Domino Michael/Oxa-Michael Reactions of the Unsymmetric Double Michael Acceptor for Access to Bicyclic Furo[2,3-]pyrrole.

By creating an unsymmetric double Michael acceptor , we were able to synthesize the nonaromatic-fused bicyclic furo[2,3-]pyrrole nucleus using a domino Michael/oxa-Michael reaction. Adopting benzoyl acetonitrile (CN as the electron-withdrawing group) as a substrate, we discovered a (DHQ)AQN-catalyzed method for high diastereo- and enantioselectivity of those products. The reaction path has been determined by isolating the reaction intermediates, and density functional theory calculations support these findings.

Green and highly effective extraction of bioactive flavonoids from Fructus aurantii employing deep eutectic solvents-based ultrasonic-assisted extraction protocol.

In China, Jiang Fructus aurantii (JFA) has attracted increasing interest as a famous traditional herbal medicine and valuable economic food for its valuable medicinal and industrial properties. In the current work, contrasted with conventional extraction techniques, natural flavonoids from JFA (naringin and neohesperidin) were extracted with remarkable effectiveness utilizing a sustainable deep eutectic solvents combined ultrasonic-assisted extraction (DESs-UAE) protocol. The optimal extraction capacity can be achieved by mixing 30 % water with a molar ratio of 1:3 for choline chloride and ethylene glycol, as opposed to the classical extraction solvents of 95 % ethanol, methanol, and water.

Base-promoted highly efficient synthesis of nitrile-substituted cyclopropanes Michael-initiated ring closure.

A convenient and efficient annulation reaction has been developed for the general synthesis of dinitrile-substituted cyclopropanes in moderate to excellent yields. A variety of 2-arylacetonitriles and α-bromoennitriles were compatible under the standard conditions. The reaction was achieved through tandem Michael-type addition followed by intramolecular cyclization.

Iron(III)-catalyzed α-cyanation and carbonylation with 2-pyridylacetonitrile: divergent synthesis of α-amino nitriles and tetrahydroisoquinolinones.

Iron-catalyzed oxidative synthesis of -aryl-substituted tetrahydroisoquinolines (THIQs) toward tetrahydroisoquinoline-based derivatives is reported. A wide range of α-amino nitriles and tetrahydroisoquinolinones are synthesized in moderate to good yields. This approach involves a new organic nitrile source, a cheap iron catalyst under an oxygen atmosphere, and temperature-controlled divergent synthesis and features complete selectivity and operational simplicity.

TA-MSCs, TA-MSCs-EVs, MIF: their crosstalk in immunosuppressive tumor microenvironment.

As an important component of the immunosuppressive tumor microenvironment (TME), it has been established that mesenchymal stem cells (MSCs) promote the progression of tumor cells. MSCs can directly promote the proliferation, migration, and invasion of tumor cells via cytokines and chemokines, as well as promote tumor progression by regulating the functions of anti-tumor immune and immunosuppressive cells. MSCs-derived extracellular vesicles (MSCs-EVs) contain part of the plasma membrane and signaling factors from MSCs; therefore, they display similar effects on tumors in the immunosuppressive TME.

Crosstalk among mA RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application.

The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, and immunosuppression. One of the most common RNA modifications, N6-methyladenosine (mA) methylation, is widely involved in the regulation of physiological and pathological processes, including tumor development.

Independent risk factors for true malignancy in atypical cytologic diagnostic category in EUS-FNA/FNB of the pancreas: A novel prediction model.

Background And Objects: An atypical cytologic diagnosis arises from inflammation or early neoplastic process. It is commonly found in EUS-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) tissue sampling of pancreatic malignancies. The aims of this study were to evaluate the diagnostic performance of EUS-FNA/FNB in patients with cytologic diagnosis of atypical cells and to develop a prediction model for malignant tumors of the pancreas in the atypical cytologic diagnostic category.

Application of engineered extracellular vesicles for targeted tumor therapy.

All cells, including prokaryotes and eukaryotes, could release extracellular vesicles (EVs). EVs contain many cellular components, including RNA, and surface proteins, and are essential for maintaining normal intercellular communication and homeostasis of the internal environment. EVs released from different tissues and cells exhibit excellent properties and functions (e.

Mesenchymal stem cell-derived exosome: A tumor regulator and carrier for targeted tumor therapy.

Mesenchymal stem cells (MSCs) are multipotent stromal cells that have the ability to differentiate into multiple cell types. Several studies have shown that exosomes secreted by MSCs (MSCs-Exo) play an important role in tumor growth, angiogenesis, invasion, and drug resistance. However, contradictory results have suggested that MSCs-Exo can also suppress tumors through specific mechanisms, such as regulating immune responses and intercellular signaling.

