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The rail transit vehicle system is an important subsystem with the most frequent operation accidents and the most direct impact on passengers. Based on the particularity of the vehicle system and the complexity of the system, the hierarchical analysis method (AHP) is used to evaluate its safety. High-order judgment matrix often has inconsistency, and the judgment matrix consistency guarantee is the key to the hierarchical analysis method applied. Based on the hierarchical analysis principle, this paper corrects the inconsistency judgment matrix and realizes the optimization calculation based on the genetic algorithm. This paper constructs a vehicle system safety evaluation index system including 26 indexes at three layers and uses the fuzzy comprehensive evaluation method to evaluate the system safety level. The results show that the calculation results based on the improved AHP-GA are significantly better than that based on the conventional AHP method. The comprehensive evaluation conclusion of the case is "average", and the safety level of the vehicle system of the case enterprise needs to be strengthened. [ABSTRACT FROM AUTHOR]

The Kuroshio Current intrudes in the bottom layer of the East China Sea continental shelf from the northeast of Taiwan via two bottom branches named the Nearshore Kuroshio Branch Current (NKBC, along the 60 m isobath) and the Offshore Kuroshio Branch Current (OKBC, along the 100 m isobath). However, knowledge on the macrofaunal responses to these bottom branches is limited. This study examined the variations in the benthic macrofaunal community in a section of the East China Sea under the influence of the NKBC. Seven sites corresponding to three regions (the west, middle and east region) were sampled using an Agassiz trawl net at a monthly rate from February to November 2015 (except in August). A total of 270 macrofaunal species were collected in this study. Cluster analysis and nMDS ordination revealed three communities: the inshore, Kuroshio and offshore communities, roughly corresponding to the west, middle and east of NKBC route. Significant differences in the species composition (one-way PERMANOVA) and diversity indices (one-way ANOVA) among the regions and communities were observed, while no statistically significant difference among the months was detected. The indicator species also varied among the communities, with Sternaspis scutata and Odontamblyopus rubicundus dominating the inshore community, Camatopsis rubida, Schizaster lacunosus and Craspidaster hesperus dominating the Kuroshio community, and Portunus argentatus, Champsodon snyderi and Coelorinchus multispinulosus dominating the offshore community. Some rare species (e.g., Neobythites sivicola) may indicate the passage of the NKBC better than the indicator species. A redundancy analysis was used to describe the relationship between the macrofaunal species and environmental variables in this study. Water depth and turbidity played important roles in the distribution of the macrofauna. S. scutata and O. rubicundus were associated with high turbidity and shallow depth, while Plesionika izumiae and P. argentatus were associated with low turbidity and deep depth. This study outlines the impact of the NKBC on the distribution patterns of the macrofaunal community of the East China Sea. More studies are needed to understand the detailed interactions between macrofauna and the NKBC in the future. [ABSTRACT FROM AUTHOR]

Background: Studies have reported inconsistent results for the existence of an association between polyunsaturated fatty acid (PUFA) intake and risk of lung cancer. The purpose of this study is to summarize the evidence regarding this relationship using a dose response meta-analytic approach. Methodology and Principal Findings: We searched the PubMed, EmBase, and Cochrane Library electronic databases for related articles published through July 2013. Only prospective studies that reported effect estimates with 95% confidence intervals (CIs) of lung cancer incidence for greater than 2 categories of PUFA intake were included. We did random-effects meta-analyses of study-specific incremental estimates to determine the risk of lung cancer associated with a 5 g per day increase in PUFA intake. Overall, we included 8 prospective cohort studies reporting data on 1,268,442 individuals. High PUFA intake had little or no effect on lung cancer risk (risk ratio [RR], 0.91; 95% CI, 0.78–1.06; P = 0.230). Furthermore, the dose-response meta-analysis also suggested that a 5 g per day increase in PUFA has no significant effect on the risk of lung cancer (RR, 0.98; 95%CI: 0.96–1.01; P = 0.142). Finally, the findings of dose response curve suggested that PUFA intake of up to 15 g/d seemed to increase the risk of lung cancer. Furthermore, PUFA intake greater than 15 g/d was associated with a small beneficial effect and borderline statistical significance. Subgroup analyses for 5 g per day increment in PUFA indicated that the protective effect of PUFA was more evident in women (RR, 0.94; 95% CI, 0.87–1.01; P = 0.095) than in men (RR, 1.00; 95% CI, 0.98–1.02; P = 0.784). Conclusion/Significance: Our study indicated that PUFA intake had little or no effect on lung cancer risk. PUFA intake might play an important role in lung cancer prevention in women. [ABSTRACT FROM AUTHOR]

Sirtuin-3 (SIRT3) is a major mitochondrial NAD(+)-dependent deacetylase and plays a key role in the progression and development of human cancers. Although the prognostic and clinicopathological features of SIRT3 expression in various cancers have been investigated by different research groups, however, inconsistent and opposing results can be observed. In this study, we therefore performed a meta-analysis to evaluate the significance of SIRT3 expression in various cancers. Systematic literature searching was performed in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang Data up to November 2015. Total effect analyses and subgroup analyses were performed to evaluate the relationship between SIRT3 expression and overall survival, cancer/non-cancer tissues, lymph node metastasis, pathological differentiation, tumor node metastasis (TNM) stage, tumor size, and gender, in various cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to clarify the risk or hazard association. A total of 14 studies comprising 2165 cancer patients were included to assess the association between SIRT3 immunohistochemical expression and overall survival or clinicopathological characteristics. SIRT3 expression was significantly associated with overall survival in gastric cancer (HR = 0.62, 95% CI = 0.43–0.89, P = 0.009) and hepatocellular carcinoma patients (HR = 0.56, 95% CI = 0.42–0.74, P<0.0001), cancer/non-cancer tissues in hepatocellular carcinoma patients (OR = 0.04, 95% CI = 0.01–0.16, P<0.0001), lymph node metastasis in breast cancer patients (OR = 2.20, 95% CI = 1.49–3.26, P<0.0001), and also pathological differentiation in hepatocellular carcinoma patients (OR = 0.69, 95% CI = 0.48–0.98, P = 0.04) and gastric cancer patients (OR = 0.33, 95% CI = 0.21–0.50, P<0.00001), by subgroup analyses. Furthermore, SIRT3 expression was significantly associated with pathological differentiation in total effect analysis (OR = 0.46, 95% CI = 0.29–0.74, P = 0.001). No detectable relation between SIRT3 expression and other clinicopathological parameters were found. This meta-analysis indicates that SIRT3 expression level is associated with prognostic and clinical features in specific cancers. [ABSTRACT FROM AUTHOR]

Cancer is a serious disease responsible for many deaths every year in both developed and developing countries. One reason is that the mechanisms underlying most types of cancer are still mysterious, creating a great block for the design of effective treatments. In this study, we attempted to clarify the mechanism underlying esophageal cancer by searching for novel genes and chemicals. To this end, we constructed a hybrid network containing both proteins and chemicals, and generalized an existing computational method previously used to identify disease genes to identify new candidate genes and chemicals simultaneously. Based on jackknife test, our generalized method outperforms or at least performs at the same level as those obtained by a widely used method - the Random Walk with Restart (RWR). The analysis results of the final obtained genes and chemicals demonstrated that they highly shared gene ontology (GO) terms and KEGG pathways with direct and indirect associations with esophageal cancer. In addition, we also discussed the likelihood of selected candidate genes and chemicals being novel genes and chemicals related to esophageal cancer. [ABSTRACT FROM AUTHOR]

