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Due to the high incidence of smartphone addiction and its harmful effects on health in recent years, it has received widespread attention from society. This study aims to examine the association between smartphone addiction and sleep quality among college students, and assess the correlation with physical exercise in a non-interventional, cross-sectional study design. The study utilized data from the 2022 Chinese College Health Tracking Survey. A total of 4670 students participated in and completed the questionnaire. The test tools comprised the smartphone addiction tendency scale, the Pittsburgh Sleep Quality Index, and the physical activity rating scale. The average score of the college students' smartphone addiction was 39.230±14.931, and the proportion of college students with average and or very poor sleep quality was 52.6%. Mobile phone addiction among college students is negatively correlated with physical exercise (r = -0.101, p

Breast cancer (BC) cells have a high risk of metastasis due to epithelial-mesenchymal transition (EMT). Palbociclib (CDK4/6 inhibitor) is an approved drug for BC treatment. However, the drug resistance and metastasis can impair the treatment outcome of Palbociclib. Understanding the mechanisms of EMT and Palbociclib drug resistance in BC is conducive to the formulation of novel therapeutic strategy. Here, we investigated the role of circHIAT1/miR-19a-3p/CADM2 axis in modulating EMT and Palbociclib resistance in BC. circHIAT1 and CADM2 were down-regulated in BC tissues and cell lines, and miR-19a-3p showed an up-regulation. circHIAT1 could interact with miR-19a-3p and suppress its activity, while miR-19a-3p functioned to negatively regulate CADM2. Forced over-expression of circHIAT1 could impaired the EMT status and migratory ability of BC cells, and this effect was inhibited by miR-19a-3p mimic. In addition, we also generated Palbociclib resistant BC cells, and showed that circHIAT1 and CADM2 were down-regulated in the resistant BC cells while miR-19a-3p showed an up-regulation. Forced circHIAT1 over-expression re-sensitized BC cells to Palbociclib treatment. Quercetin, a bioactive flavonoid, could suppressed the migration and invasion of BC cells, and re-sensitized BC cells to Palbociclib. The anti-cancer effect of quercetin could be attributed to its regulatory effect on circHIAT1/miR-19a-3p/CADM2 axis. In vivo tumorigenesis experiment further revealed that quercetin administration enhanced the anti-cancer effect of Palbociclib, an effect was dependent on the up-regulation of circHIAT1 by quercetin. In summary, this study identified quercetin as a potential anti-cancer compound to reverse Palbociclib resistance and impair EMT in BC cells by targeting circHIAT1/miR-19a-3p/CADM2 axis.

In this paper, we focus on a dynamic Cournot game in the market with a nonlinear (isoelastic) demand function. In our model, there are N competing firms featured by nonlinear cost functions, which enhances our model's resemblance to real-world scenarios. Firstly, we focus on the homogeneous case where firms' marginal costs change at equal rates. We establish analytical expressions of the market supply at equilibrium and perform comparative static analysis. In addition, we investigate the local stability under different economies of scale and show that there could be multiple stable equilibria if firms face economies of scale. The heterogeneous case where firms' marginal costs change at distinct rates is much more complex, thus we investigate the duopoly game with only two firms involved. Methods of symbolic computations such as triangular decomposition and partial cylindrical algebraic decomposition are employed in the analytical investigations of the equilibrium, which is nearly impossible by using the pencil-and-paper approach since the closed-form equilibrium is quite complicated. According to the computational results, we derive that two stable positive equilibria may coexist if both firms face economies of scale. Additionally, we conduct preliminary numerical simulations and find two different types of complex dynamics of the model considered in this paper: complex trajectories such as periodic and chaotic orbits may appear; the topological structure of the basins of attraction may be complex.

Single image raindrop removal aims at recovering high-resolution images from degraded ones. However, existing methods primarily employ pixel-level supervision between image pairs to learn spatial features, thus ignoring the more discriminative frequency information. This drawback results in the loss of high-frequency structures and the generation of diverse artifacts in the restored image. To ameliorate this deficiency, we propose a novel frequency-oriented Hierarchical Fusion Network (HFNet) for raindrop image restoration. Specifically, to compensate for spatial representation deficiencies, we design a dynamic adaptive frequency loss (DAFL), which allows the model to adaptively handle the high-frequency components that are difficult to recover. To handle spatially diverse raindrops, we propose a hierarchical fusion network to efficiently learn both contextual information and spatial features. Meanwhile, a calibrated attention mechanism is proposed to facilitate the transfer of valuable information. Comparative experiments with existing methods indicate the advantages of the proposed algorithm.

The automatic cutting of coal and rock surface morphology modeling based on the actual geological environment of coal mine underground excavation and mining is of great significance for improving the surface quality of coal and rock after cutting and enhancing the safety and stability of advanced support. To this end, using the principle of coordinate transformation, the kinematic trajectory of the cutting head of the tunneling machine is established, and the contour morphology of the cutting head under variable cutting technology is obtained. Then, based on the regenerative vibration theory of the cutting head, a dynamic model of the cutting head coal wall is established, and the coordinate relationship of the cutting head in the tunnel coordinate system under vibration induction is analyzed. Based on fractal theory and Z-MAP method, a simulation method for the surface morphology of coal and rock after cutting is proposed, which is driven by the cutting trajectory Under the coupling effect of cutting vibration induction and random fragmentation of coal and rock, simulation of the surface morphology of comprehensive excavation tunnels was conducted, and relevant experiments were conducted to verify the results. A 1:3 similarity experimental model of EBZ160 tunneling machine was used to build a cutting head coal and rock system cutting experimental platform for comparative experiments of cutting morphology. Furthermore, statistical methods were used to compare and evaluate the simulated roof with the actual roof. The results show that the relative errors between the maximum range of peaks and valleys, the peak skewness coefficient of height standard deviation, and the kurtosis coefficient of the actual roof are 1.3%, 24.5%, 16%, and 2.9%, respectively. Overall, this indicates that the surface morphology distribution characteristics of the simulated roof and the actual roof are similar, verifying the effectiveness of the modeling and simulation method proposed in this paper, and providing theoretical support for the design and optimization of advanced support in the future.

BackgroundFatigue is a common symptom after viral infection. Chinese herbal medicine (CHM) is thought to be a potential effective intervention in relieving fatigue.PurposeTo assess the effectiveness and safety of CHM for the treatment of post-viral fatigue.Study designSystematic review and meta-analysis of randomized controlled trials (RCTs).MethodsThe protocol of this systematic review was registered on PROSPERO (CRD42022380356). Trials reported changes of fatigue symptom, which compared CHM to no treatment, placebo or drugs, were included. Six electronic databases and three clinical trial registration platforms were searched from inception to November 2023. Literature screening, data extraction, and risk bias assessment were independently carried out by two reviewers. Quality of the included trials was evaluated using Cochrane risk of bias tool, and the certainty of the evidence was evaluated using GRADE. The meta-analysis was performed using Review Manager 5.4, mean difference (MD) and its 95% confidence interval (CI) was used for estimate effect of continuous data. Heterogeneity among trials was assessed through I2 value.ResultsOverall, nineteen studies with 1921 patients were included. Results of individual trial or meta-analysis showed that CHM was better than no treatment (MD = -0.80 scores, 95%CI -1.43 to -0.17 scores, P = 0.01, 60 participants, 1 trial), placebo (MD = -1.90 scores, 95%CI -2.38 to -1.42 scores, PConclusionCurrent systematic review found that the participation of CHM can improve the symptoms of post-viral fatigue and some immune indicators. However, the safety of CHM remains unknown and large sample, high quality multicenter RCTs are still needed in the future.

