Titanium dioxide nanoparticles alleviates polystyrene nanoplastics induced growth inhibition by modulating carbon and nitrogen metabolism via melatonin signaling in maize.

BACKGROUND: Nanoplastics, are emerging pollutants, present a potential hazard to food security and human health. Titanium dioxide nanoparticles (Nano-TiO2), serving as nano-fertilizer in agriculture, may be important in alleviating polystyrene nanoplastics (PSNPs) toxicity. RESULTS: Here, we performed transcriptomic, metabolomic and physiological analyzes to identify the role of Nano-TiO2 in regulating the metabolic processes in PSNPs-stressed maize seedlings (Zea mays L.). The growth inhibition by PSNPs stress was partially relieved by Nano-TiO2. Furthermore, when considering the outcomes obtained from RNA-seq, enzyme activity, and metabolite content analyses, it becomes evident that Nano-TiO2 significantly enhance carbon and nitrogen metabolism levels in plants. In comparison to plants that were not subjected to Nano-TiO2, plants exposed to Nano-TiO2 exhibited enhanced capabilities in maintaining higher rates of photosynthesis, sucrose synthesis, nitrogen assimilation, and protein synthesis under stressful conditions. Meanwhile, Nano-TiO2 alleviated the oxidative damage by modulating the antioxidant systems. Interestingly, we also found that Nano-TiO2 significantly enhanced the endogenous melatonin levels in maize seedlings. P-chlorophenylalanine (p-CPA, a melatonin synthesis inhibitor) declined Nano-TiO2-induced PSNPs tolerance. CONCLUSIONS: Taken together, our data show that melatonin is involved in Nano-TiO2-induced growth promotion in maize through the regulation of carbon and nitrogen metabolism.

Plasma BDNF/Irisin Ratio Associates with Cognitive Function in Older People.

Background: Reliable blood biomarkers are crucial for early detection and treatment evaluation of cognitive impairment, including Alzheimer's disease and other dementias. Objective: To examine whether plasma biomarkers and their combination are different between older people with mild cognitive impairment (MCI) and cognitively normal individuals, and to explore their relations with cognitive performance. Methods: This cross-sectional study included 250 older adults, including 124 participants with MCI, and 126 cognitively normal participants. Plasma brain-derived neurotrophic factor (BDNF), irisin and clusterin were measured, and BDNF/irisin ratio was calculated. Global cognition was evaluated by the Montreal Cognitive Assessment. Results: Plasma irisin levels, but not BDNF, were significantly different between MCI group and cognitively normal group. Higher irisin concentration was associated with an increased probability for MCI both before and after controlling covariates. By contrast, plasma BDNF concentration, but not irisin, was linearly correlated with cognitive performance after adjusting for covariates. Higher BDNF/irisin ratios were not only correlated with better cognitive performance, but also associated with lower risks of MCI, no matter whether we adjusted for covariates. Plasma BDNF and irisin concentrations increased with aging, whereas BDNF/irisin ratios remained stable. No significant results of clusterin were observed. Conclusions: Plasma BDNF/irisin ratio may be a reliable indicator which not only reflects the odds of the presence of MCI but also directly associates with cognitive performance.

Can motor decline be a modifiable marker of clinical progression in subjective cognitive decline? A national prospective cohort study.

OBJECTIVES: Subjective cognitive decline represents a critical stage for preventing mild cognitive impairment and dementia, but the links between clinical progression in the subjective cognitive decline stage and various motor functions remain inconclusive. This cohort study aimed to elucidate the independent and joint associations between the clinical progression of subjective cognitive decline and motor functions. METHODS: We enrolled 4880 community-dwelling elderly participants from a national cohort and used Cox proportional hazard regression model and restricted cubic spline models to explore the longitudinal associations between motor functions (gait, strength, balance, and endurance) and the clinical progression of subjective cognitive decline. RESULTS: During 5-years follow-up, 1239 participants experienced clinical progression. After adjusting for demographics, vascular burden, body components, and polypharmacy, gait speed [hazard ratios (HRs)= 0.96, 95% confidence interval (CI) 0.94-0.99], chair stand test (HRs=1.02, 95%CI 1.01-1.03), and endurance limitation in jogging 1 kilometer (HRs=1.18, 95%CI 1.04-1.34) were significantly associated with clinical progression. Among all participants, individuals characterized by poor upper- and lower-body strength, as well as those with slow pace and reduced endurance, faced the highest risk of cognitive impairment. CONCLUSIONS: This study emphasizes the potential of gait speed, muscle strength, and endurance as non-cognitive indicators of clinical progression in subjective cognitive decline. Understanding their combined effectiveness may reveal primary physiological mechanisms contributing to the dual decline of motor and cognition.

