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ObjectiveTo study the false memory among senile normal people with high neuroticism and low neuroticism using neuropsychological scales and event-related potentials (ERPs), and to explore the effects of high neuroticism on false memory and its neuroelectrophysiological mechanism.MethodsA cross-sectional study was conducted, in which the general situation questionnaire, adult version of Eysenck personality questionnaire (EPQ) and Montreal cognitive assessment (MoCA) scale were used to establish a multi-dimensional survey in senile normal people over 60 years old from communities in Zhengzhou, and the EPQ and general situation questionnaire were used to comprehensively screen and divide the study subjects into high neuroticism group and low neuroticism group from 206 senile people. The population was matched by 1:1 according to gender, age (±2 years), and years of education (±2 years), and 40 subjects were finally enrolled for detection of electroencephalograph (EEG) components using ERPs. The Deese-Roediger-McDermott (DRM) paradigm of false memory was designed using E-prime2.0 system, and the stimulus program was presented. The EEG signals of the study subjects were recorded in real time and acquired using 64-channel Neuroscan EEG signals acquisition system.ResultsHigh neuroticism group was evidently lower in the mean accuracy than low neuroticism group, and the difference in the mean accuracy was statistically significant (P = 0.013), but the difference in reaction time was not statistically significant. 2. The mean amplitude of EEG component N400: The difference in the main effect of N400 in the brain region was significantly different (PConclusionsHigh neuroticism can significantly increase the false memory of senile normal people. The EEG components N400 and LPC are potential early indicators of high neuroticism affecting false memory. High neuroticism may influence false memory by affecting the frontal cortex function.

Background and study aimThe klotho protein, a multifunctional protein, has been shown to be associated with a wide range of endocrine diseases and has been linked to thyroid tumourigenesis. However, the relationship between serum klotho levels and thyroid hormones remains poorly understood. This study aimed to explore the correlation between serum klotho levels and thyroid hormones.MethodsData was obtained from the NHANES cycles 2007-2008, 2009-2010, and 2011-2012. A total of 4674 participants were recruited for this study. Statistical analysis was using multiple linear regression analyses, and restricted cubic spline plots (RCS) to investigate the association between serum klotho levels and serum levels of thyroid hormones.ResultsIn the unadjusted covariate model, ln(klotho) significantly positively correlated with tT3, tT4, fT3, tT4/fT4, and tT3/fT3 (all PConclusionThere is an L-shaped nonlinear relationship between ln(klotho) and fT3, tT3, suggesting that klotho could be involved in the physiological regulation of thyroid function.

BackgroundBone mineral density is an important indicator of osteoporosis, and its variation with volatile organic compounds exposure has rarely been studied. However, the relationship between chloroform (an essential volatile organic compounds component) and bone mineral density remains unclear. Consequently, we aimed to explore the relationship between chloroform alone and bone mineral density or bone mineral content.MethodsHerein, 2,553 individuals aged 18 and above from the National Health and Nutrition Examination Surveys (NHANES) in 2009-2010, 2013-2014, and 2017-2020, were included. We employed two independent t-tests and multi-linear regression models to statistically assess the relationship between chloroform exposure and BMD/BMC in the spine and femoral area.ResultsA "V"-shaped correlation between chloroform exposure and bone mineral density or bone mineral content (BMD/BMC) was observed in the unadjusted model, particularly in the Ward's triangle and femoral neck as a whole. A negative correlation was specifically observed for the Ward's triangle BMD/BMC and L4 BMD/BMC. On the other hand, in the adjusted model, a dominantly negative correlation between the L4 BMC and chloroform exposure was observed over a range of exposure levels. The subgroup analysis revealed a negative correlation between chloroform concentrations and BMC in the femur and spine, especially in women and the 65-80 age population.ConclusionOur study revealed a "V" shaped correlation between chloroform and BMD/BMC of the femur and spine in U.S. adults. This finding highlights the fact that prolonged exposure to chloroform may cause the changes in BMD/BMC.

With economic progression in China, Yellow River Basin serves as a critical economic belt, which has also been recognized as a cradle of Chinese culture. A watershed is a complex structure of social, economic, and natural factors, and the diversity of its components determines its complexity. Studies on the spatiotemporal distribution characteristics and factors influencing the tourism eco-efficiency at the watershed scale are crucial for the sustainable regional socio-economic development, maintaining a virtuous cycle of various ecosystems, and comprehensively considering the utilization and coordinated development of various elements. Based on tourism eco-efficiency, the coordination degree of regional human-land system and the sustainable development levels can be accurately measured. With the tourism eco-efficiency in the Yellow River Basin from 2009 to 2019, the present study considers 63 cities in the Yellow River Basin as the research area by adopting the super-efficiency slacks-based measure (Super-SBM) model. Methods such as trend surface analysis, spatial autocorrelation analysis, elliptic standard deviation analysis, and hot spot analysis were used to explore their spatiotemporal distribution and evolution characteristics. The geographical and temporal weighted regression (GTWR) model was used to determine the factors influencing the tourism eco-efficiency value. The findings are as follows: ①The level of tourism eco-efficiency in the Yellow River Basin is not high, exhibiting a fluctuating upward trend. ②The tourism eco-efficiency in the Yellow River Basin shows significant spatial interdependence and agglomeration. Furthermore, the track of the center of gravity moves from northeast to southwest. ③ The tourism eco-efficiency in the Yellow River Basin is affected by various factors, with the economic development level having the greatest influence.

With the wide application of the "Tender, Auction, and Listing" system for land in China, it is of paramount importance to establish a sound land auction mechanism so as to avoid unreasonable land allocation. However, existing studies only focus on developers who are merely concerned about land combinations and offline auctions with low efficiency and high land unsold rate. To further improve land auction mechanism, we modeled the problem of land allocation as an online combinatorial auction. On this basis, we defined a land correction coefficient and designed an optimal online combinatorial auction mechanism that enabled developers to submit multiple combinations of land. Our designed mechanism proved to satisfy both incentive compatibility (IC) and individual rationality (IR), which can prevent developers from lying in the auction while winning higher revenue, reducing land unsold rate, increasing developer turnover rate and promoting the stability of land resource allocation rate. Therefore, online combinatorial auction mechanism, both applicable and efficient, is a practical solution for improving land auctions in China.

Depression is of increasing concern as its prevalence increases. Our study's objective was to create and evaluate a nomogram to predict the likelihood that hypertension patients may experience depression. 13293 people with hypertension who were under 20 years old were chosen from the National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2018 for this study. The training and validation sets were split up into the dataset at random in a 7:3 ratio. To find independent predictors, univariate and multivariate logistic regression were employed on the training set. Using information from the validation set, nomogram was subsequently created and internally validated. The effectiveness of the nomogram is assessed using calibration curve and receiver operator characteristic (ROC) curve. Combining univariate logistic regression analysis and multifactor logistic regression analysis, the results showed that age, sex, race, marital, education level, sleep time on workdays, poverty to income ratio, smoking, alcohol consumption, sedentary time and heart failure status were risk factors for hypertensive patients suffering from depression and were included in the nomogram model, and ROC analysis showed that the AUC of the training set was 0.757 (0.797-0.586), with a sensitivity of 0.586; the AUC of the test set was 0.724 (0.712-0.626), with a sensitivity of 0.626, which was a good fit. Decision curve analysis further confirms the value of nomogram for clinical application. In the civilian non-institutionalized population of the United States, our study suggests a nomogram that can aid in predicting the likelihood of depression in hypertension patients and aiding in the selection of the most effective treatments.

