Reactive Oxygen-Correlated Photothermal Imaging of Smart COF Nanoreactors for Monitoring Chemodynamic Sterilization and Promoting Wound Healing.

Chemodynamic therapy (CDT) has emerged as a promising approach for treating infected diabetic wounds, while reliable imaging technology for simultaneous monitoring of ROS and therapeutic processes is still a formidable challenge. Herein, smart covalent organic framework (COF) nanoreactors (COF NRs) are constructed by hyaluronic acid (HA) packaged glucose oxidase (GOx) covalently linked Fe-COF for diabetic wound healing. Upon the breakdown of the HA protective layer, GOx consumes glucose to produce gluconic acid and hydrogen peroxide (H2 O2 ), resulting in decreased local pH and H2 O2 supplementation. Density functional theory (DFT) calculations show that Fe-COF has high catalytic activity towards H2 O2 , leading to in situ generation of hydroxyl radicals (·OH) for sterilization, and the localized downregulation of glucose effectively improved the microenvironment of diabetic wounds. Meanwhile, based on the near-infrared photothermal imaging of oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), the authors showed that TMB can be applied for the point-of-care testing of ·OH and glucose, and assessing the sterilization progress in vivo. More significantly, the facile photothermal signaling strategy can be extended to monitor various ROS-mediated therapeutic systems, enabling accurate prediction of treatment outcomes.

Ambient Synthesis of Porphyrin-Based Fe-Covalent Organic Frameworks for Efficient Infected Skin Wound Healing.

Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.

Honokiol attenuates high glucose-induced peripheral neuropathy via inhibiting ferroptosis and activating AMPK/SIRT1/PGC-1α pathway in Schwann cells.

Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC-1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC-1 staining results demonstrated that honokiol reduced HG-induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT-qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG-induced inhibition of AMPK/SIRT1/PGC-1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG-induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin-induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG-induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.

Copper nanoclusters trigger muscle cell apoptosis and atrophy in vitro and in vivo.

Copper nanoclusters (CuNCs) are increasingly being used in nanomedicine owing to their utility in cellular imaging and as catalysts. Additionally, nanotoxicology research of CuNCs is gaining attention. We report here the synthesis and characterization of CuNCs and their cytotoxic impact on muscle cells. A simple protein-directed synthesis of stable CuNCs was prepared, using bovine serum albumin as the stabling agent. Physicochemical characterization of the synthesized CuNCs was performed using transmission electron microscopy. To evaluate the in vitro cytotoxicity, C2C12 cells were exposed to increasing doses (from 0.1 to 50 µg ml(-1)) of CuNCs. CuNCs affected the viability of C2C12 cells in a dose-dependent manner, as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and a lactate dehydrogenase release assay. Further studies indicated that CuNCs induced the formation of reactive oxygen species and decreased the activities of catalase and glutathione. CuNC treatment decreased the mitochondrial membrane potential and induced apoptosis, accompanied by an increase in the protein expression ratio of Bax/Bcl-2 and caspase-3/9 activity in C2C12 cells. CuNCs treatment resulted in atrophy of the C2C12 myotubes, which was characterized by the increased expression of atrophy-related genes, such as atrogin-1 and MuRF1. Finally, CuNCs induce morphological atrophy of primary muscle cells and mouse gastrocnemius muscle. Taken together, these results suggest that exposure to CuNCs may be a risk factor for the skeletal muscle system.

Astragaloside I Stimulates Osteoblast Differentiation Through the Wnt/ß-catenin Signaling Pathway.

Astragaloside I (As-I), one of the main active ingredients in Astragalus membranaceus, is believed to have osteogenic properties, but this hypothesis has not been investigated in detail. In the present work, the As-I-induced osteogenic effects and its underlying mechanism were studied in MC3T3-E1 cells. The results indicated that the cellular levels of ALP and extracellular matrix calcium increased in a dose-dependent manner by As-I. To clarify the mechanisms involved in this process, the effect of As-I on the key osteogenic-related genes was investigated. We found that As-I stimulated the expression of ß-catenin and Runx2 in MC3T3-E1 cells, which play central roles in the Wnt/ß-catenin signaling pathway, suggesting that As-I could promote osteoblastic differentiation by regulating the Wnt/ß-catenin signaling pathway. Moreover, the osteogenic effect of As-I could be inhibited by DKK-1, which is the classical inhibitor of Wnt/ß-catenin-signaling pathway. Furthermore, As-I also increased BMP-2, BGP and OPG/RANKL expression, which are also activated by Wnt/ß-catenin signaling pathway. Taken together, our findings show that As-I stimulates osteoblast differentiation through the Wnt/ß-catenin signaling pathway, which also activates the BMP pathway and RANK pathway, thus highlighting the As-I for pharmaceutical and medicinal applications such as treating bone disease. Copyright © 2016 John Wiley & Sons, Ltd.

