Vangtorp8696

This study examined the effect of sacral neuromodulation on persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PudNS). In 10 α-chloralose-anesthetized cats, repetitive application of 30-min PudNS induced bladder underactivity evident as an increase in bladder capacity during a cystometrogram (CMG). S1 or S2 dorsal root stimulation (15 or 30 Hz) at 1 or 1.5 times threshold intensity (T) for inducing reflex hindlimb movement (S1) or anal sphincter twitch (S2) was applied during a CMG to determine if the stimulation can reverse the bladder underactivity. Persistent (>3 h) bladder underactivity consisting of a significant increase in bladder capacity to 163.1 ± 11.3% of control was induced after repetitive (1-10 times) application of 30-min PudNS. S2 but not S1 dorsal root stimulation at 15 Hz and 1 T intensity reversed the PudNS-induced bladder underactivity by significantly reducing the large bladder capacity to 124.3 ± 12.9% of control. GANT61 Other stimulation parameters were not effective. After the induction of persistent underactivity, recordings of reflex bladder activity under isovolumetric conditions revealed that S2 dorsal root stimulation consistently induced the largest bladder contraction at 15 Hz and 1 T when compared with other frequencies (5-40 Hz) or intensities (0.25-1.5 T). This study provides basic science evidence consistent with the hypothesis that abnormal pudendal afferent activity contributes to the bladder underactivity in Fowler's syndrome and that sacral neuromodulation treats this disorder by reversing the bladder inhibition induced by pudendal nerve afferent activity.Inspired by a previously reported biomimetic synthesis study, four new naturally occurring phloroglucinol trimers 1-4 with unusual 6/5/5/6/6/6-fused hexacyclic ring systems, along with two known analogues (5 and 6) and two known biogenetically related dimers (10 and 11), were isolated from Rhodomyrtus tomentosa. Their structures and absolute configurations were unambiguously elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism calculation. By mimicking two potentially alternative biosynthetic pathways, the first asymmetric syntheses of 1-4 and the racemic syntheses of 5 and 6 were achieved in only five to six steps without the need for protecting groups. Furthermore, phloroglucinol dimers 10 and 11 exhibited significant in vitro antiviral activity against the respiratory syncytial virus.A concise total synthesis of rucaparib, an FDA-approved drug for ovarian and prostate cancers, is reported. The Heck reaction of the commercially available aryl iodide with acrylonitrile provided the desired (E)-2-aminocinnamonitrile derivative. A subsequent imino-Stetter reaction of the aldimine derived from 2-aminocinnamonitrile and aldehyde furnished indole-3-acetonitrile bearing the desired substituents at appropriate positions. The construction of the final azepinone scaffold via reduction of the nitrile group followed by seven-membered lactamization afforded rucaparib. Notably, the synthesis of rucaparib is achieved using commercially available starting materials in only three separation operations with 54% overall yield.Small-molecule irreversible tyrosine kinase inhibitors as high potent agents have led to improvements in disease-free and overall survival in patients with HER2-amplified cancer. The approved irreversible HER2 inhibitors, neratinib and pyrotinib, both lack HER2 selectivity, leading to off-target adverse events in patients. The development of HER2 mutation during treatment also hampers the progress of the treatment. We used a molecular hybridization strategy for structural optimizations, in conjunction with in vitro and in vivo drug-like property screening, to obtain a clinical candidate SPH5030. Overall, SPH5030 showed excellent activities against four frequent kinds of HER2 mutants and high relative HER2 selectivity compared with neratinib and pyrotinib, good pharmacokinetic characteristics with desirable bioavailabilities, and significant in vivo antitumor efficacy in xenograft mouse models, especially in a HER2 mutation A775_G776insYVMA xenograft mouse model with its potency much higher than those of neratinib and pyrotinib.We described a novel palladium-catalyzed C-H glycosylation of indole or tryptophan for a one-pot stereoselective synthesis of 2,3-diglycosylindoles and tryptophan-C-glycosides. In this strategy, the use of air and base-free and ligand-free conditions provided a highly efficient route to construct C-glycosides. The method can be applied to a wide range of cost-effective and convenient glycosyl chloride donors. Mechanistic studies indicated that the indole 2,3-diglycosylation sequence was C3 and then C2.This paper deals with the preparation, characterization, and application of a crosslinked poly(vinyl alcohol)/ZnO-vitamin M (PVA/ZnO-VM) nanocomposite film for the removal of Congo red (CR) from an aqueous solution. The characterization of a crosslinked PVA/ZnO-VM nanocomposite film showed that the structure became more regular and also the surface morphology appeared smooth in comparison with pure PVA. The obtained data from Brunauer-Emmett-Teller (BET) proved the mesoporous structure for this nanocomposite film. Several effective factors were examined for the adsorption ability of the nanocomposite film, including solution pH (2-10), sorbent amount (0.02-0.08 g), contact time (3-240 min), initial concentration of the adsorbate (30-300 mg·L-1), and temperature (318-358 K). The optimal conditions are as follows pH = 10, adsorbent amount = 0.06 g, and C0 = 200 mg·L-1. The removal efficiency of the nanocomposite film was 92% after 4 h at the ambient temperature. To interpret the adsorption process, nonlinear and linear