Type 2 diabetes mellitus (T2DM) has caused a huge clinical and economic burden worldwide. The management strategy of T2DM has been mentioned in many guidelines. However, controversy still exists in the recommendation of anti-hyperglycemic agents. To this end, this protocol has been written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will make an overview of systematic reviews based-on network meta-analysis firstly that report on safety and efficacy of different category of anti-hyperglycemic agents for T2DM patients. We will identify network meta-analysis by applying a robust and standardized search strategy within Embase, PubMed, Web of Science, and Cochrane Database of Systematic Reviews. Hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) will be defined as the primary outcomes. We will assess the methodological quality of included reviews by applying the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR-2) tool, and quality of evidence for all outcomes will be judged by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). This will provide an accessible narrative synthesis to clinicians, patients, policy makers, and developers of clinical guidelines based on published high-quality network meta-analysis. We will submit our results for peer-review publication and presentation at domestic and international conferences. We will also disseminate our results through established clinical networks and consumer networks, using pamphlet where appropriate. Ethics approval is not required for this overview as we will analysis published network meta-analysis only. Trial registration number: INPLASY202070118.

IntroductionHypertension, one of the most common chronic diseases worldwide, usually requires lifetime managing blood pressure (BP) with medications. Due to quite large number of hypertension patients co-exist with depression and/or anxiety, and non-cooperated with medical instruction, consequently management of BP is impaired with serious complications, resulting in compromised quality of life. Consequently quality of life of such patients is impaired with serious complications. Therefore, management of depression and/or anxiety is equally important as the treatment of hypertension. Depression and/or anxiety are independent risk factors of hypertension, which is supported by the finding that there is close correlation between hypertension are depression/or anxiety. Psychotherapy (non-drug treatment) maybe useful for hypertensive patients with depression and/or anxiety to improve their negative emotions. We aim to quantify the effective of psychological therapies in the management of hypertension patients with depression or anxiety, by comparing and ranking a network meta-analysis (NMA).Materials and methodsLiterature search for randomized controlled trials (RCTs) will be performed in five electronic databases from inception to December 2021, including PubMed, the Cochrane library, Embase, Web of Science, and China Biology Medicine disc (CBM). The search terms mainly include "hypertension", "mindfulness-based stress reduction" (MBSR), "cognitive behavioral therapy" (CBT) and "dialectical behavior therapy" (DBT). Cochrane Collaboration quality assessment tool will be used for the risk of bias assessment. A Bayesian network meta-analysis will be performed, using WinBUGS 1.4.3, and Stata 14 will be applied to draw the network diagram, while RevMan 5.3.5 will be used to produce funnel plot for assessing the risk of publication bias. Recommended rating, development and grade methodology will also be utilized to assess the quality of evidence.ResultsEffect of MBSR, CBT and DBT will be evaluated by traditional meta-analysis directly and Bayesian network meta-analysis indirectly. Our study will provide the evidence on the efficacy and safety of psychological treatments in the hypertension patients with anxiety. There is no research ethical requirement because this is a systematic review of published literature. The results of this study will be published in a peer-reviewed journal.Trial registrationProspero registration number: CRD42021248566.

ObjectiveType 2 diabetes mellitus(T2DM) is closely related to sarcopenic obesity(SO). Body composition measurement including body weight, body mass index, waist circumference, percentage body fat, fat mass, muscle mass, visceral adipose tissue and subcutaneus adipose tissue, plays a key role in evaluating T2DM and SO. The weight reduction effect of sodium-glucose cotransporter 2(SGLT-2) inhibitors has been demonstrated. However, there are warnings that SGLT-2 inhibitors should be used with caution because they may increase the risk of sarcopenia. The effect of SGLT-2 inhibitors on body composition in T2DM is inconclusive. In this work, a meta-analysis of randomized controlled trials was conducted to evaluate the effect of SGLT-2 inhibitors on body composition in T2DM.MethodsPubMed, the Cochrane Library, EMbase and Web of Science databases were searched by computer. All statistical analyses were carried out with Review Manager version 5. 3. Results were compared by weight mean difference(WMD), with 95% confidence intervals(CI) for continuous outcomes. A random effects model was applied regardless of heterogeneity. The I2 statistic was applied to evaluate the heterogeneity of studies. Publication bias was assessed using Funnel plots.Results18 studies with 1430 participants were eligible for the meta-analysis. SGLT-2 inhibitors significantly reduced body weight(WMD:-2. 73kg, 95%CI: -3. 32 to -2. 13, pConclusionSGLT-2 inhibitors improve body composition in T2DM including body weight, body mass index, waist circumference, visceral fat area, subcutaneous fat area, percentage body fat and fat mass reduction, but cause adverse effects of reducing muscle mass. Therefore, until more evidence is obtained to support that SGLT-2 inhibitors increase the risk of sarcopenia, not only the benefit on body composition, but also the adverse effect of the reduction in muscle mass by SGLT-2 inhibitors in T2DM should be considered.

BackgroundHematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD.ObjectivesTo assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects.Study designMeta-analysis.Search methodsRandomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger's test, and the trim and fill method were used to assess publication bias.ResultsIn total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9-67.4) and 80.3% (95% CI 69.7-87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6-81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5-81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4-90.2%; skin, 52.5-80.6%; and liver, 41.8-71.8%. In cGVHD, the response rates were gastrointestinal, 30.1-70.4%; skin, 30.1-84.4%; lung, 27.0-83.0%; and mouth 3.5-98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications.ConclusionsOur systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.

BackgroundEmerging evidence shows allergic diseases, such as atopic dermatitis and asthma, are risk factors of heart failure. However, the causal relationship between allergic diseases and heart failure is not clear.MethodsWe performed a two-sample Mendelian randomization analysis between allergic diseases and heart failure using summary statistics of genome-wide association studies from large GWAS consortia, with total sample size of 1.2 million. Independent instrumental variables for asthma and atopic dermatitis (PResultsWe have identified 55 independent single nucleotide polymorphisms (SNPs) for asthma 54 independent SNPs for atopic dermatitis as our instrumental variables. The inverse variance-weighted (IVW) analysis showed asthma was significantly associated with increased risk of heart failure (ORIVW = 1.04, 95% CI, 1.01-1.07, P = 0.03). The Mendelian randomization analysis using the other four models also showed consistent results with the IVW analysis. Similarly, atopic dermatitis was also significantly associated with an increased risk of heart failure (ORIVW = 1.03, 95% CI, 1.01-1.06, P = 0.01), consistent with the other four models. The sensitivity analysis showed no evidence of horizontal pleiotropy or results were driven by single SNPs.ConclusionOur study identified asthma and atopic dermatitis as a causal risk factor for heart failure and suggest inflammatory pathogenesis as a key factor contributing to the underlying mechanism. These findings emphasize the importance of asthma and allergy control in the prevention and management of heart failure.

BackgroundVitamin D is related to human immunity, so we used Bayesian network model to analyze and infer the relationship between vitamin D level and the acid-fast bacilli (AFB) smear-positive after two months treatment among pulmonary tuberculosis (TB) patients.MethodsThis is a cross-sectional study. 731 TB patients whose vitamin D level were detected and medical records were collected from December 2019 to December 2020 in XinJiang of China. Logistic regression was used to analyze the influencing factors of second AFB smear-positive. Bayesian network was used to further analyze the causal relationship among vitamin D level and the second AFB smear-positive.ResultsBaseline AFB smear-positive (OR = 6.481, 95%CI: 1.604~26.184), combined cavity (OR = 3.204, 95%CI: 1.586~6.472), full supervision (OR = 8.173, 95%CI:1.536~43.492) and full management (OR = 6.231, 95%CI:1.031~37.636) were not only the risk factors and can also be considered as the reasons for second AFB smear-positive in TB patients (Ensemnle > 0.5). There was no causal relationship between vitamin D level and second AFB smear-positive (Ensemnle = 0.0709).ConclusionsThe risk factors of second AFB smear-positive were baseline AFB smear-positive, combined cavity, full supervision and full management. The vitamin D level in TB patients was not considered as one of the reasons for the AFB smear-positive.

