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Hong Kong imposed a partial restriction on application of organotin-based antifouling paints in 1992. Since September 2008, the International Maritime Organization prohibited the use of such antifouling systems on all sea-going vessels globally. Therefore, it is anticipated a gradual reduction of organotin contamination in Hong Kong's marine waters. Using the rock shell Reishia clavigera as a biomonitor, we evaluated the organotin contamination along Hong Kong's coastal waters over the past two decades (1990-2015). In 2010 and 2015, adult R. clavigera were examined for imposex status and analysed for tissue concentrations of six organotins. We consistently found 100% imposex incidence in female R. clavigera across all sites. Tissue triphenyltin (TPT) concentrations were high in most samples. A probabilistic risk assessment showed that there were over 69% of chance that local R. clavigera would be at risk due to exposure to phenyltins. Comparing with those of previous surveys (2004-2010), both imposex levels and tissue concentrations of organotins did not decline, while the ecological risks due to exposure to organotins were increasing. We also observed high concentrations of monobutyltin and TPT in seawater and sediment from locations with intense shipping activities and from stormwater or sewage discharge. Overall, organotins are still prevalent in Hong Kong's marine waters showing that the global convention alone may be inadequate in reducing organotin contamination in a busy international port like Hong Kong. Appropriate management actions should be taken to control the use and release of organotins in Hong Kong and South China.

Sudden social hot events spread rapidly in the Internet era, which can easily cause group behaviors. Therefore, studying the law of public opinion communication has important theoretical and practical significance for controlling public opinion. This paper constructs the DBUS (Divorced-Burning-Unburning-Stable) model according to the social combustion theory deduced from the analogy of natural combustion phenomena. This paper comprehensively considers the influence of individual characteristics and external environment on the dissemination of online public opinion, introduces indicators such as individuals' self-awareness ability, authority to reflect individual differences, and takes the surrounding individual influence as an external environment factor. Through simulations, we find that (1) the speed of public opinion communication and the dissipation speed are related to cognitive ability, conformity and the network structure; (2) the credibility of the government and the media and the transparency of the information released are the most important factors affecting the scale of public opinion communication; In addition, the rationality and effectiveness of the model established in this paper are verified by an example., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The aim of this study was to investigate the association between sleep duration and muscle quality index (MQI) in middle-aged and older age groups, as limited evidence exists on this topic., Methods: In order to assess the relationship between sleep duration and MQI, a cross-sectional study was undertaken, utilizing data from the National Health and Nutrition Examination Survey (NHANES) acquired during the period from 2011 to 2014. The study comprised a total of 4598 participants aged 20 years and above. To examine the association between sleep duration and MQI, sophisticated weighted multivariate linear regression models were employed. Additionally, smooth curve fitting techniques were applied to examine the possibility of any non-linear relationship between the two variables., Results: The average age of the adults who were enrolled in the study was 38.48±11.69 years, and 46.75% of them were female. The results of the multivariable linear regression models showed that sleep duration had a positive correlation with MQI. However, when subgroup analysis was conducted, it was found that this positive correlation only existed among women (β = 0.09, 95% CI: 0.014 to 0.167). To further confirm the differences between sexes in the relationship between sleep duration and MQI, a weighted generalized additive model (GAM) was used., Conclusions: This research study provides evidence that there is a positive correlation between the duration of sleep and MQI specifically in females, while no such association was observed in males. These findings shed light on the existence of gender disparities in the connection between sleep duration and MQI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The complex vibration phenomenon occurs in the downhole environment of the gas-liquid hydrocyclone, which affects the flow field in the hydrocyclone. In order to study the influence of vibration on hydrocyclone separation, the characteristics of the flow field in the downhole gas-liquid hydrocyclone were analyzed and studied under the condition of vibration coupling. Based on Computational Fluid Dynamics (CFD), Computational Solid Mechanics Method (CSM) and fluid-solid coupling method, a fluid-solid coupling mechanical model of a gas-liquid cyclone is established. It is found that under the condition of vibration coupling, the velocity components in the three directions of the hydrocyclone flow field change obviously. The peak values of tangential velocity and axial velocity decrease, and the asymmetry of radial velocity increases. The distribution regularity of vorticity and turbulence intensity in the overflow pipe becomes worse. Among them, the vorticity intensity of the overflow pipe is obviously enhanced, and the higher turbulence intensity near the wall occupies more area distribution range. The gas-liquid separation efficiency of the hydrocyclone will decrease with the increase of the rotational speed of the screw pump, and the degree of reduction can reach more than 10%. However, this effect will decrease with the increase of the rotational speed of the screw pump, so the excitation effect caused by the rotational speed has a maximum limit on the flow field., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The positional workload characteristics in rugby union on three acquisition days (i.e. strength, endurance, and speed days) of tactical periodization are still relatively unknown. Therefore, the primary aim of this study was to shed light on the positional external workload variables (10 Hz Global Positioning System and accelerometer microtechnology) and internal workload indicators (the session rating of perceived exertion) of players in a professional rugby union team by utilizing and comparing two tactical periodization models. Twenty-six male players (15 forwards and 11 backs) were recruited from a French second-division rugby club. Data were obtained over 10 weeks of in-season home games: a total of 780 observations were analyzed. Student's t-test observed different external workload profiles between positions among acquisition days. Mean external workload values, except PlayerLoadslow, were significantly higher (p≤0.01; effect size: 0.41-1.93) for backs than forwards for all acquisition days. Moreover, forwards perceived a higher internal workload than backs on the strength day of both models. The findings demonstrate that applying these two tactical periodization models could result in effective rugby union training. Validating external and internal workload characteristics on tactical periodization acquisition days enables extensive analysis of training load monitoring data; these data can be utilized to discover the unique characteristics of each position and design position-specific acquisition days to improve performance., Competing Interests: NO authors have competing interests Enter: The authors have declared that no competing interests exist., (Copyright: © 2024 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To establish and validate an individualized nomogram to predict mortality risk within 30 days in patients with sepsis from the emergency department., Methods: Data of 1205 sepsis patients who were admitted to the emergency department in a tertiary hospital between Jun 2013 and Sep 2021 were collected and divided into a training group and a validation group at a ratio of 7:3. The independent risk factors related to 30-day mortality were identified by univariate and multivariate analysis in the training group and used to construct the nomogram. The model was evaluated by receiver operating characteristic (ROC) curve, calibration chart and decision curve analysis. The model was validated in patients of the validation group and its performance was confirmed by comparing to other models based on SOFA score and machine learning methods., Results: The independent risk factors of 30-day mortality of sepsis patients included pro-brain natriuretic peptide, lactic acid, oxygenation index (PaO2/FiO2), mean arterial pressure, and hematocrit. The AUCs of the nomogram in the training and verification groups were 0.820 (95% CI: 0.780-0.860) and 0.849 (95% CI: 0.783-0.915), respectively, and the respective P-values of the calibration chart were 0.996 and 0.955. The DCA curves of both groups were above the two extreme curves, indicating high clinical efficacy. The AUC values were 0.847 for the model established by the random forest method and 0.835 for the model established by the stacking method. The AUCs of SOFA model in the model and validation groups were 0.761 and 0.753, respectively., Conclusion: The sepsis nomogram can predict the risk of death within 30 days in sepsis patients with high accuracy, which will be helpful for clinical decision-making., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Smart services are expected to solve the dilemma of development and emission reduction, but there is still no conclusive evidence on whether and how they work. This article aims to explore the relationship between smart services and sustainable green transformation and the effect mechanism. To achieve this goal, a text mining analysis is performed to assess 970 Chinese listed manufacturing enterprises' smart services development; a regression analysis is then conducted. The results show that smart services have a significant positive impact on the quality and quantity of green innovation, especially for heavily polluting enterprises. The substitution of technology and labor for capital, as well as the upgrading of human resource quality, are effective mechanisms. Smart services can assist as a management strategic tool to balance environmental protection and development, but such an effect fails to work in areas not covered by new infrastructure and is weaker for private enterprises., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study explores the relationship between the proportion of basic research investment in R&D expenditure and regional economic growth efficiency and its influence path. A panel of data from 31 China's provincial was analysed by the fixed-effects model over 2009 to 2019. Empirical results highlight that: (1) the increase in the proportion of basic research investment has a significant promoting effect on regional economic growth efficiency, but it presents an "inverted U-shaped" impact path. Meanwhile, the threshold effect model test results reveal that basic research investment plays a more significant role in promotion when the per capita income level exceeds a certain threshold. (2) The test results of the mediating effect model indicate that the improvement of the level of human capital is the intermediate channel through which the investment in basic research affects regional economic growth efficiency, while the mediating effect of the increase of knowledge storage on the process of the investment in basic research affecting regional economic growth efficiency is not supported by data. Potential policy measures are discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Forest colors are important elements for public enjoying the scenery. So increasing attention has been acquired on forest color cognition. However researches on relationship between forest colors and public response are still insufficient, which cannot provide sufficient theoretical basis for the regulation of forest landscape in color. Therefore, We seek to examine the relationship between forest color and visual behavior based on eye tracking technology, and further interpret the visual indicators through the value of scenic beauty. This study researched Jiaozi Mountain in China by selecting 29 sampling points, counting up 116 photographs in 4 seasons by a mountainous region. On this basis, Matlab was performed to quantitatively extract color elements, while ArcGIS and Fragstats were applied to extract the spatial index of color patches. A total of 10 indicators were obtained to explain the color characteristics of each forest image. Through both visual behavior experiment and landscape preference evaluation, the results showed that people tend to have different visual behaviors and preference cognition when observing forest colors of different seasonal types. Based on the study of forest landscape color in all seasons, the subjects tend to judge the image in comparison to other seasonal forest landscape color photos to identify it more easily. For a single-season forest colors, diversified color information and abundant visual attention are important factors influencing the correlation between visual behavior, landscape preference, and forest color characteristics. This study aims to further reveal people's perceptions and psychological preference to forest colors, contribute to the establishment of a more quantitative and scientific scenery evaluation system, and provide a scientific basis for forest color planning and design., Competing Interests: The authors have declared that no competing interests exist.

