Three-Component Regioselective Aryl- and Alkenyl-Aminoalkylation of Alkenes via Cooperative Photoredox/Nickel Catalysis.

Recently, metallaphotoredox-catalyzed alkene dicarbofunctionalization reactions have been extensively investigated. Most cases are related to alkyl-arylation processes by conjugate coupling of alkyl radical precursors and aryl electrophiles across alkenes. By contrast, reported examples of alkylvinylation by coupling of vinyl electrophiles are largely limited.

SARS-CoV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice.

The coronavirus disease of 2019 (COVID-19) pandemic has led to more than 700 million confirmed cases and nearly 7 million deaths. Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus mainly infects the respiratory system, neurological complications are widely reported in both acute infection and long-COVID cases. Despite the success of vaccines and antiviral treatments, neuroinvasiveness of SARS-CoV-2 remains an important question, which is also centered on the mystery of whether the virus is capable of breaching the barriers into the central nervous system.

Preclinical evaluation of therapeutic vaccines for chronic hepatitis B that stimulate antiviral activities of T cells and NKT cells.

Background & Aims: Liver diseases resulting from chronic HBV infection are a significant cause of morbidity and mortality. Vaccines that elicit T-cell responses capable of controlling the virus represent a treatment strategy with potential for long-term effects. Here, we evaluated vaccines that induce the activity of type I natural killer T (NKT) cells to limit viral replication and license stimulation of conventional antiviral T-cells.

Construction of Bridged Benzazepines via Photo-Induced Dearomatization.

Bridged benzazepine scaffolds, possessing unique structural and physicochemical activities, are widespread in various natural products and drugs. The construction of these skeletons often requires elaborate synthetic effort with low efficiency. Herein, we develop a simple and divergent approach for constructing various bridged benzazepines by a photocatalytic intermolecular dearomatization of naphthalene derivatives with readily available α-amino acids.

Nickel/Photoredox Dual-Catalyzed Regiodivergent Aminoalkylation of Unactivated Alkyl Halides.

A mild and regiodivergent aminoalkylation of unactivated alkyl halides is disclosed via a dual photoredox/nickel catalysis. Bipyridyl-type ligands without an -substituent control the site-selective coupling at the original position, while -disubstituted ligands tune the site-selectivity at a remote, unprefunctionalized position. Mechanistic studies combined with DFT calculations give insight into the mechanism and the origins of the ligand-controlled regioselectivity.

α-Tertiary Primary Amine Synthesis via Photocatalytic C(sp)-H Aminoalkylation.

Facile access to sterically hindered α-tertiary primary amines via photocatalytic radical coupling of native C(sp)-H substrates with -unsubstituted ketimines is reported. LiBr was used as a hydrogen atom transfer reagent to cleave C(sp)-H bonds to get alkyl radicals. The in situ-generated HBr can then serve as a Bronsted acid to activate -unsubstituted ketimines readily for single-electron reduction to deliver α-amino radicals.

Neural Oscillation Disorder in the Hippocampal CA1 Region of Different Alzheimer's Disease Mice.

Background: Alzheimer's disease (AD) is a well-known neurodegenerative disease that gradually induces neural network dysfunction and progressive memory deficits. Neural network activity is represented by rhythmic oscillations that influence local field potentials (LFPs). However, changes in hippocampal neural rhythmic oscillations in the early stage of AD remain largely unexplored.

Potent NKT cell ligands overcome SARS-CoV-2 immune evasion to mitigate viral pathogenesis in mouse models.

One of the major pathogenesis mechanisms of SARS-CoV-2 is its potent suppression of innate immunity, including blocking the production of type I interferons. However, it is unknown whether and how the virus interacts with different innate-like T cells, including NKT, MAIT and γδ T cells. Here we reported that upon SARS-CoV-2 infection, invariant NKT (iNKT) cells rapidly trafficked to infected lung tissues from the periphery.

Three-component reductive conjugate addition/aldol tandem reaction enabled by nickel/photoredox dual catalysis.

A three-component reductive cross-coupling of aryl halides, aldehydes, and alkenes by nickel/photoredox dual catalysis is disclosed. The key to success for this tandem transformation is to identify α-silylamine as a unique organic reductant, which releases silylium ions instead of protons to prevent unwanted protonation processes, and meanwhile serves as Lewis acid to activate aldehydes . This dual catalytic protocol completes a traditional conjugate addition/aldol sequence that eliminates the requirement of organometallic reagents and metal-based reductants, thus providing a mild synthetic route to highly valuable β-hydroxyl carbonyl compounds with contiguous 1,2-stereocenters.

Microglia innate immune response contributes to the antiviral defense and blood-CSF barrier function in human choroid plexus organoids during HSV-1 infection.

The choroid plexus (ChP) is the source of cerebrospinal fluid (CSF). The ChP-CSF system not only provides the necessary cushion for the brain but also works as a sink for waste clearance. During sepsis, pathogens and host immune cells can weaken the ChP barrier and enter the brain, causing cerebral dysfunctions known as sepsis-associated encephalophagy.

Evaluation of strategies for the occupational health risk assessment of chemical toxicants in the workplace based on a quantitative analysis model.

Objectives: The commonly used methods for the occupational health risk assessment (OHRA) of chemical toxicants cannot fully meet the needs of practical work. This study evaluated OHRA strategies for chemical toxicants in the workplace by establishing a quantitative analysis model.

Methods: Five typical industries in China that implement OHRA using the six common models (the Environmental Protection Agency, Australian, Romanian, Singaporean, International Council on Mining and Metals, and the Control of Substances Hazardous to Health models) were selected as the research objects.

Remote and Proximal Hydroaminoalkylation of Alkenes Enabled by Photoredox/Nickel Dual Catalysis.

