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IntroductionThis study aimed to investigate the effect of aerobic exercise on the expression of neitrin-1,DCC receptor and myocardial fibrosis in rats with acute myocardial infarction.MethodsTwenty-four rats were randomly divided into three groups: the sham group (n = 8), the acute myocardial infarction (AMI) model group (n = 8), and the aerobic exercise treatment after acute myocardial infarction group (ET) (n = 8). After 10 weeks, the serum levels of netrin-1, tumor necrosis factor alpha α (TNF-α), and interleukin 6 (IL-6) were measured. The expression of matrix metalloproteinase 2 and 9 (MMP2, 9), and their inhibitor, tissue inhibitor of metalloproteinase 2 (TIMP2), myocardial netrin-1, and the deleted in colorectal cancer (DCC) receptor were evaluated. Histopathological results were also evaluated. The collagen volume fraction of the myocardial tissues was also calculated.ResultsCompared with the sham group, in the AMI and ET groups, left ventricular end diastolic pressure (LVEDP) were increased, while left ventricular systolic pressure (LVSP), and left ventricular pressure maximal rate of rise and fall (± dp/dtmax) were significantly decreased (PConclusionsAerobic exercise increased levels of serum netrin-1, myocardial netrin-1, and the DCC receptor and reduced the expression of myocardial MMP2 and MMP9 proteins, to improve the degree of fibrosis following myocardial infarction in rats.

Short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) have been already used to perform noninvasive prenatal paternity testing from maternal plasma DNA. The frequently used technologies were PCR followed by capillary electrophoresis and SNP typing array, respectively. Here, we developed a noninvasive prenatal paternity testing (NIPAT) based on SNP typing with maternal plasma DNA sequencing. We evaluated the influence factors (minor allele frequency (MAF), the number of total SNP, fetal fraction and effective sequencing depth) and designed three different selective SNP panels in order to verify the performance in clinical cases. Combining targeted deep sequencing of selective SNP and informative bioinformatics pipeline, we calculated the combined paternity index (CPI) of 17 cases to determine paternity. Sequencing-based NIPAT results fully agreed with invasive prenatal paternity test using STR multiplex system. Our study here proved that the maternal plasma DNA sequencing-based technology is feasible and accurate in determining paternity, which may provide an alternative in forensic application in the future.

Quantifying carbon (C) sequestration in paddy soils is necessary to help better understand the effect of agricultural practices on the C cycle. The objective of the present study was to assess the effects of tillage practices [conventional tillage (CT) and no-tillage (NT)] and the application of nitrogen (N) fertilizer (0 and 210 kg N ha(-1)) on fluxes of CH(4) and CO(2), and soil organic C (SOC) sequestration during the 2009 and 2010 rice growing seasons in central China. Application of N fertilizer significantly increased CH(4) emissions by 13%-66% and SOC by 21%-94% irrespective of soil sampling depths, but had no effect on CO(2) emissions in either year. Tillage significantly affected CH(4) and CO(2) emissions, where NT significantly decreased CH(4) emissions by 10%-36% but increased CO(2) emissions by 22%-40% in both years. The effects of tillage on the SOC varied with the depth of soil sampling. NT significantly increased the SOC by 7%-48% in the 0-5 cm layer compared with CT. However, there was no significant difference in the SOC between NT and CT across the entire 0-20 cm layer. Hence, our results suggest that the potential of SOC sequestration in NT paddy fields may be overestimated in central China if only surface soil samples are considered.

Plant diurnal oscillation is a 24-hour period based variation. The correlation between diurnal genes and biological pathways was widely revealed by microarray analysis in different species. Rice (Oryza sativa) is the major food staple for about half of the world's population. The rice flag leaf is essential in providing photosynthates to the grain filling. However, there is still no comprehensive view about the diurnal transcriptome for rice leaves. In this study, we applied rice microarray to monitor the rhythmically expressed genes in rice seedling and flag leaves. We developed a new computational analysis approach and identified 6,266 (10.96%) diurnal probe sets in seedling leaves, 13,773 (24.08%) diurnal probe sets in flag leaves. About 65% of overall transcription factors were identified as flag leaf preferred. In seedling leaves, the peak of phase distribution was from 2:00am to 4:00am, whereas in flag leaves, the peak was from 8:00pm to 2:00am. The diurnal phase distribution analysis of gene ontology (GO) and cis-element enrichment indicated that, some important processes were waken by the light, such as photosynthesis and abiotic stimulus, while some genes related to the nuclear and ribosome involved processes were active mostly during the switch time of light to dark. The starch and sucrose metabolism pathway genes also showed diurnal phase. We conducted comparison analysis between Arabidopsis and rice leaf transcriptome throughout the diurnal cycle. In summary, our analysis approach is feasible for relatively unbiased identification of diurnal transcripts, efficiently detecting some special periodic patterns with non-sinusoidal periodic patterns. Compared to the rice flag leaves, the gene transcription levels of seedling leaves were relatively limited to the diurnal rhythm. Our comprehensive microarray analysis of seedling and flag leaves of rice provided an overview of the rice diurnal transcriptome and indicated some diurnal regulated biological processes and key functional pathways in rice.