The development of human respiratory syncytial virus (hRSV) vaccine has been hampered by the risk of enhanced respiratory disease (ERD) which was induced by highly skewed toward Th2 immune response. In our previous study, we expressed the recombinant pre-F protein using Escherichia coli BL21, called RBF. To verify if the RBF protein could cause ERD, we tested the immunogenicity and safety of RBF with a commercial alum adjuvant (GMP-grade Adju-Phos). RBF alone and RBF/Adju-Phos elicited long-lasting protective antibodies and a cellular immune response in mice after three immunizations. Unfortunately, compared with the mice in RBF group, mice in RBF/Adju-Phos generated a serious Th2 humoral immune response that elicited Th2-mediated lung pathology. From the IL-4+:IFNγ+ ratio, there was also a robust Th2 cellullar immunologic response in the RBF/Adju-Phos group. This study demonstrates that it may not be enough for RBF to increase the titer of neutralizing antibodies. A balanced immune response must be induced for hRSV vaccine safety.

Human genetics has been proposed to play an essential role in inter-individual differences in respiratory virus infection occurrence and outcomes. To systematically understand human genetic contributions to respiratory virus infection, we developed the database dbGSRV, a manually curated database that integrated the host genetic susceptibility and severity studies of respiratory viruses scattered over literatures in PubMed. At present, dbGSRV contains 1932 records of genetic association studies relating 1010 unique variants and seven respiratory viruses, manually curated from 168 published articles. Users can access the records by quick searching, batch searching, advanced searching and browsing. Reference information, infection status, population information, mutation information and disease relationship are provided for each record, as well as hyperlinks to public databases in convenient of users accessing more information. In addition, a visual overview of the topological network relationship between respiratory viruses and associated genes is provided. Therefore, dbGSRV offers a convenient resource for researchers to browse and retrieve genetic associations with respiratory viruses, which may inspire future studies and provide new insights in our understanding and treatment of respiratory virus infection. Database URL: http://www.ehbio.com/dbGSRV/front/

Indoor air pollution is complex and serious. In fact, an on-site investigation of an office building revealed that the concentration of three typical pollutants (CO2, VOCs, PM2.5) exceeded the Chinese standard. To identify a better control method to achieve good indoor air quality, an orthogonal experiment was carried out in an environmental chamber to compare the control time and energy consumption of four control methods (purifier+ and window+, purifier+ and window-, purified fresh air 240 m3/h and purified fresh air 400 m3/h) to meet the standard established for pollutants. The purifier+ and window+ method was found to be more effective in most conditions, with a control time reduced by 8.06% and energy consumption reduced by 11.91% compared with the traditional control method of purified fresh air 240 m3/h. This research highlights the optimal control strategy for the air quality in office buildings under different pollution conditions.

Identifying whether and how merger and acquisition (M&A) goodwill influences corporate technology innovation is a critical topic in the context of growing M&A activities. Based on the panel data of 2,634 Chinese non-financial listed companies from 2007 to 2019, this paper adopts multiple linear regression and the Bootstrap method to investigate the impact of M&A goodwill on corporate technological innovation and the mechanism through which M&A goodwill affects technological innovation. The results show that: (1) There is a significant negative correlation between M&A goodwill and technological innovation input, with financial constraints acting as the main channels. (2) Non-private corporations enjoy a higher level of financing capacity in terms of debt and equity compared with private corporations, resulting in the absence of the disincentive effect of M&A goodwill on corporate technological innovation inputs, despite the fact that M&A activities also cause massive resource consumption. (3) Stock pledges by controlling shareholders are effective in alleviating the negative impact of M&A goodwill on technological innovation inputs. Furthermore, our results highlight that simple stock pledge measures capture a significant influence of alleviating financing constraints, thereby decreasing the adverse impact of M&A, and hence need to be adequately considered in future M&A and innovation studies. While enriching the literature on the economic consequences of M&A and the research on stock pledge, this paper also provides micro-evidence for an in-depth understanding of the effect of M&A goodwill on technological innovation.

AimsThe renin-angiotensin system (RAS) is over-activated and the serum angiotensin II (Ang II) level increased in obese patients, while their correlations were incompletely understood. This study aims to explore the role of Ang II in diet-induced obesity by focusing on adipose lipid anabolism and catabolism.MethodsRat model of AT1aR gene knockout were established to investigate the special role of Ang II on adipose lipid metabolism. Wild-type (WT) and AT1aR gene knockout (AT1aR-/-) SD rats were fed with normal diet or high-fat diet for 12 weeks. Adipose morphology and adipose lipid synthesis and lipolysis were examined.ResultsAT1aR deficiency activated lipolysis-related enzymes and increased the levels of NEFAs and glycerol released from adipose tissue in high-fat diet rats, while did not affect triglycerides synthesis. Besides, AT1aR knockout promoted energy expenditure and fatty acids oxidation in adipose tissue. cAMP levels and PKA phosphorylation in the adipose tissue were significantly increased in AT1aR-/- rats fed with high-fat. Activated PKA could promote adipose lipolysis and thus improved adipose histomorphology and insulin sensitivity in high-fat diet rats.ConclusionsAT1aR deficiency alleviated adipocyte hypertrophy in high-fat diet rats by promoting adipose lipolysis probably via cAMP/PKA pathway, and thereby delayed the onset of obesity and related metabolic diseases.

CRISPR/LbCas12a system (LbCpf1) has been widely used for genome modification including plant species. However, the efficiency of CRISPR/LbCas12a varied considerably in different plant species and tissues, and the editing efficiency needs to be further improved. In this study, we tried to improve the editing efficiency of CRISPR/LbCas12a in Arabidopsis by optimizing the crRNA expression strategies and Pol II promoters. Notably, the combination of tRNA-crRNA fusion strategy and RPS5A promoter in CRISPR/LbCas12a system has highest editing efficiency, while CRISPR/LbCas12a driven by EC1f-in(crR)p had the highest ratio of homozygous & bi-allelic mutants. In addition, all homozygous & bi-allelic mutants can be stably inherited to the next generation and have no phenotypic separation. In this study, the editing efficiency of the CRISPR/LbCas12a system was improved by selecting the optimal crRNA expression strategies and promoter of LbCas12a in Arabidopsis, which will prove useful for optimization of CRISPR/LbCas12a methods in other plants.

