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1.
J Am Chem Soc ; 146(5): 2919-2927, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38277794

RESUMO

Dicarboxylic acids and derivatives are important building blocks in organic synthesis, biochemistry, and the polymer industry. Although catalytic dicarboxylation with CO2 represents a straightforward and sustainable route to dicarboxylic acids, it is still highly challenging and limited to generation of achiral or racemic dicarboxylic acids. To date, catalytic asymmetric dicarboxylation with CO2 to give chiral dicarboxylic acids has not been reported. Herein, we report the first asymmetric dicarboxylation of 1,3-dienes with CO2 via Cu catalysis. This strategy provides an efficient and environmentally benign route to chiral dicarboxylic acids with high regio-, chemo-, and enantioselectivities. The copper self-relay catalysis, that is, Cu-catalyzed boracarboxylation of 1,3-dienes to give carboxylated allyl boronic ester intermediates and subsequent carboxylation of C-B bonds to give dicarboxylates, is key to the success of this dicarboxylation. Moreover, this protocol exhibits broad substrate scope, good functional group tolerance, easy product derivatizations, and facile synthesis of chiral liquid crystalline polyester and drug-like scaffolds.

2.
Acta Pharmacol Sin ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719954

RESUMO

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

3.
Angew Chem Int Ed Engl ; 63(22): e202403401, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38527960

RESUMO

Upgrading CO2 to value-added chiral molecules via catalytic asymmetric C-C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel-catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza-biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale-up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis.

4.
J Fluoresc ; 33(1): 191-199, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36333647

RESUMO

Endogenous sulfur dioxide (SO2), as a gas signal molecule, has a certain physiological functions. Understanding the role of endogenous SO2 in human physiology and pathology is of great significance to the biological characteristics of SO2,which bring challenges to develop fluorescent probes with excellent performance. Herein, we rationally designed and constructed a novel near-infrared bioprobe benzaldehyde-benzopyrylium (BBp) by employing the nucleophilic addition benzopyrylium perchlorate fluorophore and benzaldehyde moiety by means of C = C/C = O group that serves as both fluorescence reporting unit. Probe BBp exhibit excellent sensing performance with fluorescent "On - Off"rapid response (100 s) and long-wavelength emission (670 nm). With the treatment of HSO3-, the color of BBp solution obviously varies from purple to colorless, and the fluorescent color varies from red to colorless. By the fluorescence and colorimetric changes, probe BBp was capable of sensitive determination HSO3- with low limits of detection (LOD) of 0.43 µM, realizing visual quantitative monitoring SO2 derivative levels. Due to the low phototoxicity and good biocompatibility, it was successfully applied to monitor SO2 derivatives and fluorescence imaging in HepG2 and HeLa living cells. Hopefully, this work supplies a new strategy for designing NIR fluorescent probes for quantitative determination SO2 derivatives in biological samples.


Assuntos
Benzaldeídos , Corantes Fluorescentes , Humanos , Percloratos , Células HeLa , Mitocôndrias
5.
Molecules ; 28(11)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37298972

RESUMO

Magnesium phosphate (MgP) has garnered growing interest in hard tissue replacement processes due to having similar biological characteristics to calcium phosphate (CaP). In this study, an MgP coating with the newberyite (MgHPO4·3H2O) was prepared on the surface of pure titanium (Ti) using the phosphate chemical conversion (PCC) method. The influence of reaction temperature on the phase composition, microstructure, and properties of coatings was systematically researched with the use of an X-ray diffractometer (XRD), a scanning electron microscope (SEM), a laser scanning confocal microscope (LSCM), a contact angle goniometer, and a tensile testing machine. The formation mechanism of MgP coating on Ti was also explored. In addition, the corrosion resistance of the coatings on Ti was researched by assessing the electrochemical behavior in 0.9% NaCl solution using an electrochemical workstation. The results showed that temperature did not obviously affect the phase composition of the MgP coatings, but affected the growth and nucleation of newberyite crystals. In addition, an increase in reaction temperature had a great impact on properties including surface roughness, thickness, bonding strength, and corrosion resistance. Higher reaction temperatures resulted in more continuous MgP, larger grain size, higher density, and better corrosion resistance.