Objective: This study focused on the gastrointestinal (GI) symptoms in the omicron variant infection and the related factors based on digestive health., Methods: A cross-sectional study was conducted on individuals infected with the omicron variant. A structured questionnaire was developed to gather their demographic characteristics, preexisting digestive problems (diseases & symptoms), and clinical manifestations during the infection., Results: 11,484 questionnaires were received from online platforms. 7,929 infected participants were selected based on inclusion and exclusion criteria. Among them, 4,225 (53.3%) were females, and the mean age was 36.0±8.8 years old. In general, the proportion of GI symptoms in the omicron variant infection was 31.4% (62.6% and 25.0% in participants with pre-existing digestive problems and those without, respectively). The participants with pre-existing digestive problems exhibited more severe clinical manifestations during infection compared to those without. Notably, participants with gastrointestinal symptoms during the infection had more severe clinical manifestations, regardless of basic digestive health. Upper, rather than lower GI symptoms were more closely associated with the severity of the clinical manifestations. NSAIDs may increase the occurrence of GI symptoms in participants with a healthy digestive system but not in those with preexisting digestive problems., Conclusion: Patients infected with the omicron variant may experience more severe clinical symptoms if they have gastrointestinal issues. Digestive health strongly influences the occurrence of gastrointestinal symptoms and the severity of clinical manifestations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Two-characters continuation, which is a string with two characters emerging in linear sequence, can break through the encapsulation and independence of long solidified language chunks (words and phrases). In this way, two-characters continuation can measure the information of not only static language units (words and phrases) but also their combination in the text. Therefore, two-characters continuation is used as a measurement unit for investigating Chinese text's difficulty, to enhance the accuracy of measuring text's difficulty. Three different measurement methods of text's difficulty are proposed, which are respectively based on "continuation index of character", "new and stable two-characters continuation" and "emerging tendency of two-characters continuation". The results show that compared to other two methods, the measurement method of text's difficulty based on new and stable two-characters continuations has better effectiveness, whose accuracies for measuring text's difficulty with 6 levels, 3 levels and 2 levels difficulties can reach 36.4%, 64.6% and 79.6%, respectively. In addition, compared to Jiang and Wu's research works, the above measurement method also shows a better effectiveness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou, Zheng. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis (AD), and provide reference for rational clinical medication., Methods: PubMed, Medline, Embase, Web of Science, Clinical Trials Website, and Cochrane Library databases were searched from the time of establishment until January 6, 2024, to compile a list of all randomized controlled trials (RCTs) including upadacitinib in the treatment of moderate-to-severe AD. The quality of the included studies was evaluated using the Cochrane Systematic Review. Review Manager 5.3 software was utilized for statistical analysis of outcome measures., Results: A total of five studies were included in the meta-analysis. The results revealed that the 15 mg and 30 mg upadacitinib significantly improved Eczema Area and Severity Index (EASI) 75% {[Odds Ratio (OR) = 8.58, 95% confidence interval (CI) (5.84-12.60), P < 0.00001] [OR = 15.62, 95% CI (10.89-22.42), P < 0.00001]}, Numerical Rating Scale (NRS) ≥ 4 {[OR = 7.13, 95% CI (5.63-9.01), P < 0.00001] [OR = 11.30, 95% CI (8.93-14.31), P < 0.00001]}, and Investigator's Global Assessment (IGA) 0/1 {[OR = 8.63, 95% CI (6.60-11.27), P < 0.00001] [OR = 16.04, 95% CI (12.26-20.99), P < 0.00001]} compared to placebo. In terms of safety, although 15 mg and 30 mg upadacitinib significantly increased the overall adverse events rate compared to placebo {[OR = 1.31, 95% CI (1.09-1.58), P = 0.004] [OR = 1.85, 95% CI (1.54-2.21), P < 0.00001]}, there was no significant difference in the serious adverse events rate {[OR = 0.73, 95% CI (0.41-1.29), P = 0.28] [OR = 0.69, 95% CI (0.39-1.23), P = 0.21]} and withdrawal rate due to adverse events {[OR = 0.66, 95% CI (0.39-1.11), P = 0.12] [OR = 0.85, 95% CI (0.52-1.38), P = 0.50]} compared to placebo., Conclusion: This meta-analysis preliminarily suggests that upadacitinib is effective and safe for usage in the treatment of moderate-to-severe AD. Additionally, upadacitinib can instantly relieve itchiness and effectively reduce symptoms and signs, with its 30-mg dose being more effective than the 15-mg dose., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The Toll-like receptor (TLR) 4-mediated nuclear factor kappa B (NF-κB) signaling pathway regulates the production of inflammatory factors and plays a key role in the pathogenesis of gouty arthritis. The aim of the present study was to investigate the link among TLR4 gene polymorphisms at various loci, protein expression, and gouty arthritis susceptibility., Methods: Between 2016 and 2021, a case-control study was used to collect a total of 1207 study subjects, including 317 male patients with gouty arthritis (gout group) and 890 healthy males (control group). The association between gout susceptibility and different genetic models was analyzed by typing three loci of the TLR4 gene (rs2149356, rs2737191, and rs10759932) using a multiplex point mutation rapid assay, and the association between protein expression and gout was confirmed by measuring TLR4 protein concentrations using enzyme-linked immunosorbent assays (ELISAs)., Results: In a codominant models AA and AG, the rs2737191 polymorphism in the gout group increased the risk of gout compared to the AA genotype (OR = 2.249, 95%CI 1.010~5.008), and the risk of gout was higher for those carrying the G allele compared to the A allele (OR = 2.227, 95%CI 1.006~4.932). TLR4 protein expression was different between the two groups with different locus genotypes. The differences in TLR4 protein expression between the gout group and control group were statistically significant between the following genotypes: the GG and GT genotypes of the rs2149356 polymorphism; the AA and AG genotypes of the rs2737191 polymorphism; and the TT and TC genotypes of the rs10759932 polymorphism(P<0.05). The TLR4 protein level in the gout group (19.19±3.09 ng/ml) was significantly higher than that in the control group (15.85±4.75 ng/ml)., Conclusion: The AG genotype of the TLR4 gene rs2737191 polymorphism may be correlated with the development of gouty arthritis. The level of TLR4 protein expression is significantly higher in patients with gouty arthritis than in controls, and there is a correlation between high TLR4 protein expression and the development of gouty arthritis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