BackgroundThe results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia.MethodsBy using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors.ResultsThe results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results.ConclusionsThis two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.

BackgroundThe association between the intake of dietary n3 and n6 fatty acids and the risk of stroke is subject to debate. The primary objective of the present research was to establish the correlation in a large sample of American adults.MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, the association of the intake of dietary n3 and n6 fatty acids with stroke events was analyzed in a sample of 29,459 adults. The intake of n3 and n6 fatty acids intake was assessed though two 24-h dietary recalls. Stroke outcomes were identified based on the responses provided in self-reported questionnaire. Logistic regression was fitted to evaluate the correlation of dietary n3, n6 fatty acids intake with stroke events.ResultsSubjects in the highest tertile (T3) of dietary n3 (OR: 0.67, 95% CI: 0.49-0.93), n6 (OR: 0.65, 95% CI: 0.45-0.95) fatty acids intake were found to have obviously lower risk of stroke compared to those in the lowest tertile (T1), but the n6:n3 ratio was not found to be associated with a stroke event. Results from stratified analysis demonstrated that dietary n3 fatty acids had an inverse correlation of stroke in both male and female, but dietary n6 fatty acids only had this correlation in male. Moreover, findings were made that the interaction was significant in terms of age in the subgroup analysis, and the negative relationship between the intake of dietary n3 and n6 fatty acids and stroke event were particularly pronounced among participants aged ≥60.ConclusionsThe present results suggested that increased dietary n3, n6 fatty acids intake correlated with a lower risk of stroke.

ObjectiveTo investigate the effect of physical exercise on sleep quality and the mediating effect of smartphone use behavior in college students.MethodsA cross-sectional study design was adopted. An online survey of 5,075 college students was conducted using the Physical Activity Rating Scale-3, the Pittsburgh Sleep Quality Index, and the Mobile Phone Addiction Tendency Scale.ResultsThe sleep quality of college students was poor, and the proportion of college students with good sleep quality was 23.567%. A significant correlation existed between sleep quality and physical exercise (r = -0.159, P < 0.001) and mobile phone addiction (r = 0.355, P < 0.001). Physical exercise can predict sleep quality in college students (β = -0.011, P < 0.001). Smartphone use plays a part in mediating the process by which physical exercise affects sleep quality.ConclusionChinese college students have poor sleep quality. Physical exercise and smartphone use behavior are important factors affecting the sleep quality of college students. Physical exercise can directly predict the sleep quality of college students and can predict the sleep quality of college students through the mediating effect of smartphone use behavior.

The purpose of this study was to examine the efficacy of ICG-mediated fluorescence molecular imaging (FMI) in debridement of necrotic tissue. 96 wound-infected rats were randomly divided into control group, ICG group, excitation light (EL)group and FMI group for debridement of necrotic tissue (n = 24). (I) Control group: only debridement; (II) ICG group: ICG injection before debridement; (III) EL group: Debridement under EL; (IV) FMI group: Debridement guided by ICG-mediated FMI. On the 3rd, 6th, and 9th days, the wound tissues of the rats in each group were collected for histological examination, and the levels of serum interleukin-4 (IL-4) and interferon-γ (INF-γ) were analyzed. The wound healing rate, wound score and body weight of the rats in each group were followed up until the wound healed. The results showed that the infected wounds of the rats in the FMI group had significant fluorescence development. The level of serum IL-4 in the FMI group was higher than that in the other three groups on the 6th day (p

Quorum sensing is a communication strategy that bacteria use to collectively alter gene expression in response to cell density. Pathogens use quorum sensing systems to control activities vital to infection, such as the production of virulence factors and biofilm formation. The Pseudomonas virulence factor (pvf) gene cluster encodes a signaling system (Pvf) that is present in over 500 strains of proteobacteria, including strains that infect a variety of plant and human hosts. We have shown that Pvf regulates the production of secreted proteins and small molecules in the insect pathogen Pseudomonas entomophila L48. Here, we identified genes that are likely regulated by Pvf using the model strain P. entomophila L48 which does not contain other known quorum sensing systems. Pvf regulated genes were identified through comparing the transcriptomes of wildtype P. entomophila and a pvf deletion mutant (ΔpvfA-D). We found that deletion of pvfA-D affected the expression of approximately 300 genes involved in virulence, the type VI secretion system, siderophore transport, and branched chain amino acid biosynthesis. Additionally, we identified seven putative biosynthetic gene clusters with reduced expression in ΔpvfA-D. Our results indicate that Pvf controls multiple virulence mechanisms in P. entomophila L48. Characterizing genes regulated by Pvf will aid understanding of host-pathogen interactions and development of anti-virulence strategies against P. entomophila and other pvf-containing strains.

IntroductionCoronavirus Disease 2019 (COVID-19) has made a serious public health threat worldwide. Recent evidence has indicated that COVID-19 patients in convalescence frequently experience insomnia, which reduces their quality of life and causes unknown risks. The positive effect of cognitive behavior on insomnia has been well addressed in previous studies. Given the high infectivity and epidemicity of COVID-19, Internet-delivered intervention may be safer than face-to-face treatment. However, whether Internet-delivered cognitive behavioral therapy can effectively improve the insomnia of COVID-19 patients in convalescence has not been completely determined yet. Therefore, we conducted a meta-analysis and systematic review to evaluate the effects of Internet-delivered cognitive behavioral therapy on insomnia in COVID-19 patients in convalescence, with the aim to confer some guidance for its clinical application.Methods and analysisThis systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). Two researchers will retrieve the relevant literature on Internet-delivered cognitive behavioral therapy for insomnia in convalescent patients with COVID-19 in PubMed, Web of Science, Embase, MEDLINE, Cochrane Library, Clinical Trials gov, Chinese Biomedical Literature Database (CBM), and Chinese National Knowledge Infrastructure (CNKI) from inception to 11th of December. In addition, we will review the relevant trials and references of the included literature and manually searched the grey literature. The two researchers will independently extracted data and information and evaluated the quality of the included literature. The Review Manager software (version 5.3) and Stata software (version 14.0) will be used for data analysis. The mean difference or the standardized mean difference of 95% CI will be used to calculate continuous variables to synthesize the data. In addition, I2 and Cochrane will be used for heterogeneity assessment.Trial registrationPROSPERO registration number CRD42021271278.

