Alzheimer disease (AD) accounts for 60-70% of dementia cases. Given the seriousness of the disease and continual increase in patient numbers, developing effective therapies to treat AD has become ...urgent. Presently, the drugs available for AD treatment, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate receptor, can only inhibit dementia symptoms for a limited period of time but cannot stop or reverse disease progression. On the basis of the amyloid hypothesis, many global drug companies have conducted many clinical trials on amyloid clearing therapy but without success. Thus, the amyloid hypothesis may not be completely feasible. The number of anti-amyloid trials decreased in 2019, which might be a turning point. An in-depth and comprehensive understanding of the contribution of amyloid beta and other factors of AD is crucial for developing novel pharmacotherapies.In ongoing clinical trials, researchers have developed and are testing several possible interventions aimed at various targets, including anti-amyloid and anti-tau interventions, neurotransmitter modification, anti-neuroinflammation and neuroprotection interventions, and cognitive enhancement, and interventions to relieve behavioral psychological symptoms. In this article, we present the current state of clinical trials for AD at clinicaltrials.gov. We reviewed the underlying mechanisms of these trials, tried to understand the reason why prior clinical trials failed, and analyzed the future trend of AD clinical trials.
We report the strong catalyst–support interaction in WC‐supported RuO2 nanoparticles (RuO2‐WC NPs) anchored on carbon nanosheets with low loading of Ru (4.11 wt.%), which significantly promotes the ...oxygen evolution reaction activity with a η10 of 347 mV and a mass activity of 1430 A gRu−1, eight‐fold higher than that of commercial RuO2 (176 A gRu−1). Theoretical calculations demonstrate that the strong catalyst–support interaction between RuO2 and the WC support could optimize the surrounding electronic structure of Ru sites to reduce the reaction barrier. Considering the likewise excellent catalytic ability for hydrogen production, an acidic overall water splitting (OWS) electrolyzer with a good stability constructed by bifunctional RuO2‐WC NPs only requires a cell voltage of 1.66 V to afford 10 mA cm−2. The unique 0D/2D nanoarchitectures rationally combining a WC support with precious metal oxides provides a promising strategy to tradeoff the high catalytic activity and low cost for acidic OWS applications.
Unique 0D/2D WC‐supported RuO2 nanoparticles anchored on carbon nanosheets with low loading of Ru (4.11 wt.%) were constructed as a bifunctional electrocatalyst, applying a cell voltage of 1.66 V to realize acidic overall water splitting (OWS) with excellent long‐term stability.
Photoredox‐catalyzed methylcyclobutanations of alkylboronic esters are described. The reactions proceed through single‐electron transfer induced deboronative radical addition to an electron‐deficient ...alkene followed by single‐electron reduction and polar 4‐exo‐tet cyclization with a pendant alkyl halide. Key to the success of the methodology was the use of easily oxidizable arylboronate complexes. Structurally diverse cyclobutanes are shown to be conveniently prepared from readily available alkylboronic esters and a range of haloalkyl alkenes. The mild reactions display excellent functional group tolerance, and the radical addition‐polar cyclization cascade also enables the synthesis of 3‐, 5‐, 6‐, and 7‐membered rings.
Arylboronate complexes formed from alkylboronic esters and phenyllithium were found to undergo facile single‐electron oxidation to form alkyl radicals. The novel use of these complexes as radical precursors enabled the development of a photoredox‐catalyzed cyclobutane synthesis proceeding through a radical‐polar crossover mechanism.