'Allen Eureka' is a bud variety of Eureka lemon with excellent fruiting traits, but severe winter defoliation affects the following year's yield, and the response mechanism of lemon defoliation is currently unknown. Two lemon cultivars ('Allen Eureka' and 'Yunning No. 1') with different defoliation traits were used as materials to investigate the molecular regulatory mechanisms of different leaf abscission periods in lemons. The petiole abscission zone was collected at three different defoliation stages, namely, the predefoliation stage (k15), the middefoliation stage (k30), and the postdefoliation stage (k45). Transcriptome sequencing was performed to analyze the gene expression differences between these two cultivars. A total of 1141, 2695, and 1433 differentially expressed genes (DEGs) were obtained in k15, k30, and k45, respectively, and the number of DEGs in k30 was the largest. GO analysis revealed that the DEGs between the two cultivars were mainly enriched in processes related to hydrolase activity, chitinase activity, oxidoreductase activity, and transcription regulator activity in the defoliation stages. KEGG analysis showed that the DEGs were concentrated in k30, which involved plant hormone signal transduction, phenylpropanoid biosynthesis, and biosynthesis of amino acids. The expression trends of some DEGs suggested their roles in regulating defoliation in Lemon. Seven genes were obtained by WGCNA, including sorbitol dehydrogenase (CL9G068822012&#95;alt, CL9G068820012&#95;alt, CL9G068818012&#95;alt), abscisic acid 8'-hydroxylase (CL8G064053012&#95;alt, CL8G064054012&#95;alt), and asparagine synthetase (CL8G065162012&#95;alt, CL8G065151012&#95;alt), suggesting that these genes may be involved in the regulation of lemon leaf abscission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The selection of construction plans for adverse geological conditions frequently encountered during the construction of bridge pile foundations will have a significant impact on the project's progress, quality, and cost. There is a need for the optimization of multi-attribute decision-making methods, considering the subjectivity in in weight allocation and the practical implementation obstacles. In this study, an evaluation framework for pile foundation construction schemes in karst areas was established. The directed graph and Bellman-Ford algorithm are employed to improve the Analytic Network Process (ANP) in the systematic structure, thereby calculating the subjective weights of various indicators. Simultaneously, based on the concept of dynamic weighting, a multiple linear regression is introduced for analyzing the weights of similar projects, resulting in the derivation of universal weights for the primary indicators within the evaluation system. The combination weights are subsequently determined through the weighted average of the two types of weights. Finally, the comprehensive scores of alternative schemes are computed using the grey-fuzzy evaluation method to enable decision-making in scheme selection. Cloud model, ELECTRE-II, and VIKOR methodologies were utilized for the comparison of results. Combining with a case study of a bridge project in karst development area in southern China, the findings indicate that the improved ANP method possesses practical applicability and yields effective computational results. The introduction of universal weights serves to ameliorate the inherent subjectivity in weight allocation. The pile foundation quality achieved using the optimal construction plan is classified as Class I, which prove the feasibility of the model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although doxorubicin (DOX) is an efficient chemotherapeutic drug for human tumors, severe cardiotoxicity restricts its clinical use. Cinnamaldehyde (CA), a bioactive component isolated from Cinnamonum cassia, possesses potent anti-oxidative and anti-apoptotic potentials. The major aim of this study was to evaluate the protective role of CA against DOX-induced cardiotoxicity. To this end, cardiomyocyte injury models were developed using DOX-treated H9c2 cells and DOX-treated rats, respectively. Herein, we found that CA treatment increased cardiomyocyte viability and attenuated DOX-induced cardiomyocyte death in vitro. CA further protected rats against DOX-induced cardiotoxicity, as indicated by elevated creatine kinase (CK) and lactate dehydrogenase (LDH) levels, myocardium injury, and myocardial fibrosis. CA alleviated DOX-induced myocardial oxidative stress by regulating reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels. Mechanistically, CA markedly accelerated nuclear translocation of nuclear erythroid factor 2-related factor 2 (Nrf2) and increased heme oxygenase-1 (HO-1) expression. Consequently, CA decreased DOX-induced cardiomyocyte ferroptosis, while Erastin (a ferroptosis agonist) treatment destroyed the effect of CA on increasing cardiomyocyte viability. Taken together, the current results demonstrate that CA alleviates DOX-induced cardiotoxicity, providing a promising opportunity to increase the clinical application of DOX., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. Most cases are diagnosed at an advanced stage using current tumor markers. Here, we aimed to identify potential novel potential biomarkers for NSCLC., Material/methods: Four independent datasets from the Gene Expression Omnibus database were analyzed. The relative expression of ribonucleotide reductase regulatory subunit M2 (RRM2) mRNA in 30 paired of NSCLC paired tissues was measured by reverse transcription quantitative PCR. Serum levels of cytokeratin fragment 21-1 (CYFRA21-1), pro-gastrin-releasing peptide (ProGRP), carcinoembryonic antigen (CEA), and neuron-specific enolase (NSE) were measured using electrochemiluminescence immunoassays, and serum RRM2 levels were evaluated by an enzyme-linked immunosorbent assay., Results: The mRNA expression level of RRM2 was significantly increased in most NSCLC lesions compared to para-adjacent tissues. Serum RRM2 levels in NSCLC patients were significantly elevated compared to healthy controls and were also associated with distant metastasis and histological type, but not with tumor size or lymph node metastasis. Receiver operating characteristic curve analysis showed a higher diagnostic ratio for NSCLC using RRM2 alone compared to other traditional tumor markers., Conclusions: RRM2 is a potential sero-diagnostic biomarker for NSCLC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This study was performed to explore the causal association between asthma and chronic obstructive pulmonary disease(COPD)., Methods: We obtained summary statistics for asthma from 408,442 Europeans in an open genome-wide association study (GWAS) from the UK Biobank to select strongly associated single nucleotide polymorphisms that could serve as instrumental variables for asthma (P < 5×10-8). Additional summary statistics for COPD were obtained from 193,638 individuals of European ancestry in the GWAS published by FinnGen. Univariable Mendelian randomization(UVMR) analysis was performed using inverse variance weighted (IVW) as the primary method of analysis. The reliability of the results was verified by multivariable MR(MVMR), reverse and replication MR analysis, and sensitivity analysis., Results: In the UVMR analysis, asthma increased the risk of COPD, with an odds ratio (OR) of 1.27 (95% confidence interval (CI) = 1.16-1.39, P = 5.44×10-7). Estimates were consistent in MVMR analyses by the adjustments of smoking initiation, age of smoking initiation, cigarettes per day, PM 2.5, and the combination of the above factors. In the reverse MR analysis, there was no evidence of a causal effect of COPD on asthma risk(OR = 1.02, 95% CI = 0.97-1.07, P = 0.3643). In the replication MR analysis, asthma still increased the risk of COPD. Sensitivity analyses validated the robustness of the above associations., Conclusions: We found that genetically predicted asthma was positively associated with the risk of COPD. Additionally, there was no evidence that COPD increases the risk of asthma. Further clarification of this link and underlying mechanisms is needed to identify feasible measures to promote COPD prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In recent years, the prevalence of T2DM has been increasing annually, in particular, the personal and socioeconomic burden caused by multiple complications has become increasingly serious. This study aimed to screen out the high-risk complication combination of T2DM through various data mining methods, establish and evaluate a risk prediction model of the complication combination in patients with T2DM. Questionnaire surveys, physical examinations, and biochemical tests were conducted on 4,937 patients with T2DM, and 810 cases of sample data with complications were retained. The high-risk complication combination was screened by association rules based on the Apriori algorithm. Risk factors were screened using the LASSO regression model, random forest model, and support vector machine. A risk prediction model was established using logistic regression analysis, and a dynamic nomogram was constructed. Receiver operating characteristic (ROC) curves, harrell's concordance index (C-Index), calibration curves, decision curve analysis (DCA), and internal validation were used to evaluate the differentiation, calibration, and clinical applicability of the models. This study found that patients with T2DM had a high-risk combination of lower extremity vasculopathy, diabetic foot, and diabetic retinopathy. Based on this, body mass index, diastolic blood pressure, total cholesterol, triglyceride, 2-hour postprandial blood glucose and blood urea nitrogen levels were screened and used for the modeling analysis. The area under the ROC curves of the internal and external validations were 0.768 (95% CI, 0.744-0.792) and 0.745 (95% CI, 0.669-0.820), respectively, and the C-index and AUC value were consistent. The calibration plots showed good calibration, and the risk threshold for DCA was 30-54%. In this study, we developed and evaluated a predictive model for the development of a high-risk complication combination while uncovering the pattern of complications in patients with T2DM. This model has a practical guiding effect on the health management of patients with T2DM in community settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The purpose of this study was to determine whether FABP1 and FAS regulate expression of collagen and its crosslinking via lysyl oxidase in isolated adipocytes from Zongdihua pigs. We aimed to identify biochemical processes affecting meat quality using molecular tools to provide a basis for breeding improvement of these animals. We measured expression levels of FABP1 and related genes using qRT-PCR in longissimus dorsi muscle and subcutaneous adipose tissues. Primary adipocytes from fat tissues were isolated and FABP1 and FAS were over-expressed from recombinant plasmids. Sequence analysis of the cloned genes indicated that FABP1 encodes a hydrophobic protein of 128 amino acids and contained 12 predicted phosphorylation sites and no transmembrane regions. The basal levels of FABP1 and FAS expression in pig tissues were 3-3.5-fold higher in subcutaneous fat compared with muscle (P < 0.01). Recombinant expression plasmids were successfully transfected into the cloned preadipocytes and (a) over-expression of FAS resulted in significantly increased expression of COL3A1 (P < 0.05) and significantly inhibited lysyl oxidase LOX expression (P < 0.01); (b) over-expression of FABP1 significantly increased COL3A1 expression (P < 0.01) and significantly inhibited LOX expression (P< 0.05) and significantly reduced lysyl oxidase activity (P < 0.01). Therefore, FAS enhanced FABP1 expression resulting in increased collagen accumulation and this preliminarily suggested that FAS and FABP1 can serve as fat-related candidate genes and provide a theoretical basis for the study of fat deposition in Zongdihua pigs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Drug repositioning allows expedited discovery of new applications for existing compounds, but re-screening vast compound libraries is often prohibitively expensive. "Connectivity mapping" is a process that links drugs to diseases by identifying compounds whose impact on expression in a collection of cells reverses the disease's impact on expression in disease-relevant tissues. The LINCS project has expanded the universe of compounds and cells for which data are available, but even with this effort, many clinically useful combinations are missing. To evaluate the possibility of repurposing drugs despite missing data, we compared collaborative filtering using either neighborhood-based or SVD imputation methods to two naive approaches via cross-validation. Methods were evaluated for their ability to predict drug connectivity despite missing data. Predictions improved when cell type was taken into account. Neighborhood collaborative filtering was the most successful method, with the best improvements in non-immortalized primary cells. We also explored which classes of compounds are most and least reliant on cell type for accurate imputation. We conclude that even for cells in which drug responses have not been fully characterized, it is possible to identify unassayed drugs that reverse in those cells the expression signatures observed in disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Scenario models of a moving subway train can help investigate the influence of different fire locations on smoke propagation characteristics in curved tunnels. To this end, this study adopts the three-dimensional Unsteady Reynolds Average Navier-Stokes equations method and the renormalization group k-ε two-equation turbulence model with buoyancy correction for numerical analysis. The motion of the train is replicated using the slip grid technique. The results indicate that when a fire breaks out on a moving train in tunnels, the piston wind leads the longitudinal movement of the smoke. If a fire erupts in the head or middle car of a moving train, the time of smoke backflow is delayed by 30 s or 17 s, respectively, compared to that for the tail car. The obtained results provide a theoretical basis for reasonably controlling the smoke flow in subway tunnels and reducing casualties in fire accidents., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rotenone is a commonly used insecticidal chemical in agriculture and it is an inhibitor of mitochondrial complex Ⅰ. Previous studies have found that rotenone induces the production of reactive oxygen species (ROS) by inhibiting electron transport in the mitochondria of somatic and germ cells. However, there is little precise information on the effects of rotenone exposure in porcine oocytes during in vitro maturation, and the mechanisms underlying these effects have not been determined. The Cumulus-oocyte complexes were supplemented with different concentrations of rotenone to elucidate the effects of rotenone exposure on the meiotic maturation of porcine oocytes during in vitro maturation for about 48 hours. First, we found that the maturation rate and expansion of cumulus cells were significantly reduced in the 3 and 5 μM rotenone-treated groups. Subsequently, the concentration of rotenone was determined to be 3 μM. Also, immunofluorescence, western blotting, and image quantification analyses were performed to test the rotenone exposure on the meiotic maturation, total and mitochondrial ROS, mitochondrial function and biogenesis, mitophagy and apoptosis in porcine oocytes. Further experiments showed that rotenone treatment induced mitochondrial dysfunction and failure of mitochondrial biogenesis by repressing the level of SIRT1 during in vitro maturation of porcine oocytes. In addition, rotenone treatment reduced the ratio of active mitochondria to total mitochondria, increased ROS production, and decreased ATP production. The levels of LC3 and active-caspase 3 were significantly increased by rotenone treatment, indicating that mitochondrial dysfunction induced by rotenone increased mitophagy but eventually led to apoptosis. Collectively, these results suggest that rotenone interferes with porcine oocyte maturation by inhibiting mitochondrial function., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Heo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The steam turbine is one of the major pieces of equipment in thermal power plants. It is crucial to predict its output accurately. However, because of its complex coupling relationships with other equipment, it is still a challenging task. Previous methods mainly focus on the operation of the steam turbine individually while ignoring the coupling relationship with the condenser, which we believe is crucial for the prediction. Therefore, in this paper, to explore the coupling relationship between steam turbine and condenser, we propose a novel approach for steam turbine power prediction based on the encode-decoder framework guided by the condenser vacuum degree (CVD-EDF). In specific, the historical information within condenser operation conditions data is encoded using a long-short term memory network. Moreover, a connection module consisting of an attention mechanism and a convolutional neural network is incorporated to capture the local and global information in the encoder. The steam turbine power is predicted based on all the information. In this way, the coupling relationship between the condenser and the steam turbine is fully explored. Abundant experiments are conducted on real data from the power plant. The experimental results show that our proposed CVD-EDF achieves great improvements over several competitive methods. our method improves by 32.2% and 37.0% in terms of RMSE and MAE by comparing the LSTM at one-minute intervals., Competing Interests: The authors have declared that no competing interests exist.

