Pd(II)-catalyzed regioselective ring opening/[3+2] annulation reaction of enaminones with cyclopropenones: divergent synthesis of γ-butenolides and γ-lactams.

A practical, effective, and regioselective palladium-catalyzed ring opening/[4+2] annulation of enaminones with cyclopropenones for the controllable synthesis of highly substituted γ-butenolides and γ-lactams has been described. This method for the first time reports the regio-selective annulation reaction on the carbon and amine groups of the enaminone structure. This reaction is characterized by its wide substrate scope, good functional group compatibility, moderate to good yields, scale-up synthesis, and versatile transformations, providing a versatile and general protocol to construct γ-butenolides and γ-lactams.

NBS-Mediated C(sp)-H Bond Chlorination of Enaminones: Using DCE as Chlorine Source.

Commercial DCE is excavated as both a "Cl" source and a solvent for the vinyl C(sp)-H chlorination. The strategy involves a metal-free NBS-mediated C(sp)-H chlorination of enaminones, and affords diverse, functionalized -chlorinated enaminones with a -configuration. This mild and effective approach not only advances the vinyl C(sp)-H chlorination, employing DCE as the "Cl" source, but also provides a new strategy for accessing chlorinated enaminone derivatives.

Predictive value of IL-10 and GFPA for postoperative prognosis in patients with brain glioma.

Objective: To investigate the prognostic value of interleukin (IL)-10 and glial fibrillary acidic protein (GFPA) in patients with brain glioma following surgery.

Methods: The clinical data of 75 patients with brain glioma (Observation group) who were treated at the Central Hospital Affiliated with Shandong First Medical University were retrospectively analyzed. Additionally, 40 healthy volunteers who underwent physical examination during the same period were selected as the control group.

Regioselective α-Phosphonylation of Unprotected Alicyclic Amines.

Unprotected alicyclic amines undergo α-C-H bond phosphonylation via a two-stage one-pot process involving the oxidation of amine-derived lithium amides with simple ketone oxidants, generating transient imines which are then captured with phosphites or phosphine oxides. Amines with an existing α-substituent undergo regioselective α'-phosphonylation. Amine α-arylation and α'-phosphonylation can be combined, generating a difunctionalized product in a single operation.

Divergent Synthesis of 2-Chromonyl-3-hydrazono-chromones and 2-Alkoxy-3-hydrazono-chromones through Switchable Annulation Reactions of -Hydroxyphenylenaminones with Aryldiazonium Salts.

An unprecedented selective chromone annulation reaction controlled by solvent for the divergent synthesis of two types of 2,3-disubstituted chromone skeletons has been developed. A variety of 2-chromonyl-3-hydrazono-chromones and 2-alkoxy-3-hydrazono-chromones were constructed efficiently from readily available -hydroxyphenylenaminones (-HPEs) and aryldiazonium salts at room temperature. This strategy is highly chemoselective and features mild reaction conditions, broad substrate scope, broad functional group tolerance, easy gram-scale preparation, and simple filtration to obtain the pure products without tedious column chromatography.

Oxidative Free-Radical C(sp)-H Bond Chlorination of Enaminones with LiCl: Access to Highly Functionalized α-Chlorinated Enaminones.

An oxidative free-radical C(sp)-H bond chlorination strategy of enaminones has been developed by using LiCl as a chlorinating reagent and KSO as an oxidant. This transformation provides a new and straightforward synthetic methodology to afford highly functionalized α-chlorinated enaminones with a -configuration in good to excellent yields.

Mitigation of myocardial ischemia/reperfusion-induced chronic heart failure via Shexiang Baoxin Pill-mediated regulation of the S1PR1 signaling pathway.

Background: Well-defined and effective pharmacological interventions for clinical management of myocardial ischemia/reperfusion (MI/R) injury are currently unavailable. Shexiang Baoxin Pill (SBP), a traditional Chinese medicine Previous research on SBP has been confined to single-target treatments for MI/R injury, lacking a comprehensive examination of various aspects of MI/R injury and a thorough exploration of its underlying mechanisms.

Purpose: This study aimed to investigate the therapeutic potential of SBP for MI/R injury and its preventive effects on consequent chronic heart failure (CHF).

DAHOS Study: Efficacy of dapagliflozin in treating heart failure with reduced ejection fraction and obstructive sleep apnea syndrome - A 3-month, multicenter, randomized controlled clinical trial.

Background: The recent discovery of new therapeutic approaches to heart failure with reduced ejection fraction (HFrEF), including sodium-glucose cotransporter-2 (SGLT-2) inhibitors, as well as improved treatment of co-morbidities has provided much needed help to HFrEF. In addition, dapagliflozin, one of the SGLT-2 inhibitors, serves as a promising candidate in treating obstructive sleep apnea (OSA) of HFrEF patients due to its likely mechanism of countering the pathophysiology of OSA of HFrEF.