Hydrosalpinx is a chronic inflammatory condition with high recurrence rate, and it is reported among female population having fallopian tubal factor infertility. Previously, we have reported that interventional ultrasound sclerotherapy improves endometrial receptivity and pregnancy rate with negligible adverse effects in patients suffering from hydrosalpinx. During present investigation, we have used next generation sequencing (NGS) to characterize the isomiR profiles from the endometrium of patients suffering from hydrosalpinx before and after interventional ultrasound sclerotherapy. Our results indicated that miRNA arm shift and switch remained unaffected when compared in patients before and after interventional ultrasound sclerotherapy. We observed that isomiRs with trimming at 3' and isomiRs with canonical sequences were lower in post-treatment than in pre-treatment group. Gene ontology (GO) annotation and KEGG pathway analysis revealed that the expression of mature mir-30 was significantly lower in the pre-treatment as compared to post treatment group while the expression of mir-30 isomiR was 4.26-fold higher in pre-treatment when compared with the post-treatment group. These different expression patterns of mir-30 mature miRNA and mir-30 isomiRs in two groups are affecting the physiological function of the endometrium. Our results suggested that differential isomiR distribution in hydrosalpinx patients before and after treatment plays an important role in hydrosalpinx incidence and can help in designing novel strategy for the treatment of hydrosalpinx in female population., Competing Interests: The authors have declared that no competing interests exist.

Migrant workers greatly contributing to China's industrialization and urbanization are confronted with increasing health risks. This study empirically investigates the effects of public employment services on the self-rated health of migrant workers in Shanghai China, by using data from the National Bureau of Statistics from 2015 to 2020. The estimation results under the Ordered Probit model illustrate that public employment services significantly improve the self-rated health of migrant workers, and vocational training, job development and other related services show an apparently positive correlation with the self-rated health. The marginal effect analysis reveals that public employment services obviously reduce the probability of health satisfaction as "average", "relatively satisfied" and "relatively dissatisfied", which translate into a significant increase in the probability of "very satisfied". The mechanism analysis verifies that public employment services enhance the self-rated health by increasing the proportion of medical insurance and injury insurance of migrant workers. The results are still reliable by adopting the methods of subsample regression, Propensity Score Matching and variable substitution to conduct robustness checks. This study further enriches the literature on public employment services and the health status of migrant workers, and provides policy implications on improving the health status of migrant workers and the public employment service system of China under the impact of the COVID-19 pandemic., Competing Interests: The authors declare that they have no competing interests.

Understanding long-term trends in marine ecosystems requires accurate and repeatable counts of fishes and other aquatic organisms on spatial and temporal scales that are difficult or impossible to achieve with diver-based surveys. Long-term, spatially distributed cameras, like those used in terrestrial camera trapping, have not been successfully applied in marine systems due to limitations of the aquatic environment. Here, we develop methodology for a system of low-cost, long-term camera traps (Dispersed Environment Aquatic Cameras), deployable over large spatial scales in remote marine environments. We use machine learning to classify the large volume of images collected by the cameras. We present a case study of these combined techniques' use by addressing fish movement and feeding behavior related to halos, a well-documented benthic pattern in shallow tropical reefscapes. Cameras proved able to function continuously underwater at deployed depths (up to 7 m, with later versions deployed to 40 m) with no maintenance or monitoring for over five months and collected a total of over 100,000 images in time-lapse mode (by 15 minutes) during daylight hours. Our ResNet-50-based deep learning model achieved 92.5% overall accuracy in sorting images with and without fishes, and diver surveys revealed that the camera images accurately represented local fish communities. The cameras and machine learning classification represent the first successful method for broad-scale underwater camera trap deployment, and our case study demonstrates the cameras' potential for addressing questions of marine animal behavior, distributions, and large-scale spatial patterns., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to uncover the molecular mechanism through which fungicide resistance develops in Podosphaera xanthii, a fungi that causes powdery mildew in hull-less pumpkin. Treatments of inoculated P. xanthii were carried out on leaves of hull-less pumpkin and subsequently treated with kinds of triazole fungicide for seven generations. Resistant strains of P. xanthii thus obtained were evaluated for their resistance levels. The resistance levels of the fungi to four fungicides of were high except that of the propiconazole-resistant strain, which showed moderate resistance. The F7 generations of five resistant strains thus obtained were cultured continuously for five generations without fungicide induction, and their resistance level were found to be relatively stable. The DNA of the sensitive strain and the five kinds of resistant strains were extracted by the sodium dodecyl sulfate (SDS) method and its internal transcribed spacer (ITS) region was amplified by using ITS1/ITS4 primer and specific primer F/R and they were sequenced respectively. The DNA sequence comparison of resistant and sensitive strains showed that the base pairs of tebuconazole-resistant strains and flusilazole-resistant strains were mutated, with mutation rates of 4.8% and 1.6%, respectively. The base pairs of the other three resistant strains did not change., Competing Interests: The authors have declared that no competing interests exist.

A feeding trial of eight weeks was conducted to examine the influence of food supplementation with lauric acid (LA) on Acanthopagrus schlegelii (juvenile black sea bream). A 24 percent fish meal baseline diet was created, while the other two diets were generated with dietary supplementation of graded points of LA at 0.1 percent and 0.8 percent, respectively. Each diet was given a triplicate tank with 20 fish weighing 6.22 ± 0.19 g. In comparison with the control group, the weight gain rate, growth rate, as well as feed efficiency of fish fed of 0.1 percent diet of LA were considerably (P < 0.05) greater. The total body and dorsal muscle proximate compositions did not change significantly between groups (P > 0.05). Triglyceride (TG) content was considerably (P < 0.05) greater in the LA-supplemented meals eating group in comparison with the control group. In the group eating LA-supplemented meals, the height of villus and the number of goblet cells/villus were considerably (P < 0.05) larger. The microbial makeup of the gut was also studied. The differences in phyla, class, and family level were not statistically significant (P > 0.05). Firmicutes in the phylum, Betaproteobacteri, Gammaproteobacteria, and Clostridia in the class, and Clostridiaceae in the family were all substantially increased with higher levels of LA supplementation (P < 0.05). According to the findings of this study, an LA-supplemented diet improves fish development, antioxidative capability, gut microbiota and intestinal health., Competing Interests: The authors have declared that no competing interests exist.