The application of saccades to assess cognitive impairment among older adults: a systematic review and meta-analysis.

BACKGROUND: Saccade is a novel and feasible method for cognition assessment and has potential to screen older people with cognitive impairment. OBJECTIVES: To systematically summarize the evidence and determine whether different saccade parameters can effectively identify patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: English and Chinese databases were searched until 19 April 2022. Studies analyzing saccade parameters in older adults with normal cognition, MCI, or AD were included. Two researchers independently performed the screening, data extraction, and quality appraisal. Meta-analyses were conducted and standard mean differences and 95% confidence intervals were estimated with a random effects model. RESULTS: Thirty-five studies were included, and 26 studies were pooled for the meta-analysis. The results demonstrated that patients with cognitive impairment exhibited longer latency and lower accuracy rates in the prosaccade and antisaccade tasks, along with lower corrected error rates in the antisaccade tasks. However, the pooled results for antisaccades were more stable, providing the ability to distinguish patients with cognitive impairment among older adults. The results of the subgroup analyses revealed that only the accuracy rates of the antisaccades differed significantly between people with MCI and AD. Regarding the differences between older adults with normal cognition and those with MCI, the effect sizes of latency and the accuracy rates of saccades as well as the corrected error rates of antisaccades were significant. CONCLUSIONS: Saccades, especially antisaccades, are a potential screening and assessment tool for distinguishing older adults with MCI or AD from those with normal cognition.

Physical activity trajectories and their determinants in patients with chronic obstructive pulmonary disease: A cohort study.

AIMS AND OBJECTIVES: The aim was to identify latent trajectories in physical activity (PA) and their determinants in adults with chronic obstructive pulmonary disease (COPD) based on the socio-ecological model. BACKGROUND: PA has been linked to poor long-term outcomes in patients with COPD. However, few studies have explored their PA trajectories and their predictors. DESIGN: Cohort study. METHODS: We used data from a national cohort and included 215 participants. PA was quantified using a short PA questionnaire, and group-based trajectory modelling was used to explore the PA trajectories. Multinomial logistic regression was conducted to identify the predictors of PA trajectories. Generalised linear mixed models were used to elucidate the associations between predictors and PA during follow-up. A STROBE checklist was used to guide the reporting of this study. RESULTS: Three PA trajectory patterns were identified among 215 COPD participants with an average age of 60.51 ± 8.87: stable inactive group (66.7%), sharp decline group (25.7%) and stable active group (7.5%). The logistic regression showed that age, sex, income, peak expiratory flow, upper limb capacity, depressive symptoms, the frequency of contact with children were PA predictors. Upper limb capacity weakness and depressive symptoms were found to be associated with a sharp decline in PA during follow-up. CONCLUSIONS: This study revealed three PA trajectories among patients with COPD. In addition to strengthening the physical functions and mental health of patients, support from the family, community and society also play a crucial role in promoting PA of patients with COPD. RELEVANCE TO CLINICAL PRACTICE: It is essential to identify distinct PA trajectories in patients with COPD to develop future interventions that promote PA. NO PATIENT OR PUBLIC CONTRIBUTION: A national cohort study was used and no patients or the public were involved in the design and implementation of this study.

Sleep Characteristics in Older Adults with Different Levels of Risk for Dementia: A Cross-sectional Study.

