Pathway-divergent coupling of 1,3-enynes with acrylates through cascade cobalt catalysis.

Catalytic cascade transformations of simple starting materials into highly functionalized molecules bearing a stereochemically defined multisubstituted alkene, which are important in medicinal chemistry, natural product synthesis, and material science, are in high demand for organic synthesis. The development of multiple reaction pathways accurately controlled by catalysts derived from different ligands is a critical goal in the field of catalysis. Here we report a cobalt-catalyzed strategy for the direct coupling of inexpensive 1,3-enynes with two molecules of acrylates to construct a high diversity of functionalized 1,3-dienes containing a trisubstituted or tetrasubstituted olefin. Such cascade reactions can proceed through three different pathways initiated by oxidative cyclization to achieve multiple bond formation in high chemo-, regio- and stereoselectivity precisely controlled by ligands, providing a platform for the development of tandem carbon-carbon bond-forming reactions.

Causal Effects of COVID-19 on the Risk of Thrombosis: A Two-Sample Mendel Randomization Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) and thrombosis are linked, but the biomolecular mechanism is unclear. We aimed to investigate the causal relationship between COVID-19 and thrombotic biomarkers. METHODS: We used two-sample Mendelian randomization (MR) to assess the effect of COVID-19 on 20 thrombotic biomarkers. We estimated causality using inverse variance weighting with multiplicative random effect, and performed sensitivity analysis using weighted median, MR-Egger regression and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods. All the results were examined by false discovery rate (FDR) with the Benjamin and Hochberg method for this correction to minimize false positives. We used R language for the analysis. RESULTS: All COVID-19 classes showed lower levels of tissue factor pathway inhibitor (TFPI) and interleukin-1 receptor type 1 (IL-1R1). COVID-19 significantly reduced TFPI (odds ratio [OR] = 0.639, 95% confidence interval [CI]: 0.435-0.938) and IL-1R1 (OR = 0.603, 95% CI = 0.417-0.872), nearly doubling the odds. We also found that COVID-19 lowered multiple coagulation factor deficiency protein 2 and increased C-C motif chemokine 3. Hospitalized COVID-19 cases had less plasminogen activator, tissue type (tPA) and P-selectin glycoprotein ligand 1 (PSGL-1), while severe cases had higher mean platelet volume (MPV) and lower platelet count. These changes in TFPI, tPA, IL-1R1, MPV, and platelet count suggested a higher risk of thrombosis. Decreased PSGL-1 indicated a lower risk of thrombosis. CONCLUSION: TFPI, IL-1R, and seven other indicators provide causal clues of the pathogenesis of COVID-19 and thrombosis. This study demonstrated that COVID-19 causally influences thrombosis at the biomolecular level.

Photoredox cobalt-catalyzed regio-, diastereo- and enantioselective propargylation of aldehydes via propargyl radicals.

Catalytic enantioselective introduction of a propargyl group constitutes one of the most important carbon-carbon forming reactions, as it is versatile to be transformed into diverse functional groups and frequently used in the synthesis of natural products and biologically active molecules. Stereoconvergent transformations of racemic propargyl precursors to a single enantiomer of products via propargyl radicals represent a powerful strategy and provide new reactivity. However, only few Cu- or Ni-catalyzed protocols have been developed with limited reaction modes. Herein, a photoredox/cobalt-catalyzed regio-, diastereo- and enantioselective propargyl addition to aldehydes via propargyl radicals is presented, enabling construction of a broad scope of homopropargyl alcohols that are otherwise difficult to access in high efficiency and stereoselectivity from racemic propargyl carbonates. Mechanistic studies and DFT calculations provided evidence for the involvement of propargyl radicals, the origin of the stereoconvergent process and the stereochemical models.

Cobalt-Catalyzed Regiodivergent and Enantioselective Intermolecular Coupling of 1,1-Disubstituted Allenes and Aldehydes.

Catalytic enantioselective coupling of 1,1-disubstituted allenes and aldehydes through regiodivergent oxidative cyclization followed by stereoselective protonation or reductive elimination promoted by chiral phosphine-Co complexes is presented. Such processes represent unprecedented and unique reaction pathways for Co catalysis that enable catalytic enantioselective generation of metallacycles with divergent regioselectivity accurately controlled by chiral ligands, affording a wide range of allylic alcohols and homoallylic alcohols that are otherwise difficult to access without the need of pre-formation of stoichiometric amounts of alkenyl- and allyl-metal reagents in up to 92 % yield, >98 : 2 regioselectivity, >98 : 2 dr and >99.5 : 0.5 er.

