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Background Physical activity (PA) is essential and effective for chronic heart failure (CHF) patients. A greater understanding of the longitudinal change in PA and its influencing factors during the postdischarge transition period may help create interventions for improving PA. The aims of this study were (1) to compare the change in PA, (2) to examine the influencing factors of PA change, and (3) to verify the mediating pathways between influencing factors and PA during the postdischarge transition period in CHF patients. Methods A total of 209 CHF patients were recruited using a longitudinal study design. The Chinese version of the International Physical Activity Questionnaire (IPAQ), Patient-reported Outcome Measure for CHF (CHF-PRO), and the Chinese version of the Tampa Scale for Kinesiophobia Heart (TSK-Heart) were used to assess PA, CHF-related symptoms, and kinesiophobia. The IPAQ score was calculated (1) at admission, (2) two weeks after discharge, (3) two months after discharge, and (4) three months after discharge. Two additional questionnaires were collected during admission. Generalized estimating equation (GEE) models were fitted to identify variables associated with PA over time. We followed the STROBE checklist for reporting the study. Results The PA scores at the four follow-up visits were 1039.50 (346.50-1953.00) (baseline/T1), 630.00 (1.00-1260.00) (T2), 693.00 (1-1323.00) (T3) and 693.00 (160.88–1386.00) (T4). The PA of CHF patients decreased unevenly, with the lowest level occurring two weeks after discharge, and gradually improving at two and three months after discharge. CHF-related symptoms and kinesiophobia were significantly associated with changes in PA over time. Compared with before hospitalization, an increase in CHF-related symptoms at two weeks and two months after discharge was significantly associated with decreased PA. According to our path analysis, CHF-related symptoms were positively and directly associated with kinesiophobia, and kinesiophobia was negatively and directly related to PA. Moreover, CHFrelated symptoms are indirectly related to PA through kinesiophobia. Conclusion PA changed during the postdischarge transition period and was associated with CHF-related symptoms and kinesiophobia in CHF patients. Reducing CHF-related symptoms helps improve kinesiophobia in CHF patients. In addition, the reduction in CHF-related symptoms led to an increase in PA through the improvement of kinesiophobia. [ABSTRACT FROM AUTHOR]

ObjectivesNon-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18F-FDG PET/CT in guiding the treatment strategy of NTM patients.MethodsWe retrospectively analyzed the cases of 23 NTM patients who underwent 18F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18F-FDG included maximum standardized uptake value (SUVmax), SUVmax of the most FDG-avid lesion (SUVTop), SUVTop/SUVmax of the liver (SURLiver), SUVTop/SUVmax of the blood (SURBlood), metabolic lesion volume (MLV), and total lesion glycolysis (TLG). The optimal cut-off values of these parameters were determined using receiver operating characteristic curves.ResultsThere were 6 patients (26.09%) with localized pulmonary diseases and 17 patients (73.91%) with disseminated diseases. The NTM lesions had high or moderate 18F-FDG uptake (median SUVTop: 8.2 ± 5.7). As for immune status, the median SUVTop in immunocompromised and immunocompetent patients were 5.2 ± 2.5 and 10.0 ± 6.4, respectively, with a significant difference (P = 0.038). As for extent of lesion involvement, SURLiver and SURBlood in localized pulmonary and disseminated diseases were 1.9 ± 1.1 vs. 3.8 ± 1.6, and 2.7 ± 1.8 vs. 5.5 ± 2.6, respectively, with a significant difference (P = 0.016 and 0.026). Moreover, for disease severity, SUVmax of the lung lesion (SUVI−lung) and SUVmax of the marrow (SUVMarrow) in the severe group were 7.7 ± 4.3 and 4.4 ± 2.7, respectively, significantly higher than those in the non-severe group (4.4 ± 2.0 and 2.4 ± 0.8, respectively) (P = 0.027 and 0.036). The ROC curves showed that SUVTop, SURLiver, SURBlood, SUVI−lung, and SUVMarrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients.Conclusion18F-FDG PET/CT is a useful tool in the diagnosis, evaluation of disease activity, immune status, and extent of lesion involvement in NTM patients, and can contribute to planning the appropriate treatment for NTM. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy is a practical therapeutic approach in breast cancer (BRCA), and the role of FLI1 in immune regulation has gradually been unveiled. However, the specific role of FLI1 in BRCA was conflicted; thus, additional convincing evidence is needed. Methods: We explored the upstream regulation of FLI1 expression via summary data-based Mendelian randomization (SMR) analysis and ncRNA network construction centering on FLI1 using BRCA genome-wide association study (GWAS) summary data with expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) from the blood and a series of in silico analyses, respectively. We illuminated the downstream function of FLI1 in immune regulation by integrating a series of analyses of single-cell RNA sequence data (scRNA-seq). Results: We verified a causal pathway from FLI1 methylation to FLI1 gene expression to BRCA onset and demonstrated that FLI1 was downregulated in BRCA. FLI1, a transcription factor, served as myeloid and T cells' communication regulator by targeting immune-related ligands and receptor transcription in BRCA tissues. We constructed a ceRNA network centering on FLI1 that consisted of three LncRNAs (CKMT2-AS1, PSMA3-AS1, and DIO3OS) and a miRNA (hsa-miR-324-5p), and the expression of FLI1 was positively related to a series of immune-related markers, including immune cell infiltration, biomarkers of immune cells, and immune checkpoints. Conclusion: Low-methylation-induced or ncRNA-mediated downregulation of FLI1 is associated with poor prognosis, and FLI1 might regulate the tumor immune microenvironment via a cell-type-specific target genes manner in BRCA. [ABSTRACT FROM AUTHOR]