This study determined the physical and mechanical characteristics of fresh black fungus during the harvesting season to provide basic data for the development of mechanical equipment for black fungus harvesting and processing. We have conducted a comprehensive test of black fungus cultivars "Heishan". The mono-factor separation force experiments of black fungus and black fungus virgulate medium were conducted. It was noted that the tension angle was an important factor affecting the separation force, which was mainly distributed between 1.06 and 3.65 N. Besides, the average value of Poisson's ratio of black fungus was measured to be 0.445 in the tensile test of black fungus leaves using image recognition and analysis techniques, with a test error within 2.5%; and the average value of tensile elastic modulus and shear elastic modulus of black fungus leaves was 0.947 MPa and 0.327 MPa, respectively; we also found that the average tensile strength at the root of black fungus was not significantly different from that at the leaf, which was around 0.436 MPa. In addition, it was obtained that the height and thickness dimensions of black fungus in the picking season conformed to a normal distribution, and concentrated around 34.39mm and 0.92mm respectively., Competing Interests: The authors have declared that no competing interests exist.

This cross-sectional study sought to identify gender differences in individual behavioral attitudes, personal traits, and entrepreneurial education based on planned behavior theory. The Smart partial least squares (PLS) structural equation model and PLS path modeling were used. A survey design was used to collect data from 309 samples using quantitative measures. The model was tested for validity and reliability and showed variance (full, R2 = 58.9% and split, R2 = 62.7% and R2 = 52.7%) in male and female model predictive power, respectively. Subjective norms (SN), personality traits (PT), and entrepreneurial education (EE) significantly impacted the male sample's intention. Females' intentions toward entrepreneurship was less affected by attitude toward behavior (ATB), subjective norms (SN), perceived behavioral control (PBC), and entrepreneurship education (EE). Further, attitudes, social norms, and behavioral controls as mediation variables indicate a significant and positive role of male and female intentions. These findings imply that behavioral beliefs (ATB, PBC, and SN) influence entrepreneurial intention-action translation. The results significantly supported the designed hypotheses and shed light on individual personality traits (PT) and entrepreneurship education (EE) underpinning enterprise intention. The study determined that EE and PT are the strongest predictors of intention, thus highlighting the role of these motives in the entrepreneurial process. This study contributes to the growing body of knowledge on youth entrepreneurs, expands our understanding of entrepreneurship as a practical career choice, and offers a novel account differentiating male and female PT. The drive to evaluate the effects of entrepreneurial intention among budding disparities in Pakistan requires a more profound knowledge of the aspects that endorse entrepreneurship as a choice of profession and enhances youth incentive abilities to engage in entrepreneurial activities based on exploitation., Competing Interests: The authors have declared that no competing interests exist.

Because large numbers of artworks are preserved in museums and galleries, much work must be done to classify these works into genres, styles and artists. Recent technological advancements have enabled an increasing number of artworks to be digitized. Thus, it is necessary to teach computers to analyze (e.g., classify and annotate) art to assist people in performing such tasks. In this study, we tested 7 different models on 3 different datasets under the same experimental setup to compare their art classification performances when either using or not using transfer learning. The models were compared based on their abilities for classifying genres, styles and artists. Comparing the result with previous work shows that the model performance can be effectively improved by optimizing the model structure, and our results achieve state-of-the-art performance in all classification tasks with three datasets. In addition, we visualized the process of style and genre classification to help us understand the difficulties that computers have when tasked with classifying art. Finally, we used the trained models described above to perform similarity searches and obtained performance improvements., Competing Interests: The authors have declared that no competing interests exist.

The coronavirus disease (COVID-19) pandemic has impacted the economy, livelihood, and physical and mental well-being of people worldwide. This study aimed to compare the mental health status during the pandemic in the general population of seven middle income countries (MICs) in Asia (China, Iran, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). All the countries used the Impact of Event Scale-Revised (IES-R) and Depression, Anxiety and Stress Scale (DASS-21) to measure mental health. There were 4479 Asians completed the questionnaire with demographic characteristics, physical symptoms and health service utilization, contact history, knowledge and concern, precautionary measure, and rated their mental health with the IES-R and DASS-21. Descriptive statistics, One-Way analysis of variance (ANOVA), and linear regression were used to identify protective and risk factors associated with mental health parameters. There were significant differences in IES-R and DASS-21 scores between 7 MICs (p<0.05). Thailand had all the highest scores of IES-R, DASS-21 stress, anxiety, and depression scores whereas Vietnam had all the lowest scores. The risk factors for adverse mental health during the COVID-19 pandemic include age <30 years, high education background, single and separated status, discrimination by other countries and contact with people with COVID-19 (p<0.05). The protective factors for mental health include male gender, staying with children or more than 6 people in the same household, employment, confidence in doctors, high perceived likelihood of survival, and spending less time on health information (p<0.05). This comparative study among 7 MICs enhanced the understanding of metal health in the general population during the COVID-19 pandemic., Competing Interests: The authors have declared that no competing interests exist.

UVA/riboflavin corneal cross-linking (CXL) is a common used approach to treat progressive keratoconus. This study aims to investigate the alteration of corneal stiffness following CXL by mimicking the inflation of the eye under the in vivo loading conditions. Seven paired porcine eye globes were involved in the inflation test to examine the corneal behaviour. Cornea-only model was constructed using the finite element method, without considering the deformation contribution from sclera and limbus. Inverse analysis was conducted to calibrate the non-linear material behaviours in order to reproduce the inflation test. The corneal stress and strain values were then extracted from the finite element models and tangent modulus was calculated under stress level at 0.03 MPa. UVA/riboflavin cross-linked corneas displayed a significant increase in the material stiffness. At the IOP of 27.25 mmHg, the average displacements of corneal apex were 307 ± 65 μm and 437 ± 63 μm (p = 0.02) in CXL and PBS corneas, respectively. Comparisons performed on tangent modulus ratios at a stress of 0.03 MPa, the tangent modulus measured in the corneas treated with the CXL was 2.48 ± 0.69, with a 43±24% increase comparing to its PBS control. The data supported that corneal material properties can be well-described using this inflation methods following CXL. The inflation test is valuable for investigating the mechanical response of the intact human cornea within physiological IOP ranges, providing benchmarks against which the numerical developments can be translated to clinic., Competing Interests: The authors have declared that no competing interests exist.

