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ObjectiveTo determine the human papillomavirus (HPV) infection status and possible influencing factors among healthy women aged 18‒45 years, and to provide a scientific evidence for the prevention of HPV infection and cervical cancer.MethodsA total of 23 HPV types were examined by PCR-reverse dot blot hybridization in 1 210 healthy women who voluntarily participated in the study. Infection status of each HPV genotype and possible factors associated with the infection were determined, including age, ethnicity, marital history, pregnancy history, number of sexual partners, and age at first sexual intercourse.ResultsA total of 1 210 healthy women were examined, of which 267 tested positive for HPV, with a prevalence of 22.07%. The prevalence did not differ significantly across age groups or ethnicities (all P>0.05). Moreover, the highest prevalence was found in the divorced/widowed participants (53.57%), compared with other marital status (χ2=35.16, P

Abstract Background To investigate the associations of methylation, expression, and protein quantitative trait loci (mQTL, eQTL, and pQTL) with ankylosing spondylitis (AS) and find out genetically supported drug targets for AS. Methods The summary-data-based Mendelian randomization (SMR) and Bayesian co-localization analysis were used to assess the potential causality between AS and relevant genes. The GWAS data obtained from the International Genetics of Ankylosing Spondylitis Consortium (IGAS) were set as the discovery stage, and the FinnGen and UK Biobank databases were used to replicate the analysis as an external validation. We further integrated the multi-omics results to screen overlapped genes at different levels. The protein–protein interaction (PPI) network and enrichment analyses were used to explore the biological effect of SMR-identified genes on AS. Drug prediction and molecular docking were used to validate the medicinal value of candidate drug targets. Results Based on the results of multi-omics evidence screening, we identified potential associations of TNFRSF1A, B3GNT2, ERAP1, and FCGR2A with AS at different regulatory levels. At the protein level, AIF1, TNXB, APOM, and B3GNT2 were found to be negatively associated with AS risk, whereas higher levels of FCGR2A, FCGR2B, IL12B, TNFRSF1A, and ERAP1 were associated with an increased risk of AS. The bioinformatics analyses showed that the SMR-identified genes were mainly involved in immune response. Molecular docking results displayed stable binding between predicted candidate drugs and these aforementioned proteins. Conclusion Our study found four AS-associated genes with multi-omics evidence and nine promising drug targets for AS, which may contribute to the understanding of the genetic mechanisms of AS and provide innovative perspectives into targeted therapy for AS.

Introduction As China is scaling up tuberculosis preventive therapy (TPT) for people living with HIV (PLHIV) in its national programmes, the objective of this study was to evaluate the feasibility and performance of 6-month regimen of isoniazid monotherapy (6H) in terms of preventive therapy acceptance, adherence, effectiveness and outcomes in minority areas with a high burden of tuberculosis (TB) and HIV/AIDS.Method A prospective observational cohort study was initiated among 461 PLHIV in Butuo County after ruling out active TB (ATB) and followed up for up to 3 years to collect incidence events in real-world settings. TB incidence and protective rates were calculated. The risk factors related to acceptance and adherence were identified using a logistic regression model.Results Of the 688 PLHIV screened for TB, 115 (16.72 %) had ATB. Among the 461 participants eligible for 6H, 392 (85.03%) initiated 6H, and 277 (70.67%) completed the therapy. In total, 15 were identified as having ATB during follow-up. The incidence of ATB in the complete group was 0.62/100 person years (95% CI 0.20 to 1.45) as compared with the incomplete group 2.96/100 person years (95% CI 1.36 to 5.63) (p=0.005), and the protective rate of 6H was 79.05%. The protection rate between the complete and incomplete and refusal groups was 69.31%. In total, 142 (36.22%) patients experienced adverse drug reactions during isoniazid preventive therapy. The logistic regression model revealed several factors associated with 6H acceptance: first CD4+ T lymphocyte count was between 200 and 350 cells/mm3 (adjusted OR (aOR)=0.30, 95% CI 0.10 to 0.92) or>500 cells/mm3 (aOR=0.25, 95% CI 0.08 to 0.77). Factors associated with 6H adherence: 36–45 years old (aOR=2.76, 95% CI 1.49 to 5.10), middle school education (aOR=0.26, 95% CI 0.08 to 0.79) and history of prior TB (aOR=0.09, 95% CI 0.05 to 0.20).Conclusion 6H can reduce the incidence of ATB in minority areas with high burdens of TB and HIV/AIDS. Periodic counselling of patients on adherence and retraining of the TPT staff are essential. Health monitoring and education for specific populations improve TPT acceptance and adherence.

Abstract The chloroplast (cp) genome sequence of Mussaenda pubescens, a promising resource that is used as a traditional medicine and drink, is important for understanding the phylogenetic relationships among the Mussaenda family and genetic improvement and reservation. This research represented the first comprehensive description of the morphological characteristics of M. pubescens, as well as an analysis of the complete cp genome and phylogenetic relationship. The results indicated a close relationship between M. pubescens and M. hirsutula based on the morphological characteristics of the flower and leaves. The cp was sequenced using the Illumina NovaSeq 6000 platform. The results indicated the cp genome of M. pubescens spanned a total length of 155,122 bp, including a pair of inverted repeats (IRA and IRB) with a length of 25,871 bp for each region, as well as a large single-copy (LSC) region and a small single-copy (SSC) region with lengths of 85,370 bp and 18,010 bp, respectively. The results of phylogenetic analyses demonstrated that species within the same genus displayed a tendency to group closely together. It was suggested that Antirhea, Cinchona, Mitragyna, Neolamarckia, and Uncaria might have experienced an early divergence. Furthermore, M. hirsutula showed a close genetic connection to M. pubescens, with the two species having partially overlapping distributions in China. This study presents crucial findings regarding the identification, evolution, and phylogenetic research on Mussaenda plants, specifically targeting M. pubescens.