Boronic acids and their derivatives are some of the most useful reagents in the chemical sciences
, with applications spanning pharmaceuticals, agrochemicals and functional materials. Catalytic C-H ...borylation is a powerful method for introducing these and other boron groups into organic molecules because it can be used to directly functionalize C-H bonds of feedstock chemicals without the need for substrate pre-activation
. These reactions have traditionally relied on precious-metal catalysts for C-H bond cleavage and, as a result, display high selectivity for borylation of aromatic C(sp
)-H bonds over aliphatic C(sp
)-H bonds
. Here we report a mechanistically distinct, metal-free borylation using hydrogen atom transfer catalysis
, in which homolytic cleavage of C(sp
)-H bonds produces alkyl radicals that are borylated by direct reaction with a diboron reagent. The reaction proceeds by violet-light photoinduced electron transfer between an N-alkoxyphthalimide-based oxidant and a chloride hydrogen atom transfer catalyst. Unusually, stronger methyl C-H bonds are borylated preferentially over weaker secondary, tertiary and even benzylic C-H bonds. Mechanistic studies indicate that the high methyl selectivity is a result of the formation of a chlorine radical-boron 'ate' complex that selectively cleaves sterically unhindered C-H bonds. By using a photoinduced hydrogen atom transfer strategy, this metal-free C(sp
)-H borylation enables unreactive alkanes to be transformed into valuable organoboron reagents under mild conditions and with selectivities that contrast with those of established metal-catalysed protocols.
Herein, we describe the development of a photoredox‐catalyzed decarboxylative radical addition–polar cyclization cascade approach to functionalized cyclopropanes. Reductive termination of ...radical–polar crossover reactions between aliphatic carboxylic acids and electron‐deficient alkenes yielded carbanion intermediates that were intercepted in intramolecular alkylations with alkyl chlorides appended to the alkene substrate. The mild conditions, which make use of a readily available organic photocatalyst and visible light, were demonstrated to be amenable to a broad range of structurally complex carboxylic acids and a wide variety of chloroalkyl alkenes, demonstrating exquisite functional group tolerance.
The development of a fragment coupling‐based cyclopropanation between carboxylic acids and chloroalkyl alkenes is described. The reaction involves a photoredox‐catalyzed decarboxylative radical addition–polar cyclization cascade and uses a readily available organic photocatalyst. The mild conditions provide access to diversely functionalized cyclopropanes from a broad range of structurally complex carboxylic acid and alkene substrates.
A group of patients with a febrile illness and a history of tick bites was identified in northeastern China. A previously unknown virus was determined to be a possible etiologic agent. This virus was ...also found in ticks in the area.
N-Containing tricyclic compounds, especially the tricyclic N-heterocycles, are important structural motifs that possess significant potential in organic chemistry for their momentous applications in ...natural and man-made bioactive molecules. Gold catalysis, which exhibits specific catalytic properties in terms of both high reactivity and selectivity for various organic transformations, has proven to be a powerful tool for the straightforward synthesis of cyclic compounds, especially the polycyclic molecules. Currently, several approaches towards polycycle synthesis have been developed
via
gold-catalyzed transformations of readily available ynamides. In this review, we will focus on the recent advances in the gold-catalyzed construction of N-containing tricycles based on ynamides by highlighting their specificity and applicability, and the mechanistic rationale is presented where possible.
The recent advances in the gold-catalyzed construction of N-containing tricycles based on ynamides are reviewed by highlighting their specificity and applicability, and the mechanistic rationale.
