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OBJECTIVES: This work aimed to determine tert-Butylhydroquinone (TBHQ)'s effects on insulin resistance (IR) and liver steatosis in diabetic animals and to explore the underpinning mechanisms. MATERIALS AND METHODS: Male ApoE-/-mice underwent streptozocin (STZ) administration while receiving a sucrose/fat-rich diet for type 2 diabetes mellitus (T2DM) establishment. This was followed by a 6-week TBHQ administration. Body weight, fasting (FBG) and postprandial (PBG) blood glucose amounts, and insulin concentrations were measured, and the oral glucose tolerance test (OGTT) was carried out. Hematoxylin and eosin (H and E) staining and immunoblot were carried out for assessing histology and protein amounts in the liver tissue samples. In addition, cultured HepG2 cells were administered HClO and insulin for IR induction, and immunoblot was carried out for protein evaluation. Finally, the cells were stained with the Hoechst dye for apoptosis evaluation. RESULTS: The model animals showed T2DM signs, and TBHQ decreased FBG, ameliorated glucose tolerance and reduced liver steatosis in these animals. In addition, TBHQ markedly upregulated AMPKα2, GLUT4 and GSK3 β, as well as phosphorylated PI3K and AKT in the liver of mice with T2DM. In agreement, TBHQ decreased HClO-and insulin-related IR in cells and suppressed apoptosis through AMPKα2/PI3K/AKT signaling. CONCLUSIONS: TBHQ alleviates IR and liver steatosis in a mouse model of T2DM likely through AMPKα2/PI3K/AKT signaling. [ABSTRACT FROM AUTHOR]

The proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important cause of pulmonary vascular remodeling in pulmonary hypertension (PH). It has been reported that miR-137 inhibits the proliferation of tumor cells. However, whether miR-137 is involved in PH remains unclear. In this study, male Sprague-Dawley rats were subjected to 10% O2 for 3 weeks to establish PH, and rat primary PASMCs were treated with hypoxia (3% O2) for 48 h to induce cell proliferation. The effect of miR-137 on PASMC proliferation and calpain-2 expression was assessed by transfecting miR-137 mimic and inhibitor. The effect of calpain-2 on PASMC proliferation was assessed by transfecting calpain-2 siRNA. The present study found for the first time that miR-137 was downregulated in pulmonary arteries of hypoxic PH rats and in hypoxia-treated PASMCs. miR-137 mimic inhibited hypoxia-induced PASMC proliferation and upregulation of calpain-2 expression in PASMCs. Furthermore, miR-137 inhibitor induced the proliferation of PASMCs under normoxia, and knockdown of calpain-2 mRNA by siRNA significantly inhibited hypoxia-induced proliferation of PASMCs. Our study demonstrated that hypoxia-induced downregulation of miR-137 expression promoted the proliferation of PASMCs by targeting calpain-2, thereby potentially resulting in pulmonary vascular remodeling in hypoxic PH. [ABSTRACT FROM AUTHOR]

