ICBcomb: a comprehensive expression database for immune checkpoint blockade combination therapy.

The success of immune checkpoint blockade (ICB) promotes the immunotherapy to be a new pillar in cancer treatment. However, the low response rate of the ICB therapy limits its application. To increase the response rate and enhance efficacy, the ICB combination therapy has emerged and its clinical trials are increasing. Nevertheless, the gene expression profile and its pattern of ICB combination were not comprehensively studied, which limits the understanding of the ICB combination therapy and the identification of new drugs. Here, we constructed ICBcomb (http://bioinfo.life.hust.edu.cn/ICBcomb/), a comprehensive database, by analyzing the human and mouse expression data of the ICB combination therapy and comparing them between groups treated with ICB, other drugs or their combinations. ICBcomb contains 1399 samples across 29 cancer types involving 52 drugs. It provides a user-friendly web interface for demonstrating the results of the available comparisons in the ICB combination therapy datasets with five functional modules: [1, 2] the 'Dataset/Disease' modules for browsing the expression, enrichment and comparison results in each dataset or disease; [3] the 'Gene' module for inputting a gene symbol and displaying its expression and comparison results across datasets/diseases; [4] the 'Gene Set' module for GSVA/GSEA enrichment analysis on the built-in gene sets and the user-input gene sets in different comparisons; [5] the 'Immune Cell' module for immune cell infiltration comparison between different groups by immune cell abundance analysis. The ICBcomb database provides the first resource for gene expression profile and comparison in ICB combination therapy, which may provide clues for discovering the mechanism of effective combination strategies and new combinatory drugs.

[Chemical Composition of VOCs from Service Stations Vapor Processing Device and Associated Contributions to Secondary Pollution].

Vapor processing device is a device that can control the headspace pressure in the underground storage tanks and recover the vapor. By analyzing the chemical composition of volatile organic compounds (VOCs) at the inlet and outlet of the vapor processing device, the ozone formation potential (OFP) and secondary organic aerosol formation potential (SOAP) were estimated by maximum incremental reaction (MIR) and fractional aerosol coefficients (FAC), and the secondary pollution formation contribution of VOCs were quantitatively evaluated. The results showed that:① the ρ(total volatile organic compounds, TVOC) at the inlet and outlet of the vapor processing device were 436-706 g·m-3 and 4.98-10.04 g·m-3, respectively. Alkanes (72%±4%), oxygenated organics (14%±2%), and olefins (11%±5%) were the dominant components of VOCs emissions. There were little differences in VOCs emissions from the different vapor processing devices; the key species were i-pentane (approximately 25%), followed by n-butane, i-butane, and n-pentane. ② The ozone source reactivity (SR) of VOCs emissions from the outlet of the vapor processing device was 2.6-3.3 g·g-1, and the OFP was 3.5-25.6 g·m-3. Olefins contributed the most (43%-69%), followed by alkanes (20%-35%) and oxygenated organics (10%-22%). Butene, cis-2-butene, trans-2-butene, i-pentane, and propionaldehyde were the species that highly contributed to OFP. ③ Aromatics in VOCs emissions contributed the most to SOAP (80%-92%), and the main active species were toluene, 1, 2, 4-trimethylbenzene, 1, 3, 5-trimethylbenzene, and p-diethylbenzene. The research showed that different VOCs species emitted by the vapor processing device contributed obvious differences to the secondary atmospheric pollution, and butene species and aromatics such as toluene were the focus of VOCs emission control of vehicle gasoline and vapor processing device.

[Annual Nitrogen Removal Efficiency and Change in Abundance of Nitrogen Cycling Microorganisms in Swine Wastewater Treated by Crop Straw Materials].