Assuntos
Ligas , Titânio , Temperatura , Titânio/química , Ligas/química , Fosfatos/química , Corrosão , Propriedades de Superfície , Materiais Revestidos Biocompatíveis/química
6.
J Periodontal Res ; 57(1): 63-74, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34610151

RESUMO

BACKGROUND AND OBJECTIVE: Limited studies are available comparing the outcomes of non-surgical periodontal therapy (NSPT) with or without adjunctive Er:YAG laser (ERL) in patients with type 2 diabetes mellitus (T2DM). This study evaluated the effects of ERL adjunctive NSPT on single-rooted teeth of inadequately controlled T2DM patients with periodontitis. METHODS: Twenty-two inadequately controlled T2DM participants with periodontitis were recruited. Adopting a double-blinded split-mouth design and under block randomization, we investigated the effects of ERL in calculus removal then degranulation mode, or a sham treatment, adjunct NSPT, which included two visits of full-mouth root surface debridement delivered within 4-10 days, to test or control single-rooted teeth (Wuxi Stomatology Hospital, trial 2017-016). We followed periodontal parameters (plaque %, bleeding on probing [BOP] %, probing pocket depth [PPD], probing attachment level [PAL]) and selected systemic parameters (fasting plasma glucose [FPG], glycosylated hemoglobin [HbA1c%], high sensitivity C-reactive protein) at baseline, one, three, and six months after periodontal treatment. RESULTS: The study was completed as planned. Periodontal parameters, FPG and HbA1c% of the 22 participants appeared significantly improved at six months (p < 0.001). The 44 ERL treated, compared to 44 sham treated single-rooted teeth exhibited significant improvement in BOP, mean PPD, and mean PAL at various postoperative follow-up time points (effect size ≥0.44; p < 0.001). No adverse event was reported. CONCLUSION: Periodontal treatment outcomes in the T2DM patients with inadequate glycemic control were better in the single-rooted teeth received ERL adjunct NSPT. Further studies are warranted to confirm the observations reported in this short-term clinical study.


Assuntos
Periodontite Crônica , Diabetes Mellitus Tipo 2 , Lasers de Estado Sólido , Periodontite Crônica/terapia , Raspagem Dentária , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Seguimentos , Humanos , Lasers de Estado Sólido/uso terapêutico , Boca , Perda da Inserção Periodontal , Aplainamento Radicular , Resultado do Tratamento
7.
J Am Chem Soc ; 143(7): 2812-2821, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33561344

RESUMO

Carboxylic acids, including amino acids (AAs), have been widely used as reagents for decarboxylative couplings. In contrast to previous decarboxylative couplings that release CO2 as a waste byproduct, herein we report a novel strategy with simultaneous utilization of both the alkyl and carboxyl components from carboxylic acids. Under this unique strategy, carboxylic acids act as bifunctional reagents in the redox-neutral carbocarboxylation of alkenes. Diverse, inexpensive, and readily available α-AAs take part in such difunctionalizations of activated alkenes via visible-light photoredox catalysis, affording a variety of valuable but otherwise difficult to access γ-aminobutyric acid derivatives (GABAs). Additionally, a series of dipeptides and tripeptides also participate in this photocatalytic carbocarboxylation. Although several challenges exist in this system due to the low concentration and quantitative amount of CO2, as well as unproductive side reactions such as hydrodecarboxylation of the carboxylic acids and hydroalkylation of the alkenes, excellent regioselectivity and moderate to high chemoselectivity are achieved. This process features low catalyst loading, mild reaction conditions, high step and atom economy, and good functional group tolerance, and it is readily scalable. The resulting products are subject to efficient derivations, and the overall process is amenable to applications in the late-stage modification of complex compounds. Mechanistic studies indicate that a carbanion is generated catalytically and it acts as the key intermediate to react with CO2, which is also generated catalytically in situ and thus remains in low concentration. The overall transformation represents an efficient and sustainable system for organic synthesis, pharmaceutics, and biochemistry.