A new Sr(II)-based metal organic framework (MOF) formulated as [Sr(HTATB)(H2O)2(DMF)4 (1) has been prepared by reaction of Sr(NO3)2 with the rigid tricarboxylic acid linker 4,4′,4″-s-triazine-2, 4, 6-triyltribenzoic acid (H3TATB) in a mixed solvent of N,N-dimethylformamide (DMF) and water. Complex 1 has been characterized by powder X-ray diffraction (PXRD), elemental analysis (EA) and single crystal X-ray diffraction (SCXRD). In light of its large inner spaces as well as widely distributed open metal sites, the guest-free 1 (1a) has been used as a crystalline vessel for delivering small-molecule chemotherapeutics such as 5-fluorouracil (5-Fu), which exhibits an outstanding loading capacity around 36.48 wt%. Furthermore, the cumulative release value of 5-Fu at 48 h was about 96.5% in phosphate buffer saline (PBS). In addition, the 3-(4,5-dimethyl-2-thiazolyl)−2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was employed to evaluate the in vitro cytotoxicity of the carrier 5-Fu loaded 1a against the human melanoma cell lines. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension (PAH) is characterized by the apoptosis resistance and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Its pathogenesis has not been revealed. Here, we carried out experiments to investigate the functions of miR‐140‐5p and tumor necrosis factor‐α (TNF‐α). Methods: We selected GSE703 from Gene Expression Omnibus (GEO) Database to conduct microarray analysis using R software and Gene Set Enrichment Analysis (GSEA). Combing bioinformatics results, the upregulation of miR‐140‐5p inhibited PAH progression through targeting TNF‐α. RNA expression was measured by quantitative real‐time polymerase chain reaction (RT‐qPCR) and protein level was measured by western blot analysis and enzyme‐linked immunosorbent assays (ELISA). We conducted monocrotaline (MCT) injection to rats to form PAH animal models. The lung tissues were observed by hematoxylin–eosin (HE) staining and Sirius red‐picric acid staining. Right ventricular systolic pressure (RVSP) and the ratio of right ventricle (RV)‐to‐left ventricle (LV) plus septum (S) weight (RV/[LV + S]) were measured in MCT‐induced animal models. Overexpression of miR‐140‐5p and TNF‐α were utilized to research the proliferation, migration, and phenotypic variation of hypoxia‐mediated PASMCs. The binding between miR‐140‐5p and TNF‐α 3′‐untranslated region (3′‐UTR) was confirmed via luciferase reporter assay. Results: Downregulation of miR‐140‐5p and upregulation of TNF‐α were observed in PAH rat model and hypoxia‐mediated PASMCs. And we proved that overexpression of miR‐140‐5p could suppress the proliferation, migration, and phenotypic variation of PASMCs, therefore inhibiting PAH pathogenesis. Luciferase assay verified that miR‐140‐5p targeted TNF‐α directly. A converse correlation was also shown between miR‐140‐5p and TNF‐α in PASMCs. Conclusions: miR‐140‐5p and TNF‐α are important regulators in PAH pathology and may serve as a therapeutic target for PAH. miR‐140‐5p might inhibit the occurrence and development of pulmonary arterial hypertension (PAH) by repressing tumor necrosis factor‐α (TNF‐α) expression via the TNF signaling pathway. These findings may help in the search of promising strategies for achieving better treatment outcome in patients diagnosed with PAH. [ABSTRACT FROM AUTHOR]

Our study explored the effects of lncRNA UCA1 on the proliferation and apoptosis in hypoxic human pulmonary artery smooth muscle cells (HPASMCs) and highlighted the endogenous relationship between UCA1, ING5, and hnRNP I in cell proliferation. Hypoxia-induced HPASMCs were used to simulate pulmonary arterial hypertension in vitro. Microarray assay was adopted to screen the dysregulated expressed lncRNAs in HPASMCs to find out the target gene of our study. And RT-qPCR was performed to detect the expression of lncRNA UCA1 under hypoxia and normoxia. After transfection, the relationship between UCA1 and cell proliferation in HPASMCs under hypoxia were determined by cell proliferation assay and relative expression of PCNA. Next, ELISA assays were conducted to measure the protein levels of PCNA and ING5. What's more, flow cytometry was employed to measure the apoptosis rate in differentially UCA1-expressed HPASMCs. RIP assays were conducted to further clarify the endogenous relationship between UCA1 and ING5 in hypoxic HPASMCs. Finally, the effects of ING5 to HPASMCs were detected after transfection of ING5 and UCA1 to figure out the role of ING5 in HPASMCs. Hypoxia was revealed to induce proliferation and inhibited apoptosis in HPASMCs. Besides, UCA1 was confirmed to be highly expressed under hypoxia compared with normoxia. UCA1 boosted cell proliferation under hypoxia in HPASMCs. However, the apoptosis was suppressed in the hypoxic HPASMCs transfected with pcDNA3.1-UCA1. Further, mechanism studies found that UCA1 competed with ING5 for hnRNP I, so that upregulating UCA1 inhibited the protein levels of ING5. And finally we found that ING5 restrained cell viability, but promoted cell apoptosis in hypoxic HPASMCs, which was reversed by UCA1 over-expression. In summary, our findings manifested that UCA1 promoted proliferation and restrained apoptosis by competing with ING5 for hnRNP I in HPASMCs induced by hypoxia, indicating their potential roles for the cure of hypoxic pulmonary hypertension. [ABSTRACT FROM AUTHOR]

The modernization of central China may highly affect the overall well-off society in China. Meanwhile, higher education plays a prominent role in determining the competitiveness of a country or region. Hence, how to bring the promotional role of higher education in economic growth of central China into play has become a focus for the government and the academia. Under this circumstance, this paper develops a comprehensive index of education and then employs the panel data model to investigate the influence of both higher education scale and quality on economic growth in the six provinces of central China from 2003 to 2014. The empirical results show that the contribution of higher education to comprehensive education level in the six provinces was all <1% within the sample period, and its contribution to economic growth was <5%, far lower than that of basic education to economic growth. Moreover, in general, higher education scale exerts significant positive effect on economic growth in central China while the effect of higher education quality appears insignificant. In addition, technological innovation plays a remarkably positive role in economic growth of all the six provinces in central China. [ABSTRACT FROM AUTHOR]

