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The importance of the time-cost-quality trade-off problem in construction projects has been widely recognized. Its goal is to minimize time and cost and maximize quality. In this paper, the bonus-penalty mechanism is introduced to improve the traditional time-cost model, and considering the nonlinear relationship between quality and time, a nonlinear time-cost quality model is established. Meanwhile, in order to better solve the time-cost-quality trade-off problem, a multi-objective immune wolf colony optimization algorithm has been proposed. The hybrid method combines the fast convergence of the wolf colony algorithm and the excellent diversity of the immune algorithm to improve the accuracy of the wolf colony search process. Finally, a railway construction project is taken as an example to prove the effectiveness of the method.

Open aorta and vena cava surgeries are usually associated with substantial blood loss which may result in postoperative acute kidney injury (AKI). The present study is designed to investigate the prevalence, outcome and risk factors of postoperative AKI associated with open aorta and vena cava surgeries, with a focus on the role of anemia in these conditions. A retrospective review of medical records of Peking Union Medical College Hospital was conducted. Patients who underwent open aorta and vena cava surgeries during January 1, 2010 and June 30, 2014 were included in this study. The primary analysis was between patients underwent open aorta and vena cava surgeryies, with or without postoperative AKI. Multivariable logistic regression models were used to determine risk factors of postoperative AKI. The study included 79 patients (63.3% male) with a mean age of 52.5±17.3 years (range, 17-81 years). Postoperative AKI occurred in 23/79 (29.1%) of the patients. Anemia was present in 11/79 (16%) at baseline, and increased to 45/79 (52%) postoperatively. After adjustment for various risk factors, postoperative anemia (OR, 5.202; 95% CI 1.403-19.285) was independently associated with postoperative AKI. AKI is a common complication in patients who undergo open aorta and vena cava surgeries, and postoperative anemia was the most relevant predictive factor of AKI. Strategies to minimize bleeding and anemia for all patients may be advisable. Further studies are needed to assess the impact of AKI on long term outcome and to examine preventive strategies to address potentially modifiable risk factors.

ObjectivesTo investigate the current status of participation and explore the characteristics of individuals with different levels of participation among stroke survivors in mainland China.DesignCross-sectional survey.SettingParticipants were recruited by convenience sampling from the neurology department of the tertiary hospitals and communities.SubjectsStroke survivors (N = 517; mean (±SD) age, 69.97±11.51 y; 36.8% female).InterventionNot applicable.Main outcome measuresParticipation was measured using the Chinese version of the Impact on Participation and Autonomy Questionnaire (IPA). Rating of disability was assessed using the Modified Rankin Scale (mRS). The Perceived Social Support Scale (PSSS), the Medical Coping Modes Questionnaire (MCMQ), and the Herth Hope Scale (HHS) were also employed to measure social support, coping strategy, and hope of stroke survivors. The latent profiles analysis (LPA) was conducted using the Mplus version 8.3.ResultsThe mean score of participation was 41.21±21.204. Participants were divided into three groups according to the participation using the LPA. The mean score on the sum of IPA for the high, medium, and low participation groups was 18.93±8.529, 42.50±8.302, and 69.44±9.516, respectively.ConclusionsStroke survivors have a low level of participation. Stroke survivors with low income, high mRS stage, bad health condition, and being dissatisfied for life tended to have low participation. Healthcare professionals should pay special attention to them and make targeted interventions based on their characteristics.

Glomerular filtration rate (GFR) is essential for renal function evaluation and classification of chronic kidney disease (CKD), while the reference method in children are cumbersome. In the Chinese children, there was no data about GFR measured through plasma or renal clearance of the exogenous markers, and therefore no validated GFR-estimating tools in this population.We measured GFR with double-sample plasma clearance of 99mTc-DTPA (mGFR) in 87 hospitalized children with renal injury. Using mGFR as the golden standard, we evaluate the efficiency of four different GFR estimation equations (the original and update Schwartz equation, the Filler equation, the CKiD equation) by statistical parameters of correlation, precision and accuracy.In our population, mGFR was 97.0± 31.9 mL/min/1.73m2. The updated Schwartz equation, the Filler equation and the CKiD equation, produced eGFR with strong correlation with mGFR, strong explanation capacity of variance in mGFR, small bias, satisfactory performance in Bland-Altman analysis, high intra-class correlation coefficients, high ratio of eGFR within mGFR±10% and eGFR within mGFR±30%, good agreement in CKD staging between eGFR and mGFR. The original Schwartz equation produced eGFR with large bias, poor precision and accuracy.The validated equations to estimate GFR in our patients are the updated Schwartz equation, which is simple for bedside use, the Filler equation and the CKiD equation, which provide more accurate eGFR. The original Schwartz equation should not be applied to estimate GFR in Chinese children with kidney injuries.

