Organoboron-Promoted Electrochemical Chlorosulfonylation of Alkenes with Sulfonyl Chlorides.

Although extraordinary advances have been achieved by the transition-metal catalysis system, there is an urgent need to explore and develop alternative methodologies that are more environmentally friendly. Herein, we report an electrochemical chlorosulfonylation of alkenes using a wide range of sulfonyl chlorides with an inexpensive, degradable, and commercially available organoboron as a promoter. Furthermore, this protocol employs convergent paired electrolysis, reducing the need for sacrificial anodes and minimizing the extent of hydrogen evolution.

Efficient and selective external activator-free cobalt catalyst for hydroboration of terminal alkynes enabled by BiPyPhos.

Herein, a robust catalyst system, composed of a bipyridine-based diphosphine ligand (BiPyPhos) and a cobalt precursor Co(acac)2, is successfully developed and applied in the hydroboration of terminal alkynes, exclusively affording various versatile ß-E-vinylboronates in high yields at room temperature.

scGAL: unmask tumor clonal substructure by jointly analyzing independent single-cell copy number and scRNA-seq data.

BACKGROUND: Accurately deciphering clonal copy number substructure can provide insights into the evolutionary mechanism of cancer, and clustering single-cell copy number profiles has become an effective means to unmask intra-tumor heterogeneity (ITH). However, copy numbers inferred from single-cell DNA sequencing (scDNA-seq) data are error-prone due to technically confounding factors such as amplification bias and allele-dropout, and this makes it difficult to precisely identify the ITH. RESULTS: We introduce a hybrid model called scGAL to infer clonal copy number substructure. It combines an autoencoder with a generative adversarial network to jointly analyze independent single-cell copy number profiles and gene expression data from same cell line. Under an adversarial learning framework, scGAL exploits complementary information from gene expression data to relieve the effects of noise in copy number data, and learns latent representations of scDNA-seq cells for accurate inference of the ITH. Evaluation results on three real cancer datasets suggest scGAL is able to accurately infer clonal architecture and surpasses other similar methods. In addition, assessment of scGAL on various simulated datasets demonstrates its high robustness against the changes of data size and distribution. scGAL can be accessed at: https://github.com/zhyu-lab/scgal . CONCLUSIONS: Joint analysis of independent single-cell copy number and gene expression data from a same cell line can effectively exploit complementary information from individual omics, and thus gives more refined indication of clonal copy number substructure.

CO2 Enrichment Boosts Highly Selective Infrared-Light-Driven CO2 Conversion to CH4 by UiO-66/Co9S8 Photocatalyst.

Photocatalytic CO2 reduction to high-value chemicals is an attractive approach to mitigate climate change, but it remains a great challenge to produce a specific product selectively by IR light. Hence, UiO-66/Co9S8 composite is designed to couple the advantages of metallic photocatalysts and porous CO2 adsorbers for IR-light-driven CO2-to-CH4 conversion. The metallic nature of Co9S8 endows UiO-66/Co9S8 with exceptional IR light absorption, while UiO-66 dramatically enhances its local CO2 concentration, revealed by finite-element method simulations. As a result, Co9S8 or UiO-66 alone does not show observable IR-light photocatalytic activity, whereas UiO-66/Co9S8 exhibits exceptional activity. The CH4 evolution rate over UiO-66/Co9S8 reaches 25.7 µmol g-1 h-1 with ca.100% selectivity under IR light irradiation, outperforming most reported catalysts under similar reaction conditions. The X-ray absorption fine structure spectroscopy spectra verify the presence of two distinct Co sites and confirm the existence of metallic Co─Co bond in Co9S8. Energy diagrams analysis and transient absorption spectra manifest that CO2 reduction mainly occurs on Co9S8 for UiO-66/Co9S8, while density functional theory calculations demonstrate that high-electron-density Co1 sites are the key active sites, possessing lower energy barriers for further protonation of *CO, leading to the ultra-high selectivity toward CH4.

Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis.

Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB-like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB-associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand-receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB-associated malignancies in patients with PN.

Bioelectro-barriers prevent nitrate leaching into groundwater via nitrogen retention.