The new compound based on Wells-Dawson-type arsenomolybdate: [{Cu 10 (pz) 11 Cl 4 }{As 2 III As 2 V Mo 6 V Mo 12 VI O 62 }]·H 2 O ( 1 ) has been hydrothermally synthesized and characterized by single-crystal X-ray diffraction analysis, X-ray powder diffraction (XRPD), XPS spectroscopy and thermogravimetric analysis (TG). Compound 1 is consisted of two As caps Wells-dawson-type arsenomolybdate and {Cu 10 (py) 11 } complexes by chloride bridge. In addition, the antitumor effects of the title compound 1 were studied on three human lung cancer cells (A549, SK-LU-1 and SW1573). The results showed that compared with the positive reference drug carboplatin, compound 1 displayed efficient antitumor activity. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) mainly results from excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and displays mitochondrial abnormalities such as mitochondrial fragmentation. Epigallocatechin-3-gallate (EGCG), an efficient antiproliferative compound in green tea, has recently been demonstrated to inhibit PASMCs proliferation. However, the pre-clinical issues as to whether EGCG attenuates PH and the underlying mechanisms have yet to be addressed. The present study was undertaken to investigate the therapeutic effects of EGCG on PH and its effects on mitochondrial fragmentation in PASMCs. Rats exposed to hypoxia (10% O 2 , 3 weeks) developed PH. EGCG (50, 100 or 200 mg/kg/d, i.g.) dose-dependently attenuated right ventricular systolic pressure, pulmonary vascular remodeling and right ventricular hypertrophy, increased expression of mitochondrial fusion protein - mitofusin-2 (MFN-2), and promoted mitochondrial fusion as evidenced by decreased number and volume of mitochondria in PASMCs of pulmonary arteries. Notably, EGCG (50 μM) downregulated hypoxia-induced (3% O 2 , 48 h) PASMCs mitochondrial fragmentation and inhibited PASMCs proliferation via KLF-4/MFN-2/p-Erk signaling pathway. Collectively, our data demonstrated that EGCG exerts antiproliferative effects via regulating mitochondrial fragmentation of PASMCs and EGCG holds the promise as a drug against PH. [ABSTRACT FROM AUTHOR]

Background Pulmonary hypertension (PH) is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Our lately study demonstrated that let-7g inhibited hypoxia-induced proliferation of PASMCs via repressing c-myc-Bmi-1-p16 signaling pathway. However, the upstream of let-7g has not yet been fully defined. Previous studies have shown that LOX-1, a target of let-7g, could also regulate the expression of let-7g in human aortic endothelial cells. In this present study, we aimed to investigate whether there is a negative feedback regulation between microRNA let-7g and LOX-1 in hypoxia-induced proliferation of PASMCs. Methods SD Rats were exposed to hypoxia (10% O 2 , 3 weeks) to induce PH. HE staining was used to evaluate pulmonary artery remodeling. in situ hybridization and immunohistochemistry were performed to assess the expression and distribution of let-7g and LOX-1, respectively. MTS, EDU and flow cytometry were performed to evaluate PASMCs proliferation. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted to assess the expression of let-7g, LOX-1, calpain-1,-2,-4, and OCT-1. Results The expression of let-7g was significantly down-regulated in pulmonary arteries of hypoxia-induced PH rats accompanied by pulmonary vascular remodeling, whereas let-7g mimic inhibited hypoxia-induced proliferation of PASMCs and up-regulation of LOX-1 expression. LOX-1 blocking reversed hypoxia-induced down-regulation of let-7g expression. Calpains, protein kinase C and OCT-1 were involved in negative feedback regulation between let-7g and LOX-1. Conclusion Negative feedback regulation between let-7g and LOX-1 mediated hypoxia-induced proliferation of in PASMCs. [ABSTRACT FROM AUTHOR]

