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Enantioenriched alcohols found in an array of bioactive natural products and pharmaceutical agents are often synthesized by asymmetric nucleophilic addition to carbonyls. However, this approach generally shows limited functional-group compatibility, requiring the use of preformed organometallic reagents in conjunction with a stoichiometric or substoichiometric amount of chiral controller to deliver optically active alcohols. Herein we report a copper-catalyzed strategy for the stereoselective nucleophilic addition of propargylic and other alkyl groups to ketones, using easily accessible (poly)unsaturated hydrocarbons as latent carbanion equivalents. Our method features the catalytic generation of highly enantioenriched organocopper intermediates and their subsequent diastereoselective addition to ketones, allowing for the effective construction of highly substituted stereochemical dyads with excellent stereocontrol. Moreover, this process is general, scalable, and occurs at ambient temperature.

In order to solve the problem that alumina based ceramic core is not easy to remove core, a certain amount of PA66 fiber was added as pore forming material to prepare porous aluminum based ceramic core by hot pressing. The influence of PA66 fiber content on the porosity, room temperature bending strength and sintering shrinkage of aluminum based ceramic core was investigated, and the mechanism of PA66 fiber content on the porosity of aluminum based ceramic core was analyzed. The results show that the porosity of alumina based ceramic core is significantly increased by adding PA66 fiber, and the sintering shrinkage of the core is effectively blocked. With the increase of PA66 fiber, the porosity of alumina based ceramic core is increased, and the bending strength and line shrinkage rate at room temperature are decreased. When the PA66 fiber content is 0.9%(mass fraction), the porosity of the aluminum based ceramic core is 41.14%, the bending strength is 15.33 MPa, and the linear shrinkage rate is 0.418%.

The vibration failure issue of the motor control unit during the vibration test was studied,and the reasons of the failure were analyzed by applying spectrum analysis method,the results showed that the coupled vibration is the main reason of the vibration failure. The optimization schemes against this problem were designed,the octave criterion was applied to design the component for avoiding coupled vibration,and the damping was increased to decrease the peak of the vibration response. The optimization schemes were verified by simulation and experiment,the results showed the vibration acceleration decreased by 23% ～ 31% using octave criterion design,and decreased by 25% ～ 34% through increasing damping. The conclusion can be drawn that two optimization ways can decrease vibration acceleration level obviously,and the fatigue durability of the product was improved.

Blastocystis sp. is an important gastrointestinal parasite with global distribution, prevalent in humans, farmed animals, and wildlife. Therefore, this study aimed to investigate the prevalence and genetic diversity of Blastocystis sp. in Asiatic brush-tailed porcupines (Atherurus macrourus), bamboo rats (Rhizomys pruinosus), and masked palm civets (Paguma larvata) in Hainan Province, China. A total of 900 fecal samples were collected from three farmed animal species including 257 porcupines, 360 rats, and 283 civets. Genomic DNA was extracted from each fecal sample and Blastocystis sp. was detected by PCR at the small subunit ribosomal RNA (SSU rRNA) gene. A phylogenetic tree was constructed using the maximum likelihood method. Blastocystis sp. was detected in 47 (5.2%) fecal samples: 12 (4.7%) Asiatic brush-tailed porcupines, 8 (2.2%) bamboo rats, and 27 (9.5%) masked palm civets. Three known Blastocystis sp. subtypes, including ST1, ST4, ST5, and one unnamed subtype (unST), were found in one, 19, 26, and one animal, respectively. Subtypes ST4 and unST were detected in porcupines, ST4 in rats, and ST1 and ST5 in civets. Our results suggest that the three farmed animal species reported in this study could serve as reservoirs for potentially zoonotic Blastocystis sp. subtypes and transmit this parasite to humans, other farmed animals, and wildlife.

We investigate the structures of hydrated electrons (e−aq) in one of water's solid phases, namely, clathrate hydrates (CHs). Using density functional theory (DFT) calculations, DFT-based ab initio molecular dynamics (AIMD), and path-integral AIMD simulations with periodic boundary conditions, we find that the structure of the e−aq@node model is in good agreement with the experiment, suggesting that an e−aq could form a node in CHs. The node is a H2O defect in CHs that is supposed to be composed of four unsaturated hydrogen bonds. Since CHs are porous crystals that possess cavities that can accommodate small guest molecules, we expect that these guest molecules can be used to tailor the electronic structure of the e−aq@node, and it leads to experimentally observed optical absorption spectra of CHs. Our findings have a general interest and extend the knowledge of e−aq into porous aqueous systems. [ABSTRACT FROM AUTHOR]