A mild and site-selective hydroaminoalkylation of activated and unactivated alkenes via dual photoredox/Ni catalysis is developed. This dual catalytic strategy enables exclusive access to α-selective products, which is complementary to previously reported photocatalytic hydroaminoalkylation of activated alkenes that provides the β-selective products. The chain-walking of a Ni-H intermediate toward a carbonyl allows for the hydroaminoalkylation of unactivated alkenes at remote C-H sites.

Nickel-Catalyzed Three-Component Alkylacylation of Alkenes Enabled by a Photoactive Electron Donor-Acceptor Complex.

An electron donor-acceptor complex-enabled, nickel-catalyzed three-component net-reductive 1,2-alkylacylation of alkenes is developed. This conjunctive reductive acyl cross-coupling process obviates the use of an exogenous photocatalyst and a stoichiometric metal-based reductant, affording various synthetically useful 1,3-dicarbonyl compounds in good yields with a broad substrate scope and excellent functional group tolerance. Both alkyl and acyl electrophiles are derived from the highly abundant and readily accessible carboxylic acids, making the catalytic 1,2-dicarbofunctionalization more synthetically general and sustainable.

Global profiling reveals common and distinct N6-methyladenosine (m6A) regulation of innate immune responses during bacterial and viral infections.

N-methyladenosine (mA) is a dynamic post-transcriptional RNA modification influencing all aspects of mRNA biology. While mA modifications during numerous viral infections have been described, the role of mA in innate immune response remains unclear. Here, we examined cellular mA epitranscriptomes during infections of Pseudomonas aeruginosa and herpes simplex virus type 1 (HSV-1), and lipopolysaccharide (LPS) stimulation to identify mA-regulated innate immune response genes.

Wavefront shaping for reconfigurable beam steering in lithium niobate multimode waveguide.

Reconfigurable photonic devices are important constituents for future optical integrated circuits, where electro-optic manipulation of the light field in a lithium niobate (LN) waveguide is one of the promising solutions. Herein, we demonstrate a paradigm shift of the beam steering mechanism where reconfigurable beam steering is enabled by the wavefront shaping technology. Furthermore, this strategy is fully compatible with the electro-optic tuning mechanism of the LN multimode waveguide, where microstructured serrated array electrodes are employed to fine tune the output beam upon its reconfigurable output position.

From Esters to Ketones via a Photoredox-Assisted Reductive Acyl Cross-Coupling Strategy.

A method was developed for ketone synthesis via a photoredox-assisted reductive acyl cross-coupling (PARAC) using a nickel/photoredox dual-catalyzed cross-electrophile coupling of two different carboxylic acid esters. A variety of aryl, 1°, 2°, 3°-alkyl 2-pyridyl esters can act as acyl electrophiles while N-(acyloxy)phthalimides (NHPI esters) act as 1°, 2°, 3°-radical precursors. Our PARAC strategy provides an alternative and reliable way to synthesize various sterically congested 3°-3°, 3°-2°, and aryl-3° ketones under mild and highly unified conditions, which have been otherwise difficult to access.

SARS-CoV-2 Nsp5 Demonstrates Two Distinct Mechanisms Targeting RIG-I and MAVS To Evade the Innate Immune Response.

Newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic with astonishing mortality and morbidity. The high replication and transmission of SARS-CoV-2 are remarkably distinct from those of previous closely related coronaviruses, and the underlying molecular mechanisms remain unclear. The innate immune defense is a physical barrier that restricts viral replication.

Experimental generation of perfect optical vortices through strongly scattering media.

Perfect optical vortices enable the unprecedented optical multiplexing utilizing orbital angular momentum of light, which, however, suffer from distortion when they propagate in inhomogeneous media. Herein, we report on the experimental demonstration of perfect optical vortice generation through strongly scattering media. The transmission-matrix-based point-spread-function engineering is applied to encode the targeted mask in the Fourier domain before focusing.

N-Cyanation of Primary and Secondary Amines with Cyanobenzio-doxolone (CBX) Reagent.

An efficient electrophilic N-cyanation of amines with a stable and less-toxic cyanobenziodoxole reagent towards the synthesis of cyanamides is disclosed. This synthetically practicable strategy allows the construction of a wide variety of cyanamides under very mild and simple conditions with a broad functional group compatibility, and showcases a huge potential in late-stage modification of complex molecules.

Exposure characterization and risk assessment of ultrafine particles from the blast furnace process in a steelmaking plant.

Objectives: This study aimed to clarify the exposure characteristics and risks of ultrafine particles from the blast furnace process and to provide a reasonable control strategy for protecting the health of workers.

Methods: The blast furnace location of a steelmaking plant was selected as a typical investigation site. A membrane-based sampling system was used to collect ultrafine particles to analyze their morphology and elemental compositions.

Characteristics and risk assessment of occupational exposure to ultrafine particles generated from cooking in the Chinese restaurant.

Ultrafine particles have been increasingly linked to adverse health effects in restaurant workers. This study aimed to clarify the exposure characteristics and risks of ultrafine particles during the cooking process, and to provide a reasonable standard for protecting the workers in the Chinese restaurant. The temporal variations in particle concentrations (number concentration (NC), mass concentration (MC), surface area concentration (SAC), and personal NC), and size distributions by number were measured by real-time system.

Facile and Modular Pipeline for Protein-Specific Antibody Customization.

Antibodies are fundamental tools for basic science; however, high-quality antibodies suitable for multiple experimental applications are often inaccessible to research laboratories. To this end, a modular and low-cost pipeline for small-scale antibody customization is developed. First, soluble antigens are designed according to the secondary structure of a desired protein.