Based on previous research, using straw material to treat swine wastewater can effectively reduce the concentration of nitrogen (N); however, the annual N-removal efficiency and change in the abundance of N-cycling functional genes remain unclear. In this study, four treatments (wheat straw, rice straw, corn stalk, and CK) were set up, with the aim of studying the annual N-removal efficiency and change in the abundance of functional genes. Our results showed that:① the total nitrogen (TN) removal and NH4+-N removal efficiency were the best in the first six months and were significantly reduced in the following six months. In addition, the TN removal and NH4+-N efficiency in straw and wheat straw were better than those in corn straw. The TN-removal efficiency in straw and wheat straw were 32.81%±11.34% and 32.99%±9.60%, respectively. The NH4+-N removal efficiency in straw and wheat straw were 35.3%±13.23% and 34.97%±12.00%, respectively. ② The abundance of N-cycling functional genes significantly increased by the addition of straw materials, compared with that of the CK (P<0.05). The average abundances of nirK, nirS, and hzsB were 6.45×109 copies·L-1, 6.18×109 copies·L-1, and 2.31×109 copies·L-1, respectively. The average abundances of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) were 6.12×1010 copies·L-1 and 4.93×109 copies·L-1, respectively. The average hzsB gene abundance was 2.31×109 copies·L-1. The average abundance of 16S rRNA in the treatment was 8.90×1010 copies·L-1. The abundances of hzsB and nirS genes in the straw and wheat straw were higher than those in the other treatment, indicating that the activities of anaerobic ammonia oxidation and denitrifying microorganisms were significantly increased by the addition of straw and wheat straw (P<0.05). In addition, the abundance of AOA and AOB genes were increased in wheat straw, suggesting that wheat straw could promote nitrification. The results provided data supporting the molecular mechanism of nitrogen removal in swine wastewater treatment with straw materials.

SUMOylation of SIRT1 activating PGC-1α/PPARα pathway mediates the protective effect of LncRNA-MHRT in cardiac hypertrophy.

Long noncoding RNA-Myosin heavy chain associated RNA transcript (LncRNA-MHRT) has been reported to prevent pathological cardiac hypertrophy. However, the underlying inhibition mechanism has not been fully elucidated. Further, whether MHRT inhibits hypertrophy by regulating post-translational modification of certain proteins remains unclear. Therefore, this study aims to find potential role of MHRT in inhibiting cardiac hypertrophy via regulating modification of certain proteins. Here, Angiotensin II (Ang II) -treated neonatal rat cardiomyocytes and transverse aortic constriction (TAC) mice were used to investigate the effect and mechanism of MHRT in cardiac hypertrophy in vitro and in vivo. Moreover, the regulatory effects of MHRT on SUMOylation of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α)/peroxisome proliferator-activated receptor-α (PPARα), specificity protein 1 (SP1)/histone deacetylase 4 (HDAC4) pathway were investigated. Here, we found that MHRT improved heart function by attenuating pathological cardiac hypertrophy in vivo and in vitro. MHRT also promoted the SUMOylation of SIRT1 protein that activated PGC1-α/PPAR-α pathway. Furthermore, MHRT enhanced SUMOylation of SIRT1 by upregulating SP1/HDAC4. Our findings suggested that SUMOylation of SIRT1 could mediate the protective effect of MHRT in cardiac hypertrophy. The new regulatory pathway provides a potential new therapeutic target for pathological cardiac hypertrophy.

Domain Stylization: A Fast Covariance Matching Framework Towards Domain Adaptation.

Generating computer graphics (CG) rendered synthetic images has been widely used to create simulation environments for robotics/autonomous driving and generate labeled data. Yet, the problem of training models purely with synthetic data remains challenging due to the considerable domain gaps caused by current limitations on rendering. In this paper, we propose a simple yet effective domain adaptation framework towards closing such gap at image level. Unlike many GAN-based approaches, our method aims to match the covariance of the universal feature embeddings across domains, making the adaptation a fast, convenient step and avoiding the need for potentially difficult GAN training. To align domains more precisely, we further propose a conditional covariance matching framework which iteratively estimates semantic segmentation regions and conditionally matches the class-wise feature covariance given the segmentation regions. We demonstrate that both tasks can mutually refine and considerably improve each other, leading to state-of-the-art domain adaptation results. Extensive experiments under multiple synthetic-to-real settings show that our approach exceeds the performance of latest domain adaptation approaches. In addition, we offer a quantitative analysis where our framework shows considerable reduction in Frechet Inception distance between source and target domains, demonstrating the effectiveness of this work in bridging the synthetic-to-real domain gap.

Thyroid disorders in Taiwanese children with Down syndrome: The experience of a single medical center.

