Palladium-Catalyzed Intramolecular Hydroaminocarbonylation to Lactams: Additive-Free Protocol Initiated by Palladium Hydride

A palladium-catalyzed intramolecular hydroaminocarbonylation of 2-vinylbenzylamines in the absence of acidic or any other additives was realized via rational designing the catalytic system on the basis of mechanistic studies, which allows for the synthesis of a variety of six-membered lactams in good to excellent yields with high regioselectivity. The postulated palladium-hydride intermediate for initiating the hydroaminocarbonylation has been identified and directly used as a catalyst for the reaction. Further kinetic studies illustrated that the reaction rate is negative first-order-dependent on the substrate concentration with palladium hydride as a catalyst

Palladium-Catalyzed Intramolecular Hydroaminocarbonylation to Lactams: Additive-Free Protocol Initiated by Palladium Hydride

A palladium-catalyzed intramolecular hydroaminocarbonylation of 2-vinylbenzylamines in the absence of acidic or any other additives was realized via rational designing the catalytic system on the basis of mechanistic studies, which allows for the synthesis of a variety of six-membered lactams in good to excellent yields with high regioselectivity. The postulated palladium-hydride intermediate for initiating the hydroaminocarbonylation has been identified and directly used as a catalyst for the reaction. Further kinetic studies illustrated that the reaction rate is negative first-order-dependent on the substrate concentration with palladium hydride as a catalyst

Membrane Wrapping Efficiency of Elastic Nanoparticles during Endocytosis: Size and Shape Matter

Using coarse-grained molecular dynamics simulations, we systematically investigate the receptor-mediated endocytosis of elastic nanoparticles (NPs) with different sizes, ranging from 25 to 100 nm, and shapes, including sphere-like, oblate-like, and prolate-like. Simulation results provide clear evidence that the membrane wrapping efficiency of NPs during endocytosis is a result of competition between receptor diffusion kinetics and thermodynamic driving force. The receptor diffusion kinetics refer to the kinetics of receptor recruitment that are affected by the contact edge length between the NP and membrane. The thermodynamic driving force represents the amount of required free energy to drive NPs into a cell. Under the volume constraint of elastic NPs, the soft spherical NPs are found to have similar contact edge lengths to rigid ones and to less efficiently be fully wrapped due to their elastic deformation. Moreover, the difference in wrapping efficiency between soft and rigid spherical NPs increases with their sizes, due to the increment of their elastic energy change. Furthermore, because of its prominent large contact edge length, the oblate ellipsoid is found to be the least sensitive geometry to the variation in NP’s elasticity among the spherical, prolate, and oblate shapes during the membrane wrapping. In addition, simulation results indicate that conflicting experimental observations on the efficiency of cellular uptake of elastic NPs could be caused by their different mechanical properties. Our simulations provide a detailed mechanistic understanding about the influence of NPs’ size, shape, and elasticity on their membrane wrapping efficiency, which serves as a rational guidance for the design of NP-based drug carriers

An Efficient Synthesis of Chiral Diamines with Rigid Backbones: Application in Enantioselective Michael Addition of Malonates to Nitroalkenes

A new and efficient route for synthesis of enantiomerically pure biisoindoline and its isomer based on the diaza-Cope rearrangement reaction with chiral 1,2-bis(2-hydroxylphenyl)-1,2-diaminoethane as starting material has been developed. The newly prepared biisoindoline was employed as a chiral ligand in the Ni(II)-catalyzed enantioselective Michael addition of malonates to conjugated nitroalkenes, and good to excellent enantioselectivities were obtained

Decarboxylative Alkylcarboxylation of α,β-Unsaturated Acids Enabled by Copper-Catalyzed Oxidative Coupling

A facile and general method for copper-catalyzed decarboxylative alkylcarboxylation of cinnamic acids with dimethyl 2,2′-azobis­(2-methyl­propionate) has been developed. The scope and versatility of the reaction was demonstrated, and a broad range of substrates bearing electron-donating and -withdrawing groups on the aromatic rings were all compatible with this reaction to provide desired β,γ-unsaturated esters in moderate to good yields. Moreover, α,β-unsaturated acids with a carbonyl group on the γ-position of acrylic acids also smoothly proceeded to furnish the desired products in good yields

Visible-Light-Triggered Self-Reporting Release of Nitric Oxide (NO) for Bacterial Biofilm Dispersal