forms of kinetic and isotherm models were considered. The obtained data followed nonlinear pseudo-second-order and linear Langmuir isotherm models, which indicated the monolayer formation of CR over the crosslinked PVA/ZnO-VM nanocomposite film with the maximum adsorption capacity of about 56.49 mg·g-1. Also, the adsorption process of CR by the crosslinked PVA/ZnO-VM nanocomposite film is a spontaneous and exothermic reaction.We describe here the application of an inexpensive event-based/neuromorphic camera in an ion imaging experiment operated at 1 kHz detection rate to study real-time velocity-resolved kinetics of thermal desorption. Such measurements involve a single gas pulse to initiate a time-dependent desorption process and a high repetition rate laser, where each pulse of the laser is used to produce an ion image. The sequence of ion images allows the time dependence of the desorption flux to be followed in real time. In previous work where a conventional framing camera was used, the large number of megapixel-sized images required data transfer and storage rates of up to 16 GB/s. This necessitated a large onboard memory that was quickly filled and limited continuous measurement to only a few seconds. Read-out of the memory became the bottleneck to the rate of data acquisition. We show here that since most pixels in each ion image contain no data, the data rate can be dramatically reduced by using an event-based/neuromorphic camera. The data stream is thus reduced to the intensity and location information on the pixels that are lit up by each ion event together with a time-stamp indicating the arrival time of an ion at the detector. This dramatically increases the duty cycle of the method and provides insights for the execution of other high rep-rate ion imaging experiments.A practical and scalable protocol for electrochemical arylation of quinoxalin(on)es with arylhydrazine hydrochlorides under mild conditions has been developed. This method exhibits high efficiency, easy scalability, and broad functional group tolerance. Various quinoxalin(on)es and arylhydrazines underwent this transformation smoothly in an undivided cell, providing the corresponding aryl-substituted quinoxalin(on)es in moderate to good yields. A radical mechanism is involved in this arylation reaction.Immunoglobulin Gs (IgGs) contain many Lys and Cys residues, which results in an unwanted complex product mixture with conventional drug conjugation methods. We selectively acylated the ε-NH2 of K248 on trastuzumab using an IgG Fc-binding peptide (FcBP) equipped with a 5-norbornene-2-carboxylic acid thioester (AbClick-1). AbClick-1 locates its thioester close to the ε-NH2 of K248 while binding to trastuzumab. Consequently, the thioester underwent proximity-driven selective acylation of ε-NH2 through an S to N acyl transfer reaction. Furthermore, N-tert-butyl maleimide accelerated the cross-linking reaction with an approximately 95% yield of the desired product by scavenging the byproduct (FcBP-SH). Only K248 was modified selectively with the 5-norbornene-2-carbonyl group, which was further modified by click reaction to afford an antibody-drug conjugate (ADC) with two drugs per antibody. The resulting ADCs showed remarkable in vitro and in vivo anticancer activity. Our results demonstrate that a thioester is a promising chemical entity for proximity-driven site-selective conjugation of antibodies.A Pd(II)-catalyzed α,β-dehydrogenation of substituted aliphatic amides assisted by a reusable bis-chelating 8-aminoquinoline ligand is demonstrated. Broad spectra of β-substituted including olefin-substituted aliphatic amides are well tolerated. The present protocol efficiently dehydrogenates the less acidic aliphatic amides via the chelation-assisted β-C-H bond activation and replaces the traditional enolate-based strategy.The interlayer silylation of a layered silicate H-RUB-18 (Si4O7(OH)2) using a new aromatic silylating reagent containing a phosphonic acid group (4-phosphonophenylsilane PPS) was demonstrated (H-PPS-RUB-18). The phosphonic acid groups were attached to the silicate layers through the reaction of H-RUB-18 with (4-diethoxyphosphorylphenyl)-triethoxysilane (p-PPS-E), and the ester moieties were subsequently hydrolyzed with hydrochloric acid. H-PPS-RUB-18 is a solid acid, as indicated by the intercalation of various alkylamines and the catalytic acetalization of ketones. A systematic increase in interlayer spacing leading to surface acidic properties was obtained through intercalation with a series of alkylamines. In addition, H-PPS-RUB-18 was exfoliated, resulting in single-layer nanosheets with ca. 2.0 nm thickness. The catalytic acetalization of ketones was related to the interlayer spacing of the modified RUB-18.All lead-free inorganic halide perovskites, as efficient solid-state light emission materials, have become ideal green optoelectronic materials to replace lead halide perovskites for diversified lighting and display applications with their excellent stability. Here, we investigated the pressure-derived optical and structural response of a zero-dimensional lead-free perovskite Rb7Sb3Cl16 through applying controllable pressure. A pressure-induced blue shift of the broadband emission was achieved, and it was followed by the emission color transformation from yellow to green, which was ascribed to the electron-phonon coupling weakening and the suppression of structural deformation upon lattice contraction. In parallel, the band gap was narrowed by about 0.5 eV as a result of enhanced metal halide orbital overlap under high pressure. This work provides a fundamental understanding for modulating the optical properties of the low-dimensional metal halide perovskites.