PurposeStudies have evaluated the application of perfusion MR for predicting survival in patients with astrocytic brain tumors, but few of them statistically adjust their results to reflect the impact of the variability of treatment administered in the patients. Our aim was to analyze the association between the perfusion values and overall survival time, with adjustment for various clinical factors, including initial treatments and follow-up treatments.Materials and methodsThis study consisted of 51 patients with astrocytic brain tumors who underwent perfusion-weighted MRI with MultiHance® at a dose of 0.1 mmol/kg prior to initial surgery. We measured the mean rCBV, the 5% & 10% maximum rCBV, and the variation of rCBV in the tumors. Comparisons were made between patients with and without 2-year survival using two-sample t-test or Wilcoxon rank-sum test for the continuous data, or chi-square and Fisher exact tests for categorical data. The multivariate cox-proportional hazard regression was fit to evaluate the association between rCBV and overall survival time, with adjustment for clinical factors.ResultsPatients who survived less than 2 years after diagnosis had a higher mean and maximum rCBV and a larger variation of rCBV. After adjusting for clinical factors including therapeutic measures, we found no significant association of overall survival time within 2 years with any of these rCBV values.ConclusionsAlthough patients who survived less than 2 years had a higher mean and maximum rCBV and a larger variation of rCBV, rCBV itself may not be used independently for predicting 2-year survival of patients with astrocytic brain tumors.

AimsWhether the circulating levels of pentraxin 3 (PTX3), an acute phase reactant (APR), are higher in active Takayasu arteritis (TAK), and if so, whether PTX3 is more accurate than C-reactive protein (CRP) in TAK activity assessment has been investigated in this study.Study designResearch works such as PubMed, Embase, ScienceDirect, Cochrane Library, and two Chinese literature databases (CNKI and WanFang) were searched for studies conducted till August 30th, 2019. Two investigators searched the studies independently, who evaluated the quality of the study using the Newcastle-Ottawa scale (NOS) and extracted data. Pooled standard mean difference (SMD) and diagnostic indexes, with a 95% confidence interval (CI), were calculated using a random-effect model.ResultsTotally, 8 studies involving 473 TAK (208 active and 265 inactive TAK) patients and 252 healthy controls were eventually included in the meta-analysis. PTX3 level in the blood in active TAK patients were found to be higher than that in dormant TAK with pooled SMD of 0.761 (95% CI = 0.38-1.14, pConclusionsPTX3 might be better than CRP in the assessment of TAK activity. Yet, it should be cautious before clinical use for moderate heterogeneity and potential publication bias of the meta-analysis.

ObjectiveThe current study investigated the mechanism underlying the therapeutic effects of berberine in the vasculature in hypertension.MethodsAngiotensin II (Ang II)-loaded osmotic pumps were implanted in C57BL/6J mice with or without berberine administration. Mouse aortae were suspended in myograph for force measurement. Microarray technology were performed to analyze expression profiles of lncRNAs and mRNAs in the aortae. These dysregulated expressions were then validated by qRT-PCR. LncRNA-mRNA co-expression network was constructed to reveal the specific relationships.ResultsAng Ⅱ resulted in a significant increase in the blood pressure of mice, which was suppressed by berberine. The impaired endothelium-dependent aortic relaxation was restored in hypertensive mice. Microarray data revealed that 578 lncRNAs and 554 mRNAs were up-regulated, while 320 lncRNAs and 377 mRNAs were down-regulated in the aortae by Ang Ⅱ; both were reversed by berberine treatment. qRT-PCR validation results of differentially expressed genes (14 lncRNAs and 6 mRNAs) were completely consistent with the microarray data. GO analysis showed that these verified differentially expressed genes were significantly enriched in terms of "cellular process", "biological regulation" and "regulation of biological process", whilst KEGG analysis identified vascular function-related pathways including cAMP signaling pathway, cGMP-PKG signaling pathway, and calcium signaling pathway etc. Importantly, we observed that lncRNA ENSMUST00000144849, ENSMUST00000155383, and AK041185 were majorly expressed in endothelial cells.ConclusionThe present results suggest that the five lncRNAs ENSMUST00000144849, NR_028422, ENSMUST00000155383, AK041185, and uc.335+ might serve critical regulatory roles in hypertensive vasculature by targeting pivotal mRNAs and subsequently affecting vascular function-related pathways. Moreover, these lncRNAs were modulated by berberine, therefore providing the novel potential therapeutic targets of berberine in hypertension. Furthermore, lncRNA ENSMUST00000144849, ENSMUST00000155383, and AK041185 might be involved in the preservation of vascular endothelial cell function.

Autophagy plays a critical role in plant heat tolerance in part by targeting heat-induced nonnative proteins for degradation. Autophagy also regulates metabolism, signaling and other processes and it is less understood how the broad function of autophagy affects plant heat stress responses. To address this issue, we performed transcriptome profiling of Arabidopsis wild-type and autophagy-deficient atg5 mutant in response to heat stress. A large number of differentially expressed genes (DEGs) were identified between wild-type and atg5 mutant even under normal conditions. These DEGs are involved not only in metabolism, hormone signaling, stress responses but also in regulation of nucleotide processing and DNA repair. Intriguingly, we found that heat treatment resulted in more robust changes in gene expression in wild-type than in the atg5 mutant plants. The dampening effect of autophagy deficiency on heat-regulated gene expression was associated with already altered expression of many heat-regulated DEGs prior to heat stress in the atg5 mutant. Altered expression of a large number of genes involved in metabolism and signaling in the autophagy mutant prior to heat stress may affect plant response to heat stress. Furthermore, autophagy played a positive role in the expression of defense- and stress-related genes during the early stage of heat stress responses but had little effect on heat-induced expression of heat shock genes. Taken together, these results indicate that the broad role of autophagy in metabolism, cellular homeostasis and other processes can also potentially affect plant heat stress responses and heat tolerance.

Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo in humans, yet the molecular etiology is currently unknown. Evidence suggests that genetic factors may play an important role in some cases of idiopathic BPPV, particularly in familial cases, but the responsible genetic variants have not been identified. In this study, we performed whole exome sequencing [including untranslated regions (UTRs)] of 12 families and Sanger sequencing of additional 30 families with recurrent BPPV in Caucasians from the United States (US) Midwest region, to identify the genetic variants responsible for heightened susceptibility to BPPV. Fifty non-BPPV families were included as controls. In silico and experimental analyses of candidate variants show that an insertion variant rs113784532 (frameshift causing truncation) in the neural cadherin gene PCDHGA10 (protocadherin-gamma A10) is an exceedingly strong candidate (p = 1.80x10-4 vs. sample controls; p = 5.85x10-19 vs. ExAC data; p = 4.9x10-3 vs. NHLBI exome data). The mutant protein forms large aggregates in BPPV samples even at young ages, and affected subjects carrying this variant have an earlier onset of the condition than those without [average 44.0±14.0 (n = 16) versus 54.4±16.1 (n = 36) years old, p = 0.054]. In both human and mouse inner ear tissues, PCDHGA10 is expressed in ganglia, hair cells and vestibular transitional epithelia. Fluorescent RNA in situ hybridization using mouse inner ear tissues shows that expression increases with age. In summary, our data show that a variant in the PCDHGA10 gene may be involved in causing or aggravating some familial cases of recurrent idiopathic BPPV.