Methods: This 3-month multicenter, prospective, randomized controlled trial enrolled participants with left ventricular ejection fraction (LVEF) less than 40% and apnea-hypopnea index (AHI) greater than 15.

Platelet Membrane Nanocarriers Cascade Targeting Delivery System to Improve Myocardial Remodeling Post Myocardial Ischemia-Reperfusion Injury.

Although treatments for myocardial infarction have advanced significantly, the global mortality due to ischemia and subsequent reperfusion injury remains high. Here, a platelet (PLT) membrane nanocarrier (PL720) that encapsulates L-arginine and FTY720 to facilitate the cascade-targeted delivery of these substances to the myocardial injury site and enable the controlled release of L-arginine and FTY720 is developed. Such an innovative approach shows enhanced cardioprotection through multiple target strategies involved in ischemia-reperfusion injury and late reperfusion inflammation.

Smart Home Sleep Respiratory Monitoring System Based on a Breath-Responsive Covalent Organic Framework.

A smart home sleep respiratory monitoring system based on a breath-responsive covalent organic framework (COF) was developed and utilized to monitor the sleep respiratory behavior of real sleep apnea patients in this work. The capacitance of the interdigital electrode chip coated with COF exhibits thousands-level reversible responses to breath humidity gases, with subsecond response time and robustness against environmental humidity. A miniaturized printed circuit board, an open-face-mask-based respiratory sensor, and a smartphone app were constructed for the wearable wireless smart home sleep respiratory monitoring system.

Rh(III)-catalyzed selective mono- and dual-functionalization/cyclization of 1-aryl-5-aminopyrazoles with iodonium ylides.

An efficient Rh(III)-catalyzed selective mono- and dual-C-H bond functionalization/cyclization with iodonium ylide as a single coupling partner was demonstrated, in which fused benzodiazepine skeletons were obtained in excellent yields. This method greatly improved an effective approach to dual C-H unsymmetrical functionalization.

Synthesis of Tetrahydro-indolones through Rh(III)-Catalyzed [3 + 2] Annulation of Enaminones with Iodonium Ylides.

An unprecedented protocol for a Rh(III)-catalyzed [3 + 2] annulation from simple and readily available enaminones and iodonium ylides has been developed. The novel strategy allows for access to a new class of structurally diverse tetrahydro-indolones with high efficiency and a broad substrate scope. In addition, this transformation represents the first example of the selective Rh(III)-catalyzed alkenyl C-H bond functionalization and annulation of enaminones.

Rh(III)-Catalyzed [3 + 2] Annulation/Pinacol Rearrangement Reaction of Enaminones with Iodonium Ylides: Direct Synthesis of 2-Spirocyclo-pyrrol-3-ones.

A novel Rh(III)-catalyzed cascade alkenyl C-H activation/[3 + 2] annulation/pinacol rearrangement reaction of enaminones with iodonium ylides has been developed. This methodology provides a new and straightforward synthetic strategy to afford highly functionalized 2-spirocyclo-pyrrol-3-ones in satisfactory yield from readily available starting materials under mild conditions. Moreover, gram-scale reactions and further derivatization experiments are implemented to demonstrate the potential utility of this developed approach.

Construction of 1,4-Dihydropyridines: The Evolution of C4 Source.

The field of cascade cyclization for the construction of 1,4-dihydropyridines (1,4-DHPs) has been continuously expanding during the last decades because of their broad-spectrum biological and synthetic importance. To date, many methods have been developed, mainly including the Hantzsch reaction, Hantzsch-like reaction and newly developed cascade cyclization, in which various synthons have been successively developed as C4 sources of 1,4-DHPs. This review presents the cascade cyclization synthesis strategy for the construction of 1,4-DHPs according to various C4 sources from carbonyl compounds, alkenyl fragments, alcohols, aliphatic amines, glycines and other C4 sources.

Synthesis of 4-Alkylated 1,4-Dihydropyridines: Fe(II)-Mediated Oxidative Cascade Cyclization Reaction of Cyclic Ethers with Enaminones.

Syntheses of highly functionalized 4-alkylated 1,4-dihydropyridines (1,4-DHPs) from cyclic ethers and enaminones via iron(II)-mediated oxidative free radical cascade C(sp)-H bond functionalization/C(sp)-O bond cleavage/cyclization reaction have been first developed. This novel synthetic strategy offers an alternative method for the construction of 1,4-DHPs by using esters as the C4 sources, as well as expands the application of ethers in heterocycle synthesis.

Fe-mediated oxidative cascade [1 + 2 + 3]-cyclization/esterification reaction: synthesis of 4-alkylated 1,4-dihydropyridines.

