Asymmetric photoredox catalytic formal de Mayo reaction enabled by sensitization-initiated electron transfer.

Visible-light-driven photoredox catalysis is known to be a powerful tool for organic synthesis. Its occurrence critically depends on the twice exothermic single-electron transfer processes of photosensitizers, which are governed by the redox properties of the species involved. Hence, the inherently narrow range of redox potentials of photosensitizers inevitably constrains their further availability. Sensitization-initiated electron transfer has recently been found to effectively overcome this substantial challenge. However, feasible and practical strategies for designing such complicated catalytic systems are rather scarce. Herein we report an elaborate dual-catalyst platform, with dicyanopyrazine as a visible light photosensitizer and a pyrenyl-incorporated chiral phosphoric acid as a co-sensitizer, and we demonstrate the applicability of this sensitization-initiated electron transfer strategy in an asymmetric formal de Mayo-type reaction. The catalysis platform enables otherwise thermodynamically unfavourable electron transfer processes to close the redox cycle and allows for precise access to valuable enantioenriched 1,5-diketones with a wide substrate range.

FUZ-SMO: A fuzzy slime mould optimizer for mitigating false alarm rates in the classification of underwater datasets using deep convolutional neural networks.

Sonar sound datasets are of significant importance in the domains of underwater surveillance and marine research as they enable experts to discern intricate patterns within the depths of the water. Nevertheless, the task of classifying sonar sound datasets continues to pose significant challenges. In this study, we present a novel approach aimed at enhancing the precision and efficacy of sonar sound dataset classification. The integration of deep long-short-term memory (DLSTM) and convolutional neural networks (CNNs) models is employed in order to capitalize on their respective advantages while also utilizing distinctive feature engineering techniques to achieve the most favorable outcomes. Although DLSTM networks have demonstrated effectiveness in tasks involving sequence classification, attaining their optimal performance necessitates careful adjustment of hyperparameters. While traditional methods such as grid and random search are effective, they frequently encounter challenges related to computational inefficiencies. This study aims to investigate the unexplored capabilities of the fuzzy slime mould optimizer (FUZ-SMO) in the context of LSTM hyperparameter tuning, with the objective of addressing the existing research gap in this area. Drawing inspiration from the adaptive behavior exhibited by slime moulds, the FUZ-SMO proposes a novel approach to optimization. The amalgamated model, which combines CNN, LSTM, fuzzy, and SMO, exhibits a notable improvement in classification accuracy, outperforming conventional LSTM architectures by a margin of 2.142%. This model not only demonstrates accelerated convergence milestones but also displays significant resilience against overfitting tendencies.

The feasibility of half-dose contrast-enhanced scanning of brain tumours at 5.0 T: a preliminary study.

PURPOSE: This study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T. METHODS: Twelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC). RESULTS: A total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p < 0.001). The CNR was also significantly greater at 5.0 T than at 3.0 T for grey matter/tumour lesions, white matter/tumour lesions, and grey matter/white matter (p < 0.001). Subjective evaluation revealed that the internal structure and outline of the tumour lesions were more clearly displayed with a half-dose at 5.0 T (Likert scale 8.1 ± 0.3 at 3.0 T, 8.9 ± 0.3 at 5.0 T, p < 0.001), and the effects of enhancement in the lesions were comparable to those with a full dose at 3.0 T (7.8 ± 0.3 at 3.0 T, 8.7 ± 0.4 at 5.0 T, p < 0.001). All subjective scores were good to excellent at both 5.0 T and 3.0 T. CONCLUSION: Both quantitative and subjective evaluation parameters suggested that half-dose enhanced scanning via 5.0 T MRI might be feasible for meeting clinical diagnostic requirements, as the image quality remains optimal. Enhanced scanning at 5.0 T with a half-dose of contrast agents might benefit patients with conditions that require less intravenous contrast agent, such as renal dysfunction.