Aim Chronic hypoxia leads to right ventricular hypertrophy (RVH). RVH is believed to result from hypoxia-induced pulmonary hypertension. However, if hypoxia impacts RVH directly awaits clarification. Hypoxia triggers oxidative stress, and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediates reactive oxygen species (ROS) generation in different cells. Therefore, this study aims to explore whether LOX-1-mediated oxidative stress accounts for hypoxia-induced RVH. Main methods Rats developed RVH after 3 weeks of hypoxia (10% O 2 ). Immunofluorescence staining was performed to evaluate H9C2 cell hypertrophy induced by hypoxia (3% O 2 ). Real-time PCR and Western-blot were performed to assess LOX-1, NADPH oxidases (NOX), collagen I/III, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) expression. DCFH-DA staining was performed to measure ROS generation. Key findings Hypoxia induced RVH and cardiac fibrosis in rats, as indicated by enlarged cardiomyocytes and deposition of extracellular matrix. Interestingly, hypoxia treatment directly induced H9C2 cardiomyocyte hypertrophy, implying direct effects of hypoxia on cell hypertrophy. Rat and H9C2 hypertrophy model revealed that cell hypertrophy was accompanied by marked increase in LOX-1 expression. Knockdown of LOX-1 significantly ameliorated H9C2 cell hypertrophy. Mechanistically, hypoxia induced prominent oxidative stress in rat right ventricles and H9C2 cells, most likely as a result from increased expression of NOX2/4, contributing to RVH. Knockdown of LOX-1 significantly attenuated H9C2 cell oxidative stress, with a concomitant decrease in NOX2/4 expression. Significance LOX-1/NOX/ROS pathway could represent a novel mechanism underlying hypoxia-induced RVH. Therapeutic targeting of LOX-1 would be exploited to treat RVH owing to chronic hypoxia exposure. [ABSTRACT FROM AUTHOR]

Pulmonary vascular remodeling (PVR) is the pathological basis of pulmonary hypertension (PH). Incomplete understanding of PVR etiology has hindered drug development for this devastating disease, which exhibits poor prognosis despite the currently available therapies. Endothelial-to-mesenchymal transition (EndMT), a process of cell transdifferentiation, has been recently implicated in cardiovascular diseases, including PH. But the questions of how EndMT occurs and how to pharmacologically target EndMT in vivo have yet to be further answered. Herein, by performing hematoxylin–eosin and immunofluorescence staining, transmission electron microscopy and Western blotting, we found that EndMT plays a key role in the pathogenesis of PH, and importantly that aspirin, a FDA-approved widely used drug, was capable of ameliorating PVR in a preclinical rat model of hypoxia-induced PH. Moreover, aspirin exerted its inhibitory effects on EndMT in vitro and in vivo by suppressing HIF-1α/TGF-β1/Smads/Snail signaling pathway. Our data suggest that EndMT represents an intriguing drug target for the prevention and treatment of hypoxic PH and that aspirin may be repurposed to meet the urgent therapeutic needs of hypoxic PH patients. [ABSTRACT FROM AUTHOR]

The experiment was conducted to explore the extraction effect of different extraction methods on red beet polysaccharide. In the experiment, red beet was used as raw material, water extraction and alcohol precipitation method and ultrasonic assisted water extraction method were used respectively. Orthogonal design was carried out to optimize the extraction process on the basis of single factor experiment, and the effect of liquid to solid ratio, extraction temperature and extraction time on the extraction rate of red beet polysaccharide were investigated. The crude polysaccharides were purified by Sevag reagent, activated carbon and petroleum ether. The results showed that the optimal extraction conditions of red beet polysaccharide by water extraction and alcohol precipitation were as follows: Liquid to solid ratio of 90 mL/g, extraction temperature of 70 °C, and an extraction time of 1.5 h. Under the conditions, the extraction yield of red beet polysaccharide was the highest, reaching 2.33%. The optimal extraction process of ultrasonic assisted water extraction was as follows: Liquid to solid ratio 40 mL/g, extraction temperature of 40 °C, extraction time of 30 min. Under the conditions, the extraction rate was 6.85%. The removal rates of protein, pigment and fat were 29.73%, 3.88% and 2.76%, respectively. The study indicates that ultrasonic assisted water extraction method is more suitable for the extraction of red beet polysaccharide with less solvent, shorter time, lower temperature and higher extraction rate. [ABSTRACT FROM AUTHOR]

Environmental pollution and its health risks to human beings have been becoming increasingly serious in China, and the health status of the individuals is not only affected by their environment but also by their own characteristics and socio-economic status. Based on the survey data of China Family Panel Studies (2014), three hierarchical linear models at three levels of individual, family, and community were developed to investigate the influencing factors of individual health status. The results indicate that: (1) there exists significant difference among individual health status, of which 16% and 9.11% are caused by the family and community levels, respectively; (2) the average health status of men is better than that of women by 6.95%. As for the difference in health effects produced by gender, total household income can reduce this difference; (3) age has significant negative health effects, while the level of education has positive effect on individual health status; and (4) the health effects of pollution is mainly reflected by its interaction with gender; in particular, when men and women face the same level of pollution exposure, men are more susceptible. [ABSTRACT FROM AUTHOR]