BACKGROUND/PURPOSE: Thyroid disorders are common in children with Down syndrome (DS), however, such data have rarely been reported in Taiwanese children. This study presents our experience with the management of these children. METHODS: Between 2006 and 2016, 51 children (31 boys and 20 girls) with DS were enrolled. Thyroid function was evaluated and natural course of thyroid status were analyzed. RESULTS: Of 51 patients with DS, 2 had congenital hypothyroidism due to dyshormonogenesis. Of the remaining 49 patients, 30 (61%) had euthyroidism (EuT), and 19 (39%) had subclinical hypothyroidism (SH). Eighteen (37%) had detectable thyroid antibodies. It occurred at any age and the incidence was not affected by sex. The mean follow-up duration for 39 DS children was 3.8 ± 2.4 years. Of the 26 children who had EuT at enrollment and were followed up, 22 remained EuT, 2 developed SH, 1 developed overt hypothyroidism, and 1 developed overt hyperthyroidism. Of the 13 patients with SH who were followed up, 1 was treated for high thyroid-stimulating hormone levels, 8 became EuT, and 4 maintained SH status. Children with DS and persistent SH had significantly higher maximum thyroid-stimulating hormone levels during follow-up than did those with transient SH. Fluctuation in thyroid status during follow-up was not uncommon in children with DS. CONCLUSION: The prevalence of thyroid disorders is higher in Taiwanese children with DS than in the general population. Because symptoms of hypothyroidism overlap those inherent to DS, regular follow-up of thyroid function in children with DS is indicated.

Models Matter, So Does Training: An Empirical Study of CNNs for Optical Flow Estimation.

We investigate two crucial and closely-related aspects of CNNs for optical flow estimation: models and training. First, we design a compact but effective CNN model, called PWC-Net, according to simple and well-established principles: pyramidal processing, warping, and cost volume processing. PWC-Net is 17 times smaller in size, 2 times faster in inference, and 11 percent more accurate on Sintel final than the recent FlowNet2 model. It is the winning entry in the optical flow competition of the robust vision challenge. Next, we experimentally analyze the sources of our performance gains. In particular, we use the same training procedure for PWC-Net to retrain FlowNetC, a sub-network of FlowNet2. The retrained FlowNetC is 56 percent more accurate on Sintel final than the previously trained one and even 5 percent more accurate than the FlowNet2 model. We further improve the training procedure and increase the accuracy of PWC-Net on Sintel by 10 percent and on KITTI 2012 and 2015 by 20 percent. Our newly trained model parameters and training protocols are available on https://github.com/NVlabs/PWC-Net.

[Treatment of Highly Concentrated Swine Wastewater and Its Degradation Processes Using Three Matrix Materials].

The direct discharge of wastewater from pig farms can restrict wetland plant growth meaning that constructed wetlands (CWs) have generally low treatment efficiency. The treatment of farming wastewater using pre-ecological treatment technologies can be used to ensure that effluent concentrations reach the tolerable limits of wetland plants. This study focused on the efficient use of crop straw for reducing the pollution load of swine wastewater. Using field-scale pilot tests, wheat straw, straw, and corn stalk were used as test biological matrix pool fillers to treat the farming wastewater. Continuous intake of wastewater and a hydraulic retention time of 7 days was adopted. When the average concentrations of COD, TN, NH4+-N, NO3--N, and TP in the influent were 1652.83 mg·L-1, 371.31 mg·L-1, 303.51 mg·L-1, 0.67 mg·L-1, and 65.22 mg·L-1, respectively, wheat straw had the greatest removal effect on COD, TN, and TP, achieving a removal rate of 32.1%, 40.9%, and 33.3%, respectively. The removal efficiency of straw on NH4+-N was highest, reaching 43.4%. After 180 days, the lignin, cellulose, and hemicellulose of the three matrix materials were not completely decomposed. The degradation rate of lignin was lower than for cellulose and hemicellulose; the degradation of lignin and cellulose in the straw was fastest; and the degradation hemicellulose in wheat straw was fastest. The results show that wheat straw and straw offer a higher efficiency treatment for swine wastewater than corn stalk, and the suggested replacement cycle period is five months. These results provide initial data to support the application of biological matrix materials in the treatment of swine wastewater.