Modern pollen records have been used to successfully distinguish between specific prairie types in North America. Whether the pollen records can be used to detect the occurrence of Eurasian steppe, or even to further delimit various steppe types was until now unclear. Here we characterized modern pollen assemblages of meadow steppe, typical steppe and desert steppe from eastern Eurasia along an ecological humidity gradient. The multivariate ordination of the pollen data indicated that Eurasian steppe types could be clearly differentiated. The different steppe types could be distinguished primarily by xerophilous elements in the pollen assemblages. Redundancy analysis indicated that the relative abundances of Ephedra, Tamarix, Nitraria and Zygophyllaceae were positively correlated with aridity. The relative abundances of Ephedra increased from meadow steppe to typical steppe and desert steppe. Tamarix and Zygophyllaceae were found in both typical steppe and desert steppe, but not in meadow steppe. Nitraria was only found in desert steppe. The relative abundances of xerophilous elements were greater in desert steppe than in typical steppe. These findings indicate that Eurasian steppe types can be differentiated based on recent pollen rain. [ABSTRACT FROM AUTHOR]

The orchestration of histone modifiers is required to establish the epigenomic status that regulates gene expression during development. Whsc1 (Wolf-Hirschhorn Syndrome candidate 1), a histone H3 lysine 36 (H3K36) trimethyltransferase, is one of the major genes associated with Wolf-Hirshhorn syndrome, which is characterized by skeletal abnormalities. However, the role of Whsc1 in skeletal development remains unclear. Here, we show that Whsc1 regulates gene expression through Runt-related transcription factor (Runx) 2, a transcription factor central to bone development, and p300, a histone acetyltransferase, to promote bone differentiation. Whsc1− / − embryos exhibited defects in ossification in the occipital bone and sternum. Whsc1 knockdown in pre-osteoblast cells perturbed histone modification patterns in bone-related genes and led to defects in bone differentiation. Whsc1 increased the association of p300 with Runx2, activating the bone-related genes Osteopontin (Opn) and Collagen type Ia (Col1a1), and Whsc1 suppressed the overactivation of these genes via H3K36 trimethylation. Our results suggest that Whsc1 fine-tunes the expression of bone-related genes by acting as a modulator in balancing H3K36 trimethylation and histone acetylation. Our results provide novel insight into the mechanisms by which this histone methyltransferase regulates gene expression. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies regarding the existence of an association between folate intake and the risk of breast cancer have been inconsistent. This study aimed to summarize the evidence regarding this relationship using a dose-response meta-analytic approach. Methodology and Principal Findings: We performed electronic searches of the PubMed, EmBase, and Cochrane Library databases to identify studies published through June 2013. Only prospective observational studies that reported breast cancer effect estimates with 95% confidence intervals (CIs) for more than 2 folate intake categories were included. We excluded traditional case-control studies because of possible bias from various confounding factors. Overall, we included 14 prospective studies that reported data on 677,858 individuals. Folate intake had little effect on the breast cancer risk (relative risk (RR) for highest versus lowest category = 0.97; 95% CI, 0.90–1.05; P = 0.451). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of breast cancer (RR = 0.99; 95% CI, 0.98–1.01; P = 0.361). Furthermore, we used restricted cubic splines to evaluate the nonlinear relationship between folate intake and the risk of breast cancer, and discovered a potential J-shaped correlation between folate intake and breast cancer risk (P = 0.007) and revealed that a daily folate intake of 200–320 µg was associated with a lower breast cancer risk; however, the breast cancer risk increased significantly with a daily folate intake >400 µg. Conclusion/Significance: Our study revealed that folate intake had little or no effect on the risk of breast cancer; moreover, a dose-response meta-analysis suggested a J-shaped association between folate intake and breast cancer. [ABSTRACT FROM AUTHOR]

Background: Studies have reported inconsistent results regarding the existence of an association between folate intake and the risk of lung cancer. The purpose of this study was to summarize the evidence from prospective cohort studies regarding this relationship by using a dose-response meta-analytic approach. Methodology and Principal Findings: In September 2013, we performed electronic searches in PubMed, Embase, and the Cochrane Library to identify studies examining the effect of folate intake on the incidence of lung cancer. Only prospective cohort studies that reported the effect estimates about the incidence of lung cancer with 95% confidence intervals (CIs) for more than 2 categories of folate intake were included. Overall, we examined 9 cohort studies reporting the data of 566,921 individuals. High folate intake had little effect on the risk of lung cancer (risk ratio [RR], 0.92; 95% CI, 0.84–1.01; P = 0.076). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of lung cancer (RR, 0.99; 95% CI, 0.97–1.01; P = 0.318). Subgroup analysis suggested that the potential protective effect of low folate intake (100–299 µg/day) was more evident in women than men, while the opposite was true of high folate intake (>400 µg/day). Finally, subgroup analyses of a 100 µg/day increment in folate intake indicated that its potential protective effect was more evident in men than in women. Conclusion/Significance: Our study revealed that folate intake had little or no effect on the risk of lung cancer. Subgroup analyses indicated that an increased folate intake was associated with a reduced risk of lung cancer in men. Furthermore, low folate intake may be a protective factor for women, and high folate intake for men. [ABSTRACT FROM AUTHOR]

The Pinus armandii and Quercus aliena var. acuteserrata mixed forest is one of the major forest types in the Qinling Mountains, China. P. armandii is considered to be a pioneer species during succession and it is usually invaded by late successional Q. aliena var. acuteserrata. However, the mechanism that underlies its invasion remains unclear. In the present study, we tracked seed dispersal of P. armandii and Q. aliena var. acuteserrata using coded plastic tags in the western, middle and eastern Qinling Mountains to elucidate the invasion process in the mixed forests. Our results indicated that the seeds of both P. armandii and Q. aliena var. acuteserrata were removed rapidly in the Qinling Mountains, and there were no differences in the seed removal rates between the two species. There were significant differences in rodent seed-eating and caching strategies between the two tree species. For P. armandii, seeds were more likely to be eaten in situ than those of Q. aliena var. acuteserrata in all plots. By contrast, the acorns of Q. aliena var. acuteserrata were less frequently eaten in situ, but more likely to be removed and cached. Q. aliena var. acuteserrata acorns had significantly longer dispersal distances than P. armandii seeds in all plots. Although P. armandii seeds were less likely to be dispersed into the Q. aliena var. acuteserrata stands, over 30% of the released acorns were transported into the P. armandii stands where they established five seedlings. Based on the coupled recruitment patterns of P. armandii and Q. aliena var. acuteserrata, we suggest that the animal-mediated seed dispersal contributes to the formation of Pinus armandii-Quercus aliena var. acuteserrata forests. [ABSTRACT FROM AUTHOR]

Depression is a type of complex psychiatric disorder with long-term, recurrent bouts, and its etiology remains largely unknown. Here, an integrated approach utilizing 1H NMR and UPLC-Q-TOF/MS together was firstly used for a comprehensive urinary metabonomics study on chronic unpredictable mild stress (CUMS) treated rats. More than twenty-nine metabolic pathways were disturbed after CUMS treatment and thirty-six potential biomarkers were identified by using two complementary analytical technologies. Among the identified biomarkers, nineteen (10, 11,16, 17, 21–25, and 27–36) were firstly reported as potential biomarkers of CUMS-induced depression. Obviously, this paper presented a comprehensive map of the metabolic pathways perturbed by CUMS and expanded on the multitude of potential biomarkers that have been previously reported in the CUMS model. Four metabolic pathways, including valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; tryptophan metabolism; synthesis and degradation of ketone bodies had the deepest influence in the pathophysiologic process of depression. Fifteen potential biomarkers (1–2, 4–6, 15, 18, 20–23, 27, 32, 35–36) involved in the above four metabolic pathways might become the screening criteria in clinical diagnosis and predict the development of depression. Moreover, the results of Western blot analysis of aromatic L-amino acid decarboxylase (DDC) and indoleamine 2, 3-dioxygenase (IDO) in the hippocampus of CUMS-treated rats indicated that depletion of 5-HT and tryptophan, production of 5-MT and altered expression of DDC and IDO together played a key role in the initiation and progression of depression. In addition, none of the potential biomarkers were detected by NMR and LC-MS simultaneously which indicated the complementary of the two kinds of detection technologies. Therefore, the integration of 1H NMR and UPLC-Q-TOF/MS in metabonomics study provided an approach to identify the comprehensive potential depression-related biomarkers and helpful in further understanding the underlying molecular mechanisms of depression through the disturbance of metabolic pathways. [ABSTRACT FROM AUTHOR]