BACKGROUND: Sleep problems are very prevalent in older adults, especially in those at risk for dementia. But the relationships between sleep parameters and subjective or objective cognitive decline are still inconclusive. AIM: The study aimed to investigate the self-reported and objectively measured sleep characteristics in older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). METHODS: This study adopted a cross-sectional design. We included older adults with SCD or MCI. Sleep quality was measured separately by the Pittsburgh sleep quality index (PSQI) and ActiGraph. Participants with SCD were divided into low, moderate, and high levels of SCD groups. Independent samples T-tests, one-way ANOVA, or nonparametric tests were used to compare the sleep parameters across groups. Covariance analyses were also performed to control the covariates. RESULTS: Around half of the participants (45.9%) reported poor sleep quality (PSQI＜7), and 71.3% of participants slept less than 7 hours per night, as measured by ActiGraph. Participants with MCI showed shorter time in bed (TIB) (p＜0.05), a tendency of shorter total sleep time (TST) at night (p = 0.074) and for each 24-hour cycle (p = 0.069), compared to those with SCD. The high SCD group reported the highest PSQI total score and longest sleep latency than all the other three groups (p＜0.05). Both the MCI and high SCD groups had shorter TIB and TST for each 24-hour cycle than the low or moderate SCD groups. Besides, participants with multiple-domain SCD reported poorer sleep quality than those with single-domain SCD (p＜0.05). CONCLUSION: Sleep dysregulation is prevalent in older adults with a risk for dementia. Our findings revealed that objectively measured sleep duration might be an early sign of MCI. Individuals with high levels of SCD demonstrated poorerself-perceived sleep quality and deserved more attention. Improving sleep quality might be a potential target to prevent cognitive decline for people with a risk for dementia.

The Chinese Translation Study of the Cognitive Reserve Index Questionnaire.

Purpose: The purpose of this study was to perform the translation and adaption of the Cognitive Reserve Index questionnaire into Chinese and assess the reliability of the Chinese version. Materials and Methods: The Chinese version of the Cognitive Reserve Index questionnaire was created from a standard forward-backward translation. A total of 371 volunteers, aged between 20 and 89 years, participated in this survey. Participants were divided into three age-groups (Young, Middle-aged, and Elderly), and subgroup differences were examined by independent samples t-tests, ANOVA analysis as well as post-hoc analysis. Pearson correlation analysis was applied to test the association between the total scores and each subscore (CRI-Education, CRI-WorkingActivity, and CRI-LeisureTime). The internal consistency and test-retest reliability of the Cognitive Reserve Index questionnaire were assessed. The test-retest reliability was measured among 40 participants with a 2-week interval using intraclass correlation coefficient. Results: Strong correlations were observed between the total scores and each subscore (CRI-Education, CRI-WorkingActivity, and CRI-LeisureTime: r = 0.65, 0.79, and 0.70, respectively). In contrast, it was found low to moderate correlations among three subscores. The internal consistency was acceptable (Cronbach's alpha coefficient = 0.68). The intraclass correlation coefficient for total scores of the Chinese version of the Cognitive Reserve Index questionnaire was 0.87 (95% CI 0.74-0.93). Conclusion: The Chinese version of the Cognitive Reserve Index questionnaire was a potentially reliable and practical tool for evaluating cognitive reserve accumulated through a person's life span.

Self-reported practices, competence and difficulties towards palliative care among nurses: A cross-sectional study.

OBJECTIVE: Nurses' palliative care practice ability is the key to evaluating the quality of palliative care. This study aimed to identify the current situation of palliative care practices, competence and difficulties among nurses and determine whether difficulties play a mediating role between practices and competence. METHODS: A cross-sectional study was conducted. The online survey comprised demographics, the Palliative Care Self-Reported Practices Scale, the Palliative Care Nursing Self-competence Scale and the Palliative Care Difficulties Scale. Data were analysed by using descriptive statistics, univariate analysis, linear regression and mediation analysis. RESULTS: A total of 284 questionnaires were included for statistical analysis. The mean scores for practices, competence and difficulties were 67.81 (SD = 13.60), 124.28 (41.21) and 44.32 (12.68), respectively. There was a correlation between practices, competence and difficulties (p < 0.01). Competence and difficulties were independent predictors of practices (R2 adj  = 0.384, p < 0.001). Furthermore, difficulties mediated the relationship between practices and competence (b = 0.052, 95% confidence interval: 0.008-0.155). CONCLUSIONS: Continuous efforts should be made to enhance nurses' practices, competence and problem-solving abilities in palliative care. This study suggested further targeted education programmes, especially in special symptom management, interagency and multidisciplinary communication.