Abstract Prophages, which enables bacterial hosts to acquire novel traits, and increase genetic variation and evolutionary innovation, are considered to be one of the greatest drivers of bacterial diversity and evolution. Stenotrophomonas maltophilia is widely distributed and one of the most important multidrug resistant bacteria in hospitals. However, the distribution and genetic diversity of S. maltophilia prophages have not been elucidated. In this study, putative prophages were predicted in S. maltophilia genomes by using virus prediction tools, and the genetic diversity and phylogeny of S. maltophilia and the prophages they harbor were further analyzed. A total of 356 prophage regions were predicted from 88 S. maltophilia genomes. Among them, 144 were intact prophages, but 77.09% of the intact prophages did not match any known phage sequences in the public database. The number of prophage carried by S. maltophilia is related to its host habitat and is an important factor affecting the size of the host genome, but it is not related to the genetic diversity of the prophage. The prediction of auxiliary genes encoded by prophage showed that antibiotic resistance genes was not predicted for any of the prophages except for one questionable prophage, while 53 virulence genes and 169 carbohydrate active enzymes were predicted from 11.24 and 44.1% prophages, respectively. Most of the prophages (72.29%) mediated horizontal gene transfer of S. maltophilia genome, but only involved in 6.25% of the horizontal gene transfer events. In addition, CRISPR prediction indicated 97.75% S. maltophilia strains contained the CRISPR-Cas system containing 818 spacer sequences. However, these spacer sequences did not match any known S. maltophilia phages, and only a few S. maltophilia prophages. Comparative genomic analysis revealed a highly conserved and syntenic organization with genomic rearrangement between the prophages and the known related S. maltophilia phages. Our results indicate a high prevalence and genetic diversity of prophages in the genome of S. maltophilia, as well as the presence of a large number of uncharacterized phages. It provides an important complement to understanding the diversity and biological characteristics of phages, as well as the interactions and evolution between bacteria and phages.

Objective To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid （Gd-EOB-DTPA） enhanced MRI in evaluating the degree of esophageal varices. Methods Clinical data of 114 patients diagnosed with hepatitis B cirrhosis and Gd-EOB-DTPA enhanced MRI examination through clinical comprehensive diagnosis at Jiangsu Provincical Hospital of Chinese Medicine from September 2021 to June 2022 was retrospective analyzed. The patients were divided into non-varicose vein group, small varicose vein group and large varicose vein group based on the diagnostic threshold of 3 mm esophageal vein width. The signal intensity (SI) of liver, spleen and erector spinae muscles were measured in each group during the plain scan and hepatobiliary phase (20 minutes after enhancement). The relative liver enhancement (RLE), contrast uptake index （CUI）, and liver-to-spleen contrast index (LSI) were calculated. The differences in indicators between each group were compared, and the receiver operating characteristic curve (ROC) were drawn. The area under the curve (AUC) was used to evaluate the diagnostic efficacy of each indicator in diagnosing varicose veins. Results There was a significant difference in RLE, CUI, and LSI between the non-varicose vein group and the large varicose vein group (P＜0.05), while there was no significant difference in RLE, CUI, and LSI between the small varicose vein group, as well as between small varicose vein group and large varicose vein group (P>0.05). The AUC of RLE, CUI and LSI for diagnosing large varicose veins was 0.668 (95%CI: 0.558-0.793), 0.676 (95%CI: 0.567-0.804) and 0.685 (95%CI: 0.550-0.780), respectively. Conclusion Gd-EOB-DTPA enhanced MRI has certain value in evaluating the degree of esophageal varices.

Abstract Objective No evidence has been found of a relationship between remnant cholesterol (RC) and the likelihood of gestational diabetes mellitus (GDM) in pregnant women. The aim of our study was to investigate the link between serum RC at 12–14 weeks of gestation and the risk of GDM. Methods This was a secondary analysis with data from a prospective cohort study in Korea. A total of 590 single pregnant women attending two hospitals in Korea, up to 14 weeks gestation, from November 2014 to July 2016 were included in the study. The formula used to calculate RC in detail was RC (mg/dL) = TC (mg/dL)-HDL-c (mg/dL)-LDL-c (mg/dL). Logistic regression models were employed to examine the relationship between RC and GDM and explore the association between other lipoprotein cholesterol parameters and the risk of GDM. Furthermore, receiver operating characteristic (ROC) analysis was performed to assess the ability of RC to identify GDM. Additionally, sensitivity and subgroup analyses were conducted. Results The mean age of participants was 32.06 ± 3.80 years. The median of RC was 34.66 mg/dL. 37 pregnant women (6.27%) were eventually diagnosed with GDM. Multivariate adjusted logistic regression analysis showed that RC was positively associated with the risk of GDM (OR = 1.458, 95% CI 1.221, 1.741). There was no significant association between other lipoprotein cholesterols (including TC, LDL-c, HDL-c) and the risk of GDM. The area under the ROC curve for RC as a predictor of GDM was 0.8038 (95% CI 0.7338–0.8738), and the optimal RC cut-off was 24.30 mg/dL. Our findings were demonstrated to be robust by performing a series of sensitivity analyses. Conclusion Serum RC levels at 12–14 weeks of gestation are positively associated with GDM risk in pregnant women. RC in early pregnancy is an early warning indicator of GDM in pregnant women, especially those with normal HDL-c, LDL-c, and TC that are easily overlooked. There is a high risk of developing GDM in pregnant women whose RC is more than 24.30 mg/dL. This study may help optimize GDM prevention in pregnant women and facilitate communication between physicians, pregnant patients, and their families.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD. The livers of patients with NASH are more likely to develop fibrosis. Xiaoyao San (XYS) is a classic traditional Chinese medicine (TCM) formula that has been widely used in treating liver diseases. In this study, we elucidated the effects and mechanism of XYS in treating NASH-related liver fibrosis by combining high-throughput sequencing-based high-throughput screening with network pharmacology analysis. Our work revealed that XYS may play a role in preventing NASH-related liver fibrosis by regulating biological functions related to the extracellular matrix (ECM), inflammation, and metabolism. Additionally, Bupleuri Radix, Poria, Zingiberis Rhizoma Recens, and Paeoniae Radix Alba are the key herbs of XYS that could partially represent the functions of XYS. These regulatory effects are mediated by targeting signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NFκB), and peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Narcissin, casuarictin, and γ-sitosterol were identified as representative active compounds in XYS targeting STAT3, NFκB, and PPARγ, respectively. Taken together, our findings provide a novel strategy for investigating the pharmacological effects and biological mechanisms of a TCM formula.

Abrin and ricin, both type II ribosome-inactivating proteins, are toxins of significant concern and are under international restriction by the Chemical Weapons Convention and the Biological and Toxin Weapons Convention. The development of a rapid and sensitive detection method for these toxins is of the utmost importance for the first emergency response. Emerging rapid detection techniques, such as surface-enhanced Raman spectroscopy (SERS) and lateral flow assay (LFA), have garnered attention due to their high sensitivity, good selectivity, ease of operation, low cost, and disposability. In this work, we generated stable and high-affinity nanotags, via an efficient freezing method, to serve as the capture module for SERS-LFA. We then constructed a sandwich-style lateral flow test strip using a pair of glycoproteins, asialofetuin and concanavalin A, as the core affinity recognition molecules, capable of trace measurement for both abrin and ricin. The limit of detection for abrin and ricin was 0.1 and 0.3 ng/mL, respectively. This method was applied to analyze eight spiked white powder samples, one juice sample, and three actual botanic samples, aligning well with cytotoxicity assay outcomes. It demonstrated good inter-batch and intra-batch reproducibility among the test strips, and the detection could be completed within 15 min, indicating the suitability of this SERS-LFA method for the on-site rapid detection of abrin and ricin toxins.

