Caffeic Acid Phenethyl Ester Administration Reduces Enterotoxigenic -Induced Colitis and Tumorigenesis.

The human colonic commensal enterotoxigenic (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling.

Enamine -oxides: Design, Synthesis, and Function in Bioorthogonal Reactions.

Enamine -oxides act as a chemical linchpin bridging two bioorthogonal associative and dissociative reactions. This article describes the design of enamine -oxides; their synthesis through the retro-Cope elimination reaction; the use of solvent, hyperconjugation, strain, and rehybridization effects to achieve bioorthogonal reactivity; and their rapid reductive cleavage with diboron reagents. The coordinated assembly and disassembly of the enamine -oxide motif constitutes a powerful chemical operation that enables the attachment and detachment of small molecules from biomacromolecules in a biological setting.

Promotion of Colitis in B Cell-Deficient C57BL/6 Mice Infected with Enterotoxigenic .

Enterotoxigenic (ETBF) causes colitis and is implicated in inflammatory bowel diseases and colorectal cancer. The ETBF-secreted toxin (BFT) causes cleavage of the adherence junction, the E-cadherin, resulting in the large intestine showing IL-17A inflammation in wild-type (WT) mice. However, intestinal pathology by ETBF infection is not fully understood in B-cell-deficient mice.

A Single-Center, Randomized, Double-Blind, and Placebo-Controlled Comparative Human Study to Verify the Functionality and Safety of the Lespedeza cuneata G. Don Extract for the Improvement of Aging Male Syndrome.

Objective: Aging male syndrome is a clinical biochemical syndrome characterized by typical aging symptoms and serum testosterone deficiency. Although it is accompanied by various health problems, directly affects life satisfaction, and requires proper management, no clear prevention or treatment other than hormone replacement therapy is currently available for this syndrome. Here, we aimed to determine the efficacy and safety of the Lespedeza cuneata extract in the management of the aging male syndrome.

Discovery of a Potent Deubiquitinase (DUB) Small-Molecule Activity-Based Probe Enables Broad Spectrum DUB Activity Profiling in Living Cells.

Deubiquitinases (DUBs) are a family of >100 proteases that hydrolyze isopeptide bonds linking ubiquitin to protein substrates, often leading to reduced substrate degradation through the ubiquitin proteasome system. Deregulation of DUB activity has been implicated in many diseases, including cancer, neurodegeneration and auto-inflammation, and several have been recognized as attractive targets for therapeutic intervention. Ubiquitin-derived covalent activity-based probes (ABPs) provide a powerful tool for DUB activity profiling, but their large recognition element impedes cellular permeability and presents an unmet need for small molecule ABPs which can account for regulation of DUB activity in intact cells or organisms.

Pulsed Electromagnetic Field (PEMF) Treatment Ameliorates Murine Model of Collagen-Induced Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease of the joint synovial membranes. RA is difficult to prevent or treat; however, blocking proinflammatory cytokines is a general therapeutic strategy. Pulsed electromagnetic field (PEMF) is reported to alleviate RA's inflammatory response and is being studied as a non-invasive physical therapy.

Synthesis of push-pull-activated ynol ethers and their evaluation in the bioorthogonal hydroamination reaction.

A new class of push-pull-activated alkynes featuring di- and trifluorinated ynol ethers was synthesized. The difluorinated ynol ether exhibited an optimal balance of stability and reactivity, displaying a substantially improved half-life in the presence of aqueous thiols over the previously reported 1-haloalkyne analogs while reacting just as fast in the hydroamination reaction with ,-diethylhydroxylamine. The trifluorinated ynol ether reacted significantly faster, exhibiting a second order rate constant of 0.

Bioorthogonal Click and Release: A General, Rapid, Chemically Revertible Bioconjugation Strategy Employing Enamine -oxides.

A chemically revertible bioconjugation strategy featuring a new bioorthogonal dissociative reaction employing enamine -oxides is described. The reaction is rapid, complete, directional, traceless, and displays a broad substrate scope. Reaction rates for cleavage of fluorophores from proteins are on the order of 82 Ms, and the reaction is relatively insensitive to common aqueous buffers and pHs between 4 and 10.

Enamine -Oxides: Synthesis and Application to Hypoxia-Responsive Prodrugs and Imaging Agents.

Tumor hypoxia induces the large-scale adaptive reprogramming of cancer cells, promoting their transformation into highly invasive and metastatic species that lead to highly negative prognoses for cancer patients. We describe the synthesis and application of a hypoxia-responsive trigger derived from previously inaccessible enamine -oxide structures. Hypoxia-dependent reduction of this motif by hemeproteins results in the concomitant activation of a caged molecule and a latent electrophile.