The feasibility and efficacy of the home-based exercise programs in patients with cognitive impairment: A pilot study.

OBJECTIVE: To examine the feasibility and efficacy of home-based aerobic and resistance exercise interventions for geriatric individuals with cognitive impairment. METHODS: Fourteen participants with cognitive impairment were allocated to either the aerobic group (n = 8) or the resistance group (n = 6), after which they implemented a two-month home-based training program. Feasibility and efficacy outcomes were evaluated. A semi-structured interview was performed after the intervention. RESULTS: All fourteen participants completed the two-month training program. The adherence rate was 0.94 for the aerobic group and 0.96 for the resistance group. No adverse events occurred. The results revealed a trend of group×time interaction effect on delayed recall. Significant group×time interaction effects were revealed on simple physical performance and body composition. Semi-structured interviews identified four motivators for participating in this program, four facilitators for and three barriers to keeping exercising, and some perceived benefits. CONCLUSION: Home-based aerobic and resistance exercise programs are feasible for geriatric individuals with cognitive impairment. The efficacy needs to be further examined.

Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: A systematic review and network meta-analysis.

BACKGROUND: Exercise is a promising nonpharmacological therapy for cognitive dysfunction, but it is unclear which type of exercise is most effective. The objective of this study was to compare and rank the effectiveness of various exercise interventions on cognitive function in patients with mild cognitive impairment (MCI) or dementia and to examine the effects of exercise on the symptoms relevant to cognitive impairment. METHODS: We searched PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, SPORTDiscus, and PsycInfo through September 2019 and included randomized controlled trials that examined the effectiveness of exercise interventions in patients with MCI or dementia. Primary outcomes included global cognition, executive cognition, and memory cognition. Secondary outcomes included activities of daily living, neuropsychiatric symptoms, and quality of life. Pairwise analyses and network meta-analyses were performed using a random effects model. RESULTS: A total of 73 articles from 71 trials with 5606 participants were included. All types of exercise were effective in increasing or maintaining global cognition, and resistance exercise had the highest probability of being the most effective intervention in slowing the decrease in global cognition (standard mean difference (SMD) = 1.05, 95% confidence interval (95%CI): 0.56-1.54), executive function (SMD = 0.85, 95%CI: 0.21-1.49), and memory function (SMD = 0.32, 95%CI: 0.01-0.63) in patients with cognitive dysfunction. Subgroup analyses for patients with MCI revealed different effects, and multicomponent exercise was most likely to be the optimal exercise therapy for preventing the decline of global cognition (SMD = 0.99, 95%CI: 0.44-1.54) and executive function (SMD = 0.72, 95%CI: 0.06-1.38). However, only resistance exercise showed significant effects on memory function for patients with MCI (SMD = 0.35, 95%CI: 0.01-0.69). Exercise interventions also showed various effects on the secondary outcomes. CONCLUSION: Resistance exercise has the highest probability of being the optimal exercise type for slowing cognitive decline in patients with cognitive dysfunction, especially in patients with dementia. Multicomponent exercise tends to be most effective in protecting global cognition and executive function in patients with MCI.

Effect of exercise on bone mineral density among patients with osteoporosis and osteopenia: A systematic review and network meta-analysis.

AIMS AND OBJECTIVES: To systematically review and compare the efficacy of different exercise interventions on bone mineral density (BMD, g/cm2 ) in patients with osteoporosis and osteopenia. BACKGROUND: It is vitally important to prevent and treat bone loss in patients with osteoporosis and osteopenia. Exercise can effectively increase bone density and slow down bone loss in middle-aged and older people. However, it is still unclear which type of exercise intervention is the most effective on bone mineral density. DESIGN: Systematic review and network meta-analysis (NMA) according to PRISMA. METHODS: Randomised controlled trials of different exercise treatments for osteopenia and primary osteoporosis were included. A Frequentist network meta-analysis was conducted to appraise the efficacy of different types of exercise. The outcome was bone mineral density of different parts of the body. RESULTS: Ninety-seven studies were included. The network meta-analysis showed that combined exercise, resistance exercise, aerobic exercise and mind-body exercise had a significant effect in improving the bone density of lumbar spine. The surface under the cumulative ranking area (SUCRA) values for mind-body exercise was 0.99 and ranked first. For BMD of the femoral neck, all kinds of exercise interventions increased the bone density significantly compared with no exercise and the optimal type was mind-body exercise (SUCRA = 0.99). In terms of the total hip bone mineral density, aerobic exercise and resistance exercise could improve hip bone density, with the resistance exercise (SUCRA = 0.95) ranking as first. CONCLUSIONS: This NMA demonstrated the mind-body exercise might be the optimal exercise type to increase the BMD of the lumbar spine and femoral neck and resistance exercise is the most promising type for total hip BMD.