Metabolic pathway analysis, one of the most important fields in biochemistry, is pivotal to understanding the maintenance and modulation of the functions of an organism. Good comprehension of metabolic pathways is critical to understanding the mechanisms of some fundamental biological processes. Given a small molecule or an enzyme, how may one identify the metabolic pathways in which it may participate? Answering such a question is a first important step in understanding a metabolic pathway system. By utilizing the information provided by chemical-chemical interactions, chemical-protein interactions, and protein-protein interactions, a novel method was proposed by which to allocate small molecules and enzymes to 11 major classes of metabolic pathways. A benchmark dataset consisting of 3,348 small molecules and 654 enzymes of yeast was constructed to test the method. It was observed that the first order prediction accuracy evaluated by the jackknife test was 79.56% in identifying the small molecules and enzymes in a benchmark dataset. Our method may become a useful vehicle in predicting the metabolic pathways of small molecules and enzymes, providing a basis for some further analysis of the pathway systems. [ABSTRACT FROM AUTHOR]

Industrial defect detection is a critical aspect of production. Traditional industrial inspection algorithms often face challenges with low detection accuracy. In recent years, the adoption of deep learning algorithms, particularly Convolutional Neural Networks (CNNs), has shown remarkable success in the field of computer vision. Our research primarily focused on developing a defect detection algorithm for the surface of Flexible Printed Circuit (FPC) boards. To address the challenges of detecting small objects and objects with extreme aspect ratios in FPC defect detection for surface, we proposed a guided box improvement approach based on the GA-Faster-RCNN network. This approach involves refining bounding box predictions to enhance the precision and efficiency of defect detection in Faster-RCNN network. Through experiments, we verified that our designed GA-Faster-RCNN network achieved an impressive accuracy rate of 91.1%, representing an 8.5% improvement in detection accuracy compared to the baseline model. [ABSTRACT FROM AUTHOR]

Background: Men who have sex with men (MSM) are at high risk of HIV acquisition. Long-acting injectable-pre-exposure prophylaxis (LAI-PrEP), requiring less frequent dosing, is being studied as an alternative method to daily oral HIV PrEP. With the addition of this potential new prevention method, it expands the scope for a wider user choice and is expected to increase the acceptability and uptake of HIV prevention measures. The aim of our study was to explore the willingness to use LAI-PrEP and associated influential factors. Methods: Participants were recruited from December 2020 to March 2021 through banner advertisements on web- and mobile app-based platforms on Blued, a large gay Chinese social media platform. MSM in our cross-sectional study was HIV-negative and currently lived in mainland China. Participants were asked about their willingness to use LAI-PrEP and reasons why they might be or not be willing to use LAI-PrEP. Multivariable logistic regression was used to analyze the factors associated with the willingness to use LAI-PrEP. Results: In total, 969 participants met the inclusion criteria and finished the survey. Nearly twenty percent (19.5%) of participants had never tested for HIV; 66.8% of MSM had multiple male partners; and 51.6% of MSM engaged in condomless sex with their partner. About three-fifths (66.3%) of MSM were aware of PrEP, and only 3.9% of MSM had used PrEP before. The willingness to use LAI-PrEP among MSM was 74.0% (95% CI: 71.4%-76.6%). MSM with higher education levels were less likely to show a willingness to use LAI-PrEP (AOR = 0.56, 95%CI: 0.38–0.84). Participants who had a history of HIV test (AOR = 1.68, 95%CI: 1.11–2.55), were willing to use daily oral PrEP (AOR = 10.64, 95%CI:7.43–15.21), had multiple male sexual partners (AOR = 1.33, 95%CI:0.93–1.90), who used rush popper(AOR = 1.49, 95%CI:1.05–2.13), and who were aware of PEP (AOR = 1.66, 95%CI: 1.02–2.70) were more likely to show willingness to use LAI-PrEP. Conclusions: In our study, MSM had quite high awareness but low uptake of PrEP. As LAI-PrEP is expected to be approved for use in China in the future, our study of MSM highlights the need for key population-focused education programs about PrEP and healthy sexual behavior. This study also provides some evidence for LAI-PrEP use among the Chinese MSM population in the future. [ABSTRACT FROM AUTHOR]

Vibrio parahaemolyticus is a leading foodborne pathogen in southeastern China. In this study, 105 strains of V. parahaemolyticus were isolated from fresh seafood in 2013 and 2014. The serotypes, virulence-associated genes and sequence types (STs) of these strains were analyzed. 26 defined serotypes were identified and 69 strains (65.7%) had untypeable O or K antigen. 8 strains (7.6%) had the virulence-associated gene tdh and no strain carried the trh gene. 45.7% (48/105) of isolates contained all four T3SS1 genes and 50% (4/8) tdh+ trh- V. parahaemolyticus isolates lacked at least one of the four tested T3SS2α genes. 105 strains could be categorized into 84 STs and only 3 STs (ST3, ST8, ST675) had appeared in clinical strains. V. parahaemolyticus strains from seafood have more diverse and untypeable serotypes, less virulence-associated genes and more STs than strains from clinical sources. [ABSTRACT FROM AUTHOR]

Rbfox1 is a splicing regulator that has been associated with various neurological conditions such as autism spectrum disorder, mental retardation, epilepsy, attention-deficit/hyperactivity disorder and schizophrenia. We show that in adult rodent retinas, Rbfox1 is expressed in all types of retinal ganglion cells (RGCs) and in certain subsets of amacrine cells (ACs), within the inner nuclear (INL) and ganglion cell (GCL) layers. In the INL, all Rbfox1-positive cells were colocalized with GABAergic ACs, however not all GABAergic ACs were immunostained for Rbfox1. In the GCL, a vast majority of GABAergic dACs were Rbfox1-immunopositive. Furthermore, all cholinergic starburst ACs (SACs) in the INL (type a) and in the GCL (type b) were Rbfox1 positive. The expression of Rbfox1 in the retina significantly overlapped with expression of Rbfox2, another member of Rbfox family of proteins. Rbfox2, in addition to RGCs and ACs, was also expressed in horizontal cells. In developing retinas at E12 and E15, Rbfox1 is localized to the cytoplasm of differentiating RGCs and ACs. Between P0 and P5, Rbfox1 subcellular localization switched from cytoplasmic to predominantly nuclear. Downregulation of Rbfox1 in adult Rbfox1loxP/loxP mice had no detectable effect on retinal gross morphology. However, the visual cliff test revealed marked abnormalities of depth perception of these animals. RNA sequencing of retinal transcriptomes of control and Rbfox1 knockout animals identified a number of Rbfox1-regulated genes that are involved in establishing neuronal circuits and synaptic transmission, including Vamp1, Vamp2, Snap25, Trak2, and Slc1A7, suggesting the role of Rbfox1 in facilitating synaptic communications between ACs and RGCs. [ABSTRACT FROM AUTHOR]

Extracellular signal-regulated kinase 8 (ERK8), proposed as a novel potential therapeutic target for cancer, has been implicated in cell transformation, apoptosis, the protection of genomic integrity, and autophagy. To facilitate ERK8 research, a highly specific anti-ERK8 antibody is needed. In this article, we use the Immune Epitope Database and Analysis Resource online tool to predict B-cell epitopes of human ERK8 protein, and choose a 28 aa-peptide sequence to generate the GST-ERK8(28aa) fusion protein as the antigen for developing polyclonal antibody against ERK8. The specificity and sensitivity of anti-ERK8 antibody were robustly validated by immunoblotting, immunocytochemical and immunohistochemical analyses; and we found that both the endogenous and ectopically-expressed human ERK8 proteins can be recognized by our anti-ERK8 antibody. This suggested that our characterized anti-ERK8 antibody will be a valuable tool for the elucidation of the distribution of ERK8 at cellular and histological levels. Finally, our tissue array analysis also demonstrated that the ERK8 protein was localized in both the nucleus and cytoplasm of human lung cancers. [ABSTRACT FROM AUTHOR]