BackgroundLung cancer, a leading cause of death, sees variable outcomes with iodine-125 seed implantation. Predictive tools are lacking, complicating clinical decisions. This study integrates radiomics and clinical features to develop a predictive model, advancing personalized treatment.ObjectiveTo construct a nomogram model combining enhanced CT image features and general clinical characteristics to evaluate the efficacy of radioactive iodine-125 seed implantation in lung cancer treatment.MethodsPatients who underwent lung iodine-125 seed implantation at the Nuclear Medicine Department of Xiling Campus, Yichang Central People's Hospital from January 1, 2018, to January 31, 2024, were randomly divided into a training set (73 cases) and a test set (31 cases). Radiomic features were extracted from the enhanced CT images, and optimal clinical factors were analyzed to construct clinical, radiomics, and combined models. The best model was selected and validated for its role in assessing the efficacy of iodine-125 seed implantation in lung cancer patients.ResultsThree clinical features and five significant radiomic features were successfully selected, and a combined nomogram model was constructed to evaluate the efficacy of iodine-125 seed implantation in lung cancer patients. The AUC values of the model in the training and test sets were 0.95 (95% CI: 0.91-0.99) and 0.83 (95% CI: 0.69-0.98), respectively. The calibration curve demonstrated good agreement between predicted and observed values, and the decision curve indicated that the combined model outperformed the clinical or radiomics model across the majority of threshold ranges.ConclusionA combined nomogram model was successfully developed to assess the efficacy of iodine-125 seed implantation in lung cancer patients, demonstrating good clinical predictive performance and high clinical value.

Abstract In recent years, postmortem brain studies have revealed that some molecular, cellular, and circuit changes associated with suicide, have an independent or additive effect on depression. The aim of the present study is to identify potential phenotypic, tissue, and sex-specific novel targets and pathways to distinguish depression or suicide from major depressive disorder (MDD) comorbid with suicide. The mRNA expression profiling datasets from two previous independent postmortem brain studies of suicide and depression (GSE102556 and GSE101521) were retrieved from the GEO database. Machine learning analysis was used to differentiate three regrouped gene expression profiles, i.e., MDD with suicide, MDD without suicide, and suicide without depression. Weighted correlation network analysis (WGCNA) was further conducted to identify the key modules and hub genes significantly associated with each of these three sub-phenotypes. TissueEnrich approaches were used to find the essential brain tissues and the difference of tissue enriched genes between depression with or without suicide. Dysregulated gene expression cross two variables, including phenotypes and tissues, were determined by global analysis with Vegan. RRHO analysis was applied to examine the difference in global expression pattern between male and female groups. Using the optimized machine learning model, several ncRNAs and mRNAs with higher AUC and MeanDecreaseGini, including GCNT1P1 and AC092745.1, etc., were identified as potential molecular targets to distinguish suicide with, or without MDD and depression without suicide. WGCNA analysis identified some key modules significantly associated with these three phenotypes, and the gene biological functions of the key modules mainly relate to ncRNA and miRNA processing, as well as oxidoreductase and dehydrogenase activity. Hub genes such as RP11-349A22.5, C20orf196, MAPK8 IP3 and RP11-697N18.2 were found in these key modules. TissueEnrich analysis showed that nucleus accumbens and subiculum were significantly changed among the 6 brain regions studied. Global analysis with Vegan and RRHO identified PRS26, ARNT and SYN3 as the most significantly differentially expressed genes across phenotype and tissues, and there was little overlap between the male and female groups. In this study, we have identified novel gene targets, as well as annotated functions of co-expression patterns and hub genes that are significantly distinctive between depression with suicide, depression without suicide, and suicide without depression. Moreover, global analysis across three phenotypes and tissues confirmed the evidence of sex difference in mood disorders.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19). We conducted a retrospective study of COVID-19 inpatients in Wuhan Pulmonary Hospital (Wuhan, China) from January 1 to February 29, 2020. The subjects were divided into four groups due to different treatment regimes. We used the Kaplan–Meier method to determine the cumulative rates of in-hospital death and the Cox proportional hazard model to calculate the risk factors and corresponding hazard ratios. A total of 185 patients were included in this study. The median age of the patients was 62 years, including 94 men and 91 women. Kaplan–Meier analysis demonstrated that mortality was higher in older patients, higher in men, and lower in the low-flow oxygen therapy group. Body mass index (BMI) had no influence on mortality, as well as high flow oxygen therapy, Lopinavir–ritonavir (LPV/r) therapy, and the interferon-alpha add LPV/r therapy. Cox proportional hazard regression confirmed that the low flow oxygen therapy was independent protective factor for in-hospital death after adjusting for age, gender, and BMI. In conclusion, the mortality was higher in older patients, higher in men, and lower in the low-flow oxygen therapy group. BMI had no influence on mortality, as well as high flow oxygen therapy, LPV/r therapy, and interferon-alpha add LPV/r therapy.

Abstract Background Due to insufficient basic medical knowledge and inappropriate learning strategies, students of 8-year medical programme encountered many obstacles in the initial stage of basic medicine learning. This study was to determine whether a prerequisite course can improve basic medicine learning performance and adjust learning strategies to adapt to basic medicine learning. Methods A prerequisite course of histology was constructed by a two-round modified Delphi study. Seventy-four students of 8-year medical programme were subjected to two groups: the prerequisite course group (PC group) and non-prerequisite course group (NPC group). The PC group take part in the prerequisite course by student-centred blended learning approach but NPC group not. The PC and NPC group underwent requisite histology teaching activities after prerequisite course. Examination of the prerequisite course and requisite histology course were carried out. Effect of the prerequisite course was evaluated by an empirical method using a questionnaire-based approach. Results The results of examinations showed students' scores of the PC group were significantly higher than those of students of NPC group in both prerequisite course and requisite histology examinations (P

