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1.
Nat Commun ; 15(1): 2433, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499545

RESUMO

Nonlinear optical processing of ambient natural light is highly desired for computational imaging and sensing. Strong optical nonlinear response under weak broadband incoherent light is essential for this purpose. By merging 2D transparent phototransistors (TPTs) with liquid crystal (LC) modulators, we create an optoelectronic neuron array that allows self-amplitude modulation of spatially incoherent light, achieving a large nonlinear contrast over a broad spectrum at orders-of-magnitude lower intensity than achievable in most optical nonlinear materials. We fabricated a 10,000-pixel array of optoelectronic neurons, and experimentally demonstrated an intelligent imaging system that instantly attenuates intense glares while retaining the weaker-intensity objects captured by a cellphone camera. This intelligent glare-reduction is important for various imaging applications, including autonomous driving, machine vision, and security cameras. The rapid nonlinear processing of incoherent broadband light might also find applications in optical computing, where nonlinear activation functions for ambient light conditions are highly sought.

2.
J Am Chem Soc ; 146(14): 9623-9630, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38533830

RESUMO

The fundamental understanding of sluggish hydrogen evolution reaction (HER) kinetics on a platinum (Pt) surface in alkaline media is a topic of considerable debate. Herein, we combine cyclic voltammetry (CV) and electrical transport spectroscopy (ETS) approaches to probe the Pt surface at different pH values and develop molecular-level insights into the pH-dependent HER kinetics in alkaline media. The change in HER Tafel slope from ∼110 mV/decade in pH 7-10 to ∼53 mV/decade in pH 11-13 suggests considerably enhanced kinetics at higher pH. The ETS studies reveal a similar pH-dependent switch in the ETS conductance signal at around pH 10, suggesting a notable change of surface adsorbates. Fixed-potential calculations and chemical bonding analysis suggest that this switch is attributed to a change in interfacial water orientation, shifting from primarily an O-down configuration below pH 10 to a H-down configuration above pH 10. This reorientation weakens the O-H bond in the interfacial water molecules and modifies the reaction pathway, leading to considerably accelerated HER kinetics at higher pH. Our integrated studies provide an unprecedented molecular-level understanding of the nontrivial pH-dependent HER kinetics in alkaline media.

3.
Adv Mater ; 35(40): e2302863, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37392013

RESUMO

Organic memory has attracted tremendous attention for next-generation electronic elements for the molecules' striking ease of structural design. However, due to them being hardly controllable and their low ion transport, it is always essential and challenge to effectively control their random migration, pathway, and duration. There are very few effective strategies, and specific platforms with a view to molecules with specific coordination-groups-regulating ions have been rarely reported. In this work, as a generalized rational design strategy, the well-known tetracyanoquinodimethane (TCNQ) is introduced with multiple coordination groups and small plane structure into a stable polymers framework to modulate Ag migration and then achieve high-performance devices with ideal productivity, low operation voltage and power, stable switching cycles, and state retention. Raman mapping demonstrates that the migrated Ag can specially coordinate with the embedded TCNQ molecules. Notably, the TCNQ molecule distribution can be modulated inside the polymer framework and regulate the memristive behaviors through controlling the formed Ag conductive filaments (CFs) as demonstrated by Raman mapping, in situ conductive atomic force microscopy (C-AFM), X-ray diffraction (XRD) and depth-profiling X-ray photoelectron spectroscopy (XPS). Thus the controllable molecule-mediated Ag movements show its potential in rationally designing high-performance devices and versatile functions and is enlightening in constructing memristors with molecule-mediated ion movements.