The antidiabetic and hepatoprotective effects of magnolol on diabetic rats induced by high-fat diet and streptozotocin.

The effects of magnolol (Mag) on hyperglycemia and hyperlipemia, hepatic oxidative stress and cytochrome P4502E1 (CYP2E1) activity of diabetic rats induced by high-fat diet (HFD) and streptozotocin (STZ) were studied. After oral administration of Mag (25, 50 and 100 mg x kg(-1) x d(-1)) for continuous 10 weeks, the blood glucose and lipids (TC, TG and LDL-C) levels, as well as the hepatic CYP2E1 activity and MDA content of diabetic rats, decreased significantly (P < 0.05 or P < 0.01), whereas the oral glucose tolerance and hepatic antioxidant enzymatic activities (CAT and GSH-Px) of diabetic rats, increased significantly (P < 0.05 or P < 0.01). The results indicated that Mag was effective against the hepatic oxidative damage, hyperglycemia and hyperlipemia of diabetic rats induced by HFD and STZ, and the inhibition of Mag on hepatic CYP2E1 activity could be an important mechanism of Mag against hepatic insulin resistance and oxidative damage.

Nano-induced endothelial leakiness-reversing nanoparticles for targeting, penetration and restoration of endothelial cell barrier.

Nano-induced endothelial leakiness (NanoEL) can improve the ability of nanoparticles (NPs) to enter the tumor environment, nevertheless, it can inadvertently trigger adverse effects such as tumor metastasis. To overcome these concerns, it becomes important to develop a NPs design strategy that capitalizes on the NanoEL effect while averting unwanted side effects during the drug delivery process. Herein, we introduce the PLGA-ICG-PEI-Ang1@M NP which has a core comprising poly (lactic-co-glycolic acid) (PLGA) and the inner shell with a highly positively charged polyethyleneimine (PEI) and the anti-permeability growth factor Angiopoietin 1 (Ang1), while the outer shell is camouflaged with a Jurkat cell membrane. During the drug delivery process, our NPs exhibit their capability to selectively target and penetrate endothelial cell layers. Once the NPs penetrate the endothelial layer, the proton sponge effect triggered by PEI in the acidic environment surrounding the tumor site can rupture the cell membrane on the NPs' surface. This rupture, in turn, enables the positively charged Ang1 to be released due to the electrostatic repulsion from PEI and the disrupted endothelial layer can be restored. Consequently, the designed NPs can penetrate endothelial layers, promote the cell layer recovery, restrict the tumor metastasis, and facilitate efficient cancer therapy. STATEMENT OF SIGNIFICANCE.

MicroRNA-29a-c decrease fasting blood glucose levels by negatively regulating hepatic gluconeogenesis.

BACKGROUND & AIMS: The expression levels of microRNA-29 (miR-29) family members (miR-29a, miR-29b, miR-29c, here denoted collectively as miR-29a-c) are increased in livers of Goto-Kakizaki diabetic rats and db/db diabetic mice. However, the functional consequences of miR-29a-c upregulation in diabetic livers are not explored. The objective of this study was to evaluate the roles of miR-29a-c in the regulation of hepatic glucose production and blood glucose levels using different mouse models. METHODS: db/m, db/db diabetic and diet-induced obese (DIO) mice were injected with adenovirus expressing miR-29a-c through the tail vein. Blood glucose levels were measured and glucose-tolerance tests and pyruvate-tolerance tests were performed. To explore the molecular mechanism by which miR-29a-c regulate hepatic glucose metabolism, gain or loss of miR-29a-c function studies were performed in primary mouse hepatocytes and the direct effectors of miR-29-mediated effects on glucose metabolism were identified. RESULTS: Adenovirus-mediated overexpression of miR-29a-c in the livers of db/m, db/db, and DIO mice decreased fasting blood glucose levels and improved glucose tolerance. Overexpression of miR-29a-c in primary hepatocytes and mouse livers decreased the protein levels of PGC-1α and G6Pase, the direct targets of miR-29a-c, thereby reducing cellular, and hepatic glucose production. In contrast, loss of miR-29a-c function in primary hepatocytes increased the protein levels of PGC-1α and G6Pase and increased cellular glucose production. Finally, enforced expression of PGC-1α increased miR-29a-c expression levels in primary hepatocytes, thus forming a negative feedback regulation loop. CONCLUSIONS: miR-29a-c can regulate hepatic glucose production and glucose tolerance in mice.