Near-infrared fluorescent indolizine-dicyanomethylene-4H-pyran hybrids for viscosity imaging in living cells.

The development of near-infrared organic fluorescent dyes with tunable emission profiles is highly required in the field of biological sensing and imaging. In this paper, we designed and synthesized two organic fluorescent dyes, DCM-1 and DCM-2, through the hybridization of indolizine and dicyanomethylene-4H-pyran skeleton. These two compounds show near-infrared fluorescence with emission maximum approximately at 640 and 680 nm, respectively. Notably, both DCM-1 and DCM-2 have specific responses to viscosity without being interfered by biological relevant species. Cell experiments demonstrate that DCM-1 and DCM-2 can detect dynamic changes in viscosity within living cells, suggesting their potential applications in chemical biology research.

Catalytic Asymmetric Redox-Neutral [3 + 2] Photocycloadditions of Cyclopropyl Ketones with Vinylazaarenes Enabled by Consecutive Photoinduced Electron Transfer.

Consecutive photoinduced electron transfer (ConPET) is a powerful and atom-economical protocol to overcome the limitations of the intrinsic redox potential of visible light-absorbing photosensitizers, thereby considerably improving the substrate and reaction types. Likely because such an exothermic single-electron transfer (SET) process usually does not require the aid of chiral catalysts, resulting in an inevitable racemic background reaction, notably, no enantioselective manifolds have been reported. Herein, we report on the viability of cooperative ConPET and chiral hydrogen-bonding catalysis for the [3 + 2] photocycloaddition of cyclopropyl ketones with vinylazaarenes. In addition to enabling the first use of olefins that preferentially interact with chiral catalysts, this catalysis platform paves the way for the efficient synthesis of pharmaceutically and synthetically important cyclopentyl ketones functionalized by azaarenes with high yields, ees and dr. The robust capacity of the method can be further highlighted by the low loading of the chiral catalyst (1.0 mol%), the good compatibility of both 2-azaarene and 3-pyridine-based olefins, and the successful concurrent construction of three stereocenters on cyclpentane rings involving an elusive but important all-carbon quaternary.

A NIR-II Photoacoustic Probe for High Spatial Quantitative Imaging of Tumor Nitric Oxide in Vivo.

Nitric oxide (NO) exhibits both pro- and anti-tumor effects. Therefore, real-time in vivo imaging and quantification of tumor NO dynamics are essential for understanding the conflicting roles of NO played in pathophysiology. The current molecular probes, however, cannot provide high-resolution imaging in deep tissues, making them unsuitable for these purposes. Herein, we designed a photoacoustic probe with an absorption maximum beyond 1000 nm for high spatial quantitative imaging of in vivo tumor NO dynamics. The probe exhibits remarkable sensitivity, selective ratiometric response behavior, and good tumor-targeting abilities, facilitating ratiometric imaging of tumor NO throughout tumor progression in a micron-resolution level. Using the probe as the imaging agent, we successfully quantified NO dynamics in tumor, liver and kidney. We have pinpointed an essential concentration threshold of around 80 nmol/cm3 for NO, which plays a crucial role in the "double-edged-sword" function of NO in tumors. Furthermore, we revealed a reciprocal relationship between the NO concentration in tumors and that in the liver, providing initial insights into the possible NO-mediated communication between tumor and the liver. We believe that the probe will help resolve conflicting aspects of NO biology and guide the design of imaging agents for tumor diagnosis and anti-cancer drug screening.

Enantioselective [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with Vinylazaarenes through Asymmetric Photoredox Catalysis.

