Catalyst-Controlled Divergent Reactions of 2,3-Disubstituted Indoles with Propargylic Alcohols: Synthesis of 3<i>H</i>‑Benzo[<i>b</i>]azepines and Axially Chiral Tetrasubstituted Allenes

Catalyst-controlled divergent reactions of 2,3-disubstituted indoles with propargylic alcohols were developed for the first time. In the presence of TsOH or B(C6F5)3 as catalyst, 2,3-disubstituted indoles reacted smoothly with 3-alkynyl-3-hydroxyisoindolinones to afford 3H-benzo[b]azepines by selective C2(sp2)–C3(sp2) ring expansion of indoles. In contrast, decreasing the catalyst strength (e.g., with chiral phosphoric acid) interrupted the cascade reactions, affording axially chiral tetrasubstituted allenes bearing an adjacent chiral quaternary carbon stereocenter. Control experiments provided insights into the reaction mechanism

Statistical process control for multistage processes with non-repeating cyclic profiles

<p>In many manufacturing processes, process data are observed in the form of time-based profiles, which may contain rich information for process monitoring and fault diagnosis. Most approaches currently available in profile monitoring focus on single-stage processes or multistage processes with repeating cyclic profiles. However, a number of manufacturing operations are performed in multiple stages, where non-repeating profiles are generated. For example, in a broaching process, non-repeating cyclic force profiles are generated by the interaction between each cutting tooth and the workpiece. This article presents a process monitoring method based on Partial Least Squares (PLS) regression models, where PLS regression models are used to characterize the correlation between consecutive stages. Instead of monitoring the non-repeating profiles directly, the residual profiles from the PLS models are monitored. A Group Exponentially Weighted Moving Average control chart is adopted to detect both global and local shifts. The performance of the proposed method is compared with conventional methods in a simulation study. Finally, a case study of a hexagonal broaching process is used to illustrate the effectiveness of the proposed methodology in process monitoring and fault diagnosis.</p

Specificity of the Ester Bond Forming Condensation Enzyme SgcC5 in C-1027 Biosynthesis

The SgcC5 condensation enzyme catalyzes the attachment of SgcC2-tethered (<i>S</i>)-3-chloro-5-hydroxy-β-tyrosine (<b>2</b>) to the enediyne core in C-1027 (<b>1</b>) biosynthesis. It is reported that SgcC5 (i) exhibits high stereospecificity toward the (<i>S</i>)-enantiomers of SgcC2-tethered β-tyrosine and analogues as donors, (ii) prefers the (<i>R</i>)-enantiomers of 1-phenyl-1,2-ethanediol (<b>3</b>) and analogues, mimicking the enediyne core, as acceptors, and (iii) can recognize a variety of donor and acceptor substrates to catalyze their regio- and stereospecific ester bond formations

Frontier Molecular Orbital Engineering of Aromatic Donor Fusion: Modularly Constructing Highly Efficient Narrowband Yellow Electroluminescence

The development of high-performance multiple resonance thermally activated delayed fluorescence (MR-TADF) materials with narrowband yellow emission is highly critical for various applications in industries, such as the automotive, aerospace, and microelectronic industries. However, the modular construction approaches to expeditiously access narrowband yellow-emitting materials is relatively rare. Here, a unique molecular design concept based on frontier molecular orbital engineering (FMOE) of aromatic donor fusion is proposed to strategically address this issue. Donor fusion is a modular approach with a “leveraging effect”; through direct polycyclization of donor attached to the MR parent core, it is facile to achieve red-shifted emission by a large margin. As a result, two representative model molecules, namely BN-Cz and BN-Cb, have been constructed successfully. The BN-Cz- and BN-Cb-based sensitized organic light-emitting diodes (OLEDs) exhibit bright yellow emission with peaks of 560 and 556 nm, full-width at half-maxima (fwhm’s) of 49 and 45 nm, Commission Internationale de L’Eclairage coordinates of (0.44, 0.55) and (0.43, 0.56), and maximum external quantum efficiencies (EQEs) of 32.9% and 29.7%, respectively. The excellent optoelectronic performances render BN-Cz and BN-Cb one of the most outstanding yellow-emitting MR-TADF materials

Image_1_Extracellular Vesicles Long Non-Coding RNA AGAP2-AS1 Contributes to Cervical Cancer Cell Proliferation Through Regulating the miR-3064-5p/SIRT1 Axis.tif