Purpose: Trabecular meshwork (TM) bypass surgeries attempt to enhance aqueous humor outflow (AHO) to lower intraocular pressure (IOP). While TM bypass results are promising, inconsistent success is seen. One hypothesis for this variability rests upon segmental (non-360 degrees uniform) AHO. We describe aqueous angiography as a real-time and physiologic AHO imaging technique in model eyes as a way to simulate live AHO imaging. Methods: Pig (n = 46) and human (n = 6) enucleated eyes were obtained, orientated based upon inferior oblique insertion, and pre-perfused with balanced salt solution via a Lewicky AC maintainer through a 1mm side-port. Fluorescein (2.5%) was introduced intracamerally at 10 or 30 mm Hg. With an angiographer, infrared and fluorescent (486 nm) images were acquired. Image processing allowed for collection of pixel information based on intensity or location for statistical analyses. Concurrent OCT was performed, and fixable fluorescent dextrans were introduced into the eye for histological analysis of angiographically active areas. Results: Aqueous angiography yielded high quality images with segmental patterns (p<0.0001; Kruskal-Wallis test). No single quadrant was consistently identified as the primary quadrant of angiographic signal (p = 0.06–0.86; Kruskal-Wallis test). Regions of high proximal signal did not necessarily correlate with regions of high distal signal. Angiographically positive but not negative areas demonstrated intrascleral lumens on OCT images. Aqueous angiography with fluorescent dextrans led to their trapping in AHO pathways. Conclusions: Aqueous angiography is a real-time and physiologic AHO imaging technique in model eyes. [ABSTRACT FROM AUTHOR]

Reference 1 Du L, Kou Z, Ma C, Tao X, Wang L, Zhao G, et al. (2013) A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines. During figure preparation, the incorrect image was inadvertently used to prepare the Fig 3 hlgG-Fc CPE 4 1.6 m/ml panel. [Extracted from the article]

Current knowledge on responses of aquatic clonal plants to resource availability is largely based on studies manipulating limited resource levels, which may have failed to capture the "big picture" for aquatic clonal plants in response to resource availability. In a greenhouse experiment, we grew the floating clonal plant Spirodela polyrhiza under ten nutrient levels (i.e., 1/64×, 1/32×, 1/16×, 1/8×, 1/4×, 1/2×, 1×, 2×, 4× and 8×full-strength Hoagland solution) and examined their responses in terms of clonal growth, morphology and biomass allocations. The responses of total biomass and number of ramets to nutrient availability were unimodal. A similar pattern was found for frond mass, frond length and frond width, even though area per frond and specific frond area fluctuated greatly in response to nutrient availability. In contrast, the responses of root mass and root length to nutrient availability were U-shaped. Moreover, S. polyrhiza invested more to roots under lower nutrient concentrations. These results suggest that nutrient availability may have distinct influences on roots and fronds of the aquatic clonal plant S. polyrhiza, resulting in a great influence on the whole S. polyrhiza population. [ABSTRACT FROM AUTHOR]

The complex tectonic events and climatic oscillations in the Qinghai-Tibetan Plateau (QTP), the largest and highest plateau in the world, are thought to have had great effects on the evolutionary history of the native plants. Of great interest is to investigate plant population genetic divergence in the QTP and its correlation with the geologic and climatic changes. We conducted a range-wide phylogeographical analysis of M. integrifolia based on the chloroplast DNA (cpDNA) trnL-trnF and trnfM-trnS regions, and defined 26 haplotypes that were phylogenetically divided into six clades dated to the late Tertiary. The six clades correspond, respectively, to highly differentiated population groups that do not overlap in geographic distribution, implying that the mountain ranges acting as corridors or barriers greatly affected the evolutionary history of the QTP plants. The older clade of M. integrifolia only occurs in the southwest of the species' range, whereas the distributions of younger clades extend northeastward in the eastern QTP, suggesting that climatic divergence resulting from the uplift of the QTP triggered the initial divergence of M. integrifolia native to the plateau. Also, the nrDNA ITS region was used to clarify the unexpected phylogenetic relationships of cpDNA haplotypes between M. integrifolia and M. betonicifolia. The topological incongruence between the two phylogenies suggests an ancestral hybridization between the two species. Our study indicates that geographic isolation and hybridization are two important mechanisms responsible for the population differentiation and speciation of Meconopsis, a species-rich genus with complex polyploids. [ABSTRACT FROM AUTHOR]

Purpose: Numerous studies have demonstrated that a variety of systemic inflammatory markers were associated with the survival of different tumors. However, the association between elevated postoperative neutrophil-lymphocyte ratio (postNLR) and long-term outcomes, including overall survival (OS), disease-free survival (DFS), in patients with solid tumors remains controversial. A systematic review was conducted to explore the association between the postNLR and long-term outcomes in solid tumors. Materials and methods: Relevant literature was identified using PubMed, Embase, Web of Science, and the Cochrane Library from the initiation of the databases to October 2020. Data were extracted from included studies reporting hazard ratio (HR) and 95% confidence intervals (CI), and were pooled using generic inverse-variance and random-effects modeling. 25 studies reporting on7539 patients were included in the analysis. Results: Elevated postNLR was associated with poor OS (HR 1.87, 95% CI = 1.53–2.28; P < 0.00001), and worse DFS (HR 1.69, 95% CI = 1.28–2.22; P = 0.0002). Subgroup analyses showed that the trend of the pooled HR for most of the subgroups was not changed, and the heterogeneity of the same tumor type was not obvious. However, there was no correlation between high postNLR obtained within 7days and poor DFS (n = 3, HR 1.25, 95CI% = 0.54–2.88; P = 0.60). Conclusions: Elevated postNLR might be a readily available and inexpensive biomarker for long-term outcomes in solid tumors. Multicenter and prospective studies are needed to explore the impact of the postNLR on the prognosis of solid tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fluctuation range and frequency are two important components of water level fluctuation, but their effects on wetland plants have not been evaluated separately. We subjected eight wetland species to a control treatment with static water level and fluctuation treatments with different ranges or frequencies to examine their effects on plant growth. Acorus calamus, Butomus umbellatus and Iris wilsonii showed high survival rates in all treatments with various fluctuation ranges and frequencies. Their survival rates were higher at the medium fluctuation frequency than at the low and high frequencies, suggesting beneficial effects of the medium frequency. In the experiment comparing the fluctuation ranges, A. calamus and I. wilsonii could maintain the capacity for asexual propagation and accumulate higher biomass compared with the control plants, while biomass of the other six species dramatically decreased. In the experiment comparing fluctuation frequency, species with relatively high survival rates (≥ 50%) maintained or increased the capacity of asexual propagation, and A. calamus and I. wilsonii allocated relatively more biomass to roots, which may enhance plant growth and survival. In contrast, these species did not show increased biomass allocation to shoots in response to both fluctuation range and frequency, presumably because shoots are prone to mechanical damage caused by streaming floodwater. Taken together, biomass accumulation in roots rather than in shoots and the ability to asexually propagate are important for the survival of these species during water fluctuation. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that vitamin D is associated with cardiovascular disease (CVD), however, the relationship between vitamin D levels and CVD risk is still unclear. The purpose of this study was to assess the relationship of serum concentration of 25-hydroxyvitamin D (25(OH)D) with CVD in rural residents of Henan province of China. Basic information and medical history were gathered through face-to-face surveys from July 2013 to August 2015, and biochemical indicators were gathered in a laboratory setting. Logistic and restricted cubic splines regression analyses were used to estimate odd ratios (ORs) and 95% confidence intervals (95%CI) of CVD. A total of 1078 participants were included, the mean serum 25(OH)D concentration was determined to be 25 ± 18 ng/ml, with 54.45% of the participants presenting vitamin D deficiency [25(OH)D < 20 ng/mL]. Moreover, the prevalence of CVD was 59.28% in the vitamin D deficient group, which was higher than in the insufficient (48.55%) and sufficient groups (52.78%). After adjusting for potential confounders, compared with the deficient group, the ORs (95%CI) of CVDs were 0.68 (0.50, 0.91) in the insufficient group and 0.81 (0.56, 1.16) in the sufficient group. A nonlinear (U-shaped) association was observed between the risk of CVD and 25(OH)D concentration. Further research suggested that the risk of CVD was higher in males than in females. In conclusion, a U-shape association between serum levels of 25(OH)D and the risk of CVD was identified in our study, suggesting a nonlinear relationship between vitamin D with the prevalence of CVD. [ABSTRACT FROM AUTHOR]