Normative modeling, a group of methods used to quantify an individual's deviation from some expected trajectory relative to observed variability around that trajectory, has been used to characterize subject heterogeneity. Gaussian Processes Regression includes an estimate of variable uncertainty across the input domain, which at face value makes it an attractive method to normalize the cohort heterogeneity where the deviation between predicted value and true observation is divided by the derived uncertainty directly from Gaussian Processes Regression. However, we show that the uncertainty directly from Gaussian Processes Regression is irrelevant to the cohort heterogeneity in general., Competing Interests: The authors have declared that no competing interests exist.

Apricot bud gall mite, Acalitus phloeocoptes (Nalepa), is a destructive arthropod pest that causes significant economic losses to apricot trees worldwide. The current study explores the ways to understand the mode of dispersal of A. phloeocoptes, the development and ultrastructure of apricot bud gall, and the role of phytohormones in the formation of the apricot bud galls. The results demonstrated that the starch granules in the bud axon were extended at the onset of the attack. During the later stages of the attack, the cytoplasm was found to deteriorate in infected tissues. Furthermore, we have observed that the accumulation of large amounts of cytokinin (zeatin, ZT) and auxin (indoleacetic acid, IAA) led to rapid bud proliferation during rapid growth period, while abscisic acid (ABA) controls the development of gall buds and plays a vital role in gall bud maturity. The reduction of gibberellic acid (GA3) content led to rapid lignification at the later phase of bud development. Overall, our results have revealed that the mechanism underlying the interaction of apricot bud gall with its parasite and have provided reliable information for designing valuable Apricot breeding programs. This study will be quite useful for pest management and will provide a comprehensive evaluation of ecology-based cost-effective control, life history and demographic parameters of A. phloeocoptes., Competing Interests: The authors have declared that no competing interests exist.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a serious infectious disease with a fatality of up to 30%. To identify the severity of SFTS precisely and quickly is important in clinical practice., Methods: From June to July 2020, 71 patients admitted to the Infectious Department of Joint Logistics Support Force No. 990 Hospital were enrolled in this study. The most frequently observed symptoms and laboratory parameters on admission were collected by investigating patients' electronic records. Decision trees were built to identify the severity of SFTS. Accuracy and Youden's index were calculated to evaluate the identification capacity of the models., Results: Clinical characteristics, including body temperature (p = 0.011), the size of the lymphadenectasis (p = 0.021), and cough (p = 0.017), and neurologic symptoms, including lassitude (p<0.001), limb tremor (p<0.001), hypersomnia (p = 0.009), coma (p = 0.018) and dysphoria (p = 0.008), were significantly different between the mild and severe groups. As for laboratory parameters, PLT (p = 0.006), AST (p<0.001), LDH (p<0.001), and CK (p = 0.003) were significantly different between the mild and severe groups of SFTS patients. A decision tree based on laboratory parameters and one based on demographic and clinical characteristics were built. Comparing with the decision tree based on demographic and clinical characteristics, the decision tree based on laboratory parameters had a stronger prediction capacity because of its higher accuracy and Youden's index., Conclusion: Decision trees can be applied to predict the severity of SFTS., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Although military veterans are at increased risk for skin cancer, little is known about the extent to which they have been screened for skin cancer. The study objective was to examine the prevalence and correlates of physician skin cancer screening among U.S. military veterans., Methods: Data were drawn from the National Health Interview Survey. The study sample consisted of 2,826 individuals who reported being military veterans. Receipt of a physician skin examination was measured using a single question that asked participants whether they had ever had all of their skin from head to toe checked for cancer by a dermatologist or some other kind of doctor., Results: Less than a third (30.88%) of participants reported ever having a physician skin examination. Factors positively associated with receipt of a physician skin examination in a multivariable logistic regression analysis included: older age, greater educational level, non-Hispanic white race/ethnicity, having TRICARE (military) health insurance, greater skin sensitivity to the sun, and engagement in more sun protection behaviors., Conclusions: The majority of military veterans have never been screened for skin cancer by a physician. Screening rates were higher among individuals with one or more skin cancer risk factors. Future research is warranted to test targeted skin cancer screening interventions for this at risk and understudied population., Competing Interests: EJC was employed by Medical Data Analytics during some portions of this project. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

With the rapid development of Unmanned Aerial Vehicles, vehicle detection in aerial images plays an important role in different applications. Comparing with general object detection problems, vehicle detection in aerial images is still a challenging research topic since it is plagued by various unique factors, e.g. different camera angle, small vehicle size and complex background. In this paper, a Feature Fusion Deep-Projection Convolution Neural Network is proposed to enhance the ability to detect small vehicles in aerial images. The backbone of the proposed framework utilizes a novel residual block named stepwise res-block to explore high-level semantic features as well as conserve low-level detail features at the same time. A specially designed feature fusion module is adopted in the proposed framework to further balance the features obtained from different levels of the backbone. A deep-projection deconvolution module is used to minimize the impact of the information contamination introduced by down-sampling/up-sampling processes. The proposed framework has been evaluated by UCAS-AOD, VEDAI, and DOTA datasets. According to the evaluation results, the proposed framework outperforms other state-of-the-art vehicle detection algorithms for aerial images., Competing Interests: NO authors have competing interests

Grasp force estimation based on surface electromyography (sEMG) is essential for the dexterous control of a prosthetic hand. Nowadays, although increasing the number of sEMG measurement positions and extracting more features are common methods to increase the accuracy of grasp force estimation, it will increase the computational burden. In this paper, an approach based on analysis of variance (ANOVA) and generalized regression neural network (GRNN) for optimal measurement positions and features is proposed, with the purpose of using fewer measurement positions or features to achieve higher estimation accuracy. Firstly, we captured six channels of sEMG from subjects' forearm and grasp force synchronously. Then, four kinds of features in time domain are extracted from each channel of sEMG. By combining different measurement position sets (MPSs) and feature set (FSs), we construct 945 data sets. These data sets are fed to GRNN to realize grasp force estimation. Normalized root mean square error (NRMS), normalized mean of absolute error (NMAE), and correlation coefficient (CC) between estimated grasp force and actual force are introduced to evaluate the performance of grasp force estimation. Finally, ANOVA and Tukey HSD testing are introduced to analyze grasp force estimation results so as to obtain the optimal measurement positions and features. We obtain the optimal MPSs for grasp force estimation when different FSs are employed, and the optimal FSs when different MPSs are utilized., Competing Interests: The authors have declared that no competing interests exist.

Introduction: HIV testing is an important strategy for controlling and ultimately ending the global pandemic. Oral rapid HIV testing (ORHT) is an evidence-based strategy and the evidence-based shows is favored over traditional blood tests in many key populations. The dental setting has been found to be a trusted, convenient, and yet untapped venue to conduct ORHT. This study assessed the HIV testing behaviors and willingness to receive ORHT among dental patients in Xi'an, China., Methods: A cross-sectional survey of dental patients from Xi'an was conducted from August to September 2017. Dental patients were recruited using a stratified cluster sampling. A 44-item survey was used to measure HIV/AIDS knowledge, HIV testing behaviors, and willingness to receive ORHT., Results: Nine hundred and nine dental patients completed the survey with a mean HIV/AIDS knowledge score of 10.7/15 (SD 2.8). Eighty-four participants (9.2%) had previously received an HIV test. Participants would have a high rate of HIV testing if they had higher monthly income (OR = 1.982, 95% CI: 1.251-3.140) and a higher HIV/AIDS knowledge score (OR = 1.137, 95% CI: 1.032-1.252). Five hundred and eighty-two participants (64.0%) were willing to receive ORHT before a dental treatment, 198 (21.8%) were not sure, and 129 (14.2%) were unwilling. Logistic regression showed that age (OR = 0.970, 95% CI: 0.959-0.982), HIV/AIDS knowledge score (OR = 1.087, 95% CI: 1.031-1.145), previous HIV test (OR = 2.057, 95% CI: 1.136-3.723), having advanced HIV testing knowledge (OR = 1.570, 95% CI: 1.158-2.128), and having advanced ORHT knowledge (OR = 2.074, 95%: CI 1.469-2.928) were the factors affecting the willingness to receive ORHT., Conclusions: The majority of dental patients had not previously received an HIV test, although many were receptive to being tested in the dental setting. The dental setting as a venue to screen people for HIV needs further exploration, particularly because many people do not associate dentistry with chairside screenings. Increasing awareness of ORHT and reducing testing price can further improve the patient's willingness to receive ORHT., Competing Interests: The authors have declared that no competing interests exist.