Introduction Chronic conditions, such as diabetes, obesity, heart disease and depression, are highly prevalent and frequently co-occur with food insecurity in communities served by community health centres in the USA. Community health centres are increasingly implementing ‘Food as Medicine’ programmes to address the dual challenge of chronic conditions and food insecurity, yet they have been infrequently evaluated.Methods and analysis The goal of this quasi-experimental study was to evaluate the effectiveness of Recipe4Health, a ‘Food as Medicine’ programme. Recipe4Health includes two components: (1) a ‘Food Farmacy’ that includes 16 weekly deliveries of produce and (2) a ‘Behavioural Pharmacy’ which is a group medical visit. We will use mixed models to compare pre/post changes among participants who receive the Food Farmacy alone (n=250) and those who receive the Food Farmacy and Behavioural Pharmacy (n=140). The primary outcome, fruit and vegetable consumption, and secondary outcomes (eg, food security status, physical activity, depressive symptoms) will be collected via survey. We will also use electronic health record (EHR) data on laboratory values, prescriptions and healthcare usage. Propensity score matching will be used to compare Recipe4Health participants to a control group of patients in clinics where Recipe4Health has not been implemented for EHR-derived outcomes. Data from surveys, EHR, group visit attendance and produce delivery is linked with a common identifier (medical record number) and then deidentified for analysis with use of an assigned unique study ID. This study will provide important preliminary evidence on the effectiveness of primary care-based strategies to address food insecurity and chronic conditions.Ethics and dissemination This study was approved by the Stanford University Institutional Review Board (reference protocol ID 57239). Appropriate study result dissemination will be determined in partnership with the Community Advisory Board.

Summary: The identification, uptake, and clearance of nanoparticles (NPs) by phagocytes are critical in NP-based therapeutics. The cell membrane coating technique has recently emerged as an ideal surface modification approach to help NP bypass phagocytosis. CD47, a regulatory protein for phagocytosis, is a cell surface glycoprotein expressed on all cell types, including platelets. Herein, we enclosed bioactive glass (BG) with a platelet membrane to bestow BG with unique cell surface functions for immune evasion and immunomodulation. Compared with the uncoated particles, platelet membrane-coated BG shows reduced cellular uptake and can generate an immune environment favorable for osteogenesis. This is evidenced by the triggering of robust osteogenic differentiation in bone mesenchymal stromal cells, suggesting the synergistic effect of platelet membrane and BG in bone regeneration. These collectively indicate that cell membrane coating is a promising approach to enhance the therapeutic efficacy of biomaterials and thus provide new insight into biomaterial-mediated bone regeneration.

Intestinal epithelial integrity is commonly disrupted in patients with critical disorders, but the exact underlying mechanisms are unclear. Long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control different cell functions and are involved in pathologies. Here, we investigated the role of T-UCRs in intestinal epithelial homeostasis and identified T-UCR uc.230 as a major regulator of epithelial renewal, apoptosis, and barrier function. Compared with controls, intestinal mucosal tissues from patients with ulcerative colitis and from mice with colitis or fasted for 48 hours had increased levels of uc.230. Silencing uc.230 inhibited the growth of intestinal epithelial cells (IECs) and organoids and caused epithelial barrier dysfunction. Silencing uc.230 also increased IEC vulnerability to apoptosis, whereas increasing uc.230 levels protected IECs against cell death. In mice with colitis, reduced uc.230 levels enhanced mucosal inflammatory injury and delayed recovery. Mechanistic studies revealed that uc.230 increased CUG-binding protein 1 (CUGBP1) by acting as a natural decoy RNA for miR-503, which interacts with Cugbp1 mRNA and represses its translation. These findings indicate that uc.230 sustains intestinal mucosal homeostasis by promoting epithelial renewal and barrier function and that it protects IECs against apoptosis by serving as a natural sponge for miR-503, thereby preserving CUGBP1 expression.

The highly toxic plant toxin ricin is one of the most known threatening toxins. Accurate and sensitive biosensing methods for the first emergency response and intoxication treatment, are always pursued in the biodefense field. Screening affinity molecules is the fundamental mainstream approach for developing biosensing methods. Compared with common affinity molecules such as antibodies and oligonucleotide aptamers, peptides have great potential as biosensing modules with more accessible chemical synthesis capability and better batch-to-batch stability than antibodies, more abundant interaction sites, and robust sensing performance towards complex environments. However, anti-ricin peptides are so scant to be screened and discovered, and an advanced screening strategy is the utmost to tackle this issue. Here, we present a new in silico-in vitro iteration-assisted affinity maturation strategy of anti-ricin peptides. We first obtained affinity peptides targeting ricin through phage display with five panning rounds of “coating-elution-amplification-enrichment” procedures. The binding affinity and kinetic parameters characterized by surface plasmon resonance (SPR) showed that we had obtained four peptides owning dissociation constants (KD) around 2~35 μM, in which peptide PD-2-R5 has the lower KD of 4.7 μM and higher stable posture to interact with ricin. We then constructed a new strategy for affinity maturity, composing two rounds of in silico-in vitro iterations. Firstly, towards the single-site alanine scanning mutation peptide library, the molecular docking predictions match the SPR evaluation results well, laying a solid foundation for designing a full saturation mutated peptide library. Secondly, plenty of in silico saturation mutation prediction results guided the discovery of peptides PD2-R5-T3 and PD-2-R5-T4 with higher affinity from only a limited number of SPR evaluation experiments. Both evolved peptides had increased affinity by about 5~20 times, i.e., KD of 230 nM and 900 nM. A primary cellular toxicity assay indicated that both peptides could protect cells against ricin damage. We further established an SPR assay based on PD-2-R5-T3 and PD-2-R5-T4 elongated with an antifouling peptide linkage and achieved good linearity with a sensitivity of 1 nM and 0.5 nM, respectively. We hope this new affinity-mature strategy will find its favorable position in relevant peptide evolution, biosensing, and medical countermeasures for biotoxins to protect society’s security and human life better.