Either metformin or liraglutide has been reported to have anti-tumor effects on pancreatic cancer cells. However, it is not clear whether their combined treatment has additive or synergistic anti-tumor effects on pancreatic cancer cells. In this study, the human pancreatic cancer cell line MiaPaca-2 was incubated with liraglutide and/or metformin. The cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and wound-healing and transwell migration assays were used to detect cell viability, clonogenic survival, cell cycle and cell migration, respectively. RT-PCR and western blot analyses were used to determine the mRNA and protein levels of related molecules. Results showed that combination treatment with liraglutide (100 nmol/L) and metformin (0.75 mmol/L) significantly decreased cell viability and colony formation, caused cell cycle arrest, upregulated the level of pro-apoptotic proteins Bax and cleaved caspase-3, and inhibited cell migration in the cells, although their single treatment did not exhibit such effects. Combination index value for cell viability indicated a synergistic interaction of liraglutide and metformin. Moreover, the combined treatment with liraglutide and metformin could activate the phosphorylation of AMP-activated protein kinase (AMPK) more potently than their single treatment in the cells. These results suggest that liraglutide in combination with metformin has a synergistic anti-tumor effect on the pancreatic cancer cells, which may be at least partly due to activation of AMPK signaling. Our study provides new insights into the treatment of patients with type 2 diabetes and pancreatic cancer. [ABSTRACT FROM AUTHOR]

The frequency of soil drying–rewetting cycles is predicted to increase under future global climate change, and arbuscular mycorrhizal fungi (AMF) are symbiotic with most plants. However, it remains unknown how AMF affect plant growth under different frequencies of soil drying–rewetting cycles. We subjected a clonal wetland plant Phragmites australis to three frequencies of drying-rewetting cycles (1, 2, or 4 cycles), two nutrient treatments (with or without), and two AMF treatments (with or without) for 64 days. AMF promoted the growth of P. australis, especially in the 2 cycles of the drying-rewetting treatment. AMF had a significant positive effect on leaf mass and number of ramets in the 2 cycles of the drying-rewetting treatment with nutrient addition. In the 2 cycles of drying-rewetting treatment without nutrient addition, AMF increased leaf area and decreased belowground to aboveground biomass ratio. These results indicate that AMF may assist P. australis in coping with medium frequency of drying-rewetting cycles, and provide theoretical guidance for predicting how wetland plants respond to future global climate change. [ABSTRACT FROM AUTHOR]

Synthesizing polycationic polymers directly from existing drugs overcomes the drug-loading limitations often associated with pharmacologically inert nanocarriers. We recently described nanocarriers formed from a first-generation polyamine analogue, bis(ethyl)norspermine (BENSpm), that could simultaneously target polyamine metabolism while delivering therapeutic nucleic acids. In the current study, we describe the synthesis and evaluation of self-immolative nanocarriers derived from the second-generation polyamine analogue PG-11047. Polyamines are absolutely essential for proliferation and their metabolism is frequently dysregulated in cancer. Through its effects on polyamine metabolism, PG-11047 effectively inhibits tumor growth in cancer cell lines of multiple origins as well as in human tumor mouse xenografts. Promising clinical trials have been completed verifying the safety and tolerance of this rotationally restricted polyamine analogue. We therefore used PG-11047 as the basis for Nano11047, a biodegradable, prodrug nanocarrier capable of targeting polyamine metabolism. Following exposure of lung cancer cell lines to Nano11047, uptake and intracellular degradation into the parent compound PG-11047 was observed. The release of PG-11047 highly induced the polyamine catabolic enzyme activities of spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX). By contrast, the activity of ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis and a putative oncogene, was decreased. Consequently, intracellular levels of the natural polyamines were depleted concurrent with tumor cell growth inhibition. This availability of Nano11047 as a novel drug form and potential nucleic acid delivery vector will potentially benefit and encourage future clinical studies. [ABSTRACT FROM AUTHOR]

The Hengduan Mountains, with a distinct altitudinal differentiation and strong vertical vegetation zonation, occupy an important position in southwestern China as a global hotspot of biodiversity. Pollen analysis of lake sediments sampled along an altitudinal gradient in this region helps us to understand how this vegetation zonation arose and how it has responded to climate change and human impacts through time. Here we present a ~30-ka pollen record and interpret it in terms of vegetational and climatic change from a 310 cm-long core from Shudu Lake, located in the Hengduan Mountains region. Our results suggest that from 30 to 22 cal. ka BP, the vegetation was dominated by steppe/grassland (comprising mainly Artemisia, Poaceae and Polygonaceae) and broad-leaved forest (primarily Quercus, Betula and Castanopsis) in the lake catchment, reflecting a relatively warm, wet climate early in this phase and slightly warmer, drier conditions late in the phase. The period between 22 and 13.9 cal. ka BP was marked by a large expansion of needle- and broad-leaved mixed forest (Pinus, Abies and Quercus) and a decline in the extent of steppe/grassland, indicating warming, drying climatic conditions followed by a cold, wet period. Between 13.9 and 3 cal. ka BP, steppe/grassland expanded and the area covered by needle- and broad-leaved mixed forest reduced, implying a fluctuating climate dominated by warm and humid conditions. After 3 cal. ka BP, the vegetation was characterized by an increase in needle-leaved forest and reduction in steppe/grassland, suggesting warming and drying climate. A synthesis of palynological investigations from this and other sites suggests that the vegetation succession patterns seen along an altitudinal gradient in northwestern Yunnan since the Late Pleistocene are comparable, but that each site has its own characteristics probably due to the influences of altitude, topography, microclimate and human impact. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the expression pattern and prognostic significance of miR-33a in non-small cell lung cancer (NSCLC) treated with adjuvant chemotherapy. Methods: MiR-33aexpression in NSCLC was analyzed in silico using the GEO database and was subsequently confirmed by quantitative RT-PCR in 147 NSCLC biopsies. Among these, 32 of these biopsies were paired with adjacent non-neoplastic tissues. The survival analysis of NSCLC by Kaplan-Meier estimates was stratified based on miR-33a expression. In addition, multivariate survival analysis in corresponding groups of NSCLC patients was conducted by Cox proportional hazards regression model. Results: The in silico analysis of miR-33a expression in NSCLC resulted to its down-regulation in different tumor types. The expression level of miR-33a was lower in each grade of NSCLC tumor biopsies than in normal lung tissues. Univariate and multivariate survival analysis further established that low miR-33a expression was an important risk factor for overall survival and disease free survival in NSCLC patients. Conclusion: Our study implied that miR-33a expression levels may have an essential role in NSCLC progression, and could act as a specific and sensitive biomarker for NSCLC patients who have undergone adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Plant litter is an indispensable component of constructed wetlands, but how the submergence of plant litter affects their ecosystem functions and services, such as water purification, is still unclear. Moreover, it is also unclear whether the effects of plant litter submergence depend on other factors such as the duration of litter submergence, water source or litter species identity. Here we conducted a greenhouse experiment by submerging the litter of 7 wetland plant species into three types of water substrates and monitoring changes in water nutrient concentrations. Litter submergence affected water quality positively via decreasing the concentration of nitrate nitrogen and negatively via increasing the concentrations of total nitrogen, ammonium nitrogen and total phosphorus. The effects of litter submergence depended on the duration of litter submergence, the water source, the litter species identity, and the plant life form. Different plant species had different effects on the water nutrient concentrations during litter submergence, and the effects of floating plants might be more negative than that of emergent plants. These results are novel evidence of how the submergence of different plant (life form) litter may affect the purification function of constructed wetlands. For water at low eutrophication levels, submerging a relative small amount of plant litter might improve water quality, via benefiting the denitrification process in water. These findings emphasized the management of floating plant litter (a potential removal) during the maintenance of human-controlled wetland ecosystems and provided a potential tool to improve the water quality of constructed wetlands via submerging plant litter of different types. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). However, few studies regarding the epidemiology of hospitalizations for RSV infection have been performed previously in China. Here, we aimed to describe the clinical and epidemiologic characteristics of hospitalized patients with laboratory-confirmed RSV infection in eastern China. Active surveillance for hospitalized ALRI patients using a broad case definition based on symptoms was performed from 2009–2013 in 12 sentinel hospitals in eastern China. Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. From 2009 to 2013, 1046 hospitalized patients with laboratory-confirmed RSV infection were enrolled in this study, and 14.7% of patients had subtype A, 24.2% of patients had subtype B, 23.8% of patients with subtype not performed, and 37.3% of patients had RSV coinfections with other viruses. RSV and influenza coinfections (33.3%) were the most common coinfections noted in this study. Moreover, young children aged <5 years (89.1%, 932/1046), particularly young infants aged <1 year (43.3%, 453/1046), represented the highest proportion of patients with RSV infections. In contrast, older adults aged ≥60 years (1.1%, 12/1046) represented the lowest proportion of patients with RSV infections among enrolled patients. The peak RSV infection period occurred mainly during autumn and winter, and 57% and 66% of patients exhibited symptoms such as fever (body temperature ≥38°C) and cough separately. Additionally, only a small number of patients were treated with broad-spectrum antiviral drugs, and most of patients were treated with antimicrobial drugs that were not appropriate for RSV infection. RSV is a leading viral pathogen and a common cause of viral infection in young children aged <5 years with ALRIs in eastern China. Effective vaccines and antiviral agents targeting RSV are needed to mitigate its large public health impact. [ABSTRACT FROM AUTHOR]