Host-associated microbiomes can play important roles in the ecology and evolution of their insect hosts, but bacterial diversity in many insect groups remains poorly understood. Here we examine the relationship between host environment, host traits, and microbial diversity in three species in the ground beetle family (Coleoptera: Carabidae), a group of roughly 40,000 species that synthesize a wide diversity of defensive compounds. This study used 16S amplicon sequencing to profile three species that are phylogenetically distantly related, trophically distinct, and whose defensive chemical secretions differ: Anisodactylus similis LeConte, 1851, Pterostichus serripes (LeConte, 1875), and Brachinus elongatulus Chaudoir, 1876. Wild-caught beetles were compared to individuals maintained in the lab for two weeks on carnivorous, herbivorous, or starvation diets (n = 3 beetles for each species-diet combination). Metagenomic samples from two highly active tissue types-guts, and pygidial gland secretory cells (which produce defensive compounds)-were processed and sequenced separately from those of the remaining body. Bacterial composition and diversity of these ground beetles were largely resilient to controlled changes to host diet. Different tissues within the same beetle harbor unique microbial communities, and secretory cells in particular were remarkably similar across species. We also found that these three carabid species have patterns of microbial diversity similar to those previously found in carabid beetles. These results provide a baseline for future studies of the role of microbes in the diversification of carabids., Competing Interests: The authors have declared that no competing interests exist.

Whether osteoarthritis (OA) is a systemic metabolic disorder remains controversial. The aim of this study was to investigate the metabolic characteristics between plasma and knee joint fluid (JF) of patients with advanced OA using a differential correlation metabolic (DCM) networks approach. Plasma and JF were collected during the joint replacement surgery of patients with knee OA. The biological samples were pretreated with standard procedures for metabolite analysis. The metabolic profiling was conducted by means of liquid mass spectrometry coupled with a AbsoluteIDQ kit. A DCM network approach was adopted for analyzing the metabolomics data between the plasma and JF. The variation in the correlation of the pairwise metabolites was quantified across the plasma and JF samples, and networks analysis was used to characterize the difference in the correlations of the metabolites from the two sample types. Core metabolites that played an important role in the DCM networks were identified via topological analysis. One hundred advanced OA patients (50 men and 50 women) were included in this study, with an average age of 65.0 ± 7.6 years (65.6 ± 7.1 years for females and 64.4 ± 8.1 years for males) and a mean BMI of 32.6 ± 5.8 kg/m2 (33.4 ± 6.3 kg/m2 for females and 31.7 ± 5.3 kg/m2 for males). Age and BMI matched between the male and female groups. One hundred and forty-five nodes, 567 edges, and 131 nodes, 407 edges were found in the DCM networks (p < 0.05) of the female and male groups, respectively. Six metabolites in the female group and 5 metabolites in the male group were identified as key nodes in the network. There was a significant difference in the differential correlation metabolism networks of plasma and JF that may be related to local joint metabolism. Focusing on these key metabolites may help uncover the pathogenesis of knee OA. In addition, the differential metabolic correlation between plasma and JF mostly overlapped, indicating that these common correlations of pairwise metabolites may be a reflection of systemic characteristics of JF and that most significant correlation variations were just a result of "housekeeping" biological reactions., Competing Interests: The authors have read the journal’s policy and have the following competing interests: BYX receives a salary from Hangzhou Heze Pharmaceutical Technology CO., LTD (http://www.hezepharm.com/index.php?lang=en). There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: This study examined the feasibility and safety of allogeneic uterus transplantation (UTx) from a living donor and assessed short-term graft viability in a rhesus model. This research is an important step towards further clinical application of UTx in humans., Materials and Methods: Four female rhesus monkeys with regular menstrual cycles were used in this study, the animals were either donors or recipients depending on ABO blood type compatibility. Retrieval surgery was performed to connect the uterus and uterine arteries together with the ovarian uterine vein from the living donor, and the vagina of the recipient was excised. After the back table had been prepared, bilateral uterine arteries were anastomosed end-to-side with the iliac externa arteries, and bilateral ovarian uterine veins were anastomosed end-to-side with the iliac externa vena. The transplanted uterus was evaluated based on the conditions of arterial blood, and flow was evaluated by transabdominal ultrasonography one month post operation. The conditions of the transplanted uterus were examined by secondary laparotomy. The reproductive function of rhesus monkeys was evaluated on the basis of the menstrual cycle., Results: All 4 rhesus monkeys received the transplantation surgery without any surgical complications. No injury occurred in the other organs, and no vascular injury was observed in the allogeneic uterus. All recipients survived after the surgery with a 100% short-term survival rate. All recipients resumed normal menstruation within two months after surgery., Conclusions: Our short follow-up shows that allogeneic UTx surgery is a safe and feasible technology in the rhesus model. The arterial conditions and blood flow of the grafted uterus can be monitored by ultrasonography examination., Competing Interests: The authors have declared that no competing interests exist.

Background: The association between polymorphisms in vitamin D-binding protein (DBP) gene and the risk of multiple sclerosis (MS) and type 1 diabetes mellitus (T1DM) has been investigated in many studies, but the studies showed controversial results. The rationale for this meta-analysis was to determine whether DBP polymorphisms increases the risk of MS and T1DM by pooling data., Methods: Potentially relevant studies were searched using GWAS Catalog, PubMed, Embase, CNKI and WANFANG databases up to November 2019. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were performed to estimate the associations in a fixed-effects or random-effects model., Results: A total of 13 studies were enrolled in this meta-analysis, including eight studies for MS and five for T1DM. The overall results showed that there was no significant association of DBP rs7041 and rs4588 polymorphisms with the risk of MS and T1DM under any genetic model. Similarly, subgroup analysis by ethnicity revealed that no significant association of rs7041 and rs4588 polymorphisms with the risk of MS and T1DM was observed in white or non-white racial groups., Conclusions: This meta-analysis provides evidence that DBP rs7041 and rs4588 polymorphisms may not be associated with an increased risk in MS and T1DM. However, these findings need further validation by larger-scale epidemiological studies and genome-wide association studies (GWASs) in different populations., Competing Interests: The authors have declared that no competing interests exist.

