Visible light driven deuteration of formyl C–H and hydridic C(sp3)–H bonds in feedstock chemicals and pharmaceutical molecules

Deuterium labelled compounds are of significant importance in chemical mechanism investigations, mass spectrometric studies, diagnoses of drug metabolisms, and pharmaceutical discovery. Herein, we report an efficient hydrogen deuterium exchange reaction using deuterium oxide (D₂O) as the deuterium source, enabled by merging a tetra-n-butylammonium decatungstate (TBADT) hydrogen atom transfer photocatalyst and a thiol catalyst under light irradiation at 390 nm. This deuteration protocol is effective with formyl C–H bonds and a wide range of hydridic C(sp³)–H bonds (e.g. α-oxy, α-thioxy, α-amino, benzylic, and unactivated tertiary C(sp³)–H bonds). It has been successfully applied to the high incorporation of deuterium in 38 feedstock chemicals, 15 pharmaceutical compounds, and 6 drug precursors. Sequential deuteration between formyl C–H bonds of aldehydes and other activated hydridic C(sp³)–H bonds can be achieved in a selective manner.

A selective hydrogen deuterium exchange reaction with formyl C–H bonds and a wide range of hydridic C(sp³)–H bonds has been achieved by merging tetra-n-butylammonium decatungstate photocatalyst and a thiol catalyst under 390 nm light irradiation.     

从蘸笔纳米刻印术到力化学打印

蘸笔纳米刻印术(dip-pen nanolithography,DPN)作为一种独特的纳米加工手段,具有在各类基底上书写精细图案的能力.自20世纪末诞生以来,研究者们对DPN中的墨水输运原理有了更深入的理解,同时受惠于材料学的发展并结合复杂生化反应体系,数种基于DPN衍生的纳米加工技术被开发出来.与此同时,依靠机械作用...     

温跃层边界提取的组合算法*

本文提出一种用于海洋温跃层边界提取的组合算法,该算法基于调整判定阈值后的垂直梯度法和一种改进函数模型几何形态后的拟阶梯函数逼近法。为验证该算法对于温跃层边界提取的适应性、客观性,利用中国Argo实时资料中心发布的全球海洋Argo网格资料集（BOA_Argo）,选取2018年夏季0°~30°N,135°E~165°E所在的太平洋区域的温度剖面数据进行处理,结果表明,该算法对低纬度海区温度剖面拟合质量较好,拟合均方根误差普遍低于1.3℃,而且提取到的温跃层上下边界在纬向更加平缓,然而对于中高纬度海区的温度剖面,组合算法的处理效果不佳,更适合直接通过垂直梯度法进行温跃层的提取。     

Surface Functionalized Magnetic Nanoparticles as a Selective Sorbent for Affinity Fishing of PPAR-γ Ligands from Choerospondias axillaris

Coronary heart disease (CHD), which has developed into one of the major diseases, was reported to be treated by the target of peroxisome proliferators-activate receptor γ (PPAR-γ). As a natural medicine long used in the treatment of CHD, there are few studies on how to screen the target active compounds with high specific activity from Choerospondias axillaris. To advance the pace of research on target-specific active compounds in natural medicines, we have combined magnetic ligand fishing and functionalized nano-microspheres to investigate the active ingredients of PPAR-γ targets in Choerospondias axillaris. The PPAR-γ functionalized magnetic nano-microspheres have been successfully synthesized and characterized by vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The specificity, reusability, and reproducibility of the nano-microspheres were investigated with the help of the specific binding of rosiglitazone to PPAR-γ. In addition, the incubation temperature and the pH of the buffer solution in the magnetic ligand fishing were optimized to improve the specific adsorption efficiency of the analytes. Finally, with the aid of ultraperformance liquid chromatography plus Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS/MS), the 16 active ligands including 9 organic acids, 5 flavonoids, and 2 phenols were found in the ethanolic extracts of Choerospondias axillaris. Therefore, the study can provide a successful precedent for realizing the designated extraction and rapid isolation of target-specific active ingredient groups in the complex mixtures.     

Ceria supported Ru~0-Ru~(δ+) clusters as efficient catalyst for arenes hydrogenation

Selective hydrogenation of aromatic amines,especially chemicals such as aniline and bis(4-aminocyclohexyl)methane for non-yellowing polyurethane,is of particular interests due to the extensive applications.To conquer the existing difficulties,in selective hydrogenation,,the Ru~0-Ru~(δ+)/CeO_2 catalyst with solid frustrated Lewis pairs was developed for aromatic amines hydrogenation with excellent activity and selectivity under relative milder conditions.The morphology,electronic and chemical properties,especially the Ru~O-Ru~(δ+) clusters and reducible ceria were characterized by X-ray diffraction(XRD),transmission electron microscopy(TEM),sca nning electronic microscopy(SEM),X-ray photoelectron sp ectroscopy(XPS),CO_2 tempe rature programmed deso rption(CO_2-TPD),H_2 tempe rature programmed reduction(H_2-TPR),H_2 diffuse reflectance Fourier transform infrared spectroscopy(H_2-DRIFT),Raman,etc.The 2% Ru/CeO_2 catalyst exhibited good conversion of 95% and selectivity greater than 99% toward cyclohexylamine.The volcano curve describing the activity and Ru state was found.Owning to the "acidic site isolation" by surrounding alkaline sites,condensation between the neighboring amine molecules could be effectively suppressed.The catalyst also showed good stability and applicability for other aromatic amines and heteroarenes containing different functional groups.     

