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Abstract Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. However, whether cGAMP plays any roles in regulating metabolic homeostasis remains unknown. Here we show that exogenous cGAMP ameliorates obesity-associated metabolic dysregulation and uniquely alters proinflammatory responses. In obese mice, treatment with cGAMP significantly decreases diet-induced proinflammatory responses in liver and adipose tissues and ameliorates metabolic dysregulation. Strikingly, cGAMP exerts cell-type-specific anti-inflammatory effects on macrophages, hepatocytes, and adipocytes, which is distinct from the effect of STING activation by DMXAA on enhancing proinflammatory responses. While enhancing insulin-stimulated Akt phosphorylation in hepatocytes and adipocytes, cGAMP weakens the effects of glucagon on stimulating hepatocyte gluconeogenic enzyme expression and glucose output and blunts palmitate-induced hepatocyte fat deposition in an Akt-dependent manner. Taken together, these results suggest an essential role for cGAMP in linking innate immunity and metabolic homeostasis, indicating potential applications of cGAMP in treating obesity-associated inflammatory and metabolic diseases.

Abstract In this paper, we establish new Poisson type inequalities with respect to a cone. As applications, the integral representations of harmonic functions are also obtained.

Abstract Background Using paradigms from game theory, researchers have reported abnormal decision-making in social context in patients with schizophrenia. However, less is known about the underpinnings of the impairment. This study aimed to test whether theory of mind (ToM) deficits and/or neurocognitive dysfunctions mediate impaired social decision-making in patients with schizophrenia. Methods We compared thirty-five patients with schizophrenia to thirty-eight matched healthy controls with regard to social decision-making using the mini Ultimatum Game (mini UG), a paradigm from game theory. Additionally, we assessed ToM using the Theory of Mind Picture Stories Task, a mental state attribution task, and assessed neurocognition using the Brief Assessment of Cognition in Schizophrenia. Mediation analyses were performed on the data. Results In contrast to the behavioral pattern of healthy controls in the mini UG, the patients with schizophrenia significantly accepted more disadvantageous offers and rejected more advantageous offers, and showed reduced sensitivity to the fairness-related context changes in the mini UG. Impaired ToM and neurocognition were also found in the patients. Mediation analyses indicated that ToM but not neurocognition partially mediated the group differences on the disadvantageous and advantageous offers in the mini UG. Conclusions Patients with schizophrenia exhibited impaired social decision-making. This impairment can be partly explained by their ToM deficits rather than neurocognitive deficits. However, the exact nature of the ToM deficits that mediate impaired social decision-making needs to be identified in future.

Each year in Taiwan, hantaviruses cause 0-4 human Cases of hemorrgagic fever with renal syndrome (HFRS) (1). Rattus norvegicus rats are a notable local reservoir host for Seoul virus (SEOV), [...]

Abstract Background Breast cancer is recognised as a major public health problem in developing countries; however, there is very limited evidence about its epidemiology in the Central African Republic. The aim of this study was to investigate the epidemiological and histopathological characteristics of breast cancer in Bangui. Methods This is a retrospective study based on the data collected from pathological anatomy records from 2003 to 2015 in Bangui. A questionnaire was designed to collect information and data was analysed using descriptive and inferential statistical methods. Results The mean age was 45.83 (SD = 13.5) years. The age group of 45–54 years represented the majority of the study population (29.3%). Over 69.5% of the women were housewives with a moderate economic status (56.9%). Less than 14% of the study population had a level of academic degree and 85.6% lived in cities. The breast cancer prevalence was 15.27%. The age-standardized incidence and death by world population (ASW) were 11.19/100,000 and 9.97/100,000 respectively. 50–54 years were most affected. Left breast cancer is mainly common and the time between first symptoms and consultation is more than 48 months. Most (69%) of the samples analysed were lumpectomy. The most common morphology of breast cancer was invasive ductal carcinoma (64.9%). Scarff Bloom Richardson III was the main grade in both common pathological types, but their proportion showed no significant increase along with time (χ2 = 7.06, p = 0.54). Invasion of regional lymph node differed significantly among the pathological type of breast cancer (χ2 = 24.6, p = 0.02). Surgery and chemotherapy were appropriate treatment yet 84.5% of the cases died. Conclusion The findings of this study showed that breast cancer is common and mostly affected women. Epidemiological trends are more or less common to those of developing countries with a predominance of invasive ductal carcinoma. However, most of the women studied live in an urban area and developed the disease in advanced stage. The establishment of an appropriate framework will effectively contribute to promoting the early detection and reducing the incidence of this disease in the population.

