies, the analysis finds (i) that green complexes enhance various public spaces and guide comprehensive development of urban spaces, (ii) that green ecological corridors play a critical role in regional ecological stability through maintaining good connectivity and high node degree (Dg) and betweenness centrality index (BC) green spaces, (iii) that greenway networks can integrate all landscape resources to provide more secured spaces for animals and beautiful public spaces for humans, (iv) that blue-green ecological networks can help rainwater and urban flooding disaster management, and (v) that green ventilation corridors provide air cleaning and urban cooling benefits, which can help ensure healthy and comfortable urban&ndash, rural environments. In our view, this integrated framework for planning and design green-space structure helps make the process scientific and relevant for guiding future regional green-space structure.

Capsaicin is a major pungent content in green and red peppers which are widely used as spice, and capsaicin may activate different receptors. To determine whether capsaicin has different effects on different types of skeletal muscle, we applied different concentrations (0, 0.01, and 0.02%) of capsaicin in the normal diet and conducted a four-week experiment on Sprague-Dawley rats. The fiber type composition, glucose metabolism enzyme activity, and different signaling molecules' expressions of receptors were detected. Our results suggested that capsaicin reduced the body fat deposition, while promoting the slow muscle-related gene expression and increasing the enzyme activity in the gastrocnemius and soleus muscles. However, fatty acid metabolism was significantly increased only in the soleus muscle. The study of intracellular signaling suggested that the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid receptors in the soleus muscle were more sensitive to capsaicin. In conclusion, the distribution of TRPV1 and cannabinoid receptors differs in different types of muscle, and the different roles of capsaicin in different types of muscle may be related to the different degrees of activation of receptors.

Skeletal muscle atrophy due to excessive protein degradation is the main cause for muscle dysfunction, fatigue, and weakening of athletic ability. Endurance exercise is effective to attenuate muscle atrophy, but the underlying mechanism has not been fully investigated. α-Ketoglutarate (AKG) is a key intermediate of tricarboxylic acid cycle, which is generated during endurance exercise. Here, we demonstrated that AKG effectively attenuated corticosterone-induced protein degradation and rescued the muscle atrophy and dysfunction in a Duchenne muscular dystrophy mouse model. Interestingly, AKG also inhibited the expression of proline hydroxylase 3 (PHD3), one of the important oxidoreductases expressed under hypoxic conditions. Subsequently, we identified the β2 adrenergic receptor (ADRB2) as a downstream target for PHD3. We found AKG inhibited PHD3/ADRB2 interaction and therefore increased the stability of ADRB2. In addition, combining pharmacologic and genetic approaches, we showed that AKG rescues skeletal muscle atrophy and protein degradation through a PHD3/ADRB2 mediated mechanism. Taken together, these data reveal a mechanism for inhibitory effects of AKG on muscle atrophy and protein degradation. These findings not only provide a molecular basis for the potential use of exercise-generated metabolite AKG in muscle atrophy treatment, but also identify PHD3 as a potential target for the development of therapies for muscle wasting.—Cai, X., Yuan, Y., Liao, Z., Xing, K., Zhu, C., Xu, Y., Yu, L., Wang, L., Wang, S., Zhu, X., Gao, P., Zhang, Y., Jiang, Q., Xu, P., Shu, G. α-Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway.

