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Circadian locomotor output cycles kaput protein (CLOCK) plays a crucial role in glucose homeostasis and controlling insulin secretion. However, the mechanism of the CLOCK regulating rhythmic insulin secretion has not been fully understood.Rhythmic expression of the CLOCK in rat pancreatic beta cell was detected. INS-1 cells were transfected with siRNAs to knockdown the CLOCK before the cells were incubated with different concentrations of glucose. Insulin secretion was analyzed by ELISA method. Expression of the L-type calcium channel protein (Cav1.2, Cacna1c) was determined both in the CLOCK-knockdown cells and the control cells. Calcium influx was probed by fluorescent. Chromatin immunoprecipitation (ChIP) test and dual-luciferase reporter gene experiments were applied to verify the relationship between the CLOCK and Cav1.2.The CLOCK is abundantly expressed in rat pancreatic beta cells. Transcription level of the CLOCK showed rhythmicity in the beta cells. Compared to the control group, insulin release was significantly impaired with 25 mM glucose incubation in the CLOCK-knockdown group, but not showed with 2.5 mM glucose incubation. The expression of Cav1.2 and the influx of calcium were significantly decreased in the CLOCK-knockdown group with 25 mM glucose incubation. ChIP test indicted that the CLOCK bound to -444∼-454 region of the Cacna1c promoter of the INS-1 cells, but the binding was significantly reduced following the CLOCK-knockdown. Luciferase experiment was in accordance with the finding of ChIP.The CLOCK mediating Cav

Both poor sleep and diabetic kidney disease are closely associated with inflammation. However, the correlation between poor sleep and diabetic kidney disease has not been well clarified. Thus, the aim of this study was to determine the mediating role that inflammatory markers play in the pathogenic effect of poor sleep on the severity of diabetic kidney disease (DKD). A cross-sectional survey was conducted on 336 patients with type 2 diabetes (T2D). DKD was diagnosed according to the guidelines of the National Kidney Foundation-Kidney Disease Outcome Quality Initiative (NKF-K/DOQI). The Pittsburg Sleep Quality Index (PSQI) score was applied to assess patients for the quality of their sleep. Patients with a PSQI score of more than 5 were assigned to the poor sleep group, and the rest of the patients were assigned to the good sleep group. Circulating levels of six inflammatory biomarkers related to poor sleep and DKD were measured. The prevalence of DKD was higher in patients with poor sleep quality than in those with good sleep quality (42% vs. 25%, P = 0.002). After adjustment, poor sleep quality (PSQI score OR 1.075 [95%CI 1.018–1.135], P = 0.009) remained independently associated with DKD. PSQI score was found to be positively related to fibroblast growth factor (FGF23), interleukin 6 (IL-6), P-selectin, and intercellular adhesion molecule-1 (ICAM-1) (P

Since 2013, the Chinese government has issued a set of action plans catered toward the ecological civilization construction. To quantify and evaluate the ecological civilization development, this study has introduced the ecological civilization index of China (ECI), using different standardization methods (extreme standardization, single-benchmark progressive standardization, and double benchmark progressive standardization), to evaluate ecological civilization development on city-level (337 cities) of China. The issues of China's ecological civilization construction were analyzed. The evaluation results suggest that in the double benchmark progressive method, every evaluation score has its practical meaning and is therefore suitable for policy making. This study obtained an average ECI score of 61.16, for 337 cities. This is China's overall ECI score, which is classified as C-grade. Only 4.75% of cities' green environment (GE) score obtained A-grade, while 53.41% of cities' GE scored below the passing level, suggesting that the quality of the ecology and environment is neglected in the development of China eco-civilization. This study provides valuable knowledge for both the ecological and environment management and eco-civilization construction.

Training deep networks with limited labeled data while achieving a strong generalization ability is key in the quest to reduce human annotation efforts. This is the goal of semi-supervised learning, which exploits more widely available unlabeled data to complement small labeled data sets. In this paper, we propose a novel framework for discriminative pixel-level tasks using a generative model of both images and labels. Concretely, we learn a generative adversarial network that captures the joint image-label distribution and is trained efficiently using a large set of unlabeled images supplemented with only few labeled ones. We build our architecture on top of StyleGAN2, augmented with a label synthesis branch. Image labeling at test time is achieved by first embedding the target image into the joint latent space via an encoder network and test-time optimization, and then generating the label from the inferred embedding. We evaluate our approach in two important domains: medical image segmentation and part-based face segmentation. We demonstrate strong in-domain performance compared to several baselines, and are the first to showcase extreme out-of-domain generalization, such as transferring from CT to MRI in medical imaging, and photographs of real faces to paintings, sculptures, and even cartoons and animal faces. Project Page: \url{https://nv-tlabs.github.io/semanticGAN/}, CVPR2021