Background: Pathogen detection in clinical samples based on 16S metagenomic sequencing technology in microbiology laboratories is an important strategy for clinical diagnosis, public health surveillance, and investigations of outbreaks. However, the implementation of the technology is limited by its accuracy and the time required for bioinformatics analysis. Therefore, a simple, standardized, and rapid analysis pipeline from the receipt of clinical samples to the generation of a test report is needed to increase the use of metagenomic analyses in clinical settings. Results: We developed a comprehensive bioinformatics analysis pipeline for the identification of pathogens in clinical samples based on 16S metagenomic sequencing data, named 16SPIP. This pipeline offers two analysis modes (fast and sensitive mode) for the rapid conversion of clinical 16S metagenomic data to test reports for pathogen detection. The pipeline includes tools for data conversion, quality control, merging of paired-end reads, alignment, and pathogen identification. We validated the feasibility and accuracy of the pipeline using a combination of culture and whole-genome shotgun (WGS) metagenomic analyses. Conclusions: 16SPIP may be effective for the analysis of 16S metagenomic sequencing data for real-time, rapid, and unbiased pathogen detection in clinical samples. [ABSTRACT FROM AUTHOR]

Background: Low-intensity pulsed ultrasound (LIPUS) is a mechanical stimulus that plays a key role in regulating the differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the way in which it affects the chondrogenic differentiation of BMSCs remains unknown. In this study, we aimed to investigate whether LIPUS is able to influence TGF-β1-induced chondrogenesis of BMSCs through the integrin-mechanistic target of the Rapamycin (mTOR) signaling pathway. Methods: BMSCs were isolated from rat bone marrow and cultured in either standard or TGF-β1-treated culture medium. BMSCs were then subjected to LIPUS at a frequency of 3 MHz and a duty cycle of 20%, and integrin and mTOR inhibitors added in order to analyze their influence on cell differentiation. BMSCs were phenotypically analyzed by flow cytometry and the degree of chondrogenesis evaluated through toluidine blue staining, immunofluorescence, and immunocytochemistry. Furthermore, expression of COL2, aggrecan, SOX9, and COL1 was assessed by qRT-PCR and western blot analysis. Results: We found that LIPUS promoted TGF-β1-induced chondrogenesis of BMSCs, represented by increased expression of COL2, aggrecan and SOX9 genes, and decreased expression of COL1. Notably, these effects were prevented following addition of integrin and mTOR inhibitors. Conclusions: Taken together, these results indicate that mechanical stimulation combined with LIPUS promotes TGF-β1-induced chondrogenesis of BMSCs through the integrin-mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Transplantation of neural stem cells (NSCs) has been proposed as a promising therapeutic strategy for the treatment of ischemia/reperfusion (I/R)-induced brain injury. However, existing evidence has also challenged this therapy on its limitations, such as the difficulty for stem cells to survive after transplantation due to the unfavorable microenvironment in the ischemic brain. Herein, we have investigated whether preconditioning of NSCs with adjudin, a small molecule compound, could enhance their survivability and further improve the therapeutic effect for NSC-based stroke therapy. Method: We aimed to examine the effect of adjudin pretreatment on NSCs by measuring a panel of parameters after their transplantation into the infarct area of ipsilateral striatum 24 hours after I/R in mice. Results: We found that pretreatment of NSCs with adjudin could enhance the viability of NSCs after their transplantation into the stroke-induced infarct area. Compared with the untreated NSC group, the adjudin-preconditioned group showed decreased infarct volume and neurobehavioral deficiency through ameliorating blood–brain barrier disruption and promoting the expression and secretion of brain-derived neurotrophic factor. We also employed H2O2-induced cell death model in vitro and found that adjudin preconditioning could promote NSC survival through inhibition of oxidative stress and activation of Akt signaling pathway. Conclusion: This study showed that adjudin could be used to precondition NSCs to enhance their survivability and improve recovery in the stroke model, unveiling the value of adjudin for stem cell-based stroke therapy. [ABSTRACT FROM AUTHOR]