[Impact of oral health promotion project on periodontal condition and life quality of the elderly in long-term care institutions].

PURPOSE: To assess the impact of oral health promotion project on periodontal condition and life quality of the elderly in long-term care institutions. METHODS: Elder people from 5 nursing homes in Wuhan city were selected and assigned to either the experimental group or the control group by random cluster grouping method. A six-month oral health promotion project was provided to the experimental group. The changes of geriatric oral health assessment index (GOHAI), oral hygiene index-simplified (OHI-S), gingival index (GI), bleeding on probing (BOP) and probing depth (PD) were compared with student's t test and repetitive measure analysis of variance using SPSS21.0 software package. RESULTS: A total of 322 subjects completed the study for 6 months, with 144 from the experimental group and 178 from the control group. No significant difference was observed between the two groups in social demographic characteristics, GOHAI scores, OHI-S, GI, BOP and PD at baseline(P>0.05). Greater improvements were observed in GOHAI scores, OHI-S, GI and BOP in the experimental group than the control group after interventions (P<0.05). CONCLUSIONS: Oral health promotion project can improve the elderly's oral health-related quality of life and periodontal condition.

[Impact of comprehensive health education on oral care knowledge, attitude and practice in the elderly in long-term care institutions].

PURPOSE: To assess the impact of comprehensive health education on oral care knowledge, attitude and practice(KAP) of the elderly in the long-term care institutions and to provide references for oral health education among the elder people. METHODS: Elder people from 2 nursing centers in Wuhan were selected. The follow-up period was 6 months. Questionnaires were used to collect social-demographic characteristics and oral care KAP data at baseline, the third month and the sixth month, respectively. Comprehensive health education, toothpaste and toothbrushes were provided at baseline and the third month. The changes of oral care KAP were observed before and after interventions. SPSS21.0 software package was used for statistical analysis. RESULTS: A total of 144 subjects with a mean age of (72.43±9.41) years completed the study after 6 months. At baseline, the KAP scores were (28.57±19.19), (70.66±21.99) and (39.86±24.18), respectively. At the sixth month, the KAP scores were (91.06±9.55), (95.31±10.23) and (90.00±13.38), respectively and significant improvements were observed (F=913.714, P＜0.001; F=114.042, P＜0.001; F=349.887, P＜0.001). Oral care knowledge and attitude, knowledge and practice, attitude and practice were positively correlated（ß=0.173, P=0.038; ß=0.269, P=0.001; ß=0.197, P=0.018）. Social-demographic characteristics had no significant effect on KAP scores (P＞0.05). CONCLUSIONS: Long-term care institutions should strengthen oral health education and improve oral care KAP, oral health status and oral health-related quality of life of the elder people.

Model-based self-optimization method for form correction in the computer controlled bonnet polishing of optical freeform surfaces.

Freeform surfaces have become increasingly widespread in the optical systems for enhanced performance and compact lightweight packaging. The geometrical complexity and high precision requirements of optical freeform surfaces for various functional optical applications, has posed great challenges in the design, precision machining, and measurement of these surfaces. This paper presents a model-based self-optimization approach for precision machining and measurement of optical freeform surfaces in the computer controlled bonnet polishing (CCBP) process. To realize the technical feasibility, the process parameters and motion control are accurately performed through modelling and simulation of machining processes, error compensation, and on-machine metrology.

Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction.

BACKGROUND/AIMS: Endothelin-1 is implicated in the pathogenesis of hypertension, but the underlying mechanisms remained elusive. Our previous study found that inhibition of mitochondrial fission of smooth muscle cells suppressed phenylephrine- and high K+-induced artery constriction. Here, we studied the effects of mitochondrial fission inhibitors on endothelin-1-induced vasoconstriction. METHODS: The tension of rat mesenteric arteries and thoracic aorta was measured by using a multi-wire myograph system. Mitochondrial morphology of aortic smooth muscle cells was observed by using transmission electron microscopy. RESULTS: Dynamin-related protein-1 selective inhibitor mdivi-1 relaxed endothelin-1-induced constriction, and mdivi-1 pre-treatment prevented endothelin-1-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Mdivi-1 had a similar inhibitory effect on rat thoracic aorta. Another mitochondrial fission inhibitor dynasore showed similar effects as mdivi-1 in rat mesenteric arteries. Mdivi-1 inhibited endothelin-1-induced increase of mitochondrial fission in smooth muscle cells of rat aorta. Rho-associated protein kinase inhibitor Y-27632 which relaxed endothelin-1-induced vasoconstriction inhibited endothelin-1-induced mitochondrial fission in smooth muscle cells of rat aorta. CONCLUSION: Endothelin-1 increases mitochondrial fission in vascular smooth muscle cells, and mitochondrial fission inhibitors suppress endothelin-1-induced vasoconstriction.