Groundwater, the main freshwater resource for humans, has been widely contaminated with nitrate from fertilizers. Here, we report a new and chemical-free strategy to prevent nitrate leaching from soil based on the enrichment of electroactive bacteria, mainly of the genus Geobacter, with bioelectro-barriers, which leads to a nearly 100 % interception of nitrate and partly conserves reactive nitrogen in the form of weakly mobile ammonium by dissimilatory nitrate reduction to ammonium (DNRA). G. sulfurreducens was recognized to efficiently secrete nitrite reductase (NrfA) for rapid DNRA because it lacks nitrate reductase, which inhibits DNRA by competing with nitrite and producing toxic intracellular nitric oxide. With an increase in G. sulfurreducens abundance, near-zero nitrate leaching and 3-fold greater N retention was achieved. Periodic application of weak electricity to the bioelectro-barrier ensured the dominance of G. sulfurreducens in the microbial community and therefore its ability to consistently prevent nitrate leaching. The ability of G. sulfurreducens to intercept nitrate was further demonstrated in more diverse agricultural soils, providing a novel way to prevent nitrate leaching and conserve bioavailable nitrogen in the soil, which has broader implications for both sustainable agriculture and groundwater protection.

Interactions among microorganisms functionally active for electron transfer and pollutant degradation in natural environments.

Compared to single microbial strains, complex interactions between microbial consortia composed of various microorganisms have been shown to be effective in expanding ecological functions and accomplishing biological processes. Electroactive microorganisms (EMs) and degradable microorganisms (DMs) play vital roles in bioenergy production and the degradation of organic pollutants hazardous to human health. These microorganisms can strongly interact with other microorganisms and promote metabolic cooperation, thus facilitating electricity production and pollutant degradation. In this review, we describe several specific types of EMs and DMs based on their ability to adapt to different environments, and summarize the mechanism of EMs in extracellular electron transfer. The effects of interactions between EMs and DMs are evaluated in terms of electricity production and degradation efficiency. The principle of the enhancement in microbial consortia is also introduced, such as improved biomass, changed degradation pathways, and biocatalytic potentials, which are directly or indirectly conducive to human health.

Ginkgo biloba Extract 50 (GBE50) Exerts Antifibrotic and Antioxidant Effects on Pulmonary Fibrosis in Mice by Regulating Nrf2 and TGF-ß1/Smad Pathways.

BACKGROUND: Pulmonary fibrosis (PF) is a progressive lung disorder with a poor prognosis. GBE50 is a new standardized Ginkgo biloba extract that has been widely used in cardiovascular diseases. However, the protective mechanism of GBE50 against PF remains to be elucidated. METHODS: C57BL/6J mice were treated with bleomycin (Bleo) to induce PF in the presence or absence of GBE50. Protein content in bronchoalveolar lavage fluid (BALF) and wet weight/dry weight ratio were examined for analysis of pulmonary edema. Hematoxylin-eosin staining and Masson trichrome staining were used for histopathological observation of murine lung tissues. Ashcroft score was used for semi-quantitation of lung fibrosis degree. RT-qPCR was utilized for assessing mRNA levels of pro-fibrotic mediators in lung tissues. TUNEL staining was implemented for cell apoptosis assessment. The levels of oxidative stress- and inflammation-related markers were evaluated by corresponding commercial assay kits. Western blotting was used to evaluate levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling- and transforming growth factor (TGF)-ß1/SMAD signaling-related proteins. RESULTS: GBE50 alleviated lung injury and severity of fibrosis, reduced collagen deposition and cell apoptosis in lung tissues, and suppressed inflammatory response and oxidative stress injury in Bleo-stimulated PF mice. GBE50 activated Nrf2 signaling pathway and inactivated TGF-ß1/SMAD signaling pathway in the lungs of Bleo-induced PF mice. Inhibition of Nrf2 signaling reversed GBE50-mediated inactivation of TGF-ß1/SMAD signaling and attenuation of inflammation and oxidative stress in Bleo-induced PF mice. CONCLUSION: GBE50 protects against Bleo-induced PF in mice by mitigating fibrosis, inflammation and oxidative stress via Nrf2 and TGF-ß1/SMAD signaling pathways.

Ketamine-induced 1-Hz oscillation of spontaneous neural activity is not directly visible in the hemodynamics.

