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.
Type 1 interferon-(alpha, beta, omega)-producing cells (IPCs), also known as plasmacytoid dendritic cell precursors (pDCs), represent 0.2%-0.8% of peripheral blood mononuclear cells in both humans ...and mice. IPCs display plasma cell morphology, selectively express Toll-like receptor (TLR)-7 and TLR9, and are specialized in rapidly secreting massive amounts of type 1 interferon following viral stimulation. IPCs can promote the function of natural killer cells, B cells, T cells, and myeloid DCs through type 1 interferons during an antiviral immune response. At a later stage of viral infection, IPCs differentiate into a unique type of mature dendritic cell, which directly regulates the function of T cells and thus links innate and adaptive immune responses. After more than two decades of effort by researchers, IPCs finally claim their place in the hematopoietic chart as the most important cell type in antiviral innate immunity. Understanding IPC biology holds future promise for developing cures for infectious diseases, cancer, and autoimmune diseases.
Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, ...standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include 'nanovesicles (NVs)', 'exosome-mimetic (EM)' and 'hybrid exosomes (HEs)', which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.
Quantifying source-oriented risk can identify primary pollution sources to help alleviate risks to ecosystems and human health posed by soil heavy metals. Taking Yulin National Energy and Chemical ...Industry Base as an example, ecosystem and human health risk assessments of each identified source category were quantitatively calculated by combining the Potential Ecological Risk (RI) and Total Carcinogenic Risk (Total-CR)/Total Hazard Index (Total-HI) assessment models with the positive matrix factorization (PMF) receptor model. In this work, an analysis of the Geoaccumulation Index (Igeo), Contamination Index (Pi), RI, CR and HI of heavy metals (As, Cr, Cu, Zn, Cd, Pb, Hg and Mn) identified universal ecosystem risks and both carcinogenic and noncarcinogenic health risks in most sites. Source apportionment results indicated that the dominant source of heavy metals in the soil was coal-related activities (52.5%), followed by industrial activities (22.0%), traffic activities (13.2%) and agricultural activities (12.3%). The source-oriented quantitative risk assessment results showed that coal-related activities are the greatest contributor to RI and Total-HI, while industrial activities are the largest source of Total-CR, which should be controlled, to reduce the carcinogenic health risk posed by exposure to heavy metals.
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•The level of heavy metals in soils from Yulin were investigated.•Igeo, Pi, RI, CR and HI values in soil indicated high risk to ecological and human health.•Four source categories were identified using PMF model.•Source contributions to ecological and human health risks were quantitatively and spatially identified.•Coal-related activities caused the greatest potential ecological risk and hazard index.
Observational and experimental evidence has revealed the functional importance of microbial diversity. However, the effects of microbial diversity loss on ecosystem functions are not consistent ...across studies, which are probably tempered by microbial functional redundancy, specific taxa and functions evaluated. Here we conducted diversity manipulation experiments in two independent soils with distinct prokaryotic communities, and investigated how the initial community traits (e.g., distinct functional redundancy and taxonomic composition) modulate the contribution of prokaryotic diversity loss and composition shift to eight ecosystem functions related to soil nutrient cycling. We found that diversity loss impaired three functions (potential nitrification rate, N2‐fixation activity and phosphatase) and multifunctionality only in the communities with low functional redundancy, but all examined functions were unaffected in the communities with high functional redundancy. All significantly affected functions belonged to specialized functions, while the broad function (soil basal respiration) was unaffected. Moreover, prokaryotic composition explained more functional variation than diversity, which was ascribed to the crucial role of specific taxa that influence particular functions. Taken together, this study provides empirical evidence for identifying the mechanism underlying the ecosystem response to changes in microbial community, with implications for improving the prediction of ecosystem process models and managing microbial communities to promote ecosystem services.
Innate immune cells are critical in protective immunity against viral infections, involved in sensing foreign viral nucleic acids. Here we report that the poly(ADP-ribose) polymerase 9 (PARP9), a ...member of PARP family, serves as a non-canonical sensor for RNA virus to initiate and amplify type I interferon (IFN) production. We find knockdown or deletion of PARP9 in human or mouse dendritic cells and macrophages inhibits type I IFN production in response to double strand RNA stimulation or RNA virus infection. Furthermore, mice deficient for PARP9 show enhanced susceptibility to infections with RNA viruses because of the impaired type I IFN production. Mechanistically, we show that PARP9 recognizes and binds viral RNA, with resultant recruitment and activation of the phosphoinositide 3-kinase (PI3K) and AKT3 pathway, independent of mitochondrial antiviral-signaling (MAVS). PI3K/AKT3 then activates the IRF3 and IRF7 by phosphorylating IRF3 at Ser385 and IRF7 at Ser437/438 mediating type I IFN production. Together, we reveal a critical role for PARP9 as a non-canonical RNA sensor that depends on the PI3K/AKT3 pathway to produce type I IFN. These findings may have important clinical implications in controlling viral infections and viral-induced diseases by targeting PARP9.
