Sintilimab-induced severe erosive hemorrhagic gastritis and pyloric obstruction: a case report and literature review.

Immune checkpoint inhibitors could restore immune surveillance to attack tumor through targeting CTLA-4, PD-1 or PD-L1, and have achieved huge success. However, immune-related adverse events (irAEs) have been attracting attention as their application is expanding. Gastritis is relatively rare as a subtype of irAEs, particularly severe gastritis.

Synthesis of gem-Difluorinated Isoxazoles via Palladium-Catalyzed Oxylallylation of Alkynone Oxime Ethers.

A novel and reliable palladium-catalyzed oxylallylation of alkynone oxime ethers with fluorine-containing alkenes was accomplished. Using the bulk industrial chemical 3-bromo-3,3-difluoroprop-1-ene as the coupling partner, this synthetic methodology offers the first example for the assembly of structurally diverse gem-difluorinated isoxazole derivatives in moderate to good yields with high atom- and step-economy and excellent functional group compatibility. More importantly, this strategy allows for the direct combination of the isoxazole motifs and gem-difluoroalkene unit, which is not easy to obtain through a general synthetic strategy.

S1PR1 attenuates pulmonary fibrosis by inhibiting EndMT and improving endothelial barrier function.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease of unknown etiology. Its pathological manifestations include excessive proliferation and activation of fibroblasts and deposition of extracellular matrix. Endothelial cell-mesenchymal transformation (EndMT), a novel mechanism that generates fibroblast during IPF, is responsible for fibroblast-like phenotypic changes and activation of fibroblasts into hypersecretory cells.

Palladium-Catalyzed Reductive Formylation of Aryl Iodides with CO under Mild Conditions.

A palladium-catalyzed reductive formylation of aryl iodides with carbon dioxide as the carbonyl source under mild reaction conditions was realized by using a combination of Pd(PCy)Cl and di-2-pyridyl ketone as the catalyst and phenylsilane as the reductive reagent, leading to a variety of aromatic aldehydes in moderate to excellent yields. The protocol features wide substrate scope, good functional group tolerance, and simple operation.

Facile synthesis of isoquinolines and isoquinoline -oxides a copper-catalyzed intramolecular cyclization in water.

A highly efficient method for the facile access of isoquinolines and isoquinoline -oxides a Cu(i)-catalyzed intramolecular cyclization of ()-2-alkynylaryl oxime derivatives in water has been developed. This protocol was performed under simple and mild conditions without organic solvent, additives or ligands. By switching on/off a hydroxyl protecting group of oximes, the selective N-O/O-H cleavage could be triggered, delivering a series of isoquinolines and isoquinoline -oxides, respectively, in moderate to high yields with good functional group tolerance and high atom economy.

Palladium-catalyzed oxidative Heck reaction of non-activated alkenes directed by fluorinated alcohol.

A novel, Pd-catalyzed oxidative Heck reaction of non-activated alkenes synergistically directed by bifunctional groups has been developed firstly by using O as a green oxidant, yielding the oxidative Heck products with excellent yields in a regio- and stereoselective manner. This bifunctional synergistic activation mechanism was demonstrated by experimental analysis and detailed computational studies, wherein the hydroxyl group directs the migratory insertion of the alkenes and the trifluoromethyl group facilitates the subsequent β-H elimination and reductive elimination. Moreover, a pesticidal active compound was synthesized using the bifunctional synergistically directed C-H arylation as the key step, which demonstrated its synthetic utility.

Palladium-Catalyzed Carbonylation of Aryl Bromides with Carbon Dioxide To Access Aryl Carboxylic Acids under Mild Conditions.

A palladium-catalyzed direct carbonylation of aryl bromides with carbon dioxide as the carbonyl source has been developed by using Pd(dba)/DPEPhos as the catalyst under mild reaction conditions, providing an efficient route to a variety of aryl carboxylic acids in moderate to high yields. The methods have many advantages such as the use of a simple palladium catalyst system, wide substrate scope, good functional group tolerance, high yields, and easy scalability.

Glucolipotoxicity induces endothelial cell dysfunction by activating autophagy and inhibiting autophagic flow.

Objectives: This study aims to determine the role and mechanism of autophagy in endothelial cell dysfunction by glucolipotoxicity.

Methods: Human umbilical vein endothelial cells (HUVECs) were treated with high glucose and high palmitic acid. The number of autophagosomes was evaluated by monodansylcadaverine (MDC) staining and transmission electron microscopy (TEM).