Here we present a highly enantioselective [2π + 2σ] photocycloaddition of bicyclo[1.1.0]butanes (BCBs). The reaction uses a variety of vinylazaarenes as partners and is catalyzed by a polycyclic aromatic hydrocarbon (PAH)-containing chiral phosphoric acid as a bifunctional chiral photosensitizer. A wide array of pharmaceutically important bicyclo[2.1.1]hexane (BCH) derivatives have been synthesized with high yields, enantioselectivity, and diastereoselectivity. In addition to the diverse 1-ketocarbonyl-3-substituted BCBs, α/ß-substituted vinylazaarenes are compatible with such an unprecedented photoredox catalytic pathway, resulting in the successful assembly of an all-carbon quaternary stereocenter or two adjacent tertiary stereocenters on the product.

Gene flow and an anomaly zone complicate phylogenomic inference in a rapidly radiated avian family (Prunellidae).

BACKGROUND: Resolving the phylogeny of rapidly radiating lineages presents a challenge when building the Tree of Life. An Old World avian family Prunellidae (Accentors) comprises twelve species that rapidly diversified at the Pliocene-Pleistocene boundary. RESULTS: Here we investigate the phylogenetic relationships of all species of Prunellidae using a chromosome-level de novo assembly of Prunella strophiata and 36 high-coverage resequenced genomes. We use homologous alignments of thousands of exonic and intronic loci to build the coalescent and concatenated phylogenies and recover four different species trees. Topology tests show a large degree of gene tree-species tree discordance but only 40-54% of intronic gene trees and 36-75% of exonic genic trees can be explained by incomplete lineage sorting and gene tree estimation errors. Estimated branch lengths for three successive internal branches in the inferred species trees suggest the existence of an empirical anomaly zone. The most common topology recovered for species in this anomaly zone was not similar to any coalescent or concatenated inference phylogenies, suggesting presence of anomalous gene trees. However, this interpretation is complicated by the presence of gene flow because extensive introgression was detected among these species. When exploring tree topology distributions, introgression, and regional variation in recombination rate, we find that many autosomal regions contain signatures of introgression and thus may mislead phylogenetic inference. Conversely, the phylogenetic signal is concentrated to regions with low-recombination rate, such as the Z chromosome, which are also more resistant to interspecific introgression. CONCLUSIONS: Collectively, our results suggest that phylogenomic inference should consider the underlying genomic architecture to maximize the consistency of phylogenomic signal.

A Small-Molecule Ratiometric Photoacoustic Probe for the High-Spatiotemporal-Resolution Imaging of Copper(II) Dynamics in the Mouse Brain.

Copper dysmetabolism is associated with various neurodegenerative disorders, making high-spatiotemporal-resolution imaging of Cu2+ in the brain essential for understanding the underlying pathophysiological processes. Nevertheless, the current probes encounter obstacles in crossing the blood-brain barrier (BBB) and providing high-spatial-resolution in deep tissues. Herein, we present a photoacoustic probe capable of imaging Cu2+ dynamics in the mouse brain with high-spatiotemporal-resolution. The probe demonstrates selective ratiometric and reversible responses to Cu2+ , while also efficiently crossing the BBB. Using the probe as the imaging agent, we successfully visualized Cu2+ in the brain of Parkinson's disease (PD) model mouse with a remarkable micron-level resolution. The imaging results revealed a significant increase in Cu2+ levels in the cerebral cortex as PD progresses, highlighting the close association between Cu2+ alternations in the region and the disease. We also demonstrated that the probe can be used to monitor changes in Cu2+ distribution in the PD model mouse brain during L-dopa intervention. Mechanism studies suggest that the copper dyshomeostasis in the PD mouse brain was dominated by the expression levels of divalent metal transporter 1. The application of our probe in imaging Cu2+ dynamics in the mouse brain offers valuable insights into the copper-related molecular mechanisms underlying neurodegenerative diseases.

An intelligent quantification system for fetal heart rhythm assessment: A multicenter prospective study.