Bioorthogonal Hydroamination of Push-Pull-Activated Linear Alkynes.

A bioorthogonal reaction between N,N-dialkylhydroxylamines and push-pull-activated halogenated alkynes is described. We explore the use of rehybridization effects in activating alkynes, and we show that electronic effects, when competing stereoelectronic and inductive factors are properly balanced, sufficiently activate a linear alkyne in the uncatalyzed conjugative retro-Cope elimination reaction while adequately protecting it against cellular nucleophiles. This design preserves the low steric profile of an alkyne and pairs it with a comparably unobtrusive hydroxylamine.

Bioorthogonal Retro-Cope Elimination Reaction of ,-Dialkylhydroxylamines and Strained Alkynes.

A bioorthogonal reaction between ,-dialkylhydroxylamines and cyclooctynes is described. This reaction features a highly regioselective transformation between small, easily functionalizable reaction components with second-order rate constants reaching 84 M s. The reaction is orthogonal to the inverse-electron demand Diels-Alder reactions between tetrazine and strained alkenes, and its components exhibit exquisite stability and chemoselectivity in cell lysate.

Conditions for CNT - Coated Textile Sensors Applied to Wearable Platforms to Monitor Limb Joint Motion.

Despite recent research on joint motion measurement to monitor human body movement, current measurement techniques and tools have significant limitations, including requiring large space for measurement and causing discomfort in test subjects wearing motion sensors. Our study aims, first, to develop carbon nanotube (CNT)-based textile joint motion sensors. Second, ours study aims to identify the most suitable CNT-based sensor structure and attachment method for use on a wearable platform during general exercise speeds.

A human protein hydroxylase that accepts D-residues.

Factor inhibiting hypoxia-inducible factor (FIH) is a 2-oxoglutarate-dependent protein hydroxylase that catalyses C3 hydroxylations of protein residues. We report FIH can accept (D)- and (L)-residues for hydroxylation. The substrate selectivity of FIH differs for (D) and (L) epimers, e.

Visible light induced alkene aminopyridylation using N-aminopyridinium salts as bifunctional reagents.

The development of intermolecular alkene aminopyridylation has great potential for quickly increasing molecular complexity with two valuable groups. Here we report a strategy for the photocatalytic aminopyridylation of alkenes using a variety of N-aminopyridinium salts as both aminating and pyridylating reagents. Using Eosin Y as a photocatalyst, amino and pyridyl groups are simultaneously incorporated into alkenes, affording synthetically useful aminoethyl pyridine derivatives under mild reaction conditions.

Site-Selective Functionalization of Pyridinium Derivatives via Visible-Light-Driven Photocatalysis with Quinolinone.

The selective installation of phosphinoyl and carbamoyl moieties on the pyridine scaffold is an important transformation in synthetic and medicinal chemistry. By employing quinolinone as an efficient organic photocatalyst, we developed a catalytic system driven by visible light that forms phosphinoyl and carbamoyl radicals, which react with various heteroarenium derivatives under mild, transition-metal-free conditions. This straightforward and environmentally friendly synthetic method represents a new approach to site-divergent pyridine functionalization that offers considerable advantages in both simplicity and efficiency.

Allylic Acetals as Acrolein Oxonium Precursors in Tandem C-H Allylation and [3+2] Dipolar Cycloaddition.

The ruthenium(II)-catalyzed C-H functionalization of (hetero)aryl azomethine imines with allylic acetals is described. The initial formation of allylidene(methyl)oxoniums from allylic acetals could trigger C(sp )-H allylation, and subsequent endo-type [3+2] dipolar cycloaddition of polar azomethine fragments to deliver valuable indenopyrazolopyrazolones. The utility of this method is showcased by the late-stage functionalization of bioactive molecules such as estrone and celecoxib.

Visible-Light Excitation of Quinolinone-Containing Substrates Enables Divergent Radical Cyclizations.

Reported herein is the photochemical activity of quinolinone-containing substrates that directly reach an excited state upon light absorption to trigger radical-based bond-forming processes. The presented transformations allow divergent construction of valuable dihydro- or tetrahydrophenanthridin-6(5 H)-ones through the generation of S- or P-centered radicals, subsequent radical addition, cyclization, and a hydrogen atom transfer/electron transfer sequence. This strategy demonstrates the potential generality of quinolinone-tethered substrates to directly participate in the photoexcitation for the development of useful synthetic methods.

