The Hengduan Mountains (HDM) biodiversity hotspot exhibits exceptional alpine plant diversity. Here, we investigate factors driving intraspecific divergence within a HDM alpine species Salix ...brachista (Cushion willow), a common component of subnival assemblages. We produce a high-quality genome assembly for this species and characterize its genetic diversity, population structure and pattern of evolution by resequencing individuals collected across its distribution. We detect population divergence that has been shaped by a landscape of isolated sky island-like habitats displaying strong environmental heterogeneity across elevational gradients, combined with population size fluctuations that have occurred since approximately the late Miocene. These factors are likely important drivers of intraspecific divergence within Cushion willow and possibly other alpine plants with a similar distribution. Since intraspecific divergence is often the first step toward speciation, the same factors can be important contributors to the high alpine species diversity in the HDM.
The biochemical response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis is a strong predictor of long‐term outcome and thus facilitates the rapid identification of patients needing new ...therapeutic approaches. Numerous criteria for predicting outcome of treatment have been studied based on biochemical response to UDCA at 1 year. We sought to determine whether an earlier biochemical response at 3 or 6 months could as efficiently identify patients at risk of poor outcome, as defined by liver‐related death, liver transplantation, and complications of cirrhosis. We analyzed the prospectively collected data of 187 patients with a median follow‐up of 5.8 years (range, 1.3‐14 years). The survival rates without adverse outcome at 5 years and 10 years were 86% and 63%. Under UDCA therapy, laboratory liver parameters experienced the most prominent improvement in the first 3 months (P < 0.0001) and then stayed relatively stable for the following months. The Paris, Barcelona, Toronto, and Ehime definitions, but not the Rotterdam definition, applied at 3, 6, and 12 months significantly discriminated the patients in terms of long‐term outcome. Compared with biochemical responses evaluated after 1 year of UDCA therapy, biochemical responses at the third month demonstrated higher positive predictive value (PPV) but lower negative predictive value (NPV) and increased negative likelihood ratio (NLR) by all definitions; biochemical responses at the sixth month showed higher or the same PPV and NPV and lower NLR by all definitions. Conclusion: For the previously published criteria, biochemical responses at the sixth month can be used in place of those evaluated after 1 year of UDCA therapy. Our findings justify a more rapid identification of patients who need new therapeutic approaches. (HEPATOLOGY 2013)
Atomically dispersed metal‐nitrogen‐carbon (M‐N‐C) catalysts have exhibited encouraging oxygen reduction reaction (ORR) activity. Nevertheless, the insufficient long‐term stability remains a ...widespread concern owing to the inevitable 2‐electron byproducts, H2O2. Here, we construct Co‐N‐Cr cross‐interfacial electron bridges (CIEBs) via the interfacial electronic coupling between Cr2O3 and Co‐N‐C, breaking the activity‐stability trade‐off. The partially occupied Cr 3d‐orbitals of Co‐N‐Cr CIEBs induce the electron rearrangement of CoN4 sites, lowering the Co‐OOH* antibonding orbital occupancy and accelerating the adsorption of intermediates. Consequently, the Co‐N‐Cr CIEBs suppress the two‐electron ORR process and approach the apex of Sabatier volcano plot for four‐electron pathway simultaneously. As a proof‐of‐concept, the Co‐N‐Cr CIEBs is synthesized by the molten salt template method, exhibiting dominant 4‐electron selectively and extremely low H2O2 yield confirmed by Damjanovic kinetic analysis. The Co‐N‐Cr CIEBs demonstrates impressive bifunctional oxygen catalytic activity (▵E=0.70 V) and breakthrough durability including 100 % current retention after 10 h continuous operation and cycling performance over 1500 h for Zn‐air battery. The hybrid interfacial configuration and the understanding of the electronic coupling mechanism reported here could shed new light on the design of superdurable M‐N‐C catalysts.
A cross‐interfacial electronic bridges (CIEBs) is constructed via interfacial electronic coupling between Cr2O3 and Co‐N‐C, breaking the trade‐off between activity and stability. The partially occupied Cr 3d‐orbitals of Co‐N‐Cr CIEBs induce the electron rearrangement of CoN4 sites, lowering the Co‐OOH* antibonding orbital occupancy and accelerating the adsorption of intermediates. Consequently, the Co‐N‐Cr CIEBs suppress the two‐electron ORR process and approach the apex of Sabatier volcano plot for four‐electron pathway simultaneously.
Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some ...biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.
Purpose
Obstructive sleep apnea (OSA) is associated with increased levels of systemic inflammatory markers, increased arterial stiffness, and endothelial dysfunction, which may lead to increased ...cardiovascular risk. We aimed to quantify the effects of continuous positive airway pressure (CPAP) on cardiovascular biomarkers and to establish predictors of response to CPAP.
Methods
We searched PubMed and the Cochrane Library from inception to May 31, 2017. Randomized controlled trials (RCTs) assessing the efficacy of CPAP on high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor- alpha (TNF-α), augmentation index (AIx), pulse wave velocity (PWV), and flow-mediated dilatation (FMD) in patients with OSA were selected by consensus.