// Lili Gu 1 , Yue Wang 1 , Yaqiong Xu 1 , Qinghua Tian 1 , Gaoxin Lei 1 , Cheng Zhao 1 , Zhan Gao 1 , Qin Pan 1 , Wenfeng Zhao 1 , Liu Nong 1 and Shuhua Tan 1 1 State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China Correspondence to: Shuhua Tan, email: tanshuhua163@163.com Keywords: lunasin, proprotein convertase subtilisin/kexin type 9, low-density lipoprotein cholesterol, low-density lipoprotein receptor, hepatocyte nuclear factor-1α Received: June 26, 2017 Accepted: August 04, 2017 Published: August 24, 2017 ABSTRACT Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease which regulates serum low-density lipoprotein cholesterol (LDL-C) levels by promoting the degradation of the hepatic low-density lipoprotein receptor (LDLR), and has become an attractive therapeutic target for cholesterol lowering intervention. Lunasin, a 43-amino acid polypeptide initially isolated from soybean, has been previously proven to possess cholesterol lowering activity. Here we identified the down-regulation of PCSK9 expression by lunasin as one new mechanism that increased cell-surface LDLR level and enhanced LDL uptake in vitro and in vivo . Treatment of HepG2 cells with lunasin inhibited the expression of PCSK9 at mRNA and protein levels in a dose-and-time dependent manner via down-regulating hepatocyte nuclear factor-1α (HNF-1α), thereby contributing to increasing LDLR level and functionally enhancing LDL uptake. ApoE -/- mice receiving lunasin administration by intraperitoneal injection at doses of 0.125~0.5 μmol/kg·day for 4 weeks had significantly lower PCSK9 and higher LDLR levels in hepatic tissue, as well as remarkably reduced total-cholesterol (T-CHO) and LDL-C in blood as compared to mice in vehicle control group. Furthermore, we identified that LDLR expression was up-regulated by lunasin via PI3K/Akt-mediated activation of SREBP-2 in HepG2 cells. Taken together, our findings suggest that lunasin inhibits PCSK9 expression by down-regulating HNF-1α and enhances LDLR expression via PI3K/Akt-mediated activation of SREBP-2 pathway, thereby functionally enhances LDL uptake in HepG2 cells and in ApoE -/- mice.

Laminarin, a type of β-glucan isolated from brown seaweeds, exhibits verity of physiological activities, which include immunology modulation and antitumor function. To investigate the effect of laminarin on energy homeostasis, mice were orally administrated with laminarin to test food intake, fat deposition, and glucose homeostasis. Chronically, laminarin treatment significantly decreases high-fat-diet-induced body weight gain and fat deposition and reduces blood glucose level and glucose tolerance. Acutely, laminarin enhances serum glucagon-like peptide-1 (GLP-1) content and the mRNA expression level of proglucagon and prohormone convertase 1 in ileum. Subsequently, laminarin suppresses the food intake of mice, the hypothalamic AgRP neuron activity, and AgRP expression but activates pancreatic function. Furthermore, laminarin-induced appetite reduction was totally blocked by Exendin (9-39), a specific competitive inhibitor of GLP-1 receptor. Then, STC-1 cells were adopted to address the underlying mechanism, by which laminarin promoted GLP-1 secretion in vitro. Results showed that laminarin dose-dependently promoted GLP-1 secretion and c-Fos protein expression in STC-1 cells, which were independent of Dectin-1 and CD18. Interestingly, BAPTA-AM, a calcium-chelating agent, potently attenuated laminarin-induced [Ca2+]i elevation, c-Fos expression, and GLP-1 secretion. In summary, our data support that laminarin counteracts diet-induced obesity and stimulates GLP-1 secretion via [Ca2+]i; this finding provides an experimental basis for laminarin application to treat obesity and maintain glucose homeostasis.

Background and aims MicroRNAs (miRs) exert important regulatory effects in cholesterol metabolism. Hepatic low density lipoprotein receptor (LDLR) pathway, as the major mechanism for clearing circulating low density lipoprotein cholesterol (LDL-C) in bloodstream, is a pivotal therapeutic target to treat hypercholesterolemia and atherosclerosis. This study aimed to identify novel miRs that regulate LDLR expression. Methods and results Hsa-miR-140-5p was predicted by bioinformatics analyses to interact with human LDLR mRNA. To evaluate its functional effects in regulating LDLR, hsa-miR-140-5p and anti-miR-140-5p were transfected into human and mouse liver cells, followed by qRT-PCR, western blot, immunofluorescence, flow cytometry, and LDL-C uptake assays. It was observed that hsa-miR-140-5p over-expression dramatically down-regulated LDLR expression and reduced LDL-C uptake, whereas inhibition of hsa-miR-140-5p significantly up-regulated LDLR expression and enhanced LDL-C uptake in human HepG2 and LO2 cells, but not in mouse Hepa1-6 cells. Luciferase reporter assay and site-directed mutagenesis identified that hsa-miR-140-5p interacts with the predicted seed sequence “AAACCACU” in the 3′-UTR of human LDLR mRNA. Hsa-miR-140-5p over-expression attenuated LDL-C uptake and decreased intracellular cholesterol levels in the presence of 50 μg/ml ox-LDL in HepG2 cells. Additionally, palmitic acid and simvastatin suppressed, whereas LDL-C up-regulated the expression of miR-140-5p in HepG2 cells. Conclusions Hsa-miR-140-5p is a negative regulator of LDLR expression in human hepatocytes, but not in mouse hepatocytes. Simvastatin inhibits hsa-miR-140-5p expression in human hepatocytes, which is likely to be a novel mechanism for treating hypercholesterolemia with statins in clinic. Antagonism of hsa-miR-140-5p could be a new therapeutic strategy for the treatment of hypercholesterolemia and atherosclerosis.