BackgroundAtrial fibrillation (AF) is a clinically common arrhythmia that affects human health. Myocardial fibrosis serves as an important contributor to AF. Recently, miRNA-1202 have been reported to be up-regulated in AF. However, the role of miRNA-1202 and its mechanism in myocardial fibrosis remain unclear.MethodsHuman cardiac fibroblasts (HCFs) were used to construct a fibrosis model by TGF-β1 induction. The expression of miR-1202 was measured by qRT-PCR. Cell proliferation was assessed by CCK-8 assays. Protein expression levels were measured by western blot. Collagen accumulation was measured by ELISA. The relationship between miR-1202 and nNOS was investigated by luciferase reporter assays.ResultsMiR-1202 expression was obviously increased in HCFs and was both time- and dose-independent. MiR-1202 could increase the proliferation and collagen I, collagen III, and α-SMA levels with or without TGF-β1. MiR-1202 could also increase TGF-β1 and p-Smad2/3 protein levels in comparison to the control group. However, they were obviously decreased after inhibitor transfection. MiR-1202 targets nNOS for negative regulation of HCFs fibrosis by decreasing cell differentiation, collagen deposition and the activity of the TGF-β1/Smad2/3 pathway. Co-transfection of miR-1202 inhibitor and siRNA of nNOS inhibited nNOS protein expression, thereby enhancing the HCFs proliferation. Furthermore, co-transfection of the miR-1202 inhibitor and siRNA of nNOS significantly promoted collagen I, collagen III, TGF-β1, Smad2/3 and α-SMA protein expression and Smad2/3 protein phosphorylation. These findings suggested that miR-1202 promotes HCFs transformation to a pro-fibrotic phenotype by targeting nNOS through activating the TGF-β1/Smad2/3 pathway.

OBJECTIVE:To investigate the performance of high-order radiomics features and models based on T2-weighted fluid-attenuated inversion recovery (T2 FLAIR) in predicting the immunohistochemical biomarkers of glioma, in order to execute a non-invasive, more precise and personalized glioma disease management. METHODS:51 pathologically confirmed gliomas patients committed in our hospital from March 2015 to June 2018 were retrospective analysis, and Ki-67, vimentin, S-100 and CD34 immunohistochemical data were collected. The volumes of interest (VOIs) were manually sketched and the radiomics features were extracted. Feature reduction was performed by ANOVA+ Mann-Whiney, spearman correlation analysis, least absolute shrinkage and selection operator (LASSO) and Gradient descent algorithm (GBDT). SMOTE technique was used to solve the data bias between two groups. Comprehensive binary logistic regression models were established. Area under the ROC curves (AUC), sensitivity, specificity and accuracy were used to evaluate the predict performance of models. Models reliability were decided according to the standard net benefit of the decision curves. RESULTS:Four clusters of significant features were screened out and four predicting models were constructed. AUC of Ki-67, S-100, vimentin and CD34 models were 0.713, 0.923, 0.854 and 0.745, respectively. The sensitivities were 0.692, 0.893, 0.875 and 0.556, respectively. The specificities were: 0.667, 0.905, 0.722, and 0.875, with accuracy of 0.660, 0.898, 0.738, and 0.667, respectively. According to the decision curves, the Ki-67, S-100 and vimentin models had reference values. CONCLUSION:The radiomics features based on T2 FLAIR can potentially predict the Ki-67, S-100, vimentin and CD34 expression. Radiomics model were expected to be a computer-intelligent, non-invasive, accurate and personalized management method for gliomas.

We report a rapid and accurate quantitative detection method using droplet digital PCR (ddPCR) technology to identify cassava adulteration in starch products. The ddPCR analysis showed that the weight of cassava (M) and cassava-extracted DNA content had a significant linear relationship-the correlation coefficient was R2 = 0.995, and the maximum coefficient of variation of replicates was 7.48%. The DNA content and DNA copy number (C) measured by ddPCR also had a linear relationship with R2 = 0.992; the maximum coefficient of variation of replicates was 8.85%. The range of cassava ddPCR DNA content was 25 ng/μL, and the formula M = (C + 32.409)/350.579 was obtained by converting DNA content into the median signal. The accuracy and application potential of the method were verified using the constructed adulteration model.

Fresh semen is most commonly used in an artificial insemination of small ruminants, because of low fertility rates of frozen sperm. Generally, when developing and applying assisted reproductive technologies, sheep and goats are classified as one species. In order to optimize sperm cryopreservation protocols in sheep and goat, differences in sperm proteomes between ram and buck are necessary to investigate, which may contribute to differences in function and fertility of spermatozoa. In the current work, a data-independent acquisition-mass spectrometry proteomic approach was used to characterize and make a comparison of ram (Ovis aries) and buck (Capra hircus) sperm proteomes. A total of 2,109 proteins were identified in ram and buck spermatozoa, with 238 differentially abundant proteins. Proteins identified in ram and buck spermatozoa are mainly involved in metabolic pathways for generation of energy and diminishing oxidative stress. Specifically, there are greater abundance of spermatozoa proteins related to the immune protective and capacity activities in ram, while protein that inhibit sperm capacitation shows greater abundance in buck. Our results not only provide novel insights into the characteristics and potential activities of spermatozoa proteins, but also expand the potential direction for sperm cryopreservation in ram and buck.

Community detection in complex networks is an important issue in network science. Several statistical measures have been proposed and widely applied to detecting the communities in various complex networks. However, due to the lack of flexibility resolution, some of them have to encounter the resolution limit and thus are not compatible with multi-scale structures of complex networks. In this paper, we investigated a statistical measure of interest for community detection, Significance [Sci. Rep. 3 (2013) 2930], and analyzed its critical behaviors based on the theoretical derivation of critical number of communities and the phase diagram in community-partition transition. It was revealed that Significance exhibits far higher resolution than the traditional Modularity when the intra- and inter-link densities of communities are obviously different. Following the critical analysis, we developed a multi-resolution version of Significance for identifying communities in the multi-scale networks. Experimental tests in several typical networks have been performed and confirmed that the generalized Significance can be competent for the multi-scale communities detection. Moreover, it can effectively relax the first- and second-type resolution limits. Finally, we displayed an important potential application of the multi-scale Significance in computational biology: disease-gene identification, showing that extracting information from the perspective of multi-scale module mining is helpful for disease gene prediction.

The human positive coactivator 4 (PC4) was originally identified as a multi-functional cofactor capable of mediating transcription activation by diverse gene- and tissue-specific activators. Recent studies suggest that PC4 might also function as a novel cancer biomarker and therapeutic target for different types of cancers. siRNA knockdown studies indicated that down-regulation of PC4 expression could inhibit tumorigeneicity of A549 non-small cell lung cancer tumor model in nude mice. Here we show that AG-1031, a small molecule identified by high throughput screening, can inhibit the double-stranded DNA binding activity of PC4, more effectively than its single-stranded DNA binding activity. AG-1031 also specifically inhibited PC4-dependent transcriptional activation in vitro using purified transcription factors. AG-1031 inhibited proliferation of several cultured cell lines derived from non-small cell lung cancers (NSCLC) and growth of tumors that formed from A549 cell xenografts in immuno-compromised mice. Moreover, pre-injection of AG-1031 in these mice not only reduced tumor size, but also prevented tumor formation in 20% of the animals. AG-1031 treated A549 cells and tumors from AG-1031 treated animals showed a significant decrease in the levels of both PC4 and VEGFC, a key mediator of angiogenesis in cancer. On the other hand, all tested mice remained constant weight during animal trials. These results demonstrated that AG-1031 could be a potential therapy for PC4-positive NSCLC.

Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012-2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isolated viruses covering from seven provinces of China. Additionally, we compared with data from representative sequences of 21 strains covering seven more provinces in China and 32 international HAdV-7 strains obtained from GenBank database to determine the phylogenetic, sequence variations, and molecular evolution of HAdV-7. The results indicated that HAdV-7 infection occurred throughout the year, and a high proportion of severe cases (27 cases, 22.1%) exhibited infantile pneumonia. Moreover, phylogenetic analysis showed that all HAdV-7 strains could be divided into two major evolutionary branches, including subtype 1 and subtype 2, and subtype 3 was also formed according to analysis of the penton base gene. Subtypes 1 and 2 co-circulated in China before 2008, and HAdV-7 strains currently circulating in China belonged to subtype 2, which was also the predominant strain circulating worldwide in recent years. Further sequence variation analysis indicated that three genes of HAdV-7 were relatively stable across time and geographic space, particularly for viruses within subtypes, which shared almost the same variation sites. Owing to continuous outbreaks caused by HAdV-7, resulting in increased illness severity and fatality rates in China, the establishment of a national HAdV surveillance system is urgently needed for the development of effective preventive and infection-control interventions for adenovirus respiratory infections in China.