We propose Neural Turtle Graphics (NTG), a novel generative model for spatial graphs, and demonstrate its applications in modeling city road layouts. Specifically, we represent the road layout using a graph where nodes in the graph represent control points and edges in the graph represent road segments. NTG is a sequential generative model parameterized by a neural network. It iteratively generates a new node and an edge connecting to an existing node conditioned on the current graph. We train NTG on Open Street Map data and show that it outperforms existing approaches using a set of diverse performance metrics. Moreover, our method allows users to control styles of generated road layouts mimicking existing cities as well as to sketch parts of the city road layout to be synthesized. In addition to synthesis, the proposed NTG finds uses in an analytical task of aerial road parsing. Experimental results show that it achieves state-of-the-art performance on the SpaceNet dataset., ICCV-2019 Oral

BACKGROUND Mobile-based interventions appear to be promising in ameliorating huge burdens experienced by patients with type 2 diabetes. However, it is unclear how effective mobile-based interventions are in glycemic management of patients with type 2 diabetes based on real-world evidence. OBJECTIVE This study aimed to evaluate the effectiveness of a mobile-based intervention on glycemic control in patients with type 2 diabetes based on real-world population data. METHODS This retrospective, propensity score-matched cohort study analyzed longitudinal data from a clinical electronic health database. The study population included 37,913 patients with type 2 diabetes at cohort entry between October 1, 2016, and July 31, 2018. A total of 2400 patients were matched 1:1, using propensity score matching, into the usual care and mobile health (mHealth) groups. The primary outcomes of glycemic control included control rates of glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial 2-hour blood glucose (P2BG). Mean values and variation trends of difference with 95% CI were the secondary outcomes. The general linear model was used to calculate repeated-measures analyses of variance to examine the differences between the two groups. Subgroup and sensitivity analyses were performed. RESULTS Of the 2400 patients included in the analysis, 1440 (60.00%) were male and the mean age was 52.24 years (SD 11.56). At baseline, the control rates of HbA1c, FBG, and P2BG in the mHealth and usual care groups were 45.75% versus 47.00% (P=.57), 38.03% versus 32.76% (P=.07), and 47.32% versus 47.89% (P=.83), respectively. At the 3-, 6-, 9-, and 12-month follow-ups, the mHealth group reported higher control rates of HbA1c than did the usual care group: 69.97% versus 46.06% (PP=.004), 75.38% versus 53.44% (PPPPPPPPPP=.001), respectively. At the four follow-up sessions, the percentages of HbA1c reduction in the mHealth group were 8.66% (95% CI 6.69-10.63), 10.60% (95% CI 8.66-12.54), 10.64% (95% CI 8.70-12.58), and 8.11% (95% CI 6.08-10.14), respectively. At the four follow-up sessions, the percentages of P2BG reduction in the mHealth group were 8.44% (95% CI 7.41-10.73), 17.77% (95% CI 14.98-20.23), 16.23% (95% CI 13.05-19.35), and 16.91% (95% CI 13.17-19.84), respectively. Starting from the sixth month, the mean HbA1c and P2BG values in the two groups increased slightly. CONCLUSIONS This mobile-based intervention delivered by a multidisciplinary team can better improve glycemic control rates of patients with type 2 diabetes than usual care. These effects were best sustained within the first 6 months. Starting from the sixth month, intensive management needs to be conducted to maintain long-term effectiveness of the mobile-based intervention.

The effects of degradation of alpine wetland meadow on soil respiration (Rs) and the sensitivity of Rs to temperature (Q10) were measured in the Napa Lake region of Shangri-La on the southeastern edge of the Qinghai-Tibet Plateau. Rs was measured for 24 h during each of three different stages of the growing season on four different degraded levels. The results showed: (1) peak Rs occurred at around 5:00 p.m., regardless of the degree of degradation and growing season stage, with the maximum Rs reaching 10.05 μmol·m−2·s−1 in non-degraded meadows rather than other meadows; (2) the daily mean Rs value was 7.14–7.86 μmol·m−2·s−1 during the mid growing season in non-degraded meadows, and declined by 48.4–62.6% when degradation increased to the severely degraded level; (3) Q10 ranged from 7.1–11.3 in non-degraded meadows during the mid growing season, 5.5–8.0 and 6.2–8.2 during the early and late growing seasons, respectively, and show a decline of about 50% from the non-degraded meadows to severely degraded meadows; (4) Rs was correlated significantly with soil temperature at a depth of 0–5 cm (p 10 and Rs (p 10. The results suggest that vegetation degradation impact both Rs and Q10 significantly. Also, we speculated that Q10 of alpine wetland meadow is probable greater at the boundary region than inner region of the Qinghai-Tibet Plateau, and shoule be a more sensitive indicator in the studying of climate change in this zone.