BackgroundThis study was conducted to investigate the relationship between the Neutrophil-Lymphocyte Ratio (NLR) and the incidence of surgery-related acute kidney injury (AKI) in non-cardiac surgery patients under general anaesthesia.MethodsIn this retrospective study, 5057 patients from Third Xiangya hospital from January 2012 to December 2016 and 1686 patients from Second Xiangya hospital from January 2016 to December 2016 for non-cardiac surgery under general anesthesia were included. According to receiver operating characteristic (ROC) curve constructed by NLR for postoperative AKI, the cut-off point was obtained as the basis for grouping low or high NLR. The baseline characteristics of two sets were compared with each other. A multi-factor model was constructed by Least absolute shrinkage and selection operator (LASSO) method with the training set, and verified by outside validation set.Results243 patients (3.604%) developed postoperative AKI. The ROC curve showed that the AUC of the NLR for predicting postoperative AKI in non-cardiac surgery was 0.743 (95% CI, 0.717-0.769), and the cut-off value was 3.555 (sensitivity, 86.4%; specificity 51.9%). There was no significant difference in the baseline characteristics of training set and validation set. The AUC in the training set was 0.817 (95% CI, 0.784-0.850), and the AUC in the validation set was 0.804 (95% CI, 0.749-0.858), the AUC deviation was 0.012 (P > 0.05) from validation set, and the likelihood ratio test showed P < 0.05.ConclusionThis study showed that preoperative high NLR (NLR≥3.555) was an independent risk factor associated with postoperative AKI (OR, 2.410; 95% CI, 1.371-4.335) in patients for non-cardiac surgery under general anesthesia.

Salt and drought stresses are major environmental conditions that severely limit grape growth and productivity, while exogenous melatonin can alleviate the drought and salt damage to grapevines. N-acetylserotonin methyltransferase (ASMT) is the key enzyme in melatonin synthesis, which plays a critical role in regulating stress responses. However, the roles of ASMTs from grapevine under drought and salt stresses responses remain largely unclear. In this study, the VvASMT1 gene was isolated from grapevine, and its physiological functions in salt and mimic drought stress tolerance were investigated. Expression pattern analysis revealed that VvASMT1 was significantly induced by different salt and osmotic stresses. Ectopic expression of VvASMT1 in Nicotiana benthamiana significantly enhanced melatonin production in transgenic plants. Compared with wild-type plants, the transgenic lines exhibited a higher germination ratio, longer root length, lower degree of leaf wilting and relative water content (RWC) under salt and osmotic stresses. In addition, under salt and osmotic stresses, overexpression of VvASMT1 improved proline and malondialdehyde (MDA) contents, increased the activity of antioxidant enzymes and decreased the accumulation of reactive oxygen species (ROS). Taken together, our results demonstrate the explicit role of VvASMT1 in salt and osmotic stress responses, which provides a theoretical foundation for the genetic engineering of grapevine.

IntroductionPublic health responses were triggered while COVID-19 was spreading. China redeployed healthcare workers to serve the most vulnerable populations and communities in the initial epicentre-Wuhan. However, it is not known how redeployment processes impacted on healthcare workers in a pandemic crisis.AimsTo explore the experiences and needs of frontline healthcare workers who were redeployed to care for COVID-19 patients in Wuhan, China, and understand the long-term impacts of the redeployment experience on their work and life.MethodsA qualitative study was conducted with redeployed healthcare workers using semi-structured interviews and thematic analysis. This study is reported in accordance with the consolidated criteria for reporting qualitative research (COREQ) guidelines.FindingsA total of 20 redeployed healthcare workers (13 nurses and seven physicians) participated, and four themes were generated: (1) Initial feelings and emotions of redeployment-Participants experienced worries and concerns, a sense of isolation and loneliness on their arrival to the epicentre. (2) 'It is like a war zone'-Healthcare workers faced a range of risks and challenges of caring for COVID-19 patients in Wuhan in the context of resource strain. (3) Uncertainty and coping strategies in patient care-Despite the hardships experienced, participants continued to deliver high-quality patient care including psychological care and palliative care, good communication and building mutual trusting relationships. (4) Reflection and far-reaching impacts of caring for COVID-19 patients-Participants felt motivated and encouraged as efforts were recognised by the government and wider society.ConclusionsRedeployed healthcare workers shared their unique needs and experiences of coping with redeployment and challenges they faced in the context of resource strain, which has significant implications for policy and future practice. The reality of a pandemic may reduce healthcare workers' willingness to work due to various reasons including inadequate preparedness of facilities and workplace safety. It is important to support frontline healthcare workers in order to maintain an adequate healthcare workforce in pandemic crises. Continuously evolving pandemic circumstances and uncertainty highlight the importance of an organized national pandemic response plan for subsequent waves of COVID-19 and future pandemics.

This study explored the roles of epidemic-spread-related behaviors, vaccination status and weather factors during the COVID-19 epidemic in 50 U.S. states since March 2020. Data from March 1, 2020 to February 5, 2022 were incorporated into panel model. The states were clustered by the k-means method. In addition to discussing the whole time period, we also took multiple events nodes into account and analyzed the data in different time periods respectively by panel linear regression method. In addition, influence of cluster grouping and different incubation periods were been discussed. Non-segmented analysis showed the rate of people staying at home and the vaccination dose per capita were significantly negatively correlated with the daily incidence rate, while the number of long-distance trips was positively correlated. Weather indicators also had a negative effect to a certain extent. Most segmental results support the above view. The vaccination dose per capita was unsurprisingly proved to be the most significant factor especially for epidemic dominated by Omicron strains. 7-day was a more robust incubation period with the best model fit while weather had different effects on the epidemic spread in different time period. The implementation of prevention behaviors and the promotion of vaccination may have a successful control effect on COVID-19, including variants' epidemic such as Omicron. The spread of COVID-19 also might be associated with weather, albeit to a lesser extent.

Rural traditional Chinese medicine hospitals bear responsibilities of providing efficient medical services for rural residents. Efficiency assessments have previously been conducted in single province. This study aimed to investigate the technical efficiency of rural traditional Chinese medicine hospitals across China from 2013 to 2018, with the application of super slack-based measure data envelopment analysis. In total, 1219 hospitals covering 28 provinces were included as sample hospitals. Overall, hospitals performed technically less efficiently but presented with an increasing trend. Redundancy and insufficiency existed in health input and output variables, respectively. Notably, optimizing input variables was found to make more substantial improvement in hospital efficiency. Provincial and regional disparities were also observed in hospital efficiency. In conclusion, rural traditional Chinese medicine hospitals have experienced slight improvement in efficiency during the study period, however, their efficiency was still in a relatively low level with ample room for improvement. Meanwhile, regional coordinated development should also be noticed in this process.