Visible-Light-Induced C-O Bond Formation for the Construction of Five- and Six-Membered Cyclic Ethers and Lactones.

Visible-light-induced intramolecular C-O bond formation was developed using 2,4,6-triphenylpyrylium tetrafluoroborate (TPT), which allows the regiocontrolled construction of cyclic ethers and lactones. The reaction is likely to proceed through the single-electron oxidation of the phenyl group, followed by the formation of a benzylic radical, thus preventing a competing 1,5-hydrogen abstraction pathway. Detailed mechanistic studies suggest that molecular oxygen is used to trap the radical intermediate to form benzyl alcohol, which undergoes cyclization.

Regiodivergent Ring-Opening Cross-Coupling of Vinyl Aziridines with Phosphorus Nucleophiles: Access to Phosphorus-Containing Amino Acid Derivatives.

Catalytic ring-opening phosphonation and phosphatation of vinyl aziridines have been developed in a regiodivergent fashion, giving linear and branched products. Generation of P-centered radicals enables S2'-type ring-opening reactions of vinyl aziridines to afford δ-amino alkylphosphorus products at room temperature. On the other hand, in situ generated phosphate anions via the Ag-catalyzed aerobic oxidation of phosphonyl reactants underwent S2 reaction to provide branched phosphorus-containing amine products.

Reactivity of Morita-Baylis-Hillman Adducts in C-H Functionalization of (Hetero)aryl Nitrones: Access to Bridged Cycles and Carbazoles.

The rhodium(III)-catalyzed cross-coupling of (hetero)aryl nitrones with Morita-Baylis-Hillman (MBH) adducts is described. An allylated intermediate derived from aryl nitrones and MBH adducts allows the formation of bridged cyclic compounds via an exotype [3 + 2] cycloaddition. In sharp contrast, electron-rich indolinyl or aniline substrates were found to couple with MBH adducts to generate naphthalene or carbazole derivatives, respectively.

Stereoselective construction of sterically hindered oxaspirocycles chiral bidentate directing group-mediated C(sp)-O bond formation.

The systematic investigation of chiral bidentate auxiliaries has resulted in the discovery of a chiral 2,2-dimethyl-1-(pyridin-2-yl)propan-1-amine-derived directing group that enables stereoselective palladium(ii)-catalyzed intramolecular C(sp)-O bond formation. This new chiral directing group exhibited high reactivity in the activation of methylene C(sp)-H bonds with excellent levels of stereoselectivity (a diastereomeric ratio of up to 39 : 1), which allowed the construction of a wide range of oxaspirocycles. Mechanistic investigations were also conducted to elucidate the reaction mechanism and understand the origin of the diastereoselectivity.

Room-Temperature Ring-Opening of Quinoline, Isoquinoline, and Pyridine with Low-Valent Titanium.

The complex (PNP)Ti═CHBu(CHBu) (PNP = N[2-PPr-4-methylphenyl]) dehydrogenates cyclohexane to cyclohexene by forming a transient low-valent titanium-alkyl species, [(PNP)Ti(CHBu)], which reacts with 2 equiv of quinoline (Q) at room temperature to form HCBu and a Ti(IV) species where the less hindered C═N bond of Q is ruptured and coupled to another equivalent of Q. The product isolated from this reaction is an imide with a tethered cycloamide group, (PNP)Ti═N[CHN] (1). Under photolytic conditions, intramolecular C-H bond activation across the imide moiety in 1 occurs to form 2, and thermolysis reverses this process.

Direct Phosphonation of Quinolinones and Coumarins Driven by the Photochemical Activity of Substrates and Products.

Light-promoted phosphonation of quinolinones and coumarins was developed without the need for an external photocatalyst. Investigations support a mechanism whereby both starting materials and products act as photosensitizers upon excitation using compact fluorescent light sources to photochemically promote the dissociation of the N-O bond in the pyridinium salt by a single electron transfer pathway. A wide range of quinolinone and coumarin substrates can be utilized in the phosphonation process under mild reaction conditions.

Anti‑inflammatory effects of Ciwujianoside C3, extracted from the leaves of Acanthopanax henryi (Oliv.) Harms, on LPS‑stimulated RAW 264.7 cells.

The present study aimed to investigate the unknown mechanisms underlying the anti‑inflammatory activity of Ciwujianoside C3 (CJS C3), extracted from the leaves of Acanthopanax henryi Harms, on lipopolysaccharide (LPS)‑stimulated RAW 264.7 cells. Cells were treated with CJS C3 for 1 h prior to the addition of 200 ng/ml LPS.