Study on Staged Damage Behaviors of Rock-like Materials with Different Brittleness Degrees Based on Multiple Parameters.

Understanding the brittle fracture behavior of rock is crucial for engineering and Earth science. In this paper, based on acoustic emission (AE) and laser Doppler vibration (LDV) monitoring technology, the staged damage behaviors of rock-like materials with different brittleness degrees under uniaxial compression are studied via multiple parameters. The results show that the brittleness degree determines the fracture mode. As the specimen's brittleness degree increases, the tensile failure increases and shear failure decreases. AE activity is enhanced at the crack damage point. With an increasing specimen brittleness degree, different instability precursor information is shown during the unstable crack growth stage: the AE b value changes from the fluctuating to continuously decreasing state, and the natural frequency changes from the stable fluctuation to upward fluctuation state. The AE b value near the stress drop is the smallest, and it decreases with an increasing brittleness degree. The natural frequency reduction indicates the rock-like fracture. The natural frequency is a symbolic index that reflects staged damage characteristics and predicts the amount of energy released by brittle failure. These findings provide guidelines for rock stability monitoring and provide support for better responses to stability evaluations of rock slopes, rock collapses, and tunnel surrounding rock in engineering.

Cobalt-Catalyzed Diastereo- and Enantioselective Carbon-Carbon Bond Forming Reactions of Cyclobutenes.

Catalytic enantioselective functionalization of cyclobutenes constitutes a general and modular strategy for construction of enantioenriched complex cyclobutanes bearing multiple stereogenic centers, as chiral four-membered rings are common motifs in biologically active molecules and versatile intermediates in organic synthesis. However, enantioselective synthesis of cyclobutanes through such a strategy remained significantly limited. Herein, we report a series of unprecedented cobalt-catalyzed carbon-carbon bond forming reactions of cyclobutenes that are initiated through enantioselective carbometalation. The protocols feature diastereo- and enantioselective introduction of allyl, alkynyl, and functionalized alkyl groups. Mechanistic studies indicated an unusual 1,3-cobalt migration and subsequent ß-carbon elimination cascade process occurred in the allyl addition. These new discoveries established a new elementary process for cobalt catalysis and an extension of diversity of nucleophiles for enantioselective transformations of cyclobutenes.

Integrative Bioinformatics Analysis of mRNA Expression Profiles of Mice to Explore the Key Genes Involved in Crim1 Mutation-Induced Congenital Cataracts.

Crim1 has been implicated in cataracts in mice and is of great importance in the development of the eye in both humans and mice. Therefore, we aimed to clarify how Crim1 mutations affect lens development and the molecular mechanism of cataracts in mice through comprehensive bioinformatics analysis. The microarray chip was downloaded from the GEO database to obtain the gene expression profile data set. Differentially expressed genes (DEGs) were screened using the limma package. GO and KEGG analyses of DEGs were performed using the DAVID database. Then, we established the protein-protein interaction (PPI) network in Cytoscape. Next, we used MCODE to analyze the data. We obtained 750 DEGs in total, including 407 upregulated DEGs and 343 downregulated DEGs. GO analysis showed that the DEGs were mainly related to biological processes, such as apoptosis, cell translation and the immune system. KEGG analysis showed that the enriched functions and pathways were related to the processing and presentation of ribosomes, lysosomes, and antigens. We identified 18 HUB genes, among which four core genes, C1qa, C1qb, C1qc, and Cd74, were closely related to congenital cataracts induced by Crim1 mutation. This study reveals the molecular pathogenesis of congenital cataracts induced by Crim1, and this information is expected to facilitate clinical genetic testing, molecular diagnosis, prognosis, and individualized chemotherapy for congenital cataracts (CC).

Profile of biological characterizations and clinical application of corneal stem/progenitor cells.

Corneal stem/progenitor cells are typical adult stem/progenitor cells. The human cornea covers the front of the eyeball, which protects the eye from the outside environment while allowing vision. The location and function demand the cornea to maintain its transparency and to continuously renew its epithelial surface by replacing injured or aged cells through a rapid turnover process in which corneal stem/progenitor cells play an important role. Corneal stem/progenitor cells include mainly corneal epithelial stem cells, corneal endothelial cell progenitors and corneal stromal stem cells. Since the discovery of corneal epithelial stem cells (also known as limbal stem cells) in 1971, an increasing number of markers for corneal stem/progenitor cells have been proposed, but there is no consensus regarding the definitive markers for them. Therefore, the identification, isolation and cultivation of these cells remain challenging without a unified approach. In this review, we systematically introduce the profile of biological characterizations, such as anatomy, characteristics, isolation, cultivation and molecular markers, and clinical applications of the three categories of corneal stem/progenitor cells.