Our previously study shown that Lysophosphatidylcholine Acyltransferase1 (LPCAT1) is overexpressed in castration resistant prostate cancer (CRPC) relative to primary prostate cancer (PCa), and androgen controls its expression via the Wnt signaling pathway. While highly expressed in CRPC, the role of LPCAT1 remains unclear. In vitro cell experiments referred to cell transfection, mutagenesis, proliferation, migration, invasion, cell cycle progression and apoptosis, Western blotting, Pulse-chase RNA labeling. BALB/c nude mice were used for in vivo experiments. We found that LPCAT1 overexpression enhanced the proliferation, migration, and invasion of CRPC cells both in vitro and in vivo. Silencing of LPCAT1 reduced the proliferation and the invasive capabilities of CRPC cells. Providing exogenous PAF to LPCAT1 knockdown cells increased their invasive capabilities; however platelet activating factor acetylhydrolase (PAF-AH) and the PAFR antagonist ABT-491 both reversed this phenotype; proliferation of CRPC cells was not affected in either model. LPCAT1 was found to mediate CRPC growth via nuclear re-localization and Histone H4 palmitoylation in an androgen-dependent fashion, increasing mRNA synthesis rates. We also found that LPCAT1 overexpression led to CRPC cell resistance to treatment with paclitaxel. LPCAT1 overexpression in CRPC cells drives tumor progression via increased mRNA synthesis and PAF production. Our results highlight LPCAT1 as a viable therapeutic target in the context of CRPC., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To assess the effects of age and refractive status on anterior segment anatomical structures, including the ciliary body, using a new swept-source anterior segment optical coherence tomography (AS-OCT) device., Methods: This prospective observational study included 63 healthy volunteers (mean age: 44.2 years). Images of the anterior segment were obtained using a new swept-source AS-OCT (ANTERION, Heidelberg Engineering GmbH, Heidelberg, Germany) with tracking and image averaging from the right eye of all participants. Repeatability as well as inter- and intra-observer reliability of biometric measurements were evaluated. The impact of image tracking and averaging on ciliary muscle measurements was tested. Univariate and multivariable statistical models were developed to evaluate the relationship of age and refractive status on anterior segment biometric measurements., Results: For all test-retest repeatability and inter- and intra-observer reproducibility of swept-source AS-OCT measurements, high intraclass correlation (ICC) was noted (0.88-1.00). The nasal maximum ciliary muscle thickness (CMTMAX) and distance between scleral spur to the thickest point of the ciliary muscle (SSMAX) were larger than those on the temporal side (p<0.001 and p = 0.006, respectively). Nasal and temporal CMTMAX (p = 0.004 and p<0.001, respectively) and lens thickness (p<0.01) increased with age. Nasal and temporal SSMAX decreased with older age and increasing hyperopia (p = 0.01 and p<0.001, respectively). Image averaging resulted in improved ciliary muscle measurements (p = 0.008 to 0.02). Lens vault increased with older age and increased hyperopia (p<0.01). OCT measurements of the angle decreased with older age and increased hyperopia (p<0.001 to 0.03). Aqueous depth decreased with older age and increased hyperopia (p<0.01). Pupil diameter decreased with older age (p<0.01)., Conclusions: Repeatability and reproducibility of biometric measurements using the ANTERION AS-OCT were excellent. Image averaging improved the accuracy of ciliary muscle measurements. The device produced measurements of biometric parameters that described superficial and deep structures including the ciliary body and full lens thickness from a single image., Competing Interests: 1) Alex Huang: I have read the journal's policy and the authors of this manuscript have the following competing interests: Heidelberg Engineering provided this device for research; Glaukos Corporation (consultant); Santen (consultant); Allergan (consultant); Gore (consultant); Diagnosys (research support); Aerie (consultant). 2) Ben Xu: I have read the journal's policy and the authors of this manuscript have the following competing interests: Heidelberg Engineering provided this device for research 3)Vas Sadda: I have read the journal's policy and the authors of this manuscript have the following competing interests: Heidelberg Engineering (consultant and research support), Amgen (consultant), Allergan (consultant), Genentech/Roche (consultant), Oxurion (consultant), Novartis (consultant), Regeneron (consultant), Bayer (consultant), 4DMT (consultant), Centervue (consultant), Optos (consultant and research support), Zeiss (research support). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The gene expression for interleukin-2 receptor subunit alpha (CD25/IL2RA) is frequently altered in adults with acute myeloid leukemia (AML). Increasing evidence indicates that the elevated expression of CD25 may be correlated with poor survival for AML patients. Thus, we performed this meta-analysis to further evaluate the prognostic value of elevated CD25 in AML. Eligible studies were gathered by searching on PubMed, Web of Science, and Embase. Using the R language 3.6.0 software, Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/event-free survival (EFS) for total and subgroup analyses were calculated to investigate the association of elevated CD25 and outcomes of AML patients. Ten studies with a total of 1640 participants were enrolled in this meta-analysis. Pooled HRs suggested that overexpression of CD25 predicted poor outcomes on both OS (HR = 2.27, 95%CI 1.95-2.64) and DFS/RFS/EFS (HR = 1.77, 95%CI 1.44-2.17) in overall population. Subgroup analyses stratified by ethnicity, AML subtype, cut-off value, statistical methodologies and detection method draw similar results. Our meta-analysis indicates that elevated CD25 expression is a poor prognostic factor for AML patients. Considering limited number of samples, further relevant studies are warranted., Competing Interests: The authors have declared that no competing interests exist.

Spatial conservation prioritization concerns trade-offs between marine conservation and resource exploitation. This approach has been increasingly used to devise spatial management strategies for fisheries because of its simplicity in the optimization model and less data requirement compared to complex dynamic models. However, most of the prioritization is based on static models or algorithms; whose solutions need to be evaluated in a dynamic approach, considering the high uncertainty and opportunity costs associated with their implementation. We developed a framework that integrates species distribution models, spatial conservation prioritization tools and a general grid-based dynamic model (Grid-DM) to support evaluation of ecological and economic trade-offs of candidate conservation plans. The Grid-DM is spatially explicit and has a tactical management focus on single species. We applied the Grid-DM to small yellow croaker (Larimichthys polyactis) in Haizhou Bay, China and validated its spatial and temporal performances against historical observations. It was linked to a spatial conservation prioritization tool Marxan to illustrate how the model can be used for conservation strategy evaluation. The simulation model demonstrated effectiveness in capturing the spatio-temporal dynamics of the target fishery as well as the socio-ecological effects of conservation measures. We conclude that the model has the capability and flexibility to address various forms of uncertainties, simulate the dynamics of a targeted fishery, and to evaluate biological and socioeconomic impacts of management plans. The modelling platform can further inform scientists and policy makers of management alternatives screening and adaptive conservation planning., Competing Interests: The authors have declared that no competing interests exist.

Presently, concern regarding the effects of selenium (Se) on the environment and organisms worldwide is increasing. Too much Se in the soil is harmful to plants. In this study, Illumina RNA sequencing and the untargeted metabolome of control and Se-treated celery seedlings were analyzed. In total, 297,911,046 clean reads were obtained and assembled into 150,218 transcripts (50,876 unigenes). A total of 36,287 unigenes were annotated using different databases. Additionally, 8,907 differentially expressed genes, including 5,319 up- and 3,588 downregulated genes, were identified between mock and Se-treated plants. "Phenylpropanoid biosynthesis" was the most enriched KEGG pathway. A total of 24 sulfur and selenocompound metabolic unigenes were differentially expressed. Furthermore, 1,774 metabolites and 237 significant differentially accumulated metabolites were identified using the untargeted metabolomic approach. We conducted correlation analyses of enriched KEGG pathways of differentially expressed genes and accumulated metabolites. Our findings suggested that candidate genes and metabolites involved in important biological pathways may regulate Se tolerance in celery. The results increase our understanding of the molecular mechanism responsible for celery's adaptation to Se stress., Competing Interests: The authors have declared that no competing interests exist.

Background: Peritoneal dialysis (PD) is increasingly used for long-term management of Cardiorenal Syndrome (CRS). We compared outcomes in incident PD patients according to their baseline heart failure status., Methods: This retrospective cohort study evaluated all-cause and cardiovascular mortality in incident PD patients with different heart failure status (non-CRS, acute heart failure [AHF], type II CRS, type IV CRS) who started PD between 2006 and 2016 in the Peking University Third Hospital., Results: Of 748 patients included in the study, there were 466 (62.3%), 214 (28.6%), 27 (3.6%), and 41 (5.5%) patients in the non-CRS, AHF, type II CRS and type IV CRS groups, respectively. Patients with CRS were older (p<0.001), with more diabetes mellitus (p<0.001), coronary heart history (p<0.001), higher estimated glomerular filtration rate (eGFR) (p<0.001), lower serum creatinine (p<0.001) and phosphorus levels (p = 0.003) compared to non-CRS patients. Respective all-cause survival rates for patients with non-CRS, AHF, type II CRS and type IV CRS were 90.6%, 87.1%, 85.2% and 84.8% at 1 year, and 63.1%, 47.7%, 27.3% and 35.1% at 5 years (p<0.001). The corresponding figures for cardiovascular survival were 93%, 92%, 84% and 81% at 1 year, and 67%, 59%, 55% and 54% at 5 years (p<0.001). However, after adjusting for confounding factors, the presence of CRS was not independently associated with all-cause mortality whereas type IV CRS (HR 2.10, 95% CI 1.03-4.28, p = 0.04) was associated with higher cardiovascular mortality as compared to without CRS., Conclusion: Incident PD patients with different types of CRS had higher rates of both all-cause and cardiovascular mortality compared with patients without CRS. However, these observed adverse outcomes may be related to associated older age and higher prevalence of comorbidities, rather than CRS per se, except for type IV CRS, treatment strategies to reduce high cardiovascular CVD mortality may needed., Competing Interests: The authors have declared that no competing interests exist.

Humans are able to achieve visual object recognition rapidly and effortlessly. Object categorization is commonly believed to be achieved by interaction between bottom-up and top-down cognitive processing. In the ultra-rapid categorization scenario where the stimuli appear briefly and response time is limited, it is assumed that a first sweep of feedforward information is sufficient to discriminate whether or not an object is present in a scene. However, whether and how feedback/top-down processing is involved in such a brief duration remains an open question. To this end, here, we would like to examine how different top-down manipulations, such as category level, category type and real-world size, interact in ultra-rapid categorization. We have constructed a dataset comprising real-world scene images with a built-in measurement of target object display size. Based on this set of images, we have measured ultra-rapid object categorization performance by human subjects. Standard feedforward computational models representing scene features and a state-of-the-art object detection model were employed for auxiliary investigation. The results showed the influences from 1) animacy (animal, vehicle, food), 2) level of abstraction (people, sport), and 3) real-world size (four target size levels) on ultra-rapid categorization processes. This had an impact to support the involvement of top-down processing when rapidly categorizing certain objects, such as sport at a fine grained level. Our work on human vs. model comparisons also shed light on possible collaboration and integration of the two that may be of interest to both experimental and computational vision researches. All the collected images and behavioral data as well as code and models are publicly available at https://osf.io/mqwjz/., Competing Interests: The authors have declared that no competing interests exist.