Gitelman syndrome (GS), an inherited autosomal recessive salt-losing renal tubulopathy caused by mutations in SLC12A3 gene, has been associated with normal prostaglandin E2 (PGE2) levels since 1995 by a study involving 11 clinically diagnosed patients. However, it is difficult to explain why cyclooxygenase-2 (COX2) inhibitors, which pharmacologically reduce PGE2 synthesis, are helpful to patients with GS, and few studies performed in the last 20 years have measured PGE2 levels. The relationships between the clinical manifestations and PGE2 levels were never thoroughly analyzed.This study involved 39 GS patients diagnosed by SLC12A3 gene sequencing. Plasma and 24-h urine samples as well as the clinical data were collected at admission. PGE2 and PGEM levels were detected in plasma and urine samples by enzyme immunoassays. The in vivo function of the sodium-chloride co-transporter (NCC) in GS patients was evaluated using a modified thiazide test. The association among PGE2 levels, clinical manifestations and the function of NCC in GS patients were analyzed.Significantly higher levels of urinary and plasma PGEM were observed in GS patients than in the healthy volunteers. Higher urinary PGEM levels indicated more severe clinical manifestations and NCC dysfunction estimated by the increase of Cl- clearance. A higher PGEM level was found in male GS patients, who showed earlier onset age and more severe hypokalemia, hypochloremia and metabolic alkalosis than female GS patients. No relationship between renin angiotensin aldosterone system activation and PGEM level was observed.Higher urinary PGEM levels indicated more severe clinical manifestations and NCC dysfunction in GS patients. COX2 inhibition might be a potential therapeutic target in GS patients with elevated PGEM levels.

Type D personality and medication nonadherence have been shown to be associated with poor health outcomes. Type D personality is associated with poor medication adherence in patients with coronary artery disease, myocardial infarction, and heart failure. However, the relationship between type D personality and medication adherence in patients with Type 2 Diabetes Mellitus (T2DM) remains unknown. This study aims to examine whether type D personality was associated with medication adherence in patients with T2DM.A follow-up study was conducted in general hospital of the People's Liberation Army in Beijing.412 T2DM patients (205 females), who were recruited by circular systematic random sampling, provided demographic and baseline data about medical information and completed measures of Type D personality. Then, 330 patients went on to complete a self-report measure of medication adherence at the sixth month after baseline data collection. Chi-square test, t tests, and hierarchical multiple regression analyses were conducted, as needed.Patients with type D personality were significantly more likely to have poor medication adherence (p

For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE's effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The changes of JNK, IRS1, and PDK1 were confirmed by western blot analysis. In conclusion, this study demonstrated the potential protective effects of MLE and MLEF against hyperglycemia induced by high-energy diet and toxic chemicals in rats for the first time. The most likely mechanism is the promotion of IRS1 phosphorylation, which leads to insulin sensitivity restoration.

As both major macronutrients and signal molecules, nitrogen metabolites, such as nitrate and nitrite, play an important role in plant growth and development. In this study, the callus growth of indica rice cv. 9311 was significantly enhanced by nitrite, whereas the soluble protein content remained unchanged. The deep RNA sequencing technology (RNA-seq) showed that the transcriptional profiles of cv. 9311 calli were significantly changed after adding nitrite to the nitrate-free medium, and these nitrite-responsive genes were involved in a wide range of plant processes, particularly in the secondary metabolite pathways. Interestingly, most of the genes involved in phenylpropanoid-related pathways were coordinately down-regulated by nitrite, such as four cinnamoyl-CoA reductase, and these in turn resulted in the decrease of lignin content of indica calli. Furthermore, several candidate genes related to cell growth or stress responses were identified, such as genes coding for expansins, SMALL AUXIN UP RNA (SAUR) and HSP20s, and these suggested that nitrite could probably serve as a transcriptome signal to enhance the indica calli growth by regulation of various downstream genes expression. This study contributes to a better understanding of the function of nitrite during the process of plant tissue culture and could aid in the application of this technology to improved indica genetic transformation efficiency.