Study on hydrological response of runoff to land use change in the Jing River Basin, China.

Land use change greatly affects the runoff characteristics of the basin, which in turn affects the distribution of surface water and groundwater in the region. Quantitative analyses of the hydrological response of watershed runoff to land use change are conducive to the formulation of sustainable water resource strategies. In this paper, the impact of land use change on runoff characteristics in the Jing River Basin was evaluated using the SWAT model, the land use pattern of the Jing River Basin in 2040 was predicted using CA-Markov model, and five land use change scenarios were set up in combination with the trend of land use transfer, and the response relationship between land use change and runoff hydrological characteristics in the basin was studied. The results show that the land use changes reduce runoff and change the hydrological cycle process of the basin. The hydrological response of different land use types varies significantly, but only has a less impact on annual runoff. Farmland has a promoting effect on production flow; woodland and grassland are not conducive to the formation of surface runoff and will increase underground runoff and evapotranspiration in the basin. The increase in vegetation coverage after returning farmland to woodlands and grasslands has reduced surface runoff, increased the recharge of groundwater, and played a positive role in ecological restoration in the river basin. The research results are of great significance for understanding the hydrological consequences of land use change and the rational planning of land use patterns in river basins.

Acid-degradable nanocomposite hydrogel and glucose oxidase combination for killing bacterial with photothermal augmented chemodynamic therapy.

Bacterial infection often delays diabetic wound healing, and even causes serious life-threatening complications. Herein, we successfully developed a Cu2O/Pt nanocubes-dopping alginate (ALG)- hyaluronic acid (HA) hydrogel (Cu2O/Pt hydrogel) by simple assembly of the Cu2O/Pt nanocubes and the ALG-HA mixture. The Cu2O/Pt hydrogel combined with the glucose oxidase (GOx) can be used for photothermal- and starving-enhanced chemodynamic therapy (CDT) against Gram-negative and Gram-positive bacteria. The GOx can catalyze the glucose to produce gluconic acid and H2O2 for starvation therapy, following which the released Cu2O/Pt nanocubes react with H2O2 in the acidic microenvironment to generate highly cytotoxic hydroxyl radicals (·OH) for CDT. Additionally, the Cu2O/Pt hydrogel can release copper ions gradually with the decrease of pH induced by gluconic acid, which can increase the protein expression and secretion of vascular endothelial growth factor (VEGF) and promote endothelial cell proliferation, migration and angiogenesis, subsequently promoting diabetic wound healing in rats. Our results suggested that the Cu2O/Pt hydrogel combined with GOx may be a potential therapeutic approach for treating the infected diabetic wound.

Formononetin attenuates high glucose-induced neurotoxicity by negatively regulating oxidative stress and mitochondrial dysfunction in Schwann cells via activation of SIRT3.

High glucose induces Schwann cells death and neurotoxicity. Formononetin was originally found in Astragalus membranaceus and showed anti-tumor and anti-neuroinflammation properties. The aim of this study is to explore the molecular mechanism underlying the neuroprotective effects of formononetin and identify its direct protein target. The effects of formononetin on oxidative stress and mitochondrial dysfunction in Schwann cells induced by high glucose were investigated. High glucose treatment significantly induced oxidative stress, mitochondrial dysfunction and apoptosis in Schwann cells, while these effects were partially or completely prevented by co-treatment with formononetin. Mechanistically, we found that SIRT3/PGC-1α/SOD2 pathway was activated by formononetin under high glucose conditions as evidenced by western blotting. Knockdown of SIRT3 by siRNA delivery reversed the protective effects of formononetin on high glucose-induced Schwann cells injury and changes in expression profile of SIRT3 downstream target genes. Molecular docking, thermal shift assay and surface plasmon resonance assay revealed a direct binding between formononetin and SIRT3. Taken together, we identified a novel SIRT3 activator formononetin and revealed its beneficial effects on high glucose-induced neurotoxicity, suggesting that targeting SIRT3 in Schwann cells may be a new approach for treatment of peripheral nerve regeneration related diseases such as diabetic peripheral neuropathy.