Depressive symptoms have become the most important global public health issue. Iron plays an important role in brain function, cognition, and behavior, and its impacts on depressive symptoms may be multifactorial with both positive and negative effects. Previous observational studies focusing on the association between iron status and depressive symptoms showed inconsistent results. Ferritin is a ubiquitous intracellular protein that can store and release iron and is widely used as a clinical biomarker to evaluate iron status. We performed a cross-sectional study to examine the relationship between serum ferritin and depressive symptoms among 3,839 subjects who were from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort. Depressive symptoms were assessed using the Chinese version of 20-item self-rating Depression Scale (SDS) with 4 cutoffs (40, 45, 48 and 50) to indicate elevated depressive symptoms (40 was the primary cut-off). The prevalence of depressive symptoms was 36.5%, 17.6%, 11.0% and 7.0% for SDS ≥40, ≥45, ≥48 and ≥50, respectively. With the primary cut-off point of 40, multiple potential confounding factors were adjusted and the odds ratios (95% confidence interval) of having elevated depressive symptoms by quartiles of serum ferritin concentrations were 1.00 (reference), 1.10 (0.91, 1.34), 0.81 (0.66, 1.01) and 1.02 (0.81, 1.28) for the first, second, third and fourth quartile, respectively (P for trend = 0.76). Similar relations were observed with the use of other cut-offs as a definition of depressive symptoms. In conclusion, there is no significant relationship between serum ferritin concentrations and depressive symptoms among Chinese adults. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher’s exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral-infection that may trigger VKH pathogenesis in genetically susceptible individuals, such as HLA-DR4 carriers. [ABSTRACT FROM AUTHOR]

Background: Semen is a major vehicle for HIV transmission. Prostatic acid phosphatase (PAP) fragments, such as PAP248-286, in human semen can form amyloid fibrils to enhance HIV infection. Other endogenous or exogenous factors present during sexual intercourse have also been reported to promote the formation of seminal amyloid fibrils. Methodology and Principal Findings: Here, we demonstrated that a synthetic 15-residue peptide derived from the HIV-1 gp120 coreceptor-binding region, designated enhancing peptide 2 (EP2), can rapidly self-assemble into nanofibers. These EP2-derivated nanofibers promptly accelerated the formation of semen amyloid fibrils by PAP248-286, as shown by Thioflavin T (ThT) and Congo red assays. The amyloid fibrils presented similar morphology, assessed via transmission electron microscopy (TEM), in the presence or absence of EP2. Circular dichroism (CD) spectroscopy revealed that EP2 accelerates PAP248-286 amyloid fibril formation by promoting the structural transition of PAP248-286 from a random coil into a cross-β-sheet. Newly formed semen amyloid fibrils effectively enhanced HIV-1 infection in TZM-bl cells and U87 cells by promoting the binding of HIV-1 virions to target cells. Conclusions and Significance: Nanofibers composed of EP2 promote the formation of PAP248-286 amyloid fibrils and enhance HIV-1 infection. [ABSTRACT FROM AUTHOR]

Background: A novel avian-origin influenza A(H7N9) caused a major outbreak in Mainland China in early 2013. Exposure to live poultry was believed to be the major route of infection. There are limited data on how the general public changes their practices regarding live poultry exposure in response to the early outbreak of this novel influenza and the frequency of population exposure to live poultry in different areas of China. Methodology: This study investigated population exposures to live birds from various sources during the outbreak of H7N9 in Guangzhou city, China in 2013 and compared them with those observed during the 2006 influenza A(H5N1) outbreak. Adults were telephone-interviewed using two-stage sampling, stratified by three residential areas of Guangzhou: urban areas and two semi-rural areas in one of which (Zengcheng) A(H7N9) virus was detected in a chicken from wet markets. Logistic regression models were built to describe practices protecting against avian influenza, weighted by age and gender, and then compare these practices across residential areas in 2013 with those from a comparable 2006 survey. Principal Findings: Of 1196 respondents, 45% visited wet markets at least daily and 22.0% reported buying live birds from wet markets at least weekly in April-May, 2013, after the H7N9 epidemic was officially declared in late March 2013. Of those buying live birds, 32.3% reported touching birds when buying and 13.7% would slaughter the poultry at home. Although only 10.1% of the respondents reported raising backyard birds, 92.1% of those who did so had physical contact with the birds they raised. Zengcheng respondents were less likely to report buying live birds from wet markets, but more likely to buy from other sources when compared to urban respondents. Compared with the 2006 survey, the prevalence of buying live birds from wet markets, touching when buying and slaughtering birds at home had substantially declined in the 2013 survey. Conclusion/Significance: Although population exposures to live poultry were substantially fewer in 2013 compared to 2006, wet markets and backyard poultry remained the two major sources of live bird exposures for the public in Guangzhou in 2013. Zengcheng residents seemed to have reduced buying live birds from wet markets but not from other sources in response to the detection of H7N9 virus in wet markets. [ABSTRACT FROM AUTHOR]

