Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Lignin is the only sustainable aromatic resource in nature, its utilization has attracted much attention worldwide. Oxidation is one of the promising strategies that can convert lignin to a range of ...value-added platform chemicals. Lignin oxidation is generally carried out in a liquid phase with employed catalytic systems and oxidants, and this process is largely influenced by operation conditions, catalyst types, presence of oxidant, and solvent species. The inter-unit linkages in lignin can be selectively oxidized with the assistance of designed catalytic systems, facilitating the formation of aromatics (phenolic aldehydes, ketones, and acids), benzoquinones, and aliphatic (di)carboxylic acids. This work aims to provide a comprehensive review on traditional and advanced lignin oxidation concerning various catalytic systems for different terminal products. Deficiency in current lignin oxidation is also mentioned which indicates the direction of further lignin oxidative valorization.
•Innovative presentation on traditional lignin oxidation including bleaching, structural identification and wet air oxidation.•Comprehensive review on advanced lignin oxidation for platform chemicals based on different catalytic oxidation mechanisms.•State-of-the-art discussion on selective oxidation of α-OH and further conversion of oxidized lignin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report ...that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1
and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies.
A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC.
http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg
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•Aromatic units and side-chain linkages within lignin were analyzed by 2D HSQC NMR.•Relevance between lignin structure and pyrolysis behaviors was explored by Py–GC/MS.•Selectivities of phenols ...derived from AOL vs. SAL reached 86.73% vs. 87.37%.•More β-O-4′ linkages led to the easier pyrolysis conversion and less demethoxylation.
In this study, the Fourier transform infrared (FTIR) spectrometry and the 13C–1H correlation two-dimensional (2D) heteronuclear single-quantum coherence (HSQC) nuclear magnetic resonance (NMR) were introduced to determine the chemical structure of soda alkali lignin (SAL) and Alcell organosolv lignin (AOL), and the relevance between chemical structure and pyrolysis behaviors was evaluated by thermogravimetric analysis (TGA) and pyrolysis–gas chromatography/mass spectrometry (Py–GC/MS). Results showed that the two lignin samples had similar functional groups and S/G ratio, excepting side-chain linkages. SAL was mainly cross-linked by β-β′ linkages, while the main linkage within AOL was β-O-4′. This difference proposed that AOL had the worse thermal stability and was easier to be pyrolyzed to phenols than SAL. Herein, the pyrolysis transformation of SAL was always promoted by the increased temperature, whereas the generated phenols from AOL would be redecomposed at high pyrolysis temperature (800°C). Moreover, the priority of demethoxylation occurring in SAL pyrolysis was higher than that in AOL pyrolysis. Further analysis on the types of phenols suggested that the formation of syringyl phenols benefitted from the increasing temperature. However, the formation of p-hydroxyphenyl phenols was inhibited as temperature increased, and the highest selectivity of guaiacyl phenols was obtained at 600°C. The reveal of the relevance between lignin chemical structure and pyrolysis behaviors is meaningful for the efficient thermal conversion of lignin to phenol compounds.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Obesity and related metabolic diseases are becoming worldwide epidemics that lead to increased death rates and heavy health care costs. Effective treatment options have not been found yet. Here, ...based on the observation that baicalin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antisteatosis activity, we performed quantitative chemoproteomic profiling and identified carnitine palmitoyltransferase 1 (CPT1), the controlling enzyme for fatty acid oxidation, as the key target of baicalin. The flavonoid directly activated hepatic CPT1 with isoform selectivity to accelerate the lipid influx into mitochondria for oxidation. Chronic treatment of baicalin ameliorated diet-induced obesity (DIO) and hepatic steatosis and led to systemic improvement of other metabolic disorders. Disruption of the predicted binding site of baicalin on CPT1 completely abolished the beneficial effect of the flavonoid. Our discovery of baicalin as an allosteric CPT1 activator opens new opportunities for pharmacological treatment of DIO and associated sequelae.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Internet adaptive video streaming is a typical form of video delivery that leverages adaptive bitrate (ABR) algorithms to provide video services with high quality of experience (QoE) for various ...users in diverse and unique network conditions. Such heterogeneous network environments, which can be viewed as exogenous input processes, often lead to the unstable performance of ABR algorithms. Unfortunately, learning-based ABR algorithm which generated by state-of-the-art reinforcement learning (RL) technologies achieves good average performance but fails to perform well in all kinds of network conditions. In this work, considering the video playback process as the Input-driven Markov Decision Process (IMDP), we propose <inline-formula> <tex-math notation="LaTeX">\text{A}^{2} </tex-math></inline-formula>BR (Adaptation of ABR), a novel meta-RL ABR approach. <inline-formula> <tex-math notation="LaTeX">\text{A}^{2} </tex-math></inline-formula>BR is mainly composed of an online stage and an offline stage. It leverages meta-RL to learn an initial meta-policy with various network conditions at the offline stage and makes decisions in personalized network conditions at the online stage. At the same time, we continually optimize the meta-policy to the tailor-made ABR policy for varying the current network environment within few shots. Moreover, in order to improve the learning efficiency, we fully utilize domain knowledge for implementing a virtual player to replay the previously experienced network. Using trace-driven experiments on various scenarios including different vehicles, users, network types, and heterogeneous user-preferences, we show that <inline-formula> <tex-math notation="LaTeX">\text{A}^{2} </tex-math></inline-formula>BR outperforming recent ABR approaches with rapidly adapting to the personalized QoE metrics and specific network conditions. Testbed experimental results also illustrate the superiority of <inline-formula> <tex-math notation="LaTeX">\text{A}^{2} </tex-math></inline-formula>BR in adapting to the unseen environments.
