Spencerespensen9605

A direct assembly of secondary benzylureas and related amine derivatives via copper-catalyzed carboamination of styrenes with potassium alkyltrifluoroborates and ureas, anilines, or an amide is reported. Terminal and 1,2-disubstituted alkenes, as well as dienes, participate in this three-component coupling reaction. The reaction mechanism likely involves the addition of an alkyl radical to the styrene, followed by metal-mediated oxidative coupling of the resulting benzylic radical with the amine derivative. Factors that impact substrate reactivity and regioselectivity are discussed.An asymmetric domino reaction combining vinylogous Michael reaction, hydration of aldehyde, and oxy-Michael reaction proceeds with α,β-unsaturated aldehydes and α-acyl α,β-unsaturated cyclic ketones in the presence of diphenylprolinol silyl ether to afford tetrahydrochromane derivatives with excellent enantioselectivity. After the domino reaction, addition of Wittig reagent and acid in the same reaction vessel promoted a second domino reaction incorporating retro oxy-Michael reaction, isomerization, and Wittig reaction to afford chiral functionalized cyclic 1,3-diene derivatives with excellent enantioselectivity. Overall, six reaction steps proceed in a one-pot procedure.A unique chiral amine organocatalyst with a bispidine structure was found to be efficient for the diastereo- and enantioselective Mannich reaction of isatin ketimines with ketones. A series of 3-substituted 3-amino-2-oxindoles bearing vicinal tertiary and quaternary chiral stereogenic centers were obtained in excellent yields with excellent dr and ee values. The gram-scale synthesis and transformation of the product showed the practicability of this methodology. In addition, a possible transition state model was proposed to explain the origin of the stereoselectivity.We present a new approach to femtosecond direct laser writing lithography to pattern nanocavities in ferromagnetic thin films. To demonstrate the concept, we irradiated 300 nm thin nickel films by single intense femtosecond laser pulses through glass substrate. Using a fluence above the ablation threshold, the process is destructive, leading to the formation of an ablation crater. By progressively lowering the laser fluence, the formation of closed spallation cavities below the ablation threshold is achieved. Systematic studies by the electron and optical interferometric microscopies, supported by molecular dynamics simulations, enabled us to gain an understanding of the thermo-mechanical spallation mechanism at the solid-molten interface. We achieved the fabrication of periodic arrangements of closed spallation nanocavities. Due to their topology, closed magnetic nanocavities can support unique couplings of multiple excitations (magnetic, optical, acoustic, spintronic). Thereby, they offer a unique physics playground for emerging fields in magnetism, magneto-photonic, and magneto-acoustic applications.Oxidation of monometallic Pd and bimetallic Pd3Au alloy surfaces are observed by in situ ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) at an elevated pressure (100 mTorr O2 ambient). It is directly evidenced that the alloying with Au hinders the surface oxidation of Pd3Au surfaces compared with monometallic Pd surfaces. Remarkably, the oxidation behavior is clearly different between Pd3Au(111) and (100) surfaces. The (100) surface has a relatively Pd-rich surface composition, and the surface oxide layer is formed, whereas the (111) surface has a Au-rich composition, and the surface oxidation is quite limited. A combined approach of experimental and theoretical techniques reveals that Pd/Au surface composition and atomic arrangement are key factors determining the oxidation behavior.Nonreactive force fields are defined by perturbations of electron density that are relatively small, whereas chemical reactivity involves wholesale electronic rearrangements that make and break bonds. Thus, reactive force fields are incredibly difficult to develop compared to nonreactive force fields, yet at the same time, they fill a critical need when ab initio molecular dynamics methods are not affordable. We introduce a new reactive force field model for water that combines modified nonbonded terms of the ReaxFF model and its embedding in the electrostatic interactions described by our recently introduced coarse-grained electron model (C-GeM). The ReaxFF/C-GeM force field is characterized for many energetic and dissociative water properties for water clusters, structure, and dynamical properties under ambient conditions in the condensed phase, as well as the temperature dependence of density and water diffusion, with very good agreement with experiment. The ReaxFF/C-GeM force field should be more transferable and more broadly applicable to a range of reactive systems involving both proton and electron transfer in the condensed phase.Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy. N-glycosylation of PD-L1 affects its interaction with PD-1, but little is known about the distribution of glycoforms at its four NXS/T sequons. We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs. We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon. Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures. Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown. The interaction of PD-L1 with clinical antibodies is also affected by glycosylation. In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.Gene therapy directly targets mutations causing disease, allowing for a specific treatment at a molecular level. Adeno-associated virus (AAV) has been of increasing interest as a gene delivery vehicle, as AAV vectors are safe, effective, and capable of eliciting a relatively contained immune response. With the recent FDA approval of two AAV drugs for treating rare genetic diseases, AAV vectors are now on the market and are being further explored for other therapies. While showing promise in immune privileged tissue, the use of AAV for systemic delivery is still limited due to the high prevalence of neutralizing antibodies (nAbs). To avoid nAb-mediated inactivation, engineered AAV vectors with modified protein capsids, materials tethered to the capsid surface, or fully encapsulated in a second, larger carrier have been explored. Many of these engineered AAVs have added benefits, including avoided immune response, overcoming the genome size limit, targeted and stimuli-responsive delivery, and multimodal therapy of two or more therapeutic modalities in one platform. Native and engineered AAV vectors have been tested to treat a broad range of diseases, including spinal muscular atrophy, retinal diseases, cancers, and tissue damage. This review will cover the benefits of AAV as a promising gene vector by itself, the progress and advantages of engineered AAV vectors, particularly synthetically engineered ones, and the current state of their clinical translation in therapy.Since the prediction of the existence of metallabenzenes in 1979, metallaaromatic chemistry has developed rapidly, due to its importance in both experimental and theoretical fields. Now six major types of metallaromatic compounds, metallabenzenes, metallabenzynes, heterometallaaromatics, dianion metalloles, metallapentalenes and metallapentalynes (also termed carbolongs), and spiro metalloles, have been reported and extensively studied. Their parent organic analogues may be aromatic, non-aromatic, or even anti-aromatic. These unique systems not only enrich the large family of aromatics, but they also broaden our understanding and extend the concept of aromaticity. This review provides a comprehensive overview of metallaaromatic chemistry. We have focused on not only the six major classes of metallaaromatics, including the main-group-metal-based metallaaromatics, but also other types, such as metallacyclobutadienes and metallacyclopropenes. The structures, synthetic methods, and reactivities are described, their applications are covered, and the challenges and future prospects of the area are discussed. Ferrostatin-1 The criteria commonly used to judge the aromaticity of metallaaromatics are presented.The wearable and integrated sensing platform is a promising choice for developing real-time analytic electronics with clear advantages but still poses challenges, such as the realization of high precision, low limit of detection (LOD), moderate mechanical capacity, integration, and miniaturization. In this work, a simple printed wearable smartsensor has been fabricated with the aid of electrochemical plating methods with bismuth (Bi) films. The excellent sensing behaviors, including linear relationship, selectivity, stability, repeatability, and the LOD at ppb levels, have been obtained by this smartsensor. Additionally, the highly flexible textile-based sensor exhibits potential application on the substrates of daily cloth, sports T-shirt, and sports wristbands, and it maintains good stability under repeated deformations of washing and twisting. Importantly, integrated with printed circuit board, single chip micyoco, and Bluetooth modules, a smartsensing platform is successfully acquired for real-time detection of heavy metals (e.g., Zn, Cd, Pb, etc.). Finally, actual samples of human sweat, seawater, cosmetics, and drinking water have been remotely successfully demonstrated for detection by this smartsensor, enabling a great promise for fast on-site screening of samples in practical application.Lycopene β-cyclase is one of the key enzymes in the biosynthesis of carotenoids, which catalyzes the β-cyclization of both ends of lycopene to produce β-carotene. Lycopene β-cyclases are found in a wide range of sources, mainly plants and microorganisms. Lycopene β-cyclases have been extensively studied for their important catalytic activity, including for use in genetic engineering to modify plants and microorganisms, as a blocking target for lycopene industrial production strains, and for their genetic and physiological effects related to microorganic and plant biological traits. This review of lycopene β-cyclases summarizes the major studies on their basic classification, functional activity, metabolic engineering, and plant science.Wide-band gap (WBG) mixed-halide perovskites have drawn much attention because of their excellent optoelectronic properties and the potential to be deployed in tandem solar cells. Nevertheless, the bromine incorporation inevitably leads to photoinduced phase segregation in WBG mixed-halide perovskites. Herein, potassium is used to effectively suppress photoinduced phase segregation, which is visualized with confocal photoluminescence microscopy imaging. Strikingly, the potassium passivation not only inhibits the formation of the narrow-band gap subphase but also enhances the crystallinity of the WBG mixed-halide perovskite. In addition, the potassium-passivated WBG perovskite exhibits lower defect density, longer charge carrier lifetime, and better photostability. As a result, the optimized KI (2 mol %)-passivated WBG perovskite solar cells (PSCs) deliver a champion power conversion efficiency of 18.3% with negligible hysteresis. They maintain 98% of their initial efficiency after 400 h under 100 mW·cm-2 white light illumination in nitrogen.