Few attempts have been made to study the alleviating effects of signal molecules on zoysiagrass (Zoysiajaponica) under drought stress. Calcium chloride has been shown to ameliorate the adverse effects of drought stress on many plants. It is necessary to investigate how to enhance drought tolerance of zoysiagrass using calcium chloride. The study elucidated the effects of calcium chloride on zoysiagrass under drought conditions by investigating the following parameters: biomass, chlorophyll (Chl) content, net photosynthetic rate (Pn), chlorophyll fluorescence, antioxidant enzymes, proline content, and malondialdehyde (MDA) content. Experimental conditions consisted of an aqueous CaCl2 solution at 5, 10, and 20 mM sprayed on zoysiagrass leaves for 3 d, following by an inducement of drought conditions by withholding water for 16 d. Under drought conditions, all CaCl2 pretreatments were found to increase the above-ground fresh biomass, as well as below-ground fresh and dry biomass. The resulting Chl (a, b, a+b) contents of the 5 and 10 mM CaCl2 pretreatment groups were higher than those of the control. In the later stages of drought conditions, the chlorophyll fluorescence parameter Fv/Fm was higher in leaves treated with 10 mM CaCl2 than in the leaves of the other two treatment groups. Zoysiagrass pretreated with 10 mM CaCl2 possessed both the maximum observed Pn and antioxidant enzyme activities. Meanwhile, lower MDA and proline contents were recorded in the plants pretreated with 5 and 10 mM CaCl2 under drought conditions. As a whole, the drought tolerance of zoysiagrass was improved to some extent by the application of a moderate calcium concentration.

Gut microbiota has shown tight and coordinated connection with various functions of its host such as metabolism, immunity, energy utilization, and health maintenance. To gain insight into whether gut microbes affect the metabolism of fish, we employed fast-growing transgenic common carp (Cyprinus carpio L.) to study the connections between its large body feature and gut microbes. Metagenome-based fingerprinting and high-throughput sequencing on bacterial 16S rRNA genes indicated that fish gut was dominated by Proteobacteria, Fusobacteria, Bacteroidetes and Firmicutes, which displayed significant differences between transgenic fish and wild-type controls. Analyses to study the association of gut microbes with the fish metabolism discovered three major phyla having significant relationships with the host metabolic factors. Biochemical and histological analyses indicated transgenic fish had increased carbohydrate but decreased lipid metabolisms. Additionally, transgenic fish has a significantly lower Bacteroidetes:Firmicutes ratio than that of wild-type controls, which is similar to mammals between obese and lean individuals. These findings suggest that gut microbiotas are associated with the growth of fast growing transgenic fish, and the relative abundance of Firmicutes over Bacteroidetes could be one of the factors contributing to its fast growth. Since the large body size of transgenic fish displays a proportional body growth, which is unlike obesity in human, the results together with the findings from others also suggest that the link between obesity and gut microbiota is likely more complex than a simple Bacteroidetes:Firmicutes ratio change.