[Reform and exploration of biopharmaceutics blended teaching in the context of "first-class undergraduate education"].

In recent years, the biopharmaceutical industry has developed rapidly, creating urgent demand for high-quality, innovative, and application-oriented talents. In the context of "first-class undergraduate education", it is of great significance to reform and explore biopharmaceutics blended learning to foster professional talents who can adapt to the industrial development. The blended teaching of biopharmaceutics course in Hubei University was based on small private online course (SPOC) and ChaoXing platform, aiming to meet the first-class "AIC (advanced, innovation, challenge)". The course strengthened the three phases of teaching: before, during, and after class, and innovated teaching methods actively to achieve curriculum goals, and integrated typical cases organically. In addition, the course improved the discriminative power of assessment by strengthening the formative performance evaluation. Moreover, the course provided guidance for students to improve the learning efficiency through investigating the students' learning behavior and employing the marginal utility curve to analyze the characteristics of group activities. Furthermore, the course also offered students personalized learning guidance based on their career planning. The reform of biopharmaceutics blended teaching has achieved significant outcomes, such as improving students' satisfaction, students' innovation and entrepreneurship ability, and curriculum construction level, thus may serve as a reference for the teaching reform and research of the related courses.

Mouse patatin-like phospholipase domain-containing 3 influences systemic lipid and glucose homeostasis.

UNLABELLED: Human patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with increased liver fat content and liver injury. Here, we show that nutritional status regulates PNPLA3 gene expression in the mouse liver. Sterol response element binding protein-1 (SREBP-1) activated PNPLA3 gene transcription via sterol regulatory elements (SREs) mapped to the promoter region. Chromatin immunoprecipitation and electrophoretic mobility shift assays confirmed that SREBP-1 proteins bound to the identified SREs. Furthermore, SREBP-1c mediated the insulin and liver X receptor agonist TO901317-dependent induction of PNPLA3 gene expression in hepatocytes. Adenovirus-mediated overexpression of mouse PNPLA3 increased intracellular triglyceride content in primary hepatocytes, and knockdown of PNPLA3 suppressed the ability of SREBP-1c to stimulate lipid accumulation in hepatocytes. Finally, the overexpression of PNPLA3 in mouse liver increased the serum triglyceride level and impaired glucose tolerance; in contrast, the knockdown of PNPLA3 in db/db mouse liver improved glucose tolerance. CONCLUSION: Our data suggest that mouse PNPLA3, which is a lipogenic gene directly targeted by SREBP-1, promotes lipogenesis in primary hepatocytes and influences systemic lipid and glucose metabolism.

Isosilybin regulates lipogenesis and fatty acid oxidation via the AMPK/SREBP-1c/PPARα pathway.

It is well known that the excessive accumulation of lipid in hepatocytes is one of the important causes of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to explore the effects of isosilybin on lipid metabolism in free fatty acids (FFAs) or TO901317-induced HepG2 cells. Cells were treated with FFAs (oleic acid: palmitic acid, 2:1) or TO901317 to induce steatosis in vitro. Intracellular triglyceride (TG) content was quantified using commercial assay kits. The mRNA and protein expression of genes involved in fatty acid uptake, synthesis and oxidation were analyzed by RT-qPCR and western blotting. Selected biological pathways regulated by isosilybin treatment were determined by GO and KEGG analysis. The results showed that isosilybin significantly reduced TG levels in FFAs- and TO901317-induced HepG2 cells. Further studies showed that isosilybin treatment decreased the mRNA and protein expression of lipid synthesis genes Srebp-1c, Pnpla3, Acc and Fas, as well as the mRNA expression of fatty acid uptake gene CD36, whereas increased the mRNA levels of lipid oxidation genes Pparα, Acox1 and Cpt1α, as well as the mRNA expression of lipid export gene Mttp, in FFAs-induced HepG2 cells. Moreover, TO901317 was employed to induce endogenous lipid synthesis and steatosis, and the expression of Srebp-1c and its target genes in TO901317-induced hepatocytes was basically similar to that in FFAs-induced hepatocytes following isosilybin treatment. We also observed the increased level of phosphorylated AMP kinase (AMPK) after isosilybin treatment, while this effect was reversed after further treatment with AMPK inhibitor, compound C. The results of GO and KEGG analysis indicated that the pathways of fatty acid and TG metabolism were regulated by isosilybin. Interestingly, we found that treatment with the diastereoisomer A of isosilybin increased TG level, while exposure to the diastereoisomer B of isosilybin decreased TG level in FFAs-induced HepG2 cells. The above results suggest that isosilybin can inhibit lipid synthesis and activate lipid oxidation through AMPK signaling pathway, thereby improving steatosis of hepatocytes, and isosilybin B is the basis of its active substance.

