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1.
Arterioscler Thromb Vasc Biol ; 44(1): 177-191, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38150518

RESUMO

BACKGROUND: The heart relies heavily on external fatty acid (FA) for energy production. VEGFB (vascular endothelial growth factor B) has been shown to promote endothelial FA uptake by upregulating FA transporters. However, its impact on LPL (lipoprotein lipase)-mediated lipolysis of lipoproteins, a major source of FA for cardiac use, is unknown. METHODS: VEGFB transgenic (Tg) rats were generated by using the α-myosin heavy chain promoter to drive cardiomyocyte-specific overexpression. To measure coronary LPL activity, Langendorff hearts were perfused with heparin. In vivo positron emission tomography imaging with [18F]-triglyceride-fluoro-6-thia-heptadecanoic acid and [11C]-palmitate was used to determine cardiac FA uptake. Mitochondrial FA oxidation was evaluated by high-resolution respirometry. Streptozotocin was used to induce diabetes, and cardiac function was monitored using echocardiography. RESULTS: In Tg hearts, the vectorial transfer of LPL to the vascular lumen is obstructed, resulting in LPL buildup within cardiomyocytes, an effect likely due to coronary vascular development with its associated augmentation of insulin action. With insulin insufficiency following fasting, VEGFB acted unimpeded to facilitate LPL movement and increase its activity at the coronary lumen. In vivo PET imaging following fasting confirmed that VEGFB induced a greater FA uptake to the heart from circulating lipoproteins as compared with plasma-free FAs. As this was associated with augmented mitochondrial oxidation, lipid accumulation in the heart was prevented. We further examined whether this property of VEGFB on cardiac metabolism could be useful following diabetes and its associated cardiac dysfunction, with attendant loss of metabolic flexibility. In Tg hearts, diabetes inhibited myocyte VEGFB gene expression and protein secretion together with its downstream receptor signaling, effects that could explain its lack of cardioprotection. CONCLUSIONS: Our study highlights the novel role of VEGFB in LPL-derived FA supply and utilization. In diabetes, loss of VEGFB action may contribute toward metabolic inflexibility, lipotoxicity, and development of diabetic cardiomyopathy.


Assuntos
Cardiomiopatias Diabéticas , Insulina , Ratos , Animais , Insulina/farmacologia , Fator B de Crescimento do Endotélio Vascular/genética , Fator B de Crescimento do Endotélio Vascular/metabolismo , Ratos Wistar , Miócitos Cardíacos/metabolismo , Ácidos Graxos/metabolismo , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Triglicerídeos/metabolismo , Lipase Lipoproteica/metabolismo , Miocárdio/metabolismo
2.
J Am Chem Soc ; 146(18): 12712-12722, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38655573

RESUMO

Persistent chiral organic open-shell systems have captured growing interest due to their potential applications in organic spintronic and optoelectronic devices. Nevertheless, the integration of configurationally stable chirality into an organic open-shell system continues to pose challenges in molecular design. The π-extended skeleton incorporated in spiro-conjugated carbocycles can provide robust chiroptical properties and a significant stabilization of the excited and ionic radical states. However, this approach has been relatively less explored in the design of persistent organic open-shell systems. We report here the (S,S)-, (R,R)-, and meso-isomers of doubly spiro-conjugated carbocycles featuring flat and rigid carbon-bridged para-phenylenevinylene (CPV) of different conjugation lengths connected by two spiro-carbon centers, which we denote D-spiro-CPV for its quasi-dimeric structure. Our synthetic method based on a double lithiation cyclization approach enables facile production of D-spiro-CPV. D-spiro-CPVs exhibit circularly polarized luminescence (CPL) with high fluorescence quantum yields (ΦFL) resulting in a high CPL brightness of 21 M-1 cm-1 and also exhibit high thermal and photostability. The monoradical cation of D-spiro-CPV absorbing near-infrared light is notably persistent, exhibiting a half-life of 570 h under ambient conditions due to doubly spiro-conjugative stabilization. Theoretical and electrochemical studies indicate the radical cation of D-spiro-CPVs presents a non-Aufbau electron filling, exhibiting inversion of the energy level of the singly occupied molecular orbital (SOMO) and the highest (doubly) occupied molecular orbitals with the SOMO level even below the HOMO-1 level (double SHI effect). Our discoveries provide valuable insights into non-Aufbau molecules and the development of configurationally stable, optically active persistent radicals.