Neural networks have recently become good at engaging in dialog. However, current approaches are based solely on verbal text, lacking the richness of a real face-to-face conversation. We propose a neural conversation model that aims to read and generate facial gestures alongside with text. This allows our model to adapt its response based on the "mood" of the conversation. In particular, we introduce an RNN encoder-decoder that exploits the movement of facial muscles, as well as the verbal conversation. The decoder consists of two layers, where the lower layer aims at generating the verbal response and coarse facial expressions, while the second layer fills in the subtle gestures, making the generated output more smooth and natural. We train our neural network by having it "watch" 250 movies. We showcase our joint face-text model in generating more natural conversations through automatic metrics and a human study. We demonstrate an example application with a face-to-face chatting avatar., Published at CVPR 2018

Rapid and periodic assessment of the impact of land cover change and climate variability on ecosystem services at regional levels is essential to understanding services and sustainability of ecosystems. This study focused on quantifying and assessing the changes in multiple ecosystem services in the Three-River Headwaters Region (TRHR), China in 2000–2012. Based on the widely used biophysical models including Integrated Valuation of Ecosystem Services and Trade-Offs (InVEST), Revised Wind Erosion Equation (RWSQ), and Carnegie-Ames-Stanford Approach (CASA) models, this study assessed the historical flow of regulating services, including soil conservation, water yield, and carbon sequestration, and provisioning service food provision. The soil conservation function of ecosystem was slightly enhanced as a whole, and water yield increased sharply, with both the soil conservation and water yield showing an increasing spatial homogenization. The net primary productivity (NPP) and food production increased substantially from 2000 to 2012. Ecosystem services are closely and complexly interlinked. The correlation analyses indicated a trade-off between the water yield and carbon sequestration, however, a synergy between soil conservation and carbon sequestration. Congruence between the three different ecosystem provisioning services, including pasture, meat, and grain, was found. There was also a synergy between food production and ecosystem carbon sequestration in the TRHR. Climatic variability and vegetation restoration are important for the ecosystem services flow. Correlation analyses showed that the increase in precipitation significantly enhanced the water yield (P

Under the impacts of climate variability and human activities, there is violent fluctuation for streamflow in the large basins in China. Therefore, it is crucial to separate the impacts of climate variability and human activities on streamflow fluctuation for better water resources planning and management. In this study, the Three Rivers Headwater Region (TRHR) was chosen as the study area. Long-term hydrological data for the TRHR were collected in order to investigate the changes in annual runoff during the period of 1956–2012. The nonparametric Mann–Kendall test, moving t test, Pettitt test, Mann–Kendall–Sneyers test, and the cumulative anomaly curve were used to identify trends and change points in the hydro-meteorological variables. Change point in runoff was identified in the three basins, which respectively occurred around the years 1989 and 1993, dividing the long-term runoff series into a natural period and a human-induced period. Then, the hydrologic sensitivity analysis method was employed to evaluate the effects of climate variability and human activities on mean annual runoff for the human-induced period based on precipitation and potential evapotranspiration. In the human-induced period, climate variability was the main factor that increased (reduced) runoff in LRB and YARB (YRB) with contribution of more than 90 %, while the increasing (decreasing) percentage due to human activities only accounted for less than 10 %, showing that runoff in the TRHR is more sensitive to climate variability than human activities. The intra-annual distribution of runoff shifted gradually from a double peak pattern to a single peak pattern, which was mainly influenced by atmospheric circulation in the summer and autumn. The inter-annual variation in runoff was jointly controlled by the East Asian monsoon, the westerly, and Tibetan Plateau monsoons.

Monthly hydrological and daily meteorological data were collected across the Three-Rivers Headwater Region (TRHR) over a period from 1956 to 2012. Modified Mann–Kendall tests, flow duration curves, and correlation statistics were performed to identify long-term trend and interrelationships between these hydro-meteorological variables and to analyse the factors influencing runoff. The results of these analyses are as follows. (1) In the last 57 years, the annual runoff in the Lancang River Basin (LRB) and the Yangtze River Basin (YARB) has shown an increasing trend, while the runoff in the main stream of the Yellow River Basin (YRB) was slightly reduced. (2) In the YRB and the YARB, both the high and low flows decreased and increased together, respectively, whereas in the LRB, the high flow decreased while the low flow increased. (3) In the TRHR, the proportional change in annual runoff due to climate variability accounted for >85% of the observed change, while anthropogenic activity and glacier melting was responsible for ∼15%. The contribution of anthropogenic activity in the YRB and LRB was higher than that in YARB due to the greater anthropogenic activity. The contribution of glacier melting in the YARB and LRB were obviously higher than that in YRB due to the higher densities of glaciers.