Developing Push-Pull Hydroxylphenylpolyenylpyridinium Chromophores as Ratiometric Two-Photon Fluorescent Probes for Cellular and Intravital Imaging of Mitochondrial NQO1.

This work highlights the use of push-pull hydroxylphenylpolyenylpyridinium fluorophores coupled with trimethyl lock quinone to engineer the ratiometric two-photon probes for cellular and intravital imaging of mitochondrial NAD(P)H:quinone oxidoreductase 1 (NQO1), a critical antioxidant enzyme responsible for detoxifying quinones. As a typical representative, showed favorable binding with NQO1 with a Michaelis constant of 12.74 μM and exhibited a suite of superior properties, including rapid response (4 min), large Stokes shift (162 nm), ultralow detection limit (0.

Ce(iii)-catalyzed highly efficient synthesis of pyridyl benzamides from aminopyridines and nitroolefins without external oxidants.

An efficient synthesis of a variety of pyridyl benzamides from 2-aminopyridines and nitroolefins is described. This rare-earth-metal-catalyzed reaction provides the corresponding products with broad substrate scope in moderate to excellent yields, in the absence of additives and external oxidants. Water is used as the source of the carbonyl oxygen atom in pyridyl benzamides.

Alterations of microRNA-124 expression in peripheral blood mononuclear cells in pre- and post-treatment patients with major depressive disorder.

Recently, increasing evidence has indicated that dysfunction of microRNA-124 (miR-124) might be involved in the pathophysiology and treatment of major depressive disorder (MDD) in some animal models of depression. However, the role of miR-124 in MDD patients remains unclear. The objective of this study was to investigate whether the miR-124 expression levels in peripheral blood mononuclear cells (PBMCs) were associated with MDD and to evaluate the effects of antidepressant treatment on miR-124 levels.

Dopamine receptor D2 and catechol-O-methyltransferase gene polymorphisms associated with anorexia nervosa in Chinese Han population: DRD2 and COMT gene polymorphisms were associated with AN.

Dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) are important in dopamine system which is proved to be associated with food-anticipatory behavior, food restriction, reward and motivation. This has made them good candidates for anorexia nervosa (AN). The aim of this work is to explore the roles of DRD2 (rs1800497) and COMT (rs4680, rs4633, rs4818) gene polymorphisms in the susceptibility of AN within the Chinese Han population.

Estrogen receptor 1 gene rs2295193 polymorphism and anorexia nervosa: new data and meta-analysis.

Introduction: Estrogen plays essential roles in the regulation of food intake, adiposity, and body weight control. The estrogen alpha receptor, encoded by estrogen receptor 1 gene (ESR1), has been implicated with anorexia nervosa (AN). A previous study indicated that the rs2295193 polymorphism in ESR1 may confer a genetic susceptibility to AN.

Ortho-dihydroxychalcones as cupric ion-dependent prooxidants: activity and mechanisms.

The activity and chemical mechanisms of ortho-dihydroxychalcones as cupric ion-dependent prooxidants were investigated under aerobic conditions. This work confirms that 3,4,3',4'-tetrahydroxychalcone and cupric ions could synergistically advance strand breakage of plasmid DNA, but also effectively induce DNA damage and apoptosis of human hepatoma HepG2 cells under low concentrations by promoting ROS production. Interestingly, ortho-dihydroxy groups on the aromatic B ring, connected by a double bond, possess higher DNA-cleaving activity than those on the aromatic A ring directly attached to a carbonyl group.

The peripheral messenger RNA expression of glycogen synthase kinase-3β genes in Alzheimer's disease patients: a preliminary study.

Objective: To explore the peripheral leucocytic messenger RNA (mRNA) expression of glycogen synthase kinase-3β (GSK-3β) gene in Alzheimer's disease (AD) patients.

Methods: Using TaqMan relative quantitative real-time polymerase chain reaction, we analyzed leucocytic gene expression of GSK-3β in 48 AD patients and 49 healthy controls. Clinical data of AD patients were also collected.

[Effect of Lycium ruthenicum anthocyanins on atherosclerosis in mice].

Objective: To study the effect of Lycium ruthenicum anthocyanins on atherosclerosis (AS) in mice.

Method: Normal mice were taken as the control group, and hyperlipemia mice were divided into the model group, Lycium ruthenicum anthocyanins low, medium and high dose groups, and the simvastatin drug control group. After the oral administration, blood lipid indicators were detected by enzymatic analysis.

[Association of cyclic adenosine monophosphate response element-binding protein gene and major depressive disorder].

Objective: To investigate the association between single nucleotide polymorphisms (SNPs) in cyclic adenosine monophosphate response element-binding protein(CREB1) gene and major depressive disorder (MDD).

Methods: We recruited 105 parent-offspring trios of Chinese descent, extracted whole blood genomic DNA, and genotyped the SNPs in rs10932201 and rs6740584 loci. Single-marker transmission disequilibrium test (TDT), pairwise SNP linkage disequilibrium(LD) and haplotype-based TDT were performed.