Microbial ferulic acid decarboxylase (FADase) catalyzes the transformation of ferulic acid to 4-hydroxy-3-methoxystyrene (4-vinylguaiacol) via non-oxidative decarboxylation. Here we report the crystal structures of the Enterobacter sp. Px6-4 FADase and the enzyme in complex with substrate analogues. Our analyses revealed that FADase possessed a half-opened bottom β-barrel with the catalytic pocket located between the middle of the core β-barrel and the helical bottom. Its structure shared a high degree of similarity with members of the phenolic acid decarboxylase (PAD) superfamily. Structural analysis revealed that FADase catalyzed reactions by an "open-closed" mechanism involving a pocket of 8 × 8 × 15 Å dimension on the surface of the enzyme. The active pocket could directly contact the solvent and allow the substrate to enter when induced by substrate analogues. Site-directed mutagenesis showed that the E134A mutation decreased the enzyme activity by more than 60%, and Y21A and Y27A mutations abolished the enzyme activity completely. The combined structural and mutagenesis results suggest that during decarboxylation of ferulic acid by FADase, Trp25 and Tyr27 are required for the entering and proper orientation of the substrate while Glu134 and Asn23 participate in proton transfer.

Human noroviruses are the major viral pathogens of epidemic acute gastroenteritis. These genetically diverse viruses comprise two major genogroups (GI and GII) and approximately 30 genotypes. Noroviruses recognize human histo-blood group antigens (HBGAs) in a diverse, strain-specific manner. Recently the crystal structures of the HBGA-binding interfaces of the GI Norwalk virus and the GII VA387 have been determined, which allows us to examine the genetic and structural relationships of the HBGA-binding interfaces of noroviruses with variable HBGA-binding patterns. Our hypothesis is that, if HBGAs are the viral receptors necessary for norovirus infection and spread, their binding interfaces should be under a selection pressure in the evolution of noroviruses.Structural comparison of the HBGA-binding interfaces of the two noroviruses has revealed shared features but significant differences in the location, sequence composition, and HBGA-binding modes. On the other hand, the primary sequences of the HBGA-binding interfaces are highly conserved among strains within each genogroup. The roles of critical residues within the binding sites have been verified by site-directed mutagenesis followed by functional analysis of strains with variable HBGA-binding patterns.Our data indicate that the human HBGAs are an important factor in norovirus evolution. Each of the two major genogroups represents an evolutionary lineage characterized by distinct genetic traits. Functional convergence of strains with the same HBGA targets subsequently resulted in acquisition of analogous HBGA binding interfaces in the two genogroups that share an overall structural similarity, despite their distinct locations and amino acid compositions. On the other hand, divergent evolution may have contributed to the observed overall differences between and within the two lineages. Thus, both divergent and convergent evolution, as well as the polymorphic human HBGAs, likely contribute to the diversity of noroviruses. The finding of genogroup-specific conservation of HBGA binding interfaces will facilitate the development of rational strategies to control and prevent norovirus-associated gastroenteritis.

This research examines the potential impact of the China-Pakistan Economic Corridor (CPEC) on the selection of trading routes between China, the Middle East, and Europe, with a specific focus on the transportation of a 40-foot standard container carrying general commodities. The study compares traditional routes with the new CPEC routes in terms of time, distance, and cost. The findings indicate that the new CPEC routes offer reduced travel time and distance when compared to the traditional routes across all provinces involved. The research reveals that the cost of road transportation along the new CPEC route is lower for Xinjiang province, but higher for the other provinces. By utilizing the new CPEC routes, the time required for goods to travel from China to the Middle East and Europe will be reduced by 10 to 20 days. Furthermore, the distance covered in this trade route will be shortened by 3,000 to 10,000 kilometres. Specifically, the province of Xinjiang in western China stands to benefit significantly from the new CPEC routes, saving approximately $2,000 on trade with the Middle East and Europe. These findings highlight the potential advantages and economic benefits that can be realized by leveraging the CPEC for trade between China, the Middle East, and Europe, particularly in terms of reduced transportation time and distance. [ABSTRACT FROM AUTHOR]

Protecting human, animal, and plant life or health from additives, toxins, and contaminants in agri-products and promoting green free trade are the main components of Sanitary and Phytosanitary (SPS) measures. However, the SPS measures are heterogeneous. This study examines the impact of SPS measures on the measured export quality and discusses their influence on the environmental protection of the exporting country. International heterogeneous measures do not necessarily promote quality upgrading but greatly increase transaction costs. By contrast, China's agri-product' quality upgrading and environmental pollution are in sharp contrast. Based on a heterogeneous firm-trade model, this study obtains three hypothetical propositions and conducts empirical regressions using the Tobit method. This study finds that heterogeneous SPS measures hinder quality upgrading because firms present a different quality upgrading trend, which in turn impedes the environmental protection of the exporting country; the quality upgrading made by diversified SOEs is higher than that of foreign firms and private firms; the quality upgrading made by general firms is higher than that of processing firms; and protective SPS measures have a stronger negative effect on quality upgrading and environmental protection.