Globally, more people and assets are concentrated on the limited coastal plains where they are exposed to frequent disasters, such as typhoons, rainstorms and floods that often result in tremendous casualties and economic losses. Based on the causal analysis of the historical typhoon cases in the Guangdong Province of China, this study indicates that structural measures alone are not sufficient to resist and offset the impacts caused by typhoon disasters. Additionally, structural measures are unsustainable due to their high investment and low security. Adaptive governance, which uses non-structural measures and resilience building, is a feasible and cost-effective strategy for responding to the cascading effects of typhoon disasters. Multi-stakeholder participation and vertical–horizontal coordination are essential for providing adaptive governance to typhoon disasters. A risk-sharing model was put forward by bringing together the government, insurance companies and victims. Furthermore, a favorable atmosphere for public participation in disaster risk reduction can be fostered and should be a long-term adaptation strategy. The views and frameworks of adaptive governance provide policy makers with insights on coastal disaster risk management within the broader context of climate change.

In this research, monthly hydrological and daily meteorological data were collected across China for the period 1956–2012. Modified Mann–Kendall tests, double mass curve analysis, and correlation statistics were performed to identify the long-term trends and interrelation of the hydrometeorological variables and to examine the influencing factors of streamflow and sediment. The results are as follows: (1) In the last 60 years, the streamflow in northern China has shown different decreasing trends. For the southern rivers, the streamflow presented severe fluctuations, but the declining trend was insignificant. For the streamflow in western China, an increasing trend was shown. (2) In the northern rivers, the streamflow was jointly controlled by the East Asian monsoon and westerlies. In the southern rivers, the runoff was mainly influenced by the Tibet–Qinghai monsoon, the South Asian monsoon, and westerlies. (3) Sediment loads in the LCRB (Lancang River Basin) and YZRB (Yarlung Zangbo River Basin) did not present significant change trends, although other rivers showed different degrees of gradual reduction, particularly in the 2000s. (4) Underlying surface and precipitation changes jointly influenced the streamflow in eastern rivers. The water consumption for industrial and residential purposes, soil and water conservation engineering, hydraulic engineering, and underlying surface changes induced by other factors were the main causes of streamflow and sediment reduction.

The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable channel activated by cAMP, is expressed on pancreatic β-cells and is responsible for the regulation of insulin secretion. It is known that glucose-stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1 (GLP-1), and that the changes in the extracellular glucose concentration alter the levels of intracellular adenosine ATP and cAMP. The present study hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin secretion. The results demonstrated that silencing of TRPM2 eliminated GLP-1-enhanced insulin secretion, indicating the involvement of TRPM2 in this process. In addition, the results of current recordings of TRPM2 and measurement of the resulting insulin secretion in β-cells in the presence of GLP-1 and various concentrations of glucose suggest that GLP-1 regulates GSIS via the TRPM2 channel. Furthermore, inhibiting the activity or expression of TRPM2 attenuated GLP-1-induced GSIS. By using specific activators or inhibitors, the present study demonstrated that the two primary downstream effectors of the GLP-1 receptor, exchange protein directly activated by cAMP and protein kinase A, differentially influence GSIS and GLP-1-potentiated GSIS. In conclusion, the present study revealed the role of TRPM2 in GLP-1-regulated insulin secretion. The results of the present study provide a novel avenue for the prevention and treatment of diabetes and its complications.

Aims A meta-analysis was conducted to evaluate the diagnostic value of glycated hemoglobin (HbA1c) ≥6.5% (48 mmol/mol) for diabetes in Chinese adults. Methods Oral glucose tolerance test (OGTT) was selected as the reference standard. PubMed, EMBASE, CNKI, Wanfang Data, and VIP were searched to obtain all diagnostic tests with HbA1c ≥6.5% (48 mmol/mol) for diabetes in Chinese adults published between January 2003 and October 2013. The qualities of the included studies were assessed by using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-DiSc software was used to conduct a comprehensive quantitative assessment, and summary receiver operating characteristic (sROC) curves were obtained. Results A total of 9 studies with 25,932 subjects were included. Pooled sensitivity was 0.518, pooled specificity 0.956, pooled positive likelihood ratio 19.007 and pooled negative likelihood ratio was 0.477. Pooled diagnostic odds ratio was 40.631. AUCsROC was 0.929. Conclusion Compared with OGTT, using HbA1c ≥6.5% (48 mmol/mol) to diagnose diabetes in Chinese adults exhibited high specificity and low sensitivity and would have failed to diagnose 48.7% of newly diagnosed diabetes. The diagnostic HbA1c value could be reduced to improve sensitivity. Long-term prospective studies are required to establish an appropriate HbA1c value as a diagnostic criterion for diabetes in China.