Oxidative stress-induced vascular endothelial cell (VEC) injury is a major mechanism in the initiation and development of atherosclerosis. Lunasin, a soybean-derived 43-aa peptide, has been previously shown to possess potent antioxidant and anti-inflammatory activities other than its established anticancer activities. This study investigated the effects of lunasin on protecting VECs from oxidative damage and inhibiting atherosclerotic plaque progression in apolipoprotein E-deficient (ApoE

The last two decades have seen tremendous progress in quantitative understanding of several major phonon scattering mechanisms (phonon-phonon, phonon-boundary, phonon-defects), as they are the determinant factors in lattice thermal transport, which is critical for the proper functioning of various electronic and energy conversion devices. However, the roles of another major scattering mechanism, electron-phonon (e-ph) interactions, remain elusive. This is largely due to the lack of solid experimental evidence for the effects of e-ph scattering in the lattice thermal conductivity for the material systems studied thus far. Here we show distinct signatures in the lattice thermal conductivity observed below the charge density wave transition temperatures in NbSe

We describe a biosensor for dopamine that is based on the use of a gold electrode modified with carbon nanoparticles (CNPs) coupled to thionine labeled gold nanoparticles (AuNPs) acting as signal amplifiers. The biosensor was constructed by first modifying the CNPs on the gold electrode and adsorbing the thionine on the surface of the AuNPs, and then linking the complementary strand of the dopamine aptamer to the AuNPs via gold-thiol chemistry. Next, dopamine aptamer is added and the duplex is formed on the surface. On addition of a sample containing dopamine, it will interact with aptamer and cause the release of the electrochemical probe which then will be adsorbed on the surface of the CNP-modified gold electrode and detected by differential pulse voltammetry. The current is linearly related to the concentration of dopamine in the 30 nM to 6.0 μM ranges. The detection limit is as low as 10 nM, and the RSD is 3.1 % at a 0.3 μM level (for n = 11). The protocol was successfully applied to the determination of dopamine in spiked human urine samples. We perceive that this method holds promise as a widely applicable platform for aptamer-based electrochemical detection of small molecules.

We describe a highly sensitive and selective peptide-based biosensor for the prostate-specific antigen (PSA). The biotinylated peptide biotin-EHSSKLQKC served as a molecular recognition element. It was self-assembled on the surface of the wells of a 96-well microtiter plate modified with gold nanoparticles (AuNPs). In parallel, streptavidin-coated magnetic beads (strep-MBs) were modified with the enzyme invertase and then added to the peptide-modified wells upon which the modified strep-MBs bind to the peptide via biotin/streptavidin interaction. If a sample containing PSA is placed in the well, PSA will cause the cleavage of the peptide, and a respective quantity of invertase-modified strep-MBs will be released. The supernatant containing the invertase-modified strep-MBs is taken out and sucrose is added which is enzymatically cleaved by invertase. The concentration of the glucose formed after 1 h is quantified with a personal glucose meter. It is linearly related to the concentration of PSA in the range from 80 pg to 7 ng∙mL−1. The detection limit is 30 pg∙mL−1 and the relative standard deviation is 3.7 % (at a level of 500 pg∙mL−1 and for n = 7). The method was successfully applied to the determination of PSA in spiked real human urine. Due to its simplicity, sensitivity and selectivity, this bioassay offers a promising approach to the detection of PSA and other biomolecules.