Because a DNA nucleotide sequence has the characteristics of large storage capacity, high parallelism, and low energy consumption, DNA cryptography is favored by information security researchers. Image encryption algorithms based on DNA coding have become a research hotspot in the field of image encryption and security. In this study, based on a comprehensive review of the existing studies and their results, we present new insights into the existing image encryption algorithms based on DNA coding. First, the existing algorithms were summarized and classified into five types, depending on the type of DNA coding: DNA fixed coding, DNA dynamic coding, different types of base complement operation, different DNA sequence algebraic operations, and combinations of multiple DNA operations. Second, we analyzed and studied each classification algorithm using simulation and obtained their advantages and disadvantages. Third, the DNA coding mechanisms, DNA algebraic operations, and DNA algebraic combination operations were compared and discussed. Then, a new scheme was proposed by combining the optimal coding mechanism with the optimal DNA coding operation. Finally, we revealed the shortcomings of the existing studies and the future direction for improving image encryption methods based on DNA coding., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: China carries a heavy burden of cervical cancer and has an alarmingly low cervical cancer screening rate. In order to achieve the goal of cervical cancer elimination, there is an urgent need for suitable methods and strategies in China., Materials and Methods: A total 9972 woman who received cervical cancer screening services of National Cervical Cancer Screening Program in Rural Areas (NCCSPRA) in 8 project counties participated in this study. TruScreen, HPV test and LBC test were performed in all participants. A total of 1945women had one or more than one positive or abnormal screening results of the above three screening tests subsequently received colposcopy. The detection rate of CIN2+ between the three tests were compared., Results: No matter what kind of screening method is used, the CIN2+ detection rate in the eastern regions was much higher than that in the central and western regions. The total detection rate of CIN2+ in HPV group was highest (0.73%), following in LBC group (0.44%) and TS group (0.31%). There was statistically significant difference in the total detection rate of CIN2+ between TS and HPV groups, LBC and HPV groups, respectively. There was no statistical difference in the total detection rate of CIN2+ between TS and LBC screening groups. Moreover, except for the eastern regions, there was no statistical difference in the detection rate of CIN2+ between TS group and the other two groups in central and western regions., Conclusion: If it can meet the requirements of the laboratory and personnel, HPV test seems to be the preferred method for cervical cancer screening in rural areas of China. The characteristics of minimal training requirements, simple operation, real-time results obtained without the collection of cervical cell samples and the help of laboratory equipment and cytologists of TS make it ideal for cervical cancer screening in low-resource regions., Competing Interests: The authors have declared that no competing interests exist.

The food industry is currently shown the concern with low-fat products. This study aims to evaluate the properties of oat β-glucan(OG)-marine collagen peptide (MCP) mixed gels induced by high pressure at different ratios, pressures, pH levels and the superiority of application in the sausage. The results indicated that the typical gel with high levels of hardness, cohesiveness, springiness, and chewiness, as well as high water holding and oil adsorption capacities was formed using the OG/MCP ratio of 10:1 under 400 MPa at pH 6.0. The mixed gel replacing with 50% fat significantly increased the springiness and chewing(P<0.05), and sausages with 80% mixed gel were significantly juicier than that of the control sausage(P<0.05). Therefore, OG-MCP mixed gel could be used in the reformulation of low-fat meat products to enhance their safety and nutritional value., Competing Interests: The authors have declared that no competing interests exist.

Background: Fecal microbiota transplantation is an effective treatment for many gastrointestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease, especially ulcerative colitis. Changes in colonic microflora may play an important role in the pathogenesis of ulcerative colitis, and improvements in the intestinal microflora may relieve the disease. Fecal bacterial transplants and oral probiotics are becoming important ways to relieve active ulcerative colitis., Purpose: This systematic review with meta-analysis compared the efficacy and safety of basic treatment combined with fecal microbiota transplantation or mixed probiotics therapy in relieving mild to moderate ulcerative colitis., Methods: The PubMed, Embase, and Cochrane libraries (updated September 2019) were searched to identify randomized, placebo-controlled, or head-to-head trials assessing fecal microbiota transplantation or probiotic VSL#3 as induction therapy in active ulcerative colitis. We analyze data using the R program to obtain evidence of direct comparison and to generate intermediate variables for indirect treatment comparisons., Results: Seven randomized, double-blind, placebo-controlled trials were used as the sources of the induction data. All treatments were superior to placebo. In terms of clinical remission and clinical response to active ulcerative colitis, direct comparisons showed fecal microbiota transplantation (OR = 3.47, 95% CI = 1.93-6.25) (OR = 2.48, 95% CI = 1.18-5.21) and mixed probiotics VSL#3 (OR = 2.40, 95% CI = 1.49-3.88) (OR = 3.09, 95% CI = 1.53-6.25) to have better effects than the placebo. Indirect comparison showed fecal microbiota transplantation and probiotic VSL#3 did not reach statistical significance either in clinical remission (RR = 1.20, 95% CI = 0.70-2.06) or clinical response (RR = 0.95, 95% CI = 0.62-1.45). In terms of safety, fecal microbiota transplantation (OR = 1.15, 95% CI = 0.51-2.61) and VSL #3 (OR = 0.90, 95% CI = 0.33-2.49) showed no statistically significant increase in adverse events compared with the control group. In terms of serious adverse events, there was no statistical difference between the fecal microbiota transplantation group and the control group (OR = 1.29, 95% CI = 0.46-3.57). The probiotics VSL#3 seems more safer than fecal microbiota transplantation, because serious adverse events were not reported in the VSL#3 articles., Conclusions: Fecal microbiota transplantation or mixed probiotics VSL#3 achieved good results in clinical remission and clinical response in active ulcerative colitis, and there was no increased risk of adverse reactions. There was no statistical difference between the therapeutic effect of fecal microbiota transplantation and that of mixed probiotics VSL#3. However, the use of fecal microbiota transplantation and probiotics still has many unresolved problems in clinical applications, and more randomized controlled trials are required to confirm its efficacy., Competing Interests: The authors have declared that no competing interests exist.

Background: Several anti-D immunoglobulin strategies exist for preventing Rh hemolytic disease of the fetus and newborn. This study systematically assessed the clinical value of those therapeutic strategies., Methods: The Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for eligible studies that evaluated the value of different anti-D immunoglobulin strategies in preventing maternal anti-D antibody sensitization. Combined odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. The network meta-analysis was conducted using Stata 14.2 and WinBUGS 1.4.3 software., Results: Twenty-four original studies involving 64860 patients were included. Among all therapeutic measures, injecting 300 μg anti-D immunoglobulin at 28 and 34 gestational weeks (antenatal 5/E) appeared to be the most effective measure for preventing maternal antibody sensitization (surface under the cumulative ranking curve [SUCRA] = 96.8%), while a single injection at 28 gestational weeks (SUCRA = 89.2%) was the second most effective. Administering no injection or a placebo (SUCRA = 0.0%) was the least effective intervention measure., Conclusion: Among the therapeutic measures, antenatal 5/E appeared to be the best method for reducing the positive incidence of anti-D antibodies in the maternal serum; thus, it may be the most effective treatment for preventing fetal hemolytic disease., Competing Interests: The authors have declared that no competing interests exist.