Cobalt-Catalyzed Regio-, Diastereo- and Enantioselective Intermolecular Hydrosilylation of 1,3-Dienes with Prochiral Silanes.

One of the most straightforward approaches to access chiral silanes is catalytic enantioselective hydrosilylation. Although significant advances have been achieved in enantioselective construction of either a carbon-stereogenic center or a silicon-stereogenic center through enantioselective hydrosilylation, simultaneous establishment of a carbon- and a silicon-stereogenic center in an acyclic molecule through a single intermolecular hydrosilylation remained undeveloped. Herein, an unprecedented cobalt-catalyzed regio-, diastereo- and enantioselective hydrosilylation of 1,3-dienes is presented, enabling construction of a carbon- and a silicon-stereogenic center in a single intermolecular transformation. A wide range of chiral silanes bearing a carbon- and a silicon-stereogenic center were generated in high efficiency and stereoselectivity. Functionalization of the enantioenriched silanes delivered a variety of valuable chiral building blocks that are otherwise difficult to access.

Cobalt-Catalyzed Sequential Site- and Stereoselective Hydrosilylation of 1,3- and 1,4-Enynes.

Catalytic sequential hydrosilylation of 1,3-enynes and 1,4-enynes promoted by cobalt complexes derived from bisphosphines are presented. Site- and stereoselective Si-H addition of primary silanes to 1,3-enynes followed by sequential intramolecular diastereo- and enantioselective Si-H addition afforded enantioenriched cyclic alkenylsilanes with simultaneous construction of a carbon-stereogenic center and a silicon-stereogenic center. Reactions of 1,4-enynes proceeded through sequential isomerization of the alkene moiety followed by site- and stereoselective hydrosilylation. A wide range of alkenylsilanes were afforded in high efficiency and selectivity. Functionalization of the enantioenriched silanes containing a stereogenic center at silicon delivered a variety of chiral building blocks that are otherwise difficult to access.

Cobalt-Catalyzed Diastereo- and Enantioselective Reductive Allyl Additions to Aldehydes with Allylic Alcohol Derivatives via Allyl Radical Intermediates.

Catalytic generation of ambiphilic π-allyl-metal complexes and their utility in enantioselective transformations constitutes a powerful approach for introduction of allyl groups to a molecule. Herein an unprecedented cobalt-catalyzed highly site-, diastereo-, and enantioselective protocol for stereoselective formation of nucleophilic allyl-Co(II) complexes followed by addition to aldehydes is presented. The reaction features diastereo- and enantioconvergent conversion of easily accessible allylic alcohol derivatives to diversified enantioenriched homoallylic alcohols with a remarkably broad scope of allyl groups that can be introduced. Mechanistic studies indicated that allyl radical intermediates were involved in this process. These new discoveries establish a new strategy for development of enantioselective transformations through capture of radicals by chiral Co complexes, pushing forward the frontier of Co complexes for enantioselective catalysis.

Effects of brewing water on the sensory attributes and physicochemical properties of tea infusions.

The effects of brewing water on the sensory attributes and physicochemical properties of tea infusions made from Chinese teas were investigated. The tea infusions brewed in water with higher pH and total dissolved solids (TDS), generally had a darker color and lower overall sensory acceptability. Moreover, those infusions had less catechins, particularly galloylated-catechins, and lower antioxidant capacity. The teas with less fermentation contained more galloylated-catechins and had higher antioxidant capacity, but were much more susceptible to high mineral brewing water. Green tea was proved to be the most susceptible one, whereas dark tea the most stable one. Green tea infusions prepared with higher pH/TDS water were more rapidly oxidized, resulting in a darker color due to polymerization of catechins, when exposed to the air. These findings suggested that low mineral brewing water was better for Chinese tea, both from the sensory and health benefit perspectives.

Cobalt-Catalyzed Diastereo- and Enantioselective Hydroalkylation of Cyclopropenes with Cobalt Homoenolates.

Catalylic diastereo- and enantioselective hydroalkylation of 3,3-disubstituted cyclopropenes with Co-homoenolate generated in situ from ring-opening of easily accessible cyclopropanols promoted by a chiral phosphine-cobalt complex is presented. Such a process represents the unprecedented and direct introduction of a wide range of functionalized alkyl groups without the need of pre-formation of stoichiometric amounts of organometallic reagents onto the cyclopropane motif, affording multi-substituted cyclopropanes in up to 99 % yield with >95:5 dr and 98:2 er. Functionalization of the products delivered enantioenriched cyclopropanes that are otherwise difficult to access.