Biomarkers for evaluating the effects of exercise interventions in patients with MCI or dementia: A systematic review and meta-analysis.

OBJECTIVES: To summarize the biomarkers for evaluating the effects of exercise interventions in patients with cognitive impairment associated with aging, as well as their responses to exercise interventions. DESIGN: A systematic review and meta-analysis METHODS: We systematically searched different electronic database, including PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, PsycINFO, SPORTDiscus up to April 2020. Clinical controlled trials with exercise interventions in patients with cognitive impairment were included. The main outcomes included all the biomarkers used to evaluate the effects of exercise interventions. If data for certain biomarkers was enough (more than 2 studies), meta-analyses would be performed to estimate the effect sizes by calculating the standard mean differences (SMDs) and 95% confidence intervals (CIs). RESULTS: Finally, we included 33 articles from 26 trials. The biomarkers included neurotrophic factors, inflammatory factors, oxidative stress markers, neuropathological hallmarks, metabolic biomarkers and genotypes. The meta-analyses indicated that exercise significantly decreased the levels of IL-6 (SMD = -0.45; 95% CI: -0.72, -0.18) and low-density lipoprotein (SMD = -0.26; 95% CI: -0.50, -0.01). Subgroup analyses showed that aerobic exercise also could decrease the levels of TNF-α (SMD = -1.21; 95% CI: -2.29, -0.14). There were some important cognition-related biomarkers which were rarely measured, such as Aß, tau and IGF-1. CONCLUSION: Regular exercise showed positive effects on reducing inflammation and regulating lipid metabolism. But the available evidence is limited and more studies with different exercise interventions should be conducted to test the effects of exercise on other important cognition-related biomarkers in patients with cognitive dysfunction.

Effects of withdrawing an atherogenic diet on the atherosclerotic plaque in rabbits.

Lifestyle interventions and pharmacotherapy are the most common of non-invasive treatments for atherosclerosis, but the individual effect of diet on plaques remains unclear. The current study aimed to investigate the effect of withdrawing the atherogenic diet on plaque in the aortas of rabbits. Experimental atheroma was induced in 33 rabbits using a 1% high cholesterol diet for 30 days (H-30 d) or 90 days (H-90 d, baseline group). After 90 days of the atherogenic diet, the remaining animals were divided into four groups: A total of 10 rabbits continued to consume the atherogenic diet for 50 days (H-90 d & H-50 d; n=5) or 140 days (H-90 d & H-140 d; n=5). Another 13 rabbits were switched to a chow diet for 50 days (H-90 d & C-50 d; n=7) or 140 days (H-90 d & C-140 d; n=6). A total of 10 age-matched rabbits in the control groups were fed a chow diet for 90 and 230 days, respectively. The en face or cross-sectional plaque areas were determined using oil red O staining and elastic van Gieson staining. Immunohistochemistry analyses were used to assess the macrophages or smooth muscle cell contents. When fed an atherogenic diet for 90 days, the rabbits' abdominal aortas exhibited severe atherosclerotic lesions (the median en face plaque area was 63.6%). After withdrawing the atherogenic diet, the plaque area did not shrink with feeding the chow diet compared with the baseline, but increased to 71.8 or 80.5% after 50 or 140 days, respectively. After removing cholesterol from the diet, the lipids content in the plaques increased during the first 50 days, and then decreased compared with the baseline group. Furthermore, withdrawing the atherogenic diet increased the total collagen content and the percentage of the smooth muscle cells, alleviated macrophage infiltration, decreased the vulnerable index and promoted the cross-linking of collagen. Feeding the rabbits an atherogenic diet followed by removal of cholesterol from the diet did not lead to the regression of established lesions but instead delayed the progression of the lesions and promoted the stabilization of the plaque.