Aim Circadian rhythm controls a wide variety of physiological processes in the body. Disruption of the circadian clock in metabolic tissues may increase the risk of diabetes, obesity, and metabolic syndrome. The following study investigated whether the expression of clock genes of peripheral blood cells is impaired in type 2 diabetes (DT2) and whether inflammatory markers are associated with circadian clock gene expression in DT2 patients. Materials and methods Blood samples were obtained from 36 DT2 patients and 14 non-diabetic volunteers. Transcript levels of circadian clock genes were analyzed using real-time quantitative PCR; plasma inflammatory markers were measured by ELISA or clinical laboratory test. Results The CLOCK, BMAL1, PER1, CRY1 and CRY2 mRNA levels were decreased in the diabetic patients. In addition, HbA1c levels were negatively correlated with BMAL1, PER1 and CRY1 mRNA levels. The levels of IL-6, TNF-α and CRP were higher in diabetic subjects compared to control subjects. Impaired expression of circadian clock gene was interrelated with the elevated levels of plasma IL-6 and TNF. Moreover, a multiple linear regression showed that plasma IL-6 level was correlated with impaired expression of circadian clock gene. Conclusions Circadian clock genes are reduced in peripheral leucocytes of DT2 patients. Furthermore, impaired expression of circadian clock gene are interrelated with the elevated levels of plasma inflammatory markers.

The prevalence of hyperuricemia and gout has been increasing, but the comparative effectiveness and safety of different treatments remain uncertain. We aimed to compare the effectiveness and safety of different treatments for hyperuricemia using network meta-analysis methodology. We systematically reviewed fifteen randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) on hyperuricemia. Drug efficacy and safety, as outcomes, were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred, respectively. We derived pooled effect sizes expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The efficacy and safety of the drugs were ranked by cumulative ranking probabilities. Our findings show that febuxostat, benzbromarone, probenecid, pegloticase, and allopurinol were all highly effective at reducing the risk of hyperuricemia compared to placebo. Febuxostat had the best efficacy and safety compared to the other drugs. Furthermore, febuxostat 120 mg QD was more effective at achieving urate-lowering targets (OR: 0.17, 95% CI: 0.12–0.24) and safer (OR: 0.72, 95% CI: 0.56–0.91) than allopurinol.

// Huafeng Wang 1, 2, 3, * , Huan Zhang 1, 4, * , Yuqing Zhang 5, * , Dan Wang 1, * , Xixi Cheng 1 , Fengrui Yang 1, 2 , Qi Zhang 1 , Zhenyi Xue 1, 2 , Yan Li 1, 2 , Lijuan Zhang 1, 2 , Luhong Yang 3 , Guolin Miao 1, 2 , Daiqing Li 6 , Zhiyu Guan 7 , Yurong Da 1, 2 , Zhi Yao 2 , Fei Gao 8 , Liang Qiao 9 , Li Kong 10 , Rongxin Zhang 1, 2 1 Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China 2 Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China, Tianjin Medical University, Tianjin, China 3 School of Life Science, Shanxi Normal University, Linfen, China 4 Clinical Laboratory, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China 5 Department of Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China 6 Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China 7 Department of Pathogenic Biology, Weifang Medical University, Shandong, China 8 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China 9 Storr Liver Unit, Westmead Millennium Institute, The Western Clinical School of the University of Sydney, Westmead, NSW, Australia 10 Department of Histology and Embryology, Dalian Medical University, Dalian, China * These authors have contributed equally to this work Correspondence to: Rongxin Zhang, email: rxzhang@tmu.edu.cn , rongxinz@yahoo.com Li Kong, email: kongli@dmu.edu.cn Keywords: plumbagin, fulminant hepatic failure, liver fibrosis, hepatic stellate cell, inflammation Received: August 08, 2016 Accepted: October 04, 2016 Published: October 14, 2016 ABSTRACT Plumbagin is a quinonoid constituent extracted from Plumbago genus, and it exhibits diverse pharmacological effects. This study thoroughly investigated the effects of plumbagin on thioacetamide-induced acute and chronic liver injury. Results shown that plumbagin increased survival rate, reduced liver congestion and inflammation, and decreased macrophages and neutrophils in the fulminant hepatic failure model, and remarkably diminished liver fibrosis and inflammation in the chronic liver injury model. Furthermore, plumbagin significantly suppress the HSCs/myofibroblasts activation by reduced expression of markers α-SMA and COL-1/3, and reduced macrophage in liver. In the in vitro study, plumbagin induced apoptosis and suppressed the proliferation of LX-2 cells (human HSCs). Plumbagin treatment increased AMPK phosphorylation and attenuated NF-κB, STAT3, and Akt/mTOR signals in LX-2 cells, while SMAD2 phosphorylation was not changed. Noticeably, plumbagin promoted AMPK binding to p300 which is a cofactor of SMAD complex, this may further competitively decreases the p300/SMAD complex initiated transcription of COL-1/3 and α-SMA. Additionally, plumbagin hampered inflammation related NF-κB signal in RAW 264.7 cells. In conclusion, these findings indicate that plumbagin may be a powerful drug candidate to protect the liver from acute and chronic damage by inhibiting inflammation and collagen production.