Risk factors and implications of progressive coronary dilatation in children with Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis that occurs in children and may lead to cardiovascular morbidity and mortality. Progressive coronary dilatation for at least 2 months is associated with worse late coronary outcomes in patients with KD having medium or giant aneurysms. However, the risk factors and occurrence of progressive coronary dilatation in patients with KD but without medium or giant aneurysms have been insufficiently explored. METHODS: We retrospectively enrolled 169 patients with KD from a tertiary medical center in Taiwan during 2009-2013. Medical records of all patients were reviewed. Echocardiography was performed during the acute KD phase and at 3-4 weeks, 6-8 weeks, 6 months, and 12 months after KD onset. Progressive coronary dilatation was defined as the progressive enlargement of coronary arteries on three consecutive echocardiograms. Logistic regression analysis was conducted to evaluate the potential risk factors for coronary aneurysms and progressive coronary dilatation. RESULTS: Of a total of 169 patients with KD, 31 (18.3%) had maximal coronary Z-scores of ≥ + 2.5 during the acute KD phase, 16 (9.5%; male/female: 9/7) had coronary aneurysms at 1 month after KD onset, and 5 (3.0%) satisfied the definition of progressive coronary dilatation. Multivariate logistic regression analysis revealed that an initial maximal coronary Z-score of ≥ + 2.5 [odds ratio (OR): 5.24, 95% confidence interval (CI): 1.31-21.3, P = 0.020] and hypoalbuminemia (OR: 4.83, 95% CI: 1.11-20.9, P = 0.035) were independent risk factors for coronary aneurysms and were significantly associated with progressive coronary dilatation. However, the association between intravenous immunoglobulin unresponsiveness and the development of coronary aneurysms at 1 month after KD onset didn't reach the level of significance (P = 0.058). CONCLUSIONS: In the present study, 3% (5/169) of patients with KD had progressive coronary dilatation, which was associated with persistent coronary aneurysms at 1 year after KD onset. Initial coronary dilatation and hypoalbuminemia were independently associated with the occurrence of progressive coronary dilatation. Therefore, such patients may require intensive cardiac monitoring and adjuvant therapies apart from immunoglobulin therapies.

Niclosamide ethanolamine inhibits artery constriction.

We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system. The protein levels were measured by using western blot techniques. Niclosamide ethanolamine (NEN) treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with NEN inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, NEN also showed antagonism against PE- and KPSS-induced constriction. NEN induced increase of cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMP-activated protein kinase (AMPK) in A10 cells and rat thoracic aorta. NEN-induced aorta relaxation was attenuated in AMPKα1 knockout (-/-) mice. SERCA inhibitors cyclopiazonic acid and thapsigargin, but not KATP channel blockers glibenclamide and 5-hydroxydecanoic acid, attenuated NEN-induced vasorelaxation in rat mesenteric arteries. NEN treatment increased cytosolic [Ca2+]i and depolarized mitochondrial membrane potential in vascular smooth muscle cells (A10). Niclosamide in non-salt form showed the similar vasoactivity as NEN in rat mesenteric arteries. Niclosamide ethanolamine inhibits artery constriction, indicating that it would be promising to be developed as an anti-hypertensive drug or it would induce vasodilation-related side effects when absorbed in vivo.

Effects of Thinning and Water Supply Manipulation on the Productivity of Pinus sylvestris var. mongolica in Northeastern China.