Assuntos
Alcenos/química , Aminoácidos/química , Dióxido de Carbono/química , Peptídeos/química , Ácidos Carboxílicos/química , Luz , Ácido gama-Aminobutírico/química
8.
Acta Obstet Gynecol Scand ; 100(10): 1806-1813, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34346055

RESUMO

INTRODUCTION: This study aimed to investigate whether maternal blood lipid levels during early pregnancy are associated with the occurrence of congenital heart disease (CHD) in their offspring. MATERIAL AND METHODS: In this single-center case-control study, mothers of offspring with CHD (n = 230) and without CHD (n = 381) were included. Maternal lipid levels were determined on fasting blood samples taken in the first trimester. Relevant demographic and clinical data were extracted from the medical records. Maternal lipid profile was compared between the two groups, and regression analysis was performed to evaluate the association between lipid profile and CHD risk in offspring. RESULTS: Compared with the control group, levels of triglyceride, apolipoprotein-A1, and apolipoprotein-B in early pregnancy were significantly higher in the CHD group. Multivariate analyses showed that triglyceride (odds ratio [OR] 2.46, 95% CI 1.62-3.73, p < 0.01), total/high-density lipoprotein cholesterol (OR 2.10, 95% CI 1.07-4.13, p = 0.03), and apolipoprotein-A1 (OR 2.73, 95% CI 1.16-6.40, p = 0.02) were positively associated with CHD risk in offspring. CONCLUSIONS: Elevated maternal lipid profile was associated with increased risk of CHD in offspring.


Assuntos
Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Cardiopatias Congênitas/epidemiologia , Hiperlipidemias/sangue , Complicações Hematológicas na Gravidez/sangue , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Cardiopatias Congênitas/etiologia , Humanos , Recém-Nascido , Masculino , Prontuários Médicos , Gravidez , Primeiro Trimestre da Gravidez , Fatores de Risco , Adulto Jovem
9.
Angew Chem Int Ed Engl ; 60(25): 14068-14075, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-33793030

RESUMO

Reductive carboxylation of organo (pseudo)halides with CO2 is a powerful method to provide carboxylic acids quickly. Notably, the catalytic reductive carbo-carboxylation of unsaturated hydrocarbons via CO2 fixation is a highly challenging but desirable approach for structurally diverse carboxylic acids. There are only a few reports and no examples of alkenes via transition metal catalysis. We report the first asymmetric reductive carbo-carboxylation of alkenes with CO2 via nickel catalysis. A variety of aryl (pseudo)halides, such as aryl bromides, aryl triflates and inert aryl chlorides of particular note, undergo the reaction smoothly to give important oxindole-3-acetic acid derivatives bearing a C3-quaternary stereocenter. This transformation features mild reaction conditions, wide substrate scope, facile scalability, good to excellent chemo-, regio- and enantioselectivities. The method highlights the formal synthesis of (-)-Esermethole, (-)-Physostigmine and (-)-Physovenine, and the total synthesis of (-)-Debromoflustramide B, (-)-Debromoflustramine B and (+)-Coixspirolactam A; thereby, opening an avenue for the total synthesis of chiral natural products with CO2 .

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(8): 916-922, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32800042

RESUMO

OBJECTIVE: To study the effect of dhfr gene overexpression on ethanol-induced abnormal cardiac and vascular development in zebrafish embryos and underlying mechanisms. METHODS: dhfr mRNA was transcribed in vitro and microinjected into zebrafish fertilized eggs to induce the overexpression of dhfr gene, and the efficiency of overexpression was verified. Wild-type zebrafish were divided into a control group, an ethanol group, and an ethanol+dhfr overexpression group (microinjection of 6 nL dhfr mRNA). The embryonic development was observed for each group. The transgenic zebrafish Tg (cmlc2:mcherry) with heart-specific red fluorescence was used to observe atrial and ventricular development. Fluorescence microscopy was performed to observe the development of cardiac outflow tract and blood vessels. Heart rate and ventricular shortening fraction were used to assess cardiac function. Gene probes were constructed, and embryo in situ hybridization and real-time PCR were used to measure the expression of nkx2.5, tbx1, and flk-1 in the embryo. RESULTS: Compared with the ethanol group, the ethanol+dhfr overexpression group had a significant reduction in the percentage of abnormal embryonic development and a significant increase in the percentage of embryonic survival (P<0.05), with significant improvements in the abnormalities of the atrium, ventricle, outflow tract, and blood vessels and cardiac function. Compared with the control group, the ethanol group had significant reductions in the expression of nkx2.5, tbx1, and flk-1 (P<0.05), and compared with the ethanol group, the ethanol+dhfr overexpression group had significant increases in the expression of nkx2.5, tbx1, and flk-1 (P<0.05), which were still lower than their expression in the control group. CONCLUSIONS: The overexpression of the dhfr gene can partially improve the abnormal development of embryonic heart and blood vessels induced by ethanol, possibly by upregulating the decreased expression of nkx2.5, tbx1, and flk-1 caused by ethanol.