BACKGROUND: The motion relationship and time intervals of the pulsed-wave Doppler (PWD) spectrum are essential for diagnosing fetal arrhythmia. However, few technologies currently are available to automatically calculate fetal cardiac time intervals (CTIs). OBJECTIVE: The purpose of this study was to develop a fetal heart rhythm intelligent quantification system (HR-IQS) for the automatic extraction of CTIs and establish the normal reference range for fetal CTIs. METHODS: A total of 6498 PWD spectrums of 2630 fetuses over the junction between the left ventricular inflow and outflow tracts were recorded across 14 centers. E, A, and V waves were manually labeled by 3 experienced fetal cardiologists, with 17 CTIs extracted. Five-fold cross-validation was performed for training and testing of the deep learning model. Agreement between the manual and HR-IQS-based values was evaluated using the intraclass correlation coefficient and Spearman's rank correlation coefficient. The Jarque-Bera test was applied to evaluate the normality of CTIs' distributions, and the normal reference range of 17 CTIs was established with quantile regression. Arrhythmia subset was compared with the non-arrhythmia subset using the Mann-Whitney U test. RESULTS: Significant positive correlation (P <.001) and moderate-to-excellent consistency (P <.001) between the manual and HR-IQS automated measurements of CTIs was found. The distribution of CTIs was non-normal (P <.001). The normal range (2.5th to 97.5th percentiles) was successfully established for the 17 CTIs. CONCLUSIONS: Using our HR-IQS is feasible for the automated calculation of CTIs in practice and thus could provide a promising tool for the assessment of fetal rhythm and function.

Phylogenetic analysis based on the complete mitochondrial genome of Discogobio brachyphysallidos (Cypriniformes: Cyprinidae) suggests the need for taxonomic revision at the genus level.

Discogobio brachyphysallidos Huang 1989 is a Cyprinidae fish species that is endemic to the upper Pearl River. In the present study, the complete mitochondrial genome of D. brachyphysallidos collected from the Nanpanjiang River was sequenced and annotated. The mitochondrial genome encompassed 13 protein-coding genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and the control region (D-loop). The total length of the mitochondrial genome was determined to be 16,594 base pairs (bp), with a GC content of 41.7%. Phylogenetic analyses revealed that D. brachyphysallidos may be a sister to D. longibarbatus and D. macrophysallidos. These findings provide insight into the genetic information and phylogenetic relationships of D. brachyphysallidos.

Radical Cross Coupling and Enantioselective Protonation through Asymmetric Photoredox Catalysis.

An unprecedented enantioselective protonation reaction enabled by photoredox catalytic radical coupling is developed. Under cooperative dicynopyrazine-derived chromophore (DPZ) as a photosensitizer and a chiral phosphoric acid catalyst, and Hantzsch ester as a sacrificial reductant, the transformations between α-substituted enones and cyanoazaarenes or 2-(chloromethyl)azaaren-1-iums can proceed a tandem reduction, radical coupling, and enantioselective protonation process efficiently. Two classes of pharmaceutically important enantioenriched azaarene variants, which contain a synthetically versatile ketone-substituted tertiary carbon stereocenter at the ß- or γ-position of the azaarenes, are synthesized with high yields and ees.

Progress of SARS-CoV-2 Main protease peptide-like inhibitors.

The pneumonia outbreak caused by Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) infection poses a serious threat to people worldwide. Although vaccines have been developed, antiviral drugs are still needed to combat SARS-CoV-2 infection due to the high mutability of the virus. SARS-CoV-2 main protein (Mpro ) is a special cysteine protease that is a key enzyme for SARS-CoV-2 replication. It is encoded by peptides and is responsible for processing peptides into functional proteins, making it an important drug target. The paper reviews the structure and peptide-like inhibitors of SARS-CoV-2 Mpro , also the binding mode and structure-activity relationship between the inhibitors and Mpro are introduced in detail. It is hoped that this review can provide ideas and help for the development of anti-coronavirus drugs such as COVID-19, and help to develop broad-spectrum antiviral drug for the treatment of coronavirus diseases as soon as possible.

Discovery a series of novel inhibitors of human dihydroorotate dehydrogenase: Biological activity evaluation and molecular docking.

