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.
Only rarely have polyoxometalates been found to form core–shell nanoclusters. Here, we succeeded in isolating a series of rare giant and all‐inorganic core–shell cobalt polyoxoniobates (Co−PONbs) ...with diverse shapes, nuclearities and original topologies, including 50‐nuclearity {Co12Nb38O132}, 54‐nuclearity {Co20Nb34O128}, 62‐nuclearity {Co26Nb36O140} and 87‐nuclearity {Co33Nb54O188}. They are the largest Co−PONbs and also the polyoxometalates containing the greatest number of Co ions and the largest cobalt clusters known thus far. These molecular Co−PONbs have intriguing and atomically precise core–shell architectures comprising unique cobalt oxide cores and niobate oxide shells. In particular, the encapsulated cobalt oxide cores with different nuclearities have identical compositions, structures and mixed‐valence Co3+/Co2+ states as the different sized Co−O moieties of the bulk cubic‐spinel Co3O4, suggesting that they can serve as various molecular models of the cubic‐spinel Co3O4. The successful construction of the series of the Co−PONbs reveals a feasible and versatile synthetic method for making rare core–shell heterometallic PONbs. Further, these new‐type core–shell bimetal species are promising cluster molecular catalysts for visible‐light‐driven CO2 reduction.
A series of rare Co−Nb‐based core–shell polyoxometalates containing 50, 54, 62 and 87 metal polyhedra is prepared. The cobalt oxide cores correspond to increasingly large molecular analogues of infinite cubic‐spinel Co3O4. They are the largest cobalt polyoxoniobates and the polyoxometalates with the greatest number of Co ions and the highest‐nuclearity cobalt clusters known thus far. They are shown to be efficient photocatalysts for CO2 reduction.
Whether ultra‐processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population‐based cohort of 98 ...265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra‐processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow‐up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra‐processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1:1.49; 95% confidence interval CI: 1.07‐2.07; Ptrend = .021) in a linear dose‐response manner (Pnonlinearity = .075). Subgroup analysis further found that the positive association of ultra‐processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1:2.17; 95% CI: 1.14‐4.15) than in those aged ≥65 years (HRquartile 4 vs 1:1.32; 95% CI: 0.88‐1.94), though the interaction test failed to achieve the statistical significance (Pinteraction = .061). These findings suggest that reducing ultra‐processed food consumption may be beneficial in decreasing pancreatic cancer incidence.
What's new?
“Ultra‐processed” foods, industrially formulated products consisting of ingredients extracted from foods, but no intact foods, now make up as much as 58.5% of Americans' daily calorie intake. Think frozen meals, hot dogs and packaged snacks. Here, the authors investigate the relationship between ultra‐processed foods and pancreatic cancer in a cohort of 98 265 American adults. High consumption of ultra‐processed foods was associated with increased risk of pancreatic cancer, and the association was more pronounced for those under age 65.
Malonic acid derivatives have been successfully applied in a Ag-catalyzed decarboxylative fluorination reaction, providing an unprecedented route to either gem-difluoroalkanes or α-fluorocarboxylic ...acids by the judicious selection of base and solvent. This reaction features the use of readily available starting materials, tunable chemoselectivity and good functional group compatibility as well as gram-scale synthetic capability. The advantage of using malonic acid derivatives in this radical decarboxylative functionalization is further highlighted by the facile transformations of the α-fluorocarboxylic acid to valuable fluorine-containing compounds. Preliminary mechanistic studies suggest that an α-carboxylic acid radical is involved in this reaction.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, placing an increasing burden on human health. NAFLD is a complex multifactorial disease involving genetic, ...metabolic, and environmental factors. It is closely associated with metabolic syndrome, obesity, and type 2 diabetes, of which insulin resistance is the main pathophysiological mechanism. Over the past few decades, investigation of the pathogenesis, diagnosis, and treatments has revealed different aspects of NAFLD, challenging the accuracy of definition and therapeutic strategy for the clinical practice. Recently, experts reach a consensus that NAFLD does not reflect the current knowledge, and metabolic (dysfunction) associated fatty liver disease (MAFLD) is suggested as a more appropriate term. The new definition puts increased emphasis on the important role of metabolic dysfunction in it. Herein, the shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy of the newly defined MAFLD, as compared with the formerly defined NAFLD, are reviewed for updating our understanding.
Natural structural materials (such as tendons and ligaments) are comprised of multiscale hierarchical architectures, with dimensions ranging from nano‐ to macroscale, which are difficult to mimic ...synthetically. Here a bioinspired, facile method to fabricate anisotropic hydrogels with perfectly aligned multiscale hierarchical fibrous structures similar to those of tendons and ligaments is reported. The method includes drying a diluted physical hydrogel in air by confining its length direction. During this process, sufficiently high tensile stress is built along the length direction to align the polymer chains and multiscale fibrous structures (from nano‐ to submicro‐ to microscale) are spontaneously formed in the bulk material, which are well‐retained in the reswollen gel. The method is useful for relatively rigid polymers (such as alginate and cellulose), which are susceptible to mechanical signal. By controlling the drying with or without prestretching, the degree of alignment, size of superstructures, and the strength of supramolecular interactions can be tuned, which sensitively influence the strength and toughness of the hydrogels. The mechanical properties are comparable with those of natural ligaments. This study provides a general strategy for designing hydrogels with highly ordered hierarchical structures, which opens routes for the development of many functional biomimetic materials for biomedical applications.