A simple and rapid method using liquid chromatography–mass spectrometry (LC-MS) for the determination of metaxalone in human plasma has been developed and validated. Letrozole was used as the internal standard (IS). The plasma samples were simply treated with acetonitrile which allowed the precipitation of plasma proteins. The chromatographic separation was achieved on a Sapphire C18 (2.1 mm × 150 mm, 5 µm, Newark, USA) column using the mobile phase (5 mM ammonium acetate containing 0.01% formic acid: acetonitrile (45:55, v/v)) at a flow rate of 0.3 ml/min. The selected ion monitoring (SIM) in the positive mode was used for the determination of [M + H]+ m/z 222.1 and 286.1 for metaxalone and letrozole, respectively. The standard curve obtained was linear (r2 ≥ 0.99) over the concentration range of 30.24−5040 ng/ml. Meanwhile, no interfering peaks or matrix effect was observed. The method established was simple and successfully applied to a pharmacokinetic study of metaxalone in healthy Chinese volunteers after a single oral dose administration of 800 mg metaxalone. The main pharmacokinetic parameters of metaxalone were as follow: Cmax, (1664 ± 1208) ng/ml and (2063 ± 907) ng/ml; AUC0−36, (13925 ± 6590) ng/ml h and (18620 ± 5717) ng/ml h; t1/2, (13.6 ± 7.7) h and (20.3 ± 7.7) h for the reference and test tablets, respectively. These pharmacokinetic parameters of metaxalone in healthy Chinese volunteers were reported for the first time.

The heterogeneity of glioblastomas, the most common primary malignant brain tumor, remains a significant challenge for the treatment of these devastating tumors. Therefore, novel combination treatments are warranted. Here, we showed that the combined inhibition of TRAP1 by gamitrinib and histone deacetylases (HDAC1/HDAC2) through romidepsin or panobinostat caused synergistic growth reduction of established and patient-derived xenograft (PDX) glioblastoma cells. This was accompanied by enhanced cell death with features of apoptosis and activation of caspases. The combination treatment modulated the levels of pro- and anti-apoptotic Bcl-2 family members, including BIM and Noxa, Mcl-1, Bcl-2 and Bcl-xL. Silencing of Noxa, BAK and BAX attenuated the effects of the combination treatment. At the metabolic level, the combination treatment led to an enhanced reduction of oxygen consumption rate and elicited an unfolded stress response. Finally, we tested whether the combination treatment of gamitrinib and panobinostat exerted therapeutic efficacy in PDX models of glioblastoma (GBM) in mice. While single treatments led to mild to moderate reduction in tumor growth, the combination treatment suppressed tumor growth significantly stronger than single treatments without induction of toxicity. Taken together, we have provided evidence that simultaneous targeting of TRAP1 and HDAC1/2 is efficacious to reduce tumor growth in model systems of glioblastoma.

In this paper, we propose a novel noniterative algorithm to simultaneously estimate optimal rigid transformations for serial section images, which is a key component in performing volume reconstructions of serial sections of biological tissue. To avoid the error accumulation and propagation caused by current algorithms, we add an extra condition: that the positions of the first and last section images should remain unchanged. This constrained simultaneous registration problem has not previously been solved. Our solution is noniterative; thus, it can simultaneously compute rigid transformations for a large number of serial section images in a short time. We demonstrate that our algorithm obtains optimal solutions under ideal conditions and shows great robustness under nonideal circumstances. Further, we experimentally show that our algorithm outperforms state-of-the-art methods in terms of speed and accuracy.