3.
Small ; : e2401815, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573922

RESUMO

Currently, research on thermal interface materials (TIMs) is primarily focused on enhancing thermal conductivity. However, strong adhesion and multifunctionality are also important characteristics for TIMs when pursing more stable interface heat conduction. Herein, a novel poly(urethane-urea-imide) (PUUI) elastomer containing abundant dynamic hydrogen bonds network and reversible disulfide linkages is successfully synthesized for application as a TIM matrix. The PUUI can self-adapt to the metal substrate surface at moderate temperatures (80 °C) and demonstrates a high adhesion strength of up to 7.39 MPa on aluminum substrates attributed its noncovalent interactions and strong intrinsic cohesion. Additionally, the PUUI displays efficient self-healing capability, which can restore 94% of its original mechanical properties after self-healing for 6 h at room temperature. Furthermore, PUUI composited with aluminum nitride and liquid metal hybrid fillers demonstrates a high thermal conductivity of 3.87 W m-1 K-1 while maintaining remarkable self-healing capability and adhesion. When used as an adhesive-type TIM, it achieves a low thermal contact resistance of 22.1 mm2 K W-1 at zero pressure, only 16.7% of that of commercial thermal pads. This study is expected to break the current research paradigm of TIMs and offers new insights for the development of advanced, reliable, and sustainable TIMs.

4.
Nutr Cancer ; 76(5): 452-462, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494910

RESUMO

Abnormal activation of the Wnt/ß-catenin signaling pathway is a driving force behind the progression of gastric cancer. Atovaquone, known as an antimalarial drug, has emerged as a potential candidate for anti-cancer therapy. This study investigated atovaquone's effects on gastric cancer and its underlying mechanisms. Using gastric cancer cell lines, we found that atovaquone, at concentrations relevant to clinical use, significantly reduced their viability. Notably, atovaquone exhibited a lower effectiveness in reducing the viability of normal gastric cells compared to gastric cancer cells. We further demonstrated that atovaquone inhibited gastric cancer growth and colony formation. Mechanism studies revealed that atovaquone inhibited mitochondrial respiration and induced oxidative stress. Experiments using ρ0 cells, deficient in mitochondrial respiration, indicated a slightly weaker effect of atovaquone on inducing apoptosis compared to wildtype cells. Atovaquone increased phosphorylated ß-catenin at Ser45 and Ser33/37/Thr41, elevated Axin, and reduced ß-catenin. The inhibitory effects of atovaquone on ß-catenin were reversed upon depletion of CK1α. Furthermore, the combination of atovaquone with paclitaxel suppressed gastric cancer growth and improved overall survival in mice. Given that atovaquone is already approved for clinical use, these findings suggest its potential as a valuable addition to the drug arsenal available for treating gastric cancer.


Assuntos
Neoplasias Gástricas , Via de Sinalização Wnt , Animais , Camundongos , Atovaquona/farmacologia , Atovaquona/uso terapêutico , beta Catenina/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular Tumoral , Caseína Quinases/metabolismo , Proliferação de Células
5.
Mol Biol Evol ; 39(7)2022 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-35687719

RESUMO

Due to extensive pleiotropy, trans-acting elements are often thought to be evolutionarily constrained. While the impact of trans-acting elements on gene expression evolution has been extensively studied, relatively little is understood about the contribution of a single trans regulator to interspecific expression and phenotypic divergence. Here, we disentangle the effects of genomic context and miR-983, an adaptively evolving young microRNA, on expression divergence between Drosophila melanogaster and D. simulans. We show miR-983 effects promote interspecific expression divergence in testis despite its antagonism with the often-predominant context effects. Single-cyst RNA-seq reveals that distinct sets of genes gain and lose miR-983 influence under disruptive or diversifying selection at different stages of spermatogenesis, potentially helping minimize antagonistic pleiotropy. At the round spermatid stage, the effects of miR-983 are weak and distributed, coincident with the transcriptome undergoing drastic expression changes. Knocking out miR-983 causes reduced sperm length with increased within-individual variation in D. melanogaster but not in D. simulans, and the D. melanogaster knockout also exhibits compromised sperm defense ability. Our results provide empirical evidence for the resolution of antagonistic pleiotropy and also have broad implications for the function and evolution of new trans regulators.