4.
ACS Appl Mater Interfaces ; 15(10): 13380-13392, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36853974

RESUMO

As an attractive prototype for neuromorphic computing, the difficultly attained three-terminal platforms have specific advantages in implementing the brain-inspired functions. Also, in these devices, the most utilized mechanisms are confined to the electrical gate-controlled ionic migrations, which are sensitive to the device defects and stoichiometric ratio. The resultant memristive responses have fluctuant characteristics, which have adverse influences on the neural emulations. Herein, we designed a specific transistor platform with light-regulated ambipolar memory characteristics. Also, based on its gentle processes of charge trapping, we obtain the impressive memristive performances featured by smooth responses and long-term endurable characteristics. The optoelectronic samples were also fabricated on flexible substrates successfully. Interestingly, based on the optoelectronic signals of the flexible devices, we endow the desirable optical processes with the brain-inspired emulations. We can flexibly emulate the light-inspired learning-memory functions in a synapse and further devise the advanced synapse array. More importantly, through this versatile platform, we investigate the mutual regulation of excitation and inhibition and implement their sensitive-mode transformations and the homeostasis property, which is conducive to ensuring the stability of overall neural activity. Furthermore, our flexible optoelectronic platform achieves high classification accuracy when implemented in artificial neural network simulations. This work demonstrates the advantages of the optoelectronic platform in implementing the significant brain-inspired functions and provides an insight into the future integration of visible sensing in flexible optoelectronic transistor platforms.

5.
Nat Nanotechnol ; 18(4): 357-364, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36702955

RESUMO

The success of the lead halide perovskites in diverse optoelectronics has motivated considerable interest in their fundamental photocarrier dynamics. Here we report the discovery of photocarrier-induced persistent structural polarization and local ferroelectricity in lead halide perovskites. Photoconductance studies of thin-film single-crystal CsPbBr3 at 10 K reveal long-lasting persistent photoconductance with an ultralong photocarrier lifetime beyond 106 s. X-ray diffraction studies reveal that photocarrier-induced structural polarization is present up to a critical freezing temperature. Photocapacitance studies at cryogenic temperatures further demonstrate a systematic local phase transition from linear dielectric to paraelectric and relaxor ferroelectric under increasing illumination. Our theoretical investigations highlight the critical role of photocarrier-phonon coupling and large polaron formation in driving the local relaxor ferroelectric phase transition. Our findings show that this photocarrier-induced persistent structural polarization enables the formation of ferroelectric nanodomains at low temperature, which suppress carrier recombination and offer the possibility of exploring intriguing carrier-phonon interplay and the rich polaron photophysics.

6.
Heart ; 109(10): 756-762, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-36539268

RESUMO

OBJECTIVE: To examine whether adherence to ideal cardiovascular health (CVH) can mitigate the genetic risk of coronary artery disease (CAD) in non-European populations. METHODS: Fine and Grey's models were used to calculate HRs and their corresponding 95% CIs, as well as the lifetime risk of CVH metrics across Polygenic Risk Score (PRS) categories. RESULTS: We included 39 755 individuals aged 30-75 years in Chinese prospective cohorts. 1275 CAD cases were recorded over a mean follow-up of 12.9 years. Compared with unfavourable CVH profile (zero to three ideal CVH metrics), favourable CVH profile (six to seven ideal CVH metrics) demonstrated similar relative effects across PRS categories, with the HRs of 0.40 (95% CI 0.24 to 0.67), 0.41 (95% CI 0.32 to 0.52) and 0.36 (95% CI 0.26 to 0.52) in low (bottom quintile of PRS), intermediate (two to four quintiles of PRS) and high (top quintile of PRS) PRS categories, respectively. For the absolute risk reduction (ARR), individuals with high PRS achieved the greatest benefit from favourable CVH, mitigating the risk to the average level of population (from 21.1% to 8.7%), and the gradient was strengthened in individuals at the top 5% of PRS. Moreover, compared with individuals at low PRS, those at high PRS obtained longer CAD-free years (2.6 vs 1.1) from favourable CVH at the index age of 35 years. CONCLUSION: Favourable CVH profile reduced the CAD relative risk by similar magnitude across PRS categories, while the ARR from favourable CVH was most pronounced in high PRS category. Attaining favourable CVH should be encouraged for all individuals, especially in individuals with high genetic susceptibility.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Adulto , Humanos , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , População do Leste Asiático , Fatores de Risco , Nível de Saúde
7.
Front Cardiovasc Med ; 9: 985121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204584