Bacterial infection poses a massive threat to our society, and bacterial biofilm is a major cause of chronic and recurrent infections. The treatment of bacterial biofilms represents a challenging task, and the development of antibacterial materials that can not only disperse bacterial biofilms but also kill bacteria is of increasing interest. Herein, we report the fabrication of well-defined nitric oxide (NO)-releasing amphiphiles, poly­(ethylene oxide)-b-polyCouNO (PEO-b-PCouNO), where CouNO is an N-nitrosoamine-based NO donor containing a coumarin chromophore, exhibiting visible-light-mediated and self-reporting NO-release behavior. Unlike conventional polymeric NO donors derived from N-diazeniumdiolate (NONOates) or N-nitrosothiol (SNOs) that could be only synthesized via the postmodification procedure due to poor stability, the newly developed N-nitrosoamine-based NO donors can be directly polymerized into amphiphiles using reversible addition-fragmentation chain transfer (RAFT) polymerization. The NO-releasing amphiphiles self-assembled into micelles and selective NO release in aqueous medium was achieved by irradiating the micelle solution with visible light, which was characterized by a remarkable fluorescence turn-on (>185-fold), thereby enabling in situ self-reporting NO release. The photoinduced NO release can efficiently disperse bacterial biofilm of Pseudomonas aeruginosa. Moreover, antibiotics (e.g., Ciprofloxacin, Cip) could be loaded into the NO-releasing micelles, and co-delivery of NO and Cip was achieved, allowing for simultaneous biofilm dispersal and bacterial killing. This work provides a new strategy to fabricate macromolecular NO donors, which can efficiently avoid uncontrolled NO leakage and display promising antibacterial applications

Tuning the Mechanical and Dynamic Properties of Elastic Vitrimers by Tailoring the Substituents of Boronic Ester

Elastic vitrimers, i.e., elastic polymers with associative dynamic covalent bonds, can afford elastomers with recyclability while maintaining their thermal and chemical stability. Herein, we report a series of boronic ester-based vitrimers with tunable mechanical properties and recyclability by varying the substitute groups of boronic acid in polymer networks. The dynamic polymer networks are formed by reacting diol-containing tetra-arm poly­(amidoamine) with boronic acid-terminated tetra-arm poly­(ethylene glycol), which possesses different substituents adjacent to boronic acid moieties. Varying the substituent adjacent to the boronic ester unit will significantly affect the binding strength of the boronic ester, therefore affecting their dynamics and mechanical performance. The electron-withdrawing substituents noticeably suppress the dynamics of boronic ester exchange and increase the activation energy and relaxation time while enhancing the mechanical strength of the resulting elastic vitrimers. On the other hand, the presence of electron-rich substituent affords relatively reduced glass transition temperature (Tg), faster relaxation, and prominent recyclability and malleability at lower temperatures. The developed pathway will guide the rational design of elastomers with well-tunable dynamics and processabilities

Growth properties of the GEE cell line.

<p>(A) Cellular growth curve of the GEE cell line. Cells at passages 20, 45 and 65 were grown at 37°C in a 6-well plate containing 2 ml of the M199 medium supplemented with 10% fetal bovine serum until they reach confluency and then were collected at indicated time points for counting. Errors bars represent standard deviations from three independent experiments. (B) Flow cytometry was used to analyze the cell cycle of the GEE cell line. Cellular DNA was stained with the Propidium Iodide fluorescent dye and fluorescence intensity of cells was measured in the G1, S and G2 phases of the cell cycle.</p

Image_2_Temporally integrated transcriptome analysis reveals ASFV pathology and host response dynamics.jpg

African swine fever virus (ASFV) causes a lethal swine hemorrhagic disease and is currently responsible for widespread damage to the pig industry. The pathogenesis of ASFV infection and its interaction with host responses remain poorly understood. In this study, we profiled the temporal viral and host transcriptomes in porcine alveolar macrophages (PAMs) with virulent and attenuated ASFV strains. We identified profound differences in the virus expression programs between SY18 and HuB20, which shed light on the pathogenic functions of several ASFV genes. Through integrated computational analysis and experimental validation, we demonstrated that compared to the virulent SY18 strain, the attenuated HuB20 quickly activates expression of receptors, sensors, regulators, as well as downstream effectors, including cGAS, STAT1/2, IRF9, MX1/2, suggesting rapid induction of a strong antiviral immune response in HuB20. Surprisingly, in addition to the pivotal DNA sensing mechanism mediated by cGAS-STING pathway, infection of the DNA virus ASFV activates genes associated with RNA virus response, with stronger induction by HuB20 infection. Taken together, this study reveals novel insights into the host-virus interaction dynamics, and provides reference for future mechanistic studies of ASFV pathogenicity.</p

Table_5_Temporally integrated transcriptome analysis reveals ASFV pathology and host response dynamics.xlsx

African swine fever virus (ASFV) causes a lethal swine hemorrhagic disease and is currently responsible for widespread damage to the pig industry. The pathogenesis of ASFV infection and its interaction with host responses remain poorly understood. In this study, we profiled the temporal viral and host transcriptomes in porcine alveolar macrophages (PAMs) with virulent and attenuated ASFV strains. We identified profound differences in the virus expression programs between SY18 and HuB20, which shed light on the pathogenic functions of several ASFV genes. Through integrated computational analysis and experimental validation, we demonstrated that compared to the virulent SY18 strain, the attenuated HuB20 quickly activates expression of receptors, sensors, regulators, as well as downstream effectors, including cGAS, STAT1/2, IRF9, MX1/2, suggesting rapid induction of a strong antiviral immune response in HuB20. Surprisingly, in addition to the pivotal DNA sensing mechanism mediated by cGAS-STING pathway, infection of the DNA virus ASFV activates genes associated with RNA virus response, with stronger induction by HuB20 infection. Taken together, this study reveals novel insights into the host-virus interaction dynamics, and provides reference for future mechanistic studies of ASFV pathogenicity.</p