Palladium-Catalyzed Solvent-Controlled Divergent C2/C5 Site-Selective Alkynylation of Pyrrole Derivatives.

Among the known aromatic -heterocycles, pyrroles are significant and versatile privileged components in pharmacologically relevant molecules. Herein, we demonstrate a protocol for the selective construction of alkynylated pyrroles in a diversity-oriented fashion through divergent C2/C5 site-selective alkynylation of pyrrole derivatives by employing a palladium catalyst with two different solvent systems. In the presence of 1,4-dioxane, the C2-alkynylation process via chelation-assisted palladation is favored.

Cross-sectional and Mendelian randomization study of fibroblast growth factor 19 reveals causal associations with metabolic diseases.

Background And Aim: Fibroblast growth factor 19 (FGF19) is an intestinal-derived factor that plays a role in metabolic diseases. We performed a differential study of circulating FGF19 levels and investigated the causal effects of FGF19 on metabolic diseases using Mendelian randomization (MR).

Methods: Firstly, 958 subjects were included in the physical examination center of affiliated hospital from January 2019 to January 2021.

Identification of FTY720 and COH29 as novel topoisomerase I catalytic inhibitors by experimental and computational studies.

The development of novel topoisomerase I (TOP1) inhibitors is crucial for overcoming the drawbacks and limitations of current TOP1 poisons. Here, we identified two potential TOP1 inhibitors, namely, FTY720 (a sphingosine 1-phosphate antagonist) and COH29 (a ribonucleotide reductase inhibitor), through experimental screening of known active compounds. Biological experiments verified that FTY720 and COH29 were nonintercalative TOP1 catalytic inhibitors that did not induce the formation of DNA-TOP1 covalent complexes.

Metabolic dysfunction-associated fatty liver disease and nonalcoholic fatty liver disease from clinical to pathological characteristics: a multi-center cross-sectional study in real world.

Background: The evaluation of patients with fatty liver as defined by metabolic dysfunction-associated fatty liver disease (MAFLD) in the real world remains poorly researched. This study aimed to analyse the clinical and histological features of patients with MAFLD and nonalcoholic fatty liver disease (NAFLD) and to characterize each metabolic subgroup of MAFLD.

Methods: A total of 2563 patients with fatty liver confirmed by ultrasonography and/or magnetic resonance tomography and/or liver biopsy-proven from three hospitals in China were included in the study.

LncRNA SNHG1: role in tumorigenesis of multiple human cancers.

Small nucleolar RNA host gene 1 (SNHG1) is an important member of the SNHG family. This family is composed of a group of host genes that can be processed into small nucleolar RNAs and play important biological functions. In an oncogenic role, the SNHG1 expression is increased in various cancers, which has immense application prospects in the diagnosis, treatment, and prognosis of malignant tumors.

Ruthenium(II)-Catalyzed Remote C-H Sulfonylation of 2-Pyridones.

Herein, a ruthenium-mediated remote C-H mono- and disulfonylation of 2-pyridones with arylsulfonyl chlorides is developed. The catalytic system consisting of a [Ru(-cymene)Cl] catalyst and KOAc additive allows 2-pyridones to undergo C3,C5-disulfonylation in 1,4-dioxane, and C5-sulfonylation when the C3-position of 2-pyridones is blocked. The successful transformation of the products and late-stage modification of estrone further highlighted the potential utility and significance of this synthetic protocol.

Identification of N-(3-(methyl(3-(orotic amido)propyl)amino)propyl) oleanolamide as a novel topoisomerase I catalytic inhibitor by rational design, molecular dynamics simulation, and biological evaluation.

DNA topoisomerase I (TOP1) catalytic inhibitors are a promising class of antitumor agents. Oleanolic acid derivatives are potential TOP1 catalytic inhibitors. However, their inhibitory activity still needs to be enhanced, and the stability and hotspot residue sites of their interaction with TOP1 remain to be elucidated.

A chiral BINOL-based supramolecular gel enabling sensitive enantioselective and chemoselective collapse toward histidine.

A chiral small molecule gelator ()-HL based on 1,1'-bi-2,2'-naphthol (BINOL)-phosphoric acid was designed and prepared, which spontaneously forms a stable water-induced gel. The gelation mechanism was revealed by single crystal X-ray diffraction analysis and a number of spectroscopic methods. Addition of Cu improved the gelation ability, and the resultant metal organic gel realized visual enantioselective and chemoselective recognition toward L-histidine from enantiomers of 19 amino acids gel collapse.