Cervical cancer is one of the most severe and prevalent female malignancies and a global health issue. The molecular mechanisms underlying cervical cancer development are poorly investigated. As a type of extracellular membrane vesicles, EVs from cancer cells are involved in cancer progression by delivering regulatory factors, such as proteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). In this study, we identified an innovative function of extracellular vesicle (EV) lncRNA AGAP2-AS1 in regulating cervical cancer cell proliferation. The EVs were isolated from the cervical cancer cells and were observed by transmission electron microscopy (TEM) and were confirmed by analyzing exosome markers. The depletion of AGAP2-AS1 by siRNA significantly reduced its expression in the exosomes from cervical cancer and in the cervical cancer treated with AGAP2-AS1-knockdown exosomes. The expression of AGAP2-AS1 was elevated in the clinical cervical cancer tissues compared with the adjacent normal tissues. The depletion of EV AGAP2-AS1 reduced cell viabilities and Edu-positive cervical cancer cells, while it enhanced cervical cancer cell apoptosis. Tumorigenicity analysis in nude mice showed that the silencing of EV AGAP2-AS1 attenuated cervical cancer cell growth in vivo. Regarding the mechanism, we identified that AGAP2-AS1 increased SIRT1 expression by sponging miR-3064-5p in cervical cancer cells. The overexpression of SIRT1 or the inhibition of miR-3064-5p reversed EV AGAP2-AS1 depletion-inhibited cancer cell proliferation in vitro. Consequently, we concluded that EV lncRNA AGAP2-AS1 contributed to cervical cancer cell proliferation through regulating the miR-3064-5p/SIRT1 axis. The clinical values of EV lncRNA AGAP2-AS1 and miR-3064-5p deserve to be explored in cervical cancer diagnosis and treatments.</p

Additional file 1: Figure S1. of NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?

Methylation status of CpG island within 2000 bp beyond the Transcription Start Site (TSS). (TIF 768 kb

Additional file 3: Figure S3. of NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?

Correlation between Epstein–Barr virus (EBV) infection and NOTCH1-4 mRNA expression. (TIF 860 kb

Additional file 2: Figure S2. of NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?

Correlation analysis between Helicobacter Pylori (H. Pylori) infection and NOTCH1-4 mRNA expression. (TIF 698 kb

DataSheet_1_Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration.docx

BackgroundThe F-box and WD repeat domain containing (FBXW) family of SCF E3 complexes has 10 members that are responsible for ubiquitination and degradation of substrate proteins involved in cell cycle regulation and tumorigenesis. Among them, FBXW1 (also called b-TrCP1/BTRC) and FBXW7 are the central proteins in this category. However, there is still a lack of elaborate exploration of the contribution of FBXW family members, especially FBXW1 and FBXW7, in various tumor types.MethodsIn this present study, we preliminarily analyzed the genetic structure characteristics of the FBXW family, and systematically investigated their expression patterns and clinical correlations based on the TCGA pan-cancer data. Survival analysis of FBXWs was also conducted through the Kaplan-Meier method. In addition, we assessed their immune infiltration level through immune-related algorithms like Timer and xCell.ResultsThere were obvious genetic heterogeneity and different clinical traits in FBXW family members. Moreover, we found that FBXW family genes may be useful in predicting prognosis and therapeutic efficacy using survival analysis. In addition, the immune infiltration of FBXW family was also clearly illustrated in this study. The results showed these genes were closely involved in immune components such as immune score, immune subtypes, tumor-infiltrating lymphocytes and immune checkpoints. Notedly, FBXW1 as an oncogene and FBXW7 as a tumor suppressor gene also show opposite relationships on immune cells.ConclusionOur results provided valuable strategies to guide the therapeutic orientation concerning the role of FBXW family genes in cancer.</p

Flavoprotein StnP2 Catalyzes the β‑Carboline Formation during the Streptonigrin Biosynthesis

β-Carboline (βC) alkaloids constitute a large family of indole alkaloids that exhibit diverse pharmacological properties, such as antitumor, antiviral, antiparasitic, and antimicrobial activities. Here, we report that a flavoprotein StnP2 catalyzes the dehydrogenation at C1–N2 of a tetrahydro-β-carboline (THβC) generating a 3,4-dihydro-β-carboline (DHβC), and the DHβC subsequently undergoes a spontaneous dehydrogenation to βC formation involved in the biosynthesis of the antitumor agent streptonigrin. Biochemical characterization showed that StnP2 catalyzed the highly regio- and stereo-selective dehydrogenation, and StnP2 exhibits promiscuity toward different THβCs. This study provides an alternative kind of enzyme catalyzing the biosynthesis of βC alkaloids and enhances the importance of flavoproteins