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The synthesis of substituted γ- and δ-lactams via palladium-catalyzed alkene carboamination reactions between aryl halides and alkenes bearing pendant amides is described. The substrates for these reactions are generated in 1-3 steps from commercially available materials, and products are obtained in good yield with up to >20:1 diastereoselectivity. The stereochemical outcome of the alkene addition is consistent with a mechanism involving anti-aminopalladation of the alkene. [ABSTRACT FROM AUTHOR]

Critical peripheral nerve deficiencies present as one of the most formidable conundrums in the realm of clinical medicine, frequently culminating in structural degradation and derangement of the neuromuscular apparatus. Engineered extracellular vesicles (EVs) exhibit the potential to ameliorate nerve impairments. However, the advent of Wallerian degeneration (WD), an inexorable phenomenon that ensues post peripheral nerve injury, serves as an insurmountable impediment to the direct therapeutic efficacy of EVs. In this investigation, we have fashioned a dynamic network for the conveyance of PTEN-induced kinase 1 (PINK1) mRNA (E-EV-P@HPCEP) using an adaptive hydrogel with reactive oxygen species (ROS)/Ca 2+ responsive ability as the vehicle, bearing dual-targeted, engineered EVs. This intricate system is to precisely deliver PINK1 to senescent Schwann cells (SCs) while concurrently orchestrating a transformation in the inflammatory-senescent milieu following injury, thereby stymying the progression of WD in peripheral nerve fibers through the stimulation of autophagy within the mitochondria of the injured cells and the maintenance of mitochondrial mass equilibrium. WD, conventionally regarded as an inexorable process, E-EV-P@HPCEP achieved functionalized EV targeting, orchestrating a dual-response dynamic release mechanism via boronate ester bonds and calcium chelation, effectuating an enhancement in the inflammatory-senescent microenvironment, which expedites the therapeutic management of nerve deficiencies and augments the overall reparative outcome.

Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3 + mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation and senescence cascade expansion in vitro . Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.

Colloidal nucleation is first observed to exist in a Sn-based perovskite solution, and its components and size are discovered to alter in real time with stirring time. Then, a simple stirring-time control approach is developed to manage the size of the colloids, and with continuous stirring for 3 days an optimal colloid with size <10 nm is confirmed to successfully form a continuous, dense, high-quality perovskite film. Herein, the colloids exist in the form of [SnI 6 ] 4- complete coordination compounds, with which a compact FA 0.75 MA 0.25 SnI 3 perovskite film with reduced defects and enhanced crystallinity concentration is obtained as nucleation sites, and a planar inverted perovskite solar cell with a champion power conversion efficiency of 10.74% is eventually realized. This work provides a novel perspective to enhance perovskite film quality and thus device performance via controlling high-quality nucleation in precursor solution.

The two lowest potential energy surfaces of cyclohexoxy which are coupled by conical intersections and the spin-orbit interaction are determined in the full 48-dimensional internal coordinate space using a feedforward neural network to fit a diabatic potential energy matrix. The electronic structure data are obtained at the multireference configuration interaction with single- and double-excitation level. Underlying parallels between these coupled surfaces and those of the alkoxy radicals methoxy and isopropoxy are established. Earlier work by Dillon and Yarkony is extended. While the parallels would have been challenging to appreciate using the concept of the Jahn-Teller active modes, they are readily seen in terms of two internal modes centered at the conical intersection: g the energy difference gradient vector and h the interstate coupling gradient vector. In other words, g and h vectors provide a unified description of the Jahn-Teller effect in molecules exhibiting C3v and quasi-C3v symmetries. A spectral simulation in the full 48-vibrational-internal coordinate space is reported. This spectrum is obtained using recently developed algorithms designed to increase the size of the systems that can be treated with a time-independent vibronic coupling approach.

We present, for systems of moderate dimension, a fitting framework to construct quasi-diabatic Hamiltonians that accurately represent ab initio adiabatic electronic structure data including the effects of conical intersections. The framework introduced here minimizes the difference between the fit prediction and the ab initio data obtained in the adiabatic representation, which is singular at a conical intersection seam. We define a general and flexible merit function to allow arbitrary representations and propose a representation to measure the fit- ab initio difference at geometries near electronic degeneracies. A fit Hamiltonian may behave poorly in insufficiently sampled regions, in which case a machine learning theory analysis of the fit representation suggests a regularization to address the deficiency. Our fitting framework including the regularization is used to construct the full 39-dimensional coupled diabatic potential energy surfaces for cyclopentoxy relevant to cyclopentoxide photoelectron detachment.