Stereodivergent synthesis of β-iodoenol carbamates with CO photocatalysis.

Photocatalytic conversion of carbon dioxide (CO) into value-added chemicals is of great significance from the viewpoint of green chemistry and sustainable development. Here, we report a stereodivergent synthesis of β-iodoenol carbamates through a photocatalytic three-component coupling of ethynylbenziodoxolones, CO and amines. By choosing appropriate photocatalysts, both - and -isomers of β-iodoenol carbamates, which are difficult to prepare using existing methods, can be obtained stereoselectively.

Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt.

Metformin, traditionally regarded as a hypoglycemic drug, has been studied in other various fields including inflammation. The specific mechanism of metformin's effect on immune cells remains unclear. Herein, it is verified that LPS-induced macrophages are characterized by enhanced endogenous fatty acid synthesis and the inhibition of fatty acid synthase (FASN) downregulates proinflammatory responses.

Niobium carbide (MXene) reduces UHMWPE particle-induced osteolysis.

Joint replacement surgery is one of the orthopedic surgeries with high successful rates; however, wear debris generated from prostheses can ultimately lead to periprosthetic osteolysis and failure of the implant. The implant-derived particulate debris such as ultrahigh molecular weight polyethylene (UHMWPE) can initiate the local immune response and recruit monocytic cells to phagocytose particles for generating reactive oxygen species (ROS). ROS induces osteoclastogenesis and macrophages to secrete cytokines which ultimately promote the development of osteolysis.

Macrocyclization of 3-triflyloxybenzynes with tetrahydrofuran via an anionic thia-Fries rearrangement.

A novel and uncommon macrocyclization reaction between 3-triflyloxybenzynes and tetrahydrofuran has been developed for the first time, providing a direct method for the synthesis of a range of functionalized 19-membered polyether macrocycles in moderate to good yields. The process was proposed to proceed through an anionic thia-Fris rearrangement under transition metal-free conditions, leading to the formation of four new C-O bonds and one new C-S bond in a single step.

Direct bromocarboxylation of arynes using allyl bromides and carbon dioxide.

An unprecedented three-component coupling involving arynes, allyl bromides, and CO2 is described, providing efficient and facile access to structurally diverse ortho-brominated aryl esters. Unlike the conventional role played in organic synthesis as electrophiles, organic bromides served as nucleophiles in this reaction, affording a new approach to multicomponent reactions (MCRs) involving aryne intermediates. Additionally, Hammett analysis suggests that two reaction mechanisms exist, depending on the electronic nature of the cinnamyl bromides used.

Direct Access to Trifluoromethyl-Substituted Carbamates from Carbon Dioxide via Copper-Catalyzed Cascade Cyclization of Enynes.

A copper-catalyzed cascade cyclization of enynes with Togni's reagent, carbon dioxide, and amines has been successfully developed. The reaction provides a direct and efficient route to a range of trifluoromethyl-substituted carbamates, which are difficult to access using existing methods. Mild reaction conditions, good functional tolerance, and wide substrate scope are the feactures of the protocol.

Copper-Catalyzed C-H Carbamoyloxylation of Aryl Carboxamides with CO and Amines at Ambient Conditions.

A copper-catalyzed, 8-aminoquinoline-assisted, one-pot three-component coupling of aryl carboxamides, CO, and amines has been developed. This protocol proceeds smoothly in the presence of inexpensive CuI and MnO at room temperature under atmospheric CO pressure, leading to simultaneous construction of C-O and C-N bonds. The reaction displays a broad substrate scope, high functional group tolerance, and excellent monoselectivity, providing an operationally simple method for the synthesis of various O-aryl carbamates.

Iridium-Catalyzed Three-component Coupling Reaction of Carbon Dioxide, Amines, and Sulfoxonium Ylides.

The first iridium-catalyzed three-component coupling reaction of carbon dioxide, amines, and sulfoxonium ylides has been developed, providing an efficient and straightforward method for the construction of a range of structurally diverse O-β-oxoalkyl carbamates in moderate to excellent yields. This novel protocol features the use of readily available substrates, wide substrate scope, and good functional group tolerance. Moreover, the phosgene-free strategy was successfully applied to the synthesis of a potential antitumor agent.

A Three-Phase Four-Component Coupling Reaction: Selective Synthesis of o-Chloro Benzoates by KCl, Arynes, CO, and Chloroalkanes.