RESUMO

Background: Single nucleotide polymorphisms that affect RNA modification (RNAm-SNPs) may have functional roles in coronary artery disease (CAD). The aim of this study was to identify RNAm-SNPs in CAD susceptibility loci and highlight potential risk factors. Methods: CAD-associated RNAm-SNPs were identified in the CARDIoGRAMplusC4D and UK Biobank genome-wide association studies. Gene expression and circulating protein levels affected by the RNAm-SNPs were identified by QTL analyses. Cell experiments and Mendelian randomization (MR) methods were applied to test whether the gene expression levels were associated with CAD. Results: We identified 81 RNAm-SNPs that were associated with CAD or acute myocardial infarction (AMI), including m6A-, m1A-, m5C-, A-to-I- and m7G-related SNPs. The m6A-SNPs rs3739998 in JCAD, rs148172130 in RPL14 and rs12190287 in TCF21 and the m7G-SNP rs186643756 in PVT1 were genome-wide significant. The RNAm-SNPs were associated with gene expression (e.g., MRAS, DHX36, TCF21, JCAD and SH2B3), and the expression levels were associated with CAD. Differential m6A methylation and differential expression in FTO-overexpressing human aorta smooth muscle cells and peripheral blood mononuclear cells of CAD patients and controls were detected. The RNAm-SNPs were associated with circulating levels of proteins with specific biological functions, such as blood coagulation, and the proteins (e.g., cardiotrophin-1) were confirmed to be associated with CAD and AMI in MR analyses. Conclusion: The present study identified RNAm-SNPs in CAD susceptibility genes, gene expression and circulating proteins as risk factors for CAD and suggested that RNA modification may play a role in the pathogenesis of CAD.

8.
Nat Nanotechnol ; 17(11): 1206-1213, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36266508

RESUMO

The miniaturization of silicon-based electronics has motivated considerable efforts in exploring new electronic materials, including two-dimensional semiconductors and halide perovskites, which are usually too delicate to maintain their intrinsic properties during the harsh device fabrication steps. Here we report a convenient plug-and-probe approach for one-step simultaneous van der Waals integration of high-k dielectrics and contacts to enable top-gated transistors with atomically clean and electronically sharp dielectric and contact interfaces. By applying the plug-and-probe top-gate transistor stacks on two-dimensional semiconductors, we demonstrate an ideal subthreshold swing of 60 mV per decade. Using this approach on delicate lead halide perovskite, we realize a high-k top-gate CsPbBr3 transistor with a low operating voltage and a very high two-terminal field-effect mobility of 32 cm2 V-1 s-1. This approach can be extended to centimetre-scale MoS2 and perovskite and generate top-gated transistor arrays, offering a rapid and convenient way of accessing intrinsic properties of delicate emerging materials.