It remains a mystery as to how neurons are connected and thereby enable use to think, and volume reconstruction from series of microscopy sections of brains is a vital technique in determining this connectivity. Image registration is a key component; the aim of image registration is to estimate the deformation field between two images. Current methods choose to directly regress the deformation field; however, this task is very challenging. It is common to trade off computational complexity with precision when designing complex models for deformation field estimation. This approach is very inefficient, leading to a long inference time. In this paper, we suggest that complex models are not necessary and solve this dilemma by proposing a dual-network architecture. We divide the deformation field prediction problem into two relatively simple subproblems and solve each of them on one branch of the proposed dual network. The two subproblems have completely opposite properties, and we fully utilize these properties to simplify the design of the dual network. These simple architectures enable high-speed image registration. The two branches are able to work together and make up for each other’s drawbacks, and no loss of accuracy occurs even when simple architectures are involved. Furthermore, we introduce a series of loss functions to enable the joint training of the two networks in an unsupervised manner without introducing costly manual annotations. The experimental results reveal that our method outperforms state-of-the-art methods in fly brain electron microscopy image registration tasks, and further ablation studies enable us to obtain a comprehensive understanding of each component of our network.

Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family of proteins. Constitutive Speg deficient (Speg−/−) mice develop a dilated cardiomyopathy, and the majority of these mice die in utero or shortly after birth. In the present study we assessed the importance of Speg in adult mice. Speg−/− mice that survived to adulthood, or adult striated muscle-specific Speg knockout mice (Speg-KO), demonstrated cardiac dysfunction and evidence of increased left ventricular (LV) internal diameter and heart to body weight ratio. To determine whether heterozygosity of Speg interferes with the response of the heart to pathophysiologic stress, Speg+/− mice were exposed to pressure overload induced by transverse aortic constriction (TAC). At baseline, Speg+/+ and Speg+/− hearts showed no difference in cardiac function. However, 4 weeks after TAC, Speg+/− mice had a marked reduction in LV function. This defect was associated with an increase in LV internal diameter and enhanced heart weight to body weight ratio, compared with Speg+/+ mice after TAC. The response of Speg+/− mice to pressure overload also included increased fibrotic deposition in the myocardium, disruption of transverse tubules, and attenuation in cell contractility, compared with Speg+/+ mice. Taken together, these data demonstrate that Speg is necessary for normal cardiac function and is involved in the complex adaptation of the heart in response to TAC. Haploinsufficiency of Speg results in decompensated heart failure when exposed to pressure overload.

Objective. To evaluate the performance of probe-based confocal laser endomicroscopy (pCLE) in diagnosis of gastric lesions. Methods. An outpatient department- (OPD-) based retrospective study was conducted for patients with suspected upper gastrointestinal (GI) tract lesions who underwent pCLE between 2014 and 2016 at a tertiary hospital in China. Final diagnosis was based on the histopathological reports. CLE reports were compared to histopathological reports to evaluate the diagnostic ability, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy. Results. 322 of 380 patients were diagnosed with gastric lesions via pCLE, including inflammation and benign ulcers (n=110), atrophy and intestinal metaplasia (n=152), intraepithelial neoplasia (n=27), adenocarcinoma (n=27), and lymphoma (n=6). In total, the diagnostic ability of CLE in evaluation of gastric lesions showed sensitivity 72.4% (95% confidence interval (CI): 67.1–77.2%); specificity 93.1% (95% CI: 5.6–8.4%); PPV 72.4% (95% CI: 67.1–77.2%); NPV 93.1% (95% CI: 5.6–8.4%); and accuracy 88.9% (95% CI: 87.3–90.4%), respectively. We further observed the capability of pCLE in diagnosing six gastric lymphoma showing those affected mucosa densely infiltrated with identical and round-shaped abnormal cells. Immunohistochemistry analysis confirmed one patient with diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL) and five with mucosa-associated lymphoid tissue (MALT) lymphoma. Conclusion. pCLE is an accurate tool for the detection of gastric lesions and shows optimal values of sensitivity and negative predictivity. Moreover, combining pCLE with white light endoscopy (WLE) may be a promising adjunct to conventional biopsy sampling in evaluating GI tract with suspected lymphoma.

The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans. The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.

