Chlorido[1-(pyridin-2-yl)ethanone oximato-κ2 N,N′][1-(2-pyrid­yl)ethanone oxime-κ2 N,N′]copper(II) trihydrate

In the title compound, [Cu(C7H7N2O)Cl(C7H8N2O)]·3H2O, the metal ion is five-coordinated by the N atoms from the 1-(pyridin-2-yl)ethanone oximate and 1-(pyridin-2-yl)ethanone oxime ligands and by the chloride anion in a distorted square-pyramidal geometry. The distortion parameter is 0.192. The two organic ligands are linked by an intra­molecular O—H⋯O hydrogen bond. In the crystal, mol­ecules are linked by O—H⋯O and O—H⋯Cl hydrogen bonds. The title compound is the hydrated form of a previously reported structure [Wu & Wu (2008 ▶). Acta Cryst. E64, m828]. There are only slight variations in the mol­ecular geometries of the two compounds

PDGF-C Mediates the Angiogenic and Tumorigenic Properties of Fibroblasts Associated with Tumors Refractory to Anti-VEGF Treatment

SummaryTumor- or cancer-associated fibroblasts (TAFs or CAFs) from different tumors exhibit distinct angiogenic and tumorigenic properties. Unlike normal skin fibroblasts or TAFs from TIB6 tumors that are sensitive to anti-VEGF treatment (TAF-TIB6), TAFs from resistant EL4 tumors (TAF-EL4) can stimulate TIB6 tumor growth even when VEGF is inhibited. We show that platelet-derived growth factor C (PDGF-C) is upregulated in TAFs from resistant tumors. PDGF-C-neutralizing antibodies blocked the angiogenesis induced by such TAFs in vivo, slowed the growth of EL4 and admixture (TAF-EL4 + TIB6) tumors, and exhibited additive effects with anti-VEGF-A antibodies. Hence, our data reveal an additional mechanism for TAF-mediated tumorigenesis and suggest that some tumors may overcome inhibition of VEGF-mediated angiogenesis through upregulation of PDGF-C

Deciphering the mechanism of PSORI-CM02 in suppressing keratinocyte proliferation through the mTOR/HK2/glycolysis axis

Hyperplasia of epidermal keratinocytes that depend on glycolysis is a new hallmark of psoriasis pathogenesis. Our previous studies demonstrated that PSORI-CM02 could halt the pathological progression of psoriasis by targeting inflammatory response and angiogenesis, but its effect(s) and mechanism(s) on proliferating keratinocytes remained unclear. In this study, we aim to identify components of PSORI-CM02 that are absorbed into the blood and to determine the effect(s) of PSORI-CM02 on keratinocyte proliferation and its molecular mechanism(s). We used the immortalized human epidermal keratinocyte cell line, HaCaT, as an in vitro model of proliferating keratinocytes and the imiquimod-induced psoriasis mouse (IMQ) as an in vivo model. Metabolite profiles of vehicle pharmaceutic serum (VPS), PSORI-CM02 pharmaceutic serum (PPS), and water extraction (PWE) were compared, and 23 components of PSORI-CM02 were identified that were absorbed into the blood of mice. Both PPS and PWE inhibited the proliferation of HaCaT cells and consequently reduced the expression of the proliferation marker ki67. Additionally, PPS and PWE reduced phosphorylation levels of mTOR pathway kinases. Seahorse experiments demonstrated that PPS significantly inhibited glycolysis, glycolytic capacity, and mitochondrial respiration, thus reducing ATP production in HaCaT cells. Upon treatments of PPS or PWE, hexokinase 2 (HK2) expression was significantly decreased, as observed from the set of glycolytic genes we screened. Finally, in the IMQ model, we observed that treatment with PSORI-CM02 or BPTES, an inhibitor of mTOR signaling, reduced hyperproliferation of epidermal keratinocytes, inhibited the expression of p-S6 and reduced the number of proliferating cell nuclear antigen (PCNA)-positive cells in lesioned skin. Taken together, we demonstrate that PSORI-CM02 has an anti-proliferative effect on psoriatic keratinocytes, at least in part, by inhibiting the mTOR/HK2/glycolysis axis

Growth Pattern in Chinese Children With 5α-Reductase Type 2 Deficiency: A Retrospective Multicenter Study