Antioxidant and antiproliferative activities of hydroxyl-substituted Schiff bases.

Eight hydroxyl-substituted Schiff bases with the different number and position of hydroxyl group on the two asymmetric aromatic rings (A and B rings) were prepared by the reaction between the corresponding aromatic aldehyde and aniline. Their antioxidant effects against the stable galvinoxyl radical (GO(.)) in ethyl acetate and methanol, and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced DNA strand breakage, and their antiproliferative effects on human hepatoma HepG2 cells, were investigated.

Antioxidant activity of alpha-pyridoin and its derivatives: possible mechanism.

alpha-Pyridoin (1, 1,2-di(2-pyridyl)-1,2-ethenediol) is a unique enediol antioxidant. To explore the detailed antioxidant mechanism of alpha-pyridoin, we synthesized alpha-pyridoin and its 5,5'- or 6,6'-bis-substituted derivatives (2-7) and compared their capacities to scavenge galvinoxyl radical (GO*) and protect human red blood cells (RBCs) from oxidative haemolysis. It was found that the compounds (5 and 6) with a methyl or methoxy group at the 5-position exhibit significantly higher GO*-scavenging and anti-haemolysis activities than other derivatives and vitamin C.

Hydroxycinnamic acids as DNA-cleaving agents in the presence of Cu(II) ions: mechanism, structure-activity relationship, and biological implications.

The effectiveness of hydroxycinnamic acids (HCAs), that is, caffeic acid (CaA), chlorogenic acid (ChA), sinapic acid (SA), ferulic acid (FA), 3-hydroxycinnamic acid (3-HCA), and 4-hydroxycinnamic acid (4-HCA), as pBR322 plasmid DNA-cleaving agents in the presence of Cu(II) ions was investigated. Compounds bearing o-hydroxy or 3,5-dimethoxy groups on phenolic rings (CaA, SA, and ChA) were remarkably more effective at causing DNA damage than the compounds bearing no such groups; furthermore, CaA was the most active among the HCAs examined. The involvement of reactive oxygen species (ROS) and Cu(I) ions in the DNA damage was affirmed by the inhibition of the DNA breakage by using specific scavengers of ROS and a Cu(I) chelator.

Family-based association study between brain-derived neurotrophic factor gene and major depressive disorder of Chinese descent.

The genetic pathogenesis of major depressive disorder (MDD) has not been elucidated. It has been proposed that brain-derived neurotrophic factor (BDNF), as a member of the neurotrophin family, may be involved in the etiology and antidepressant response of MDD. The present study investigated the possible presence of an association between the BDNF gene and MDD.

Radical-scavenging activity and mechanism of resveratrol-oriented analogues: influence of the solvent, radical, and substitution.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene, 3,5,4'-THS) is a well-known natural antioxidant and cancer chemopreventive agent that has attracted much interest in the past decade. To find a more active antioxidant and investigate the antioxidative mechanism with resveratrol as the lead compound, we synthesized 3,5-dihydroxy-trans-stilbene (3,5-DHS), 4-hydroxy-trans-stilbene (4-HS) 3,4-dihydroxy-trans-stilbene (3,4-DHS), 4,4'-dihydroxy-trans-stilbene (4,4'-DHS), 4-hydroxy-3-methoxy-trans-stilbene (3-MeO-4-HS), 4-hydroxy-4'-methoxy-trans-stilbene (4'-MeO-4-HS), 4-hydroxy-4'-methyl-trans-stilbene (4'-Me-4-HS), 4-hydroxy-4'-nitro-trans-stilbene (4'-NO(2)-4-HS), and 4-hydroxy-4'-trifluoromethyl-trans-stilbene (4'-CF(3)-4-HS). The radical-scavenging activity and detailed mechanism of resveratrol and its analogues (ArOHs) were investigated by the reaction kinetics with galvinoxyl (GO(*)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH(*)) radicals in ethanol and ethyl acetate at 25 degrees C, using UV-vis spectroscopy.

Antioxidant-based lead discovery for cancer chemoprevention: the case of resveratrol.

Resveratrol is a well-known natural antioxidant and cancer chemopreventive agent that has attracted much interest in the past decade. Resveratrol-directed compounds were synthesized, and their antioxidant effects against reactive oxygen species (ROS)-induced DNA damage, their prooxidant effects on DNA damage in the presence cupric ions, and their cytotoxic and apoptosis-inducing effects on human promyelocytic leukemia (HL-60) cells were investigated in vitro. It was found that the compounds bearing o-diphenoxyl groups exhibited remarkably higher activities in inhibiting ROS-induced DNA damage, accelerating DNA damage in the presence cupric ions, and inducing apoptosis of HL-60 cells compared with the ones bearing no such groups.