Vegetative propagule pressure may affect the establishment and structure of aquatic plant communities that are commonly dominated by plants capable of clonal growth. We experimentally constructed aquatic communities consisting of four submerged macrophytes (Hydrilla verticillata, Ceratophyllum demersum, Elodea nuttallii and Myriophyllum spicatum) with three levels of vegetative propagule pressure (4, 8 and 16 shoot fragments for communities in each pot) and two levels of water depth (30 cm and 70 cm). Increasing vegetative propagule pressure and decreasing water level significantly increased the growth of the submerged macrophyte communities, suggesting that propagule pressure and water depth should be considered when utilizing vegetative propagules to re-establish submerged macrophyte communities in degraded aquatic ecosystems. However, increasing vegetative propagule pressure and decreasing water level significantly decreased evenness of the submerged macrophyte communities because they markedly increased the dominance of H. verticillata and E. nuttallii, but had little impact on that of C. demersum and M. spicatum. Thus, effects of vegetative propagule pressure and water depth are species-specific and increasing vegetative propagule pressure under lower water level can facilitate the establishment success of submerged macrophyte communities. [ABSTRACT FROM AUTHOR]

Thuja, a genus of Cupressaceae comprising five extant species, presently occurs in both East Asia (3 species) and North America (2 species) and has a long fossil record from Paleocene to Pleistocene in the Northern Hemisphere. Two distinct hypotheses have been proposed to account for the origin and present distribution of this genus. Here we recognize and describe T. sutchuenensis Franch., a new fossil Thuja from the late Pliocene sediments of Zhangcun, Shanxi, North China, based on detailed comparisons with all living species and other fossil ones, integrate the global fossil records of this genus plotted in a set of paleomaps from different time intervals, which show that Thuja probably first appeared at high latitudes of North America in or before the Paleocene. This genus reached Greenland in the Paleocene, then arrived in eastern Asia in the Miocene via the land connection between East Asia and western North America. In the late Pliocene, it migrated into the interior of China. With the Quaternary cooling and drying, Thuja gradually retreated southwards to form today’s disjunctive distribution between East Asia and North America. [ABSTRACT FROM AUTHOR]

To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC) patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. TGFβR2 expression was also significantly correlated with other clinical parameters such as tumor differentiation, invasion of lung membrane, and chemotherapy. Moreover, overall survival (OS) and disease free survival (DFS) was increased in patients with low TGFβR2 expressing NSCLC and who had undergone chemotherapy. Thus, high expression of TGFβR2 is a significant risk factor for decreased OS and DFS in NSCLC patients. Thus, TGFβR2 is a potential prognostic tumor biomarker for chemotherapy. [ABSTRACT FROM AUTHOR]

Flowering is an essential stage of plant growth and development. The successful transition to flowering not only ensures the completion of plant life cycles, it also serves as the basis for the production of economically important seeds and fruits. NSTANS (CO) and LOWERING LOCUS (FT) are two genes playing critical roles in flowering time control in Arabidopsis. Through homology-based cloning and rapid-amplifications of cDNA ends (RACE), we obtained full-lengths cDNA sequences of runus ersica (PpCO) and runus ersica (PpFT) from peach (Prunus persica (L.) Batsch) and investigated their functions in flowering time regulation. PpCO and PpFT showed high homologies to Arabidopsis CO and FT at DNA, mRNA and protein levels. We showed that PpCO and PpFT were nucleus-localized and both showed transcriptional activation activities in yeast cells, consistent with their potential roles as transcription activators. Moreover, we established that the over-expression of PpCO could restore the late flowering phenotype of the Arabidopsis co-2 mutant, and the late flowering defect of the Arabidopsis ft-1 mutant can be rescued by the over-expression of PpFT, suggesting functional conservations of CO and FT genes in peach and Arabidopsis. Our results suggest that PpCO and PpFT are homologous genes of CO and FT in peach and they may function in regulating plant flowering time. [ABSTRACT FROM AUTHOR]

To determine the proteomic-level responses of drought tolerant wild wheat (Triticum boeoticum), physiological and comparative proteomic analyses were conducted using the roots and the leaves of control and short term drought-stressed plants. Drought stress was imposed by transferring hydroponically grown seedlings at the 3-leaf stage into 1/2 Hoagland solution containing 20% PEG-6000 for 48 h. Root and leaf samples were separately collected at 0 (control), 24, and 48 h of drought treatment for analysis. Physiological analysis indicated that abscisic acid (ABA) level was greatly increased in the drought-treated plants, but the increase was greater and more rapid in the leaves than in the roots. The net photosynthetic rate of the wild wheat leaves was significantly decreased under short-term drought stress. The deleterious effects of drought on the studied traits mainly targeted photosynthesis. Comparative proteomic analysis identified 98 and 85 differently changed protein spots (DEPs) (corresponding to 87 and 80 unique proteins, respectively) in the leaves and the roots, respectively, with only 6 mutual unique proteins in the both organs. An impressive 86% of the DEPs were implicated in detoxification and defense, carbon metabolism, amino acid and nitrogen metabolism, proteins metabolism, chaperones, transcription and translation, photosynthesis, nucleotide metabolism, and signal transduction. Further analysis revealed some mutual and tissue-specific responses to short-term drought in the leaves and the roots. The differences of drought-response between the roots and the leaves mainly included that signal sensing and transduction-associated proteins were greatly up-regulated in the roots. Photosynthesis and carbon fixation ability were decreased in the leaves. Glycolysis was down-regulated but PPP pathway enhanced in the roots, resulting in occurrence of complex changes in energy metabolism and establishment of a new homeostasis. Protein metabolism was down-regulated in the roots, but enhanced in the leaves. These results will contribute to the existing knowledge on the complexity of root and leaf protein changes that occur in response to drought, and also provide a framework for further functional studies on the identified proteins. [ABSTRACT FROM AUTHOR]

Proper leaf development is essential for plant growth and development, and leaf morphogenesis is under the control of intricate networks of genetic and environmental cues. We are interested in dissecting these regulatory circuits genetically and report here the isolation of two Arabidopsis dominant mutants, abnormal shoot5-1D (abs5-1D) and abs7-1D identified through activation tagging screens. Both abs5-1D and abs7-1D display an intriguing upwardly curly leaf phenotype. Molecular cloning showed that the elevated expression of a bHLH transcription factor ABS5/T5L1/bHLH30 or a MYB transcription factor ABS7/MYB101 is the cause for the abnormal leaf phenotypes found in abs5-1D or abs7-1D, respectively. Protoplast transient expression assays confirmed that both ABS5/T5L1 and ABS7/MYB101 are targeted to the nucleus. Interestingly, the expression domains of auxin response reporter DR5::GUS were abnormal in leaves of abs5-1D and ABS5/T5L1 over-expression lines. Moreover, cotyledon venation analysis showed that more areoles and free-ending veins are formed in abs5-1D. We found that the epidermis-specific expressions of ABS5/T5L1 or ABS7/MYB101 driven by the Arabidopsis Meristem Layer 1 promoter (PAtML1) were sufficient to recapitulate the curly leaf phenotype of abs5-1D or abs7-1D. In addition, PAtML1::ABS5 lines exhibited similar changes in DR5::GUS expression patterns as those found in 35S-driven ABS5/T5L1 over-expression lines. Our work demonstrated that enhanced expressions of two transcription factors, ABS5/T5L1 and ABS7/MYB101, are able to alter leaf lamina development and reinforce the notion that leaf epidermis plays critical roles in regulating plant organ morphogenesis. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs) investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base. Methodology and Principal Findings: In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR) was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE) occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI) occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93–1.03; P = 0.37), total mortality (RR, 1.01; 95% CI: 0.97–1.05; P = 0.77), cardiac death (RR, 0.96; 95% CI: 0.90–1.02; P = 0.21), MI (RR, 0.99; 95% CI: 0.93–1.06; P = 0.82), or stroke (RR, 0.94; 95% CI: 0.85–1.03; P = 0.18). Conclusion/Significance: B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke. [ABSTRACT FROM AUTHOR]