Abstract Background Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF. Methods This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group. Results The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts. Conclusions The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx

BackgroundAlthough Latino men have the highest prevalence (45%) of obesity among all men in the United States, traditional weight loss interventions have not effectively engaged this hard-to-reach and diverse group. Offering choices among technology-mediated weight loss interventions may offer advantages. ObjectiveThe aim of this study is to examine Latino men’s preferences among 3 weight loss intervention options. We also examined whether attendance in group sessions (videoconference and in person) and weight loss differed according to intervention choice. MethodsLatino men (n=200; mean age 47.3, SD 11.8 years) participated in a comparative effectiveness trial based on primary care and were randomized to receive the 1-year HOMBRE (Hombres con Opciones para Mejorar su Bienestar para Reducir Enfermedades Crónicas; English translation: Men With Options to Improve Their Well-being and Reduce Chronic Disease) intervention. HOMBRE is a weight loss intervention that offers 3 delivery options. During an orientation session, a trained bilingual coach helped men select 1 of the 3 intervention options that differed in coach, peer support, and available language. We used canonical discriminant analysis to assess multivariate associations of demographic, clinical, employment, cultural, and technology use and access factors with men’s intervention choices. We used generalized linear models to estimate weight loss at 6, 12, and 18 months for men in each intervention option. ResultsAmong Latino men, 28% (56/200) chose videoconference groups, 31% (62/200) chose web-based videos, and 41% (82/200) chose in-person groups. The canonical discriminant analysis identified 1 orthogonal dimension that distinguished between men who chose an in-person group and men who chose web-based videos. Men who were older, spoke Spanish, and did not use a computer frequently had a higher probability of choosing in-person groups versus web-based videos. For men who selected a group delivery option, 86.9% (107/123) attended ≥25% of the sessions, 83.7% (103/123) attended ≥50% of the sessions, and 73.2% (90/123) attended ≥75% of the sessions, with no differences by type of group (videoconference or in person). Men who chose videoconference and in-person group sessions lost significantly more weight at 6 months (both P

Background: Depression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity. Methods: This study (‘ENGAGE’) was a pre-planned element of the randomized controlled trial, ‘RAINBOW’ (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging using an established facial emotion task at baseline and two months (coinciding with the first two months of intervention focused on problem-solving therapy (‘PST’)). Amygdala, insula and anterior cingulate cortex activation was extracted using pre-planned definitions and standardized methods. The primary health and behavioural outcomes were depression symptom severity and problem-solving ability respectively, assessed at baseline, the main 6-month outcome point and at 12-month follow up. Mediation analyses used an intent-to-treat approach. Findings: PST, relative to usual care, reduced amygdala activation engaged by threat stimuli at two months. This reduction mediated subsequent improvements in depression severity in an intervention-dependent manner. PST did not change insula activation at two months but did temper the strength of the relationship between insula activation and improvements in problem-solving ability. Interpretation: The negative affect circuit may be an important neural target and potential mediator of PST in patients with comorbid obesity. Funding: US National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368

The objective of this study is to characterize profiles of obese depressed participants using baseline data collected from October 2014 through December 2016 for an ongoing randomized controlled trial (n=409) in Bay Area, California, USA. Four comorbidity severity categories were defined by interaction of the binary levels of body mass index (BMI) and depression Symptom Checklist 20 (SCL20) scores. Sociodemographic, behavioral, clinical and psychosocial characteristics were measured. Mean (SD) age was 51 (12.1) years, BMI 36.7 (6.4) kg/m2, and SCL20 1.5 (0.5). Participants in the 4 comorbidity severity categories had similar sociodemographic characteristics, but differed significantly in the other characteristics. Two statistically significant canonical dimensions were identified. Participants with BMI≥35 and SCL20≥1.5 differed significantly from those with BMI

Abstract Background Despite great advances, China’s postgraduate education faces many problems, for example traditional lecture-based learning (LBL) method provides fewer oppotunities to apply knowledge in a working situation. Task-based learning (TBL) is an efficient strategy for increasing the connections among skills, knowledge and competences. This study aimed to evaluate the effect of a modified TBL model on problem-solving abilities among postgraduate medical students in China. Methods We allocated 228 first-year postgraduate students at Third Military Medical University into two groups: the TBL group and LBL group. The TBL group was taught using a TBL program for immunohistochemistry. The curriculum consisted of five phases: task design, self-learning, experimental operations, discussion and summary. The LBL group was taught using traditional LBL. After the course, learning performance was assessed using theoretical and practical tests. The students’ preferences and satisfaction of TBL and LBL were also evaluated using questionnaires. Results There were notable differences in the mean score rates in the practical test (P 80) in the TBL group was higher than that in the LBL group. We observed no substantial differences in the theoretical test between the two groups (P > 0.05). The questionnaire results indicated that the TBL students were satisfied with teaching content, teaching methods and experiment content. The TBL program was also beneficial for the postgraduates in completing their research projects. Furthermore, the TBL students reported positive effects in terms of innovative thinking, collaboration, and communication. Conclusions TBL is a powerful educational strategy for postgraduate education in China. Our modified TBL imparted basic knowledge to the students and also engaged them more effectively in applying knowledge to solve real-world issues. In conclusion, our TBL established a good foundation for the students’ future in both medical research and clinical work.

Abstract Single-walled carbon nanotubes (SWCNTs) offer great potential for field-effect transistors and integrated circuit applications due to their extraordinary electrical properties. To date, as-made SWCNT transistors are usually p-type in air, and it still remains challenging for realizing n-type devices. Herein, we present efficient and reversible electron doping of semiconductor-enriched single-walled carbon nanotubes (s-SWCNTs) by firstly utilizing decamethylcobaltocene (DMC) deposited by a simple spin-coating process at room temperature as an electron donor. A n-type transistor behavior with high on current, large I on /I off ratio and excellent uniformity is obtained by surface charge transfer from the electron donor DMC to acceptor s-SWCNTs, which is further corroborated by the Raman spectra and the ab initio simulation results. The DMC dopant molecules could be reversibly removed by immersion in N, N-Dimethylformamide solvent, indicating its reversibility and providing another way to control the carrier concentration effectively as well as selective removal of surface dopants on demand. Furthermore, the n-type behaviors including threshold voltage, on current, field-effect mobility, contact resistances, etc. are well controllable by adjusting the surface doping concentration. This work paves the way to explore and obtain high-performance n-type nanotubes for future complementary CMOS circuit and system applications.

Abstract An air-insulated microfluidic chip was designed for the automatic centrifugal distribution of samples to 24-test cells, enabling the parallel identification of multiple clinical pneumonia-related pathogens in 1.45-μL reactions without cross-contamination in 45 min. A portable nucleic acid analyzer that integrates mechanical, confocal optical, electronic, and software functions was also developed to collect fluorescence data in a Ø3 mm imaging field near the optical diffraction limit for highly sensitive fluorescence detection of nucleic acid amplification in real time. This microfluidic chip-based portable nucleic acid analyzer could detect low abundance nucleic acids present at as few as 10 copies. In a blinded experiment, specific identification of Mycoplasma pneumoniae, Staphylococcus aureus, and methicillin-resistant S. aureus was achieved with 229 clinical patient sputum samples. The total coincidence rate of our system and traditional RT-PCR with an ABI 7500 was 99.56%. Four samples accounting for the 0.44% inconformity were retested by gene sequencing, revealing that our system reported the correct results. This novel microfluidic chip-based detection system is cost-effective, rapid, sensitive, specific, and has a relatively high throughput for parallel identification, which is especially suitable for resource-limited facilities/areas and point-of-care testing.