9.
Arterioscler Thromb Vasc Biol ; 42(11): 1378-1397, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36172865

RESUMO

BACKGROUND: Migration of human aortic smooth muscle cells (HASMCs) contributes to the pathogenesis of atherosclerosis. This study aims to functionally characterize long noncoding RNA TPRG1-AS1 (tumor protein p63 regulated 1, antisense 1) in HASMCs and reveal the underlying mechanism of TPRG1-AS1 in HASMCs migration, neointima formation, and subsequent atherosclerosis. METHODS: The expression of TPRG1-AS1 in atherosclerotic plaques was verified a series of in silico analysis and quantitative real-time polymerase chain reaction analysis. Northern blot, rapid amplification of cDNA ends and Sanger sequencing were used to determine its full length. In vitro transcription-translation assay was used to investigate the protein-coding capacity of TPRG1-AS1. RNA fluorescent in situ hybridization was used to confirm its subcellular localization. Loss- and gain-of-function studies were used to investigate the function of TPRG1-AS1. Furthermore, the effect of TPRG1-AS1 on the pathological response was evaluated in carotid balloon injury model, wire injury model, and atherosclerosis model, respectively. RESULTS: TPRG1-AS1 was significantly increased in atherosclerotic plaques. TPRG1-AS1 did not encode any proteins and its full length was 1279nt, which was bona fide a long noncoding RNA. TPRG1-AS1 was mainly localized in cytoplasmic and perinuclear regions in HASMCs. TPRG1-AS1 directly interacted with MYH9 (myosin heavy chain 9) protein in HASMCs, promoted MYH9 protein degradation through the proteasome pathway, hindered F-actin stress fiber formation, and finally inhibited HASMCs migration. Vascular smooth muscle cell-specific transgenic overexpression of TPRG1-AS1 significantly reduced neointima formation, and attenuated atherosclerosis in apolipoprotein E knockout (Apoe-/-) mice. CONCLUSIONS: This study demonstrated that TPRG1-AS1 inhibited HASMCs migration through interacting with MYH9 protein and consequently suppressed neointima formation and atherosclerosis.


Assuntos
Aterosclerose , MicroRNAs , Placa Aterosclerótica , RNA Longo não Codificante , Humanos , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Músculo Liso Vascular/metabolismo , Neointima/metabolismo , Placa Aterosclerótica/metabolismo , Actinas/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , DNA Complementar/metabolismo , DNA Complementar/farmacologia , Hibridização in Situ Fluorescente , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Proliferação de Células , Miócitos de Músculo Liso/metabolismo , Movimento Celular , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , MicroRNAs/genética , Proteínas do Citoesqueleto/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas/metabolismo
11.
Science ; 375(6583): 852-859, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35201882

RESUMO

The conformal integration of electronic systems with irregular, soft objects is essential for many emerging technologies. We report the design of van der Waals thin films consisting of staggered two-dimensional nanosheets with bond-free van der Waals interfaces. The films feature sliding and rotation degrees of freedom among the staggered nanosheets to ensure mechanical stretchability and malleability, as well as a percolating network of nanochannels to endow permeability and breathability. With an excellent mechanical match to soft biological tissues, the freestanding films can naturally adapt to local surface topographies and seamlessly merge with living organisms with highly conformal interfaces, rendering living organisms with electronic functions, including leaf-gate and skin-gate transistors. On-skin transistors allow high-fidelity monitoring and local amplification of skin potentials and electrophysiological signals.

12.
Eur Heart J ; 43(18): 1702-1711, 2022 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-35195259

RESUMO

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.


Assuntos
Doença da Artéria Coronariana , Povo Asiático , China/epidemiologia , Estudos de Coortes , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Herança Multifatorial/genética , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
13.
J Atheroscler Thromb ; 29(2): 200-220, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33536383