The extent to which resting-state hemodynamics reflects the underlying neural activity is still under debate. Especially in the delta frequency band (0.5-4 Hz), it is unclear whether the hemodynamics can directly track the dynamics of underlying neural activity. Based on a recent report showing that ketamine administration induced a 1-Hz neural activity oscillation in the retrosplenial cortex, we conducted simultaneous recordings of the calcium signal and hemodynamics in mice and examined whether the hemodynamics tracked the oscillatory neural activity. Although we observed that the oscillation induced by ketamine appeared in the calcium signal, no sign of oscillation was detected in the simultaneously recorded hemodynamics. Consistently, there was a notable decrease in the correlation between simultaneously recorded calcium signal and hemodynamics. However, on a much longer time scale (10-60 min), we unexpectedly observed an ultraslow increase of hemodynamic signals specifically in the same cortical region exhibiting the neural activity oscillation. These results indicated that hemodynamics cannot track the 1-Hz oscillation in neural activity, although the presence of neural activity oscillation was detectable on a longer timescale. Such ultraslow hemodynamics may be useful for detecting abnormal neural activity induced by psychotic drugs or mental disorders.

Transcriptome analysis of immune-related genes of Asian corn borer (Ostrinia furnacalis [Guenée]) after oral bacterial infection.

The Asian corn borer (Ostrinia furnacalis) is an important agricultural pest causing serious damage to economic crops, such as corn and sorghum. The gut is the first line of defense against pathogens that enter through the mouth. Staphylococcus aureus was used to infect the O. furnacalis midgut to understand the midgut immune mechanism against exogenous pathogens to provide new ideas and methods for the prevention and control of O. furnacalis. A sequencing platform was used for genome assembly and gene expression. The unigene sequences were annotated and functionally classified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Significant differences were found in the induced expression profiles before and after infection. Some differentially expressed genes have important relations with lipid metabolism and immune mechanism, suggesting that they play an important role in the innate immune response of O. furnacalis. Furthermore, quantitative real-time polymerase chain reaction assay was used to identify the key genes involved in the signaling pathway, and the expression patterns of these key genes were confirmed. The results could help study the innate immune system of lepidopteran insects and provide theoretical support for the control of related pests and the protection of beneficial insects.

Pyrazole-pyridine-pyrazole (NNN) ruthenium(II) complex catalyzed acceptorless dehydrogenation of alcohols to aldehydes.

A new series of cationic ruthenium(II) complexes, [RuCl(PPh3)2(κ3-NNN-L1)]Cl (1), [RuH(PPh3)2(κ3-NNN-L2)]Cl (2), and [RuH(PPh3)2(κ3-NNN-L3)]Cl (3), bearing a 2,6-bis (1-R-5-methyl-pyrazol-3-yl) pyridine ligand (L1: R = H, L2: R = C6H4-p-CF3, L3: R = C6H4-p-OCH3), were synthesized and characterized with NMR, HRMS, and single-crystal X-ray diffraction. Their catalytic application was investigated in the acceptorless dehydrogenation (AD) of primary alcohols. Complex 1 outperformed 2 and 3 in terms of the selectivity towards the aldehydes, and provided the aldehydes with a yield of up to 99%, with good functional group tolerance under mild conditions. In addition, the only by-product of the reaction was dihydrogen, which can be collected as clean energy, and the reaction meets the requirements of environment-friendly chemistry. Complex 1 also proved to be a promising catalyst in the sequential AD/condensation reaction between the primary and secondary alcohols, affording α,ß-unsaturated ketones in moderate to good selectivity.

Copper-Mediated and Palladium-Catalyzed Cross-Coupling of Indoles and N-Methylpyridinium Salts: A Practical Way to Prepare 3-(Pyridin-2-yl)indoles.

Herein, a Pd/Cu bimetallic-catalyzed direct C-H heteroarylation of pyridines via the traceless protecting group strategy is described. A series of N-methyl-activated pyridines and 1-methylindoles are coupled with high regioselectivity to produce the corresponding 3-(pyridin-2-yl)indoles in moderate to good yields, wherein related electron-rich heterocycles (e.g., indole, 1-methylpyrrole, benzofuran, benzo[b]thiophene) are also applicable. Streamlined operation, good functional group tolerance, and late-stage modifications make this twofold C-H activation protocol an attractive route for the synthesis of 3-(pyridin-2-yl)indole derivatives.