Effective Antibacterial Glass Fiber Membrane Prepared by Plasma-Enhanced Chemical Grafting.

This paper reports a novel glass fiber membrane with an effective antibacterial performance by chemical grafting of quaternary ammonium salt (QAS) which is enhanced by a plasma bombardment technique. Plasma bombardment as a pretreatment of the membrane can increase the QAS anchored on the membrane from 0.8 to 1.3 wt %. The chemical grafting technique can increase the membrane zeta potential from negative values to positive values in aqueous solutions at various pHs. Furthermore, the plasma-enhanced chemical-grafting membrane has more positive zeta potentials (49.0 mV at pH = 7) than the chemical-grafting membrane without the plasma bombardment technique (38.9 mV at pH = 7). In the antibacterial performance evaluation, the Escherichia coli survival rate decreased from 127.0% of the pristine membrane to 4.1 and 11.3% of the plasma-enhanced chemical-grafting membrane and the chemical-grafting membrane, respectively. In addition, the plasma-enhanced chemical-grafting membrane shows durable antibacterial activity against E. coli with copious water rinsing as much as 3 L·cm-2.

Cobalt-Catalyzed Diastereo- and Enantioselective Hydroalkenylation of Cyclopropenes with Alkenylboronic Acids.

Catalytic diastereo- and enantioselective hydroalkenylation of 3,3-disubstituted cyclopropenes with readily accessible alkenylboronic acids, promoted by a chiral phosphine/Co complex, is presented. Such a process constitutes the unprecedented and direct introduction of a wide range of alkenyl groups onto the cyclopropane motif to afford multisubstituted cyclopropanes in up to 95 % yield with greater than 95:5 d.r. and 99:1 e.r. Functionalization of the products delivered enantioenriched cyclopropanes that are otherwise difficult to access.

Cu-Catalyzed Enantioselective Reductive Coupling of 1,3-Dienes and Aldimines.

Catalytic chemo- and enantioselective generation of 1,3-disubstituted allyl-Cu complexes from a Cu-H addition to 1,3-dienes followed by in situ reactions with aldimines to construct homoallylic amines is presented. The method is distinguished by an unprecedented pathway to generate enantiomerically enriched allyl-Cu species, allowing reactions with a wide range of aldimines in high chemo-, site-, diastereo-, and enantioselectivity. Functionalization provides useful building blocks that are otherwise difficult to access.

N-Heterocyclic Carbene-Cu-Catalyzed Enantioselective Allenyl Conjugate Addition.

A catalytic enantioselective conjugate addition with commercially available allenylboronic acid pinacol ester as nucleophile promoted by a chiral copper complex of N-heterocyclic carbene (NHC) is disclosed. This process constitutes an unprecedented instance of the conjugate addition that introduces an allenyl group into α,ß-unsaturated carbonyl compounds, affording products that are otherwise difficult to access in up to 92% yield, >98% allenyl addition selectivity and 96:4 enantiomeric ratio. DFT calculations were performed to elucidate the origins of enantioselectivity.

Cu-catalyzed regioselective borylcyanation of 1,3-dienes.

Catalytic regioselective generation of an allyl-Cu complex through Cu-B(pin) (pin = pinacolato) addition to 1,3-dienes followed by reaction with an electrophilic cyanation reagent to afford multifunctional organoboron compounds is presented. Reactions of a wide range of 1,3-dienes with different substitution patterns promoted by an easily accessible phosphine-Cu complex proceed with high yields and regioselectivity.

Cu-catalyzed enantioselective synthesis of tertiary benzylic copper complexes and their in situ addition to carbonyl compounds.

Catalytic chemo- and enantioselective generation of tertiary benzylic copper complexes from Cu-B(pin) (pin = pinacolato) additions to 1,1-disubstituted alkenes followed by in situ reactions with ketones and carboxylic acid phenol esters to construct multifunctional alkylboron compounds that contain quaternary stereogenic centers is presented. The method is distinguished by the unprecedented reaction mode of tertiary benzylic Cu complexes, allowing reaction with a wide range of carbonyl electrophiles in good yields and with high chemo-, site-, diastereo- and enantioselectivity. The catalytic protocol was performed with easily accessible chiral ligands and copper salts at ambient temperature. Functionalization of multifunctional alkylboron products provides useful building blocks that are otherwise difficult to access.