Coping capacity is a key aspect of driver-vehicle interaction when drivers observe and make decisions, and is of great importance for drivers. However, different drivers have different self-cognition and assess their driving abilities differently, especially for novice drivers. Based on questionnaire data, this study has investigated the coping capacities of drivers in both static environments and dynamic environments. With the ANOVA analysis method and the structural equation model (SEM), this study has verified the effects of gender and driving factors (driving years, driving frequency, driving time) on drivers' coping capacities based on drivers' self-assessment scores and mutual assessment scores. Drivers' self-assessment scores show significant effects of all factors on drivers' coping capacities, and drivers' mutual assessment scores show significant effects of all factors, excluding driving time, on drivers' coping capacities. Also, it has been found that all drivers in the driving year group have cognitive biases. It seems that first-year drivers are always overconfident with their driving skills, while drivers with a driving experience of more than three years usually score driving skills of themselves and other drivers most conservatively. With increased exposure to various traffic conditions, experienced drivers are more aware of their limitations in dealing with complex traffic situations, while novice drivers do not know their lack of capability to properly respond to any unexpected situation they could encounter.

In order to explore the sustainable growth of Chinese agriculture, this paper assesses how the heterogeneous SPS measures affect China’s growth margins and quality upgrading in the agricultural sector. We estimate improved gravity-model that exploit the cross-country differences in SPS measures over the period from 2000 to 2014. Our findings show that the heterogeneous SPS measures restrict the intensive margin and extensive margin, but significantly promote the product quality-even with no significant effect on price index. Conditional on quality upgrading, the heterogeneous SPS measures decrease the extent of quality upgrading. On one hand, because of cross-country differences in SPS standards, standards from developed countries have less effective trade effect on China’s agri-products export quality upgrading; On the other hand, because of cross-firm differences in the ability to deal with SPS standards, the laggards in China have the higher probability to switch to lower entrance barrier countries. Therefore, it is possible for China to trap in the low-quality agricultural growth in the long term.

Observation ability, which is the basis of following decision-making and vehicle manipulation behaviour, is of great importance while driving. However, the subject self-cognition and objective assessment of driving ability are usually different, especially for the young novice drivers. In this paper, drivers' observation abilities for both static traffic signs and markings and dynamic surrounding vehicles were investigated based on questionnaire data. Effects of gender and driving characteristics (driving year, driving frequency, driving time) on drivers' observation abilities were verified by ANOVA analysis and structural equation model (SEM) from two aspects: drivers' self-assessment scores (self-assessment) and mutual assessment scores (evaluated by others). Significant difference could be found between all the factors and drivers' self-assessment scores, while only driving year had a significant effect on drivers' mutual assessment scores. Besides, cognitive bias was found between all the driving year groups. It seemed that drivers with driving experience less than one year were always overconfident with their driving abilities. And drivers with driving experience more than three years usually gave the most conservative assessment scores for themselves and others. With more exposures to various traffic conditions, experienced drivers are more aware of their limitations on observing surrounding information, while young novice drivers still not realized their limitations on observing traffic signs and other vehicles in a right way.