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C₁₈H₁₆O₈) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.     

Comparison of the Structural Evolution of β Polypropylene during the Sequential and Simultaneous Biaxial Stretching Process

In this work, the lamellar structural evolution and microvoids variations of β polypropylene(β-PP) during the processing of two different stretching methods, sequential biaxial stretching and simultaneous biaxial stretching, were investigated in detail. It was found that different stretching methods led to significantly different lamellae deformation modes, and the microporous membranes obtained from the simultaneous biaxial stretching exhibited better mechanical properties. For the sequential biaxial stretching, abundant coarse fibers originated from the tight accumulation of the lamellae parallel to the longitudinal stretching direction, whereas the lamellae perpendicular to the stretching direction were easily deformed and separated. Those coarse fibers were difficult to be separated to form micropores during the subsequent transverse stretching process, resulting in a poor micropores distribution. However, for the simultaneous biaxial stretching, the β crystal had the same deformation mode, that is, the lamellae distributed in different directions were all destroyed, forming abundant microvoids and little coarse fibers.     

Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells

Enterovirus 71 (EV71) is a dominant pathogenic agent that may cause severe central nervous system (CNS) diseases among infants and young children in the Asia-pacific. The inflammasome is closely implicated in EV71-induced CNS injuries through a series of signaling pathways. However, the activation pathway of NLRP3 inflammasome involved in EV71-mediated CNS injuries remains poorly defined. In the studies, EV71 infection, ERK1/2 phosphorylation, and activation of NLRP3 are abolished in glioblastoma cells with low vimentin expression by CRISPR/Cas9-mediated knockdown. PD098059, an inhibitor of p-ERK, remarkably blocks the vimentin-mediated ERK1/2 phosphorylation in EV71-infected cells. Nuclear translocation of NF-κB p65 is dependent on p-ERK in a time-dependent manner. Moreover, NLRP3 activation and caspase-1 production are limited in EV71-infected cells upon the caffeic acid phenethyl ester (CAPE) administration, an inhibitor of NF-κB, which contributes to the inflammasome regulation. In conclusion, these results suggest that EV71-mediated NLRP3 inflammasome could be activated via the VIM-ERK-NF-κB pathway, and the treatment of the dephosphorylation of ERK and NF-κB inhibitors is beneficial to host defense in EV71-infected CNS.     

Common (π,π) Band Folding and Surface Reconstruction in Fe As-Based Superconductors

High resolution angle-resolved photoemission spectroscopy(ARPES) measurements are carried out on CaKFe_4 As_4,KCa_2 Fe_4 As_4 F_2 and(Ba_(0.6)K_(0.4))Fe_2 As_2 superconductors.Clear evidence of band folding between the Brillouin zone center and corners with a(π,π) wave vector has been found from the measured Fermi surface and band structures in all the three kinds of superconductors.A dominant ~(1/2)×~(1/2) surface reconstruction is observed on the cleaved surface of CaKFe_4As_4 by scanning tunneling microscopy(STM) measurements.We propose that the commonly observed ~(1/2)×~(1/2) reconstruction in the FeAs-based superconductors provides a general scenario to understand the origin of the(π,π) band folding.Our observations provide new insights in understanding the electronic structure and superconductivity mechanism in iron-based superconductors.     

MiR-1224-5p modulates osteogenesis by coordinating osteoblast/osteoclast differentiation via the Rap1 signaling target ADCY2

MicroRNAs (miRNAs) broadly regulate normal biological functions of bone and the progression of fracture healing and osteoporosis. Recently, it has been reported that miR-1224-5p in fracture plasma is a potential therapy for osteogenesis. To investigate the roles of miR-1224-5p and the Rap1 signaling pathway in fracture healing and osteoporosis development and progression, we used BMMs, BMSCs, and skull osteoblast precursor cells for in vitro osteogenesis and osteoclastogenesis studies. Osteoblastogenesis and osteoclastogenesis were detected by ALP, ARS, and TRAP staining and bone slice resorption pit assays. The miR-1224-5p target gene was assessed by siRNA-mediated target gene knockdown and luciferase reporter assays. To explore the Rap1 pathway, we performed high-throughput sequencing, western blotting, RT-PCR, chromatin immunoprecipitation assays and immunohistochemical staining. In vivo, bone healing was judged by the cortical femoral defect, cranial bone defect and femoral fracture models. Progression of osteoporosis was evaluated by an ovariectomy model and an aged osteoporosis model. We discovered that the expression of miR-1224-5p was positively correlated with fracture healing progression. Moreover, in vitro, overexpression of miR-1224-5p slowed Rankl-induced osteoclast differentiation and promoted osteoblast differentiation via the Rap1-signaling pathway by targeting ADCY2. In addition, in vivo overexpression of miR-1224-5p significantly promoted fracture healing and ameliorated the progression of osteoporosis caused by estrogen deficiency or aging. Furthermore, knockdown of miRNA-1224-5p inhibited bone regeneration in mice and accelerated the progression of osteoporosis in elderly mice. Taken together, these results identify miR-1224-5p as a key bone osteogenic regulator, which may be a potential therapeutic target for osteoporosis and fracture nonunion.Subject terms: Translational research, Cell signalling