Revealing the Active Constituents and Mechanisms of Semiliquidambar cathayensis Chang Roots against Rheumatoid Arthritis through Network Pharmacology, Molecular Docking, and in Vivo Experiment.

Semiliquidambar cathayensis Chang roots (SC) are traditional Chinese medicine for treating rheumatoid arthritis (RA). However, the effect and potential mechanism of SC remain unclear. This study aims to reveal the anti-RA constituents and mechanisms of SC based on network pharmacology, molecular docking, and adjuvant-induced arthritis (AIA) model rat experiment.

Natural phenylethanoid glycosides diuretics derived from Lagopsis supina: Biological activity, mechanism, molecular docking, and structure-activity relationship.

Aquaporins (AQPs) and vasopressin type 2 receptor (V2R) play a crucial role in urine excretion and are widely used to explore novel diuretics. In this study, three phenylpropanoids including stachysoside A (L1), acteoside (L2), and glucopyranosyl (1 → 6) martynoside (L3) were isolated from Lagopsis supina (Steph. ex Willd.

An Approach for Predicting the Low-Cycle-Fatigue Crack Initiation Life of Ultrafine-Grained Aluminum Alloy Considering Inhomogeneous Deformation and Microscale Multiaxial Strain.

In this paper, a low-cycle-fatigue (LCF) crack initiation life prediction approach that explicitly distinguishes nucleation and small crack propagation regimes is presented for ultrafine-grained (UFG) aluminum alloy by introducing two fatigue indicator parameters (FIPs) at the grain level. These two characterization parameters, the deformation inhomogeneity measured by the standard deviation of the dot product of normal stress and longitudinal strain and the microscale multiaxial strain considering the non-proportional cyclic additional hardening and mean strain effect, were proposed and respectively regarded as the driving forces for fatigue nucleation and small crack propagation. Then, the nucleation and small crack propagation lives were predicted by correlating these FIPs with statistical variables and cyclic J-integrals, respectively.

[Effects of acupuncture on endoplasmic reticulum pathway in exercise-induced skeletal muscle damage in rats and its mechanism].

To observe the effects of acupuncture on the endoplasmic reticulum (ER) functional enzymes sarcoplasmic reticulum Ca-ATPase (SERCA), protein disulfide isomerase (PDI), glucose-regulated protein 78(GRP78) and PERK pathways in rats with exercise-induced skeletal muscle damage, and to explore the mechanisms of acupuncture in preventing and treating exercise-induced skeletal muscle damage. Eight-week-old male SD rats were randomly divided into control group (group C, =6), exercise group (group E, =30), acupuncture group (group A, =30) and exercise acupuncture group (group EA, =30). Among them, the E and EA group were established an exercise-induced skeletal muscle damage model by a single eccentric exercise, and acupuncture intervention was applied 0.

F- and F-Arene Deoxyfluorination via Organic Photoredox-Catalysed Polarity-Reversed Nucleophilic Aromatic Substitution.

Nucleophilic aromatic substitution (SAr) is routinely used to install F and F in aromatic molecules, but is typically limited to electron-deficient arenes due to kinetic barriers associated with C-F bond formation. Here we demonstrate that a polarity-reversed photoredox-catalysed arene deoxyfluorination operating via cation radical-accelerated nucleophilic aromatic substitution (CRA-SAr) enables the fluorination of electron-rich arenes with F and F under mild conditions, thus complementing the traditional arene polarity requirements necessary for SAr-based fluorination. The utility of our radiofluorination strategy is highlighted by short reaction times, compatibility with multiple nucleofuges, and high radiofluorination yields, especially that of an important cancer positron emission tomography (PET) agent [F]5-fluorouracil ([F]FU).

Transcriptional regulation of telomeric repeat-containing RNA by acridine derivatives.

Telomere is a specialized DNA-protein complex that plays an important role in maintaining chromosomal integrity. Shelterin is a protein complex formed by six different proteins, with telomeric repeat factors 1 (TRF1) and 2 (TRF2) binding to double-strand telomeric DNA. Telomeric DNA consists of complementary G-rich and C-rich repeats, which could form G-quadruplex and intercalated motif (i-motif), respectively, during cell cycle.

Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands.

Vascular endothelial growth factor (VEGF) is an angiogenic growth factor and plays a key role in tumor progression. The C-rich DNA sequence of promoter can form i-motif structure, which is a potential target for the development of novel anticancer agents. However, there is a limited number of chemotypes as the selective ligands of promoter i-motif, which leaves much room for development.

