The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we ...present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.
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•SARS-CoV-2 interacts with hACE2 via S protein CTD•A 2.5-Å structure of SARS-CoV-2-CTD in complex with hACE2 is resolved•The SARS-CoV-2-CTD displays stronger affinity for hACE2 compared with SARS-RBD•SARS-CoV-2 -CTD is antigenically different from SARS-RBD
The crystal structure of the C-terminal domain of the SARS-CoV-2 spike protein in complex with human ACE2 reveals insights into the mechanisms of binding of this virus and its differences from SARS.
The intensive application of inorganic nitrogen underlies marked increases in crop production, but imposes detrimental effects on ecosystems
: it is therefore crucial for future sustainable ...agriculture to improve the nitrogen-use efficiency of crop plants. Here we report the genetic basis of nitrogen-use efficiency associated with adaptation to local soils in rice (Oryza sativa L.). Using a panel of diverse rice germplasm collected from different ecogeographical regions, we performed a genome-wide association study on the tillering response to nitrogen-the trait that is most closely correlated with nitrogen-use efficiency in rice-and identified OsTCP19 as a modulator of this tillering response through its transcriptional response to nitrogen and its targeting to the tiller-promoting gene DWARF AND LOW-TILLERING (DLT)
. A 29-bp insertion and/or deletion in the OsTCP19 promoter confers a differential transcriptional response and variation in the tillering response to nitrogen among rice varieties. The allele of OsTCP19 associated with a high tillering response to nitrogen is prevalent in wild rice populations, but has largely been lost in modern cultivars: this loss correlates with increased local soil nitrogen content, which suggests that it might have contributed to geographical adaptation in rice. Introgression of the allele associated with a high tillering response into modern rice cultivars boosts grain yield and nitrogen-use efficiency under low or moderate levels of nitrogen, which demonstrates substantial potential for rice breeding and the amelioration of negative environment effects by reducing the application of nitrogen to crops.
Early diagnosis of oral squamous cell carcinoma (OSCC) is an attractive strategy to increase survival rate of patient. An integrated separation approach of reversed phase liquid chromatography and ...hydrophilic interaction chromatography combining with time of flight mass spectrometer has been firstly developed for performing global saliva metabonomics analysis for early diagnosis of OSCC. This approach was designed to overcome the limitations of a single chromatographic method due to different polarity of endogenous metabolites. As a result, 14 potential salivary metabolites were identified. Eight biomarkers up-regulated in OSCC patients are compared with control and six down-regulated groups. Receiver operating characteristic analysis was exploited to evaluate the diagnostic power of the candidate biomarkers, and related metabolic pathways have also been studied. Five salivary biomarkers (propionylcholine, N-Acetyl-L-phenylalanine, sphinganine, phytosphingosine, and S-carboxymethyl-L-cysteine) in combination yielded satisfactory accuracy (AUC = 0.997), sensitivity (100%), and specificity (96.7%) in distinguishing early stage of OSCC from the control. In this study, a comprehensive saliva metabonomics analysis for identifying potential biomarkers to early diagnose OSCC is successfully demonstrated, which has the advantages of non-invasive, simple, reliable, and low-cost. These novel metabolic biomarkers have obvious clinical utility that will help to diagnose OSCC at its early stage.
An outbreak of coronavirus disease 2019 (COVID-19)
, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
, has spread globally. Countermeasures are needed to treat and prevent ...further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.
Neutralizing antibodies could potentially be used as antivirals against the coronavirus disease 2019 (COVID-19) pandemic. Here, we report isolation of four human-origin monoclonal antibodies from a ...convalescent patient, all of which display neutralization abilities. The antibodies B38 and H4 block binding between the spike glycoprotein receptor binding domain (RBD) of the virus and the cellular receptor angiotensin-converting enzyme 2 (ACE2). A competition assay indicated different epitopes on the RBD for these two antibodies, making them a potentially promising virus-targeting monoclonal antibody pair for avoiding immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.
Despite the discovery of animal coronaviruses related to SARS-CoV-2, the evolutionary origins of this virus are elusive. We describe a meta-transcriptomic study of 411 bat samples collected from a ...small geographical region in Yunnan province, China, between May 2019 and November 2020. We identified 24 full-length coronavirus genomes, including four novel SARS-CoV-2-related and three SARS-CoV-related viruses. Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome, although it possessed a more divergent spike gene. The other three SARS-CoV-2-related coronaviruses carried a genetically distinct spike gene that could weakly bind to the hACE2 receptor in vitro. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species, with the largest contiguous hotspots extending from South Laos and Vietnam to southern China. Our study highlights the remarkable diversity of bat coronaviruses at the local scale, including close relatives of both SARS-CoV-2 and SARS-CoV.