Pepsin plays an important role in laryngopharyngeal reflux (LPR), a risk factor for the development of hypopharyngeal squamous cell carcinomas (HPSCC). However, the role of pepsin in HPSCC is not clear. We show by immunohistochemistry that pepsin positivity occurs in a significant proportion of human primary HPSCC specimens, and in many cases matched adjacent uninvolved epithelia are negative for pepsin. Pepsin positivity is associated with nodal involvement, suggesting that pepsin may have a role in metastasis. Treatment of FaDu cancer cells with pepsin increased cell proliferation, possibly by inducing G1/S transition. We also observed significant changes in expression of genes involved in NF-kappaB, TRAIL and Notch signaling. Our data suggest that pepsin plays an important role in HPSCC and that targeting pepsin could have potential therapeutic benefits., Competing Interests: The authors have declared that no competing interests exist.

High pressure, an emerging nonthermal technology has been widely applied in food product modifications. The effects of oat β-glucan concentration and pressure on the properties of mixed gels with the different ratios of varying molecular weight (MW) β-gulcan induced by HPP were investigated. The results showed that the lowest β-glucan concentration forming a gel was 15% at 200 MPa, while 8% β-glucan was required to form a gel at 500 MPa. The gel intensity and textural properties increased with elevating β-glucan total concentration and pressure. The characteristic compact and smooth mixed gel formed with 12% β-glucan at a ratio of 50:50 at 400 MPa for 30 min. Under this optimal parameters, the mixed solution showed a relatively lower particle size and turbidity, and the hydrogen bonding and electrostatic interaction played the main role during the gel formation process by high pressure. In addition, the core molecular structure of β-glucan was maintained in the mixed gel formed under the optimal parameters., Competing Interests: The authors have declared that no competing interests exist.

Q fever is a worldwide zoonosis caused by Coxiella burnetii. Human Q fever is typically acquired through inhalation of contaminated aerosols, resulting in an initial pulmonary infection. In this study, BALB/c mice were infected with C. burnetii via an intratracheal (IT) route using a non-invasive aerosol pulmonary delivery device to directly place the living C. burnetii organisms into the lungs of the mice. The bacterial loads, pathological lesions, and antibody and cellular responses were analyzed and compared with those of mice infected via an intraperitoneal (IP) route. Compared with mice infected via an IP route, mice infected via an IT route exhibited a higher bacterial load and more severe pathological lesions in the heart and lungs at days 3 and 7 post-infection (pi). The levels of interferon-γ and IL-12p70 in the serum of mice infected via the IT route were significantly higher than those of mice infected via the IP route at day 3 pi. In conclusion, this murine model of acute C. burnetii infection via IT inoculation closely resembles the natural route of C. burnetii infection than that of IP injection. Thus, this newly developed model will be useful for investigating the pathogenesis and immunity of C. burnetii aerosol infection, as well as for the evaluation of therapeutic drugs and preventive vaccines of Q fever., Competing Interests: The authors have declared that no competing interests exist.

In this study, the spatial distribution of the transient pressure and the slipstream caused by a 1/10 scaled metro train passing through a tunnel was studied with moving model test. We hereby investigate the mechanism underlying the mitigation of the transient pressure on both the train surface and tunnel wall, as well as that of the slipstream in the tunnel. Experimental results showed that the airshaft at different locations in a tunnel had different pressure relief effects. The most significant pressure amplitude decreased by 36.0% with the airshaft locating in the middle of the tunnel. Meanwhile, the slipstream speed was also relieved from 0.45 to 0.36 after an airshaft. We also assessed and analyzed the impact of train speed on the transient pressures and slipstream. It was found that the increase of the train speed would increase the transient pressure and slipstream speed, but it did not effect their spatial distribution., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the impact of soft contact lens eye-fit on optical power by computational modelling and to produce correction maps for reversing this impact during the design process., Methods: Finite element models of spherical and toric hydrogel contact lenses at varying nominal powers of -20 D to +20 D, base curves radii (R1b) of 8.2, 8.5, 8.8 mm, and overall diameters (d3) of 14.5, 15.0, 15.5 mm were generated. Lenses were fitted to computational eye models generated with human eyes' topography data. Combined eye-lens simulations were run under the boundary conditions of the tears' surface tension between the contact lens and the eye in addition to the eyelid blink pressure. Lens optical zone power changes were calculated through computational light-ray tracing methods following each simulation., Results: Effective power changes (EPC) were affected negatively for all toric simulated lenses with power varying from -20 D to +20 D. Spherical lenses demonstrated similar behaviour, however with some positive EPC over the power range from -20 D to -10 D for spherical power (SPH) lenses. EPC assessment was between +0.25 D and -0.5 D for most lenses, however, lenses with prescriptions from +10 D to +20 D incurred EPC outside this range. The spherical lenses showed a maximum effective power change of +1.046 ± 0.338 D (Average Eye), and a minimum of -3.278 ± 0.731 D (Steep Eye). Similarly, the toric lenses showed a maximum of +1.501 ± 0.338 D (Average Eye), and a minimum of -3.514 ± 0.731 D (Steep Eye). EPC trends, along with minimum and maximum power, generally increased negatively as nominal lens prescription increased positively. Contact lens base curve selection affected the assessed effective power change for both spherical and toric lenses. The effect from lens total diameter for spherical lenses was less substantial than that for toric lenses., Conclusions: This study considered the impact of soft contact lens design parameters on effective optical power changes (EPC) after eye-fit. Spherical lenses experienced more EPC of clinical significance (>0.25 D) than toric lenses. Both types of lenses, spherical and toric (simple astigmatism), demonstrated similar trends in EPC on fitting from -20 D to +20 D, with lenses in the extremely positive and the extremely negative prescriptions demonstrating the highest EPCs. The lens base curve impacted the extent of EPC observed, with flatter base curves experiencing less power change. Diameter proved to impact toric lenses more than spherical ones, however generally the diameter has less effect on power change than base curve selection., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: AA was a paid employee of an Innovate UK Knowledge Transfer Partnership Programme Grant till November 2017. AS, CEO of Eaglet Eye BV, and both IF and RS, the clinicians in Eaglet Eye BV, may use the figures in this manuscript to improve the performance of the Eye Surface Profiler (ESP). All other authors declare no potential financial or non-financial competing interests including employment, consultancy, patents, products in development, or marketed products. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

This study aimed to analyse microstructure data on the density and orientation of collagen fibrils in whole eye globes and to propose an effective method for the preparation of data for use in numerical simulations of the eye's biomechanical performance. Wide-angle X-ray scattering was applied to seven healthy ex-vivo human eyes. Each eye was dissected into an anterior and a posterior cup, and radial incisions were used to flatten the tissue before microstructure characterisation. A method was developed to use the microstructure data obtained for the dissected tissue to build realistic 3D maps of fibril density and orientation covering the whole eye globe. At the central cornea, 61.5±2.3% of fibrils were aligned within 45° sectors surrounding the two orthogonal directions. In contrast, more than one-third of the total fibril content was concentrated along the circumferential direction at the limbus (37.0±2.4%) and around the optic nerve head (34.8±2.1%). The insertion locations of the four recti muscles exhibited a preference in the meridional direction near the equator (38.6±3.9%). There was also a significant difference in fibril density between the limbus and other regions (ratio = 1.91±0.45, p <0.01 at the central cornea and ratio = 0.80±0.21, p <0.01 at the posterior pole). Characterisation of collagen fibril density and orientation across the whole ocular surface has been possible but required the use of a technique that involved tissue dissection and hence caused tissue damage. The method presented in this paper aimed to minimise the effect of dissection on the quality of obtained data and was successful in identifying fibril distribution trends that were compatible with earlier studies, which concentrated on localised areas of the ocular globe., Competing Interests: The authors have declared that no competing interests exist.