Speech recognition (SR) has been improved significantly by artificial neural networks (ANNs), but ANNs have the drawbacks of biologically implausibility and excessive power consumption because of the nonlocal transfer of real-valued errors and weights. While spiking neural networks (SNNs) have the potential to solve these drawbacks of ANNs due to their efficient spike communication and their natural way to utilize kinds of synaptic plasticity rules found in brain for weight modification. However, existing SNN models for SR either had bad performance, or were trained in biologically implausible ways. In this paper, we present a biologically inspired convolutional SNN model for SR. The network adopts the time-to-first-spike coding scheme for fast and efficient information processing. A biological learning rule, spike-timing-dependent plasticity (STDP), is used to adjust the synaptic weights of convolutional neurons to form receptive fields in an unsupervised way. In the convolutional structure, the strategy of local weight sharing is introduced and could lead to better feature extraction of speech signals than global weight sharing. We first evaluated the SNN model with a linear support vector machine (SVM) on the TIDIGITS dataset and it got the performance of 97.5%, comparable to the best results of ANNs. Deep analysis on network outputs showed that, not only are the output data more linearly separable, but they also have fewer dimensions and become sparse. To further confirm the validity of our model, we trained it on a more difficult recognition task based on the TIMIT dataset, and it got a high performance of 93.8%. Moreover, a linear spike-based classifier-tempotron-can also achieve high accuracies very close to that of SVM on both the two tasks. These demonstrate that an STDP-based convolutional SNN model equipped with local weight sharing and temporal coding is capable of solving the SR task accurately and efficiently., Competing Interests: The authors have declared that no competing interests exist.

Crab species are economically and ecologically important in coastal ecosystems, and their spatial distributions are pivotal for conservation and fisheries management. This study was focused on modelling the spatial distributions of three Portunidae crabs (Charybdis bimaculata, Charybdis japonica, and Portunus trituberculatus) in Haizhou Bay, China. We applied three analytical approaches (Generalized additive model (GAM), random forest (RF), and artificial neural network (ANN)) to spring and fall bottom trawl survey data (2011, 2013-2016) to develop and compare species distribution models (SDMs). Model predictability was evaluated using cross-validation based on the observed species distribution. Results showed that sea bottom temperature (SBT), sea bottom salinity (SBS), and sediment type were the most important factors affecting crab distributions. The relative importance of candidate variables was not consistent among species, season, or model. In general, we found ANNs to have less stability than both RFs and GAMs. GAMs overall yielded the least complex response curve structure. C. japonica was more pronounced in southwestern portion of Haizhou Bay, and C. bimaculata tended to stay in offshore areas. P. trituberculatus was the least region-specific and exhibited substantial annual variations in abundance. The comparison of multiple SDMs was informative to understand species responses to environmental factors and predict species distributions. This study contributes to better understanding the environmental niches of crabs and demonstrates best practices for the application of SDMs for management and conservation planning., Competing Interests: The authors have declared that no competing interests exist.

Background: Dietary protein restriction has long been thought to play an important role in the progression of chronic kidney disease (CKD); however, the effect of dietary protein on the rate of decline in kidney function remains controversial., Objective: We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the influence of protein restriction on chronic kidney disease., Method: Ovid MEDLINE (from 1946 to March 5, 2016), EMBASE (from 1966 to March 5, 2016), and the Cochrane Library (Inception to March 5, 2016) were searched to identify RCTs comparing different levels of protein intake for at least 24 weeks in adult patients with CKD. The outcomes included kidney failure events, the rate of change in estimated glomerular filtration rate (eGFR) per year, all cause death events, and changes in proteinuria, serum phosphorus concentration, serum albumin, and body mass index (BMI)., Results: Nineteen trials with 2492 subjects were analyzed. A low protein diet reduced the risk of kidney failure (odds ratio (OR) = 0.59, 95% CI: 0.41 to 0.85) and end-stage renal disease (ESRD) (OR = 0.64, 95% CI: 0.43 to 0.96), but did not produce a clear beneficial effect for all cause death events (OR = 1.17, 95% CI: 0.67 to 2.06). The change in the mean difference (MD) for the rate of decline in the eGFR was significant (MD: -1.85, P = 0.001), and for proteinuria (MD: -0.44, P = 0.02). A low protein diet also reduced the serum phosphorus concentration (MD: -0.37, 95% CI: -0.5 to -0.24) and BMI (MD: -0.61, 95% CI: -1.05 to -0.17). However the change in albumin presented no significant difference between two groups (MD: 0.23, 95% CI: -0.51 to 0.97)., Conclusions: Based on the findings of our meta-analysis, protein-restricted diet may reduce the rate of decline in renal function and the risk of kidney failure for CKD populations, but did not produce a clear beneficial effect for all cause death events. Besides However, the optimal level of protein intake in different participants is left unanswered, and the nutritional status should be regarded with caution., Competing Interests: The authors have declared that no competing interests exist.

Osteoporosis (OP) is a systemic skeletal disorder, manifesting with a reduction in bone mass and deterioration of the microarchitecture. Mesenchymal stem cells (MSCs) have an innate ability to differentiate into several cell types, including osteoblasts (OB). Ginsenoside Rb1 (GRb1) is an ethanol extract from ginseng and contains a highly concentrated form of ginsenoside. GRb1 shows extensive beneficial health effects such as anti-oxidative and anti-inflammatory functions, modulating the immune system and inhibiting osteoclastogenesis. We hypothesized that GRb1 can promote MSC differentiation into OBs and inhibit bone loss. In the present study, we aimed to address two questions: (1) Will GRb1 have a positive effect on osteogenic differentiation of MSCs? and (2) Will GRb1 halt bone loss in ovariectomized (OVX) rats? We investigated the effects of GRb1 on viability and osteogenic differentiation of rat mesenchymal stem cells (rMSCs). Our results showed that GRb1 at concentrations of 10-8 M and 10-6 M can increase alkaline phosphatase activity, mineralization and the expression of osteogenic related proteins, such as osteopontin and osteoprotegerin, while incubating rMSCs with osteogenic induction medium and GRb1. Adding GRb1 into the medium can prevent rMSCs from Oxidative damage at the concentration of 25μM H2O2. Furthermore, 40 4-month-old rats were assigned to 5 groups(8 rats per group): the basal group, the sham group, the OVX group, the high dose of GRb1 group (6 mg/kg/day) and the low dose of GRb1 group (3 mg/kg/day). Rats recrived treatment 3days after surgery and last for 14 weeks. Examinations included serum analysis, mechanical testing, Masson-Goldner trichrome staining and bone histomorphometry analysis. The results showed that OVX can lead to dyslipidemia and excessive oxidative stress, whereas GRb1 cannot significantly halt dyslipidemia and excessive oxidative stress in OVX rats. In addition, the bone density of the lumbar vertebra and femur were decreased significantly in the OVX rats, and GRb1 could not inhibit bone loss. Bone histomorphometry analysis showed that the number and width of bone trabecula of the tibia were reduced in OVX rats, and GRb1 could not prevent their occurrence. A bone biomechanics assay showed that GRb1 cannot improve the ability of bone structure to resist fracture of the femur in OVX rats. The current study demonstrated that GRb1 has an obvious effect on osteogenic differentiation in rMSCs but no obvious effect on bone loss in OVX rats. These findings indicate GRb1 has a positive effect on rMSCs but does not have an effect on bone loss in OVX rats at the concentration we used., Competing Interests: The authors have declared that no competing interests exist.