Assuntos
Drosophila , MicroRNAs , Animais , Drosophila/genética , Drosophila melanogaster/genética , Masculino , MicroRNAs/genética , Sêmen , Especificidade da Espécie , Espermatogênese/genética
6.
Angew Chem Int Ed Engl ; 62(13): e202218151, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36727590

RESUMO

Lithium metal batteries hold great promise for promoting energy density and operating at low temperatures, yet they still suffer from insufficient Li compatibility and slow kinetic, especially at ultra-low temperatures. Herein, we rationally design and synthesize a new amphiphilic solvent, 1,1,2,2-tetrafluoro-3-methoxypropane, for use in battery electrolytes. The lithiophilic segment is readily to solvate Li+ to induce self-assembly of the electrolyte solution to form a peculiar core-shell-solvation structure. Such unique solvation structure not only largely improves the ionic conductivity to allow fast Li+ transport and lower the desolvation energy to enable facile desolvation, but also leads to the formation of a highly robust and conductive inorganic SEI. The resulting electrolyte demonstrates high Li efficiency and superior cycling stability from room temperature to -40 °C at high current densities. Meanwhile, anode-free high-voltage cell retains 87 % capacity after 100 cycles.

7.
J Am Chem Soc ; 144(47): 21692-21701, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36383691

RESUMO

C-H/C-H coupling via C-H activation provides straightforward synthetic access to the construction of complex π-conjugated organic molecules. The palladium-catalyzed Fujiwara-Moritani (FM) coupling between an arene and an electron-deficient olefin presents an early example but is not applicable to enamines such as N-vinylcarbazoles and N-vinylindoles. We report herein iron-catalyzed C-H/C-H heterocoupling between enamines and thiophenes and its application to copolymerization of bisenamine and bisthiophene using diethyl oxalate as an oxidant and AlMe3 as a base, as a result of our realization that synthetic limitations in oxidative C-H/C-H couplings imposed by the high redox potential of the Pd(II)/Pd(0) catalytic cycle can be circumvented by the use of iron, which has a lower Fe(III)/Fe(I) redox potential. The trisphosphine ligand provides a coordination environment for iron to achieve the reaction's regio-, stereo-, and chemoselectivity. The reaction includes C-H activation of thiophene via σ-bond metathesis and subsequent enamine C-H cleavage triggered by nucleophilic enamine addition to the Fe(III) center, thereby differing from the FM reaction in mechanism and synthetic scope. The copolymers synthesized by the new reaction possess a new type of enamine-incorporated polymer backbone.


Assuntos
Ferro , Tiofenos , Ferro/química , Catálise , Paládio/química , Polimerização
8.
J Am Chem Soc ; 144(46): 21146-21156, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36346318

RESUMO

As a crystal approaches a few nanometers in size, atoms become nonequivalent, bonds vibrate, and quantum effects emerge. To study quantum dots (QDs) with structural control common in molecular science, we need atomic precision synthesis and analysis. We describe here the synthesis of lead bromide perovskite magic-sized nanoclusters via self-organization of a lead malate chelate complex and PbBr3- under ambient conditions. Millisecond and angstrom resolution electron microscopic analysis revealed the structure and the dynamic behavior of individual QDs─structurally uniform cubes made of 64 lead atoms, where eight malate molecules are located on the eight corners of the cubes, and oleylammonium cations lipophilize and stabilize the edges and faces. Lacking translational symmetry, the cube is to be viewed as a molecule rather than a nanocrystal. The QD exhibits quantitative photoluminescence and stable electroluminescence at ≈460 nm with a narrow half-maximum linewidth below 15 nm, reflecting minimum structural defects. This controlled synthesis and precise analysis demonstrate the potential of cinematic chemistry for the characterization of nanomaterials beyond the conventional limit.


