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.
For many regenerative electrochemical energy‐conversion systems, hybrid electrocatalysts comprising transition metal (TM) oxides and heteroatom‐doped (e.g., nitrogen‐doped) carbonaceous materials are ...promising bifunctional oxygen reduction reaction/oxygen evolution reaction electrocatalysts, whose enhanced electrocatalytic activities are attributed to the synergistic effect originated from the TM–N–C active sites. However, it is still ambiguous which configuration of nitrogen dopants, either pyridinic or pyrrolic N, when bonded to the TM in oxides, predominately contributes to the synergistic effect. Herein, an innovative strategy based on laser irradiation is described to controllably tune the relative concentrations of pyridinic and pyrrolic nitrogen dopants in the hybrid catalyst, i.e., NiCo2O4 NPs/N‐doped mesoporous graphene. Comparative studies reveal the dominant role of pyridinic‐NCo bonding, instead of pyrrolic‐N bonding, in synergistically promoting reversible oxygen electrocatalysis. Moreover, density functional theory calculations provide deep insights into the corresponding synergistic mechanism. The optimized hybrid, NiCo/NLG‐270, manifests outstanding reversible oxygen electrocatalytic activities, leading to an overpotential different ΔE among the lowest value for highly efficient bifunctional catalysts. In a practical reversible Zn–air battery, NiCo/NLG‐270 exhibits superior charge/discharge performance and long‐term durability compared to the noble metal electrocatalysts.
An innovative strategy based on laser irradiation is developed to selectively regulate relative contents of pyridinic and pyrrolic nitrogen in NiCo2O4/N‐graphene hybrids. Strong chemical bonding forms between nitrogen and cobalt, and pyridinic‐NCo bonds, instead of pyrrolic‐NCo bonds, are identified to predominantly contribute to synergistic catalysis, leading to substantially enhanced oxygen electrocatalytic activities, outperforming a combination of benchmark noble metal catalysts.
Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its ...significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods： A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging exalnination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein （HDL） and low-density lipoprotein （LDL） levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results： NONFH was diagnosed in 218 subjects （0.725%） and the estimated NONFH cases were 8.12 million among Chinesepeople aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females （1.02% vs. 0.51%, x^2 = 24.997, P 〈 0.001 ）. Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents （0.85% vs. 0.61%,x^2= 5.847, P = 0.016）. Our multivariate regression analysis showed that high blood levels oftriglycerides, total cholesterol, LDL-cholesterol, and non-H DL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head. heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions： Our findings highlight that NONFH is a significantpublic health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.
Purpose
Probiotics have been reported to be beneficial for inflammatory bowel disease (IBD), but the types, number of strains, dosage, and intervention time of probiotics used remain controversial. ...Furthermore, the changes of gut microbiota in IBD’s patients are also intriguing. Thus, this meta-analysis was to explore the clinical effects and gut microbiota changes of using probiotics, prebiotics and synbiotics in IBD.
Methods
The search was performed in PubMed, Web of Science and the Cochrane library from inception to April 2020. Qualified randomized controlled trials were included. IBD’s remission rate, disease activity index and recurrence rate were extracted and analyzed. Changes in the gut microbiota of patients with IBD are comprehensively described.
Results
Thirty-eight articles were included. Probiotics, prebiotics and synbiotics can induce/maintain IBD’s remission and reduce ulcerative colitis (UC) disease activity index (RR = 1.13, 95% CI 1.02, 1.26,
P
< 0.05; SMD = 1.00, 95% CI 0.27, 1.73,
P
< 0.05). In subgroup analyses of IBD remission rate and UC disease activity index, we obtained some statistically significant results in some subgroup (
P
< 0.05). To some extent, probiotic supplements can increase the number of beneficial bacteria (especially
Bifidobacteria
) in the intestinal tract of patients with IBD.
Conclusions
Our results support the treatment of IBD (especially UC) with pro/pre/synbiotics, and synbiotics are more effective. Probiotic supplements that are based on
Lactobacillus
and
Bifidobacterium
or more than one strain are more likely to be beneficial for IBD remission. The dose of 10
10
–10
12
CFU/day may be a reference range for using probiotics to relieve IBD.
Abstract
Glucose electrolysis offers a prospect of value-added glucaric acid synthesis and energy-saving hydrogen production from the biomass-based platform molecules. Here we report that ...nanostructured NiFe oxide (NiFeO
x
) and nitride (NiFeN
x
) catalysts, synthesized from NiFe layered double hydroxide nanosheet arrays on three-dimensional Ni foams, demonstrate a high activity and selectivity towards anodic glucose oxidation. The electrolytic cell assembled with these two catalysts can deliver 100 mA cm
−2
at 1.39 V. A faradaic efficiency of 87% and glucaric acid yield of 83% are obtained from the glucose electrolysis, which takes place via a guluronic acid pathway evidenced by in-situ infrared spectroscopy. A rigorous process model combined with a techno-economic analysis shows that the electrochemical reduction of glucose produces glucaric acid at a 54% lower cost than the current chemical approach. This work suggests that glucose electrolysis is an energy-saving and cost-effective approach for H
2
production and biomass valorization.