Background: Human noroviruses are the major viral pathogens of epidemic acute gastroenteritis. These genetically diverse viruses comprise two major genogroups (GI and GII) and approximately 30 genotypes. Noroviruses recognize human histoblood group antigens (HBGAs) in a diverse, strain-specific manner. Recently the crystal structures of the HBGA-binding interfaces of the GI Norwalk virus and the GII VA387 have been determined, which allows us to examine the genetic and structural relationships of the HBGA-binding interfaces of noroviruses with variable HBGA-binding patterns. Our hypothesis is that, if HBGAs are the viral receptors necessary for norovirus infection and spread, their binding interfaces should be under a selection pressure in the evolution of noroviruses. Methods and Findings: Structural comparison of the HBGA-binding interfaces of the two noroviruses has revealed shared features but significant differences in the location, sequence composition, and HBGA-binding modes. On the other hand, the primary sequences of the HBGA-binding interfaces are highly conserved among strains within each genogroup. The roles of critical residues within the binding sites have been verified by site-directed mutagenesis followed by functional analysis of strains with variable HBGA-binding patterns. Conclusions and Significance: Our data indicate that the human HBGAs are an important factor in norovirus evolution. Each of the two major genogroups represents an evolutionary lineage characterized by distinct genetic traits. Functional convergence of strains with the same HBGA targets subsequently resulted in acquisition of analogous HBGA binding interfaces in the two genogroups that share an overall structural similarity, despite their distinct locations and amino acid compositions. On the other hand, divergent evolution may have contributed to the observed overall differences between and within the two lineages. Thus, both divergent and convergent evolution, as well as the polymorphic human HBGAs, likely contribute to the diversity of noroviruses. The finding of genogroup-specific conservation of HBGA binding interfaces will facilitate the development of rational strategies to control and prevent norovirus-associated gastroenteritis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate potential associations between resting heart rate, blood pressure and the product of both, and the brachial-ankle pulse wave velocity (baPWV) as a maker of arterial stiffness. METHODS: The community-based "Asymptomatic Polyvascular Abnormalities in Community (APAC) Study" examined asymptomatic polyvascular abnormalities in a general Chinese population and included participants with an age of 40+ years without history of stroke and coronary heart disease. Arterial stiffness was defined as baPWV≥1400 cm/s. We measured and calculated the product of resting heart rate and systolic blood pressure (RHR-SBP) and the product of resting heart rate and mean arterial pressure (RHR-MAP). RESULTS: The study included 5153 participants with a mean age of 55.1 ± 11.8 years. Mean baPWV was 1586 ± 400 cm/s. Significant (P

BACKGROUND: While pathogenic mutations in BSCL2/Seipin cause congenital generalized lipodystrophy, the underlying mechanism is largely unknown. In this study, we investigated whether and how the pathogenic missense A212P mutation of Seipin (Seipin-A212P) inhibits adipogenesis. METHODOLOGY/RESULTS: We analyzed gene expression and lipid accumulation in stable 3T3-L1 cell lines expressing wild type (3T3-WT), non-lipodystrophic mutants N88S (3T3-N88S) and S90L (3T3-S90L), or lipodystrophic mutant A212P Seipin (3T3-A212P). When treated with adipogenic cocktail, 3T3-WT, 3T3-N88S and 3T3-S90L cells exhibited proper differentiation into mature adipocytes, indistinguishable from control 3T3-L1 cells. In contrast, adipogenesis was significantly impaired in 3T3-A212P cells. The defective adipogenesis in 3T3-A212P cells could be partially rescued by either PPARγ agonist or PPARγ overexpression. Gene expression profiling by microarray revealed that inhibition of adipogenesis was associated with activation of inflammatory genes including IL-6 and iNOS. We further demonstrated that Seipin-A212P expression at pre-differentiation stages significantly activated inflammatory responses by using an inducible expression system. The inflammation-associated inhibition of adipogenesis could be rescued by treatment with anti-inflammatory agents. CONCLUSIONS: These results suggest that pathogenic Seipin-A212P inhibits adipogenesis and the inhibition is associated with activation of inflammatory pathways at pre-differentiation stages. Use of anti-inflammatory drugs may be a potential strategy for the treatment of lipodystrophy.