Usher syndrome is an autosomal recessive disease characterized by sensorineural hearing loss, age-dependent retinitis pigmentosa (RP), and occasionally vestibular dysfunction. The most severe form is Usher syndrome type 1 (USH1). Mutations in the MYO7A gene are responsible for USH1 and account for 29–55% of USH1 cases. Here, we characterized a Chinese family (no. 7162) with USH1. Combining the targeted capture of 131 known deafness genes, next-generation sequencing, and bioinformatic analysis, we identified two deleterious compound heterozygous mutations in the MYO7A gene: a reported missense mutation c.73G>A (p.G25R) and a novel nonsense mutation c.462C>A (p.C154X). The two compound variants are absent in 219 ethnicity-matched controls, co-segregates with the USH clinical phenotypes, including hearing loss, vestibular dysfunction, and age-dependent penetrance of progressive RP, in family 7162. Therefore, we concluded that the USH1 in this family was caused by compound heterozygous mutations in MYO7A. [ABSTRACT FROM AUTHOR]

Novel hybrid magnetic cross-linked enzyme aggregates of phenylalanine ammonia lyase (HM-PAL-CLEAs) were developed by co-aggregation of enzyme aggregates with magnetite nanoparticles and subsequent crosslinking with glutaraldehyde. The HM-PAL-CLEAs can be easily separated from the reaction mixture by using an external magnetic field. Analysis by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) indicated that PAL-CLEAs were inlayed in nanoparticle aggregates. The HM-PAL-CLEAs revealed a broader limit in optimal pH compared to free enzyme and PAL-CLEAs. Although there is no big difference in Km of enzyme in CLEAs and HM-PAL-CLEAs, Vmax of HM-PAL-CLEAs is about 1.75 times higher than that of CLEAs. Compared with free enzyme and PAL-CLEAs, the HM-PAL-CLEAs also exhibited the highest thermal stability, denaturant stability and storage stability. The HM-PAL-CLEAs retained 30% initial activity even after 11 cycles of reuse, whereas PAL-CLEAs retained 35% of its initial activity only after 7 cycles. These results indicated that hybrid magnetic CLEAs technology might be used as a feasible and efficient solution for improving properties of immobilized enzyme in industrial application. [ABSTRACT FROM AUTHOR]

Background: The incidence and burden of stroke in China is increasing rapidly. However, little is known about trends in mortality during stroke hospitalization. The objectives of this study were to assess trends of in-hospital mortality among patients with stroke and explore influence factors of in-hospital death after stroke in China. Methods: 109 grade III class A hospitals were sampled by multistage stratified cluster sampling. All patients admitted to hospitals between 2007 and 2010 with a discharge diagnosis of stroke were included. Trends in in-hospital mortality among patients with stroke were assessed. Influence factors of in-hospital death after stroke were explored using multivariable logistic regression. Results: Overall stroke hospitalizations increased from 79,894 in 2007 to 85,475 in 2010, and in-hospital mortality of stroke decreased from 3.16% to 2.30% (P<0.0001). The percentage of severe patients increased while odds of mortality (2010 versus 2007) decreased regardless of stroke type: subarachnoid hemorrhage (OR 0.792, 95% CI = 0.636 to 0.987), intracerebral hemorrhage (OR 0.647, 95% CI = 0.591 to 0.708), and ischemic stroke (OR 0.588, 95% CI = 0.532 to 0.649). In multivariable analyses, older age, male, basic health insurance, multiple comorbidities and severity of disease were linked to higher odds of in-hospital mortality. Conclusions: The mortality of stroke hospitalizations decreased likely reflecting advancements in stroke care and prevention. Decreasing of mortality with increasing of severe stroke patients indicated that we should pay more attention to rehabilitation and life quality of stroke patients. Specific individual and hospital-level characteristics may be targets for facilitating further declines. [ABSTRACT FROM AUTHOR]

TECTA-related deafness can be inherited as autosomal-dominant nonsyndromic deafness (designated DFNA) or as the autosomal-recessive version. The α-tectorin protein, which is encoded by the TECTA gene, is one of the major components of the tectorial membrane in the inner ear. Using targeted DNA capture and massively parallel sequencing (MPS), we screened 42 genes known to be responsible for human deafness in a Chinese family (Family 3187) in which common deafness mutations had been ruled out as the cause, and identified a novel mutation, c.257–262CCTTTC>GCT (p. Ser86Cys; p. Pro88del) in exon 3 of the TECTA gene in the proband and his extended family. All affected individuals in this family had moderate down-sloping hearing loss across all frequencies. To our knowledge, this is the second TECTA mutation identified in Chinese population. This study demonstrates that targeted genomic capture, MPS, and barcode technology might broaden the availability of genetic testing for individuals with undiagnosed DFNA. [ABSTRACT FROM AUTHOR]

Background: Although international guideline recommended routine intracranial pressure (ICP) monitoring for patients with severe traumatic brain injury(TBI), there were conflicting outcomes attributable to ICP monitoring according to the published studies. Hence, we conducted a meta-analysis to evaluate the efficacy and safety of ICP monitoring in patients with TBI. Methods: Based on previous reviews, PubMed and two Chinese databases (Wangfang and VIP) were further searched to identify eligible studies. The primary outcome was mortality. Secondary outcomes included unfavourable outcome, adverse events, length of ICU stay and length of hospital stay. Weighted mean difference (WMD), odds ratio (OR) and 95% confidence intervals (CIs) were calculated and pooled using fixed-effects or random-effects model. Results: two randomized controlled trials (RCTs) and seven cohort studies involving 11,038 patients met the inclusion criteria. ICP monitoring was not associated with a significant reduction in mortality (OR, 1.16; 95% CI, 0.87–1.54), with substantial heterogeneity (I2 = 80%, P<0.00001), which was verified by the sensitivity analyses. No significant difference was found in the occurrence of unfavourable outcome (OR, 1.40; 95% CI, 0.99–1.98; I2 = 4%, P = 0.35) and advese events (OR, 1.04; 95% CI, 0.64–1.70; I2 = 78%, P = 0.03). However, we should be cautious to the result of adverse events because of the substantial heterogeneity in the comparison. Furthermore, longer ICU and hospital stay were the consistent tendency according to the pooled studies. Conclusions: No benefit was found in patients with TBI who underwent ICP monitoring. Considering substantial clinical heterogeneity, further large sample size RCTs are needed to confirm the current findings. [ABSTRACT FROM AUTHOR]

An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367–606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients’ lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection. [ABSTRACT FROM AUTHOR]

Background: Plesiomonas shigelloides can cause gastroenteritis and extra-intestinal diseases in humans. However, the prevalence of P. shigelloides infections has not been investigated in China. Methods: Consecutive fecal specimens from outpatients with acute diarrhea and non-diarrheal patients at nine sentinel hospitals in southeast China were collected from March 2010 to May 2012. Bacterial pathogens were detected by culture, and P. shigelloides isolates were subjected to antimicrobial susceptibility testing. We also retrospectively reviewed the hospital microbiology laboratory and infection-control databases for all P. shigelloides isolates identified from 2001–2012 at our institution in addition to data on the patients' clinical and demographic characteristics. Results: A total of 3,536 outpatients with acute diarrhea were enrolled in the study. P. shigelloides was isolated from 104 (2.9%) patients and accounted for 7.3% of bacterial isolates. Single-pathogen infections with P. shigelloides were present in 76 (73.1%) patients. No strain of P. shigelloides was isolated from the 478 non-diarrheal patients. Based on 444,684 nonfecal specimens, eight patients developed P. shigelloides-related extra-intestinal infections over the 12-year period. All eight patients had underlying diseases, including four with biliary tract diseases and three with liver diseases. Six cases were classified as nosocomial, and five cases were polymicrobial. P. shigelloides was sensitive to most antimicrobial drugs, except ampicillin. Conclusions: In southeast China, P. shigelloides has significant clinical relevance, although the isolation rate is low. [ABSTRACT FROM AUTHOR]