Pro­angiogenic activity of salvianolate and its potential therapeutic effect against acute cerebral ischemia.

Salvianolate (Sal) is a medicinal composition that is widely used in China for the treatment of coronary heart disease and angina pectoris. The aim of the present study was to investigate the potential macrophage-mediated pro-angiogenic effects of Sal in vitro. In addition, another aim was to explore the effects of Sal in a rat model of transient middle cerebral artery occlusion (tMCAO) along with the potential mechanism by which it promotes angiogenesis. In this study, human umbilical vein endothelial cells (HUVECs) and Raw264.7 macrophages in vitro, and a rat tMCAO model in vivo were used to detect the pro-angiogenic effect and mechanism of Sal. The results of in vitro experiments showed that the viability, migration and tube formation of HUVECs were promoted by the supernatant of Sal-treated Raw264.7 macrophages (s-Sal) but not by Sal alone. s-Sal also increased the levels of phosphorylated (p-)VEGFR-2, p-AKT and p-p38 MAPK in HUVECs while Sal alone did not. In vivo, treatment with Sal significantly reduced the cerebral infarction volume and neurological deficit scores in the rat tMCAO model. Similar to the mechanism observed in the in vitro experiments, Sal treatment upregulated the protein expression of VEGF and VEGFR-2, in addition to the phosphorylation of VEGFR-2, AKT and p38, in the brain tissues of the tMCAO model rats. In summary, the results of the present study suggest that the mechanism of Sal-mediated angiogenesis is associated with stimulation of the VEGF/VEGFR-2 signaling pathway by macrophages. This suggests the potential of Sal as a therapeutic option for the treatment of acute cerebral ischemic injury, which may act via the promotion of angiogenesis.

Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1.

Hyperinsulinemia and insulin resistance in T2D have a potent suppressive effect on hepatic autophagy, however, the underlying mechanisms remain unclear. To explore the effect of insulin on hepatic autophagy and its possible signaling pathways, HL-7702 cells were treated with insulin with or without insulin signaling inhibitors. The interaction between insulin and the promoter region of GABARAPL1 was assessed through luciferase assay and EMSA. There were significant dose-dependent decreases in the number of intracellular autophagosomes and the protein levels of GABARAPL1 and beclin1 in insulin-treated HL-7702 cells. Insulin signaling inhibitors reversed the inhibitory effect of insulin on rapamycin-induced autophagy and autophagy-related gene upregulation. Insulin blocks the binding of FoxO1 to putative insulin response elements in GABARAPL1 gene promoter, leading to the repressed transcription of GABARAPL1 gene and the suppression of hepatic autophagy. Our study identified GABARAPL1 as a novel target of insulin in suppressing hepatic autophagy.

Exogenous Electroactive Microbes Regulate Soil Geochemical Properties and Microbial Communities by Enhancing the Reduction and Transformation of Fe(III) Minerals.

Electroactive microbes can conduct extracellular electron transfer and have the potential to be applied as a bioresource to regulate soil geochemical properties and microbial communities. In this study, we incubated Fe-limited and Fe-enriched farmland soil together with electroactive microbes for 30 days; both soils were incubated with electroactive microbes and a common iron mineral, ferrihydrite. Our results indicated that the exogenous electroactive microbes decreased soil pH, total organic carbon (TOC), and total nitrogen (TN) but increased soil conductivity and promoted Fe(III) reduction. The addition of electroactive microbes also changed the soil microbial community from Firmicutes-dominated to Proteobacteria-dominated. Moreover, the total number of detected microbial species in the soil decreased from over 700 to less than 500. Importantly, the coexistence of N-transforming bacteria, Fe(III)-reducing bacteria and methanogens was also observed with the addition of electroactive microbes in Fe-rich soil, indicating the accelerated interspecies electron transfer of functional microflora.

The antinociceptive activity and mechanism of action of cannabigerol.