Human dihydroorotate dehydrogenase (hDHODH) is a key enzyme that catalyzes the de novo synthesis of pyrimidine. In recent years, various studies have shown that inhibiting this enzyme can treat autoimmune diseases such as rheumatoid arthritis (RA) and cancer. This study designed and synthesized a series of novel thiazolidone hDHODH inhibitors. Through biological activity evaluation, Compound 14 was found to have high inhibitory activity, with an IC50 value reaching nanomolar level. Preliminary structure-activity relationship studies found that the carboxyl group in R1 and the naphthalene in R2 are key factors in improving activity. Through molecular docking, the binding mode between inhibitors and proteins was elucidated. This study provides an important reference for further optimizing hDHODH inhibitors.

[A new xanthone from hulls of Garcinia mangostana and its cytotoxic activity].

Eight compounds were isolated from ethyl acetate fraction of 80% ethanol extract of the hulls of Garcinia mangostana by silica gel, Sephadex LH-20 column chromatography, as well as prep-HPLC methods. By HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the eight compounds were identified as 16-en mangostenone E(1), α-mangostin(2), 1,7-dihydroxy-2-(3-methy-lbut-2-enyl)-3-methoxyxanthone(3), cratoxyxanthone(4), 2,6-dimethoxy-para-benzoquinone(5), methyl orselinate(6), ficusol(7), and 4-(4-carboxy-2-methoxyphenoxy)-3,5-dimethoxybenzoic acid(8). Compound 1 was a new xanthone, and compound 4 was a xanthone dimer, compound 5 was a naphthoquinone. All compounds were isolated from this plant for the first time except compounds 2 and 3. Cytotoxic bioassay suggested that compounds 1, 2 and 4 possessed moderate cytotoxicity, suppressing HeLa cell line with IC_(50) va-lues of 24.3, 35.5 and 17.1 µmol·L~(-1), respectively. Compound 4 also could suppress K562 cells with an IC_(50) value of 39.8 µmol·L~(-1).

RPA-CRISPR/Cas12a-Based Detection of Haemophilus parasuis.

Haemophilus parasuis (H. parasuis, HPS) is a prominent pathogenic bacterium in pig production. Its infection leads to widespread fibrinous inflammation in various pig tissues and organs, often in conjunction with various respiratory virus infections, and leads to substantial economic losses in the pig industry. Therefore, the rapid diagnosis of this pathogen is of utmost importance. In this study, we used recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR) technology to establish a convenient detection and analysis system for H. parasuis that is fast to detect, easy to implement, and accurate to analyze, known as RPA-CRISPR/Cas12a analysis. The process from sample to results can be completed within 1 h with high sensitivity (0.163 pg/µL of DNA template, p < 0.05), which is 104 -fold higher than the common PCR method. The specificity test results show that the RPA-CRISPR/Cas12a analysis of H. parasuis did not react with other common pig pathogens, including Streptococcus suis type II and IX, Actinobacillus pleuropneumoniae, Escherichia coli, Salmonella, Streptococcus suis, and Staphylococcus aureus (p < 0.0001). The RPA-CRISPR/Cas12a assay was applied to 15 serotypes of H. parasuis clinical samples through crude extraction of nucleic acid by boiling method, and all of the samples were successfully identified. It greatly reduces the time and cost of nucleic acid extraction. Moreover, the method allows results to be visualized with blue light. The accurate and convenient detection method could be incorporated into a portable format as point-of-care (POC) diagnostics detection for H. parasuis at the field level.

Unlocking mild-condition benzene ring contraction using nonheme diiron N-oxygenase.