An Fe-mediated four-component reaction of enaminones, anhydrides and tetrahydrofuran through a cascade [1 + 2 + 3]-cyclization/esterification process is presented. This protocol provides a new and effective method to construct 4-alkylated 1,4-dihydropyridines with an ester fragment. Cyclic ether is employed as the C4 source of 1,4-dihydropyridines for the first time.

Efficacy of dapagliflozin in the treatment of HFrEF with obstructive sleep apnea syndrome (DAHOS study): study protocol for a multicentric, prospective, randomized controlled clinical trial.

Background: Heart failure with reduced ejection fraction (HFrEF) is associated with sleep dyspnea (SDB), which plays an adverse role in the pathophysiology of the condition. SDB management in HFrEF, however, remains controversial. HFrEF's medical management has recently made significant progress with the discovery of new therapeutic avenues, namely sodia-glucose cotransporter-2 (SGLT-2) inhibitors, and better treatment of co-morbidities.

Access to thiionized-, selenolized-, and alkylated 5-alkylidene 3-pyrrolin-2-one derivatives a regioselective oxidative annulation reaction.

A metal-free regioselective oxidative annulation reaction of readily available 2,4-pentanediones with primary amines has been described. This protocol provides a divergent strategy for the incorporation of various radical donors into 5-alkylidene 3-pyrrolin-2-one skeletons, producing a variety of thiionized-, selenolized-, and alkylated 5-alkylidene 3-pyrrolin-2-one derivatives. Moreover, the diverse synthetic transformations of the 5-alkylidene 3-pyrrolin-2-one products were also investigated.

Copper-Catalyzed Oxidative [1+2+1+2] Cascade Cyclization of N,N-Dimethyl Enaminones with Benzylamines: A Facile Access to Functionalized 1,4-Dihydropyridines.

Using benzylamines as the C4 source of 1,4-dihydropyridines (1,4-DHPs), a Cu-catalyzed oxidative [1+2+1+2] cascade cyclization for the synthesis of 1,4-DHPs was firstly developed. A broad range of easily available N,N-dimethyl enaminones and benzylamines are employed smoothly to provide a diverse range of 1,4-DHPs with high efficiency. This method is performed by a one-pot cascade C(sp )-H bond functionalization/C(sp )-N cleavage/cyclization strategy to form simultaneously two C(sp )-C(sp ) bonds, two C(sp )-N bonds, and a 1,4-DHP ring.

Facile access to the 2,2-difluoro-2,3-dihydrofuran skeleton without extra additives: DMF-promoted difluorocarbene formation of ClCFCONa.

A practical and facile difluorocarbene-triggered cycloaddition reaction of enaminones was developed, which delivered 2,2-difluoro-2,3-dihydrofurans with a broad substrate scope. Notably, the reaction proceeded smoothly without any extra additives. Readily available sodium chlorodifluoroacetate (ClCFCONa, SCDA) served as a difluorocarbene precursor in this transformation through DMF-promotion.

Transition-metal-free approach to quinolines direct oxidative cyclocondensation reaction of ,-dimethyl enaminones with -aminobenzyl alcohols.

A transition-metal-free method for the construction of 3-substituted or 3,4-disubstituted quinolines from readily available ,-dimethyl enaminones and -aminobenzyl alcohols is reported. The direct oxidative cyclocondensation reaction tolerates broad functional groups, allowing the efficient synthesis of various quinolines in moderate to excellent yields. The reaction involves a C (sp)-O bond cleavage and a C=N bind and a C=C bond formation during the oxidative cyclization process, and the mechanism was proposed.

Bpin-Mediated Cascade Cyclization/Aromatization Reaction: Facial Access to Functionalized Indolizines.

Herein, a Bpin-mediated radical cascade cyclization/aromatization reaction of enaminone with pyridine is described. This strategy provides a practical way for the construction of valuable functionalized indolizines under metal-, external oxidant-, and base-free conditions, which could be compatible with various kinds of functional groups, such as halogen, π-system, heterocycle, ferrocenyl, etc. A preliminary mechanism investigation indicated that the pyridine-boryl radical formed in situ triggered the reaction to occur.

Chronic intermittent hypoxia accelerates cardiac dysfunction and cardiac remodeling during cardiac pressure overload in mice and can be alleviated by PHD3 overexpression.

Obstructive sleep apnea (OSA) accelerates the progression of chronic heart failure (CHF). OSA is characterized by chronic intermittent hypoxia (CIH), and CIH exposure accelerates cardiac systolic dysfunction and cardiac remodeling in a cardiac afterload stress mouse model. Mechanistic experiments showed that long-term CIH exposure activated hypoxia-inducible factor 1α (HIF-1α) expression in the mouse heart and upregulated miR-29c expression and that both HIF-1α and miR-29c simultaneously inhibited sarco-/endoplasmic reticulum calcium ATPase 2a (SERCA2a) expression in the mouse heart.