Based on the lattice Boltzmann method (LBM), the lattice Boltzmann flux solver (LBFS), which combines the advantages of conventional Navier–Stokes solvers and lattice Boltzmann solvers, was proposed recently. Specifically, LBFS applies the finite volume method to solve the macroscopic governing equations which provide solutions for macroscopic flow variables at cell centers. In the meantime, numerical fluxes at each cell interface are evaluated by local reconstruction of LBM solution. In other words, in LBFS, LBM is only locally applied at the cell interface for one streaming step. This is quite different from the conventional LBM, which is globally applied in the whole flow domain. This paper shows three different versions of LBFS respectively for isothermal, thermal and compressible flows and their relationships with the standard LBM. In particular, the performance of isothermal LBFS in terms of accuracy, efficiency and stability is investigated by comparing it with the standard LBM. The thermal LBFS is simplified by using the D2Q4 lattice velocity model and its performance is examined by its application to simulate natural convection with high Rayleigh numbers. It is demonstrated that the compressible LBFS can be effectively used to simulate both inviscid and viscous flows by incorporating non-equilibrium effects into the process for inviscid flux reconstruction. Several numerical examples, including lid-driven cavity flow, natural convection in a square cavity at Rayleigh numbers of 107 and 108 and transonic flow around a staggered-biplane configuration, are tested on structured or unstructured grids to examine the performance of three LBFS versions. Good agreements have been achieved with the published data, which validates the capability of LBFS in simulating a variety of flow problems.

Significant advancements have been made in cyber aggression literature, with many studies revealing the consequences associated with adolescents’ involvement in these behaviors. Few studies have focused on cyber aggression involvement in China, India, and Japan. The present study examined differences in cyber aggression perpetration and victimization among 1637 adolescents living in China, India, and Japan, while controlling for face-to-face bullying involvement, individualism, and collectivism. Another aim of the present study was to examine country of origin and cyber aggression involvement (i.e., the uninvolved, cyberaggressor-cybervictims, cyberaggressors, and cybervictims) differences in peer attachment. Findings revealed that adolescents from India had the highest levels of cyber aggression involvement when compared to adolescents from China or Japan. Chinese adolescents engaged in more cyber aggression perpetration and were victimized more by cyber aggression when compared to Japanese adolescents. No country of origin differences were found for peer attachment. However, uninvolved adolescents reported higher levels of peer attachment when compared to the other groups. Cyberaggressor-cybervictims had the lowest levels of peer attachment, followed by cybervictims and cyberaggressors. These results suggest that there should be concern about cyber aggression involvement among adolescents in these countries, especially in India, where cyber aggression research has been slow to develop.

A coupled immersed boundary–lattice Boltzmann method (IB–LBM) is introduced to solve biomimetic problems. Compared to the conventional IB–LBM, the strict satisfaction of no-slip boundary condition is implemented in the current method. Consequently, the phenomenon of flow penetration that is frequently observed in the conventional IB–LBM is fully prevented, and subsequently the force on the boundary can be calculated more accurately. This feature is of importance for the simulation of biomimetic problems. Moreover, by applying the relationship between the velocity correction and forcing term, the boundary force can be calculated easily. Several biomimetic problems are then simulated. Based on the good agreement between the current results and those in the literature, it may be concluded that the present IB–LBM has the capability to handle various biomimetic problems.

RNA-induced silencing complex (RISC) is composed of miRNAs and AGO proteins. AGOs use miRNAs as guides to slice target mRNAs to produce truncated 5' and 3' RNA fragments. The 5' cleaved RNA fragments are marked with uridylation for degradation. Here, we identified novel cofactors of Arabidopsis AGOs, named RICE1 and RICE2. RICE proteins specifically degraded single-strand (ss) RNAs in vitro; but neither miRNAs nor miRNA*s in vivo. RICE1 exhibited a DnaQ-like exonuclease fold and formed a homohexamer with the active sites located at the interfaces between RICE1 subunits. Notably, ectopic expression of catalytically-inactive RICE1 not only significantly reduced miRNA levels; but also increased 5' cleavage RISC fragments with extended uridine tails. We conclude that RICEs act to degrade uridylated 5’ products of AGO cleavage to maintain functional RISC. Our study also suggests a possible link between decay of cleaved target mRNAs and miRNA stability in RISC.