RESUMO

AIM: ATP-binding cassette (ABC) transporters and endonuclease-exonuclease-phosphatase family domain containing 1 (EEPD1) are reported to regulate cellular cholesterol efflux in macrophages. Bioinformatics analysis has revealed that ABCG1 and EEPD1 might be potential targets of microRNA (miR)-320b. This study aimed to elucidate the roles of miR-320b in cholesterol efflux from macrophages and the pathogenesis of atherosclerosis. METHODS: Microarray was conducted to profile microRNA (miRNA) expression, and quantitative real-time PCR (qPCR) was used to validate the differentially expressed miRNAs in peripheral blood mononuclear cells of coronary artery disease (CAD) patients and healthy controls. Luciferase assay was conducted to evaluate the activity of reporter construct containing the 3´-untranslated region (3´-UTR) of target genes. Besides, NBD-cholesterol efflux induced by high-density lipoprotein (HDL) and lipid-free apolipoprotein A1 (apoA1) was detected using fluorescence intensity, respectively. Apoe-/- mice were injected with adeno-associated virus (AAV)2-miR-320b or control via tail vein, thereafter fed with 14 week atherogenic diet to study the roles of miR-320b in vivo. RESULTS: MiR-320b was highly expressed in CAD patients compared with that in the healthy controls in both the microarray analysis and qPCR analysis. In vitro study showed that miR-320b decreased HDL- and apoA1-mediated cholesterol efflux from macrophages partly by directly targeting ABCG1 and EEPD1 genes and partly via suppressing the LXRα-ABCA1/G1 pathway. Consistently, in vivo administration of AAV2-miR-320b into Apoe-/- mice attenuated cholesterol efflux from peritoneal macrophages, which showed reduced expression of ABCA1/G1 and EEPD1, and increased lipid LDL-C level, with a down-regulation of hepatic LDLR and ABCA1. AAV2-miR-320b treatment also increased atherosclerotic plaque size and lesional macrophage content and enhanced pro-inflammatory cytokines levels through the elevated phosphorylation level of nuclear factor-κB p65 in macrophages. CONCLUSION: We identify miR-320b as a novel modulator of macrophage cholesterol efflux and that it might be a promising therapeutic target for atherosclerosis treatment.


Assuntos
Aterosclerose/etiologia , Colesterol/metabolismo , Doença da Artéria Coronariana/metabolismo , Macrófagos/metabolismo , MicroRNAs/genética , Animais , Estudos de Casos e Controles , Doença da Artéria Coronariana/etiologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Análise Serial de Tecidos
14.
Chronic Dis Transl Med ; 7(4): 227-234, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34786542

RESUMO

BACKGROUND: High sodium intake is an important risk factor for hypertension and cardiovascular disease. However, the association between gut microbiota composition and metabolomic profiles with dietary sodium intake and blood pressure (BP) is not well-understood. The metabolome, microbiome, and dietary salt intervention (MetaSalt) study aimed to investigate microbial and metabolomic profiles related to dietary sodium intake and BP regulation. METHODS: This family-based intervention study was conducted in four communities across three provinces in rural northern China in 2019. Probands with untreated prehypertension or stage-1 hypertension were identified through community-based BP screening, and family members including siblings, offspring, spouses, and parents were subsequently included. All participants participated in a 3-day baseline examination with usual diet consumption, followed by a 10-day low-salt diet (3 g/d of salt or 51.3 mmol/d of sodium) and a 10-day high-salt diet (18 g/d of salt or 307.8 mmol/d of sodium). Differences in mean BP levels were compared according to the intervention phases using a paired Student's t-test. RESULTS: A total of 528 participants were included in this study, with a mean age of 48.1 years, 36.7% of whom were male, 76.8% had a middle school (69.7%) or higher (7.1%) diploma, 23.4% had a history of smoking, and 24.4% were current drinkers. The mean arterial pressure at baseline was 97.2 ± 10.5 mm Hg for all participants, and significantly decreased during the low-salt intervention (93.8 ± 9.3, P < 0.0001) and subsequently increased during the high-salt intervention (96.4 ± 10.0, P < 0.0001). CONCLUSIONS: Our dietary salt intervention study has successfully recruited participants and will facilitate to evaluate the effects of gut microbiota and metabolites on BP regulation in response to sodium burden, which will provide important evidence for investigating the underlying mechanisms in the development of hypertension and subsequent cardiovascular diseases. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry database (ChiCTR1900025171).