Benzene ring contractions are useful yet rare reactions that offer a convenient synthetic route to various valuable chemicals. However, the traditional methods of benzene contraction rely on noble-metal catalysts under extreme conditions with poor efficiency and uncontrollable selectivity. Mild-condition contractions of the benzene ring are rarely reported. This study presents a one-step, one-pot benzene ring contraction reaction mediated by an engineered nonheme diiron N-oxygenase. Using various aniline substrates as amine sources, the enzyme causes the phloroglucinol-benzene-ring contraction to afford a series of 4-cyclopentene-1,3-dione structures. A reaction detail study reveals that the nonheme diiron N-oxygenase first oxidizes the aromatic amine to a nitroso intermediate, which then attacks the phloroglucinol anion and causes benzene ring contraction. Besides, we have identified two potent antitumor compounds from the ring-contracted products.

Investigation on large-scale 3D seepage characteristics of a pumped-storage power station: a case study in Zhejiang Province, China.

Pumped-storage power stations (PSPSs) have higher requirements for anti-seepage compared with regular power stations. As a result, investigating the seepage distributions of PSPSs is particularly important. However, existing researches remain limited in assessing engineering needs such as ensuring the efficiency of a power station. Taking the Qingyuan PSPS as a typical case, this study aims to investigate the large-scale seepage field distribution while exploring the efficiency of the anti-seepage system. Considering the geological characteristics and structural location, a 3D finite element model is established. Based on the continuous medium model while combined with seepage control measures, the change in leakage while the anti-seepage system failed is further assessed. It is concluded that the operation status of anti-seepage measures will have a certain impact on the leakage volumes of each part. Using a comprehensive assessment, anti-seepage measures can effectively prevent seepage. When failure occurs on anti-seepage curtains, the leakage volume at the corresponding position will show an obvious growth. In summary, the findings of this study highlight the significance of avoiding excessive leakage caused by anti-seepage structure failure, the effective operation of anti-seepage measures must be ensured. The abovementioned results can provide scientific support for the seepage optimization design of PSPSs.

Asymmetric Olefin Isomerization via Photoredox Catalytic Hydrogen Atom Transfer and Enantioselective Protonation.

Asymmetric olefin isomerization can be appreciated as an ideal synthetic approach to access valuable enantioenriched C═C-containing molecules due to the excellent atom economy. Nonetheless, its occurrence usually requires a thermodynamic advantage, namely, a higher stability of the product to the substrate. It has thus led to rather limited examples of success. Herein, we report a photoredox catalytic hydrogen atom transfer (HAT) and enantioselective protonation strategy for the challenging asymmetric olefin isomerization. As a paradigm, by establishing a dual catalyst system involving a visible light photosensitizer DPZ and a chiral phosphoric acid, with the assistance of N-hydroxyimide to perform HAT, a wide array of allylic azaarene derivatives, featuring α-tertiary carbon stereocenters and ß-C═C bonds, was synthesized with high yields, ees, and E/Z ratios starting from the conjugated α-substituted alkenylazaarene E/Z-mixtures. The good compatibility of assembling deuterium on stereocenters by using inexpensive D2O as a deuterium source further underscores the broad applicability and promising utility of this strategy. Moreover, mechanistic studies have provided clear insights into its challenges in terms of reactivity and enantioselectivity. The exploration will robustly inspire the development of thermodynamically unfavorable asymmetric olefin isomerizations.

Enantioselective Chemodivergent Three-Component Radical Tandem Reactions through Asymmetric Photoredox Catalysis.

Chemodivergent synthesis has been achieved in asymmetric photocatalysis. Under a dual catalyst system consisting of a chiral phosphoric acid and DPZ as a photosensitizer, different inorganic bases enabled the formation of two sets of valuable products from the three-component radical tandem transformations of 2-bromo-1-arylenthan-1-ones, styrenes, and quinoxalin-2(1H)-ones. The key to success was the distinct pKa environment, in which the radicals that formed on the quinoxalin-2(1H)-one rings after two radical addition processes underwent either single-electron oxidation or single-electron reduction. In addition, this work represents the first use of quinoxalin-2(1H)-ones in asymmetric photoredox catalysis.