The hydrogenation of esters catalyzed by a manganese complex of phosphine‐aminopyridine ligand was developed. Using this protocol, a variety of (hetero)aromatic and aliphatic carboxylates including ...biomass‐derived esters and lactones were hydrogenated to primary alcohols with 63–98% yields. The manganese catalyst was found to be active for the hydrogenation of methyl benzoate, providing benzyl alcohol with turnover numbers (TON) as high as 45,000. Investigation of catalyst intermediates indicated that the amido manganese complex was the active catalyst species for the reaction.
Network Motif Discovery: A GPU Approach Lin, Wenqing; Xiao, Xiaokui; Xie, Xing ...
IEEE transactions on knowledge and data engineering,
03/2017, Letnik:
29, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The identification of network motifs has important applications in numerous domains, such as pattern detection in biological networks and graph analysis in digital circuits. However, mining network ...motifs is computationally challenging, as it requires enumerating subgraphs from a real-life graph, and computing the frequency of each subgraph in a large number of random graphs. In particular, existing solutions often require days to derive network motifs from biological networks with only a few thousand vertices. To address this problem, this paper presents a novel study on network motif discovery using Graphical Processing Units (GPUs). The basic idea is to employ GPUs to parallelize a large number of subgraph matching tasks in computing subgraph frequencies from random graphs, so as to reduce the overall computation time of network motif discovery. We explore the design space of GPU-based subgraph matching algorithms, with careful analysis of several crucial factors (such as branch divergences and memory coalescing) that affect the performance of GPU programs. Based on our analysis, we develop a GPU-based solution that (i) considerably differs from existing CPU-based methods in how it enumerates subgraphs, and (ii) exploits the strengths of GPUs in terms of parallelism while mitigating their limitations in terms of the computation power per GPU core. With extensive experiments on a variety of biological networks, we show that our solution is up to two orders of magnitude faster than the best CPU-based approach, and is around 20 times more cost-effective than the latter, when taking into account the monetary costs of the CPU and GPUs used.
A Ni‐catalyzed hydroarylation of styrenes and 1,3‐dienes with organoboron compounds has been developed. The reaction offers a highly selective approach to diarylalkanes and allylarenes under ...redox‐neutral conditions. In this hydroarylation reaction, a new strategy that uses the proton of methanol to generate the active catalyst species Ni−H was developed. The Ni‐catalyzed hydroarylation, combined with a Ir‐catalyzed C−H borylation, affords a very efficient and straightforward access to a retinoic acid receptor agonist.
OH yeah: A nickel(0)‐catalyzed hydroarylation of alkenes with organoboron reagents using an alcohol OH group as the H‐atom source is reported. The reaction offers a highly selective approach to diarylalkanes and allylarenes under redox‐neutral conditions.
Piwi‐interacting RNAs (piRNAs), a novel class of small non‐coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also ...been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR‐823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR‐823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR‐823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD‐1, whereas overexpression of piR‐823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR‐823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR‐823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR‐823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR‐823 plays a tumor‐promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR‐823 as a potential therapeutic target for CRC.
piR‐823 is up‐regulated in colorectal cancer tissues .piR‐823 promotes proliferation and inhibits apoptosis in colorectal cancer carcinogenesis.piR‐823 elevates the expression of HSP27, 60 and 70 by binding to HSF1 and enhancing its activity.
A highly enantio‐ and regioselective hydrosulfonylation of 1,3‐dienes with sulfonyl hydrazides has been realized by using a palladium catalyst containing a monodentate chiral spiro phosphoramidite ...ligand. The reaction provided an efficient approach to synthetically useful chiral allylic sulfones. Mechanistic studies suggest that the reaction proceeds through the formation of an allyl hydrazine intermediate and subsequent rearrangement to the chiral allylic sulfone product. The transformation of the allyl hydrazine intermediate to the product is the enantioselectivity‐determining step.
A highly enantio‐ and regioselective hydrosulfonylation of 1,3‐dienes with sulfonyl hydrazides by using a palladium catalyst containing a monodentate chiral spiro phosphoramidite ligand is reported. The reaction provides a new strategy for the synthesis of chiral allylic sulfones in high enantioselectivity.
Zika virus (ZIKV) has evolved into a global health threat because of its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated ...multiple substitutions from their Asian ancestor. Here we show that a single serine-to-asparagine substitution Ser139→Asn139 (S139N) in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.
Gastroenteritis accounts for approximately 1.7 million visits to the emergency department (ED) by children in the United States every year. Data to determine whether the use of probiotics improves ...outcomes in these children are lacking.
We conducted a randomized, double-blind trial involving 886 children 3 to 48 months of age with gastroenteritis who presented to six pediatric EDs in Canada. Participants received a 5-day course of a combination probiotic product containing Lactobacillus rhamnosus R0011 and L. helveticus R0052, at a dose of 4.0×10
colony-forming units twice daily or placebo. The primary outcome was moderate-to-severe gastroenteritis, which was defined according to a post-enrollment modified Vesikari scale symptom score of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease). Secondary outcomes included the duration of diarrhea and vomiting, the percentage of children who had unscheduled physician visits, and the presence or absence of adverse events.
