A Pd‐catalyzed regio‐ and stereoselective alkynylallylation of a specific C−C σ bond in cyclopropenes, using allyl propiolates as both allylation and alkynylation reagents, has been achieved for the ...first time. By merging selective C(sp2)‐C(sp3) bond scission with conjunctive cross‐couplings, this decarboxylative reorganization reaction features fascinating atom and step economy and provides an efficient approach to highly functionalized dienynes from readily available substrates. Without further optimization, gram‐scale products can be easily obtained by such a simple, neutral, and low‐cost catalytic system with high TONs. DFT calculations afford a rationale toward the formation of the products and indicate that the selective insertion of the double bond of cyclopropenes into the C‐Pd bond of ambidentate Pd complex and the subsequent nonclassical β‐C elimination promoted by 1,4‐palladium migration are critical for the success of the reaction.
1,2‐Alkynylallylation of a specific C−C σ bond in cyclopropenes was realized by a simple, neutral, low‐cost palladium catalytic system with high TONs. This decarboxylative reorganization reaction is an efficient way to construct highly functionalized dienynes in excellent regio‐ and stereoselectivity. A nonclassical β‐C elimination promoted by 1,4‐palladium migration was described herein for the first time.
Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular ...basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.
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.
Abstract
Metagenomic and metatranscriptomic sequencing approaches are more frequently being used to link microbiota to important diseases and ecological changes. Many analyses have been used to ...compare the taxonomic and functional profiles of microbiota across habitats or individuals. While a large portion of metagenomic analyses focus on species-level profiling, some studies use strain-level metagenomic analyses to investigate the relationship between specific strains and certain circumstances. Metatranscriptomic analysis provides another important insight into activities of genes by examining gene expression levels of microbiota. Hence, combining metagenomic and metatranscriptomic analyses will help understand the activity or enrichment of a given gene set, such as drug-resistant genes among microbiome samples. Here, we summarize existing bioinformatics tools of metagenomic and metatranscriptomic data analysis, the purpose of which is to assist researchers in deciding the appropriate tools for their microbiome studies. Additionally, we propose an Integrated Meta-Function mapping pipeline to incorporate various reference databases and accelerate functional gene mapping procedures for both metagenomic and metatranscriptomic analyses.
Objectives
To assess temporal patterns and regional differences in the incidence rate, and factors associated with survival of urinary tract urothelial carcinoma.
Methods
The medical records of 8830 ...patients with new diagnoses of urinary tract urothelial carcinoma in the years 2001–2010 were retrieved from Taiwan National databases. Temporal trends, regional disparity and related survival factors were evaluated using the Cochran–Armitage trend test, local Moran’s I statistic and log‐rank test, respectively.
Results
The annual urinary tract urothelial carcinoma incidence rates (standardized by age) were steady at approximately 3.14–3.41 per 100 000 person‐years. Notably, women had a significantly higher annual urinary tract urothelial carcinoma incidence than men in most of the years studied (range of female‐to‐male annual standardized rate ratio: 2.08–3.25), and diabetes prevalence in urinary tract urothelial carcinoma increased significantly from 12.3% to 23.4% per year over the 10 years. High urinary tract urothelial carcinoma incidence cluster areas other than the latest endemic area of “blackfoot disease” were newly identified by local Moran’s I statistic (P < 0.05). Furthermore, older age, male sex, end‐stage kidney disease and more advanced tumor grade were associated with lower 5‐year overall survival probabilities in the 2001–2015 cohort.
Conclusions
The incidence and survival of urinary tract urothelial carcinoma over the decade 2001–2010 were different according to population and regional features. Various urinary tract urothelial carcinoma screening, prevention, treatment and care plans should be developed depending on age, sex, comorbidity and area of residence.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we ...obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.
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•The complex structure of RaTG13 RBD with hACE2 was determined•Binding of RaTG13 RBD to 24 additional ACE2 orthologs was evaluated•Residue 501 plays a key role in determining the potential host range of RaTG13•SARS-CoV-2 induces strong cross-protective antibodies to RaTG13 RBD
Structural and molecular analysis of the receptor binding domain of RaTG13, a coronavirus phylogenetically closely related to SARS-CoV-2, bound to the human receptor ACE2 as well as ACE2 orthologs in 24 other species provides a framework to understand its host range as well as the basis of antibody cross-reactivity between the two viruses.
A copper-catalyzed three-component reaction of in situ formed arynes, terminal alkynes, and O-benzoylhydroxylamines has been developed. By adjusting reaction conditions, the nucleophiles in this ...transformation can be extended from terminal alkynes to benzoxazoles. These procedures provide a modular and facile approach to o-alkynyl anilines and o-benzoxazolyl anilines from easily available substrates in only one step.