Promotion of diabetic wound healing using novel Cu2O/Pt nanocubes through bacterial killing and enhanced angiogenesis in rats.

Chronic bacterial infection, local inflammation, and insufficient angiogenesis contribute to poor healing of diabetic wounds. Here, Cu2O/Pt nanocubes (CPN) are successfully developed with good biocompatibility for treatment of diabetic wounds in rats. The synthesized CPN are characterized using SEM, XPS, and XRD. CPN exhibit triple-enzyme mimetic activity: oxidase-like, peroxidase-like, and catalase-like activities. Moreover, CPN show significant antibacterial activity against Gram-negative and Gram-positive bacteria when combined with low concentration of H2O2, via generation of highly reactive ROS. CPN also exhibit significantly accelerated wound healing in a full-layer deprivation rat model infected by Staphylococcus aureus, which is ascribed to the constant release of copper ions, subsequently activating the VEGF/AKT/ERK1/2 signaling pathway and promoting angiogenesis. CPN are able to catalyze H2O2 to generate O2 for local hypoxia alleviation. Furthermore, in vivo results indicate that treatment with CPN promotes the expression of transforming growth factor and matrix metalloproteinases, causing enhanced cell proliferation and collagen deposition, as well as extracellular matrix remodeling. In contrast, CPN decrease the expression of proinflammatory cytokines, such as TNF-ɑ and IL-1ß, which are induced by bacterial infection and hyperglycemia. These results suggest a novel strategy for the treatment of diabetic wound healing.

Synthesis of tetraphenylethene-based D-A conjugated molecules with near-infrared AIE features, and their application in photodynamic therapy.

Herein, five aggregation-induced emission (AIE) photosensitizers (PSs) with D-π-A structures are smoothly designed and synthesized through donor and acceptor engineering. The photophysical properties and theoretical calculation results show that the synergistic effect of methoxy substituted tetraphenylethene (MTPE), 3,4-ethylenedioxythiophene can enhance the intramolecular charge transfer effect (ICT), and promote the intersystem crossing (ISC) process of the whole molecule. In these AIE-PSs, the best-performing AIE-PS (MTPE-DT-Py) has bright NIR (740 nm) emission, the highest 1O2 generation efficiency (5.9-fold that of Rose Bengal) and efficient mitochondrial targeting ability. Subsequently, PDT anti-cancer and anti-bacterial experiments indicate that MTPE-DT-Py could obviously target mitochondria and kill breast cancer cells (MCF-7), and selectively inactivate S. aureus (G(+)) under white light irradiation. This work mainly proposes a practical design strategy for high effect AIE-PSs and provides more excellent candidates for fluorescence imaging-guided photodynamic therapy.

Assessment of vegetation growth and drought conditions using satellite-based vegetation health indices in Jing-Jin-Ji region of China.

Terrestrial vegetation growth activity plays pivotal roles on regional development, which has attracted wide attention especially in water resources shortage areas. The paper investigated the spatiotemporal change characteristics of vegetation growth activity using satellite-based Vegetation Health Indices (VHIs) including smoothed Normalized Difference Vegetation Index (SMN), smoothed Brightness Temperature (SMT), Vegetation Condition Index (VCI), Temperature Condition Index (TCI) and VHI, based on 7-day composite temporal resolution and 16 km spatial resolution gridded data, and also estimated the drought conditions for the period of 1982-2016 in Jing-Jin-Ji region of China. The Niño 3.4 was used as a substitution of El Niño Southern Oscillation (ENSO) to reveal vegetation sensitivity to ENSO using correlation and wavelet analysis. Results indicated that monthly SMN has increased throughout the year especially during growing season, starts at approximate April and ends at about October. The correlation analysis between SMN and SMT, SMN and precipitation indicated that the vegetation growth was affected by joint effects of temperature and precipitation. The VCI during growing season was positive trends dominated and vice versa for TCI. The relationships between VHIs and drought make it possible to identify and quantify drought intensity, duration and affected area using different ranges of VHIs. Generally, the intensity and affected area of drought had mainly decreased, but the trends varied for different drought intensities, regions and time periods. Large-scale global climate anomalies such as Niño 3.4 exerted obvious impacts on the VHIs. The Niño 3.4 was mainly negatively correlated to VCI and positively correlated to TCI, and the spatial distributions of areas with positive (negative) correlation coefficients were mainly opposite. The linear relationships between Niño 3.4 and VHIs were in accordance with results of nonlinear relationships revealed using wavelet analysis. The results are of great importance to assess the vegetation growth activity, to monitor and quantify drought using satellite-based VHIs in Jing-Jin-Ji region.