Scientific Reports 6: Article number: 19445; published online: 18 January 2016; updated: 31 May 2016 This Article contains typographical errors in the Methods section under subheading ‘Chemicals and Animals’, “Thioacetamide (TAA) (Sigma-Aldrich, Switzerland), ADP355 (H-Asn-Ile-Pro-Nva-Leu-Tyr-Ser-Phe-Ala- DSer-NH2) and scramble (H-Pro-Ile-Asn-Tyr-Ala-Nva-Ser-Phe-Leu-Ser-NH2) (Lysine Bio-system, China) were all dissolved in PBS”.

Adiponectin is an adipocyte-derived circulating protein with beneficial effects on injured livers. Adiponectin-deficient (adipo(−/−)) mice develop enhanced liver fibrosis, suggesting that adiponectin could be a therapeutic target for liver injury. In the present study, we investigated the protective role of ADP355, an adiponectin-based active short peptide, in thioacetamide (TAA)-induced acute injury and chronic liver fibrosis in mice. ADP355 remarkably reduced TAA-induced necroinflammation and liver fibrosis. ADP355 treatment increased liver glycogen, decreased serum alanine transaminase and alkaline phosphatase activity and promoted body weight gain, hyper-proliferation and hypo-apoptosis. In addition, ADP355 administration suppressed the TAA-induced activation of hepatic stellate cells and macrophages in the liver. These were associated with the inactivation of TGF-β1/SMAD2 signaling and the promotion of AMPK and STAT3 signaling. Sensitivity of adipo(−/−) mice to chronic liver injury was decreased with ADP355. In conclusion, ADP355 could mimic adiponectin’s action and may be suitable for the preclinical or clinical therapy of chronic liver injury.

We utilized a modified double-emulsion method with poly(lactic-co-glycolic acid) as the carrier to prepare recombinant human epidermal growth factor (rhEGF) nanoparticles. The morphology of the nanoparticles was detected by a transmission electron microscope. The particle size distribution was measured by a laser analyzer with a zeta potential meter. Enzyme-linked immunosorbent assays were performed to determine the rhEGF encapsulation efficiency and release model, and the proliferation of the mouse fibroblasts was analyzed by the MTT method. Diabetic rats with full-thickness wounds were divided into four groups according to different treatments: rhEGF nanoparticles, rhEGF stock solution, empty nanoparticles, and phosphate-buffered saline. Photographs were taken after the treatments to calculate the wound healing rates, and the granulation tissue of the wounds was sampled for pathologic slides. Proliferating cell nuclear antigen was assayed by immunohistochemistry. Our results showed that the rhEGF nanoparticles were around 193.5 nm (diameter), and the particle size distribution was uniform and dispersible. The encapsulation efficiency was 85.6% and rhEGF release lasted 24 hours. Compared with other groups, the rhEGF nanoparticles promoted the highest level of fibroblast proliferation, and this group showed the fastest healing rate. The number of proliferating cell nuclear antigen positive cells in the rhEGF nanoparticles group was higher than the other groups. We concluded that controlled release of rhEGF encapsulated in the nanoparticles enhanced rhEGF effects to stimulate cell proliferation and shorten the wound healing time.

The aim of our study was to investigate whether pre-existing type 2 diabetes and insulin therapy have an impact on the prognosis of breast cancer patients.We performed a retrospective analysis of 462 type 2 diabetic breast cancer patients and 1644 non-diabetic breast cancer patients treated in our institute from January 2005 to August 2010. Patients were divided by diabetes status and insulin use. The clinicopathological characteristics and clinical outcomes of patients within 5 years following breast cancer diagnosed were analysed.Diabetic patients tended to have higher body mass index and higher histological grade tumours. Five-year disease-free survival and overall survival were reduced in diabetic patients (P 0.001), and diabetes was an independent predictor for an increased risk of breast cancer relapse and death within 5 years (P 0.001). Insulin treatment was associated with reduced 5-year disease-free survival and overall survival (P 0.05); the risk of 5-year relapse and breast cancer mortality in the insulin group increased compared to that of non-insulin group after adjusting for age, tumour size, histological grade, oestrogen receptor, progesterone receptor, chemotherapy and hormone therapy (P 0.05). After adjusting for age and other factors, the risk of breast cancer relapse was also increased in the insulin subgroup, while the risk of breast cancer mortality did not increase statistically.Type 2 diabetes and insulin treatment might be independently associated with poorer prognosis of breast cancer. However, caution is needed when interpreting our results, and further investigations are needed. Copyright © 2016 John WileySons, Ltd.