Assuntos
Nanopartículas , Nanoestruturas , Pontos Quânticos , Pontos Quânticos/química , Malatos
9.
Angew Chem Int Ed Engl ; 61(27): e202203949, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35404499

RESUMO

Polytriarylamine is a popular hole-transporting materials (HTMs) despite its suboptimal conductivity and significant recombination at the interface in a solar cell setup. Having noted insufficient conjugation among the triarylamine units along the polymer backbone, we inserted a bithiophene unit between two triarylamine units through iron-catalyzed C-H/C-H coupling of a triarylamine/thiophene monomer so that two units conjugate effectively via four quinoidal rings when the molecule functions as HTM. The obtained triarylamine/bithiophene copolymer (TABT) used as HTM showed a high-performance in methylammonium lead iodide perovskite (MAPbI3 ) solar cells. Mesityl substituted TABT forms a uniform film, shows high hole-carrier mobility, and has an ionization potential (IP=5.40 eV) matching that of MAPbI3 . We fabricated a solar cell device with a power conversion efficiency of 21.3 % and an open-circuit voltage of 1.15 V, which exceeds the performance of devices using reference standard such as poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine (PTAA) and Spiro-OMeTAD.

10.
J Am Chem Soc ; 143(18): 6823-6828, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33929185

RESUMO

Carbon bridging in a form of a strained 1,4-dihydropentalene framework is an effective strategy for flattening and stabilizing oligophenylenevinylene systems for the development of optoelectronic materials. However, efficient and flexible methods for making such a strained ring system are lacking. We report herein a mild and versatile synthetic access to the 1,4-dihydropentalene framework enabled by iron-catalyzed single-pot tandem cyclization of a diarylacetylene using FeCl2 and PPh3 as catalyst, magnesium/LiCl as a reductant, and 1,2-dichloropropane as a mild oxidant. The new annulation method features two iron-catalyzed transformations used in tandem, a reductive acetylenic carboferration and an oxidation-induced ring contraction of a ferracycle under mild oxidative conditions. The new method provides access not only to a variety of substituted indeno[2,1-a]indenes but also to their thiophene congeners, 4,9-dihydrobenzo[4,5]pentaleno[1,2-b]thiophene (CPTV) and 4,8-dihydropentaleno[1,2-b:4,5-b']dithiophenes (CTV). With its high highest occupied molecular orbital level and narrow optical gap, CTV serves as a donor unit in a narrow-band-gap non-fullerene acceptor, which shows absorption extending over 1000 nm in the film state, and has found use in a near-infrared photodetector device that exhibited an external quantum efficiency of 72.4% at 940 nm.

11.
Am J Physiol Endocrinol Metab ; 321(6): E753-E765, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34747201

RESUMO

Cardiac muscle uses multiple sources of energy including glucose and fatty acid (FA). The heart cannot synthesize FA and relies on obtaining it from other sources, with lipoprotein lipase (LPL) breakdown of lipoproteins suggested to be a key source of FA for cardiac use. Recent work has indicated that cardiac vascular endothelial growth factor B (VEGFB) overexpression expands the coronary vasculature and facilitates metabolic reprogramming that favors glucose utilization. We wanted to explore whether this influence of VEGFB on cardiac metabolism involves regulation of LPL activity with consequent effects on lipotoxicity and insulin signaling. The transcriptomes of rats with and without cardiomyocyte-specific overexpression of human VEGFB were compared by using RNA sequencing. Isolated perfused hearts or cardiomyocytes incubated with heparin were used to enable measurement of LPL activity. Untargeted metabolomic analysis was performed for quantification of cardiac lipid metabolites. Cardiac insulin sensitivity was evaluated using fast-acting insulin. Isolated heart and cardiomyocytes were used to determine transgene-encoded VEGFB isoform secretion patterns and mitochondrial oxidative capacity using high-resolution respirometry and extracellular flux analysis. In vitro, transgenic cardiomyocytes incubated overnight and thus exposed to abundantly secreted VEGFB isoforms, in the absence of any in vivo confounding regulators of cardiac metabolism, demonstrated higher basal oxygen consumption. In the whole heart, VEGFB overexpression induced an angiogenic response that was accompanied by limited cardiac LPL activity through multiple mechanisms. This was associated with a lowered accumulation of lipid intermediates, diacylglycerols and lysophosphatidylcholine, that are known to influence insulin action. In response to exogenous insulin, transgenic hearts demonstrated increased insulin sensitivity. In conclusion, the interrogation of VEGFB function on cardiac metabolism uncovered an intriguing and previously unappreciated effect to lower LPL activity and prevent lipid metabolite accumulation to improve insulin action. VEGFB could be a potential cardioprotective therapy to treat metabolic disorders, for example, diabetes.NEW & NOTEWORTHY In hearts overexpressing vascular endothelial growth factor B (VEGFB), besides its known angiogenic response, multiple regulatory mechanisms lowered coronary LPL. This was accompanied by limited cardiac lipid metabolite accumulation with an augmentation of cardiac insulin action. Our data for the first time links VEGFB to coronary LPL in regulation of cardiac metabolism. VEGFB may be cardioprotective in metabolic disorders like diabetes.