Aims Pulmonary hypertension (PH) is a proliferative disorder characterized by enhanced proliferation and suppressed apoptosis of intrapulmonary vascular smooth muscle cells. Recently, network-based bioinformatics have identified let-7 family, a tumor suppressive microRNA, regulate multiple interacting targets relevant to PH. However, the role of let-7 in vascular homeostasis in PH remains unknown. Thus, we wanted to investigate the role of let-7 in hypoxia-induced PASMCs proliferation and the underlying mechanism in hypoxic pulmonary hypertension (HPH). Main methods The male Sprague–Dawley (SD) rats were exposed to hypoxia (10% O 2 ) for 21 days to induce HPH. The expression of let-7 was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Primary rat PASMCs were exposed to hypoxia (3% O 2 ). MTS and EDU were performed to evaluate PASMCs proliferation. The mRNA and protein expression of c-myc, Bmi-1 and p16 were determined by qRT-PCR and Western blotting, respectively. The functions of let-7g on PASMCs proliferation, c-myc, Bmi-1 and p16 expression were assessed by let-7g mimic and inhibitor transfection. Key findings Among let-7 family members, only let-7b and let-7g were significantly down-regulated in remodeled pulmonary artery in HPH rats. Furthermore, only let-7g level was decreased in hypoxic PASMCs. Either hypoxia or let-7g inhibitor stimulated proliferation of PASMCs, let-7g mimic inhibited hypoxia-induced PASMCs proliferation. C-myc was the target of let-7g in PASMCs. Transfect of let-7g mimic inhibited hypoxia-induced c-myc, Bmi-1 up-regulation and p16 down-regulation, which ultimately controls cell cycle progression. Significance Loss of inhibition on c-myc-Bmi-1-p16 signaling pathway by let-7g may lead to PASMCs proliferation and vascular remodeling in HPH. [ABSTRACT FROM AUTHOR]

[Display omitted] The pulmonary vascular remodeling (PVR), the pathological basis of pulmonary hypertension (PH), entails pulmonary artery smooth muscle cells (PASMCs) phenotypic switching, but appreciation of the underlying mechanisms is incomplete. Exosomes, a novel transfer machinery enabling delivery of its cargos to recipient cells, have been recently implicated in cardiovascular diseases including PH. The two critical questions of whether plasma-derived exosomes drive PASMCs phenotypic switching and what cargo the exosomes transport, however, remain unclear. Herein, by means of transmission electron microscopy and protein detection, we for the first time, characterized lectin like oxidized low-density lipoprotein receptor-1 (LOX-1) as a novel cargo of plasma-derived exosomes in PH. With LOX-1 knockout (Olr1-/-) rats-derived exosomes, we demonstrated that exosomal LOX-1 could be transferred into PASMCs and thus elicited cell phenotypic switching. Of importance, Olr1-/- rats exhibited no cell phenotypic switching and developed less severe PH, but administration of wild type rather than Olr1-/- exosomes to Olr1-/- rats recapitulated the phenotype of PH with robust PASMCs phenotypic switching. We also revealed that exosomal LOX-1 triggered PASMCs phenotypic switching, PVR and ultimately PH via ERK1/2-KLF4 signaling axis. This study has generated proof that plasma-derived exosomes confer PH by delivering LOX-1 into PASMCs. Hence, exosomal LOX-1 represents a novel exploitable target for PH prevention and treatment. [ABSTRACT FROM AUTHOR]

• Spermidine (SPD) can attenuate pulmonary arterial hypertension and pulmonary vascular remodeling. • SPD attenuates pulmonary arterial hypertension and pulmonary vascular remodeling by inhibiting purine metabolism and polyamine synthesis. • SPD's protective role in counteracting MCT-induced PAH via a dual mechanism: the inhibition of PNP and AMD1 expression. This modulation reduces ATP consumption, subsequently mitigating oxidative stress and apoptotic processes. Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 μM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment. [ABSTRACT FROM AUTHOR]

Abstract Objective: This study aimed to investigate the functions of lncRNA H19 on glomerular endothelial structural damage of diabetic nephropathy (DN). Materials and Methods: Rats were fed a high sugar and fat high feed die, and intraperitoneally administrated with streptozotocin (30 mg/kg) to induce DN model. Meanwile, rat glomerular endothelial cells (rGEnCs) were treated with high a level of glucose （HG, 30 mM glucose）to induce structural damage. Results: Our results showed that H19 level was drastically increased in diabetic glomeruli and high-glucose (HG)-stimulated rat glomerular endothelial cells (rGEnCs). Deficiency of H19 ameliorated microalbumin, creatinine, BUN, and histopathological alterations in diabetic rats. In addition, H19 deficiency significantly attenuated the damage of endothelial structure by upregulating the expression of junction proteins ZO-1 and Occludin, glycolcalyx protein Syndecan-1, and endothelial activation marker sVCAM-1 and sICAM-1 in diabetic rats. The in vitro results also showed that H19-siRNA alleviated glycocalyx shedding, tight junctions damage, and endothelial activation in HG-stimulated rGEnCs. Moreover, H19 deficiency significantly enhanced the expression of p-Akt and p-eNOS and NO concentration in vitro and in vivo. Pre-treatment with Akt inhibitor LY294002 abrogated these favourable effects mediated by H19 deficiency. Discussion and Conclusion: These results indicate that H19 deficiency could mitigate the structural damage of glomerular endothelium in DN via activating Akt/eNOS pathway. [ABSTRACT FROM AUTHOR]