Neutral triple gauge couplings (nTGCs) are absent in the standard model effective theory up to dimension-6 operators, but could arise from dimension-8 effective operators. In this work, we study the ...pure gauge operators of dimension-8 that contribute to nTGCs and are independent of the dimension-8 operator involving the Higgs doublet. We show that the pure gauge operators generate both
ZγZ*
and
Zγγ*
vertices with rapid energy dependence ∝
E
5
, which can be probed sensitively via the reaction
e
+
e
−
→
Zγ
. We demonstrate that measuring the nTGCs via the reaction
e
+
e
−
→
Zγ
followed by
Z
→
q
q
¯
decays can probe the new physics scales of dimension-8 pure gauge operators up to the range (1-5) TeV at the CEPC, FCC-ee and ILC colliders with
s
=
(
0.25
−
1
)
TeV, and up to the range (10–16) TeV at CLIC with
s
=
(
3
−
5
)
TeV, assuming in each case an integrated luminosity of 5 ab
−1
. We compare these sensitivities with the corresponding probes of the dimension-8 nTGC operators involving Higgs doublets and the dimension-8 fermionic contact operators that contribute to the
e
+
e
−
Zγ
vertex.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Lithium–sulfur batteries possess favorable potential for energy-storage applications because of their high specific capacity and the low cost of sulfur. Intensive understanding of the interfacial ...mechanism, especially the polysulfide formation and transformation under complex electrochemical environment, is crucial for the buildup of advanced batteries. Here, we report the direct visualization of interfacial evolution and dynamic transformation of the sulfides mediated by the lithium salts via real-time atomic force microscopy monitoring inside a working battery. The observations indicate that the lithium salts influence the structures and processes of sulfide deposition/decomposition during discharge/charge. Moreover, the distinct ion interaction and the diffusion in electrolytes manipulate the interfacial reactions determining the kinetics of the sulfide transformation. Our findings provide deep insights into surface dynamics of lithium–sulfur reactions revealing the salt-mediated mechanisms at nanoscale, which contribute to the profound understanding of the interfacial processes for the optimized design of lithium–sulfur batteries.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract
Identifying new indications for drugs plays an essential role at many phases of drug research and development. Computational methods are regarded as an effective way to associate drugs with ...new indications. However, most of them complete their tasks by constructing a variety of heterogeneous networks without considering the biological knowledge of drugs and diseases, which are believed to be useful for improving the accuracy of drug repositioning. To this end, a novel heterogeneous information network (HIN) based model, namely HINGRL, is proposed to precisely identify new indications for drugs based on graph representation learning techniques. More specifically, HINGRL first constructs a HIN by integrating drug–disease, drug–protein and protein–disease biological networks with the biological knowledge of drugs and diseases. Then, different representation strategies are applied to learn the features of nodes in the HIN from the topological and biological perspectives. Finally, HINGRL adopts a Random Forest classifier to predict unknown drug–disease associations based on the integrated features of drugs and diseases obtained in the previous step. Experimental results demonstrate that HINGRL achieves the best performance on two real datasets when compared with state-of-the-art models. Besides, our case studies indicate that the simultaneous consideration of network topology and biological knowledge of drugs and diseases allows HINGRL to precisely predict drug–disease associations from a more comprehensive perspective. The promising performance of HINGRL also reveals that the utilization of rich heterogeneous information provides an alternative view for HINGRL to identify novel drug–disease associations especially for new diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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