Assuntos
Resistência à Insulina/genética , Lipase Lipoproteica/metabolismo , Miocárdio/metabolismo , Fator B de Crescimento do Endotélio Vascular/genética , Animais , Células Cultivadas , Ativação Enzimática/genética , Feminino , Coração/fisiologia , Insulina/metabolismo , Masculino , Especificidade de Órgãos/genética , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Regulação para Cima/genética , Fator B de Crescimento do Endotélio Vascular/metabolismo
12.
Sensors (Basel) ; 21(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199807

RESUMO

As one of the main errors that affects Global Navigation Satellite System (GNSS) positioning accuracy, ionospheric delay also affects the improvement of smartphone positioning accuracy. The current ionospheric error correction model used in smartphones has a certain time delay and low accuracy, which is difficult to meet the needs of real-time positioning of smartphones. This article proposes a method to use the real-time regional ionospheric model retrieved from the regional Continuously Operating Reference Stations (CORS) observation data to correct the GNSS positioning error of the smartphone. To verify the accuracy of the model, using the posterior grid as the standard, the electron content error of the regional ionospheric model is less than 5 Total Electron Content Unit (TECU), which is about 50% higher than the Klobuchar model, and to further evaluate the impact of the regional ionosphere model on the real-time positioning accuracy of smartphones, carrier-smoothing pseudorange and single-frequency Precise Point Positioning (PPP) tests were carried out. The results show that the real-time regional ionospheric model can significantly improve the positioning accuracy of smartphones, especially in the elevation direction. Compared with the Klobuchar model, the improvement effect is more than 34%, and the real-time regional ionospheric model also shortens the convergence time of the elevation direction to 1 min. (The convergence condition is that the range of continuous 20 s is less than 0.5 m).

13.
J Am Chem Soc ; 142(4): 2059-2067, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31922417

RESUMO

Spiro-conjugated systems are attracting considerable interest for their chiroptical properties and because of their compact structure the small reorganization energy upon electronic excitation or ionization. We report here a modular and convergent synthesis of axially chiral spiro-conjugated carbon-bridged p-phenylenevinylenes (spiro-CPVs) in a racemic and optically active form where two carbon-bridged p-phenylenevinylene molecules are connected by a spiro carbon atom. Our synthetic design focuses on the C2 symmetry of the spiro-CPV molecules, relying on coupling of two 3-lithio-2-arylindene molecules on a carbon monooxide molecule that serves as the spiro carbon center in the target molecule. We prepared derivatives including those possessing phenol groups that facilitate optical resolution and also serve as a platform for the synthesis of a variety of optically active derivatives, which exhibit circularly polarized photoluminescence with high fluorescence quantum yields, large dissymmetry factors, and high photostability. For example, a bis(phenylethynyl) derivative exhibited a fluorescence quantum yield of 0.99 and a dissymmetry factor in luminescence of |glum| = 2.7 × 10-4, values highest among and comparable to those of reported CPL compounds, respectively. A tetrakis-diarylamine derivative shows hole mobility (µh = 3.84 × 10-5 cm2 V-1 s-1; space charge-limited current measurement of a spin-coated film) comparable to that of a popularly used hole-transporting material, spiro-OMeTAD (µh = 2.6 × 10-5 cm2 V-1 s-1), as well as high thermal and phase stability (T5d = 382 °C, Tg = 171 °C).