The global pandemic of COVID-19 poses a huge threat to the health and lives of people all over the world, and brings unprecedented pressure to the medical system. We need to establish a practical method to improve the efficiency of treatment and optimize the allocation of medical resources. Due to the influx of a large number of patients into the hospital and the running of medical resources, blood routine test became the only possible check while COVID-19 patients first go to a fever clinic in a community hospital. This study aims to establish an efficient method to identify key indicators from initial blood routine test results for COVID-19 severity prediction. We determined that age is a key indicator for severity predicting of COVID-19, with an accuracy of 0.77 and an AUC of 0.92. In order to improve the accuracy of prediction, we proposed a Multi Criteria Decision Making (MCDM) algorithm, which combines the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) and Naïve Bayes (NB) classifier, to further select effective indicators from patients' initial blood test results. The MCDM algorithm selected 3 dominant feature subsets: {Age, WBC, LYMC, NEUT} with a selection rate of 44%, {Age, NEUT, LYMC} with a selection rate of 38%, and {Age, WBC, LYMC} with a selection rate of 9%. Using these feature subsets, the optimized prediction model could achieve an accuracy of 0.82 and an AUC of 0.93. These results indicated that Age, WBC, LYMC, NEUT were the key factors for COVID-19 severity prediction. Using age and the indicators selected by the MCDM algorithm from initial blood routine test results can effectively predict the severity of COVID-19. Our research could not only help medical workers identify patients with severe COVID-19 at an early stage, but also help doctors understand the pathogenesis of COVID-19 through key indicators.

Hereditary spastic paraplegias (HSPs) are a group of rare neurodegenerative disorders. HSPs are complex disorders and are clinically and genetically heterogeneous. To date, more than 80 genes or genetic loci have been reported to be responsible for HSPs in a Mendelian-dependent manner. Most recently, ubiquitin-associated protein 1 (UBAP1) has been recognized to be involved in HSP. Here, we identified novel protein truncating variants in two families with pure form of HSP. A novel deletion (c.468_469delTG) in the UBAP1 gene was found in the first family, whereas a nonsense variant (c.512T>G) was ascertained in the second family. The variants were confirmed in all patients but were not detected in unaffected family members. The mutations resulted in truncated proteins of UBAP1. The variants did not result in different subcellular localizations in neuro-2a cells. However, each of the two variants impaired neurite outgrowth. Taken together, our findings expand the pathogenic spectrum of UBAP1 variants in HSP.

PurposeNecrotizing enterocolitis (NEC) is one of the most distressing gastrointestinal emergencies affecting neonates. Amniotic fluid stem cells (AFSC) improve intestinal injury and survival in experimental NEC but are difficult to administer. In this study, we evaluated whether conditioned medium (CM) derived from human AFSC have protective effects.MethodsThree groups of C57BL/6 mice were studied: (i) breast-fed mice as control; (ii) experimental NEC mice receiving PBS; and (iii) experimental NEC mice receiving CM. NEC was induced between post-natal days P5 through P9 via: (A) gavage feeding of hyperosmolar formula four-time a day; (B) 10 minutes hypoxia prior to feeds; and (C) lipopolysaccharide administration on P6 and P7. Intra-peritoneal injections of either PBS or CM were given on P6 and P7. All mice were sacrificed on P9 and terminal ileum were harvested for analyses.ResultsCM treatment increased survival and reduced intestinal damage, decreased mucosal inflammation (IL-6; TNF-α), neutrophil infiltration (MPO), and apoptosis (CC3), and also restored angiogenesis (VEGF) in the ileum. Additionally, CM treated mice had increased levels of epithelial proliferation (Ki67) and stem cell activity (Olfm4; Lgr5) compared to NEC+PBS mice, showing restored intestinal regeneration and recovery during NEC induction. CM proteomic analysis of CM content identified peptides that regulated immune and stem cell activity.ConclusionsCM derived from human AFSC administered in experimental NEC exhibited various benefits including reduced intestinal injury and inflammation, increased enterocyte proliferation, and restored intestinal stem cell activity. This study provides the scientific basis for the use of CM derived from AFSC in neonates with NEC.

Radish (Raphanus sativus L.), is an important root vegetable crop grown worldwide, and it contains phyto-anthocyanins. However, only limited studies have been conducted to elucidate the molecular mechanisms underlying anthocyanin biosynthesis in the different color variants of the radish fleshy root. In this study, Illumina paired-end RNA-sequencing was employed to characterize the transcriptomic changes in seven different types of radish fleshy roots. Approximately, 126 co-modulated differentially expressed genes were obtained, and most DEGs were more likely to participate in anthocyanin biosynthesis, including two transcription factors RsMYB_9 and RsERF070, and four functional genes RsBRICK1, RsBRI1-like2, RsCOX1, and RsCRK10. In addition, some related genes such as RsCHS, RsCHI, RsANS, RsMT2-4, RsUF3GT, glutathione S-transferase F12, RsUFGT78D2-like and RsUDGT-75C1-like significantly contributed to the regulatory mechanism of anthocyanin biosynthesis in the radish cultivars. Furthermore, gene ontology analysis revealed that the anthocyanin-containing compound biosynthetic process, anthocyanin-containing compound metabolic process, and significantly enriched pathways of the co-modulated DEGs were overrepresented in these cultivars. These results will expand our understanding of the complex molecular mechanism underlying anthocyanin synthesis-related genes in radish.

Scutellaria, or skullcaps, are medicinally important herbs in China, India, Japan, and elsewhere. Though Scutellaria is the second largest and one of the more taxonomically challenging genera within Lamiaceae, few molecular systematic studies have been undertaken within the genus; in part due to a paucity of available informative markers. The lack of informative molecular markers for Scutellaria hinders our ability to accurately and robustly reconstruct phylogenetic relationships, which hampers our understanding of the diversity, phylogeny, and evolutionary history of this cosmopolitan genus. Comparative analyses of 15 plastomes, representing 14 species of subfamily Scutellarioideae, indicate that plastomes within Scutellarioideae contain about 151,000 nucleotides, and possess a typical quadripartite structure. In total, 590 simple sequence repeats, 489 longer repeats, and 16 hyper-variable regions were identified from the 15 plastomes. Phylogenetic relationships among the 14 species representing four of the five genera of Scutellarioideae were resolved with high support values, but the current infrageneric classification of Scutellaria was not supported in all analyses. Complete plastome sequences provide better resolution at an interspecific level than using few to several plastid markers in phylogenetic reconstruction. The data presented here will serve as a foundation to facilitate DNA barcoding, species identification, and systematic research within Scutellaria, which is an important medicinal plant resource worldwide.

Small heat shock proteins (sHsps) function in the response of insects to abiotic stress; however, their role in response to biotic stress has been under-investigated. Mythimna separata, the oriental armyworm, is polyphenetic and exhibits gregarious and solitary phases in response to high and low population density, respectively. In this study, three genes were identified encoding sHsps, namely MsHsp19.7, MsHsp19.8 and MsHsp21.4, and expression levels in solitary and gregarious M. separata were compared. The deduced protein sequences of the three MsHsps had molecular weights of 19.7, 19.8 and 21.4 kDa, respectively, and contained a conserved α-crystalline domain. Real-time PCR analyses revealed that the three sHsps were transcribed in all developmental stages and were dramatically up-regulated at the 6th larval stage in gregarious individuals. Expression of the three MsHsps was variable in different tissues of 6th instar larvae, but exhibited consistent up- and down-regulation in the hindgut and Malpighian tubules of gregarious individuals, respectively. In addition, MsHsp19.7 and MsHsp19.8 were significantly induced when solitary forms were subjected to crowding for 36 h, but all three MsHsps were down-regulated when gregarious forms were isolated. Our findings suggest that population density functions as a stress factor and impacts MsHsps expression in M. separata.