Background5α-reductase type 2 deficiency (5αRD) is an autosomal recessive hereditary disease of the group of 46, XY disorders of sex development (DSD).ObjectiveTo study the growth pattern in Chinese pediatric patients with 5αRD.SubjectsData were obtained from 141 patients with 5αRD (age: 0–16 years old) who visited eight pediatric endocrine centers from January 2010 to December 2017.MethodsIn this retrospective cohort study, height, weight, and other relevant data were collected from the multicenter hospital registration database. Baseline luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) after human chorionic gonadotropin (HCG) stimulation test were measured by enzyme enhanced chemiluminescence assay. Bone age (BA) was assessed using the Greulich-Pyle (G-P) atlas. Growth curve was constructed based on λ-median-coefficient of variation method (LMS).ResultsThe height standard deviation scores (HtSDS) and weight standard deviation scores (WtSDS) in 5αRD children were in the normal range as compared to normal boys. Significantly higher HtSDS was observed in patients with 5αRD who were <1 year old (t = 3.658, 2.103, P = 0.002, 0.048, respectively), and higher WtSDS in those <6 months old (t = 2.756, P = 0.012). Then HtSDS and WtSDS decreased gradually and fluctuated near the median of the same age until 13 years. WtSDS in 5αRD children from northern China were significantly higher than those from the south (Z = -2.670, P = 0.008). The variation tendency of HtSDS in Chinese 5αRDs was consistent with the trend of stimulating T. HtSDS and stimulating T in the external masculinization score (EMS) <7 group were slightly higher than those in EMS ≥ 7 group without significant difference. Additionally, the ratio of BA over chronological age (BA/CA) was significantly <1 in children with 5αRD.ConclusionChildren with 5αRD had a special growth pattern that was affected by high levels of T, while DHT played a very small role in it. Their growth accelerated at age <1 year, followed by slowing growth and fluctuating height near normal median boys’ height. The BA was delayed in 5αRD children. Androgen treatment, which may be considered anyway for male 5αRD patients with a micropenis, may also be beneficial for growth

Arterial Function in Experimental Hypertension. Influence of Dietary Potassium and Exercise

This study was designed to examine arterial function in three different models of experimental hypertension, and study the influences of Whey supplementation, increased dietary K+ intake, and regular physical exercise on the control of arterial tone in experimental hypertension. The major findings and conclusions are: 1. Experimental models of genetic, mineralocorticoid-NaCl-induced, and obesity-related hypertension were associated with attenuated arterial dilatation. The defect of endothelium-mediated relaxation most likely resulted from impaired endothelium-dependent hyperpolarization of vascular smooth muscle in these hypertensive models, whereas the endothelial L-arginine-NO pathway appeared to be preserved. The function of voltage-dependent Ca2+ channels, as evaluated by enhanced inhibitory effect of nifedipine on the arterial contractions, was abnormal in smooth muscle of SHR and DOC-treated animals, while such an abnormality was not observed in obesity-related hypertension. 2. Supplementation with Whey and a comparable dose of K+ similarly opposed the development of experimental genetic hypertension, an effect which was associated with improved arterial dilatory properties. Supplementation with Whey had a protective effect on endothelium-mediated control of arterial tone in experimental DOC-NaCl hypertension even in the absence of a significant effect on blood pressure. Both supplements augmented the hyperpolarization-related component of arterial relaxation, increased the sensitivity of smooth muscle to NO, and decreased the production of vasoconstrictor prostanoids. Altogether the beneficial effects of the Whey diet could be attributed to increased intake of K+ in SHR and DOC. 3. The antihypertensive effect of long-term exercise in experimental obesity-related hypertension was associated with improved vasodilation. This was expressed as enhanced relaxation via endogenous and exogenous NO, and increased endothelial PGI2 production. The improved control of arterial tone after training could be attributed to the alleviation of hyperlipidemia and insulin resistance, whereas hyperinsulinaemia per se remained unaffected. 4. The sensitivity of NOS to induction by IL-1ß was higher in arterial smooth muscle of the OZR than the lean controls. Thus, this model of hyperinsuli-naemia was not associated with reduced sensitivity of smooth muscle NOS to induction by IL-1ß. Regular exercise did not change plasma insulin concentrations, but it enhanced the action of insulin in both rats strains as reflected by reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1ß. 5. In the absence of preceding myocardial hypertrophy the long-term exercise-induced workload was not deleterious to the heart in experimental OZR, since no changes in plasma and tissue atrial natriuretic peptide were detected.This study was designed to examine arterial function in three different models of experimental hypertension, and study the influences of Whey supplementation, increased dietary K+ intake, and regular physical exercise on the control of arterial tone in experimental hypertension. The major findings and conclusions are: 1. Experimental models of genetic, mineralocorticoid-NaCl-induced, and obesity-related hypertension were associated with attenuated arterial dilatation. The defect of endothelium-mediated relaxation most likely resulted from impaired endothelium-dependent hyperpolarization of vascular smooth muscle in these hypertensive models, whereas the endothelial L-arginine-NO pathway appeared to be preserved. The function of voltage-dependent Ca2+ channels, as evaluated by enhanced inhibitory effect of nifedipine on the arterial contractions, was abnormal in smooth muscle of SHR and DOC-treated animals, while such an abnormality was not observed in obesity-related hypertension. 2. Supplementation with Whey and a comparable dose of K+ similarly opposed the development of experimental genetic hypertension, an effect which was associated with improved arterial dilatory properties. Supplementation with Whey had a protective effect on endothelium-mediated control of arterial tone in experimental DOC-NaCl hypertension even in the absence of a significant effect on blood pressure. Both supplements augmented the hyperpolarization-related component of arterial relaxation, increased the sensitivity of smooth muscle to NO, and decreased the production of vasoconstrictor prostanoids. Altogether the beneficial effects of the Whey diet could be attributed to increased intake of K+ in SHR and DOC. 3. The antihypertensive effect of long-term exercise in experimental obesity-related hypertension was associated with improved vasodilation. This was expressed as enhanced relaxation via endogenous and exogenous NO, and increased endothelial PGI2 production. The improved control of arterial tone after training could be attributed to the alleviation of hyperlipidemia and insulin resistance, whereas hyperinsulinaemia per se remained unaffected. 4. The sensitivity of NOS to induction by IL-1ß was higher in arterial smooth muscle of the OZR than the lean controls. Thus, this model of hyperinsuli-naemia was not associated with reduced sensitivity of smooth muscle NOS to induction by IL-1ß. Regular exercise did not change plasma insulin concentrations, but it enhanced the action of insulin in both rats strains as reflected by reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1ß. 5. In the absence of preceding myocardial hypertrophy the long-term exercise-induced workload was not deleterious to the heart in experimental OZR, since no changes in plasma and tissue atrial natriuretic peptide were detected