14.
J Am Chem Soc ; 142(10): 4883-4891, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32068410

RESUMO

Among base metals used for C-H activation reactions, chromium(III) is rather unexplored despite its natural abundance and low toxicity. We report herein chromium(III)-catalyzed C(sp2)-H functionalization of an ortho-position of aromatic and α,ß-unsaturated secondary amides using readily available AlMe3 as a base and using bromoalkynes, allyl bromide, and 1,4-dihydro-1,4-epoxynaphthalene as electrophiles. This redox-neutral reaction taking place at 70-90 °C, requires as low as 1-2 mol % of CrCl3 or Cr(acac)3 as a catalyst without any added ligand, and tolerates functional groups such as aryl iodide, boronate, and thiophene groups. Stoichiometric and kinetics studies as well as kinetic isotope effects suggest that the catalytic cycle consists of a series of thermally stable but reactive intermediates bearing two molecules of the amide substrate on one chromium atom and also that one of these chromate(III) complexes takes part in the alkynylation, allylation, and naphthalenation reactions. The proposed mechanism accounts for the effective suppression of methyl group delivery from AlMe3 for ortho-C-H methylation.

15.
J Am Chem Soc ; 142(44): 18990-18996, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33089998

RESUMO

Linearly conjugated systems have long served as an archetype of conjugated materials, but suffer from two intrinsic structural problems: potential instability due to intermolecular interactions and the flexibility of the C-C bonds connecting C═C bonds. Efforts to solve these problems have included the insertion of aromatic units as a part of the conjugation and the introduction of carbon bridges to stop the bond rotation. We report here B/N-doped p-arylenevinylene chromophores synthesized through the incorporation of a cyclopenta[c][1,2]azaborole framework as a part of the conjugated system. The ring strain intrinsic to this new skeleton both flattens and rigidifies the conjugation, and the B--N+ dative bond is much easier to form than a C-C bond, which simplifies the synthetic design. The B-N dative bond also reduces the HOMO-LUMO gap, thereby causing a significant redshift of the absorption and emission compared with their all-carbon congeners while retaining high photostability and high fluorescence quantum yield in both solution and film states. A doubly B/N-doped compound showed emission peaks at 540 nm with a small Stokes shift of 20 nm and a fluorescence quantum yield of 98%. The molecules serve as excellent lipophilic fluorescent dyes for live-cell imaging, showing a higher photostability than that of commercially available BODIPY-based dyes.

16.
Adv Exp Med Biol ; 1221: 721-745, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32274734

RESUMO

Traditionally, the management of diabetes has focused mainly on controlling high blood glucose levels. Unfortunately, despite valiant efforts to normalize this blood glucose, poor medication management predisposes these patients to heart failure. Following diabetes, how the heart utilizes different sources of fuel for energy is key to the development of heart failure. The diabetic heart switches from using both glucose and fats, to predominately using fats as an energy resource for maintaining its activities. This transformation to using fats as an exclusive source of energy is helpful in the initial stages of the disease and is tightly controlled. However, over the progression of diabetes, there is a loss of this controlled supply and use of fats, which ultimately has terrible consequences since the uncontrolled use of fats produces toxic by-products which weaken heart function and cause heart disease. Heparanase is a key player that directs how much fats are provided to the heart and does so in association with several partners like LPL and VEGFs. Together, they regulate the amount of fats supplied, and their subsequent breakdown to provide energy. Following diabetes, there is a disruption in this network resulting in fat oversupply and cell death. Understanding how the heparanase-LPL-VEGFs "ensemble" cooperates, and its dysfunction in the diabetic heart would be useful in restoring metabolic equilibrium and limiting diabetes-related cardiac damage.