This study aims to provide estimates, trends and projections of vision loss burden in Pakistan from 1990 to 2025. Global Burden of Diseases, Injuries, and Risk Factors Study (GBD 2017) was used to observe the vision loss burden in terms of prevalence and Years Lived with Disability (YLDs). As of 2017, out of 207.7 million people in Pakistan, an estimated 1.12 million (95% Uncertainty Interval [UI] 1.07-1.19) were blind (Visual Acuity [VA]

Necrotizing enterocolitis (NEC) is characterized by intestinal injury and impaired mucin synthesis. We recently showed that breast milk exosomes from rodents promote intestinal cell viability, epithelial proliferation, and stem cell activity, but whether they also affect mucus production is unknown. Therefore, the aim of this study was to investigate the effects of bovine milk-derived exosomes on goblet cell expression in experimental NEC and delineate potential underlying mechanisms of action. Exosomes were isolated from bovine milk by ultracentrifugation and confirmed by Nanoparticle Tracking Analysis and through the detection of exosome membrane markers. To study the effect on mucin production, human colonic LS174T cells were cultured and exposed to exosomes. Compared to control, exosomes promoted goblet cell expression, as demonstrated by increased mucin production and relative expression levels of goblet cell expression markers trefoil factor 3 (TFF3) and mucin 2 (MUC2). In addition, exosome treatment enhanced the expression of glucose-regulated protein 94 (GRP94), the most abundant intraluminal endoplasmic reticulum (ER) chaperone protein that aids in protein synthesis. Furthermore, experimental NEC was induced in mouse pups by hyperosmolar formula feeding, lipopolysaccharide administration and hypoxia exposure on postnatal days 5-9. Milk exosomes were given with each gavage feed. NEC was associated with ileal morphological injury and reduction in MUC2+ goblet cells and GRP94+ cells per villus. Exosome administration to NEC pups prevented these changes. This research highlights the potential novel application of milk-derived exosomes in preventing the development of NEC in high-risk infants when breast milk is not available.

The brown planthopper, Nilaparvata lugens (Stål), severely damages rice production and develops high level resistance to several classes of insecticides. To find potential insecticidal resources is always important. As an environmentally friendly compound, aconitine exhibits potential pesticide features. In the present study, the pesticide and knockdown effects of aconitine were first tested on the brown planthopper. The results showed that the knockdown rates for an aconitine concentration of 200 ppm was 83.6%. The insecticidal LD50 was 22.68 ng/pest (95% CI, 17.75-28.99). The molecular mechanisms responding to aconitine application were analyzed through transcriptional sequencing. Compared to that of the knockdown nymphs of the brown planthoppers, the enzymes CYP3A4, UDP-glucuronosyltransferase (UGT), GST, carboxylesterase (EC3.1.1.1), and GABAergic synapse were up-regulated. We inferred that aconitine might be neurotoxic to the brown planthoppers, and the conscious nymphs resist the drug neurotoxicity through the upregulation of CYP3A4, UGT, and GABA receptor mutation. Although aconitine is not safe for mammals, it may be a leading compound to develop novel insecticides.

BackgroundTo assess the mRNA expression profile and explore the hub mRNAs and potential molecular mechanisms in the pathogenesis of human thoracic aortic dissection (TAD).MethodologymRNA microarray expression signatures of TAD tissues (n = 6) and non-TAD tissues (NT; n = 6) were analyzed by an Arraystar human mRNA microarray. Real-time PCR (qRT-PCR) was used to validate the results of the mRNA microarray. Bioinformatic tools, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, were utilized. Protein-protein interaction (PPI) networks were constructed based on data from the STRING database. Molecular Complex Detection (MCODE) and cytoHubba analyses were used to predict the strongest hub gene and pathway.ResultsThe top 10 hub genes were CDK1, CDC20, CCNB2, CCNB1, MAD2L1, AURKA, C3AR1, NCAPG, CXCL12 and ASPM, which were identified from the PPI network. Module analysis revealed that TAD was associated with the cell cycle, oocyte meiosis, the p53 signaling pathway, and progesterone-mediated oocyte maturation. The qRT-PCR results showed that the expression of all hub genes was significantly increased in TAD samples (p < 0.05). Immunostaining of Ki-67 and CDK1 showed a high proliferation state and high expression in TAD, respectively.ConclusionsCDK1 could be used as a potential diagnostic biomarker and therapeutic target of TAD.

ObjectiveTo evaluate the dependability and accuracy of midkine (MK) in the diagnosis of hepatocellular carcinoma (HCC).MethodsPubMed, EMBASE, Web of Science, China Biology Medicine disc and grey literature sources were searched from the date of database inception to January 2019. Two authors (B-H.Z. and B.L.) independently extracted the data and evaluated the study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were estimated using a bivariate model. Moreover, hierarchical summary receiver operating characteristic curves were generated. The diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled using a univariate model.ResultsNine articles (11 studies) were included (1941 participants). The bivariate analysis revealed that the sensitivity and specificity of MK for HCC diagnosis were 0.85 (95% CI 0.78-0.91) and 0.83 (95% CI 0.76-0.88), respectively. We also found a LR+ of 5.05 (95% CI 3.33-7.40), a LR- of 0.18 (95% CI 0.11-0.28), a DOR of 31.74 (95% CI 13.98-72.09) and an AUC of 0.91 (95% CI 0.84-0.99). Subgroup analyses showed that MK provided the best efficiency for HCC diagnosis when the cutoff value was greater than 0.5 ng/mL.ConclusionsMK has an excellent diagnostic value for hepatocellular carcinoma.

BackgroundGenital herpes simplex infection affects more than 500 million people worldwide. We have previously shown that COR-1, a therapeutic HSV-2 polynucleotide vaccine candidate, is safe and well tolerated in healthy subjects.ObjectiveHere, we present a single center double-blind placebo-controlled, randomized phase I/IIa trial of COR-1 in HSV-2 positive subjects in which we assessed safety and tolerability as primary endpoints, and immunogenicity and therapeutic efficacy as exploratory endpoints.MethodsForty-four HSV-2+ subjects confirmed by positive serology or pathology, and positive qPCR during baseline shedding, with a recurrent genital HSV-2 history of at least 12 months including three to nine reported lesions in 12 months prior to screening, aged 18 to 50 years females and males with given written informed consent, were randomized into two groups. Three immunizations at 4-week intervals and one booster immunization at 6 months, each of 1 mg COR-1 DNA or placebo, were administered intradermally as two injections of 500 μg each to either one forearm or both forearms.ResultsNo serious adverse events, life-threatening events or deaths occurred throughout the study. As expected, HSV-2 infected subjects displayed gD2-specific antibody titers prior to immunization. COR-1 was associated with a reduction in viral shedding after booster administration compared with baseline.ConclusionsThis study confirms the previously demonstrated safety of COR-1 in humans and indicates a potential for use of COR-1 as a therapy to reduce viral shedding in HSV-2 infected subjects.