ObjectiveTo evaluate the location of transferred embryos under various parameters during embryo transfer in in vitro fertilization (IVF) by applying an in vitro experimental model for embryo transfer (ET).MethodsMock ET simulations were conducted with a laboratory model of the uterine cavity. The transfer catheter was loaded with a sequence of air and liquid volumes, including development-arrested embryos donated by patients. The transfer procedure was recorded using a digital video camera. An orthogonal design, including three independent variables (uterine orientation, distance of the catheter tip to the fundus, and injection speed) and one dependent variable (final embryo position), was applied.ResultsThe uterine cavity was divided into six regions. The distribution of the transferred matter within the uterine cavity varied according to the uterine orientation. Medium speed-injected embryos were mostly found in the static region while fast- and slow-speed injected embryos were mostly found in the fundal region and the cervical-left region, respectively. The possibility of embryo separation from the air bubble increased from 11.1% in slow injection cases to 29.6% and 48.1% in medium and fast injection cases, respectively.ConclusionThe experimental model provides a new method for investigating ET procedures. Fast injection of embryos into a retroverted uterus may be more likely to result in embryo separation from the air bubble.

[This corrects the article DOI: 10.1371/journal.pone.0231743.].

IntroductionThe RAINBOW randomized clinical trial validated the efficacy of an integrated collaborative care intervention for obesity and depression in primary care, although the effect was modest. To inform intervention optimization, this study investigated within-treatment variability in participant engagement and progress.MethodsData were collected in 2014-2017 and analyzed post hoc in 2018. Cluster analysis evaluated patterns of change in weekly self-monitored weight from week 6 up to week 52 and depression scores on the Patient Health Questionnaire-9 (PHQ-9) from up to 15 individual sessions during the 12-month intervention. Chi-square tests and ANOVA compared weight loss and depression outcomes objectively measured by blinded assessors to validate differences among categories of treatment engagement and progress defined based on cluster analysis results.ResultsAmong 204 intervention participants (50.9 [SD, 12.2] years, 71% female, 72% non-Hispanic White, BMI 36.7 [6.9], PHQ-9 14.1 [3.2]), 31% (n = 63) had poor engagement, on average completing self-monitored weight in ConclusionsParticipants demonstrating poor engagement or poor progress could be identified early during the intervention and were more likely to fail treatment at the end of the intervention. This insight could inform individualized and timely optimization to enhance treatment efficacy.Trial registrationClinicalTrials.gov# NCT02246413.

BACKGROUND:China has a substantial tuberculosis (TB) disease burden and an aging population. Seniors have a higher risk of developing TB disease compared to younger age groups. Active case finding (ACF) could help identify seniors with TB disease. METHODS:From March to June 2017, we included ACF during annual physical check-ups for persons aged ≥ 65 years in Bayi, Sichuan Province. Seniors with clinical TB symptoms (i.e., cough lasting ≥ 2 weeks and/or hemoptysis) or one or more risk factors (e.g., previous TB disease, diabetes, and heavy alcohol consumption) were offered chest x-rays. We used acid-Fast Bacilli smear and solid culture laboratory testing for TB confirmation. We calculated the yield (i.e., cases identified among seniors screened) and cost per new each TB case detected. Focus group-interviews were conducted with health care workers and seniors to evaluate project acceptability. Participation rates and acceptability were used to assess feasibility. RESULTS:Of the 2,393 seniors residing in Bayi, 2,049 (85.6%) were enrolled in the pilot project. Of these seniors, 794 (38.7%) presented with at least one TB risk factor and 74 (3.6%) had symptoms consistent with active TB disease. Three seniors (0.2%)-each presenting with at least one risk factor-were diagnosed with active TB. The project yielded 146 TB cases per 100,000 seniors screened; the cost per case detected was $4,897. Most workers supported ACF if additional resources and staff could be provided. Seniors appreciated the convenience of this integrated health service approach. CONCLUSIONS:Although the yield was lower than expected, ACF appeared feasible in Bayi. Targeting seniors with at least one known TB risk factor could help detect previously unidentified TB cases. However, similar projects in communities with a higher TB prevalence are needed to further evaluate the yield and required resources prior to implementation on a larger scale. Findings from our pilot project should be combined with data from these future ACF projects to improve TB screening criteria.

Background:. Our previous study has confirmed that one bout of exhaustion (Ex) can cause hippocampus neurocyte damage, excessive apoptosis, and dysfunction. Its initial reason is intracellular calcium overload in hippocampus triggered by N-methyl-D-aspartic acid receptor (NMDAR) over-activation. NMDAR activation can be suppressed by γ-aminobutyric acid (A) receptor (GABAAR). Whether GABAAR can prevent intense exercise-induced hippocampus apoptosis, damage, or dysfunction will be studied in this study. Methods:. According to dose test, rats were randomly divided into control (Con), Ex, muscimol (MUS, 0.1 mg/kg) and bicuculline (BIC, 0.5 mg/kg) groups, then all rats underwent once swimming Ex except ones in Con group only underwent training. Intracellular free calcium concentration ([Ca2+]i) was measured by Fura-2-acetoxymethyl ester; glial fibrillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were also performed; apoptosis were displayed by dUTP nick end labeling (TUNEL) stain; endoplasmic reticulum stress-induced apoptosis pathway was detected by Western blotting analysis; Morris water maze was used to detect learning ability and spatial memory. Results:. The appropriate dose was 0.1 mg/kg for MUS and 0.5 mg/kg for BIC. Ex group showed significantly increased [Ca2+]i and astrogliosis; TUNEL positive cells and levels of GFAP, B cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase-3, caspase-12 cleavage, CCAAT/enhancer binding protein homologous protein (CHOP), and p-Jun amino-terminal kinase (p-JNK) in Ex group also raised significantly compared to Con group, while SYP, synapse plasticity, and Bcl-2 levels in Ex group were significantly lower than those in Con group. These indexes were back to normal in MUS group. BIC group had the highest levels of [Ca2+]i, astrogliosis, TUNEL positive cell, GFAP, Bax, caspase-3, caspase-12 cleavage, CHOP, and p-JNK, it also gained the lowest SYP, synapse plasticity, and Bcl-2 levels among all groups. Water maze test showed that Ex group had longer escape latency (EL) and less quadrant dwell time than Con group; all indexes between MUS and Con groups had no significant differences; BIC had the longest EL and least quadrant dwell time among all groups. Conclusions:. Activation of GABAA R could prevent intense exercise-induced synapses damage, excessive apoptosis, and dysfunction of hippocampus.