Background: Ovulation rate and litter size are important reproductive traits in sheep with high economic value. Recent work has revealed a potential link between DNA methylation and prolificacy. However, a genome-wide study that sought to identify potential DNA methylation sites involved in sheep prolificacy indicated that it is still unknown. Here, we aimed to investigate the genome-wide DNA methylation profiles of Hu sheep ovaries by comparing a highprolificacy group (HP, litter size of three for at least 2 consecutive lambings) and low prolificacy group (LP, litter size of one for at least 2 consecutive lambings) using deep whole-genome bisulfite sequencing (WGBS). Results: First, our results demonstrated lower expression levels of DNA methyltransferase (DNMT) genes in the ovaries of the HP group than that in the ovaries of the LP group. Both groups showed similar proportions of methylation at CpG sites but different proportions at non-CpG sites. Subsequently, we identified 70,899 differential methylated regions (DMRs) of CG, 16 DMRs of CHG, 356 DMRs of CHH and 12,832 DMR-related genes(DMGs). Gene Ontology (GO) analyses revealed that some DMGs were involved in regulating female gonad development and ovarian follicle development. Finally, we found that 10 DMGs, including BMP7, BMPR1B, CTNNB1, FST, FSHR, LHCGR, TGFB2 and TGFB3, are more likely to be involved in prolificacy of Hu sheep, as assessed by correlation analysis and listed in detail. Conclusions: This study revealed the global DNA methylation pattern of sheep ovaries associated with high and low prolificacy groups, which may contribute to a better understanding of the epigenetic regulation of sheep reproductive capacity. [ABSTRACT FROM AUTHOR]

Background: Th1, Th2, Th17, Treg and Tfh cells play important roles in schistosomiasis. Th9 cells secrete IL-9 as a signature cytokine and contribute to several classes of inflammatory disease. However, the effects of Th9 cells in schistosomiasis are unknown. We aimed to explore the dynamic changes and potential roles of Th9 cells in the pathogenesis of hepatic egg granulomatous inflammation in mice infected with Schistosoma japonicum. Methods: Twenty mice with S. japonicum infection and five normal controls (NC) were used as models. The average areas of egg granulomas were estimated by hematoxylin-eosin (H & E) staining. Hepatic IL-9 and transcription factor PU.1 levels were detected by immunohistochemistry. Flow cytometry techniques were used to analyze the proportions of Th9 cells. With the help of ELISA, serum levels of IL-9 were examined. Results: The egg granulomas began to form from four weeks after infection and continued to develop. In parallel with the development of egg granulomas, the hepatic levels of IL-9 and PU.1 increased very slowly during the first four weeks post-infection and increased rapidly thereafter. Moreover, the proportions of splenic Th9 cells and levels of serum IL-9 had similar developmental trends with the egg granulomas. Conclusion: The proliferation of Th9 cells and levels of IL-9 were significantly higher in S. japonicum-infected mice compared to NC. In addition, dynamic changes of Th9 and IL-9 were synchronous with the developmental trend of hepatic egg granulomatous inflammation, suggesting that Th9 cells might be a new subset in the pathogenesis of schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: Development of biofuels is considered as one of the important ways to replace conventional fossil energy and mitigate climate change. However, rapid increase of biofuel production could cause other environmental concerns in China such as water stress. This study is intended to evaluate the life-cycle water footprints (WF) of biofuels derived from several potential non-edible feedstocks including cassava, sweet sorghum, and Jatropha curcas in China. Different water footprint types including blue water, green water, and grey water are considered in this study. Based on the estimated WF, water deprivation impact and water stress degree on local water environment are further analyzed for different regions in China. Results: On the basis of the feedstock resource availability, sweet sorghum, cassava, and Jatropha curcas seeds are considered as the likely feedstocks for biofuel production in China. The water footprint results show that the feedstock growth is the most water footprint intensive process, while the biofuel conversion and transportation contribute little to total water footprints. Water footprints vary significantly by region with climate and soil variations. The life-cycle water footprints of cassava ethanol, sweet sorghum ethanol, and Jatropha curcas seeds biodiesel were estimated to be 73.9-222.2, 115.9-210.4, and 64.7-182.3 L of water per MJ of biofuel, respectively. Grey water footprint dominates the life-cycle water footprint for each type of the biofuels. Development of biofuels without careful water resource management will exert significant impacts on local water resources. The water resource impacts vary significantly among regions. For example, based on blue and grey water consumption, Gansu province in China will suffer much higher water stress than other regions do due to limited available water resources and large amount of fertilizer use in that province. In term of blue water, Shandong province is shown with the most severe water stress issue, followed by Gansu province, which is attributed to the limited water resources in both provinces. Conclusions: By considering feedstock resource distribution, biofuel production potentials, and estimated water footprints, this study provides insight into the impact of biofuel production on the local water environment in China. Biofuel development policies need to be carefully designed for the sustainable development of biofuels in China. [ABSTRACT FROM AUTHOR]