Breast cancer is recognized as a major public health problem in developing countries; however, there is very little evidence of behavioral factors associated with breast cancer risk. This study was conducted to identify lifestyles as risk factors for breast cancer among Central African women. A case-control study was conducted with 174 cases confirmed histologically by the pathology unit of the National Laboratory and 348 age-matched controls. Data collection tools included a questionnaire with interviews and medical records of patients. Data were analyzed using SPSS software version 20. Odd ratio (OR) and 95% confidence intervals (95% CI) were obtained by unconditional logistic regression. In total, 522 women were studied with a mean age of 45.8 (SD = 13.4) years. By unconditional logistic regression model, women with breast cancer were more likely to have attained illiterate and elementary education level [11.23 (95% CI, 4.65-27.14) and 2.40 (95% CI, 1.15-4.99)], married [2.09 (95% CI, 1.18-3.71)], positive family history [2.31 (95% CI, 1.36-3.91)], radiation exposure [8.21 (95% CI, 5.04-13.38)], consumption charcuterie [10.82 (95% CI, 2.39-48.90)], fresh fish consumption [4.26 (95% CI, 1.56-11.65)], groundnut consumption [6.46 (95% CI, 2.57-16.27)], soybean consumption [16.74 (95% CI, 8.03-39.84)], alcohol [2.53 (95% CI, 1.39-4.60)], habit of keeping money in bras[3.57 (95% CI, 2.24-5.69)], overweight [5.36 (95% CI, 4.46-24.57)] and obesity [3.11(95% CI, 2.39-20.42)]. However, decreased risk of breast cancer was associated with being employed [0.32 (95% CI, 0.19-0.56)], urban residence [0.16 (95% CI, 0.07-0.37)], groundnut oil consumption [0.05 (95% CI, 0.02-0.14)], wine consumption [0.16 (95% CI, 0.09-0.26)], non habit of keeping cell phone in bras [0.56 (95% CI, 0.35-0.89)] and physical activity [0.71(95% CI, 0.14-0.84)]. The study showed that little or no education, marriage, positive family history of cancer, radiation exposure, charcuterie, fresh fish, groundnut, soybean, alcohol, habit of keeping money in bras, overweight and obesity were associated with breast cancer risk among Central African women living in Bangui. Women living in Bangui should be more cautious on the behavioral risk associated with breast cancer.

A novel scheme using fuzzy logic based interacting multiple model (IMM) unscented Kalman filter (UKF) is employed in which the Fuzzy Logic Adaptive System (FLAS) is utilized to address uncertainty of measurement noise, especially for the outlier types of multipath errors for the Global Positioning System (GPS) navigation processing. Multipath is known to be one of the dominant error sources, and multipath mitigation is crucial for improvement of the positioning accuracy. It is not an easy task to establish precise statistical characteristics of measurement noise in practical engineering applications. Based on the filter structural adaptation, the IMM nonlinear filtering provides an alternative for designing the adaptive filter in the GPS navigation processing for time varying satellite signal quality. The uncertainty of the noise can be described by a set of switching models using the multiple model estimation. An UKF employs a set of sigma points by deterministic sampling, which avoids the error caused by linearization as in an extended Kalman filter (EKF). For enhancing further system flexibility, the fuzzy logic system is introduced. The use of IMM with FLAS enables tuning of appropriate values for the measurement noise covariance so as to obtain improved estimation accuracy. Performance assessment will be carried out to show the effectiveness of the proposed approach for positioning improvement in GPS navigation processing.