• The impact of air pollution on urban innovation capability is tested. • The innovation capability index is reconstructed based on innovation output. • Air pollution inhibits the urban innovation capability significantly. • The "human resource loss effect" and "resource crowding out effect" are justified. • The inhibition of air pollution on innovation capability has urban heterogeneity. Technological innovation may help to reduce air pollution, but existing relevant studies have not clarified whether and how air pollution affects urban innovation capability. Therefore, based on the fixed-effect model, we examine a panel of 281 prefecture-level cities in China from 2003 to 2015, and find that air pollution significantly inhibits the improvement of urban innovation capability on the whole in China. Meanwhile, affected by the "human resource loss effect", air pollution in cities of large scale or eastern China has a significantly greater inhibitory effect on innovation capabilities. Besides, affected by the "resource crowding out effect", the negative impact of air pollution on urban innovation capability in key environmental protection cities is far greater than that in non-key cities. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a complex and fatal cardio-pulmonary vascular disease. Decompensated right ventricular hypertrophy (RVH) caused by cardiomyocyte hypertrophy often leads to fatal heart failure, the leading cause of mortality among patients. Sodium butyrate (SB), a compound known to reduce cardiac hypertrophy, was examined for its potential effect and the underlying mechanism of SB on PAH-RVH. The in vivo study showed that SB alleviated RVH and cardiac dysfunction, as well as improved life span and survival rate in MCT-PAH rats. The in vivo and in vitro experiments showed that SB could attenuate cardiomyocyte hypertrophy by reversing the expressions of H19, let-7g-5p, insulin-like growth factor 1 receptor (IGF1 receptor), and p ERK. H19 inhibition restored the level of let-7g-5p and prevented the overexpression of IGF1 receptor and p ERK in hypertrophic cardiomyocytes. In addition, dual luciferase assay revealed that H19 demonstrated significant binding with let-7g-5p, acting as its endogenous RNA. Briefly, SB attenuated PAH-RVH by inhibiting the H19 overexpression, restoring the level of let-7g-5p, and hindering IGF1 receptor/ERK activation. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: This paper summarizes the comprehensive statistical results of constant damage inelastic displacement ratios which allow the evaluation of maximum inelastic displacement demand for structures with constant damage performance. The inelastic displacement ratios are calculated with modified Park-Ang damage index and inelastic single-degree-of-freedom systems subjected to 573 ground motions. The influences of period of vibration, levels of damage, site conditions, earthquake magnitude, rupture distance, post-yield stiffness, stiffness degradation, strength deterioration, parameter β and ultimate ductility factor μ u in damage index model are evaluated and discussed statistically. It is found that the effect of site conditions is not very significant. Specifically, coefficients of variation are approximately period-independent and site-independent. The degrading systems with short period of vibration would experience larger inelastic displacement than non-degrading systems. The effects of parameter β and ultimate ductility factor μ u are moderate in short period region. A simplified expression is proposed for the application of constant damage inelastic displacement ratios. [Copyright &y& Elsevier]