Background: Acupuncture has been widely used as a treatment for alcohol dependence. An updated and rigorously conducted systematic review is needed to establish the extent and quality of the evidence on the effectiveness of acupuncture as an intervention for reducing alcohol dependence. This review aimed to ascertain the effectiveness of acupuncture for reducing alcohol dependence as assessed by changes in either craving or withdrawal symptoms. Methods: In this systematic review, a search strategy was designed to identify randomised controlled trials (RCTs) published in either the English or Chinese literature, with a priori eligibility criteria. The following English language databases were searched from inception until June 2015: AMED, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and PubMed; and the following Chinese language databases were similarly searched: CNKI, Sino-med, VIP, and Wan Fang. Methodological quality of identified RCTs was assessed using the Jadad Scale and the Cochrane Risk of Bias tool. Results: Fifteen RCTs were included in this review, comprising 1378 participants. The majority of the RCTs were rated as having poor methodological rigour. A statistically significant effect was found in the two primary analyses: acupuncture reduced alcohol craving compared with all controls (SMD = -1.24, 95% CI = -1.96 to -0.51); and acupuncture reduced alcohol withdrawal symptoms compared with all controls (SMD = -0.50, 95% CI = -0.83 to -0.17). In secondary analyses: acupuncture reduced craving compared with sham acupuncture (SMD = -1.00, 95% CI = -1.79 to -0.21); acupuncture reduced craving compared with controls in RCTs conducted in Western countries (SMD = -1.15, 95% CI = -2.12 to -0.18); and acupuncture reduced craving compared with controls in RCTs with only male participants (SMD = -1.68, 95% CI = -2.62 to -0.75). Conclusion: This study showed that acupuncture was potentially effective in reducing alcohol craving and withdrawal symptoms and could be considered as an additional treatment choice and/or referral option within national healthcare systems. [ABSTRACT FROM AUTHOR]

Neuroinflammation mediated by activation of microglia and interruption of the blood-brain barrier (BBB) is an important factor that contributes to neuron death and infarct area diffusion in ischemia reperfusion injury. Finding novel molecules to regulate neuroinflammation is of significant clinical value. We have previously shown that adjudin, a small molecule compound known to possess antispermatogenic function, attenuates microglia activation by suppression of the NF-κB pathway. In this study we continued to explore whether adjudin could be neuroprotective by using the transient middle cerebral artery occlusion (tMCAO) model. Adjudin treatment after reperfusion significantly decreased the infarction volume and neuroscore compared to the vehicle group. Staining of CD11b showed that adjudin markedly inhibited microglial activation in both the cortex and the striatum, accompanied by a reduction in the expression and release of cytokines TNF-α, IL-1β and IL- 6. Concomitantly, adjudin noticeably prevented BBB disruption after ischemia and reperfusion, as indicated by the reduction of IgG detection in the brain cortex and striatum versus the vehicle group. This finding was also corroborated by immunofluorescence staining and immunoblotting of tight junction-related proteins ZO-1, JAM-A and Occludin, where the reduction of these proteins could be attenuated by adjudin treatment. Moreover, adjudin obviously inhibited the elevated MMP-9 activity after stroke. Together these data demonstrate that adjudin protects against cerebral ischemia reperfusion injury, and we present an effective neuroinflammation modulator with clinical potential. [ABSTRACT FROM AUTHOR]