Functional Evaluation and Genetic Evolution of Human T-Cell Responses After Vaccination With a Conditionally Replication-Defective Cytomegalovirus Vaccine.

BACKGROUND: Cytomegalovirus (CMV) can cause congenital infection and is the leading cause of nongenetic newborn disabilities. V160, a conditionally replication-defective virus, is an investigational vaccine under evaluation for prevention of congenital CMV. The vaccine was well tolerated and induced both humoral and cellular immunity in CMV-seronegative trial participants. T-cell-mediated immunity is important for immune control of CMV. Here we describe efforts to understand the quality attributes of the T-cell responses induced by vaccination. METHODS: Using multicolor flow cytometry, we analyzed vaccine-induced T cells for memory phenotype, antigen specificity, cytokine profiles, and cytolytic potential. Moreover, antigen-specific T cells were sorted from 4 participants, and next-generation sequencing was used to trace clonal lineage development during the course of vaccination using T-cell receptor ß-chain sequences as identifiers. RESULTS: The results demonstrated that vaccination elicited polyfunctional CD4 and CD8 T cells to 2 dominant antigens, pp65 and IE1, with a predominantly effector phenotype. Analysis of T-cell receptor repertoires showed polyclonal expansion of pp65- and IE1-specific T cells after vaccination. CONCLUSION: V160 induced a genetically diverse and polyfunctional T-cell response and the data support further clinical development of V160 for prevention of CMV infection and congenital transmission. CLINICAL TRIALS REGISTRATION: NCT01986010.

The effectiveness of different exercise modalities on sleep quality: A protocol for systematic review and network meta-analysis.

BACKGROUND: Recently, the effect of exercise on sleep quality has been paid increasing attention by researchers. A number of systematic reviews and direct meta-analyses have explored the effectiveness of exercise on sleep quality. However, which type of exercise is optimal for sleep quality is still not clear. Therefore, this study aims to adopt network meta-analysis to evaluate the effect of different exercise modalities on sleep quality and find the most effective one for improving sleep quality. METHODS: The databases searched included PubMed, Web of Science, EMBASE, CENTRAL, PsycINFO, and SPORTDiscus. Studies published in English and from the dates of database inception to October 8, 2019, were included. Besides, we also checked the reference lists of systematic reviews published in recent years. Two independent researchers screened all studies, included the studies that met eligible criteria and will then extract data. The risk of bias will be assessed by the 2 researchers according to the modified Cochrane Risk of Bias Tool. During these processes, any disagreement will be discussed to reach a consensus. STATA 14.0 software will be used for direct meta-analysis and network meta-analysis. RESULTS: High-quality synthesis of current evidences will be provided from Pittsburgh sleep quality index. And the effectiveness of different exercise modalities for sleep quality will also be shown. CONCLUSION: This study will provide the evidence of the most effective exercise for better sleep quality. REGISTRATION: This study was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (registration number: INPLASY202050096).

Activation of TGR5 promotes mitochondrial biogenesis in human aortic endothelial cells.

Impairment of mitochondrial biogenesis has been associated with vascular pathophysiology. The G-protein-coupled receptor (TGR5) is an important mediator of bile acid signaling and glucose metabolism. However, the effects of TGR5 on mitochondrial biogenesis in endothelial cells remain elusive. In this study, we found that activation of TGR5 using its specific agonist taurolithocholic acid (TLCA) promoted the expression of PGC-1α, a master regulator of mitochondrial biogenesis in human aortic endothelial cells (HAECs). Additionally, activation of TGR5 increased the expression of PGC-1α target genes, such as NRF1 and TFAM. Indeed, we found that TLCA treatment promoted mitochondrial biogenesis by increasing mitochondrial mass, mitochondrial-to-nuclear DNA (mtDNA/nDNA), COX-Ⅰ expression, and cytochrome c oxidase activity in HAECs. Notably, our results displayed that activation of TGR5 resulted in a functional gain in mitochondria by increasing the rate of respiration and ATP production. Mechanistically, we found that TLCA treatment activated the transcriptional factor CREB by inducing the phosphorylation of CREB at Ser133. Using the PKA/CREB inhibitor H89 abolished the effects of TLCA on PGC-1α, NRF1 and TFAM expression as well as the increase in mtDNA/nDNA and ATP production. These findings suggest that activation of TGR5 promoted mitochondrial biogenesis in endothelial cells, which is mediated by the CREB/PGC-1α signaling pathway.