This paper examines the influence of the materials on the electrical properties of conductors for both high speed MCM structures and microstrip applications. Calculated figures for attenuation in microstrip lines are compared with published results. It is seen that the nature and physical structure as well as the geometrical shape of a conductor track all strongly influence the microwave performance. However, it is also clear that real materials have been developed for these applications which closely approach the behavior predicted for ideal conductors. It is proposed that microwave performance can be predicted by modelling the d.c. conductor materials and extrapolating to high frequencies.

The thermal constant (K) and the threshold temperature (T0) for development of eggs were estimated by using linear regression for 16 species (17 populations) of spiders. T0 ranged between 4.2 and 16.8°C, K between 64.1 and 217.4 day-degrees (dd). When T0 was plotted against K, the data were scattered along a single regression line (T0 = 18.05−0.063 K) which predicted a 0.63°C decrease in T0 per 10 dd increase in K. The present paper is the first report, in spiders, of a linear relationship between T0 and K at interspecific level. The typical development time (VDT) and the extent of its deceleration by low temperature (DD) varied between species. DD increased with increasing VDT, but the relative effect of low temperature on development time (DDVDT ratio) varied independently of VDT, reflecting thermal adaptations consistent with the life history of the species. There is evidence that the DDVDT ratio for eggs of spiders is smaller than that of insects.

The biggest challenge for ecosystem management in China is how to control ecological degradation and maximize generation of ecosystem services with ecological conservation and restoration. The Task Force focused on four issues when analyzing the domestic and international case studies, namely, how to (a) balance the inter-linkages among various ecosystem services so as not to emphasize one ecosystem service while neglecting others, considering that people focus on different ecosystem services in different areas and development stages; (b) better coordinate the participation of different stakeholders in ecosystem management; (c) effectively leverage and enhance scientific support; and (d) draw on the experiences and best practices identified in the case studies to inform more effective models, policies, and guidelines.

The rapid industrial development and urbanization processes that occurred in China over the past 30 years has increased dramatically the consumption of natural resources and raw materials, thus exacerbating the human pressure on environmental ecosystems. In result, large scale environmental pollution of soil, natural waters and urban air were recorded. The development of effective industrial planning to support regional sustainable economy development has become an issue of serious concern for local authorities which need to select safe sites for new industrial settlements (i.e. industrial plants) according to assessment approaches considering cumulative impacts, synergistic pollution effects and risks of accidental releases. In order to support decision makers in the development of efficient and effective regional land-use plans encompassing the identification of suitable areas for new industrial settlements and areas in need of intervention measures, this study provides a spatial regional risk assessment methodology which integrates relative risk assessment (RRA) and socio-economic assessment (SEA) and makes use of spatial analysis (GIS) methodologies and multicriteria decision analysis (MCDA) techniques. The proposed methodology was applied to the Chinese region of Hulunbeier which is located in eastern Inner Mongolia Autonomous Region, adjacent to the Republic of Mongolia. The application results demonstrated the effectiveness of the proposed methodology in the identification of the most hazardous and risky industrial settlements, the most vulnerable regional receptors and the regional districts which resulted to be the most relevant for intervention measures since they are characterized by high regional risk and excellent socio-economic development conditions. Keywords: Spatial regional risk assessment, Industrial pollution, Regional land planning

Inappropriate surface expression of voltage-gated Ca(2+)channels (CaV) in pancreatic ß-cells may contribute to the development of type 2 diabetes. First, failure to increase intracellular Ca(2+) concentrations at the sites of exocytosis impedes insulin release. Furthermore, excessive Ca(2+) influx may trigger cytotoxic effects. The regulation of surface expression of CaV channels in the pancreatic β-cells remains unknown. Here, we used real-time 3D confocal and TIRFM imaging, immunocytochemistry, cellular fractionation, immunoprecipitation and electrophysiology to study trafficking of L-type CaV1.2 channels upon β-cell stimulation. We found decreased surface expression of CaV1.2 and a corresponding reduction in L-type whole-cell Ca(2+) currents in insulin-secreting INS-1 832/13 cells upon protracted (15-30 min) stimulation. This internalization occurs by clathrin-dependent endocytosis and could be prevented by microtubule or dynamin inhibitors. eIF3e (Eukaryotic translation initiation factor 3 subunit E) is part of the protein translation initiation complex, but its effect on translation are modest and effects in ion channel trafficking have been suggested. The factor interacted with CaV1.2 and regulated CaV1.2 traffic bidirectionally. eIF3e silencing impaired CaV1.2 internalization, which resulted in an increased intracellular Ca(2+) load upon stimulation. These findings provide a mechanism for regulation of L-type CaV channel surface expression with consequences for β-cell calcium homeostasis, which will affect pancreatic β-cell function and insulin production.

