There is a growing need to better characterise senescent cells in the CNS and retina. The recently published SenMayo gene panel was developed to identify transcriptomic signatures of senescence across multiple organ systems, but the retina was not included. While other approaches have identified senescent signatures in the retina, these have largely focused on experimental models in young animals.
View Article and Find Full Text PDFThe morpholine heterocycle is a structural unit found in many bioactive compounds and FDA-approved drugs, but the generation of more complex C-functionalized morpholine derivatives remains considerably underexplored. Using systematic chemical diversity (SCD), a concept that guides the expansion of saturated drug-like scaffolds through regiochemical and stereochemical variation, we describe the synthesis of a collection of methyl-substituted morpholine acetic acid esters starting from enantiomerically pure amino acids and amino alcohols. In total, 24 diverse substituted morpholines were produced that vary systematically in regiochemistry and stereochemistry (relative and absolute).
View Article and Find Full Text PDFCell Mol Biol (Noisy-le-grand)
December 2023
Hand, foot, and mouth disease (HFMD) can cause fatal encephalitis in 0-5-year-old infants and children. There is no effective antiviral drug available to treat HFMD caused by enterovirus 71 (EV71). Our study investigates the relationship between levels of IL-22 expression and the severity of disease after EV71 infection in a mouse model.
View Article and Find Full Text PDFA phytochemical research on the twigs of Dichapetalum longipetalum (Turcz.) Engl. Resulted in five undescribed dichapetalin-type triterpenoids 1-5.
View Article and Find Full Text PDFThe hallmark of a molecular glue is its ability to induce cooperative protein-protein interactions, leading to the formation of a ternary complex, despite weaker binding toward one or both individual proteins. Notably, the extent of cooperativity distinguishes molecular glues from bifunctional compounds, which constitute a second class of inducers of protein-protein interactions. However, apart from serendipitous discovery, there have been limited rational screening strategies for the high cooperativity exhibited by molecular glues.
View Article and Find Full Text PDFThe hallmark of a molecular glue is its ability to induce cooperative protein-protein interactions, leading to the formation of a ternary complex, despite weaker binding towards one or both individual proteins. Notably, the extent of cooperativity distinguishes molecular glues from bifunctional compounds, a second class of inducers of protein-protein interactions. However, apart from serendipitous discovery, there have been limited rational screening strategies for the high cooperativity exhibited by molecular glues.
View Article and Find Full Text PDFBlumeatin, reported herein, bearing two hydroxyl groups at C3' and C5' of ring B, is isolated from the traditional Chinese medicine . But the isolation procedure of blumeatin from plants has limitations of prolonged duration and high cost. A procedure featuring Lewis acid-catalyzed ring closure and chiral resolution via Schiff base intermediates is provided here to prepare optically pure blumeatin and its -isomer efficiently.
View Article and Find Full Text PDFMedicine (Baltimore)
September 2022
Rationale: Desmoid-type fibromatosis is a rare benign mesenchymal neoplasm. Only 8% of desmoid-type fibromatosis develops in the abdominal cavity. The mesentery is seldom affected and gastrointestinal stromal tumors need to be considered in the differential diagnosis, particularly when imaging examination shows a tumor containing gases in the abdominal cavity.
View Article and Find Full Text PDFWe report a short synthetic route for synthesizing 2,3-substituted piperazine acetic acid esters. Optically pure amino acids were efficiently converted into 1,2-diamines that could be utilized to deliver the title 2,3-substituted piperazines in five steps with a high enantiomeric purity. The novel route facilitated, for the first time, the synthesis of 3-phenyl substituted-2-piperazine acetic acid esters that were difficult to achieve using other methods; however, in this case, the products underwent racemization.
View Article and Find Full Text PDFTo explore the reaction universality of bridge nitration, the mononitration of different butylcalix[4]arene derivatives was executed with -butyl nitrite as a nitration reagent. The effects of calix[4]arene conformations, substituents on the lower rim, and reaction conditions on bridge mononitration are systematically studied. The bridge nitration of butylcalix[4]arene derivatives in 1,3-alternate, 1,2-alternate, and partial cone conformations can be smoothly executed while that of butylcalix[4]arene derivatives strictly regulated in a cone conformation cannot.
View Article and Find Full Text PDFJ Asian Nat Prod Res
January 2023
Marine natural products are promising sources of green antifoulants. Here, a new compound () was isolated from the soft coral . This compound, another nine cembranoids (-) from , and three eunicellin-type diterpenoids (-) from the gorgonian sp.
View Article and Find Full Text PDFGraphic design thinking is a key skill for landscape architects, but little is known about the links between the design process and brain activity. Based on Goel's frontal lobe lateralization hypothesis (FLLH), we used functional magnetic resonance imaging (fMRI) to scan the brain activity of 24 designers engaging in four design processes-viewing, copy drawing, preliminary ideas, and refinement-during graphic design thinking. The captured scans produced evidence of dramatic differences between brain activity when copying an existing graphic and when engaging in graphic design thinking.