Benefits and Challenges with Applying Unique Molecular Identifiers in Next Generation Sequencing to Detect Low Frequency Mutations.

Indexing individual template molecules with a unique identifier (UID) before PCR and deep sequencing is promising for detecting low frequency mutations, as true mutations could be distinguished from PCR errors or sequencing errors based on consensus among reads sharing same index. In an effort to develop a robust assay to detect from urine low-abundant bladder cancer cells carrying well-documented mutations, we have tested the idea first on a set of mock templates, with wild type and known mutants mixed at defined ratios. We have measured the combined error rate for PCR and Illumina sequencing at each nucleotide position of three exons, and demonstrated the power of a UID in distinguishing and correcting errors. In addition, we have demonstrated that PCR sampling bias, rather than PCR errors, challenges the UID-deep sequencing method in faithfully detecting low frequency mutation.

Phylogenetic relationship of Wolverine Gulo gulo in Mustelidae revealed by complete mitochondrial genome.

The Wolverine Gulo gulo is an endangered species in China. We first obtained blood sample, extracted the sample DNA and sequenced the whole mtDNA genome of wolverine in Northeast China. We built the phylogenetic tree of wolverine and 10 other most closely related Mustelidae species. The wolverine's complete mitogenome is 16 575 bp in length, includes 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and one control region. The phylogenetic tree indicates that Wolverine is mostly close to the genus Martes.

DNA methylation Landscape of body size variation in sheep.

Sub-populations of Chinese Mongolian sheep exhibit significant variance in body mass. In the present study, we sequenced the whole genome DNA methylation in these breeds to detect whether DNA methylation plays a role in determining the body mass of sheep by Methylated DNA immunoprecipitation - sequencing method. A high quality methylation map of Chinese Mongolian sheep was obtained in this study. We identified 399 different methylated regions located in 93 human orthologs, which were previously reported as body size related genes in human genome-wide association studies. We tested three regions in LTBP1, and DNA methylation of two CpG sites showed significant correlation with its RNA expression. Additionally, a particular set of differentially methylated windows enriched in the "development process" (GO: 0032502) was identified as potential candidates for association with body mass variation. Next, we validated small part of these windows in 5 genes; DNA methylation of SMAD1, TSC1 and AKT1 showed significant difference across breeds, and six CpG were significantly correlated with RNA expression. Interestingly, two CpG sites showed significant correlation with TSC1 protein expression. This study provides a thorough understanding of body size variation in sheep from an epigenetic perspective.

Co-expression analysis of fetal weight-related genes in ovine skeletal muscle during mid and late fetal development stages.

BACKGROUND: Muscle development and lipid metabolism play important roles during fetal development stages. The commercial Texel sheep are more muscular than the indigenous Ujumqin sheep. RESULTS: We performed serial transcriptomics assays and systems biology analyses to investigate the dynamics of gene expression changes associated with fetal longissimus muscles during different fetal stages in two sheep breeds. Totally, we identified 1472 differentially expressed genes during various fetal stages using time-series expression analysis. A systems biology approach, weighted gene co-expression network analysis (WGCNA), was used to detect modules of correlated genes among these 1472 genes. Dramatically different gene modules were identified in four merged datasets, corresponding to the mid fetal stage in Texel and Ujumqin sheep, the late fetal stage in Texel and Ujumqin sheep, respectively. We further detected gene modules significantly correlated with fetal weight, and constructed networks and pathways using genes with high significances. In these gene modules, we identified genes like TADA3, LMNB1, TGF-ß3, EEF1A2, FGFR1, MYOZ1, and FBP2 correlated with fetal weight. CONCLUSION: Our study revealed the complex network characteristics involved in muscle development and lipid metabolism during fetal development stages. Diverse patterns of the network connections observed between breeds and fetal stages could involve some hub genes, which play central roles in fetal development, correlating with fetal weight. Our findings could provide potential valuable biomarkers for selection of body weight-related traits in sheep and other livestock.