Background: The aim of our study was to investigate whether pre-existing type 2 diabetes and insulin therapy have an impact on the prognosis of breast cancer patients. Methods: We performed a retrospective analysis of 462 type 2 diabetic breast cancer patients and 1644 non-diabetic breast cancer patients treated in our institute from January 2005 to August 2010. Patients were divided by diabetes status and insulin use. The clinicopathological characteristics and clinical outcomes of patients within 5 years following breast cancer diagnosed were analysed. Results: Diabetic patients tended to have higher body mass index and higher histological grade tumours. Five-year disease-free survival and overall survival were reduced in diabetic patients (P < 0.001), and diabetes was an independent predictor for an increased risk of breast cancer relapse and death within 5 years (P < 0.001). Insulin treatment was associated with reduced 5-year disease-free survival and overall survival (P < 0.05); the risk of 5-year relapse and breast cancer mortality in the insulin group increased compared to that of non-insulin group after adjusting for age, tumour size, histological grade, oestrogen receptor, progesterone receptor, chemotherapy and hormone therapy (P < 0.05). After adjusting for age and other factors, the risk of breast cancer relapse was also increased in the insulin subgroup, while the risk of breast cancer mortality did not increase statistically. Conclusions: Type 2 diabetes and insulin treatment might be independently associated with poorer prognosis of breast cancer. However, caution is needed when interpreting our results, and further investigations are needed. Copyright © 2016 John Wiley & Sons, Ltd.

A simple yet rigorous method has been developed to enable the loss tangent of dielectrics, having a known relative permittivity, to be accurately measured using a waveguide resonant cavity. The novel method eliminates the need for any physical measurement, either on the cavity or dielectric sample under test. The only electrical parameters that need to be measured are resonant frequencies and Q-factors of a reference cavity and those of the same cavity loaded with the dielectric sample. One of the advantages of the new technique is that dielectrics, of arbitrary shape, can be characterized at very high microwave frequencies. The new method has been verified through measurement over X-band.

We utilized a modified double-emulsion method with poly(lactic-co-glycolic acid) as the carrier to prepare recombinant human epidermal growth factor (rhEGF) nanoparticles. The morphology of the nanoparticles was detected by a transmission electron microscope. The particle size distribution was measured by a laser analyzer with a zeta potential meter. Enzyme-linked immunosorbent assays were performed to determine the rhEGF encapsulation efficiency and release model, and the proliferation of the mouse fibroblasts was analyzed by the MTT method. Diabetic rats with full-thickness wounds were divided into four groups according to different treatments: rhEGF nanoparticles, rhEGF stock solution, empty nanoparticles, and phosphate-buffered saline. Photographs were taken after the treatments to calculate the wound healing rates, and the granulation tissue of the wounds was sampled for pathologic slides. Proliferating cell nuclear antigen was assayed by immunohistochemistry. Our results showed that the rhEGF nanoparticles were around 193.5 nm (diameter), and the particle size distribution was uniform and dispersible. The encapsulation efficiency was 85.6% and rhEGF release lasted 24 hours. Compared with other groups, the rhEGF nanoparticles promoted the highest level of fibroblast proliferation, and this group showed the fastest healing rate. The number of proliferating cell nuclear antigen positive cells in the rhEGF nanoparticles group was higher than the other groups. We concluded that controlled release of rhEGF encapsulated in the nanoparticles enhanced rhEGF effects to stimulate cell proliferation and shorten the wound healing time.

The W-band remains the most suitable band for high resolution near-real-time imaging in security, airborne and defence applications. The benefits of higher frequencies are counteracted by reduced penetration and also by very high component costs, due to the need for precision machining of metal, assembly of semiconductors, supporting circuit boards and manual tuning to achieve the required performance. Novel multi-layer circuit technologies are now achieving excellent performance at 94GHz, allowing the integration of high frequency components and supporting DC circuitry, along with automated assembly which delivers substantially lower manufacturing costs. Liquid Crystal Polymer (LCP) has excellent electrical properties: a dielectric constant of 3.16±0.05 and a dielectric loss tangent of 0.0049 to 100GHz, as well as good repeatability. These properties result in the simulated insertion loss of 0.04dB/mm in stripline waveguides. This paper describes the design and measurement of direct detection receiver modules based on LCP substrates for imaging applications in the W-band. The measured substrate loss at 94GHz is believed to be the lowest reported in the literature, and contributes to achieving receiver sensitivities of