Chemosensory proteins (CSP) are soluble carrier proteins that may function in odorant reception in insects. CSPs have not been thoroughly studied at whole-genome level, despite the availability of insect genomes. Here, we identified/reidentified 283 CSP genes in the genomes of 22 mosquitoes. All 283 CSP genes possess a highly conserved OS-D domain. We comprehensively analyzed these CSP genes and determined their conserved domains, structure, genomic distribution, phylogeny, and evolutionary patterns. We found an average of seven CSP genes in each of 19 Anopheles genomes, 27 CSP genes in Cx. quinquefasciatus, 43 in Ae. aegypti, and 83 in Ae. albopictus. The Anopheles CSP genes had a simple genomic organization with a relatively consistent gene distribution, while most of the Culicinae CSP genes were distributed in clusters on the scaffolds. Our phylogenetic analysis clustered the CSPs into two major groups: CSP1-8 and CSE1-3. The CSP1-8 groups were all monophyletic with good bootstrap support. The CSE1-3 groups were an expansion of the CSP family of genes specific to the three Culicinae species. The Ka/Ks ratios indicated that the CSP genes had been subject to purifying selection with relatively slow evolution. Our results provide a comprehensive framework for the study of the CSP gene family in these 22 mosquito species, laying a foundation for future work on CSP function in the detection of chemical cues in the surrounding environment.

Background and objectivesFine particulate matter (PM2.5, particulate matter with an aerodynamic diameter less than or equal to 2.5 μm) has multiple adverse effects on human health, especially on the respiratory and circulatory system. The purpose of this study was to evaluate the short-term effect of PM2.5 on the mortality risk of non-accidental and circulatory diseases, and to explore the potential effect modification by sex, education and death location.MethodsWe collected daily mortality counts of Changchun (China) residents, daily meteorology and air pollution data, from January 1, 2014, to January 1, 2017. We focused on the elderly (≥65 years old) population who died from non-accidental causes and circulatory diseases, and stratified them by sex, education, and death location. A generalized additive Poisson regression model (GAM) was used to analyse the impact of air pollutants on mortality. We fit single pollutant models to examine PM2.5 effects with different lag structures of single-day (distributed lag:lag0-lag3) and multi-day (moving average lag: lag01-lag03). To test the sensitivity of the model, a multi-pollutant model was established when the PM2.5 effect was strongest.ResultsIn the single pollutant models, an increment of PM2.5 by 10 μg/m3 at lag0-3 was associated with a 0.385% (95% CI: 0.069% to 0.702%) increase in daily non-accidental mortality and a 0.442% (95% CI: 0.038% to 0.848%) increase in daily circulatory disease mortality. NO2 (lag1) and O3 (lag0, lag1, lag2, lag01,lag02, lag03) were associated with daily non-accidental death and NO2 (lag1, lag3, lag03) and O3 (lag0, lag1, lag01,lag02, lag03) were associated with daily circulatory disease mortality. In the co-pollutant models, the risk estimates for PM2.5 changed slightly. The excess mortality risk of non-accidental and circulatory diseases was higher for women, people with low education, and died outside hospital.ConclusionsWe found that short-term exposure to PM2.5 increased the mortality risk of non-accidental and circulatory diseases among the elderly in Changchun. Women, people with low education and died outside hospital are more susceptible to PM2.5. NO2 and O3 were also associated with an increase in mortality from non-accidental and circulatory diseases and the O3 is a high effect.

INTRODUCTION:Hepatitis B is a serious public health problem across sub-Saharan Africa. Sierra Leone has no national hepatitis B strategy plan or high quality estimates of prevalence. Healthcare workers are perceived as an at-risk group for hepatitis B. We assessed the prevalence of hepatitis B among healthcare workers at two hospital sites in Freetown, Sierra Leone. METHODS:In October 2017, healthcare workers were offered voluntary testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) using rapid lateral flow assay for all samples, followed by Enzyme Immunosorbent Assay to confirm positive results. Participants completed a questionnaire about knowledge, attitudes and practices concerning hepatitis B. HBsAg positive participants were invited to a clinic for further assessment. RESULTS:Overall, 447 participants were tested for hepatitis B. Most (90.6%, 405/447) participants were nurses, 72.3% (323/447) were female and 71.6% (320/447) were 30 years or older. The prevalence of chronic hepatitis B (HBsAg positivity) was 8.7% (39 / 447, 95% CI 6.3-11.7%). There was no significant difference in prevalence by sex, age group, site of work or type of job. None of the 66.7% (26 / 39) of participants with chronic hepatitis B who attended the clinic met the 2015 WHO criteria to start treatment for hepatitis B on the basis of cirrhosis. Most participants (96.9% 432 / 446) stated that they were worried about their risk of hepatitis B at work. CONCLUSIONS:Hepatitis B is highly prevalent among healthcare workers in Sierra Leone. It is unclear whether this reflects high community prevalence or is due to occupational risk. No participants with chronic hepatitis B needed to start treatment. In order to achieve the WHO target of elimination of viral hepatitis by 2030, introduction of birth dose vaccine for infants and catch-up vaccines for healthcare workers and healthcare students, together with a national hepatitis B screen and treat programme is advisable for Sierra Leone.

[This corrects the article DOI: 10.1371/journal.pone.0193025.].

The oriental armyworm, Mythimna separata, is a major insect pest in China and other Asian countries. Unfortunately, suitable reference genes for quantitative real-time PCR (qRT-PCR) have not been previously identified in M. separata for normalizing target gene expression. In this study, we evaluated the expression stability of eight candidate genes (18S, ACT, EF1-α, GAPDH, RPS7, RPS13, RPL32 and TUB) in M. separata using the comparative ΔCt method, BestKeeper, Normfinder geNorm and ReFinder, a comprehensive software platform. The results indicated that the appropriate reference gene varied depending on the experimental conditions. We found that ACTIN, EF1-α and TUB were optimal for different developmental stages; TUB, RPS13 and EF1-α showed the most stable expresssion in different tissues; RPS13 and 18S were the best reference genes for monitoring expression under high temperature conditions; TUB, RPS13 and RPS7 exhibited the most stable expression under larval-crowding conditions; RPS7, EF1-α, RPL32 and GAPDH were the best for pesticide exposure experiments. This study provides tools for reliable normalization of qRT-PCR data and forms a foundation for functional studies of target gene expression in M. separata.