Understanding, predicting, and ultimately controlling exciton band structure and exciton dynamics are central to diverse chemical and materials problems. Here, we have developed a first-principles method to determine exciton dispersion and exciton–phonon interaction in semiconducting and insulating solids based on time-dependent density functional theory. The first-principles method is formulated in planewave bases and pseudopotentials and can be used to compute exciton band structures, exciton charge density, ionic forces, the non-adiabatic coupling matrix between excitonic states, and the exciton–phonon coupling matrix. Based on the spinor formulation, the method enables self-consistent noncollinear calculations to capture spin-orbital coupling. Hybrid exchange-correlation functionals are incorporated to deal with long-range electron–hole interactions in solids. A sub-Hilbert space approximation is introduced to reduce the computational cost without loss of accuracy. For validations, we have applied the method to compute the exciton band structure and exciton–phonon coupling strength in transition metal dichalcogenide monolayers; both agree very well with the previous GW-Bethe–Salpeter equation and experimental results. This development paves the way for accurate determinations of exciton dynamics in a wide range of solid-state materials. [ABSTRACT FROM AUTHOR]

In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, China).sup.1; it soon spread across the world. In this ongoing pandemic, public health concerns and the urgent need for effective therapeutic measures require a deep understanding of the epidemiology, transmissibility and pathogenesis of COVID-19. Here we analysed clinical, molecular and immunological data from 326 patients with confirmed SARS-CoV-2 infection in Shanghai. The genomic sequences of SARS-CoV-2, assembled from 112 high-quality samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) dataset, showed a stable evolution and suggested that there were two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially reduced CD4.sup.+ and CD8.sup.+ T cell counts upon hospital admission, was predictive of disease progression. High levels of interleukin (IL)-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such as age and lymphocytopenia (and its associated cytokine storm), whereas viral genetic variation did not significantly affect outcomes. Genome sequences from 112 patients with confirmed SARS-CoV-2 infection showed two clades of SARS-CoV-2 virus with similar virulence and clinical outcome, and clinical data from 326 cases suggest that T cell depletion and cytokine bursts are associated with a worse prognosis., Author(s): Xiaonan Zhang [sup.1] , Yun Tan [sup.2] , Yun Ling [sup.1] , Gang Lu [sup.2] , Feng Liu [sup.2] , Zhigang Yi [sup.1] [sup.3] , Xiaofang Jia [sup.1] , [...]

Viruses rely on host chaperone network to support their infection. In particular, the endoplasmic reticulum (ER) resident chaperones play key roles in synthesizing and processing viral proteins. Influx of a large amount of foreign proteins exhausts the folding capacity in ER and triggers the unfolded protein response (UPR). A fully-executed UPR comprises signaling pathways that induce ER folding chaperones, increase protein degradation, block new protein synthesis and may eventually activate apoptosis, presenting both opportunities and threats to the virus. Here, we define a role of the MHV-68M1 gene in differential modulation of UPR pathways to enhance ER chaperone production. Ectopic expression of M1 markedly induces ER chaperone genes and expansion of ER. The M1 protein accumulates in ER during infection and this localization is indispensable for its function, suggesting M1 acts from the ER. We found that M1 protein selectively induces the chaperon-producing pathways (IRE1, ATF6) while, interestingly, sparing the translation-blocking arm (PERK). We identified, for the first time, a viral factor capable of selectively intervening the initiation of ER stress signaling to induce chaperon production. This finding provides a unique opportunity of using viral protein as a tool to define the activation mechanisms of individual UPR pathways.

Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. It is expressed in advanced primary melanoma and metastasis but rarely in benign naevi or normal melanocytes. More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in melanoma progression and metastasis. However, the natural MCAM binding ligand that initiates MCAM activation in melanoma so far remains elusive. This study revealed that galectin-3, a galactoside-binding protein that is commonly overexpressed in many cancers including melanoma, is naturally associated with MCAM on the surface of both skin and uveal melanoma cells. Binding of galectin-3 to MCAM, via O-linked glycans on the MCAM, induces MCAM dimerization and clustering on cell surface and subsequent activation of downstream AKT signalling. This leads to the increases of a number of important steps in melanoma progression of cell proliferation, adhesion, migration, and invasion. Thus, galectin-3 is a natural binding ligand of MCAM in melanoma, and their interaction activates MCAM and promotes MCAM-mediated melanoma progression. Targeting the galectin-3–MCAM interaction may potentially be a useful therapeutic strategy for melanoma treatment.

The three EglN prolyl hydroxylases (EglN1, EglN2, and EglN3) regulate the stability of the HIF transcription factor. We recently showed that loss of EglN2, however, also leads to down-regulation of Cyclin D1 and decreased cell proliferation in a HIF-independent manner. Here we report that EglN2 can hydroxylate FOXO3a on two specific prolyl residues in vitro and in vivo. Hydroxylation of these sites prevents the binding of USP9x deubiquitinase, thereby promoting the proteasomal degradation of FOXO3a. FOXO transcription factors can repress Cyclin D1 transcription. Failure to hydroxylate FOXO3a promotes its accumulation in cells, which in turn suppresses Cyclin D1 expression. These findings provide new insights into post-transcriptional control of FOXO3a and provide a new avenue for pharmacologically altering Cyclin D1 activity.