The aims of this study are to identify the most important predictors of total diagnosed and undiagnosed diabetes and estimate the mean change in the predicted probability among aged 45+ adults in China. We used baseline data collected from 2011 wave of the China Health and Retirement Longitudinal Study (CHARLS) (n = 9,513). First, we estimated the prevalence of diagnosed, measured, total diagnosed, and undiagnosed diabetes. Second, we used probit models to determine whether individual attributes, socioeconomic characteristics and behavioral health factors, including smoking, alcohol consumption, obesity, central obesity, are associated with total diagnosed and undiagnosed diabetes. We also consider other factors, including contact with medical system, hypertension and urban/rural settings. Third, we estimated average marginal effects of variables in probit models. Among Chinese people aged 45+, the prevalence of diagnosed, measured, total diagnosed and undiagnosed diabetes were 5.8% (95%CI, 5.3%-6.3%), 14.7% (95%CI, 14.0%-15.4%), 17.0% (95%CI, 16.3%-17.7%), 11.3% (95%CI, 10.6%-12.0%), respectively. The probability of total diagnosed diabetes is 3.3% (95% CI, 1.2%-5.3%) and 10.2% (95% CI, 7.0%-13.5%) higher for overweight and obesity than normal BMI, 5.0% (95% CI, 3.0%-7.1%) higher for central obesity than normal waist circumference, 5.4% (95% CI, 3.7%-7.0%) higher for hypertensive than normotensive and 1.8% (95% CI, 0.8%- 2.7%) higher in urban areas than in rural areas, respectively. The probability of undiagnosed diabetes is 2.7% (95% CI, 1.2%-4.2%) and 7.2% (95% CI, 4.7%-9.6%) higher for overweight and obesity than normal BMI, 2.6% (95% CI, 0.9%-4.4%) higher for central obesity than normal waist circumference and 2.6% (95% CI, 1.2%-4.0%) higher for hypertensive than normotensive, respectively, and -1.5% (95% CI, -2.5% to -0.5%) lower for individuals who were in contact with the medical system. Greater focus on prevention of diabetes is necessary for obesity, central obesity, hypertensive and in urban areas for middle-aged and older in China.

Objective: The present study aimed to determine whether postoperative fractionated radiotherapy, at a total dose of 35 Gy, affected expanded polytetrafluoroethylene (ePTFE) graft anastomotic stoma healing and neointima formation. Methods: The subrenal abdominal aortas of 20 mongrel dogs were replaced with an ePTFE graft. The dogs were randomly divided into either a radiotherapy or nonradiotherapy control group. Grafts were harvested at 4 or 8 weeks after surgery. Hematoxylin–eosin staining, and immunohistochemistry tests for proliferating cell nuclear antigen (PCNA) and CD34 were undertaken to analyze the anastomotic healing and neointima formation. Results: The patency rate of grafts was 100% in each group. No disunion, rupture, or aneurysm was observed in the anastomotic stoma. Eight weeks after surgery, the graft neointima and anastomotic vessel wall of the radiotherapy group were significantly thinner than those of the control group (p

This study aims to understand the level of contraceptive knowledge and attitudes towards contraception, and then to explore the association between the contraceptive behavior and unintended pregnancy in unmarried female university students in China. A cross-sectional study was conducted of university students in 49 universities across 7 cities in China from September 2007 to January 2008. We distributed 74,800 questionnaires, of which 69,842 were returned. In this paper, the data from 35,383 unmarried female university students were analyzed. The prevalence of sexual intercourse in unmarried female university students was 10.2%. The prevalence of unintended pregnancy in those sexually active female university students, was 31.8%. Among students with pregnancy, 53.5% experienced two or more pregnancies. 28.3% of the students with sexual intercourse reported that they always adopted contraceptive methods, and of those 82.9% chose to use male condoms. The majority (83.9%) of students with unintended pregnancy chose to terminate the latest pregnancy by surgical abortion or medical abortion. The contraceptive knowledge level of students who experienced unintended pregnancy was lower than those who did not. In China, about one third of unmarried female students with sexual intercourse experience unintended pregnancy. A variety of contraceptive methods are adopted, but the frequency of contraceptive use is low. Most of unmarried female students who experienced unintended pregnancy would choose to terminate the pregnancy with surgical or medical abortion. University students, especially the ones who have experienced unintended pregnancy, lack contraceptive and reproductive health knowledge.