This paper presents a reassessment of the archaeological record at Leang Burung 2, a key early human occupation site in the Late Pleistocene of Southeast Asia. Excavated originally by Ian Glover in 1975, this limestone rock-shelter in the Maros karsts of Sulawesi, Indonesia, has long held significance in our understanding of early human dispersals into 'Wallacea', the vast zone of oceanic islands between continental Asia and Australia. We present new stratigraphic information and dating evidence from Leang Burung 2 collected during the course of our excavations at this site in 2007 and 2011-13. Our findings suggest that the classic Late Pleistocene modern human occupation sequence identified previously at Leang Burung 2, and proposed to span around 31,000 to 19,000 conventional 14C years BP (~35-24 ka cal BP), may actually represent an amalgam of reworked archaeological materials. Sources for cultural materials of mixed ages comprise breccias from the rear wall of the rock-shelter-remnants of older, eroded deposits dated to 35-23 ka cal BP-and cultural remains of early Holocene antiquity. Below the upper levels affected by the mass loss of Late Pleistocene deposits, our deep-trench excavations uncovered evidence for an earlier hominin presence at the site. These findings include fossils of now-extinct proboscideans and other 'megafauna' in stratified context, as well as a cobble-based stone artifact technology comparable to that produced by late Middle Pleistocene hominins elsewhere on Sulawesi.

Premna vietnamensis, a distinct new species which is endemic to Gia Lai Province in Central Highlands of Vietnam, is described and illustrated. It is characterized by its calyx tube bearing a semi-globose fleshy appendage, which has not been reported before from all known congeneric taxa, as well as from the Lamiaceae. A phylogenetic analysis of the whole Lamiaceae based on a sampling including representatives from all 12 currently recognized subfamilies confirmed the placement of this new species within Premna of the Premnoideae. Morphologically and geographically, P. vietnamensis is most similar to P. stenobotrys, but differs significantly in many aspects.

Anopheles sinensis is a major malarial vector in China and Southeast Asia. The mitochondria is involved in many important biological functions. Nuclear mitochondrial DNA segments (NUMTs) are common in eukaryotic organisms, but their characteristics are poorly understood. We sequenced and analyzed the complete mitochondrial (mt) genome of An. sinensis. The mt genome is 15,418 bp long and contains 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs and a large non-coding region. Its gene arrangement is similar to previously published mosquito mt genomes. We identified and analyzed the NUMTs of 19 mosquito species with both nuclear genomes and mt genome sequences. The number, total length and density of NUMTs are significantly correlated with genome size. About half of NUMTs are short (< 200 bp), but larger genomes can house longer NUMTs. NUMTs may help explain genome size expansion in mosquitoes. The expansion due to mitochondrial insertion segments is variable in different insect groups. PCGs are transferred to nuclear genomes at a higher frequency in mosquitoes, but NUMT origination is more different than in mammals. Larger-sized nuclear genomes have longer mt genome sequences in both mosquitoes and mammals. The study provides a foundation for the functional research of mitochondrial genes in An. sinensis and helps us understand the characteristics and origin of NUMTs and the potential contribution to genome expansion.

In this study, we examined the role of mRNAs and miRNAs in variations in intramuscular fat content in the longissimus dorsi muscle in Xinjiang brown cattle. Two groups of Xinjiang brown cattle with extremely different intramuscular fat content in the longissimus dorsi were selected for combined of miRNA and mRNA analysis using an RNA-Seq. In total, 296 mRNAs and 362 miRNAs were significantly differentially expressed, including 155 newly predicted miRNAs, 275 significantly upregulated genes, 252 significantly upregulated miRNAs, 21 significantly downregulated genes and 110 significantly downregulated miRNAs. The combined miRNA and mRNA analysis identified 96 differentially expressed miRNAs and 27 differentially expressed mRNAs. In all, 47 upregulated miRNAs had a regulatory effect on 14 differentially downregulated target genes, and 49 downregulated miRNAs had a regulatory effect on 13 upregulated target genes. To verify the sequencing results, 10 differentially expressed genes (DEGs) and 10 differentially expressed miRNAs were selected for qRT-PCR. The qRT-PCR results confirmed the sequencing results. The results of this study shed light on the molecular regulation of bovine adipose tissue, which might help with the development of new strategies for improving meat quality and animal productivity in beef cattle to provide healthier meat products for consumers.

OBJECTIVES:Sickness situation in the past two weeks, an indicator of health service needs, is an increasing major health concern. However, data on the relationship between obesity and two-week morbidity in the female population, particularly in middle-aged and elderly women, is sparse. The present study aimed to examine the association between obesity and two-week morbidity among middle-aged and elderly women in Southern China, and to explore the independent contributions of socio-demographic variables, health-related factors, and obesity to two-week morbidity. METHODS:In total, 2364 middle-aged and elderly women were included in this cross-sectional, community-based survey. Obesity was assessed using body mass index (BMI). The outcome variable was sickness situation over the past two weeks (two-week morbidity). Clustered logistic regression was applied to analyze the independent contribution of obesity to two-week morbidity. RESULTS:Approximately 14.6% of participants experienced sickness in the past two weeks. Obesity (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.02-2.12) was significantly associated with two-week morbidity and its independent contribution accounted for 3.7%, lower than that of socio-demographic variables (73.7%) and health-related factors(22.6%). CONCLUSIONS:Some degree of correlation was observed between obesity and two-week morbidity among middle-aged and elderly women in Southern China, which can be used as a reference for health-related decision-making.

miR-155 is one of the most important miRNAs and plays a very important role in numerous biological processes. However, few studies have characterized this miRNA in mice under normal physiological conditions. We aimed to characterize miR-155 in vivo by using a comparative analysis. In our study, we compared miR-155 knockout (KO) mice with C57BL/6 wild type (WT) mice in order to characterize miR-155 in mice under normal physiological conditions using many evaluation methods, including a reproductive performance analysis, growth curve, ultrasonic estimation, haematological examination, and histopathological analysis. These analyses showed no significant differences between groups in the main evaluation indices. The growth and development were nearly normal for all mice and did not differ between the control and model groups. Using a comparative analysis and a summary of related studies published in recent years, we found that miR-155 was not essential for normal physiological processes in 8-week-old mice. miR-155 deficiency did not affect the development and growth of naturally ageing mice during the 42 days after birth. Thus, studying the complex biological functions of miR-155 requires the further use of KO mouse models.