Results
We included 15 RCTs comprising 1090 patients in the meta-analysis. The pooled standard mean difference (SMD) of effect of CPAP on hs-CRP was − 0.64 (95% confidence interval (CI) − 1.19 to − 0.09;
P
= 0.02). CPAP was associated with a reduction in AIx of 1.53% (95% CI, 0.80 to 2.26%;
P
< 0.001) and a significant increase in FMD of 3.96% (95% CI 1.34 to 6.59%;
P
= 0.003). Subgroup analyses found CPAP was likely to be more effective in improving FMD levels in severe OSA patients or patients with effective CPAP use ≥ 4 h/night.
Conclusions
Among patients with OSA, CPAP improves inflammatory marker hs-CRP, arterial stiffness marker AIx, and endothelial function marker FMD. These biomarkers may provide information related to response to treatment. Future studies will need to clarify the efficacy of these biomarkers in assessing cardiovascular risk reduction among OSA treated with CPAP.
The coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2 virus) has been sustained in China since December 2019, and has become a ...pandemic. The mental health of frontline medical staff is a concern. In this study, we aimed to identify the factors influencing medical worker anxiety in China during the COVID-19 outbreak. We conducted a cross-sectional study to estimate the prevalence of anxiety among medical staff in China from 10 February 2020 to 20 February 2020 using the Zung Self-rating Anxiety Scale (SAS) to assess anxiety, with the criteria of normal (⩽49), mild (50-59), moderate (60-70) and severe anxiety (⩾70). We used multivariable linear regression to determine the factors (e.g. having direct contact when treating infected patients, being a medical staff worker from Hubei province, being a suspect case) for anxiety. We also used adjusted models to confirm independent factors for anxiety after adjusting for gender, age, education and marital status. Of 512 medical staff in China, 164 (32.03%) had had direct contact treating infected patients. The prevalence of anxiety was 12.5%, with 53 workers suffering from mild (10.35%), seven workers suffering from moderate (1.36%) and four workers suffering from severe anxiety (0.78%). After adjusting for sociodemographic characteristics (gender, age, education and marital status), medical staff who had had direct contact treating infected patients experienced higher anxiety scores than those who had not had direct contact (β value = 2.33, confidence interval (CI) 0.65-4.00; P = 0.0068). A similar trend was observed in medical staff from Hubei province, compared with those from other parts of China (β value = 3.67, CI 1.44-5.89; P = 0.0013). The most important variable was suspect cases with high anxiety scores, compared to non-suspect cases (β value = 4.44, CI 1.55-7.33; P = 0.0028). In this survey of hospital medical workers during the COVID-19 outbreak in China, we found that study participants experienced anxiety symptoms, especially those who had direct clinical contact with infected patients; as did those in the worst affected areas, including Hubei province; and those who were suspect cases. Governments and healthcare authorities should proactively implement appropriate psychological intervention programmes, to prevent, alleviate or treat increased anxiety.
The Hengduan Mountains region is an important hotspot of alpine plant diversity and endemism. Acanthochlamys bracteata is a species of a threatened monotypic genus endemic to the Hengduan Mountains. ...In this study, we present a high‐quality, chromosome‐level reference genome for A. bracteata, constructed using long reads, short reads and Hi‐C technology. We characterized its genetic diversity, population structure, demographic history and gene flow by resequencing individuals collected across its distribution. Comparative genomics analyses based on sequence information from single‐copy orthologous genes revealed that A. bracteata and Dioscorea rotundata diverged ~104.5 million years ago. Whole‐genome resequencing based on population genetic analysis revealed that the division of the 14 populations into 10 distinct clusters reflected geographical divergence, and three separate high levels of gene flow occurred sequentially between isolated populations of the Hengduan Mountains, a finding which is consistent with the turnover between ice ages and interglacial periods. Our findings indicate that Quaternary climatic changes played an important role in shaping the genetic structure and demographic trajectories of A. bracteata, and provide critical insights into the genetic status and evolutionary history of this poorly understood species, and possibly other alpine plants with a similar distribution. This study demonstrates the usefulness of population genomics for evaluating the effects of past climatic changes and identifying conservation units for the conservation and management of threatened species. Our high‐quality genome represents a valuable resource for future studies of the underlying molecular mechanisms of adaptive evolution and provides insight for further comparative genomic analysis with other Velloziaceae species.
Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of ...lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC.
The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5' and 3' rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p.
We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue.
Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target.
The low-cost room-temperature sodium-sulfur battery system is arousing extensive interest owing to its promise for large-scale applications. Although significant efforts have been made, resolving low ...sulfur reaction activity and severe polysulfide dissolution remains challenging. Here, a sulfur host comprised of atomic cobalt-decorated hollow carbon nanospheres is synthesized to enhance sulfur reactivity and to electrocatalytically reduce polysulfide into the final product, sodium sulfide. The constructed sulfur cathode delivers an initial reversible capacity of 1081 mA h g
with 64.7% sulfur utilization rate; significantly, the cell retained a high reversible capacity of 508 mA h g
at 100 mA g
after 600 cycles. An excellent rate capability is achieved with an average capacity of 220.3 mA h g
at the high current density of 5 A g
. Moreover, the electrocatalytic effects of atomic cobalt are clearly evidenced by operando Raman spectroscopy, synchrotron X-ray diffraction, and density functional theory.
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