Bifunctional Phosphorylcholine-Modified Adsorbent with Enhanced Selectivity and Antibacterial Property for Recovering Uranium from Seawater.

The recovery of uranium from seawater is of great concern because of the growing demand for nuclear energy. Though amidoxime-functionalized adsorbents as the most promising adsorbents have been widely used for this purpose, their low selectivity and vulnerability to biofouling have limited their application in real marine environments. Herein, a new bifunctional phosphorylcholine-modified adsorbent (PVC-PC) is disclosed.

Copper-mediated tandem ring-opening/cyclization reactions of cyclopropanols with aryldiazonium salts: synthesis of N-arylpyrazoles.

A general method for the synthesis of structurally diverse N-arylpyrazoles from readily available cyclopropanols and aryldiazonium salts is disclosed. The reaction was conducted at room temperature within minutes with a broad substrate scope and excellent regioselectivity.

Direct arene C-H fluorination with F via organic photoredox catalysis.

Positron emission tomography (PET) plays key roles in drug discovery and development, as well as medical imaging. However, there is a dearth of efficient and simple radiolabeling methods for aromatic C-H bonds, which limits advancements in PET radiotracer development. Here, we disclose a mild method for the fluorine-18 (F)-fluorination of aromatic C-H bonds by an [F]F salt via organic photoredox catalysis under blue light illumination.

MicroRNA-139-3p Suppresses Tumor Growth and Metastasis in Hepatocellular Carcinoma by Repressing ANXA2R.

The direct roles of miR-139-3p on hepatocellular carcinoma (HCC) cell growth and metastasis remain poorly understood. We attempted to demonstrate the regulatory role of miR-139-3p in HCC progression and its underlying mechanisms. Here we showed that miR-139-3p expression was significantly reduced in the HCC tissues compared to paratumor tissues.

Significant enhanced uranyl ions extraction efficiency with phosphoramidate-functionalized ionic liquids via synergistic effect of coordination and hydrogen bond.

The influence of the linking group between the phosphoryl and bridging moieties in phosphoryl-containing task-specific ionic liquids (TSILs) on the extraction of uranyl ions was experimentally and theoretically investigated. A novel phosphoramidate-based TSIL with an amine group as the linking moiety resulted in a higher uranyl ion extraction efficiency compared with that of other phosphoryl-based TSILs. A distribution ratio of 4999 ± 51 can be achieved for uranyl ions.

Water-based fractionation of a commercial humic acid. Solid-state and colloidal characterization of the solubility fractions.

Background And Hypothesis: Humic acid (HA) is of considerable environmental significance, being a major component of soil, as well as being considered for application in other technological areas. However, its structure and colloidal properties continue to be the subject of debate, largely owing to its molecular complexity and association with other humic substances and mineral matter. As a class, HA is considered to comprise supramolecular assemblies of heterogeneous species, and herein we consider a simple route for the separation of some HA sub-fractions.

Fabrication of silicon films from patterned protruded seeds.

Thin, flexible silicon crystals are starting up applications such as light-weighted flexible solar cells, SOI, flexible IC chips, 3D ICs imagers and 3D CMOS imagers on the demand of high performance with low cost. Kerfless wafering technology by direct conversion of source gases into mono-crystalline wafers on reusable substrates is highly cost-effective and feedstock-effective route to cheap wafers with the thickness down to several microns. Here we show a prototype for direct conversion of silicon source gases to wafers by using the substrate with protruded seeds.

Remote Postconditioning Alone and Combined with Hypothermia Improved Postresuscitation Cardiac and Neurological Outcomes in Swine.

. Previously, we demonstrated that remote ischemic postconditioning (RIpostC) improved postresuscitation myocardial and cerebral functions in rat. Here, we investigated the effects of RIpostC alone and combined with therapeutic hypothermia (TH) on cardiac and neurological outcomes after CPR in swine.

Aggregation-induced emission active tetraphenylethene-based sensor for uranyl ion detection.

A novel tetraphenylethene-based fluorescent sensor, TPE-T, was developed for the detection of uranyl ions. The selective binding of TPE-T to uranyl ions resulted in a detectable signal owing to the quenching of its aggregation-induced emission. The developed sensor could be used to visually distinguish UO2(2+) from lanthanides, transition metals, and alkali metals under UV light; the presence of other metal ions did not interfere with the detection of uranyl ions.

The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory.

Objective: To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction.

Methods: Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.