Development of multidrug resistance (MDR) is a continuous clinical challenge partially due to the overexpression of P-glycoprotein (P-gp) for chronic myelogenous leukemia (CML) patients. Herein, we evaluated the inhibitory potency of emodin, a natural anthraquinone derivative isolated from Rheum palmatum L, on P-gp in P-gp positive K562/ADM cells. Competition experiments combined with molecular docking analysis were utilized to investigate the binding modes between emodin and binding sites of P-gp. Emodin reversed adriamycin resistance in K562/ADM cells accompanied with the decrease of P-gp protein expression, further increasing the uptake of rhodamine123 in both K562/ADM and Caco-2 cells, indicating the inhibition of P-gp efflux function. Moreover, when incubated with emodin under different conditions where P-gp was inhibited, K562/ADM cells displayed increasing intracellular uptake of emodin, suggesting that emodin may be the potential substrate of P-gp. Importantly, rhodamine 123 could increase the Kintrinsic (Ki) value of emodin linearly, whereas, verapamil could not, implying that emodin competitively bound to the R site of P-gp and noncompetition existed between emodin and verapamil at the M site, in a good accordance with the results of molecular docking that emodin bound to the R site of P-gp with higher affinity. Based on our results, we suggest that emodin might be used to modulate P-gp function and expression.

Glycolipids might become a new type of promising non-viral gene delivery systems because of their low cytotoxicity, structural diversity, controllable aqua- and lipo-solubility, appropriate density and distribution of positive charges, high transfer efficiency and potential targeting function. In this study, four kinds of L-arabinose-based cationic glycolipids (Ara-DiC12MA, Ara-DiC14MA, Ara-DiC16MA and Ara-DiC18MA) containing quaternary ammonium as hydrophilic headgroup and two alkane chains as hydrophobic domain were synthesized and characterized. They were observed to have strong affinities for plasmid DNA (pDNA) and siRNA, the pDNA can be completely condensed at N/P ratio less than 2, and the siRNA can be completely retarded at N/P ratio less than 3. The dynamic light scattering (DLS) experiment and atomic force microscopy (AFM) experiment demonstrated that cationic lipids and their lipoplexes possessed suitable particle sizes with near-spherical shape and proper ζ-potentials for cell transfection. The Ara-DiC16MA liposome was found to have good transfection efficacy in HEK293, PC-3 and Mat cells compared with other three kinds of liposomes, and also maintain low cytotoxicity and better uptake capability in vitro. Furthermore, the gene silencing assay showed that Ara-DiC14MA and Ara-DiC16MA liposomes have demonstrated effective delivery and higher gene knockdown activity (>80%) in the above mentioned cells than Lipofectamine 2000. These results indicated Ara-DiC16MA can be developed for efficient and low toxic gene delivery.

In smart parking environments, how to choose suitable parking facilities with various attributes to satisfy certain criteria is an important decision issue. Based on the multiple attributes decision making (MADM) theory, this study proposed a smart parking guidance algorithm by considering three representative decision factors (i.e., walk duration, parking fee, and the number of vacant parking spaces) and various preferences of drivers. In this paper, the expected number of vacant parking spaces is regarded as an important attribute to reflect the difficulty degree of finding available parking spaces, and a queueing theory-based theoretical method was proposed to estimate this expected number for candidate parking facilities with different capacities, arrival rates, and service rates. The effectiveness of the MADM-based parking guidance algorithm was investigated and compared with a blind search-based approach in comprehensive scenarios with various distributions of parking facilities, traffic intensities, and user preferences. Experimental results show that the proposed MADM-based algorithm is effective to choose suitable parking resources to satisfy users' preferences. Furthermore, it has also been observed that this newly proposed Markov Chain-based availability attribute is more effective to represent the availability of parking spaces than the arrival rate-based availability attribute proposed in existing research.

Human involvement influences traditional service quality evaluations, which triggers an evaluation's low accuracy, poor reliability and less impressive predictability. This paper proposes a method by employing a support vector machine (SVM) and Dempster-Shafer evidence theory to evaluate the service quality of a production process by handling a high number of input features with a low sampling data set, which is called SVMs-DS. Features that can affect production quality are extracted by a large number of sensors. Preprocessing steps such as feature simplification and normalization are reduced. Based on three individual SVM models, the basic probability assignments (BPAs) are constructed, which can help the evaluation in a qualitative and quantitative way. The process service quality evaluation results are validated by the Dempster rules; the decision threshold to resolve conflicting results is generated from three SVM models. A case study is presented to demonstrate the effectiveness of the SVMs-DS method.

Whole-genome shotgun (WGS) sequencing has become a routine method in genome research over the past decade. However, the assembly of highly polymorphic regions in WGS projects remains a challenge, especially for large genomes. Employing BAC library constructing, PCR screening and Sanger sequencing, traditional strategy is laborious and expensive, which hampers research on polymorphic genomic regions. As one of the most highly polymorphic regions, the major histocompatibility complex (MHC) plays a central role in the adaptive immunity of all jawed vertebrates. In this study, we introduced an efficient procedure based on recombination screening and short-reads assembly. With this procedure, we constructed a high quality 488-kb region of crested ibis MHC that consists of 3 superscaffolds and contains 50 genes. Our sequence showed comparable quality (97.29% identity) to traditional Sanger assembly, while the workload was reduced almost 7 times. Comparative study revealed distinctive features of crested ibis by exhibiting the COL11A2-BLA-BLB-BRD2 cluster and presenting both ADPRH and odorant receptor (OR) gene in the MHC region. Furthermore, the conservation of the BF-TAP1-TAP2 structure in crested ibis and other vertebrate lineages is interesting in light of the hypothesis that coevolution of functionally related genes in the primordial MHC is responsible for the appearance of the antigen presentation pathways at the birth of the adaptive immune system.

Wheat germ (WG) is quite susceptible to deterioration due to the presence of lipase (LA) and lipoxygenase (LOX). Therefore it is indispensable to adopt a stabilization step to decrease the activity of LA and LOX while retaining a maximum level of nutrients. But over-drying can make foodstuffs more susceptible to autoxidation. So a stabilization protocol for inactivating LA and LOX of WG with a temperature- controlled short wave infrared (SIR) radiation system was adopted to retard its rancidity and retain a maximum level of fat-soluble nutrients. Meanwhile, the critical storage water activity (Aw) of WG for inhibiting both hydrolytic and oxidative rancidity was appraised. Results indicate that WG irradiated at 90°C for 20 min acquired the optimal stabilization effect, and its residual LA and LOX activity were 18.02% and 19.21%, respectively. At this condition, the free fatty acids (FFA) content and peroxide value (PV) increment of WG oil at 40°C remained below 5% and 2.24 meq O2/kg for 60 days, respectively. The residual Aw of this WG sample was 0.13, and it is near the Aw corresponding to its monolayer. No significant decrease of fatty acids was observed during SIR processing, while about 96.42% of its original tocopherols still retained in WG treated at 90°C for 20 min.

[This corrects the article DOI: 10.1371/journal.pone.0142708.].

A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research.This current systematic review aimed to evaluate the available evidence for the association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400.PubMed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were systematically searched. Manual searching was also applied. Both RCTs and observational studies comparing the clinical outcomes of high AUC0-24/MIC groups versus low AUC0-24/MIC groups were eligible. Two reviewers independently extracted the data. The primary outcomes were mortality and infection treatment failure. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated.No RCTs were retrieved. Nine cohort studies were included in the meta-analysis. Mortality rates were significantly lower in high AUC0-24/MIC groups (RR = 0.47, 95%CI = 0.31-0.70, p