[This corrects the article DOI: 10.1371/journal.pone.0232092.].

BACKGROUND:The expression of the L-type amino acid transporter 1 (LAT1) plays a significant role in tumor progression. However, it remains unclear whether high LAT1 expression correlates with poor prognosis of solid tumor patients. Here, we conducted a meta-analysis to assess the potential of LAT1 in predicting the prognosis of tumor patients. METHODS AND FINDINGS:A total of 4,579 cases were analyzed from 35 qualified studies. In patients with solid tumors, elevated expression of LAT1 is associated with poor prognosis (overall survival [OS]: pooled hazard ratio (HR) = 1.848, 95% confidence interval (CI) = 1.620-2.108, P < 0.001; disease free survival [DFS]: pooled HR = 1.923, 95% CI = 1.585-2.333, P < 0.001; progression free survival [PFS]: pooled HR = 1.345, 95% CI = 1.133-1.597, P = 0.001). Furthermore, in subgroup analysis, we found an association between high LAT1 expression and poor OS in non-small cell lung cancer (HR = 1.554, 95% CI = 1.345-1.794, P < 0.001), pancreatic cancer (HR = 2.052, 95% CI = 1.613-2.724, P < 0.001) and biliary tract cancer (HR = 2.253, 95% CI = 1.562-3.227, P < 0.001). CONCLUSION:The results of this meta-analysis indicate the reliability and potential of using LAT1 expression as a predictive biomarker in solid cancers prior to treatment. However, further studies with larger sample sizes would be beneficial for fully evaluating the predictive value of LAT1 expression for clinical applications.

The intrinsic factors (IF) influencing visual attention performance (VAP) might cause potential human errors, such as "error/mistake", "forgetting" and "omission". It is a key issue to develop a systematic assessment of IF in order to distinguish the levels of VAP. Motivated by the Stimulus-Response (S-R) model, we take an interactive cancellation test-Neuron Type Test (NTT)-to explore the IF and present the corresponding systematic assessment. The main contributions of this work include three elements: a) modeling the IF on account of attention span, attention stability, distribution-shift of attention with measurable parameters by combining the psychological and statistical concepts; b) proposing quantitative analysis methods for assessing the IF via its computational representation-intrinsic qualities (IQ)-in the sense of computational model; and c) clustering the IQ of air traffic control (ATC) students in the feature space of interest. The response sequences of participants collected with the NTT system are characterized by three parameters: Hurst exponent, normalized number of decisions (NNoD) and error rate of decisions (ERD). The K-means clustering is applied to partition the feature space constructed from practical data of VAP. For the distinguishable clusters, the statistical inference is utilized to refine the assessment of IF. Our comprehensive analysis shows that the IQ can be classified into four levels, i.e., excellent, good, moderate and unqualified, which has a potential application in selecting air traffic controllers subject to reducing the risk of the inadequacy of attention performances in aviation safety management.

PurposeThe principal excitatory neurotransmitter glutamate plays an important role in many central nervous system disorders. Because glutamate resides predominantly in glutamatergic neurons, its relaxation properties reflect the intracellular environment of glutamatergic neurons. This study developed an improved echo time-independent technique for measuring transverse relaxation time and demonstrated that this radio frequency (RF)-driven longitudinal steady state technique can reliably measure glutamate transverse relaxation in the frontal cortex, where structural and functional abnormalities have been associated with psychiatric symptoms.MethodBloch and Monte Carlo simulations were performed to improve and optimize the RF-driven, longitudinal, steady-state (MARzss) technique to significantly shorten scan time and increase measurement precision. Optimized four-flip angle measurements at 0°,12°, 24°, and 36° with matched repetition time were used in nine human subjects (6F, 3M; 27-49 years old) at 7 Tesla. Longitudinal and transverse relaxation rates for glutamate were measured from a 2 x 2 x 2 cm3 voxel placed in three different brain regions: gray matter-dominated medial prefrontal lobe, white matter-dominated left frontal lobe, and gray matter-dominated occipital lobe.ResultsCompared to the original MARzss technique, the scan time per voxel for measuring glutamate transverse relaxation was shortened by more than 50%. In the medial frontal, left frontal, and occipital voxels, the glutamate T2 was found to be 117.5±12.9 ms (mean ± standard deviation, n = 9), 107.3±12.1 (n = 9), and 124.4±16.6 ms (n = 8), respectively.ConclusionsThe improvements described in this study make the MARZSS technique a viable tool for reliably measuring glutamate relaxation from human subjects in a typical clinical setting. It is expected that this improved technique can be applied to characterize the intracellular environment of glutamatergic neurons in a variety of brain disorders.

Due to the Expanded Program on Immunization (EPI) and supplementary immunization activities (SIAs) in China, the incidence of measles in China has decreased extensively. The incidence reached its lowest levels in contemporary history in 2012 and 2017, with incidence rates of 4.6 and 4.3 per million population, respectively. However, more than 147,000 measles cases were reported from 2013 to 2016. Furthermore, the proportions of cases in infants < 8 months and adults have been increasing since 2013, representing a considerable challenge for measles elimination in China. A total of 14,868 measles viruses were isolated from confirmed measles cases from 2011 to 2017, of which 14,631 were identified as the predominant endemic genotype, H1; 87 were identified as genotype A viruses that were vaccine associated strains; and 150 were identified as non-H1 genotype viruses. The non-H1 genotype viruses included 62 D8 viruses, 70 D9 viruses, 3 D11 viruses, 14 B3 viruses, and 1 G3 virus, which were identified as imported or import-related viruses that caused sporadic cases or small outbreaks. Most of the transmission chains detected during the period 2011-2012 were interrupted and were followed by many new transmission chains of unknown origin that spread, causing a large measles resurgence in China during 2013-2016. After 4 years of measles resurgence and continuous implementation of the routine immunization program and SIAs, the population immunity reached a sufficiently high level to interrupt most of the transmission chains; only a few strains survived, which continued to be sporadically detected in China in 2017. In the present study, the results from the combined epidemiological and molecular virological data demonstrated the great progress towards measles elimination in China by the further analysis of circulation dynamics for the endemic H1 genotype measles virus from 2011 to 2017. And this study accumulated critical baseline data on circulating wild-type measles viruses in China and provides comprehensive information to the world. These comprehensive baseline data provide evidence to support measles elimination in the future, not only in China but also in other countries worldwide. In addition, the information will be very useful to other countries for tracing their sources of measles cases and for identifying transmission links, which can help prevent potential measles outbreaks.