Assuntos
Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Células Endoteliais/enzimologia , Glucuronidase/metabolismo , Cardiopatias/metabolismo , Cardiopatias/patologia , Miócitos Cardíacos/enzimologia , Diabetes Mellitus/enzimologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Cardiopatias/enzimologia , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia
17.
Sensors (Basel) ; 20(3)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32012752

RESUMO

Real-time dynamic displacement and spectral response on the midspan of Jiangyin Bridge were calculated using Global Navigation Satellite System (GNSS) and a speedometer for the purpose of understanding the dynamic behavior and the temporal evolution of the bridge structure. Considering that the GNSS measurement noise is large and the velocity/acceleration sensors cannot measure the low-frequency displacement, the Variational Mode Decomposition (VMD) algorithm was used to extract the low-frequency displacement of GNSS. Then, the low-frequency displacement extracted from the GNSS time series and the high-frequency vibration calculated by speedometer were combined in this paper in order to obtain the high precision three-dimensional dynamic displacement of the bridge in real time. Simulation experiment and measured data show that the VMD algorithm could effectively resist the modal aliasing caused by noise and discontinuous signals compared with the commonly used Empirical Mode Decomposition (EMD) algorithm, which is guaranteed to get high-precision fusion data. Finally, the fused displacement results can identify high-frequency vibrations and low-frequency displacements of a mm level, which can be used to calculate the spectral characteristics of the bridge and provide reference to evaluate the dynamic and static loads, and the health status of the bridge in the full frequency domain and the full time domain.

18.
Chem Rev ; 117(13): 9086-9139, 2017 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-28378590

RESUMO

Catalytic C-H bond activation, which was an elusive subject of chemical research until the 1990s, has now become a standard synthetic method for the formation of new C-C and C-heteroatom bonds. The synthetic potential of C-H activation was first described for ruthenium catalysis and is now widely exploited by the use of various precious metals. Driven by the increasing interest in chemical utilization of ubiquitous metals that are abundant and nontoxic, iron catalysis has become a rapidly growing area of research, and iron-catalyzed C-H activation has been most actively explored in recent years. In this review, we summarize the development of stoichiometric C-H activation, which has a long history, and catalytic C-H functionalization, which emerged about 10 years ago. We focus in this review on reactions that take place via reactive organoiron intermediates, and we excluded those that use iron as a Lewis acid or radical initiator. The contents of this review are categorized by the type of C-H bond cleaved and the type of bond formed thereafter, and it covers the reactions of simple substrates and substrates possessing a directing group that anchors the catalyst to the substrate, providing an overview of iron-mediated and iron-catalyzed C-H activation reported in the literature by October 2016.

19.
J Cell Mol Med ; 22(4): 2518-2522, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29441687

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys variant was an independent risk factor for acute coronary syndrome (ACS). However, there are lacking researches about the relationship between the variant and prognosis of ACS. In the prospective study, 377 ACS patients were grouped into the wild-type (*1/*1) and the mutation (*2/*2 + *1/*2) groups according to genotype detection. Compared with the wild-type group, incidences of major adverse cardiac events (MACE) and cardiac death were both higher in the mutation group (9.2% vs 21.0%, P = .002; 5.2% vs 12.2%, P = .026); the MACE-free and the cardiac-death-free cumulative survival rates were obviously lower in the mutation group. Moreover, the mutant genotypes were associated with significantly increased risk of MACE and cardiac death (HR 2.443, 95%CI: 1.390-4.296, P = .002; HR 2.727, 95%CI: 1.303-5.708, P = .008). These results suggested that ALDH2 Glu504Lys variant could predict a worse prognosis of ACS patients.


Assuntos
Síndrome Coronariana Aguda/genética , Aldeído-Desidrogenase Mitocondrial/genética , Predisposição Genética para Doença , Prognóstico , Síndrome Coronariana Aguda/patologia , Idoso , Povo Asiático , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
20.
J Am Chem Soc ; 140(15): 5018-5022, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29624381

RESUMO

Hole-transporting material (HTM) is an indispensable constituent in organic electronic devices, generally comprising a donor/dopant combination. We report that a disodium salt of substituted benzo[1,2- b:4,5- b']dipyrrole bearing two racemic alkanediylsulfonate anion side chains (BDPSOs) serves as a neutral, nonhygroscopic, dopant-free HTM for lead perovskite (MAPbI3) solar cells. These organic/inorganic hybrid molecules are useful for tunable orbital level and controllable solubility. A fluorinated BDPSO has an energy level matched with MAPbI3, affording an inverted-structure solar cell that performs with 17.2% efficiency with minimal hysteresis. The solar cell devices fabricated using BDPSOs showed remarkable storage and operational stability.

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