View Article and Find Full Text PDFLongipetalol A () is an unprecedented highly modified triterpenoid with a unique 1,2--3-(2-oxo-phenylethyl)-17α-13,30-cyclodammarane skeleton, featuring an acetal-lactone fragment. It was isolated from along with two additional derivatives, namely, longipetalols B () and C (). Their structures were elucidated using spectroscopic analyses combined with single-crystal X-ray diffraction.
View Article and Find Full Text PDFNine previously undescribed dichapetalin-type triterpenoids (1-9), along with 12 reported compounds (10-21), were isolated from the twigs of Dichapetalum gelonioides. Their chemical structures were mainly elucidated by comprehensive analysis of HRMS, 1D and 2D NMR spectroscopic data. The absolute configuration of compound 1 was further determined based on single-crystal X-ray diffraction.
View Article and Find Full Text PDFIn order to prepare bridging chiral --butylcalix[4]crown-5 with a mononitro bridge substituent in a 1,3-alternate conformation, a mononitration method of calix[4]arene bridging methylene has been first developed with -butyl nitrite as a nitration reagent. The effects of solvent, reaction temperature, reaction time, and nitration reagent dosage on bridge mononitration have been deeply explored to obtain an optimal nitration condition. The facile nitration presents a new key for calix[4]arene bridge derivatization.
View Article and Find Full Text PDFA single nanoparticle (NP) mass spectrometry method was used to measure sublimation rates as a function of nanoparticle temperature (T) for sets of individual graphite and graphene NPs. Initially, the NP sublimation rates were ∼400 times faster than those for bulk graphite, and there were large NP-to-NP variations. Over time, the rates slowed substantially, though they remained well above the bulk rate.
View Article and Find Full Text PDFThe human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies. Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways. Here, we elucidated the global transcriptomic changes during H3N2 infection of human nasal epithelial cells from multiple individuals.
View Article and Find Full Text PDFFour new steroidal saponins, 3-O-β-D-glucopyranosyl(1→4)-β-D-fucopyranosyl -(25R)-spirost-5-en-3β,17α-diol (1), 3-O-β-D-glucopyranosyl(1→4)-β-D- fucopyranosyl-(25S)-spirost-5-en-3β,17α-diol (2), 3-O-β-D-glucopyranosyl(1→2) -β-D-glucopyranosyl(1→4)-β-D-fucopyranosyl-(25R)-spirost-5-en-3β,17α-diol (3), 3-O-β-D-glucopyranosyl(1→4)-β-D-fucopyranosyl-(25R/S)-spirost-5-en-3β,12β-diol (4), together with five known steroidal saponins were isolated from the ethanolic extract of the rhizome of Polygonatum sibiricum. Chemical structures of these compounds were elucidated by spectroscopic techniques. Anti-inflammatory activities of these new compounds were evaluated.
View Article and Find Full Text PDFZhongguo Yi Xue Ke Xue Yuan Xue Bao
October 2017
Objective To explore the efficacy and safety of ultrasound-guided cervical root block (CRB) in patients undergoing minimally invasive parathyroidectomy (MIP).Methods We enrolled 35 patients with hyperparathyroidism undergoing MIP in Peking Union Medical College Hospital.C4-7 nerve roots were identified in ultrasound imaging by the shape of the transverse process.
View Article and Find Full Text PDF1,6-O,O-Diacetylbritannilactone (OODBL), a plant sesquiterpene lactone, was previously reported to show multiple pharmacological effects such as anti-cancer and anti-inflammatory activities. In this study, we investigated the anti-inflammatory effect of OODBL on interleukin (IL)-4-induced signal transducer and activator of transcription 6 (STAT6) signaling pathway in human lung A549 cells. We found that OODBL dramatically inhibited IL-4-induced messenger RNA (mRNA) expression of eotaxin-1 and arachidonate 15-lipoxygenase-1 (ALOX15) in a dose-dependent manner.
View Article and Find Full Text PDFApproximately 20% early-stage (I/II) colorectal cancer (CRC) patients develop metastases despite curative surgery. We aim to develop a formalin-fixed and paraffin-embedded (FFPE)-based predictor of metastases in early-stage, clinically-defined low risk, microsatellite-stable (MSS) CRC patients. We considered genome-wide mRNA and miRNA expression and mutation status of 20 genes assayed in 150 fresh-frozen tumours with known metastasis status.
View Article and Find Full Text PDFImmunopharmacol Immunotoxicol
August 2017
Mast cells play critical roles in allergic disorders such as atopic dermatitis and allergic asthma. The aim of this study was to investigate the anti-inflammatory and anti-asthmatic activities of 1,6-O,O-diacetylbritannilactone (OODBL) isolated from Inula japonica Thunb. (I.
View Article and Find Full Text PDFZ Naturforsch C J Biosci
August 2016
A new isomalabaricane-type triterpenoid, jaspiferin G (1), together with four known isomalabaricane-type triterpenoids, isogeoditin A (2), 13-(E)-isogeoditin A (3), jaspolide E (4), and 22,23-dihydrostellettin D (5), was isolated from the marine sponge Jaspis stellifera. The structures were elucidated on the basis of spectroscopic data ((1)H and (13)C NMR, (1)H(-1)H COSY, HSQC, HMBC, and ROESY) and mass spectrometry.
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