Arterial Function in Experimental Hypertension. Influence of Dietary Potassium and Exercise

This study was designed to examine arterial function in three different models of experimental hypertension, and study the influences of Whey supplementation, increased dietary K+ intake, and regular physical exercise on the control of arterial tone in experimental hypertension. The major findings and conclusions are: 1. Experimental models of genetic, mineralocorticoid-NaCl-induced, and obesity-related hypertension were associated with attenuated arterial dilatation. The defect of endothelium-mediated relaxation most likely resulted from impaired endothelium-dependent hyperpolarization of vascular smooth muscle in these hypertensive models, whereas the endothelial L-arginine-NO pathway appeared to be preserved. The function of voltage-dependent Ca2+ channels, as evaluated by enhanced inhibitory effect of nifedipine on the arterial contractions, was abnormal in smooth muscle of SHR and DOC-treated animals, while such an abnormality was not observed in obesity-related hypertension. 2. Supplementation with Whey and a comparable dose of K+ similarly opposed the development of experimental genetic hypertension, an effect which was associated with improved arterial dilatory properties. Supplementation with Whey had a protective effect on endothelium-mediated control of arterial tone in experimental DOC-NaCl hypertension even in the absence of a significant effect on blood pressure. Both supplements augmented the hyperpolarization-related component of arterial relaxation, increased the sensitivity of smooth muscle to NO, and decreased the production of vasoconstrictor prostanoids. Altogether the beneficial effects of the Whey diet could be attributed to increased intake of K+ in SHR and DOC. 3. The antihypertensive effect of long-term exercise in experimental obesity-related hypertension was associated with improved vasodilation. This was expressed as enhanced relaxation via endogenous and exogenous NO, and increased endothelial PGI2 production. The improved control of arterial tone after training could be attributed to the alleviation of hyperlipidemia and insulin resistance, whereas hyperinsulinaemia per se remained unaffected. 4. The sensitivity of NOS to induction by IL-1ß was higher in arterial smooth muscle of the OZR than the lean controls. Thus, this model of hyperinsuli-naemia was not associated with reduced sensitivity of smooth muscle NOS to induction by IL-1ß. Regular exercise did not change plasma insulin concentrations, but it enhanced the action of insulin in both rats strains as reflected by reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1ß. 5. In the absence of preceding myocardial hypertrophy the long-term exercise-induced workload was not deleterious to the heart in experimental OZR, since no changes in plasma and tissue atrial natriuretic peptide were detected.This study was designed to examine arterial function in three different models of experimental hypertension, and study the influences of Whey supplementation, increased dietary K+ intake, and regular physical exercise on the control of arterial tone in experimental hypertension. The major findings and conclusions are: 1. Experimental models of genetic, mineralocorticoid-NaCl-induced, and obesity-related hypertension were associated with attenuated arterial dilatation. The defect of endothelium-mediated relaxation most likely resulted from impaired endothelium-dependent hyperpolarization of vascular smooth muscle in these hypertensive models, whereas the endothelial L-arginine-NO pathway appeared to be preserved. The function of voltage-dependent Ca2+ channels, as evaluated by enhanced inhibitory effect of nifedipine on the arterial contractions, was abnormal in smooth muscle of SHR and DOC-treated animals, while such an abnormality was not observed in obesity-related hypertension. 2. Supplementation with Whey and a comparable dose of K+ similarly opposed the development of experimental genetic hypertension, an effect which was associated with improved arterial dilatory properties. Supplementation with Whey had a protective effect on endothelium-mediated control of arterial tone in experimental DOC-NaCl hypertension even in the absence of a significant effect on blood pressure. Both supplements augmented the hyperpolarization-related component of arterial relaxation, increased the sensitivity of smooth muscle to NO, and decreased the production of vasoconstrictor prostanoids. Altogether the beneficial effects of the Whey diet could be attributed to increased intake of K+ in SHR and DOC. 3. The antihypertensive effect of long-term exercise in experimental obesity-related hypertension was associated with improved vasodilation. This was expressed as enhanced relaxation via endogenous and exogenous NO, and increased endothelial PGI2 production. The improved control of arterial tone after training could be attributed to the alleviation of hyperlipidemia and insulin resistance, whereas hyperinsulinaemia per se remained unaffected. 4. The sensitivity of NOS to induction by IL-1ß was higher in arterial smooth muscle of the OZR than the lean controls. Thus, this model of hyperinsuli-naemia was not associated with reduced sensitivity of smooth muscle NOS to induction by IL-1ß. Regular exercise did not change plasma insulin concentrations, but it enhanced the action of insulin in both rats strains as reflected by reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1ß. 5. In the absence of preceding myocardial hypertrophy the long-term exercise-induced workload was not deleterious to the heart in experimental OZR, since no changes in plasma and tissue atrial natriuretic peptide were detected