Assuntos
Peixe-Zebra , Animais , Etanol , Regulação da Expressão Gênica no Desenvolvimento , Coração , Ventrículos do Coração , Proteínas de Peixe-Zebra
11.
J Am Chem Soc ; 141(47): 18825-18835, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31703165

RESUMO

The catalytic asymmetric functionalization of readily available 1,3-dienes is highly important, but current examples are mostly limited to the construction of tertiary chiral centers. The asymmetric generation of acyclic products containing all-carbon quaternary stereocenters from substituted 1,3-dienes represents a more challenging, but highly desirable, synthetic process for which there are very few examples. Herein, we report the highly selective copper-catalyzed generation of chiral all-carbon acyclic quaternary stereocenters via functionalization of 1,3-dienes with CO2. A variety of readily available 1,1-disubstituted 1,3-dienes, as well as a 1,3,5-triene, undergo reductive hydroxymethylation with high chemo-, regio-, E/Z-, and enantioselectivities. The reported method features good functional group tolerance, is readily scaled up to at least 5 mmol of starting diene, and generates chiral products that are useful building blocks for further derivatization. Systemic mechanistic investigations using density functional theory calculations were performed and provided the first theoretical investigation for an asymmetric transformation involving CO2. These computational results indicate that the 1,2-hydrocupration of 1,3-diene proceeds with high π-facial selectivity to generate an (S)-allylcopper intermediate, which further induces the chirality of the quaternary carbon center in the final product. The 1,4-addition of an internal allylcopper complex, which differs from previous reports involving terminal allylmetallic intermediates, to CO2 kinetically determines the E/Z- and regioselectivity. The rapid reduction of a copper carboxylate intermediate to the corresponding silyl-ether in the presence of Me(MeO)2SiH provides the exergonic impetus and leads to chemoselective hydroxymethylation rather than carboxylation. These results provide new insights for guiding further development of asymmetric C-C bond formations with CO2.

12.
Pediatr Res ; 85(3): 378-383, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30262811

RESUMO

BACKGROUND: Tbx2 plays a critical role in determining fates of cardiomyocytes. Little is known about the contribution of TBX2 3' untranslated region (UTR) variants to the risk of congenital heart defect (CHD). Thus, we aimed to determine the association of single-nucleotide polymorphisms (SNPs) in TBX2 3' UTR with CHD susceptibility. METHODS: We recruited 1285 controls and 1241 CHD children from China. SNPs identification and genotyping were detected using Sanger Sequencing and SNaPshot. Stratified analysis was conducted to explore the association between rs59382073 polymorphism and CHD subtypes. Functional analyses were performed by luciferase assays in HEK-293T and H9c2 cells. RESULTS: Among five TBX2 3'UTR variants identified, rs59382073 minor allele T carriers had a 1.89-fold increased CHD risk compared to GG genotype (95% CI = 1.48-2.46, P = 4.48 × 10-7). The most probable subtypes were right ventricular outflow tract obstruction, conotruncal, and septal defect. G to T variation decreased luciferase activity in cells. This discrepancy was exaggerated by miR-3940 and miR-708, while their corresponding inhibitors eliminated it. CONCLUSION: T allele of rs59382073 in TBX2 3'UTR contributed to greater CHD risk in the Han Chinese population. G to T variation created binding sites for miR-3940 and miR-708 to inhibit gene expression.


Assuntos
Predisposição Genética para Doença , Cardiopatias Congênitas/genética , Polimorfismo de Nucleotídeo Único , Proteínas com Domínio T/genética , Regiões 3' não Traduzidas , Alelos , Animais , Povo Asiático , Sítios de Ligação , Estudos de Casos e Controles , Criança , China/etnologia , Ecocardiografia , Feminino , Regulação da Expressão Gênica , Genótipo , Células HEK293 , Cardiopatias Congênitas/etnologia , Ventrículos do Coração , Humanos , Masculino , MicroRNAs/genética , Fenótipo , Plasmídeos/metabolismo , Ratos , Medição de Risco
13.
J Am Chem Soc ; 140(50): 17338-17342, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30518213

RESUMO

Cross-electrophile couplings between two electrophiles are powerful and economic methods to generate C-C bonds in the presence of stoichiometric external reductants. Herein, we report a novel strategy to realize the first external-reductant-free cross-electrophile coupling via visible-light photoredox catalysis. A variety of tetraalkyl ammonium salts, bearing primary, secondary, and tertiary C-N bonds, undergo selective couplings with aldehydes/ketone and CO2. Notably, the in situ generated byproduct, trimethylamine, is efficiently utilized as the electron donor. Moreover, this protocol exhibits mild reaction conditions, low catalyst loading, broad substrate scope, good functional group tolerance, and facile scalability. Mechanistic studies indicate that benzyl radicals and anions might be generated as the key intermediates via photocatalysis, providing a new direction for cross-electrophile couplings.