Hypoglycemic activity of Origanum vulgare L. and its main chemical constituents identified with HPLC-ESI-QTOF-MS.

Origanum vulgare L. (O. vulgare) is an important medicine food homology in diabetes. The present study aimed to assess the hypoglycemic effect of the leaf extract of O. vulgare in HepG2 and HepG2-GFP-CYP2E1 (E47) cells, and disclose its potential active components by the HPLC-ESI-QTOF-MS method. Firstly, we evaluated the anti-diabetic capacity of the leaf extract of O. vulgare through inhibition of α-glucosidase activity, promotion of glucose uptake, inhibition of glycosylation and relieving of oxidative stress. Secondly, the promoter activity, the mRNA and protein expression of PEPCK and SREBP-1c, and the expression of CPY2E1 and GLUT2 in the O. vulgare mediated anti-diabetic capacity were analyzed in HepG2 and E47 cells. Finally, HPLC-ESI-QTOF-MS analysis was performed to identify the herb's main components under 280 nm irradiation. In vitro assays demonstrated that the extract inhibited α-glucosidase activity, promoted glucose uptake, inhibited glycosylation and relieved oxidative stress, which suggested that O. vulgare leaf extract has a strong hypoglycemic capacity. Moreover, mechanistic analysis also showed that the extract decreased the promoter activity and the mRNA and protein expression of PEPCK and SREBP-1c. In addition, the extract inhibited the expression of CPY2E1 and enhanced the expression of GLUT2. Moreover, the UV chromatogram at 280 nm showed six main peaks, identified as amburoside A (or 4-(3',4'-dihydroxybenzoyloxymethyl) phenyl O-ß-d-glucopyranoside), luteolin 7-O-glucuronide, apigenin 7-O-glucuronide, rosmarinic acid, lithospermic acid and a novel compound, demethylbenzolignanoid, based on accurate MS data. This work supported the ethnopharmacological usage of O. vulgare as an antidiabetic herbal medicine or dietary supplement and identified its main phenolic compounds.

Effects of Smart City Construction on the Quality of Public Occupational Health: Empirical Evidence From Guangdong Province, China.

This article takes the Guangdong Province of China as the research object and uses the difference-in-difference model to evaluate the impact of smart city construction on the quality of public occupational health and intercity differences. The obtained results show that smart city construction significantly improves the quality of public occupational health, and it is still valid after a series of robustness tests. The effect of this policy is stronger in cities that belong to the Pearl River Delta region or sub-provincial level cities. This study indicates that the central government should improve the pilot evaluation system and the performance appraisal mechanism of smart cities from the perspective of top-level design during the process of promoting smart city construction, which aims to correctly guide local governments to promote the construction of smart cities. To achieve the full improvement effect of smart city construction on the quality of public occupational health, local governments should implement smart city strategies in a purposeful and planned way according to the actual situation of the development of the jurisdiction.

PGC-1alpha coactivates estrogen-related receptor-alpha to induce the expression of glucokinase.

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) is a key regulator of cellular energy metabolism and regulates processes such as adaptive thermogenesis, hepatic gluconeogenesis, fatty acid oxidation, and mitochondrial biogenesis by coactivating numerous nuclear receptors and transcription factors. Here, we demonstrate the presence of the ERRalpha binding site in the regulatory sequence of the glucokinase gene and that PGC-1alpha coactivates ERRalpha to stimulate the transcription of glucokinase. Simultaneous overexpression of PGC-1alpha and ERRalpha potently induced the glucokinase gene expression and its enzymatic activity in primary hepatocytes; however, expression of either PGC-1alpha or ERRalpha alone had no significant effect. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed the interaction of ERRalpha with the glucokinase promoter. Finally, the knockdown of endogenous ERRalpha with specific siRNA (siERRalpha) or pharmacological inhibition of ERRalpha with XCT790 attenuated insulin-induced glucokinase expression. Taken together, this research identifies glucokinase as a novel target of PGC-1alpha/ERRalpha and underscores the regulatory function of ERRalpha in insulin-dependent enzyme regulation.