Factors Influencing Food Enterprises' Implementation of ISO9000 Series Standards from the Perspective of Economy and System

Currently, the food security situation is increasingly serious, and a growing number of food companies choose to implement the internationally accepted ISO9000 Series Standards. Based on the analysis of economic rationality and system drive for food enterprises to implement ISO9000 Series Standards, we determine the economic factors and institutional factors influencing enterprises' implementation of ISO9000 Series Standards, and establish corresponding indicator system. According to survey data on 86 enterprises in Sichuan Province, we draw the following conclusion using the Logit model: enterprise age and enterprise size in economic factors, government's food safety control intensity, consumers, public and media pressure, awareness of senior managers, strategic orientation of quality safety, employees' average educational level in institutional factors, have a significant effect on enterprises' implementation of ISO9000 Series Standards. According to research results, we put forth some recommendations for promoting food enterprises to implement ISO9000 Series Standards

Study on the Characteristics of Competition in Sichuan Tea Industry

Nowadays, there is huge potential in the domestic sales and export of tea in China. However, the tea leaf products are less competitive in the international market because of the lack of brand. As a province with large amount of tea leaves, characteristics of tea leaf industry in Sichuan Province were analyzed from three aspects, namely fundamental industrial characteristics, the competition strategy of a company and main competition measures. The tea industry in Sichuan Province was featured by its large amount of companies and low industrial concentration. The competition among tea companies often uses the strategy of different brands and low cost. The major way to compete was to build tea brand and to publicize the tea culture. Organic green tea was the main issue. Electronic business platform was applied. Study on the competition characteristics of tea industry in Sichuan can improve the regional competitiveness of tea industry and can make contribution to the entire tea industry in China

Measurement and convergence analysis of agricultural green development level in China

Based on the panel data of 30 provinces and regions (except Taiwan, Hong Kong, Macao and Tibet) from 2010 to 2019, this paper measures the green development level of agriculture in China by using critic-entropy weight combined weight method, and then uses σ convergence and absolute β convergence methods to test its change trend. Based on the research conclusions, countermeasures and suggestions were put forward to make up for the shortcomings, promote the exchange and cooperation between provinces and regions, and narrow the differences between provinces, in order to provide reference for policy formulation and promote the green development of agriculture in China