Anisotropic hydrogels with perfectly aligned hierarchical fibrous structures are fabricated by a simple method. Drying a physical hydrogel by confining its length direction generates a 1D tensile force that controls polymeric alignment and supramolecular interactions. A tunable structure and mechanical properties are realized in different types of rigid polymeric hydrogels and the properties are comparable with those of natural ligaments.
Abstract Lysosomes have recently been regarded as the attractive pharmacological targets for selectively killing of cancer cells via lysosomal cell death (LCD) pathway that is closely associated with ...reactive oxygen species (ROS). However, the details on the ROS-induced LCD of cancer cells are still poorly understood, partially due to the absence of a lysosome-targetable, robust, and biocompatible imaging tool for ROS. In this work, we brought forward a Si-rhodamine-based fluorescent probe, named PSiR , which could selectively and sensitively image the pathologically more relavent highly reactive oxygen species (hROS: HClO, HO , and ONOO− ) in lysosomes of cancer cells. Compared with many of the existing hROS fluorescent probes, its superiorities are mainly embodied in the high stability against autoxidation and photoxidation, near-infrared exitation and emission, fast fluorescence off−on response, and specific lysosomal localization. Its practicality has been demonstrated by the real-time imaging of hROS generation in lysosomes of human non-small-cell lung cancer cells stimulated by anticancer drug β-lapachone. Moreover, the probe was sensitive enough for basal hROS in cancer cells, allowing its further imaging applications to discriminate not only cancer cells from normal cells, but also tumors from healthy tissues. Overall, our results strongly indicated that PSiR is a very promising imaging tool for the studies of ROS-related LCD of cancer cells, screening of new anticancer drugs, and early diagnosis of cancers.
Abstract
TcpC is a multifunctional virulence factor of uropathogenic
E. coli
(UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we ...show the influence of TcpC on NETosis and related mechanisms. We show NETosis in the context of a pyelonephritis mouse model induced by TcpC-secreting wild-type
E. coli
CFT073 (CFT073
wt
) and LPS-induced in vitro NETosis with CFT073
wt
or recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses show that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion.
Hydrogels have promising applications in diverse areas, especially wet environments including tissue engineering, wound dressing, biomedical devices, and underwater soft robotics. Despite strong ...demands in such applications and great progress in irreversible bonding of robust hydrogels to diverse synthetic and biological surfaces, tough hydrogels with fast, strong, and reversible underwater adhesion are still not available. Herein, a strategy to develop hydrogels demonstrating such characteristics by combining macroscale surface engineering and nanoscale dynamic bonds is proposed. Based on this strategy, excellent underwater adhesion performance of tough hydrogels with dynamic ionic and hydrogen bonds, on diverse substrates, including hard glasses, soft hydrogels, and biological tissues is obtained. The proposed strategy can be generalized to develop other soft materials with underwater adhesion.
Tough hydrogels with fast, strong, and reversible underwater adhesion are developed by combining a clingfish‐inspired macroscale surface structure and nanoscale dynamic bonds. The surface structure accelerates water drainage, prevents water trapping and delays crack propagation; the dynamic bonds of the gel form reversible bridges at the interface and dissipate a significant amount of energy in bulk during detachment.
Organic–inorganic halide perovskite solar cells have rapidly come to prominence in the photovoltaic field. In this context, CH3NH3PbI3, as the most widely adopted active layer, has been attracting ...great attention. Generally, in a CH3NH3PbI3 layer, unreacted PbI2 inevitably coexists with the perovskite crystals, especially following a two‐step fabrication process. There appears to be a consensus that an appropriate amount of unreacted PbI2 is beneficial to the overall photovoltaic performance of a device, the only disadvantageous aspect of excess residual PbI2 being viewed as its insulating nature. However, the further development of such perovskite‐based devices requires a deeper understanding of the role of residual PbI2. In this work, PbI2‐enriched and PbI2‐controlled perovskite films, as two extreme cases, have been prepared by modulating the crystallinity of a pre‐deposited PbI2 film. The effects of excess residual PbI2 have been elucidated on the basis of spectroscopic and optoelectronic studies. The initial charge separation, the trap‐state density, and the trap‐state distribution have all been found to be adversely affected in PbI2‐enriched devices, to the detriment of photovoltaic performance. This leads to a biphasic recombination process and accelerates the charge carrier recombination dynamics.
Too much of a good thing? Excess residual PbI2 in perovskite solar cells has been found to affect their charge‐separation/trap‐state properties (see figure), which impairs their photovoltaic performance.
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