This paper deals with a multiperiod portfolio selection problem in an uncertain investment environment, in which the returns of securities are assumed to be uncertain variables and determined by ...experts' subjective evaluation. Based on uncertain theory, we present a novel multiperiod multiobjective mean-variance-skewness model by considering multiple realistic investment constraints such as transaction cost, bounds on holdings, cardinality, etc. For the proposed solution, we first apply a weighted max-min fuzzy goal programming approach to convert the proposed multiobjective programming model into a single-objective one. After that, we design a novel hybrid of an imperialist competitive algorithm (ICA) and a firefly algorithm (FA), termed ICA-FA, to solve it. Finally, we provide a numerical example to demonstrate the effectiveness of the proposed model and corresponding algorithm.
2D nanomaterials with flexibly modifiable surfaces are highly sought after for various applications, especially in room‐temperature chemiresistive gas sensing. Here, we have prepared a series of COF ...2D nanomaterials (porphyrin‐based COF nanosheets (NS)) that enabled highly sensitive and specific‐sensing of NO2 at room temperature. Different from the traditional 2D sensing materials, H2‐TPCOF was designed with a largely reduced interlayer interaction and predesigned porphyrin rings as modifiable sites on its surfaces for post‐metallization. After post‐metallization, the metallized M‐TPCOF (M=Co and Cu) showed remarkably improved sensing performances. Among them, Co‐TPCOF exhibited highly specific sensing toward NO2 with one of the highest sensitivities of all reported 2D materials and COF materials, with an ultra‐low limit‐of‐detection of 6.8 ppb and fast response/recovery. This work might shed light on designing and preparing a new type of surface‐highly‐modifiable 2D material for various chemistry applications.
A series of metalloporphyrin covalent organic framework based nanosheets has been synthesized and successfully applied in specific sensing of NO2 at room temperature.
The characteristics and evolution of pulmonary fibrosis in patients with coronavirus disease 2019 (COVID-19) have not been adequately studied. AI-assisted chest high-resolution computed tomography ...(HRCT) was used to investigate the proportion of COVID-19 patients with pulmonary fibrosis, the relationship between the degree of fibrosis and the clinical classification of COVID-19, the characteristics of and risk factors for pulmonary fibrosis, and the evolution of pulmonary fibrosis after discharge. The incidence of pulmonary fibrosis in patients with severe or critical COVID-19 was significantly higher than that in patients with moderate COVID-19. There were significant differences in the degree of pulmonary inflammation and the extent of the affected area among patients with mild, moderate and severe pulmonary fibrosis. The IL-6 level in the acute stage and albumin level were independent risk factors for pulmonary fibrosis. Ground-glass opacities, linear opacities, interlobular septal thickening, reticulation, honeycombing, bronchiectasis and the extent of the affected area were significantly improved 30, 60 and 90 days after discharge compared with at discharge. The more severe the clinical classification of COVID-19, the more severe the residual pulmonary fibrosis was; however, in most patients, pulmonary fibrosis was improved or even resolved within 90 days after discharge.
Cervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Aberrant mitochondrial dynamics play a crucial role in the pathogenesis of various neurodegenerative ...diseases. Thus, regulation of mitochondrial dynamics may offer therapeutic benefit for the treatment of CSM. Muscone, the active ingredient of an odoriferous animal product, exhibits anti‐inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. We hypothesized that muscone might ameliorate inflammatory responses and neuronal damage by regulating mitochondrial dynamics. To this end, the effects of muscone on a rat model of chronic cervical cord compression, as well as activated BV2 cells and injured neurons, were assessed. The results showed that muscone intervention improved motor function compared with vehicle‐treated rats. Indeed, muscone attenuated pro‐inflammatory cytokine expression, neuronal‐apoptosis indicators in the lesion area, and activation of the nod‐like receptor family pyrin domain‐containing 3 inflammasome, nuclear transcription factor‐κB, and dynamin‐related protein 1 in Iba1‐ and βIII‐tubulin‐labeled cells. Compared with vehicle‐treated rats, compression sites of muscone‐treated animals exhibited elongated mitochondrial morphologies in individual cell types and reduced reactive oxygen species. In vitro results indicated that muscone suppressed microglial activation and neuronal damage by regulating related‐inflammatory or apoptotic molecules. Moreover, muscone inhibited dynamin‐related protein 1 activation in activated BV2 cells and injured neurons, whereby it rescued mitochondrial fragmentation and reactive oxygen species production, which regulate a wide range of inflammatory and apoptotic molecules. Our findings reveal that muscone attenuates neuroinflammation and neuronal damage in rats with chronic cervical cord compression by regulating mitochondrial fission events, suggesting its promise for CSM therapy.
Cervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Muscone, the ingredient from an animal product, exhibits anti‐inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. In this study, we explored the effects of muscone on a classic CSM rat model, microglial and neuronal cell. Results indicated that muscone could attenuate both inflammatory responses and neuronal damage in a rat CSM model and in vitro. Such effects may be associated with its role on mitochondrial dynamics and downstream signaling, suggesting that mitochondrial dynamics and muscone may be new highlights for the treatment of CSM.
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