Cannabis has been used for centuries to treat pain. The antinociceptive activity of tetrahydrocannabinol (THC) or cannabidiol (CBD) has been widely studied. However, the antinociceptive effects of other cannabis components, such as cannabichromene (CBC) and cannabigerol (CBG), have rarely been revealed. The antinociceptive mechanism of CBG is not yet clear, so we investigated the antinociceptive effect of CBG on different pain models, and explored the mechanism of action of CBG to exert antinociceptive effects. In the current study, we compared the antinociceptive effects of CBC, CBD, and CBG on the carrageenan-induced inflammatory pain model in mice, and the results showed that CBG had a better antinociceptive effects through intraplantar administration. On this basis, we further investigated the antinociceptive effect of CBG on CIA-induced arthritis pain model and nerve pain model in mice, and found that CBG also relieved on both types of pain. Then, we explored the antinociceptive mechanism of CBG, which revealed that CBG can activate TRPV1 and desensitize it to block the transmission of pain signals. In addition, CBG can further activate CB2R, but not CB1R, to stimulate the release of ß-endorphin, which greatly promotes the antinociceptive effect. Finally, the safety test results showed that CBG had no irritating effect on the rabbits' skin, and it did not induce significant biochemical and hematological changes in mice. Transdermal delivery results also indicated that CBG has certain transdermal properties. Overall, this study indicates that CBG is promising for developing a transdermal dosage for pain management.

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis.

Prurigo nodularis (PN) is an intensely pruritic, chronic inflammatory skin disease that disproportionately affects black patients. However, the pathogenesis of PN is poorly understood. We performed single-cell transcriptomic profiling, ligand receptor analysis and cell trajectory analysis of 28,695 lesional and non-lesional PN skin cells to uncover disease-identifying cell compositions and genetic characteristics. We uncovered a dysregulated role for fibroblasts (FBs) and myofibroblasts as a key pathogenic element in PN, which were significantly increased in PN lesional skin. We defined seven unique subclusters of FBs in PN skin and observed a shift of PN lesional FBs towards a cancer-associated fibroblast (CAF)-like phenotype, with WNT5A+ CAFs increased in the skin of PN patients and similarly so in squamous cell carcinoma (SCC). A multicenter PN cohort study subsequently revealed an increased risk of SCC as well as additional CAF-associated malignancies in PN patients, including breast and colorectal cancers. Systemic fibroproliferative diseases were also upregulated in PN patients, including renal sclerosis and idiopathic pulmonary fibrosis. Ligand receptor analyses demonstrated increased FB1-derived WNT5A and periostin interactions with neuronal receptors MCAM and ITGAV, suggesting a fibroblast-neuronal axis in PN. Type I IFN responses in immune cells and increased angiogenesis/permeability in endothelial cells were also observed. As compared to atopic dermatitis (AD) and psoriasis (PSO) patients, increased mesenchymal dysregulation is unique to PN with an intermediate Th2/Th17 phenotype between atopic dermatitis and psoriasis. These findings identify a pathogenic role for CAFs in PN, including a novel targetable WNT5A+ fibroblast subpopulation and CAF-associated malignancies in PN patients.

Self-assembly formation of CuI hybrid micron phosphors with tunable emission for multifunctional applications.

Low-cost and eco-friendly CuI hybrid compounds with various structures have recently attracted increasing attention due to their excellent optical properties and promising phosphor applications. However, the poor solubility and solution processability of bulk powders with agglomerated particle limited their practical applications greatly. In this work, we reported the self-assembly formation of CuI hybrid micron phosphors via the aqueous PVP micelle-assisted assembly route. Seven CuI hybrid micron phosphors with the emission from blue 450 nm to red 636 nm have been successfully synthesized. Among them, CuI-pyridine hybrid micron phosphors can be obtained via the reaction of CuI with various pyridines. PVP limits the size growth of the phosphors efficiently and it also plays an important role in controlling the distinct crystal phase formation. Whereas, micron phosphors based on bidentate ligands including 2-propylpyrazine, 5-bromopyrimidine or 4,4'-bipyridine need to be prepared via ligand exchange reaction. The micron phosphors present excellent stability in water and can be dispersed in the aqueous solution of PVP or PVA to form homogenous luminescent composites. The luminescent composites based on PVP are easy to use for fabricating anti-counterfeiting patterns via brush-painting or screen-printing. On the other hand, PVA composites can be applied for preparing free standing monochromatic or multichromatic emitting films as color convertor for display backlight. The PVA composites also exhibit the promising phosphor application for light-emitting diode (LED). Especially, the white LED can be directly realized via optimizing the mixing ratio of blue and orange phosphors.