PURPOSE:Perfusion and diffusion magnetic resonance imaging (MRI) provide important biomarkers for brain tumor analysis. Our aim was to investigate if regions of increased perfusion or tumor with restricted diffusion on the immediate post-operative MRI examination would be predictive of time to tumor progression in patients with high-grade gliomas. MATERIALS AND METHODS:Twenty-three patients with high-grade gliomas were retrospectively analyzed. We measured the perfusion at the resection area and evaluated the presence or absence of the restricted diffusion in residual tumor masses. The associations of the perfusion, diffusion and contrast enhancement (delayed static enhancement (DSE)) characteristics with time to tumor progression were statistically calculated. We also evaluated if the location of the tumor progression was concordant to the areas of the elevated perfusion, tumor type restricted diffusion and enhancement. RESULTS:Patients with >200 days to progression are more likely to have no elevated relative cerebral blood volume (rCBV) ratio (p = 0.0004), no tumor restriction (p = 0.024), and no DSE (p = 0.052). The elevated mean rCBV ratio (p1.5 progressed in 275 days or earlier. Tumors tended to progress at the area where patients with post-operative MRIs showed elevated perfusion (p = 0.006), tumor-type restricted diffusion (p = 0.005) and DSE (p = 0.008). CONCLUSIONS:Post-operative analysis of rCBV, tumor type restricted diffusion and enhancement characteristics are predictive of time to progression, risk of progression and where tumor progression is likely to occur.

OBJECTIVE:The immune rejection mediated by CD4+ T cell and antigen presenting macrophages is the leading cause of corneal transplantation failure. Bone marrow-derived mesenchymal stem cells (BM-MSCs) possess robust immunomodulatory potentials, and have been shown by us and others to promote corneal allograft survival. However, the immunological mechanism underlying the protective effects of BM-MSCs remains unclear. Therefore, in the current study, this mechanism was investigated in a BM-MSC-treated rat model of corneal allograft rejection, in the hope to facilitate the search for novel interventional targets to corneal allograft rejection. METHODS:Lewis rats were subjected to corneal transplantation and then received subconjunctival injections of BM-MSCs (2×106 cells / 100 μl PBS) immediately and at day 3 post-transplantation. The control group received the injections of PBS with the same volume. The clinical parameters of the corneal allografts, including opacity, edema, and neovascularization, were regularly evaluated after transplantation. On day 10 post-transplantation, the corneal allografts were collected and subjected to flow cytometry and high-throughput RNA sequencing (RNA-seq). GO enrichment and KEGG pathways were analyzed. The quantitative realtime PCR (qPCR) and immunohistochemistry (IHC) were employed to validate the expression of the selected target genes at transcript and protein levels, respectively. RESULTS:BM-MSC subconjunctival administration prolonged the corneal allograft survival, with reduced opacity, alleviated edema, and diminished neovascularization. Flow cytometry showed reduced CD4+ T cells and CD68+ macrophages as well as boosted regulatory T cells (Tregs) in the BM-MSC-treated corneal allografts as compared with the PBS-treated counterparts. Moreover, the RNA-seq and qPCR results demonstrated that the transcript abundance of Cytotoxic T-Lymphocyte Associated Protein 4 (Ctla4), Protein Tyrosine Phosphatase, Receptor Type C (Ptprc), and C-X-C Motif Chemokine Ligand 9 (Cxcl9) genes were increased in the allografts of BM-MSC group compared with PBS group; whereas the expression of Heat Shock Protein Family A (Hsp70) Member 8 (Hspa8) gene was downregulated. The expression of these genes was confirmed by IHC at protein level. CONCLUSION:Subconjunctival injections of BM-MSCs promoted corneal allograft survival, reduced CD4+ and CD68+ cell infiltration, and enriched Treg population in the allografts. The BM-MSC-induced upregulation of Ctla4, Ptprc, Cxcl9 genes and downregulation of Hspa8 gene might contribute to the protective effects of BM-MSCs and subserve the potential interventional targets to corneal allograft rejection.

Powerful shovel-like forelimbs with special shape, structure and biological materials enable mole cricket to digging efficiently. During digging, the tip of the claw needs to wedge into the soil, and the base needs to withstand considerable anti-shear force. In this study, we analysed the structural characteristics, material composition and mechanical properties of the claw teeth using scanning electron microscopy, plasma atomic emission spectroscopy, nanoindentation and finite element analysis. The results show that the tips of claw teeth have a dense and homogeneous structure and a higher hardness and contents of Mn and Zn compared with the base. The structure of the base of claw teeth has an obvious laminar structure and higher fracture resistance. Moreover, it is speculated from the simulation results that basal position of the claw teeth is tough enough to withstand high stress, and the presence of the ribs effectively improves the mechanical stability and load-bearing capacity of the teeth during excavation. The results of this study can provide inspiration for the design of efficient mechanical components and agricultural implements.

Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies.

Learning a powerful representation for a class with few labeled samples is a challenging problem. Although some state-of-the-art few-shot learning algorithms perform well based on meta-learning, they only focus on novel network architecture and fail to take advantage of the knowledge of every classification task. In this paper, to accomplish this goal, it proposes to combine the channel attention and spatial attention module (C-SAM), the C-SAM can mine deeply more effective information using samples of different classes that exist in different tasks. The residual network is used to alleviate the loss of the underlying semantic information when the network is deeper. Finally, a relation network including a C-SAM is applied to act as a classifier, which avoids learning more redundant information and compares the relation between difference samples. The experiment was carried out using the proposed method on six datasets, such as miniimagenet, Omniglot, Caltech-UCSD Birds, describable textures dataset, Stanford Dogs and Stanford Cars. The experimental results show that the C-SAM outperforms many state-of-the-art few-shot classification methods.

The blood-brain barrier (BBB) is a dynamic and complex interface between blood and the central nervous system (CNS). It protects the brain by preventing toxic substances from entering the brain but also limits the entry of therapeutic agents. ATP-binding cassette (ABC) efflux transporters are critical for the functional barrier and present a formidable impediment to brain delivery of therapeutic agents including antibiotics. The aim of this study was to investigate the possible involvement of multidrug resistance-associated protein 1 and 4 (MRP1 and MRP4), two ABC transporters, in benzylpenicillin efflux transport using wild-type (WT) MDCKII cells and cells overexpressing those human transporters, as well as non-selective and selective inhibitors. We found that inhibiting MRP1 or MRP4 significantly increased [3H]benzylpenicillin uptake in MDCKII-WT, -MRP1 or -MRP4 cells. Similar results were also found in HepG2 cells, which highly express MRP1 and MRP4, and hCMEC/D3 cells which express MRP1. The results indicate that human and canine MRP1 and MRP4 are involved in benzylpenicillin efflux transport. They could be potential therapeutic targets for improving the efficacy of benzylpenicillin for treating CNS infections since both MRP1 and MRP4 express at human blood-brain barrier.

Total variation (TV) based models are very popular in image denoising but suffer from some drawbacks. For example, local TV methods often cannot preserve edges and textures well when they face excessive smoothing. Non-local TV methods constitute an alternative, but their computational cost is huge. To overcome these issues, we propose an image denoising method named non-local patch graph total variation (NPGTV). Its main originality stands for the graph total variation method, which combines the total variation with graph signal processing. Schematically, we first construct a K-nearest graph from the original image using a non-local patch-based method. Then the model is solved with the Douglas-Rachford Splitting algorithm. By doing so, the image details can be well preserved while being denoised. Experiments conducted on several standard natural images illustrate the effectiveness of our method when compared to some other state-of-the-art denoising methods like classical total variation, non-local means filter (NLM), non-local graph based transform (NLGBT), adaptive graph-based total variation (AGTV).

