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31,268 result(s) for "Yang, Fang"
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Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development
To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.
Graph-based prediction of Protein-protein interactions with attributed signed graph embedding
Background Protein-protein interactions (PPIs) are central to many biological processes. Considering that the experimental methods for identifying PPIs are time-consuming and expensive, it is important to develop automated computational methods to better predict PPIs. Various machine learning methods have been proposed, including a deep learning technique which is sequence-based that has achieved promising results. However, it only focuses on sequence information while ignoring the structural information of PPI networks. Structural information of PPI networks such as their degree, position, and neighboring nodes in a graph has been proved to be informative in PPI prediction. Results Facing the challenge of representing graph information, we introduce an improved graph representation learning method. Our model can study PPI prediction based on both sequence information and graph structure. Moreover, our study takes advantage of a representation learning model and employs a graph-based deep learning method for PPI prediction, which shows superiority over existing sequence-based methods. Statistically, Our method achieves state-of-the-art accuracy of 99.15% on Human protein reference database (HPRD) dataset and also obtains best results on Database of Interacting Protein (DIP) Human, Drosophila , Escherichia coli ( E. coli ), and Caenorhabditis elegans ( C. elegan ) datasets. Conclusion Here, we introduce signed variational graph auto-encoder (S-VGAE), an improved graph representation learning method, to automatically learn to encode graph structure into low-dimensional embeddings. Experimental results demonstrate that our method outperforms other existing sequence-based methods on several datasets. We also prove the robustness of our model for very sparse networks and the generalization for a new dataset that consists of four datasets: HPRD, E.coli , C.elegan , and Drosophila .
الحصن المحاصر
في هذا الكتاب الحصن المحاصر للمؤلف تشيان جونغ شو يتحدث ويتناول المؤلف عن حصار المجتمع الصيني وبالأخص طبقة المثقفين في تلك الفترة داخل أنفسها قبل أن يكون حصارا بأسوار الاحتلال وكما تناول غلبة الصراع من النزاع الداخلي والتزاحم في جو من المكائد بدلا من التركيز في مواجهة العدو الياباني المشترك في هذا الوقت.
Integrative transcriptomic and metabolomic analyses unveil tanshinone biosynthesis in Salvia miltiorrhiza root under N starvation stress
Salvia miltiorrhiza is a model plant for Chinese herbal medicine with significant pharmacologic effects due to its tanshinone components. Our previous study indicated that nitrogen starvation stress increased its tanshinone content. However, the molecular mechanism of this low nitrogen-induced tanshinone biosynthesis is still unclear. Thus, this study aimed to elucidate the molecular mechanism of tanshinone biosynthesis in S . miltiorrhiza under different N conditions [N-free (N0), low-N (Nl), and full-N (Nf, as control) conditions] by using transcriptome and metabolome analyses. Our results showed 3,437 and 2,274 differentially expressed unigenes between N0 and Nf as well as Nl and Nf root samples, respectively. N starvation (N0 and Nl) promoted the expression of the genes involved in the MVA and MEP pathway of tanshinone and terpenoid backbone biosynthesis. Gene ontology and KEGG analyses revealed that terpenoid backbone biosynthesis, hormone signal transduction, and phenylpropanoid biosynthesis were promoted under N starvation conditions, whereas starch and sucrose metabolisms, nitrogen and phosphorus metabolisms, as well as membrane development were inhibited. Furthermore, metabolome analysis showed that metabolite compounds and biosynthesis of secondary metabolites were upregulated. This study provided a novel insight into the molecular mechanisms of tanshinone production in S . miltiorrhiza in response to nitrogen stress.