The Majorana fermion, which is its own antiparticle and obeys non-Abelian statistics, plays a critical role in topological quantum computing. It can be realized as a bound state at zero energy, ...called a Majorana zero mode (MZM), in the vortex core of a topological superconductor, or at the ends of a nanowire when both superconductivity and strong spin orbital coupling are present. A MZM can be detected as a zero-bias conductance peak (ZBCP) in tunneling spectroscopy. However, in practice, clean and robust MZMs have not been realized in the vortices of a superconductor because of contamination from impurity states or other closely packed Caroli–de Gennes-Matricon (CdGM) states, which hampers further manipulations of MZMs. Here, using scanning tunneling spectroscopy, we show that a ZBCP well separated from the other discrete CdGM states exists ubiquitously in the cores of free vortices in the defect-free regions of(Li0.84Fe0.16)OHFeSe, which has a superconducting transition temperature of 42 K. Moreover, a Dirac-cone-type surface state is observed by angle-resolved photoemission spectroscopy, and its topological nature is confirmed by band calculations. The observed ZBCP can naturally be attributed to a MZM arising from the chiral topological surface state of a bulk superconductor. Thus,(Li0.84Fe0.16)OHFeSeprovides an ideal platform for studying MZMs and topological quantum computing.
A pandemic of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. ...We conducted a retrospective, multicenter study, and followed‐up with all children from the families with SARS‐CoV‐2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS‐CoV‐2 RNA with real‐time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal‐viral excretion times among groups with different antiviral regiments were compared with Kaplan‐Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS‐CoV‐2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty‐three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS‐CoV‐2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal‐viral‐excreting children. Children have lower susceptibility of SARS‐CoV‐2 infection, longer incubation, and fecal‐viral excretion time. Positive results of fecal SARS‐CoV‐2 RNA detection were not used as indication for hospitalization or quarantine.
Highlights
Children had lower susceptibility for SARS‐CoV‐2 infection than adults.
Children had longer incubation period and fecal viral excretion time after infected by SARS‐CoV‐2.
Viral clearance time was not different among the groups treated with different antiviral regiments.
Children had milder clinical symptoms, better clinical outcome, and more common fecal viral excretion.
Positive results of fecal SARS‐CoV‐2 RNA detection are not used as indication for hospitalization or quarantine.
Identifying novel drug targets to overcome resistance to tyrosine kinase inhibitors (TKIs) and eradicating leukemia stem/progenitor cells are required for the treatment of chronic myelogenous ...leukemia (CML). Here, we show that ubiquitin-specific peptidase 47 (USP47) is a potential target to overcome TKI resistance. Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo. The knockout of Usp47 significantly inhibits BCR-ABL and BCR-ABL
-induced CML in mice with the reduction of Lin
Sca1
c-Kit
CML stem/progenitor cells. Mechanistic studies show that stabilizing Y-box binding protein 1 contributes to USP47-mediated DNA damage repair in CML cells. Inhibiting USP47 by P22077 exerts cytotoxicity to CML cells with or without TKI resistance in vitro and in vivo. Moreover, P22077 eliminates leukemia stem/progenitor cells in CML mice. Together, targeting USP47 is a promising strategy to overcome TKI resistance and eradicate leukemia stem/progenitor cells in CML.
Abstract Whole tumor cell lysates (TCL) have been implemented as tumor antigens for cancer vaccine development, although clinical outcomes of TCL-based antitumor immunotherapy remain unsatisfactory. ...In order to improve the efficacy of TCL-based vaccines, biomaterials have been employed to enhance antigen delivery and presentation. Here, we have developed chitosan nanoparticles (CTS NPs) with surface mannose (Man) moieties for specific dendritic cells (DCs) targeting (Man-CTS NPs). The Man-CTS NPs were then loaded with TCL generated from B16 melanoma cells (Man-CTS-TCL NPs) for in vitro and in vivo assessment. Potency of the Man-CTS-TCL NPs as cancer vaccine was also assessed in vivo by immunization of mice with Man-CTS-TCL NPs followed by re-challenge with B16 melanoma cell inoculation. We have shown here that Man-CTS-TCL NPs promote bone marrow-derived dendritic cells (BMDCs) maturation and antigen presentation in vitro. In vivo evaluation further demonstrated that the Man-CTS-TCL NPs were readily taken up by endogenous DCs within the draining lymph node (DLN) following subcutaneous administration accompanied by increase in serum IFN-γ and IL-4 levels. Tumor growth was also significantly delayed in mice primed with Man-CTS-TCL NPs vaccine, attributable at least in part to cytotoxic T lymphocytes response. Moreover, Man-CTS-TCL NPs vaccine also exhibited therapeutic effects in mice with melanoma. Thus, we report here the Man-CTS-TCL NPs as effective anti-tumor vaccine for cancer immunotherapy.
Background
High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID‐19 patients, but the characteristics of symptomatic VTE in general COVID‐19 patients have not ...been described.
Objectives
To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID‐19 patients.
Methods/Results
This retrospective study enrolled all COVID‐19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID‐19. In comparison to 23,434 non‐COVID‐19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non‐severe hospitalized COVID‐19 patients were 5.94 (95% confidence interval CI 3.91–10.09) and 2.79 (95% CI 1.43–5.60), respectively. When 104 VTE cases and 208 non‐VTE cases were compared, pulmonary embolism cases had a higher rate for in‐hospital death (OR 6.74, 95% CI 2.18–20.81). VTE developed at a median of 21 days (interquartile range 13.25–31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D‐dimer on admission, and D‐dimer increment (DI) ≥1.5‐fold; of these, DI ≥1.5‐fold had the most significant association (OR 14.18, 95% CI 6.25–32.18, p = 2.23 × 10−10). A novel model consisting of three simple coagulation variables (fibrinogen and D‐dimer levels on admission, and DI ≥1.5‐fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822–0.907, sensitivity 0.930, specificity 0.710).
Conclusions
There is an excess risk of VTE in hospitalized COVID‐19 patients. This novel model can aid early identification of patients who are at high risk for VTE.
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