Previous studies have suggested that treatment plans for segmental bone defects (SBDs) are affected by the bone defect sizes. If the selected treatment was not the most appropriate, it would not contribute to bone healing, but increase complications. The induced membrane technique (IM) and distraction osteogenesis (DO) have been proved to be effective in treating SBDs. However, the differences between the two in therapeutic effects on SBDs with different sizes are still unclear. Thus, we aimed to observe the effects of IM and DO on different sizes of SBDs and to further determine what method is more appropriate for what defect size. Rat models of 4-, 6-and 8-mm mid-diaphyseal defects using IM and DO techniques were established. X-rays, micro-CT, histological and immunohistochemical examinations were performed to assess bone repair. Faster bone formation rate, shorter treatment duration, higher expressions of OPN and OCN and higher parameters of bone properties including bone mineral density (BMD), bone volume/total tissue volume (BV/TV), mineral apposition rate (MAR) and mineral surface/bone surface (MS/BS) were found in 4-mm SBDs treated with DO than in those with IM treatment. However, the results were reversed and IM outperformed DO in bone repair capacity for 8-mm SBDs, while no significant difference emerges in the case of 6-mm SBDs. This study suggests that the therapeutic effects of IM and DO may be subjected to sizes of bone defects and the best treatment size of defects is different between the two. For small-sized SBDs, DO may be more suitable and efficient than IM, but IM has advantages over DO for over-sized SBDs, while DO and IM show similar bone repair capability in moderate-sized SBDs, which would offer a new insight into how to choose DO and IM for SBDs in clinical practice and provide references for further clinical research.

ObjectivesAlthough several studies have shown that cigarette smoking is associated with thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), the exact relationship between smoking and thyroid function is controversial. As little is known about the effects of smoking on TSH, TPOAb and TgAb in Chinese residents. This study aimed to evaluate the association between cigarette smoking and TSH, TPOAb and TgAb in ten-city residents of China.Study designThis was a population-based cross-sectional study.MethodsIn this cross-sectional study, 15,181 subjects from ten major cities of China were investigated. Data regarding demographic characteristics, smoking status and consumption of iodine status were collected using in-person interviews based on a self-designed structured questionnaire. Serum concentrations of TSH, TPOAb and TgAb were measured using electrochemiluminescence immunoassays. Univariate analysis and multivariate linear stepwise regression analyses were used to analyze the data.ResultsThe regular smokers had lower concentrations of TSH, TPOAb and TgAb than occasional smokers, former smokers and never smokers. Multivariate analysis demonstrated that regular smoking was associated with the decreased concentrations of TSH (β = -0.178), TPOAb (β = -0.287) and TGAb (β = -0.453) after adjusting other factors. Furthermore, daily smoking number was significantly associated with the decreased level of TSH (β = -0.045) and TPOAb(β = -0.080), and smoking duration was associated with the decreased TSH level (β = -0.030).ConclusionsOur findings suggest that cigarette smoking is related to a significant decline in the concentrations of TSH, TPOAb and TgAb. In addition, daily smoking number and long-term smoking decrease serum TSH and TPOAb levels. Cigarette smoking plays a significant role in the development of thyroid dysfunction.

In addition to high vaccination coverage, timely and accurate laboratory confirmation of measles cases is critical to interrupt measles transmission. To evaluate the role of real-time reverse transcription-polymerase chain reaction (RT-PCR) in the diagnosis of measles cases, 46,363 suspected measles cases with rash and 395 suspected measles cases without rash were analyzed in this study; the cases were obtained from the Chinese measles surveillance system (MSS) during 2014-2017 and simultaneously detected by measles-specific IgM enzyme-linked immunosorbent assay (ELISA) and real-time RT-PCR. However, some IgM-negative measles cases were identified by real-time RT-PCR. The proportion of these IgM-negative and viral nucleic acid-positive measles cases was high among measles cases with measles vaccination history, cases without rash symptoms, and cases within 3 days of specimen collection after onset. The proportion of IgM-negative and viral nucleic acid-positive measles cases in the 0-3 day group was up to 14.4% for measles cases with rash and 40% for measles cases without rash. Moreover, the proportions of IgM-negative and nucleic acid-positive measles cases gradually increased with the increase in the measles vaccination dose. Therefore, integrated with IgM ELISA, real-time RT-PCR would greatly improve the accurate diagnosis of measles cases and avoid missing the measles cases, especially for measles cases during the first few days after onset when the patients were highly contagious and for measles cases with secondary vaccine failure. In conclusion, our study reconfirmed that IgM ELISA is the gold-standard detection assay for measles cases confirmation. However, real-time RT-PCR should be introduced and used to supplement the laboratory diagnosis, especially in the setting of pre-elimination and/or elimination wherever appropriate.

Neoadjuvant chemotherapy before radical gastrectomy is preferred for locally advanced gastric cancer. To avoid the problematic use of pTNM for patients after neoadjuvant chemotherapy, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer TNM staging system (8th edition) added ypTNM for the first time. But patients achieving pathological complete response were not covered by the new ypTNM staging system. To investigate whether pathological complete response is associated with better outcome in gastric cancer, as was reported in rectal, breast and bladder cancer.We systematically searched the databases of PubMed, EMBASE, Web of Science and Cochrane Collaboration's Central register of controlled trials from January 1988 to April 2015 for publications which reported outcomes of patients with and without pathological complete response (pCR) (pT0N0M0) to investigate whether pCR after neoadjuvant chemotherapy in gastric or gastroesophageal junction (GEJ) treated with radical surgery is associated with better survival. The primary outcome was overall survival (OS). The secondary outcome was disease-free survival (DFS). Both were measured with a relative risk (RR). A meta-analysis was performed using the fixed effects model. Forest plots and the Q test was used to evaluate overall heterogeneity for OS and DFS.A total of seven trials, 1143 patients were included and analyzed after neoadjuvant chemotherapy and radical surgery with no other preoperative treatment. The average rate of pCR was 6.74% (range: 3%-15%). The RR of patients who achieved pCR in the primary tumor and lymph nodes is 0.5 (95% confidence interval [CI], 0.25-0.98; p = 0.04), 0.34 (95% CI, 0.21-0.55; p

Community structures are ubiquitous in various complex networks, implying that the networks commonly be composed of groups of nodes with more internal links and less external links. As an important topic in network theory, community detection is of importance for understanding the structure and function of the networks. Optimizing statistical measures for community structures is one of most popular strategies for community detection in complex networks. In the paper, by using a type of self-loop rescaling strategy, we introduced a set of global modularity functions and a set of local modularity functions for community detection in networks, which are optimized by a kind of the self-consistent method. We carefully compared and analyzed the behaviors of the modularity-based methods in community detection, and confirmed the superiority of the local modularity for detecting community structures on large-size and heterogeneous networks. The local modularity can more quickly eliminate the first-type limit of modularity, and can eliminate or alleviate the second-type limit of modularity in networks, because of the use of the local information in networks. Moreover, we tested the methods in real networks. Finally, we expect the research can provide useful insight into the problem of community detection in complex networks.

This study examined the predictors of loss to follow-up in long-term supportive periodontal therapy in patients with chronic periodontitis.A total of 280 patients with moderate to severe chronic periodontitis in a tertiary care hospital in China were investigated and followed over the course of study. Questionnaires on clinical and demographic characteristics, self-efficacy for oral self-care and dental fear at baseline were completed. Participants were followed to determine whether they could adhere to long-term supportive periodontal therapy. Binary logistic regression analysis was used to examine the association between clinical and demographic characteristics, self-efficacy for oral self-care, dental fear and loss to follow-up in long-term supportive periodontal therapy.The loss to follow-up in long-term supportive periodontal therapy was significantly associated with age [adjusted OR = 1.042, 95% confidence interval (CI): 1.012-1.074, p = 0.006], severe periodontitis [adjusted OR = 4.892, 95%CI: 2.280-10.499, p