Plant neighbor detection and allelochemical response are driven by root-secreted signaling chemicals
Plant neighbor detection and response strategies are important mediators of interactions among species. Despite increasing knowledge of neighbor detection and response involving plant volatiles, less is known about how soil-borne signaling chemicals may act belowground in plant–plant interactions. Here, we experimentally demonstrate neighbor detection and allelopathic responses between wheat and 100 other plant species via belowground signaling. Wheat can detect both conspecific and heterospecific neighbors and responds by increasing allelochemical production. Furthermore, we show that (-)-loliolide and jasmonic acid are present in root exudates from a diverse range of species and are able to trigger allelochemical production in wheat. These findings suggest that root-secreted (-)-loliolide and jasmonic acid are involved in plant neighbor detection and allelochemical response and may be widespread mediators of belowground plant-plant interactions. Plant growth and physiology respond to the presence of neighboring plants. Here the authors show that the chemicals (-)-loliolide and jasmonic acid, which were present in the root exudates of a range of plant species, can be detected by wheat and induce allelochemical production.
Kin recognition in rice (Oryza sativa) lines
Kin recognition is an important mediator of interactions within individuals of a species. Despite increasing evidence of kin recognition in natural plant populations, relatively little is known about kin recognition in crop species where numerous cultivars have been generated by artificial selection. We identified rice (Oryza sativa) cultivars with the ability for kin recognition from two sets of indica-inbred and indica-hybrid lines at different levels of genetic relatedness. We then assessed this ability among kin and nonkin and tested potential mechanisms in a series of controlled experiments and field trails. Rice cultivars with the ability for kin recognition were capable of detecting the presence of kin and nonkin and responded to them by altering root behavior and biomass allocation, particularly for grain yield. Furthermore, we assessed the role of root exudates and found a root-secreted nitrogen-rich allantoin component to be responsible for kin recognition in rice lines. Kin recognition in rice lines mediated by root exudates occurs in a cultivar-dependent manner. Rice cultivars with the ability for kin recognition may increase grain yield in the presence of kin. Such an improvement of grain yield by kin recognition of cultivar mixtures offers many implications and applications in rice production.
Acute myocardial injury is common in patients with COVID-19 and impairs their prognosis
ObjectiveWe sought to explore the prevalence and immediate clinical implications of acute myocardial injury in a cohort of patients with COVID-19 in a region of China where medical resources are less stressed than in Wuhan (the epicentre of the pandemic).MethodsWe prospectively assessed the medical records, laboratory results, chest CT images and use of medication in a cohort of patients presenting to two designated covid-19 treatment centres in Sichuan, China. Outcomes of interest included death, admission to an intensive care unit (ICU), need for mechanical ventilation, treatment with vasoactive agents and classification of disease severity. Acute myocardial injury was defined by a value of high-sensitivity troponin T (hs-TnT) greater than the normal upper limit.ResultsA total of 101 cases were enrolled from January to 10 March 2020 (average age 49 years, IQR 34–62 years). Acute myocardial injury was present in 15.8% of patients, nearly half of whom had a hs-TnT value fivefold greater than the normal upper limit. Patients with acute myocardial injury were older, with a higher prevalence of pre-existing cardiovascular disease and more likely to require ICU admission (62.5% vs 24.7%, p=0.003), mechanical ventilation (43.5% vs 4.7%, p<0.001) and treatment with vasoactive agents (31.2% vs 0%, p<0.001). Log hs-TnT was associated with disease severity (OR 6.63, 95% CI 2.24 to 19.65), and all of the three deaths occurred in patients with acute myocardial injury.ConclusionAcute myocardial injury is common in patients with COVID-19 and is associated with adverse prognosis.
Design of catalysts for site-selective and enantioselective functionalization of non-activated primary C–H bonds
C–H functionalization represents a promising approach for the synthesis of complex molecules. Instead of relying on modifying the functional groups present in a molecule, the synthetic sequence is achieved by carrying out selective reactions on the C–H bonds, which traditionally would have been considered to be the unreactive components of a molecule. A major challenge is to design catalysts to control both the site- and stereoselectivity of the C–H functionalization. We have been developing dirhodium catalysts with different selectivity profiles in C–H functionalization reactions with donor/acceptor carbenes as reactive intermediates. Here we describe a new dirhodium catalyst capable of the functionalization of non-activated primary C–H bonds with high levels of site selectivity and enantioselectivity.