Reduction of Li+ within a borate anion.

Group 1 elements exhibit the lowest electronegativity values in the Periodic Table. The chemical reduction of Group 1 metal cations M+ to M(0) is extremely challenging. Common tetraaryl borates demonstrate limited redox properties and are prone to decomposition upon oxidation. In this study, by employing simple yet versatile bipyridines as ligands, we synthesized a series of redox-active borate anions characterized by NMR and X-ray single-crystal diffraction. Notably, the borate anion can realize the reduction of Li+, generating elemental lithium metal and boron radical, thereby demonstrating its potent reducing ability. Furthermore, it can serve as a powerful two-electron-reducing reagent and be readily applied in various reductive homo-coupling reactions and Birch reduction of acridine. Additionally, this borate anion demonstrates its catalytic ability in the selective two-electron reduction of CO2 into CO.

Charge Separation in Metal-Organic Framework Enables Heterogeneous Thiol Catalysis.

Photoinduced metal-organic framework (MOF) enabled heterogeneous thiol catalysis has been achieved for the first time. MOF Zr-TPDCS-1, consisting of Zr6 -clusters and TPDCS linkers (TPDCS=3,3'',5,5''-tetramercapto[1,1':4',1''-terphenyl]-4,4''-dicarboxylate), effectively catalyzed the borylation, silylation, phosphorylation, and thiolation of organic molecules. Upon irradiation, the fast electron transfer from TPDCS to Zr6 -cluster is believed to facilitate the formation of the thiyl radical, a hydrogen atom transfer catalyst, which competently abstracts the hydrogen from borane, silane, phosphine, or thiol for generating the corresponding element radical to engender the chemical transformations. The elaborate control experiments evidenced the generation of thiyl radicals in MOF and illustrated a radical reaction pathway. The gram-scale reaction worked well, and the product was conveniently separated via centrifugation and vacuum with a turnover number (TON) of ≈3880, highlighting the practical application potential of heterogeneous thiyl-radical catalysis.

Unsupervised Stain Decomposition via Inversion Regulation for Multiplex Immunohistochemistry Images.

Multiplex Immunohistochemistry (mIHC) is a cost-effective and accessible method for in situ labeling of multiple protein biomarkers in a tissue sample. By assigning a different stain to each biomarker, it allows the visualization of different types of cells within the tumor vicinity for downstream analysis. However, to detect different types of stains in a given mIHC image is a challenging problem, especially when the number of stains is high. Previous deep-learning-based methods mostly assume full supervision; yet the annotation can be costly. In this paper, we propose a novel unsupervised stain decomposition method to detect different stains simultaneously. Our method does not require any supervision, except for color samples of different stains. A main technical challenge is that the problem is underdetermined and can have multiple solutions. To conquer this issue, we propose a novel inversion regulation technique, which eliminates most undesirable solutions. On a 7-plexed IHC images dataset, the proposed method achieves high quality stain decomposition results without human annotation.

Extracellular vesicle miRNAs promote the intestinal microenvironment by interacting with microbes in colitis.

Inflammatory bowel disease (IBD) is a global disease with no cure. Disruption of the microbial ecosystem is considered to be an important cause of IBD. Extracellular vesicles (EVs) are vital participants in cell-cell and cell-organism communication. Both host-derived EVs and bacteria-derived membrane vesicles (OMVs) contribute to homeostasis in the intestine. However, the roles of EVs-miRNAs and MVs in host-microbe interactions in colitis remain unclear. In the present study, the animal model of colitis was established by dextran sulfate sodium (DSS) to investigate the changes of miRNAs in colonic EVs from colitis. Several miRNAs were significantly altered in colitis EVs. miR-181b-5p transplantation inhibited M1 macrophage polarization and promoted M2 polarization to reduce the levels of inflammation both in acute and remission of chronic colitis. miR-200b-3p could interact with bacteria and regulate the composition of the microbiota, which contributed to intestinal barrier integrity and homeostasis. Notably, MVs from normal feces could effectively reverse the composition of the intestinal microbiota, restore the intestinal barrier and rescue colitis, and BMVs from colitis would also have similar effects after miR-200b-3p treatment. Our results preliminarily identify a vesicle-based host-microbe interaction cycle in colitis and provide new ideas for colitis treatment.

Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease.

Background: The intestinal tract is a complicated ecosystem with dynamic homeostasis via interaction of intestine and microbiota. Inflammatory bowel disease (IBD) is chronic intestinal inflammation involving dysbiosis of intestinal microenvironment. Extracellular vesicles (EVs), as vital characteristics of cell-cell and cell-organism communication, contribute to homeostasis in intestine. Recently, EVs showed excellent potential for clinical applications in disease diagnoses and therapies. Aim of Review: Our current review discusses the modulatory functions of EVs derived from different sources in intestine, especially their effects and applications in IBD clinical therapy. EV-mediated interaction systems between host intestine and microbiota were established to describe possible mechanisms of IBD pathogenesis and its cure. Key Scientific Concepts of Review: EVs are excellent vehicles for delivering molecules containing genetic information to recipient cells. Multiple pieces of evidence have illustrated that EVs participate the interaction between host and microbiota in intestinal microenvironment. In inflammatory intestine with dysbiosis of microbiota, EVs as regulators target promoting immune response and microbial reconstruction. EVs-based immunotherapy could be a promising therapeutic approach for the treatment of IBD in the near future.

Evaluation of the predictive performance of Bayesian dosing for warfarin in Chinese patients.

AIM: To evaluate the accuracy and predictive performance of Bayesian dosing for warfarin in Chinese patients. MATERIALS & METHODS: Six multiple linear regression algorithms (Wei, Lou, Miao, Huang, Gage and IWPC) and a Bayesian method implemented in Warfarin Dose Calculator were compared with each other. RESULTS: Six multiple linear regression warfarin dosing algorithms had similar predictive ability, except Miao and Lou. The mean prediction error of Bayesian priori and posteriori method were 0.01 mg/day (95% CI: -0.18 to 0.19) and 0.17 mg/day (95% CI: -0.05 to 0.29), respectively, and Bayesian posteriori method demonstrated better performance in all dose ranges. CONCLUSION: The Bayesian method showed a good potential for warfarin maintenance dose prediction in Chinese patients requiring less than 6 mg/day.

Efficacy and safety of CYP2C19 genotype in stroke or transient ischemic attack patients treated with clopidogrel monotherapy or clopidogrel plus aspirin: Protocol for a systemic review and meta-analysis.

BACKGROUND: The relationship of CYP2C19 genotype and clinical efficacy in stroke or transient ischemic attack (TIA) patients treated with clopidogrel monotherapy or clopidogrel plus aspirin remains unknown. We thus aim to conduct a meta-analysis to appraise evidence on the association of CYP2C19 genotype and clinical efficacy for stroke or TIA. METHODS: An electronic search will be performed for clinical trials that reported the interested efficacy data (stroke, myocardial infarction, or vascular death) and safety data (any bleeding) in clopigogrel-treated patients with stroke or TIA. Odds ratios (ORs) with their confidence intervals (CIs) will be calculated using a meta-analysis. RESULTS: This study will provide the evidence of the relationship between CYP2C19 genotype and clinical efficacy and safety in stroke/TIA patients taking clopidogrel by pooling the results of individual studies. CONCLUSIONS: The results will bring about vigorous evidence in this issue and guide both clinical decision-making and future research.