Pulmonary artery smooth muscle cells (PASMCs) phenotypic switching and pulmonary artery endothelial cells (PAECs) endothelial-mesenchymal transition (EndMT) are important in promoting pulmonary hypertension (PH)-pulmonary vascular remodeling (PVR). Resveratrol can efficiently inhibit the proliferation of PASMCs, but its application is limited due to its low bioavailability and solubility. In this study, we modified resveratrol to assess the role of A ring N(CH 3) 2 -based derivatives of resveratrol (Res4) in PVR-PASMCs phenotypic switching and PVR-PAECs EndMT. Chemical methods were used for the preparation of Res4; NMRS and HPLC were used to authenticate Res4. Mice developed PVR after 4 weeks of hypoxia (10% O 2). Res4 (50 mg/kg/d) attenuated right ventricular systolic pressure, right ventricular hypertrophy, and PVR. PASMCs developed phenotypic switching and PAECs developed EndMT after 2 days of hypoxia (3% O 2). Res4 (10 μM) could inhibit PASMCs and PAECs viability. Res4 could decrease proliferating cell nuclear antigen (PCNA) and osteopontin (OPN) expression, and increase α-smooth muscle actin (α-SMA) and vimentin expression in PASMCs. It could also decrease PCNA, α-SMA, vimentin expression and increase platelet endothelial cell adhesion molecule (CD31) expression in PAECs. Notably, Res4 inhibited the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated protein kinase (ERK), Jun-N-terminal kinase (JNK), and p38 kinase in hypoxia-treated PASMCs and PAECs, indicating MAPK pathway may be involved in Res4-induced inhibition of PASMCs phenotypic switching and PAECs EndMT. Our data demonstrated that Res4 exerts antiproliferative effects by regulating PASMCs phenotypic switching and PAECs EndMT. Res4 may be potentially used as a drug against PH-PVR. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that H 2 S has an antihypertension effect on hypertension, but the mechanism involved is unclear until now. The aim of the study is to elucidate the effect of H 2 S on PH and the mechanism involved. In this study, GYY4137 (a H 2 S donor) were administered to spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) by intraperitoneally injection daily for consecutive 14 days. Systolic blood pressure (SBP), endothelial-dependent relaxation (EDR), plasma malondialdehyde (MDA), superoxide dismutase (SOD), and H 2 S levels were measured. Human umbilical vein endothelial cells (HUVECs) were also used to elucidate the mechanism involved in the protect effect of H 2 S on the injured vessels. Our results showed that GYY4137 normalized the SBP (P < 0.0001), increased EDR (P < 0.01), reduced oxidative stress (increased the content of SOD and reduced the content of MDA) of SHR. Meanwhile, GYY4137 could promote the proliferation (P < 0.01) and migration (P < 0.01) of HUVECs, increase the expression of endothelial NO synthase (eNOS) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) both in SHR and HUVECs treated with GYY4137. In addition to the above results, the PIP3/Akt signaling pathway was activated and the expression of caspase 3 was increased by GYY4137. However, all the above effects of GYY4137 were blocked by ZD6474 (a VEGFR2 inhibitor). GYY4137 had a hypotensive and vascular protect effect on PH. This effect might be mediated through upregulating the expression of VEGFR2, which subsequently alleviating oxidant-provoked vascular endothelial dysfunction, and promoting the proliferation and migration of endothelial cells in SHR. [ABSTRACT FROM AUTHOR]

Background and objective Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. Methods The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg). Typical lesions of diabetic pulmonary fibrosis were observed 8 weeks after STZ injection by hematoxylin-eosin (HE) and Masson staining. Human bronchial epithelial cells (HBECs) and A549 cells were treated by high glucose. Gene or protein expression was measured by real-time PCR, Western blot, immunohistochemistry or immunofluorescence. The knockdown of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) or transforming growth factor-β1 (TGF-β1) was conducted by siRNA. Results Activation of EMT was observed in lung tissues of STZ-induced diabetic rats, exhibiting a loss in the epithelial cell marker E-cadherin and an increase in the mesenchymal marker Vimentin. The protein and mRNA levels of LOX-1, TGF-β1 and krüppel-like factor 6 (KLF6) in the lung tissues were increased. Incubation of HBECs and A549 cells with high glucose activated EMT and induced an increase in LOX-1, TGF-β1 and KLF-6 expression. LOX-1 siRNA inhibited high glucose-induced EMT in HBECs and A549 cells, which correlated with the reduction of TGF-β1. TGF-β1 siRNA decreased the expression of LOX-1 and KLF6. Conclusions EMT was involved in the pathological process of diabetic pulmonary fibrosis, which was activated by LOX-1/TGF-β1/KLF6 signaling pathway. [ABSTRACT FROM AUTHOR]