In order to assess the optimal window-wall ratio and the proper glazing type in different air conditioning system operation modes of residential buildings for each orientation in three typical cities in hot summer and cold winter zone: Chongqing, Shanghai, and Wuhan simulation models were built and analyzed using Designer’s Simulation Toolkit (DeST). The study analyzed the variation of annual heating energy demand, annual cooling energy demand, and the annual total energy consumption in different conditions, including different orientations, patterns of utilization of air conditioning system, window-wall ratio, and types of windows. The results show that the total energy consumption increased when the window-wall ratio is also increased. It appears more obvious when the window orientation is east or west. Furthermore, in terms of energy efficiency, low-emissivity (Low-E) glass performs better than hollow glass. From this study, it can be concluded that the influence and sensitivity of window-wall ratio on the total energy consumption are related to the operation mode of air conditioning system, the orientation of outside window, and the glazing types of window. The influence of the factors can be regarded as reference mode for the window-wall ratio when designing residential buildings.

An unconditionally stable thermal lattice Boltzmann method (USTLBM) is proposed in this paper for simulating incompressible thermal flows. In USTLBM, solutions to the macroscopic governing equations that are recovered from lattice Boltzmann equation (LBE) through Chapman–Enskog (C-E) expansion analysis are resolved in a predictor–corrector scheme and reconstructed within lattice Boltzmann framework. The development of USTLBM is inspired by the recently proposed simplified thermal lattice Boltzmann method (STLBM). Comparing with STLBM which can only achieve the first-order of accuracy in time, the present USTLBM ensures the second-order of accuracy both in space and in time. Meanwhile, all merits of STLBM are maintained by USTLBM. Specifically, USTLBM directly updates macroscopic variables rather than distribution functions, which greatly saves virtual memories and facilitates implementation of physical boundary conditions. Through von Neumann stability analysis, it can be theoretically proven that USTLBM is unconditionally stable. It is also shown in numerical tests that, comparing to STLBM, lower numerical error can be expected in USTLBM at the same mesh resolution. Four typical numerical examples are presented to demonstrate the robustness of USTLBM and its flexibility on non-uniform and body-fitted meshes.

Evaluating the values of patents is critical for both managers and investors. Patent maintenance time is an ideal proxy indicator for evaluating commercial patent value. This study investigated the survival rates of patents in the semiconductor industry by using a survival analysis and incorporated a predictive model for patent maintenance times. The technical characteristics of the patents, the assignee factors, and the statuses of the patents were used as the predictive factors for patent maintenance time. The results revealed a small entity size and the number of assignees are the risk factors that increase the likelihood of the maintenance time of a patent decreasing. The litigation status of a patent and the number of its international patent classifications, claims, forward citations, and assignments were determined to be the protection factors that raise the likelihood of its maintenance time extending. Additionally, substantial differences were noted between small entities and nonsmall entities and between being litigated and not in their effects on the survival rates of patents. This study examined the factors that affect the survival rates of patents and provides a reference for the managers and investors of intellectual property rights to use when assessing technical and commercial patent values.

Purpose. To investigate the prognostic significance of endocan, compared with procalcitonin (PCT), C-reactive protein (CRP),white blood cells (WBC), neutrophils (N), and clinical severity scores in patients with ARDS. Methods. A total of 42 patients with ARDS were initially enrolled, and there were 20 nonsurvivors and 22 survivors based on hospital mortality. Plasma levels of biomarkers were measured and the acute physiology and chronic health evaluation II (APACHE II) was calculated on day 1 after the patient met the defining criteria of ARDS. Results. Endocan levels significantly correlated with the APACHE II score in the ARDS group (r=0.676, P=0.000, n=42). Of 42 individuals with ARDS, 20 were dead, and endocan was significantly higher in nonsurvivors than in survivors (median (IQR) 5.01 (2.98–8.44) versus 3.01 (2.36–4.36) ng/mL, P=0.017). According to the results of the ROC-curve analysis and COX proportional hazards models, endocan can predict mortality of ARDS independently with a hazard ratio of 1.374 (95% CI, 1.150–1.641) and an area of receiver operator characteristic curve (AUROC) of 0.715 (P=0.017). Moreover, endocan can predict the multiple-organ dysfunction of ARDS. Conclusion. Endocan is a promising biomarker to predict the disease severity and mortality in patients with ARDS.

Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia.