It is difficult to determine ages of eels via otoliths, because multiple alternating translucent and opaque zones in the otoliths are hard to identify. In this study, we developed an efficient age determination method for whitespotted conger (Conger myriaster), using random forest models with otolith weight and length, total body length, capture location and season as predictors. 409 specimens were collected from six locations in Yellow and East China Sea between October 2016 and December 2017. Overall OOB error rate was 17.36% compared with 16.26% for the external cross-validation dataset, and the error of age was within one year. Otolith weight and total length were the most important predictors, followed by otolith length, capture locations and seasons. There were no significant differences between the results derived from otolith/somatic morphometrics and otoliths annuli in the estimation of age composition and von Betalanffy Growth Functions growth curve. Our results demonstrated that random forest model with otolith and somatic morphometrics is an efficient and reliable approach for age determination of C. myriaster, which may also be applied to other eel species., Competing Interests: The authors have declared that no competing interests exist.

[This corrects the article DOI: 10.1371/journal.pone.0180804.].

Background: Icariin, a major active flavonoid glucoside, is widely used for the treatment of bone injury and rebuilding in the clinic because of its roles in suppressing osteoblastogenesis and promoting osteogenesis. The senescence-accelerated mouse SAMP6 was accepted as a useful murine model to reveal the mechanism of senile osteoporosis and the therapeutic mechanism of drug activity. However, little is known about the characteristics of SAMP6 osteoblasts and the associated regulatory roles of icariin., Methods: We isolated and cultured osteoblasts from SAMP6 or SAMR1 mice and compared their proliferation, migration, and differentiation by performing the CCK-8 assay, cell counting assay, EdU staining, cell cycle analysis, ALP staining and activity measurement, Alizarin red staining, and RT-qPCR analysis to measure the levels of osteoblast markers, including RUNX2, Colla1 and Oc. To assess the effects of icariin on BMP-2-induced osteoblast differentiation, after BMP-2 treatment, osteoblast markers were analyzed by RT-qPCR and semi-quantitative Western blotting. The effects of icariin on connective tissue growth factor (CTGF) were measured by RT-qPCR. shRNA targeting CTGF mRNA was employed to knockdown its expression level in osteoblasts., Results: The SAMP6 osteoblasts presented decreased the development and differentiation activity compared with SAMR1 osteoblasts, indicating that they are the potential mechanisms underlying age-associated disease. Moreover, SAMP6 osteoblasts presented upregulated CTGF compared with SAMR1 osteoblasts. Icariin enhanced BMP-2-induced osteoblast differentiation by downregulating CTGF expression, which tightly regulates osteoblast differentiation. By downregulating CTGF, icariin treatment upregulated phosphate-Smad1/5/8, indicating its activating effects on the BMP signaling pathway., Conclusion: These results suggest that decreased osteoblast development and function potentially contributes to age-associated disease. Icariin exerts enhancing effects on BMP-2-mediated osteoblast development via downregulating CTGF., Competing Interests: The authors have declared that no competing interests exist.

Objective: Lung cancer is one of the deadliest malignancies. The immune checkpoint-blockade (ICB) tumor therapy has led to striking improvement of long-term survival for some lung cancer patients. However, the response rate of immunotherapy is still low for lung cancer. Studying the tumor microenvironment (TME) should shed light on improvement of immunotherapy of lung cancer. Interleukin-33 (IL-33), an "alarmin" cytokine, has been implicated in tumor associated immune responses and inflammatory diseases of the lung. The role of IL-33 in lung cancer progression, however, remains elusive. This study is designed to characterize IL-33 expression in lung tumor tissues and establish the clinical significance of IL-33 in non-small cell lung cancer lung cancer (NSCLC)., Materials and Methods: Tumor tissue specimens from patients suffering from NSCLC were analyzed for expression of IL-33 protein by immunohistochemistry and expression of IL-33 and ST2 mRNA by RT-quantitative PCR (RT-QPCR). The expression data were analyzed for their association with clinical and pathological parameters of NSCLC. In addition, the association between expression levels of IL-33 mRNA and patient survival was determined using 5 independent expression profiling datasets of human lung cancer., Results and Conclusion: The expression levels of IL-33 and ST2 were significantly down-regulated in both adenocarcinoma and squamous cell carcinoma of the lung when compared to adjacent normal lung tissues. In addition, the level of IL-33 protein was inversely correlated with tumor grade and size. Moreover, analysis of TCGA and GEO lung cancer expression datasets revealed that higher expression levels of IL-33 mRNA were correlated with longer overall survival of patients suffering from adenocarcinoma of the lung. These data indicate that the expression levels of IL-33 are inversely associated with lung cancer progression, consistent with the hypothesis that IL-33 is involved in immune surveillance of NSCLC.

Background and Objectives: The effects of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of uric acid-lowering agents on major clinical outcomes of CKD., Design, Setting, Participants, and Measurements: According to the pre-specified protocol that was registered with PROSPERO (No. CRD42016038030), we searched systematically in MEDLINE, EMBASE, and the Cochrane Library for trials up to February 2016. Prospective, randomized, controlled trials assessing the effects of uric acid-lowering agents on cardiovascular and kidney outcomes in patients with CKD were included. Random-effects analytical methods were used., Results: Sixteen eligible trials were identified, providing data for 1,211 patients with CKD, including 146 kidney failure events and 69 cardiovascular events. Uric acid-lowering therapy produced a 55% relative risk (RR) reduction (95% confidence interval [95% CI], 31-64) for kidney failure events (P < 0.001), and a 60% RR reduction (95% CI, 17-62) for cardiovascular events (P < 0.001), but had no significant effect on the risk of all-cause death (RR, 0.86; 95% CI, 0.50-1.46). The mean differences in rate of decline in the estimated glomerular filtration rate (4.10 mL/min/1.73 m2 per year slower in uric acid-lowering therapy recipients, 95% CI, 1.86-6.35) and the standardized mean differences in the change in proteinuria or albuminuria (-0.23 units of standard deviation greater in uric acid-lowering therapy recipients; 95% CI, -0.43 to -0.04) were also statistically significant., Conclusions: Uric acid-lowering therapy seemed to improve kidney outcomes and reduce the risk of cardiovascular events in adults with CKD.

Objective: Our previous study has found that circulating microRNA (miRNA, or miR) -122, -140-3p, -720, -2861, and -3149 are significantly elevated during early stage of acute coronary syndrome (ACS). This study was conducted to determine the origin of these elevated plasma miRNAs in ACS., Methods: qRT-PCR was performed to detect the expression profiles of these 5 miRNAs in liver, spleen, lung, kidney, brain, skeletal muscles, and heart. To determine their origins, these miRNAs were detected in myocardium of acute myocardial infarction (AMI), and as well in platelets and peripheral blood mononuclear cells (PBMCs, including monocytes, circulating endothelial cells (CECs) and lymphocytes) of the AMI pigs and ACS patients., Results: MiR-122 was specifically expressed in liver, and miR-140-3p, -720, -2861, and -3149 were highly expressed in heart. Compared with the sham pigs, miR-122 was highly expressed in the border zone of the ischemic myocardium in the AMI pigs without ventricular fibrillation (P < 0.01), miR-122 and -720 were decreased in platelets of the AMI pigs, and miR-122, -140-3p, -720, -2861, and -3149 were increased in PBMCs of the AMI pigs (all P < 0.05). Compared with the non-ACS patients, platelets miR-720 was decreased and PBMCs miR-122, -140-3p, -720, -2861, and -3149 were increased in the ACS patients (all P < 0.01). Furthermore, PBMCs miR-122, -720, and -3149 were increased in the AMI patients compared with the unstable angina (UA) patients (all P < 0.05). Further origin identification revealed that the expression levels of miR-122 in CECs and lymphocytes, miR-140-3p and -2861 in monocytes and CECs, miR-720 in monocytes, and miR-3149 in CECs were greatly up-regulated in the ACS patients compared with the non-ACS patients, and were higher as well in the AMI patients than that in the UA patients except for the miR-122 in CECs (all P < 0.05)., Conclusion: The elevated plasma miR-122, -140-3p, -720, -2861, and -3149 in the ACS patients were mainly originated from CECs and monocytes.