Schematic diagram for synthesis of porous α-Fe2O3 nanostructures from MIL-100(Fe).
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•Preservation of the morphology structure of the MIL-100(Fe) as both precursor and template via ...two-step calcination.•The BET surface area of α-Fe2O3 far higher than most of the previously reported values for α-Fe2O3 samples.•The reducible and acid properties of the catalyst were superior to the reference sample.•Excellent NH3-SCR activity with 100% NOx conversion in a broadened temperature window and high SO2 and H2O resistances.
A novel porous α-Fe2O3 nanocatalyst (Fe2O3-2S) was prepared via two-step controlled calcination process using MIL-100(Fe) as both precursor and template. The experimental results showed the preservation of the morphology structure of the original solid. A reference α-Fe2O3 catalyst (Fe2O3-1S) was also developed by one-step calcination, whose original morphology and structure collapsed. The samples were systematically characterized to assess structure, texture, morphology and surface composition, as well as reducibility and surface acidity. The Fe2O3-2S catalyst showed excellent NH3-SCR activity with 100 % NOx conversion from 250 to 325 °C and high SO2/H2O duration and stability. The catalytic performance of Fe2O3-2S was explained by the structural, morphological, and chemical properties of the sample, particularly, the high surface area (227 m2/g) and surface oxygen (Oα). In addition, the reducible and acid properties of this sample were superior to those of Fe2O3-1S, which were beneficial for the catalytic performance.
Aims
To investigate whether metabolic syndrome (MetS) could predict renal outcome in patients with established chronic kidney disease (CKD).
Materials and Methods
We enroled 2500 patients with CKD ...stage 1–4 from the Integrated CKD care programme, Kaohsiung for delaying Dialysis (ICKD) prospective observational study. 66.9% and 49.2% patients had MetS and diabetes (DM), respectively. We accessed three clinical outcomes, including all‐cause mortality, RRT, and 50% decline in estimated glomerular filtration rate events.
Results
The MetS score was positively associated with proteinuria, inflammation, and nutrition markers. In fully adjusted Cox regression, the hazard ratio (HR) (95% confidence interval) of MetS for composite renal outcome (renal replacement therapy, and 50% decline of renal function) in the DM and non‐DM subgroups was 1.56 (1.15–2.12) and 1.31 (1.02–1.70), respectively, while that for all‐cause mortality was 1.00 (0.71–1.40) and 1.27 (0.92–1.74). Blood pressure is the most important component of MetS for renal outcomes. In the 2 by 2 matrix, compared with the non‐DM/non‐MetS group, the DM/MetS group (HR: 1.62 (1.31–2.02)) and the non‐DM/MetS group (HR: 1.33 (1.05–1.69)) had higher risks for composite renal outcome, whereas the DM/MetS group had higher risk for all‐cause mortality (HR: 1.43 (1.09–1.88)).
Conclusions
MetS could predict renal outcome in patients with CKD stage 1–4 independent of DM.
Halloysite nanotubes (HNTs) as a natural and inexpensive clay mineral with hollow nanotubular structures, good biocompatibility and active surfaces have been ubiquitously applied in many fields. In ...this work, a novel multifunctional core-shell sorbent based on HNTs, CuCl2-HNTs encapsulated magnetic microspheres (SiO2@Fe3O4), was successfully fabricated and applied for Hg0 removal from flue gas with good performance for the first time. The core-shell structure prevented the composites from aggregating but kept their magnetism, which enabled the adsorbents being easily separated for reuse by an external magnetic field. In addition, the special structure also significantly enhanced the adsorption capacity of the composites by dispersing the CuCl2 modified HNTs on the prepared magnetic microspheres. The adsorption performance was comprehensively investigated and fitted by dynamic models. The adsorption followed surface adsorption, particle diffusion and chemisorption with very good SO2 tolerance. The Cu+, Cl- and lattice oxygen were the crucial components for Hg0 removal. In order to further understand the possible mechanism, an online home-made coupling system of temperature-programmed decomposition (TPD) was used to investigate the mercury species on the spent adsorbent in addition to X-ray photoelectron spectroscopy analysis. The results confirmed the mercury species adsorbed were primarily Hg0, HgO and HgCl2.
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•The novel Fe3O4@SiO2@Cu-MHNTs core-shell microspheres was firstly fabricated.•The composite was applied to remove Hg0 in flue gas with high efficiency.•The core-shell nano-material was reusable with thermal stability.•An online home-made coupling system of temperature-programmed decomposition studied the mercury fate.•Cl- and lattice oxygen play an important role in oxidation of Hg0.
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