Currently about 2 billion adults globally are estimated to be overweight and ~13% of them are obese. High fat diet (HFD) is one of the major contributing factor to obesity, heart disease, diabetes and cancer. Recent findings on the role of HFD in inducing abnormalities in neurocognition and susceptibility to Alzheimer's disease are highly intriguing. Since fundamental molecular pathways are often conserved across species, studies involving Drosophila melanogaster as a model organism can provide insight into the molecular mechanisms involving human disease. In order to study some of such mechanisms in the central nervous system as well in the rest of the body, we investigated the effect of HFD on the transcriptome in the heads and bodies of male and female flies kept on either HFD or regular diet (RD). Using comprehensive genomic analyses which include high-throughput transcriptome sequencing, pathway enrichment and gene network analyses, we found that HFD induces a number of responses that are sexually dimorphic in nature. There was a robust transcriptional response consisting of a downregulation of stress-related genes in the heads and glycoside hydrolase activity genes in the bodies of males. In the females, the HFD led to an increased transcriptional change in lipid metabolism. A strong correlation also existed between the takeout gene and hyperphagic behavior in both males and females. We conclude that a) HFD induces a differential transcriptional response between males and females, in heads and bodies and b) the non-dimorphic transcriptional response that we identified was associated with hyperphagia. Therefore, our data on the transcriptional responses in flies to HFD provides potentially relevant information to human conditions including obesity., Competing Interests: The authors have declared that no competing interests exist.

Physical activity promotes metabolic and cardiovascular health benefits that derive in part from the transcriptional responses to exercise that occur within skeletal muscle and other organs. There is interest in discovering a pharmacologic exercise mimetic that could imbue wellness and alleviate disease burden. However, the molecular physiology by which exercise signals the transcriptional response is highly complex, making it challenging to identify a single target for pharmacological mimicry. The current studies evaluated the transcriptome responses in skeletal muscle, heart, liver, and white and brown adipose to novel small molecule activators of AMPK (pan-activators for all AMPK isoforms) compared to that of exercise. A striking level of congruence between exercise and pharmacological AMPK activation was observed across the induced transcriptome of these five tissues. However, differences in acute metabolic response between exercise and pharmacologic AMPK activation were observed, notably for acute glycogen balances and related to the energy expenditure induced by exercise but not pharmacologic AMPK activation. Nevertheless, intervention with repeated daily administration of short-acting activation of AMPK was found to mitigate hyperglycemia and hyperinsulinemia in four rodent models of metabolic disease and without the cardiac glycogen accretion noted with sustained pharmacologic AMPK activation. These findings affirm that activation of AMPK is a key node governing exercise mediated transcription and is an attractive target as an exercise mimetic., Competing Interests: All authors are or were employees of Merck & Co., Inc., Kenilworth, NJ, USA, and may own shares of company stock. Merck & Co., Inc., Kenilworth, NJ, USA, provisional patent applications for LA1, LA2, SA1 and SA2 and related AMPK activators were filed on 23 February 2012 (WO2012116145; Novel Cyclic Azabenzimidazole derivatives useful as anti-diabetic agents). All of the authors employed by Merck & Co., Inc., Kenilworth, NJ, USA, have a potential conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Ground subsidence and surface cracks caused by coal mining are typical man-made geological hazards that can severely damage the ecological environment and buildings. In China, within the theme of sustained and stable development, accurate assessment of mining-related building damage is paramount in order to address the contradiction between coal mining enterprises and building owners. Previous research in China focused mainly on the mining areas of plains, and only a few studies have considered building damage caused by intensive mining in mountainous areas. First, based on field investigation, this study located ground surface cracks and assessed the damage to buildings in the village of Nanyetou in Shanxi Province (China) attributable to the exploitation of the 15110 working face of the Baiyangling coal mine. Second, based on the mining subsidence law and boundary angle, the surface influenced boundary caused by underground mining was determined. However, as the existing subsidence theory cannot adequately explain the phenomenon of building damage, the damage was investigated from the perspective of slope stability analysis, and the slope safety factor before and after working face mining were calculated using the Janbu method. The analytical results showed that slope instability due to a decrease of the safety factor because of the coal mining activity was the principal reason for damage to the village buildings, a finding that was confirmed by field survey and InSAR monitoring displacement. The results of this study could provide guidance and reference for the assessment of building damage caused by underground mining in mountain areas., Competing Interests: The authors have declared that no competing interests exist.

Frequency analysis is a fundamental function of the auditory system, and it is essential to study the auditory response properties using behavior-related sounds. Our previous study has shown that the inferior collicular (IC) neurons of CF-FM (constant frequency-frequency modulation) bats could be classified into single-on (SO) and double-on (DO) neurons under CF-FM stimulation. Here, we employed Pratt's roundleaf bats, Hipposideros pratti, to investigate the frequency selectivity of SO and DO neurons in response to CF and behavior-related CF-FM sounds using in vivo extracellular recordings. The results demonstrated that the bandwidths (BWs) of iso-frequency tuning curves had no significant differences between the SO and the DO neurons when stimulated by CF sounds. However, the SO neurons had significant narrower BWs than DO neurons when stimulated with CF-FM sounds. In vivo intracellular recordings showed that both SO and DO neurons had significantly shorter post-spike hyperpolarization latency and excitatory duration in response to CF-FM in comparison to CF stimuli, suggesting that the FM component had an inhibitory effect on the responses to the CF component. These results suggested that SO neurons had higher frequency selectivity than DO neurons under behavior-related CF-FM stimulation, making them suitable for detecting frequency changes during echolocation., Competing Interests: The authors have declared that no competing interests exist.

Due to the complexity of large production systems, maintenance events are diverse, simultaneous and dynamic. Appropriate maintenance management of complex large production systems can guarantee high availability and save maintenance costs. However, current maintenance decision-making methods mainly focus on the maintenance events of single-components and series connection multi-components; little research pays attention to the combination maintenance of different maintenance events. Therefore, this paper proposes a multi-event combination maintenance model based on event correlation. First, the maintenance downtime and cost of three types of maintenance events under different maintenance beginning times and degrees are analysed. Then, shared maintenance downtime and cost models are established by maintenance event correlations. In addition, a multi-event combination maintenance model is constructed to achieve the goal of the highest availability and the lowest cost rate in both the decision-making cycle and the remaining life. Moreover, a particle swarm optimization algorithm based on interval segmentation for model solving is designed. Finally, a numerical example is presented to illustrate the model., Competing Interests: The authors have declared that no competing interests exist.

Aim: Diabetes is a complex metabolic disease characterized by chronic low-grade inflammation in which genetic and environmental factors are involved. Growing evidence implicates that alterations of the gut microbiota potentially contribute to the emergence of metabolic diseases. The human appendix has more recently been recognized as a microbial reservoir for repopulating the gastrointestinal tract and an important part of the immune system. Thus, appendectomy may influence microbial ecology and immune function. This study investigated the association between appendectomy and type 2 diabetes risk., Methods: We analyzed a cohort of 10954 patients who underwent appendectomy between 1998 and 2013 based on the Taiwan National Health Insurance Program database. A comparison cohort of 43815 persons without appendectomy was selected randomly and matched by sex, age, comorbidities, and index year. To ensure reliability of the results, a sensitivity analysis using a propensity score-matched study was performed. We observed the subsequent development of type 2 diabetes in both cohorts., Results: Although the overall incidence of type 2 diabetes in the appendectomy patients was 7.9% higher than that in the non-appendectomy patients, it was not statistically significant (95% confidence interval [CI], 0.997-1.168) after the adjustment of confounding factors. Multivariate regression analysis revealed that the adjusted hazard ratio (HR) of type 2 diabetes was 1.347 for appendectomy patients < 30 years of age (95% CI, 1.009-1.798) compared to non-appendectomy patients. The incidence of type 2 diabetes was higher within 3 years of post-appendectomy follow-up than for non-appendectomy patients (HR, 2.017; 95% CI, 1.07-3.802). Age impacted the association between appendectomy and type 2 diabetes risk (Pinteraction = 0.002); in contrast, sex did not affect the association between appendectomy and type 2 diabetes risk (Pinteraction = 0.88)., Conclusions: Our study results suggest that appendectomy increases type 2 diabetes risk, particularly when performed prior to middle age., Competing Interests: The authors have declared that no competing interests exist.