Background: Many recent trials have investigated the long-term efficacy and safety of endarterectomy versus stenting in treating patients with carotid artery stenosis. We aimed to determine the long-term comparative efficacy and safety of both procedures by pooling this evidence in a meta-analysis., Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for studies published until May 6, 2016. Randomized controlled trials, which reported outcomes of interest with a median follow-up of at least 4-year, were included., Results: Eight trials involving 7005 patients and 41824 patient-years of follow-up were included. In terms of the periprocedural outcomes, stenting was associated with a lower risk of myocardial infarction (OR: 0.51; 95% CI: 0.33 to 0.80; P = 0.003) but a higher risk of death or stroke (the composite endpoint, OR: 1.76; 95% CI: 1.38 to 2.25; P < 0.0001), a result that was primarily driven by minor stroke (OR: 2.19; 95% CI: 1.59 to 3.01; P < 0.0001), less so by periprocedural death (OR: 1.68; 95% CI: 0.82 to 3.44; P = 0.16) and major stroke (OR: 1.41; 95% CI: 0.95 to 2.09; P = 0.09). In terms of the long-term outcomes, stenting was associated with a higher risk of stroke (OR 1.45; 95% CI: 1.22 to 1.73; P < 0.0001) and the composite outcome of death or stroke (OR 1.25; 95% CI: 1.05 to 1.48; P = 0.01). No difference was found in long-term all-cause mortality between stenting and endarterectomy (OR: 1.09; 95% CI: 0.95 to 1.26; P = 0.21) and restenosis (OR: 1.48 (95% CI: 0.93 to 2.35; P = 0.10). No evidence of significant heterogeneity was found in any of the analyses., Conclusions: Carotid endarterectomy was found to be superior to stenting for short- and long-term outcomes, although endarterectomy was associated with a higher risk of periprocedural myocardial infarction. Carotid endarterectomy should be offered as the first choice for carotid stenosis at present, however, more evidence is needed because rapid progress in concurrent devices and medical treatments is being made.

Background: Recent studies have reported prognosis differences between male and female heart failure patients following cardiac resynchronization therapy (CRT). However, the potential clinical factors that underpin these differences remain to be elucidated., Methods: A meta-analysis was performed to investigate the factors that characterize sex-specific differences following CRT. This analysis involved searching the Medline (Pubmed source) and Embase databases in the period from January 1980 to September 2016., Results: Fifty-eight studies involving 33445 patients (23.08% of whom were women) were analyzed as part of this study. Only patients receiving CRT with follow-up greater than six months were included in our analysis. Compared with males, females exhibited a reduction of 33% (hazard ratio, 0.67; 95% confidence interval, 0.62-0.73; P < 0.0001) and 42% (hazard ratio, 0.58; 95% confidence interval, 0.46-0.74; P = 0.003) in all-cause mortality and heart failure hospitalization or heart failure, respectively. Following a stratified analysis of all-cause mortality, we observed that ischemic causes (p = 0.03) were likely to account for most of the sex-specific differences in relation to CRT., Conclusion: These data suggest that women have a reduced risk of all-cause mortality and heart failure hospitalization or heart failure following CRT. Based on the results from the stratified analysis, we observed more optimal outcomes for females with ischemic heart disease. Thus, ischemia are likely to play a role in sex-related differences associated with CRT in heart failure patients. Further studies are required to determine other indications and the potential mechanisms that might be associated with sex-specific CRT outcomes.

Background: Although pemetrexed plus cis/carboplatin has become the most effective chemotherapy regimen for patients with advanced lung adenocarcinoma, predictive biomarkers are not yet available, and new tools to identify chemosensitive patients who would likely benefit from this treatment are desperately needed. In this study, we constructed and validated predictive peptide models using the serum peptidome profiles of two datasets., Methods: One hundred eighty-three patients treated with first-line platinum-based pemetrexed treatment for advanced lung adenocarcinoma were retrospectively enrolled and randomized into the training (n = 92) or validation (n = 91) set, and pre-treatment serum samples were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and ClinProTools software. Serum peptidome profiles from the training set were used to identify potential predictive peptide biomarkers and construct a predictive peptide model for accurate group discrimination; which was then used to classify validation samples into "good" and "poor" outcome groups. The clinical outcomes of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were analyzed based on the classification result., Results: Eight potential peptide biomarkers were identified. A predictive peptide model based on four distinct m/z features (2,142.12, 3,316.19, 4,281.94, and 6,624.02 Da) was developed based on the clinical outcomes of training set patients after first-line pemetrexed plus platinum treatment. In the validation set, the good group had significantly higher ORR (49.1% vs. 8.3%, P <0.001) and DCR (96.4% vs. 47.2%, P <0.001), and longer PFS (7.3 months vs. 2.7 months, P <0.001) vs. the poor group. However, the model did not predict OS (13.6 months vs. 12.7 months, P = 0.0675)., Conclusion: Our predictive peptide model could predict pemetrexed plus platinum treatment outcomes in patients with advanced lung adenocarcinoma and might thus facilitate appropriate patient selection. Further studies are needed to confirm these findings.

The polyphagous mirid bug Apolygus lucorum (Heteroptera: Miridae) has more than 200 species of host plants and is an insect pest of important agricultural crops, including cotton (Gossypium hirsutum) and mungbean (Vigna radiata). Previous field trials have shown that A. lucorum adults prefer mungbean to cotton plants, indicating the considerable potential of mungbean as a trap crop in cotton fields. However, direct evidence supporting the migration of A. lucorum adults from cotton to mungbean is lacking. We developed a DNA-based polymerase chain reaction (PCR) approach to reveal the movement of A. lucorum between neighboring mungbean and cotton fields. Two pairs of PCR primers specific to cotton or mungbean were designed to target the trnL-trnF region of chloroplast DNA. Significant differences in the detectability half-life (DS50) were observed between these two host plants, and the mean for cotton (8.26 h) was approximately two times longer than that of mungbean (4.38 h), requiring weighted mean calculations to compare the detectability of plant DNA in the guts of field-collected bugs. In field trials, cotton DNA was detected in the guts of the adult A. lucorum individuals collected in mungbean plots, and the cotton DNA detection rate decreased successively from 5 to 15 m away from the mungbean-cotton midline. In addition to the specific detection of cotton- and mungbean-fed bugs, both cotton and mungbean DNA were simultaneously detected within the guts of single individuals caught from mungbean fields. This study successfully established a tool for molecular gut-content analyses and clearly demonstrated the movement of A. lucorum adults from cotton to neighboring mungbean fields, providing new insights into understanding the feeding characteristics and landscape-level ecology of A. lucorum under natural conditions.

Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat expansion within exon1 of the HTT gene. The gene generates two mRNA variants that carry either a short or long 3' untranslated region (3'UTR) while encoding the same protein. It remains unknown whether the two mRNA variants play distinct roles in HD pathogenesis. We found that the long HTT 3'UTR was capable of guiding mRNA to neuronal dendrites, suggesting that some long-form HTT mRNA is transported to dendrites for local protein synthesis. To assay roles of two HTT mRNA variants in cell bodies, we expressed mRNA harboring HTT exon1 containing 23x or 145x CAGs with the short or long 3'UTR. We found that mutant mRNA containing the short 3'UTR produced more protein aggregates and caused more apoptosis in both cultured neurons and HEK293 cells, compared with mutant mRNA containing the long 3'UTR. Although the two 3'UTRs did not affect mRNA stability, we detected higher levels of protein synthesis from mRNA containing the short 3'UTR than from mRNA containing the long 3'UTR. These results indicate that the long HTT 3'UTR suppresses translation. Thus, short-form mutant HTT mRNA will be more efficient in producing toxic protein than its long-form counterpart.

Large outbreaks of hand, foot, and mouth disease (HFMD) have repeatedly occurred in mainland of China since 2007. In this study, we investigated the epidemiological and aetiological characteristics of HFMD in Shijiazhuang City, one of the biggest northern cities of China. A total of 57,173 clinical HFMD cases, including 911 severe and 32 fatal cases, were reported in Shijiazhuang City during 2009-2012. The disease incidence peaked during March-July, with a small increase in the number of cases observed in November of each year. Seventeen potential HFMD-causing enterovirus serotypes were detected, with the most frequent serotypes being EV-A71 and CV-A16. CV-A10 was also a frequently detected causative serotype, and was associated with the second largest number of severe HFMD cases, following EV-A71. Phylogenetic analysis revealed that all EV-A71, CV-A16 and CV-A10 strains from Shijiazhuang City had co-evolved and co-circulated with those from other Chinese provinces. Our findings underscore the need for enhanced surveillance and molecular detection for HFMD, and suggest that EV-A71 vaccination may be an effective intervention strategy for HFMD prevention and vaccines against CV-A10 and CV-A16 are also urgently needed.