Background: Although a number of medicines are available for the management of hypertension, the organ damage induced by hypertension is not resolved. The aim of this study was to investigate the protection of ginsenoside Rg1 (Rg1) against vascular remodeling and organ damage in spontaneously hypertensive rats (SHR). Methods: Male SHR were treated with 5, 10 or 20 mg/kg Rg1 through intraperitoneal injection per day for 1 month. SHR or Wistar-Kyoto rats (WKY) receiving vehicle (saline) was used as control. Blood pressure detection and pathological stain, transmission electron microscope, immunohistochemical assay were used to elucidate the protection of Rg1. Results: Blood pressures were not different between control SHR rats and Rg1 treated SHR rats, but Rg1 improved the aortic outward remodeling by lowering the lumen diameter and reducing the media thickness according the histopathological and ultrastructural detections. Rg1 also protected the retinal vessels against inward remodeling detected by immunohistochemical assay. Furthermore, Rg1 attenuated the target heart and kidney damage with improvement on cardiac and glomerular structure. Conclusions: These results suggested that Rg1 held beneficial effects on vascular structure and further protected against the organ-damage induced by hypertension. These findings also paved a novel and promising approach to the treatment of hypertensive complications. [ABSTRACT FROM AUTHOR]

Background: Gene fusion is ubiquitous over the course of evolution. It is expected to increase the diversity and complexity of transcriptomes and proteomes through chimeric sequence segments or altered regulation. However, chimeric mRNAs in pigs remain unclear. Here we identified some chimeric mRNAs in pigs and analyzed the expression of them across individuals and breeds using RNA-sequencing data. Results: The present study identified 669 putative chimeric mRNAs in pigs, of which 251 chimeric candidates were detected in a set of RNA-sequencing data. The 618 candidates had clear trans-splicing sites, 537 of which obeyed the canonical GU-AG splice rule. Only two putative pig chimera variants whose fusion junction was overlapped with that of a known human chimeric mRNA were found. A set of unique chimeric events were considered middle variances in the expression across individuals and breeds, and revealed non-significant variance between sexes. Furthermore, the genomic region of the 50 partner gene shares a similar DNA sequence with that of the 30 partner gene for 458 putative chimeric mRNAs. The 81 of those shared DNA sequences significantly matched the known DNA-binding motifs in the JASPAR CORE database. Four DNA motifs shared in parental genomic regions had significant similarity with known human CTCF binding sites. Conclusions: The present study provided detailed information on some pig chimeric mRNAs. We proposed a model that trans-acting factors, such as CTCF, induced the spatial organisation of parental genes to the same transcriptional factory so that parental genes were coordinatively transcribed to give birth to chimeric mRNAs. [ABSTRACT FROM AUTHOR]

Background: Sequence context is an important aspect of base mutagenesis, and three-base periodicity is an intrinsic property of coding sequences. However, how three-base periodicity is influenced in the vicinity of substitutions is still unclear. The effect of context on mutagenesis should be revealed in the usage of nucleotides that flank substitutions. Relative entropy (also known as Kullback-Leibler divergence) is useful for finding unusual patterns in biological sequences. Results: Using relative entropy, we visualized the periodic patterns in the context of substitutions in human orthologous genes. Neighbouring patterns differed both among substitution categories and within a category that occurred at three codon positions. Transition tended to occur in periodic sequences relative to transversion. Periodic signals were stronger in a set of flanking sequences of substitutions that occurred at the third-codon positions than in those that occurred at the first- or second-codon positions. To determine how the three-base periodicity was affected near the substitution sites, we fitted a sine model to the values of the relative entropy. A sine of period equal to 3 is a good approximation for the three-base periodicity at sites not in close vicinity to some substitutions. These periods were interrupted near the substitution site and then reappeared away from substitutions. A comparative analysis between the native and codon-shuffled datasets suggested that the codon usage frequency was not the sole origin of the three-base periodicity, implying that the native order of codons also played an important role in this periodicity. Synonymous codon shuffling revealed that synonymous codon usage bias was one of the factors responsible for the observed three-base periodicity. Conclusions: Our results offer an efficient way to illustrate unusual periodic patterns in the context of substitutions and provide further insight into the origin of three-base periodicity. This periodicity is a result of the native codon order in the reading frame. The length of the period equal to 3 is caused by the usage bias of nucleotides in synonymous codons. The periodic features in nucleotides surrounding substitutions aid in further understanding genetic variation and nucleotide mutagenesis. [ABSTRACT FROM AUTHOR]

An abstract of the article "InfoMax gene networks constructed from intervention in the animal models of Parkinson's disease," by Hesam T. Dasht, and colleagues, is presented.