Management is an effective tool for increasing the productivity of Mongolian pine (Pinus sylvestris var. mongolica). This species has been widely planted in China, especially in sandy lands. However, optimization of management practices had not been fully explored. We established a system dynamic model to evaluate the effects of thinning and of manipulation of water supply on the productivity and population density of a Mongolian pine forest (17 scenarios in total). Different levels of thinning increased the mean biomass of Mongolian pine over no-management to a range from 202 to 256 t·ha-1. Increasing water supply decreased the mean biomass of Mongolian pine to a range from 176 to 199 t·ha-1. These results indicated that thinning at different levels may lead to an increase in biomass accumulation, while manipulating water supply may decrease biomass. Further, thinning appeared more effective than increasing water supply in efforts at maintaining high productivity of Mongolian pine forests. Moreover, the highest biomass occurred in a scenario with a thinning intensity of 30% in over-mature trees, indicating that this thinning intensity was the most effective choice for to the maintenance of the highest biomass in Mongolian pine forests. This study informs about the interactions between Mongolian pine and forest management, and provides guidelines for the practice of management of this forest type.

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction.

Mitochondria are dynamic organelles and continuously undergo fission and fusion processes. Mitochondrial fission is involved in multiple physiological or pathological processes, but the role of mitochondrial fission of smooth muscle cells in artery constriction is unknown. The role of mitochondrial fission of smooth muscle cells in arterial function was investigated by measuring the tension of rat mesenteric arteries and thoracic aorta and by evaluating mitochondrial fission, mitochondrial reactive oxygen species, and cytosolic [Ca2+]i in rat vascular smooth muscle cells. Mitochondrial fission inhibitors mdivi-1 and dynasore antagonized phenylephrine- and high K+-induced constriction of rat mesenteric arteries. Mdivi-1 relaxed phenylephrine-induced constriction, and mdivi-1 pretreatment prevented phenylephrine-induced constriction in mice, rat aorta, and human mesenteric arteries. Phenylephrine- and high K+-induced increase of mitochondrial fission in smooth muscle cells of rat aorta and the increase was inhibited by mdivi-1. Mdivi-1 inhibited high K+-induced increases of mitochondrial fission, mitochondrial reactive oxygen species, and cytosolic [Ca2+]i in rat vascular smooth muscle cells. Prechelation of cytosolic Ca2+ prevented high K+-induced cytosolic [Ca2+]i increase, mitochondrial fission, and mitochondrial reactive oxygen species overproduction. Mitochondria-targeted antioxidant mito-TEMPO antagonized phenylephrine- and high K+-induced constriction of rat mesenteric arteries. Nitroglycerin and ROCK (Rho-associated protein kinase) inhibitor Y27632, the 2 vasodilators with different vasorelaxant mechanisms, relaxed high K+-induced vasoconstriction and inhibited high K+-induced mitochondrial fission. In conclusion, the mitochondrial fission of smooth muscle cells is involved in artery constriction.

Mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone induces vasorelaxation without involving KATP channel activation in smooth muscle cells of arteries.

BACKGROUND AND PURPOSE: The effects and mechanisms of chemical mitochondrial uncouplers on vascular function have never been identified. Here, we characterized the effects of the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) on vascular function in rat mesenteric arteries and aorta and elucidated the potential mechanisms. EXPERIMENTAL APPROACH: Isometric tension of mesenteric artery and thoracic aorta was recorded by using a multiwire myograph system. Protein levels were measured by western blot analyses. Cytosolic [Ca2+ ]i , mitochondrial ROS (mitoROS) and mitochondrial membrane potential of smooth muscle cells (A10) were measured by laser scanning confocal microscopy. KEY RESULTS: Acute treatment with CCCP relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Pretreatment with CCCP prevented PE- and KPSS-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Similarly, CCCP prevented PE- and KPSS-induced constriction of rat thoracic aorta. CCCP increased the cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMPK in A10 cells and rat thoracic aorta tissues. CCCP-induced aorta relaxation was attenuated in AMPK α1 knockout (-/-) mice. SERCA inhibitors thapsigargin and cyclopiazonic acid (CPA) but not the KATP channel blocker glibenclamide partially inhibited CCCP-induced vasorelaxation in endothelium-denuded rat mesenteric arteries. CCCP increased cytosolic [Ca2+ ]i , mitoROS production and depolarized mitochondrial membrane potential in A10 cells. FCCP, the analogue of CCCP, had similar vasoactivity as CCCP in rat mesenteric arteries. CONCLUSIONS AND IMPLICATIONS: CCCP induces vasorelaxation by a mechanism that does not involve KATP channel activation in smooth muscle cells of arteries.