A transition-metal-free three-phase four-component coupling reaction (3P-4CR) involving KCl, arynes, chloroalkanes and CO has been reported for the first time, enabling the incorporation of both chloro and CO into an aryne simultaneously. The reactions for the synthesis of different types of o-chloro benzoates can be selectively modulated by the chloroalkane utilized. The corresponding products can be alternatively transformed for postsynthetic functionalizations conveniently.

A four-component coupling reaction of carbon dioxide, amines, cyclic ethers and 3-triflyloxybenzynes for the synthesis of functionalized carbamates.

A novel four-component coupling reaction of carbon dioxide, amines, cyclic ethers and 3-triflyloxybenzynes has been developed for the first time, providing an efficient method for the synthesis of a series of functionalized carbamate derivatives in moderate to high yields. The process proceeds under mild, transition metal-free and fluoride-free conditions, leading to the formation of two new C-O bonds, one new C-N bond and one C-H bond in a single step.

Palladium-Catalyzed Four-Component Cascade Reaction for the Synthesis of Highly Functionalized Acyclic O,O-Acetals.

A palladium-catalyzed four-component cascade reaction of carbon dioxide, amines, allenyl ethers, and aryl iodides has been developed for the first time. The novel reaction allows simultaneous construction of three different new bonds (C-N, C-O, and C-C) in a single step, affording an efficient method for the synthesis of a variety of highly functionalized acyclic O,O-acetals. Excellent chemo- and regioselectivity, wide substrate scope, and good functional group tolerance are features of the method.

Palladium-Catalyzed Synthesis of 1H-Indenes and Phthalimides via Isocyanide Insertion.

A new and versatile multicomponent domino strategy has been developed for the synthesis of a series of 1H-indene and phthalimide derivatives from simple and readily available starting materials. This process operating under mild conditions shows a broad substrate scope with moderate to excellent yields.

Base-Promoted Formal [4 + 3] Annulation between 2-Fluorophenylacetylenes and Ketones: A Route to Benzoxepines.

The first base-promoted formal [4 + 3] annulation between 2-fluorophenylacetylenes and ketones has been disclosed. The reaction proceeds through a tandem α-vinylation of ketones followed by an intramolecular nucleophilic aromatic substitution (SNAr) reaction of the in situ generated β,γ-unsaturated ketone intermediates, providing a straightforward access to a wide range of functionalized benzoxepines in moderate to high yields. The transition-metal-free methodology featured a wide substrate scope, the use of easily available starting materials, and a high functional group tolerance.

Base-promoted coupling of carbon dioxide, amines, and diaryliodonium salts: a phosgene- and metal-free route to O-aryl carbamates.

A phosgene- and metal-free synthesis of O-aryl carbamates is realized through a three-component coupling of carbon dioxide, amines and diaryliodonium salts. The reaction only requires a base as the promoter, providing access to a diverse array of O-aryl carbamates in moderate to high yields with excellent chemoselectivity.

Pd-Catalyzed Highly Regio- and Stereoselective Formation of C-C Double Bonds: An Efficient Method for the Synthesis of Benzofuran-, Dihydrobenzofuran-, and Indoline-Containing Alkenes.

A highly regio- and stereoselective C-C double bond formation reaction via Pd-catalyzed Heck-type cascade process with N-tosylhydrazones has been developed. Various N-tosylhydrazones derived from both ketones and aldehydes are found to be efficient substrates to provide di- and trisubstituted olefins with high regio- and stereoselectivity. Furthermore, this reaction has a good functional group tolerance and different benzofuran-, dihydrobenzofuran-, and indoline-containing alkene products were obtained with high selectivity.

Copper-Catalyzed [4 + 1] Annulation between α-Hydroxy Ketones and Nitriles: An Approach to Highly Substituted 3(2H)-Furanones.

A copper-catalyzed [4 + 1] annulation between α-hydroxy ketones and nitriles has been developed. The reaction provides a facile and efficient method for the construction of a wide range of highly substituted 3(2H)-furanones, a class of important compounds known to be associated with several biological activities.

Base-promoted coupling of carbon dioxide, amines, and N-tosylhydrazones: a novel and versatile approach to carbamates.

A base-promoted three-component coupling of carbon dioxide, amines, and N-tosylhydrazones has been developed. The reaction is suggested to proceed via a carbocation intermediate and constitutes an efficient and versatile approach for the synthesis of a wide range of organic carbamates. The advantages of this method include the use of readily available substrates, excellent functional group tolerance, wide substrate scope, and a facile work-up procedure.