Information technology has been previously used for the research and practice of health promotion. Appropriate and effective health promotion methods used by professional groups remain to be investigated. This study aimed to assess the feasibility and effectiveness of a weight management program among the Chinese occupational population using and a novel information technology exercise prescription.A 3-month open, self-monitored intervention trial, involving individualized pedometer-assisted exercise prescription and a one-time targeted dietary guidance prior to exercise was conducted on the Chinese occupational population aged 18-65 years in China from 2015 to 2016. Data were collected from March 2015 to May 2016 and analyzed from June 2016 to August 2016. Participants were also asked to synchronize exercise data of the pedometer to the Internet-based Health System Center daily (at least weekly), by connecting to the personal computer (PC) using a USB cable or via Bluetooth.Eligible participants included 802 Chinese occupational persons, and 718 of them followed exercise interventions with 89.5% (718/802) adherence to the exercise programs. Of them, 688 participants completed the program with 85.8% (688/802) adherence to the exercise program and their data were analyzed. Weight decreased by 2.2% among all overweight/obese participants, with 1.8% reduction in waist circumference and 3.3% reduction in body fat percentage (p< 0.001). Weight and body fat percentage in normal-weight individuals decreased by 0.7% and 2.5%, respectively (p < 0.01). A weight gain of 1.0% was observed in all underweight participants (p< 0.05), and 68.2% (208/305) of overweight/obese participants experienced weight loss, with an average reduction of 3.5%, with 20.2% (42/208) of them achieving weight loss ≥5%. Blood pressure and fasting serum glucose decreased significantly in both the overweight/obese and the normal-weight individuals (p < 0.05). The incidence of hypertension was significantly lower and lifestyle behavior significantly improved (p < 0.05).The prescription pedometer-assisted walking intervention can effectively improve exercise adherence and manage weight. This approach was also effective in controlling the risk factors of weight-related chronic diseases.Chinese Clinical Trial Registry (ChiCTR) ChiCTR-OOh-16010229.

Few studies have used nationally representative data to focus specifically on gender differences in weight-related outcomes. This article examines gender differences in weight-related outcomes across the body mass index (BMI) spectrum in overweight and obese adults. Data from the National Health and Nutrition Examination Survey 2009–2010 was analyzed. Weight-related outcomes were accurate weight perception, weight dissatisfaction, attempted weight loss, successful weight loss, and weight loss strategies. Compared with women, overweight and obese men were less likely to have accurate weight perception (odds ratio [OR] = 0.36; 95% confidence interval [CI] = 0.30–0.44), weight dissatisfaction (OR = 0.39; 95% CI = 0.32–0.47), and attempted weight loss (OR = 0.55; 95% CI = 0.48–0.63). The modifying effect of gender on these associations decreased as BMI increased. By BMI 35, the mean probability of women and men to have accurate weight perception and weight dissatisfaction was 90%; attempted weight loss was 60% (women) and 50% (men). At lower BMIs, men had up to 40% less probability than women for these weight loss outcomes. Men who attempted weight loss were more likely than women to lose and maintain ≥10 lb over 1 year (OR = 1.41; 95% CI = 1.20–1.65) and increase exercise and eat less fat as weight loss strategies; women were more likely to join weight loss programs, take prescription diet pills, and follow special diets. A need exists for male-specific interventions to improve overweight and obese men’s likelihood for accurate weight perception, attempted weight loss, and ultimately, successful weight loss.

Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination.

γ-AlOOH whisker is one of the most popular precursors for the formation of Al2O3 whisker. In this paper, a facile hydrothermal method was developed to prepare γ-AlOOH whiskers, using hydrated alumina with different crystallinity as the hydrothermal precursors. Amorphous hydrated alumina precursors were prepared by mixing HCl and NaAlO2 at room temperature, while crystalline hydrated alumina precursors were produced by precipitation of NaAlO2 solution. γ-AlOOH whiskers with a length of 800-1500 nm and a diameter of 20-40 nm were formed by hydrothermal treatment (220 ℃, 8.0 h) of the mixing of two kinds of precursors. The experimental results indicated that the different dissolving rates of hydrated alumina precursors were one of the main reasons for the formation of γ-AlOOH whiskers with high aspect ratio.

BACKGROUND:The routine application of neoadjuvant chemoradiotherapy for T3N0 rectal cancer remains controversial. The aim of this study was to use clinical, Magnetic resonance imaging, and pathological parameters to identify a subgroup of patients with low risk of local recurrence who might be precluded from neoadjuvant chemoradiotherapy. METHODS:We retrospectively reviewed a prospectively maintained database of consecutive rectal cancer patients who underwent curative resection. 166 pathologic confirmed T3N0 rectal cancer patients with tumor located 5-12 cm above the anal verge and preoperative circumferential resection margin >1 mm were included in analysis. The primary outcomes measured were 3- and 5-year local recurrence rates. RESULTS:Local recurrence was demonstrated during follow-up in 5 patients; the actuarial overall 3- and 5-year local recurrence rates were 2.5% and 3.4%, respectively. Inadequate sampling of lymph nodes (≤12) was associated with higher local recurrence (P = 0.03) in this group of patients. CONCLUSION:For upper and middle T3N0 rectal cancer with preoperative circumferential resection margin >1 mm, local recurrence rate after total mesorectal excision is low and surgery alone may be enough for this group of patients.

NBN plays a crucial role in carcinogenesis as a core component for both homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA double-strand breaks (DSBs) repair pathways. Genetic variants in the NBN gene have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants in the NBN gene may modify the risk of gastric cancer. To test this hypothesis, we evaluated the association between four potentially functional single nucleotide polymorphisms in NBN and gastric cancer risk in a case-control study of 1,140 gastric cancer cases and 1,547 controls in a Chinese population. We found that the A allele of rs10464867 (G>A) was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.81, 95% confidence interval [95% CI] = 0.71-0.94; P = 4.71×10-3). Furthermore, the association between A allele of rs10464867 and decreased risk of gastric cancer was more significantly in elder individuals (per-allele OR = 0.72[0.59-0.88], P = 1.07×10-3), and male individuals (per-allele OR = 0.73[0.62-0.87], P = 3.68×10-4). We further conducted a haplotype analysis and identified that the NBN Ars10464867Grs14448Grs1063053 haplotype conferred stronger protective effect on gastric cancer (OR = 0.76[0.65-0.89], P = 6.39×10-4). In summary, these findings indicate that genetic variants at NBN gene may contribute to gastric cancer susceptibility and may further advance our understanding of NBN gene in cancer development.

Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism.Exome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals.Altogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians.The increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit.

Background: Most reports have indicated the antioxidant capacity of quinoa seeds. However, the leaves of Quinoa (Chenopodium quinoa Willd.) are usually worthless and little known about their biological activities. In this study, the antioxidant and immunomodulatory potential of the quinoa leaf extracts were explored. Methods: The crude leaf extracts of quinoa were extracted using water, 50% ethanol or 95% ethanol as solvent, denoted WQL, 50% EQL and 95% EQL, respectively. The antioxidant activities of quinoa leaf extracts were assessed by the ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging and iron chelating. The total phenolic content was determined. Inhibition of nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells was examined to gauge the anti-inflammatory activity. Results: The 95% EQL showed a higher level of total phenolic content (569.5 mg GAE/g extract) and better DPPH scavenging activity. The WQL exhibited a better iron chelating capacity (28.9% at 10 mg/ml). The iron chelating activity of the 95% EQL increased in a concentration-dependent manner, which ranged from 10.9% up to 53.9%. The 50% EQL and 95% EQL significantly inhibited NO production in the LPSstimulated RAW 264.7 cells. Conclusion: We demonstrate that the extracts of quinoa leaves possess the biological activities of antioxidant and anti-inflammatory. Our finding suggests that the leaf extract of quinoa has potential to be utilized for natural health products.

OBJECTIVE: To evaluate the predictive value of the symptoms of an intrauterine hematoma (IUH) for adverse pregnancy outcomes. METHODS: A literature review was performed with the search terms, including intrauterine/subchorionic/retroplacental/subplacental hematoma/hemorrhage/bleeding/collection/fluid, covering the period from January, 1981 to January, 2014. We just focused on the pregnancy outcomes associated with different symptoms of an IUH. RESULTS: It is generally agreed that a retroplacental, posterior or subchorionic in the fundus of uterus, and/or persistent IUH is associated with adverse outcomes in the ongoing pregnancy. However, the prognosis value of both volume and gestational age at diagnosis of IUH still remains controversial. Some researchers argue that a large IUH is associated with an increased risk of adverse events during pregnancy while others refuted. It is believed by some that the earlier an IUH was detected, the higher the risk for adverse outcomes would be, while no or weak association were reported by other studies. The prognostic value of the simultaneous presence of vaginal bleeding on pregnancy outcome is also controversial. CONCLUSIONS: Both the position relative to the placenta or uterus and duration of IUH have strong predictive value on the prognosis in the ongoing pregnancy. However, the prognostic values of the IUH volume, gestational age at diagnosis and the simultaneous presence of vaginal bleeding remain controversial up to now. Moreover, most of previous reports are small, uncontrolled studies with incomplete information. Prospective, large sample, cohorts studies which take all detailed symptoms of an IUH into consideration are needed when we evaluate its clinical significance in the prognosis of pregnancy.

The hypothalamus-pituitary-target gland axis is thought to be linked with insomnia, yet there has been a lack of further systematic studies to prove this. This study included 30 patients with primary insomnia (PI), 30 patients with depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the alterations in the hypothalamus-pituitary-adrenal/thyroid axes' hormones and gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was used to evaluate sleep quality in all subjects. The serum concentrations of corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH), GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal levels were elevated in the insomniacs, except ACTH and TSH in the PI group. Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol, TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman's correlation analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were positively correlated with the severity of insomnia. The linear regression analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI scores among all subjects, and only CRH was included in the regression model by the "stepwise" method in the insomnia patients. Our results indicated that PI patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid axes and an elevated level of GnRH in the morning.

Mutated mouse lipoprotein lipase (LPL) containing a leucine (L) to histidine (H) substitution at position 452 was transferred into mouse liver by hydrodynamics-based gene delivery (HD). Mutated-LPL (MLPL) gene transfer significantly increased the concentrations of plasma MLPL and triglyceride (TG) but significantly decreased the activity of plasma LPL. Moreover, the gene transfer caused adiposis hepatica and significantly increased TG content in mouse liver. To understand the effects of MLPL gene transfer on energy metabolism, we investigated the expression of key functional genes related to energy metabolism in the liver, epididymal fat, and leg muscles. The mRNA contents of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), fatty acid-binding protein (FABP), and uncoupling protein (UCP) were found to be significantly reduced. Furthermore, we investigated the mechanism by which MLPL gene transfer affected fat deposition in the liver, fat tissue, and muscle. The gene expression and protein levels of forkhead Box O3 (FOXO3), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) were found to be remarkably decreased in the liver, fat and muscle. These results suggest that the Leu452His mutation caused LPL dysfunction and gene transfer of MLPL in vivo produced resistance to the AMPK/PGC-1α signaling pathway in mice.

Quetiapine (Que), a commonly used atypical antipsychotic drug (APD), can prevent myelin from breakdown without immune attack. Multiple sclerosis (MS), an autoimmune reactive inflammation demyelinating disease, is triggered by activated myelin-specific T lymphocytes (T cells). In this study, we investigated the potential efficacy of Que as an immune-modulating therapeutic agent for experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. Que treatment was initiated on the onset of MOG(35-55) peptide induced EAE mice and the efficacy of Que on modulating the immune response was determined by Flow Cytometry through analyzing CD4(+)/CD8(+) populations and the proliferation of effector T cells (CD4(+)CD25(-)) in peripheral immune organs. Our results show that Que dramatically attenuates the severity of EAE symptoms. Que treatment decreases the extent of CD4(+)/CD8(+) T cell infiltration into the spinal cord and suppresses local glial activation, thereby diminishing the loss of mature oligodendrocytes and myelin breakdown in the spinal cord of EAE mice. Our results further demonstrate that Que treatment decreases the CD4(+)/CD8(+) T cell populations in lymph nodes and spleens of EAE mice and inhibits either MOG(35-55) or anti-CD3 induced proliferation as well as IL-2 production of effector T cells (CD4(+)CD25(-)) isolated from EAE mice spleen. Together, these findings suggest that Que displays an immune-modulating role during the course of EAE, and thus may be a promising candidate for treatment of MS.