Work spaces for assembly or maintenance operations are considered in the design stage of products. Maintenance space is a key factor in determining how well a product can be maintained. If the work space is sufficiently considered in the design stage, it will benefit both the user and the maintainer. From a maintenance perspective, this paper proposes a quantitative method to evaluate the maintenance space by virtual simulation and consideration of ergonomics. In this method, maintenance operations are concisely classified into three types. Based on the virtual simulation of the maintenance process and maintainer data, the swept volume of a hand is built using envelope theory. The operation range of the maintainer is derived by establishing a mathematical model for the upper limb. Combining the swept volume and operation range, the maintenance space can be quantitatively evaluated. A concise validation demonstrates that the proposed method is effective for evaluating the maintenance space to improve the space design. The proposed method could be applied to the space design of a complex product., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Haploidentical and human leukocyte antigen (HLA)-identical sibling hematopoietic stem transplantation are two main ways used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, remarkable progress has been made in haploidentical allo-HSCT (HID-SCT), and some institutions found HID-SCT had similar outcomes as HLA-identical sibling allo-HSCT (ISD-SCT). To clarify if HID-SCT has equal effects to ISD-SCT in hematologic malignancies, we performed this meta-analysis., Methods: Relevant articles published prior to February 2017 were searched on PubMed. Two reviewers assessed the quality of the included studies and extracted data independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated for statistical analysis., Results: Seven studies including 1919 patients were included. The rate of platelet engraftment is significantly lower after HID-SCT versus ISD-SCT while there is no difference in neutrophil engraftment (OR = 2.58, 95% CI = 1.70-3.93, P < 0.00001). The risk of acute graft-versus-host disease (GVHD) is significantly higher after HID-SCT versus ISD-SCT (OR = 1.88, 95% CI = 1.42-2.49, P < 0.00001), but the relapse rate is lower in HID-SCT group (OR = 0.70, 95% CI = 0.55-0.90, P = 0.005). The incidence rates of overall survival (OS) and disease-free-survival/leukemia-free survival/relapse-free survival (DFS/LFS/RFS) after ISD-SCT are all significantly superior to HID-SCT (OR = 1.32, 95% CI = 1.08-1.62, P = 0.006; OR = 1.25, 95% CI = 1.03-1.52, P = 0.02). There is no significant difference in transplantation related mortality (TRM) rate after HID-SCT and ISD-SCT., Conclusion: After myeloablative conditioning, patients receiving ISD-SCT have a faster engraftment, lower acute GVHD and longer life expectancy compared to HID-SCT with GVHD prophylaxis (cyclosporine A, methotrexate, mycophenolate mofetil and antithymoglobulin; CsA + MTX + MMF + ATG). Currently, HID-SCT with GVHD prophylaxis (CsA + MTX + MMF + ATG) may not replace ISD-SCT when HLA-identical sibling donor available.

Conventional education results in unsatisfactory morphological understanding of acetabular fractures due to lack of three-dimensional (3D) details and tactile feedback of real fractures. Virtual reality (VR) and 3D printing (3DP) techniques are widely applied in teaching. The purpose of this study was to identify the effect of physical model (PM), VR and 3DP models in education of morphological understanding of acetabular fractures. 141 students were invited to participate in this study. Participants were equally and randomly assigned to the PM, VR and 3DP learning groups. Three-level objective tests were conducted to evaluate learning, including identifying anatomical landmarks, describing fracture lines, identifying classification, and inferring fracture mechanism. Four subjective questions were asked to evaluate the usability and value of instructional materials. Generally, the 3DP group showed a clear advantage over the PM and VR groups in objective tests, while there was no significant difference between the PM and VR groups. 3DP was considered to be the most valuable learning tool for understanding acetabular fractures. The findings demonstrate that 3DP modelling of real fractures is an effective learning instrument that can be used to understand the morphology of acetabular fractures and promote subjective interest.

Trains with different numbers of cars running in the open air were simulated using the delayed detached-eddy simulation (DDES). The numbers of cars included in the simulation are 3, 4, 5 and 8. The aim of this study was to investigate how train length influences the boundary layer, the wake flow, the surface pressure, the aerodynamic drag and the friction drag. To certify the accuracy of the mesh and methods, the drag coefficients from numerical simulation of trains with 3 cars were compared with those from the wind tunnel test, and agreement was obtained. The results show that the boundary layer is thicker and the wake vortices are less symmetric as the train length increases. As a result, train length greatly affects pressure. The upper surface pressure of the tail car reduced by 2.9%, the side surface pressure of the tail car reduced by 8.3% and the underneath surface pressure of the tail car reduced by 19.7% in trains that included 3 cars to those including 8 cars. In addition, train length also has a significant effect on the friction drag coefficient and the drag coefficient. The friction drag coefficient of each car in a configuration decreases along the length of the train. In a comparison between trains consisting of 3 cars to those consisting of 8 cars, the friction drag coefficient of the tail car reduced by 8.6% and the drag coefficient of the tail car reduced by 3.7%.

Although cascading failures caused by overload on interdependent/interconnected networks have been studied in the recent years, the effect of overlapping links (inter-similarity) on robustness to such cascades in coupled networks is not well understood. This is an important issue since shared links exist in many real-world coupled networks. In this paper, we propose a new model for load-based cascading failures in multiplex networks. We leverage it to compare different network structures, coupling schemes, and overload rules. More importantly, we systematically investigate the impact of inter-similarity on the robustness of the whole system under an initial intentional attack. Surprisingly, we find that inter-similarity can have a negative impact on robustness to overload cascades. To the best of our knowledge, we are the first to report the competition between the positive and the negative impacts of overlapping links on the robustness of coupled networks. These results provide useful suggestions for designing robust coupled traffic systems.

During deep space missions, astronauts will be exposed to low doses of charged particle irradiation. The long-term health effects of these exposures are largely unknown. We previously showed that low doses of oxygen ion (16O) irradiation induced acute damage to the hematopoietic system, including hematopoietic progenitor and stem cells in a mouse model. However, the chronic effects of low dose 16O irradiation remain undefined. In the current study, we investigated the long-term effects of low dose 16O irradiation on the mouse hematopoietic system. Male C57BL/6J mice were exposed to 0.05 Gy, 0.1 Gy, 0.25 Gy and 1.0 Gy whole body 16O (600 MeV/n) irradiation. The effects of 16O irradiation on bone marrow (BM) hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) were examined three months after the exposure. The results showed that the frequencies and numbers of BM HPCs and HSCs were significantly reduced in 0.1 Gy, 0.25 Gy and 1.0 Gy irradiated mice compared to 0.05 Gy irradiated and non-irradiated mice. Exposure of mice to low dose 16O irradiation also significantly reduced the clongenic function of BM HPCs determined by the colony-forming unit assay. The functional defect of irradiated HSCs was detected by cobblestone area-forming cell assay after exposure of mice to 0.1 Gy, 0.25 Gy and 1.0 Gy of 16O irradiation, while it was not seen at three months after 0.5 Gy and 1.0 Gy of γ-ray irradiation. These adverse effects of 16O irradiation on HSCs coincided with an increased intracellular production of reactive oxygen species (ROS). However, there were comparable levels of cellular apoptosis and DNA damage between irradiated and non-irradiated HPCs and HSCs. These data suggest that exposure to low doses of 16O irradiation induces long-term hematopoietic injury, primarily via increased ROS production in HSCs.

Dempster-Shafer evidence theory has been widely used in various applications. However, to solve the problem of counter-intuitive outcomes by using classical Dempster-Shafer combination rule is still an open issue while fusing the conflicting evidences. Many approaches based on discounted evidence and weighted average evidence have been investigated and have made significant improvements. Nevertheless, all of these approaches have inherent flaws. In this paper, a new weighting factor is proposed to address this problem. First, a modified dissimilarity measurement is proposed which is characterized by both distance and conflict between evidences. Second, a measurement of information volume of each evidence based on Deng entropy is introduced. Then two kinds of weight derived from aforementioned measurement are combined to obtain a new weighting factor and a weighted average method based on the new weighting factor is proposed. Numerical examples are used to illustrate the validity and effectiveness of the proposed method. In the end, the new method is applied to a real-life application of river water quality monitoring, which effectively identify the major land use activities contributing to river pollution.