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•Four novel SARS-CoV-2-related viruses were identified in rhinolophid bats•RpYN06 is the closest relative of SARS-CoV-2 in most of the virus genome•A high diversity of bat coronaviruses was present in a very small geographic area•Ecological modeling reveals a broad range of rhinolophid bats in parts of Asia
A study of 411 bat samples collected in Yunnan province, China between 2019 and 2020 yields 24 full-length coronavirus genomes, including four viruses highly related to SARS-CoV-2 and three to SARS. The closest relative to SARS-CoV-2 infects a species of bats that is found in regions that extend from South Laos and Vietnam to southern China.
The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and ...therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.
Candida auris is a new pathogen called "superbug fungus" which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic review and meta-analysis was ...undertaken to determine the epidemic situation, drug resistance patterns and mortality of C. auris. We systematically searched studies on the clinical report of Candida auris in Pubmed, Embase and Cochrane databases until October 6, 2019. A standardized form was used for data collection, and then statics was performed with STATA11.0. It showed that more than 4733 cases of C. auris were reported in over 33 countries, with more cases in South Africa, United States of America, India, Spain, United Kingdom, South Korea, Colombia and Pakistan. C. auirs exhibited a decrease in case count after 2016. Clade I and III were the most prevalent clades with more cases reported and wider geographical distribution. Blood stream infection was observed in 32% of the cases, which varied depending on the clades. Resistance to fluconazole, amphotericin B, caspofungin, micafungin and anidulafungin in C. auris were 91, 12, 12.1, 0.8 and 1.1%. The overall mortality of C. auris infection was 39%. Furthermore, subgroup analyses showed that mortality was higher in bloodstream infections (45%), and lower in Europe (20%).
Reducing ammonia (NH3) volatilization from croplands while satisfying the food demand is strategically required to mitigate haze pollution. However, the global pattern of NH3 volatilization remains ...uncertain, primarily because of the episodic nature of NH3 volatilization rates and the high variation of fertilization practices. Here, we improve a global estimate of crop-specific NH3 emissions at a high spatial resolution using an updated data-driven model with a survey-based dataset of the fertilization scheme. Our estimate of the globally averaged volatilization rate (12.6% ± 2.1%) is in line with previous data-driven studies (13.7 ± 3.1%) but results in one-quarter lower emissions than process-based models (16.5 ± 3.1%). The associated global emissions are estimated at 14.4 ± 2.3 Tg N, with more than 50% of the total stemming from three stable crops or 12.2% of global harvested areas. Nearly three-quarters of global cropland-NH3 emissions could be reduced by improving fertilization schemes (right rate, right type, and right placement). A small proportion (20%) of global harvested areas, primarily located in China, India, and Pakistan, accounts for 64% of abatement potentials. Our findings provide a critical reference guide for the future abatement strategy design when considering locations and crop types.
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•The introduced Mn on Fe2O3 improved the interfacialconductivity and adsorption.•The kinetic degradation rate of BPA was increased by 235 times through Mn-Fe2O3.•Surface active ...complexes, O2− and 1O2 were the main reactive species.•Mn-Fe2O3 could operate continuously in the reactor for 23 days.
Intrinsically inferior electron transfer rate between catalyst and oxidant was considered as a limiting factor to inhibit the catalytic efficiency of peroxymonosulfate (PMS). In this work, the introduction of Mn atoms into iron oxide (Fe2O3) (Mn-Fe2O3) effectively altered the electronic structure of catalyst surface and promoted the adsorption of PMS, which increased the removal rate of Bisphenol A (BPA) by 235 times, with an extensive pH range (3–11). The main active species contained surface active complexes, superoxide radical (O2−), and singlet oxygen (1O2). The reactor unit could operate continuously for 23 days and still maintain a removal rate of more than 95%. In addition, it had good adaptability to actual water bodies and could effectively reduce the toxicity of BPA. This work shed new light on the regulation of the interfacial electron transfer process between catalyst and oxidant.
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