In this paper a highly sensitive and selective aptamer biosensor for quantitative detection of a model target, dopamine, was developed by using a ubiquitous personal glucose meter (PGM). Dopamine aptamer was combined on the gold nanoparticles (AuNPs) modified 96-well plate. The signal probe, dopamine aptamer complementary strand (DNA2)–invertase–AuNPs, which was prepared with DNA2, invertase and AuNPs was immobilized onto the 96-well plate through the hybridization of aptamer and DNA2. Upon the addition of dopamine, aptamer would interact with it, and the hybridization of aptamer and DNA2 was destroyed and the DNA2–invertase–AuNPs probe was forced away from the surface of the 96-well plate. The invertase carried on AuNPs catalyzed the hydrolysis of sucrose to produce a large amount of glucose for quantitative readout by the PGM. PGM signal versus the concentration of dopamine was linear in the range from 0.08 to 100 μmol L−1. The detection limit was 0.03 μmol L−1 in 2 μL (∼60 femtomol), and the relative standard deviation (RSD) was 3.7% at 5 μmol L−1 (n = 7). The developed method is successfully demonstrated for dopamine determination in human blood serum. Due to its simplicity, sensitivity and selectivity, this biosensor offers a promising approach for the detection of dopamine and other biomolecules.

It is well known that endurance training is effective to attenuate skeletal muscle atrophy. Succinate is a typical TCA metabolite, of which exercise could dramatically increase the content. The present study aimed to investigate the effect of succinate on protein synthesis in skeletal muscle, and try to delineate the underlying mechanism. The in vitro study revealed that succinate dose-dependently increased protein synthesis in C2C12 myotube along with the enhancement of phosphorylation levels of AKT Serine/Threonine Kinase 1(Akt), mammalian target of rapamycin, S6, eukaryotic translation initiation factor 4E, 4E binding protein 1 and forkhead box O (FoxO) 3a. Furthermore, it was demonstrated that 20 mM succinate markedly increased [Ca2+]i. Then, the phospho-extracellular regulated kinase (Erk), -Akt level and the crosstalk between Erk and Akt were elevated in response to succinate. Notably, the Erk antagonist (U0126) or mTOR inhibitor (rapamycin) abolished the effect of succinate on protein synthesis. The in vivo study verified that succinate dose-dependently increased the protein synthesis, in addition to phosphorylation levels of Erk, Akt and FoxO3a in gastrocnemius muscle. In summary, these findings demonstrated that succinate promoted skeletal muscle protein deposition via Erk/Akt signaling pathway.

Skeletal muscle weight loss is accompanied by small fiber size and low protein content. Alpha-ketoglutarate (AKG) participates in protein and nitrogen metabolism. The effect of AKG on skeletal muscle hypertrophy has not yet been tested, and its underlying mechanism is yet to be determined. In this study, we demonstrated that AKG (2%) increased the gastrocnemius muscle weight and fiber diameter in mice. Our in vitro study also confirmed that AKG dose increased protein synthesis in C2C12 myotubes, which could be effectively blocked by the antagonists of Akt and mTOR. The effects of AKG on skeletal muscle protein synthesis were independent of glutamate, its metabolite. We tested the expression of GPR91 and GPR99. The result demonstrated that C2C12 cells expressed GPR91, which could be upregulated by AKG. GPR91 knockdown abolished the effect of AKG on protein synthesis but failed to inhibit protein degradation. These findings demonstrated that AKG promoted skeletal muscle hypertrophy via Akt/mTOR signaling pathway. In addition, GPR91 might be partially attributed to AKG-induced skeletal muscle protein synthesis.

Skeletal muscle weight loss is accompanied by small fiber size and low protein content. Alpha-ketoglutarate (AKG) participates in protein and nitrogen metabolism. The effect of AKG on skeletal muscle hypertrophy has not yet been tested, and its underlying mechanism is yet to be determined. In this study, we demonstrated that AKG (2%) increased the gastrocnemius muscle weight and fiber diameter in mice. Our in vitro study also confirmed that AKG dose increased protein synthesis in C2C12 myotubes, which could be effectively blocked by the antagonists of Akt and mTOR. The effects of AKG on skeletal muscle protein synthesis were independent of glutamate, its metabolite. We tested the expression of GPR91 and GPR99. The result demonstrated that C2C12 cells expressed GPR91, which could be upregulated by AKG. GPR91 knockdown abolished the effect of AKG on protein synthesis but failed to inhibit protein degradation. These findings demonstrated that AKG promoted skeletal muscle hypertrophy via Akt/mTOR signaling pathway. In addition, GPR91 might be partially attributed to AKG-induced skeletal muscle protein synthesis.