Angiogenesis is a key step for tumour growth and metastasis, and anti-angiogenesis has been proposed as an important strategy for cancer therapy. Tryptanthrin is a weakly basic alkaloid isolated from the dried roots of medicinal indigo plants and has been shown to possess anti-tumour activities on various cancer cell types. This study aims to investigate the in vitro and in vivo anti-angiogenic activities of tryptanthrin and to unravel its underlying molecular action mechanisms. Our results show that tryptanthrin inhibited the in vitro proliferation, migration, and tube formation of the human microvascular endothelial cells (HMEC-1) in a concentration-dependent manner and significantly suppressed angiogenesis in Matrigel plugs in mice. Mechanistic studies indicated that tryptanthrin reduced the expression of several pro-angiogenic factors (Ang-1, PDGFB and MMP2). Tryptanthrin was also found to suppress the VEGFR2-mediated ERK1/2 signalling pathway in HMEC-1 cells and molecular docking simulation indicated that tryptanthrin could bound to the ATP-binding site of VEGFR2. Collectively, the present study demonstrated that tryptanthrin exhibited both in vitro and in vivo anti-angiogenic activities by targeting the VEGFR2-mediated ERK1/2 signalling pathway and might have therapeutic potential for the treatment of angiogenesis-related diseases.

BackgroundIschemia/reperfusion (I/R) injury is associated with systemic inflammatory response. Macrophage migration inhibitory factor (MIF) has been implicated in many inflammatory processes. Tanshinone IIA (TSA) is one of the active ingredients in danshen, which derived from the dried root or rhizome of Salviae miltiorrhizae Bge. Recent studies have demonstrated that TSA has protective effects against focal cerebral I/R injury. However, little is known about the underlying mechanisms. Here we put forward the hypothesis that TSA acts through inhibition of MIF expression during focal cerebral I/R injury in rats.Methodology/principal findingsRats were subjected to middle cerebral artery occlusion (MCAO) for 2 hours. This was followed by reperfusion. We measured neurological deficits, brain water content, and infarct volume, and found that neurological dysfunction, brain edema, and brain infarction were significantly attenuated by TSA 6 hours after reperfusion. We also measured myeloperoxidase (MPO) activity at 6 and 24 hours, and found that neutrophil infiltration was significantly higher in the vehicle+I/R group than in the TSA+I/R group. ELISA demonstrated that TSA could inhibit MIF expression and the release of TNF-α and IL-6 induced by I/R injury. Western blot analysis and immunofluorescence staining showed that MIF expression was significantly lower in the TSA+I/R group than in the vehicle+I/R group. MIF was found almost all located in neurons and hardly any located in astrocytes in the cerebral cortex. Western blot analysis and EMSA demonstrated that NF-κB expression and activity were significantly increased in the vehicle+I/R group. However, these changes were attenuated by TSA.Conclusion/significanceOur results suggest that TSA helps alleviate the proinflammatory responses associated with I/R-induced injury and that this neuroprotective effect may occur through down-regulation of MIF expression in neurons.

BACKGROUND: Result publication is the key step to improve the transparency of clinical trials. OBJECTIVE: To investigate the result publication rate of Chinese trials registered in World Health Organization (WHO) primary registries. METHOD: We searched 11 WHO primary registries for Chinese trials records. The progress of each trial was analyzed. We searched for the full texts of result publications cited in the registration records. For completed trials without citations, we searched PubMed, Embase, Chinese Biomedical Literature Database (Chinese), China Knowledge Resource Integrated Database, and Chinese Science and Technology Periodicals Database for result publications. The search was conducted on July 14, 2009. We also called the investigators of completed trials to ask about results publication. RESULTS: We identified 1294 Chinese trials records (428 in ChiCTR,743 in clinicaltrials.gov,55 in ISRCTN, 21 in ACTRN). A total of 443 trials had been completed. The publication rate of the Chinese trials in WHO primary registries is 35.2% (156/443).The publication rate of Chinese trials in clinicaltrials.gov, ChiCTR, ISRCTN, and ACRTN was 36.5% (53/145), 36.3% (89/245), 26.0% (9/44), and 55.6% (5/9), respectively. The publication rate of trials sponsored by industry (23.8%) was lower than that of sponsored by central and local government (31.7%), hospital (35.1%), and universities (40.7%). The publication rate for randomized trials was higher than that of cohort study and case-control study (33.2% versus 16.7%, 22.2%). The publication rate for interventional studies and observational studies was similar (33.4% versus 33.3%). CONCLUSION: The publication rate of the registered Chinese trials was low, with no significant difference between ChiCTR and clinicaltrials.gov. An effective mechanism is needed to promote publication of results for registered trials in China.