14.
Nanotechnology ; 29(4): 045101, 2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-29182157

RESUMO

Great effort has recently been devoted to the preparation of nanoscale surfaces on titanium-based implants to achieve clinically fast osteoinduction and osseointegration, which relies on the unique characteristics of the nanostructure. In this work, we used induction heating treatment (IHT) as a rapid oxidation method to fabricate a porous nanoscale oxide layer on the Ti6Al4V surface for better medical application. Well-distributed vertical nanopillars were yielded by IHT for 20-35 s on the alloy surface. The composition of the oxides contained rutile/anatase TiO2 and a small amount of Al2O3 between the TiO2 grain boundaries (GBs). This technology resulted in a reduction and subsequent increase of surface roughness of 26-32 nm when upregulating the heating time, followed by the successive enhancement of the thickness, wettability and adhesion strength of the oxidation layer to the matrix. The surface hardness also distinctly rose to 554 HV in the IHT-35 s group compared with the 350 HV of bare Ti6Al4V. The massive small-angle GBs in the bare alloy promoted the formation of nanosized oxide crystallites. The grain refinement and deformation texture reduction further improved the mechanical properties of the matrix after IHT. Moreover, in vitro experiments on a mesenchymal stem cell (BMSC) culture derived from human bone marrow for 1-7 days indicated that the nanoscale layers did not cause cytotoxicity, and facilitated cell differentiation in osteoblasts by enhancing the gene and osteogenesis-related protein expressions after 1-3 weeks of culturing. The increase of the IHT time slightly advanced the BMSC proliferation and differentiation, especially during long-term culture. Our findings provide strong evidence that IHT oxidation technology is a novel nanosurface modification technology, which is potentially promising for further clinical development.


Assuntos
Diferenciação Celular , Calefação , Células-Tronco Mesenquimais/citologia , Nanopartículas/química , Osteogênese , Titânio/química , Fosfatase Alcalina/metabolismo , Ligas , Adesão Celular , Proliferação de Células , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Nanopartículas/ultraestrutura , Oxirredução , Óxidos/química , Espectroscopia Fotoeletrônica , Termodinâmica , Molhabilidade , Difração de Raios X
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(7): 594-597, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30022765

RESUMO

Kawasaki disease has become the leading cause of acquired heart disease in children in North America and Japan. The incidence rate of Kawasaki disease varies significantly across regions and races. The first-degree relatives of patients with Kawasaki disease have a significantly higher risk of this disease than the general population. This article reviews the onset of familial Kawasaki disease and possible pathogenesis.


Assuntos
Síndrome de Linfonodos Mucocutâneos/patologia , Animais , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/genética , Síndrome de Linfonodos Mucocutâneos/imunologia
16.
J Am Chem Soc ; 139(47): 17011-17014, 2017 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-29125759

RESUMO

Herein, we report a highly regio- and enantioselective copper-catalyzed reductive hydroxymethylation of styrenes and 1,3-dienes with 1 atm of CO2. Diverse important chiral homobenzylic alcohols were readily prepared from styrenes. Moreover, a variety of 1,3-dienes also were converted to chiral homoallylic alcohols with high yields and excellent regio-, enantio-, and Z/E-selectivities. The utility of this transformation was demonstrated by a broad range of styrenes and 1,3-dienes, facile product modification, and synthesis of bioactive compounds (R)-(-)-curcumene and (S)-(+)-ibuprofen. Mechanistic studies demonstrated the carboxylation of phenylethylcopper complexes with CO2 as one key step.