Disinfection by-products (DBPs) formed upon water treatment is an emerging issue worldwide. While monitoring of DBP precursors can easily be achieved for high specific UV absorbance (SUVA) organic ...(>6 L/mg·m), low and extremely low SUVA precursors (<2 L/mg·m) are difficult to monitor or even to predict their DBP formation behaviour. This study investigated the relationships among NOM characteristics, such as molecular weight (MW), fluorescence, and chemical composition, with DBP formation resulting from the chlorination of relatively high and low SUVA precursors. High SUVA precursors were formed by C-rich substances (82–85% of total mass) corresponding with high C/N and C/O (>100 and >5, respectively). Such precursors exhibited the fluorescence of long-wavelength humic-like signal and occurred at a high MW range (>30 kDa). By contrast, low SUVA precursors were either N-rich and/or O-rich substances, associated with much lower carbon content (40–70%). Low SUVA, N-rich precursors particularly also occurred at a high MW region (>100 kDa) and produced a strong protein-like fluorescence signal. When SUVA values of O-rich precursors were extremely low (<1 L/mg·m) they were accompanyied by short-wavelength humic-like fluorescence. During DBP tests, high SUVA produced only high yields of carbonaceous DBPs (e.g trichloromethane, haloacetic acids, haloketones), whereas low SUVA N-rich precursors yielded high levels of both C and NDBPs (e.g. haloacetonenitrile, chloropicrin). By contrast, extremely low SUVA precursors produced significantly low levels of both C and NDBPs (total < 30 μg/mgC). Furthermore, 19 of 20 regression models of DBP formation using log-transformed MW gave R2 = 0.50–0.97. The strong regressions and correlations of NOM characteristics with DBPs in this study provide a better understanding of the influence of precursors characteristics on DBP monitoring, especially for low SUVA NOM.
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•High SUVA NOMs were C-rich, while low SUVA NOMs were either N-rich or O-rich.•High SUVA, C-rich NOM produced high yields of C-DBPs.•Low SUVA, N-rich NOM yielded high levels of both C-and N-DBPs.•Extremely low SUVA, O-rich NOM produced significantly low levels of C- and N-DBPs.•A great number of DBP models (19 of 20) using log-transformed MW were well fit.
This article proposes an advanced THz multiple-input-multiple-output (MIMO) near-field sparse imaging scheme for target detection that uses single-pass synthetic aperture focusing and multipass ...interferometric synthetic aperture focusing techniques to improve imaging effectiveness and efficiency. It benefits from the MIMO of the linear sparse periodic array (SPA) and random undersampling sparse imaging to reduce sampling data and system cost. Both simulated and proof-of-concept experimental results have verified the scheme, revealing that the single-pass synthetic aperture imaging approach is sufficient to identify pure metallic targets with 3.87% of <inline-formula> <tex-math notation="LaTeX">\lambda /2 </tex-math></inline-formula> sampling data. The multipass interferometric synthetic aperture imaging approach is capable of improving image quality on the image signal-to-noise ratio (SNR) and contrast, which is ideal for detecting more challenging targets. The random sparse imaging with help of the low-rank matrix completion (LRMC) technique has shown the promising potential of achieving equivalent image quality when further reducing 43.75% data in the experiment of five-pass imaging on a complex target; this corresponds to 82.51% data reduction compared to <inline-formula> <tex-math notation="LaTeX">\lambda /2 </tex-math></inline-formula> sampling.
Cardiac hypertrophy is the main cause of heart failure and sudden death in patients. But the pathogenesis is unclear. Angiotensin II may contribute to cardiac hypertrophy in response to pressure ...overload. In angiotensin II‐treated cardiomyocytes, there is a larger cross‐sectional area, more apoptosis cells, and a reduction of irisin expression. An increase in P62, an autophagy flux index, as well as LC3II, were observed in cardiomyocytes after angiotensin II‐induced injury. Surprisely, irisin supplementation increased LC3II expression and decreased P62 expression, consisted of results of RFP‐GFP‐LC3B adenovirus transfection, and reduced cardiomyocyte apoptosis, meanwhile, the protection of irisin was reversed by the autophagy inhibitor 3‐methyladenine. In animal experiments, overexpression of irisin reduced cardiomyocyte apoptosis and alleviated myocardial hypertrophy caused by pressure overload. The above results indicate that irisin‐induced protective autophagy and alleviated the apoptosis signaling pathway in cardiomyocytes, consequently reducing cardiomyocyte apoptosis after angiotensin II‐induced injury. Hence, increasing irisin expression may be a new way to improve cardiac function and quality of life in patients with cardiac hypertrophy.
Irisin reduces myocardial apoptosis by increasing autophagy activity and autophagy flux and inhibiting the apoptosis signaling factor in myocardial cells damaged by angiotensin II.
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