Moderate-to-severe gastroenteritis within 14 days after enrollment occurred in 108 of 414 participants (26.1%) who were assigned to probiotics and 102 of 413 participants (24.7%) who were assigned to placebo (odds ratio, 1.06; 95% confidence interval CI, 0.77 to 1.46; P=0.72). After adjustment for trial site, age, detection of rotavirus in stool, and frequency of diarrhea and vomiting before enrollment, trial-group assignment did not predict moderate-to-severe gastroenteritis (odds ratio, 1.06; 95% CI, 0.76 to 1.49; P=0.74). There were no significant differences between the probiotic group and the placebo group in the median duration of diarrhea (52.5 hours interquartile range, 18.3 to 95.8 and 55.5 hours interquartile range, 20.2 to 102.3, respectively; P=0.31) or vomiting (17.7 hours interquartile range, 0 to 58.6 and 18.7 hours interquartile range, 0 to 51.6, P=0.18), the percentages of participants with unscheduled visits to a health care provider (30.2% and 26.6%; odds ratio, 1.19; 95% CI, 0.87 to 1.62; P=0.27), and the percentage of participants who reported an adverse event (34.8% and 38.7%; odds ratio, 0.83; 95% CI, 0.62 to 1.11; P=0.21).
In children who presented to the emergency department with gastroenteritis, twice-daily administration of a combined L. rhamnosus-L. helveticus probiotic did not prevent the development of moderate-to-severe gastroenteritis within 14 days after enrollment. (Funded by the Canadian Institutes of Health Research and others; PROGUT ClinicalTrials.gov number, NCT01853124 .).
•This review compared the features of children's COVID-19 with children's SARS•There were differences between children's SARS and COVID-19•Some thoughts and recommendations were given to contain ...children's COVID-19 from a pediatrician's perspective
Coronaviruses, both SARS-CoV and SARS-CoV-2, first appeared in China. They have certain biological, epidemiological and pathological similarities. To date, research has shown that their genes exhibit 79% of identical sequences and the receptor-binding domain structure is also very similar. There has been extensive research performed on SARS; however, the understanding of the pathophysiological impact of coronavirus disease 2019 (COVID-19) is still limited.
This review drew upon the lessons learnt from SARS, in terms of epidemiology, clinical characteristics and pathogenesis, to further understand the features of COVID-19.
By comparing these two diseases, it found that COVID-19 has quicker and wider transmission, obvious family agglomeration, and higher morbidity and mortality. Newborns, asymptomatic children and normal chest imaging cases emerged in COVID-19 literature. Children starting with gastrointestinal symptoms may progress to severe conditions and newborns whose mothers are infected with COVID-19 could have severe complications. The laboratory test data showed that the percentage of neutrophils and the level of LDH is higher, and the number of CD4+ and CD8+T-cells is decreased in children's COVID-19 cases.
Based on these early observations, as pediatricians, this review put forward some thoughts on children's COVID-19 and gave some recommendations to contain the disease.
Summary
Phosphorus (P) is an essential macronutrient required for plant development and production. The mechanisms regulating phosphate (Pi) uptake are well established, but the function of ...chloroplast Pi homeostasis is poorly understood in Oryza sativa (rice). PHT2;1 is one of the transporters/translocators mediating Pi import into chloroplasts. In this study, to gain insight into the role of OsPHT2;1‐mediated stroma Pi, we analyzed OsPHT2;1 function in Pi utilization and photoprotection. Our results showed that OsPHT2;1 was induced by Pi starvation and light exposure. Cell‐based assays showed that OsPHT2;1 localized to the chloroplast envelope and functioned as a low‐affinity Pi transporter. The ospht2;1 had reduced Pi accumulation, plant growth and photosynthetic rates. Metabolite profiling revealed that 52.6% of the decreased metabolites in ospht2;1 plants were flavonoids, which was further confirmed by 40% lower content of total flavonoids compared with the wild type. As a consequence, ospht2;1 plants were more sensitive to UV‐B irradiation. Moreover, the content of phenylalanine, the precursor of flavonoids, was also reduced, and was largely associated with the repressed expression of ADT1/MTR1. Furthermore, the ospht2;1 plants showed decreased grain yields at relatively high levels of UV‐B irradiance. In summary, OsPHT2;1 functions as a chloroplast‐localized low‐affinity Pi transporter that mediates UV tolerance and rice yields at different latitudes.
Significance Statement
Phosphorus (P) is an essential macronutrient for plant development and production, although the function of chloroplast phosphate (Pi) homeostasis is poorly understood in Oryza sativa (rice). Here, we found that OsPHT2;1 functions as a chloroplast‐localized low‐affinity Pi transporter that mediates UV tolerance and rice yields at different latitudes through modulating flavonoid homeostasis.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved ...vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.
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