17.
Sheng Li Xue Bao ; 69(3): 267-275, 2017 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-28638918

RESUMO

Cardiac troponin T (cTnT) serves as a structural protein of myocardial fiber, and participates in heart excitation-contraction coupling process. Here, we generated tnnt2a (cTnT-coding gene) deletion mutant zebrafish via CRISPR/Cas9 technique, and performed phenotypic analysis of the identified tnnt2a mutants. We observed that there was no significant difference between heterozygous mutant and wild type zebrafish, and the homozygous mutants displayed significant malformations in heart, including cardiac arrest, atrium and ventricle enlargement, pericardium effusion, and the individuals usually died before 7 day post fertilization (dpf). We further analyzed the expression alternations of heart sarcomere genes (tnnt2a, actc1a, tpm4a, myl7, vmhc) at transcriptional level in tnnt2a-/-(Δ2) zebrafish by performing real time RT-PCR, and found that the RNA expression level of tnnt2a in tnnt2a-/- zebrafish decreased constantly at each time point of developmental stages, and actc1a, tpm4a, myl7 and vmhc all showed higher expressions at early developmental stages and lower expressions at late developmental stages, in comparison with those of wild type zebrafish. Lastly, electron microscopy on cardiac tissues suggested that there were significant changes of the thick or thin filament structures in tnnt2a-/-(Δ2) zebrafish, which was further confirmed by F-actin and Tpm4 immunofluorescence staining. The tnnt2a-/- zebrafish generated by CRISPR/Cas9 bears the most common symptoms of patients with dilated cardiomyopathy, and therefore can be used as a tool to study TNNT2-deficiency related cardiomyopathy.


Assuntos
Sistemas CRISPR-Cas , Modelos Animais de Doenças , Troponina T/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra , Animais , Técnicas de Inativação de Genes , Miocárdio/patologia , Deleção de Sequência
18.
Angew Chem Int Ed Engl ; 56(49): 15683-15687, 2017 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-29048716

RESUMO

Reported herein is a novel visible-light photoredox system with Pd(PPh3 )4 as the sole catalyst for the realization of the first direct cross-coupling of C(sp3 )-H bonds in N-aryl tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra- and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp3 )-C(sp3 ) and C(sp2 )-C(sp3 ) bonds in moderate to excellent yields. These redox-neutral reactions feature broad substrate scope (>60 examples), good functional-group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible-light photocatalyst and radicals are involved in the process.

19.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(12): 1297-1300, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29237533

RESUMO

Congenital heart disease (CHD) is the most common birth defect at present and has a complex etiology which involves the combined effect of genetic and environmental factors. Pregestational diabetes mellitus is significantly associated with the development of CHD, but the detailed mechanism remains unknown. This article reviews the research advances in the molecular mechanism of CHD caused by pregestational diabetes mellitus.


Assuntos
Cardiopatias Congênitas/etiologia , Gravidez em Diabéticas , Animais , Apoptose , Movimento Celular , Feminino , Humanos , Crista Neural/fisiologia , Gravidez , Espécies Reativas de Oxigênio/metabolismo
20.
Med Sci Monit ; 22: 2852-8, 2016 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-27521289

RESUMO

BACKGROUND In this study we investigated the effect of urinary kallidinogenase (UK) on transforming growth factor beta 1 (TGF-ß1) expression in brain tissue. We also explored the neuroprotective mechanism of UK against ischemic injury by measuring serum high-sensitivity C-reactive protein (hs-CRP) level changes after rat cerebral ischemic injury. MATERIAL AND METHODS The rat middle cerebral artery ischemia/reperfusion model was established using the suture method. Sprague-Dawley rats were randomly divided into 3 groups: treatment, Gegen control, and blank control. Each group was subsequently divided into 5 subgroups according to time (6, 12, 24, 48, and 72 h). Rats in the treatment group were administered UK as treatment. TGF-ß1 expression was observed at each time point using SABC and immunohistochemical staining methods to estimate cerebral infarct volume percentage. Serum hs-CRP levels were also measured. RESULTS TGF-ß1 protein expression in ischemic brain tissues of the treatment group significantly increased at each time point (P<0.01) compared with both control groups. Treatment group serum hs-CRP levels significantly decreased at each time point (P<0.05) compared with both control groups. CONCLUSIONS UK exerts a neuroprotective effect by upregulating TGF-ß1 expression and inhibiting excessive inflammatory responses.


Assuntos
Isquemia Encefálica/metabolismo , Proteína C-Reativa/biossíntese , Calicreínas/metabolismo , Fator de Crescimento Transformador beta1/biossíntese , Animais , Isquemia Encefálica/enzimologia , Isquemia Encefálica/urina , Modelos Animais de Doenças , Calicreínas/urina , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/metabolismo
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