Resistance to apoptosis is a paramount issue in the treatment of Glioblastoma (GBM). We show that targeting PARP by the small molecule inhibitors, Olaparib (AZD-2281) or PJ34, reduces proliferation and lowers the apoptotic threshold of GBM cells in vitro and in vivo.The sensitizing effects of PARP inhibition on TRAIL-mediated apoptosis and potential toxicity were analyzed using viability assays and flow cytometry in established GBM cell lines, low-passage neurospheres and astrocytes in vitro. Molecular analyses included western blots and gene silencing. In vivo, effects on tumor growth were examined in a murine subcutaneous xenograft model.The combination treatment of PARP inhibitors and TRAIL led to an increased cell death with activation of caspases and inhibition of formation of neurospheres when compared to single-agent treatment. Mechanistically, pharmacological PARP inhibition elicited a nuclear stress response with up-regulation of down-stream DNA-stress response proteins, e.g., CCAAT enhancer binding protein (C/EBP) homology protein (CHOP). Furthermore, Olaparib and PJ34 increased protein levels of DR5 in a concentration and time-dependent manner. In turn, siRNA-mediated suppression of DR5 mitigated the effects of TRAIL/PARP inhibitor-mediated apoptosis. In addition, suppression of PARP-1 levels enhanced TRAIL-mediated apoptosis in malignant glioma cells. Treatment of human astrocytes with the combination of TRAIL/PARP inhibitors did not cause toxicity. Finally, the combination treatment of TRAIL and PJ34 significantly reduced tumor growth in vivo when compared to treatment with each agent alone.PARP inhibition represents a promising avenue to overcome apoptotic resistance in GBM.

We propose a new method for family-based tests of association and linkage called transmission/disequilibrium tests incorporating unaffected offspring (TDTU). This new approach, constructed based on transmission/disequilibrium tests for quantitative traits (QTDT), provides a natural extension of the transmission/disequilibrium test (TDT) to utilize transmission information from heterozygous parents to their unaffected offspring as well as the affected offspring from ascertained nuclear families. TDTU can be used in various study designs and can accommodate all types of independent nuclear families with at least one affected offspring. When the study sample contains only case-parent trios, the TDTU is equivalent to TDT. Informative-transmission disequilibrium test (i-TDT) and generalized disequilibrium test(GDT) are another two methods that can use information of both unaffected offspring and affected offspring. In contract to i-TDT and GDT, the test statistic of TDTU is simpler and more explicit, and can be implemented more easily. Through computer simulations, we demonstrate that power of the TDTU is slightly higher compared to i-TDT and GDT. All the three methods are more powerful than method that uses affected offspring only, suggesting that unaffected siblings also provide information about linkage and association.

OBJECTIVE:The aim of this study was to confirm the association of RHOB and FAM167A-BLK gene polymorphisms with susceptibility to systemic sclerosis (SSc) in a Chinese Han population. METHODS:A total of 248 SSc patients and 251 healthy controls of Chinese Han ethnicity, which visited the department of dermatology of Peking Union Medical College Hospital, were included in the study. Six selected single nucleotide polymorphisms (SNPs) in the RHOB and FAM167A-BLK regions were selected as markers and were genotyped using a MassARRAY system, which is based on the matrix-assisted laser desorption/ionization time of flight mass spectrometry technique. RESULTS:Three SNPs in the coding regions of the RHOB and FAM167A-BLK genes displayed an association with SSc: (1) rs1062292T, which is a newly discovered SNP in the RHOB gene (P = 0.03, odds ratio [OR] = 1.62, 95% confidence interval (CI) = 1.05-2.50), (2) rs2736340T (P = 0.03, OR = 1.39, 95%CI = 1.03-1.85), and (3) rs13277113A (P = 0.04, OR = 1.34, 95%CI = 1.01-1.76), both in the FAM167A-BLK gene. Our results support previous findings that vaiants in the RHOB and FAM167A-BLK genes may be associated with susceptibility to SSc. However, the loci of the SNPs in RHOB region that displayed an association with SSc are quite different from the loci which were identified in studies of Caucasian populations. CONCLUSION:Our results confirm that RHOB and FAM167A-BLK polymorphisms exist in Chinese Han SSc patients. Therefore, variants of the RHOB and FAM167A-BLK genes are promising genetic markers for SSc.