Background Endothelial cell apoptosis contributes to cardiovascular diseases such as hypertension, atherosclerosis. MicroRNA regulates endothelial cell function but its role in endothelial cell apoptosis remains to be fully elucidated. This study aims to investigate the role of miR-590-5p in endothelial cell apoptosis and dissect the underlying mechanisms. Methods Flow cytometric analysis, Hoechst 33258 staining and Western blotting were performed to evaluate human umbilical vein endothelial cell (HUVEC) apoptosis induced by Angiotensin (Ang) II. Western blotting and real-time quantitative PCR were conducted to assess the expression of LOX-1. DCFH-DA staining was carried out to measure the generation of reactive oxygen species (ROS). Results Ang II-induced HUVEC apoptosis was accompanied by downregulation of miR-590-5p; administration of miR-590-5p mimics attenuated HUVEC apoptosis and decreased ROS generation, as indicated by reduced fraction of apoptotic HUVECs and decreased caspase-3 activity. LOX-1 expression was increased by Ang II, and miR-590-5p mimics reduced LOX-1 expression in HUVECs in the absence or presence of Ang II. Pharmacologic or genetic block of LOX-1 with small interference RNA or TS92 (LOX-1 neutralizing antibody) significantly ameliorated HUVEC apoptosis, as evidenced by reduced number of apoptotic HUVECs, inhibited caspase-3 activation and suppressed mitochondrial cytochrome C release. Moreover, LOX-1 siRNA or TS92 treatment dramatically reduced ROS production in HUVECs treated with Ang II. Conclusion Our data demonstrated that miR-590-5p downregulation promoted Ang II-induced endothelial cell apoptosis by elevating LOX-1 expression and consequently increasing ROS generation. Thus, restoration of miR-590-5p or block of LOX-1 could be therapeutically exploited to alleviate endothelial cell apoptosis. [ABSTRACT FROM AUTHOR]

• Dynamic network data envelopment analysis and Tobit regression are used for study. • The efficiency of production process is higher than the waste treatment process. • Significant regional differences exist in the industrial eco-efficiency in China. • Industrial agglomeration impedes the eco-efficiency of industrial sector. • Industrial structure rationalization promotes the industrial eco-efficiency. The industrial sector is the largest energy consumption sector and major source of environmental pollution in China. Improving the industrial eco-efficiency is significant for China to realize high-quality development. Based on the panel data of industrial sector in China's 30 provinces from 2006 to 2015, this paper first adopts a dynamic network data envelopment analysis to evaluate the eco-efficiency of industrial sector, and then uses panel Tobit regression model to investigate the impacts of industrial policies on the eco-efficiency of industrial sector. The results reveal that, (1) the overall eco-efficiency of China's provincial industrial sector is 0.7581 during 2006–2015, and the average efficiency of the industrial production process is higher than that of the waste treatment process. (2) The eco-efficiency of the industrial sector differs greatly by region, the eastern region is the highest, followed by the western and central regions, and the northeast is the lowest. (3) Industrial agglomeration impedes the improvement of industrial eco-efficiency, while industrial structure rationalization can promote industrial eco-efficiency. (4) The influence of industrial agglomeration and industrial structure rationalization on the efficiency of industrial waste treatment process is larger than that of the industrial production process. The findings of this paper reveal the importance of improving the efficiency of industrial sub-processes, and can also offer lessons for other industrialized nations to improve the industrial eco-efficiency. [ABSTRACT FROM AUTHOR]

• A flexible and comprehensive assessment framework of ISID is proposed. • Two formulations of ISID – ISID regime and ISIDsdg9 regime are established. • MEA approach and RAM approach are utilized to measure ISID. • Current status and improving potentials of ISID for China's 30 provinces are evaluated. • Policy paths toward mainstreaming ISID for China's 30 provinces are put forward. Inclusive and sustainable industrial development (ISID) is a call for action to promote industrialization by minimizing the environmental footprint and enhancing social inclusion. This study proposes a new framework of an evaluation system to assess the ISID for 30 provinces in China (2011–2016). As there does not exist a generally accepted evaluation system of ISID, this study proposes a dual-formulation of ISID to rationalize the trade-offs among externalities brought by industrialization: (i) ISID represents the aspiration of countries to promote industrialization and consequently sustain economic growth by reducing the adverse environmental and social effects which manifest in the overall economy (ii) ISIDsdg9 considers the same aspects of ISID but limits the externalities within the industrial sector. This study applied two newly developed efficiency evaluation approaches, Multi-Directional Efficiency Analysis (MEA) and Range-Adjusted Measure (RAM), to evaluate and analyze the ISID for China. This study finds that: Among the 30 provinces, (i) Beijing and Tianjin are the benchmark provinces for promoting ISID and ISIDsdg9 regimes, respectively. (ii) Throughout the 2011–2016, the overall performance of China on ISID and ISIDsdg9 regimes has improved modestly. (iii) Based on the analysis of the barrel effect, SO 2 emission is the key binding constraint to achieving the frontier status of ISID and ISIDsd9 regimes (v) Under the evaluation of ISID and ISIDsdg9 regimes, the average annual growth potentials of industrial value added (IVA) is 280.52 billion CNY and 927.54 billion CNY, respectively. This present study recommends local government in China to advance their ISID performance by exploiting the policies targeting emission mitigation concerning fossil fuels while considering Beijing and Tianjin as the benchmark provinces. [ABSTRACT FROM AUTHOR]