Taurochenodeoxycholate relaxes rat mesenteric arteries through activating eNOS: Comparing with glycochenodeoxycholate and tauroursodeoxycholate.

The bile acids (BAs) and their conjugates have vascular activities and the serum levels of BAs and their conjugates are increased in liver diseases. In the present study, we examined the in vitro vasoactivities of BAs conjugates taurochenodeoxycholate (TCDC) (5-80 µM), glycochenodeoxycholate (GCDC) (20-150 µM) and tauroursodeoxycholate (TUDC) (20-150 µM) in rat mesenteric arteries and thoracic aorta. The isometric tension of rat mesenteric arteries and thoracic aorta was recorded by using multi-wire myograph systems. TCDC induced significant concentration-dependent relaxation in endothelium-intact but not endothelium-denuded rat mesenteric arteries pre-contracted with phenylephrine (PE). TCDC also showed vasorelaxant effects on high K(+) induced contraction in rat mesenteric arteries. L-NAME treatment inhibited TCDC-induced relaxation in mesenteric arteries pre-contracted with PE. Acute treatment with TCDC increased protein expression of P-eNOS (ser1177) in human umbilical vein endothelial cells. GCDC dose-dependently relaxed PE-induced vasoconstriction in both endotheium-intact and endothelium-denuded rat mesenteric arteries, but GCDC showed no effect on high K(+)-induced vasoconstriction. Both GCDC and TCDC showed no apparent relaxation on PE and high K(+)-induced vasoconstriction in rat thoracic aorta. TUDC showed no effect on PE and high K(+)-induced vasoconstriction in rat mesenteric arteries and thoracic aorta. The study demonstrates that TCDC relaxes rat mesenteric arteries through activating eNOS. TCDC might be the major BAs conjugate for vasorelaxation in vivo.

[Study and Application of Test Method for VOCs Emission Factor of Refueling in Service Station].

VOCs emission of service station is one of the main sources of VOCs in Beijing. Uncontrolled emission factor (UEF) of refueling in China, US EPA, EEA respectively is 2.16, 1.31 and 1.00 times of CARB UEF (1008 mg·L-1). China's gasoline standards have changed in the last 20 years, and there is an urgent need to carry out the localization of gasoline refueling VOCs emission factor research. This paper compared test methods for refueling emission factors of European Union (EU) and California Air Resources Board (CARB) and found that the EU method was simpler and easier to operate than the CARB method, so we processed refueling VOCs emission factors test device in reference to EU test methods and chose a set of United States Stage Ⅱ vapor recovery system in Beijing service stations to carry out studies on VOCs emission factors. The results showed that: 1 For the fuel test tank, refueling vapor recovery efficiencies were 0.93 and 0.83 times of air to liquid volume ratio (A/L) of Stage Ⅱ respectively in winter and summer. Refueling emission factor in summer was greater than that in winter, and its recovery efficiency was lower than that in winter. 2 For the social vehicles, winter and summer refueling UEF respectively was (525±42) mg·L-1 and (963±174) mg·L-1, at the same time was 0.52 and 0.95 times of CARB refueling UEF (1008 mg·L-1) in A/L=0.The average value of emission factors respectively was (55±30) mg·L-1 and (112±108) mg·L-1 in A/L 1.05-1.07 in winter and summer. 3Refueling UEF without vapor recovery of social vehicles was chosen as the localized summer and winter refueling UEF in Beijing, we could calculate the emission factor of vapor recovery in different A/L combining with the linear equation of the fuel test tank.

The copper-catalyzed aerobic oxidative amidation of tertiary amines.

A general and efficient method for the synthesis of tertiary amides has been developed via the copper-catalyzed aerobic oxidative amidation of tertiary amines. Due to the use of the O2 oxidant, various functional groups were well tolerated under the present conditions. Extensive substrates studies demonstrated its potential as a practical approach for the synthesis of tertiary amides.