15.
Adv Mater ; 33(43): e2104370, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34510593

RESUMO

Neural systems can selectively filter and memorize spatiotemporal information, thus enabling high-efficient information processing. Emulating such an exquisite biological process in electronic devices is of fundamental importance for developing neuromorphic architectures with efficient in situ edge/parallel computing, and probabilistic inference. Here a novel multifunctional memristor is proposed and demonstrated based on metalloporphyrin/oxide hybrid heterojunction, in which the metalloporphyrin layer allows for dual electronic/ionic transport. Benefiting from the coordination-assisted ionic diffusion, the device exhibits smooth, gradual conductive transitions. It is shown that the memristive characteristics of this hybrid system can be modulated by altering the metal center for desired metal-oxygen bonding energy and oxygen ions migration dynamics. The spike voltage-dependent plasticity stemming from the local/extended movement of oxygen ions under low/high voltage is identified, which permits potentiation and depression under unipolar different positive voltages. As a proof-of-concept demonstration, memristive arrays are further built to emulate the signal filtering function of the biological visual system. This work demonstrates the ionic intelligence feature of metalloporphyrin and paves the way for implementing efficient neural-signal analysis in neuromorphic hardware.

16.
Neurology ; 97(6): e619-e628, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34031205

RESUMO

OBJECTIVE: To construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke. METHODS: Using a meta-analytic approach and large genome-wide association results for stroke and stroke-related traits in East Asians, we generated a combined PRS (metaPRS) by incorporating 534 genetic variants in a training set of 2,872 patients with stroke and 2,494 controls. We then validated its association with incident stroke using Cox regression models in large Chinese population-based prospective cohorts comprising 41,006 individuals. RESULTS: During a total of 367,750 person-years (mean follow-up 9.0 years), 1,227 participants developed stroke before age 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.66-2.38), with the lifetime risk of stroke being 25.2% (95% CI 22.5%-27.7%) and 13.6% (95% CI 11.6%-15.5%), respectively. Individuals with both high polygenic risk and family history displayed lifetime risk as high as 41.1% (95% CI 31.4%-49.5%). Individuals with high polygenic risk achieved greater benefits in terms of absolute risk reductions from adherence to ideal fasting blood glucose and total cholesterol than those with low polygenic risk. Maintaining favorable cardiovascular health (CVH) profile could substantially mitigate the increased risk conferred by high polygenic risk to the level of low polygenic risk (from 34.6% to 13.2%). CONCLUSIONS: Our metaPRS has great potential for risk stratification of stroke and identification of individuals who may benefit more from maintaining ideal CVH. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that metaPRS is predictive of stroke risk.


Assuntos
Predisposição Genética para Doença , Fatores de Risco de Doenças Cardíacas , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Adulto , Idoso , Povo Asiático , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Modelos Estatísticos , Herança Multifatorial , Reprodutibilidade dos Testes , Medição de Risco/métodos , Medição de Risco/normas , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/prevenção & controle
17.
Biochem Pharmacol ; 188: 114540, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33819467

RESUMO

MiR-520b belongs to the miR-373/520 family, is expressed only in human and nonhuman primates. Previous reports indicated that the expression of miR-520b was repressed in human atherosclerotic plaque tissue compared with healthy vessels. However, the role of miR-520b in coronary artery disease still remains to be uncovered. In this study, we demonstrated that endothelial cells (ECs) in human atherosclerotic plaques expressed miR-520b and aimed to elucidate the impact of miR-520b on EC activation and inflammatory response. To determine the potential targets of miR-520b, we performed RNA-seq analysis by transfecting miR-520b mimics in ECs. The quantitative real-time PCR (qPCR) validation suggested that miR-520b over-expression reduced pro-inflammatory gene expression (e.g. ICAM1, VCAM1, SELE) while the inhibition of miR-520b induced their expression. By combining bioinformatics prediction and functional assays, we identified that RELA (Nuclear Factor-κB (NF-κB) Transcription Factor P65) was a direct target of miR-520b. Moreover, miR-520b mimics attenuated monocyte adhesion and monocyte trans-endothelial migration (the initial steps of atherosclerotic formation) in response to lipopolysaccharides (LPS) stimulation. Re-expression of a non-miR-targetable version of p65 could rescue the reduced monocyte cell attachment, suggesting that this process is NF-κB p65 dependent. MiR-520b reduced the abundance of NF-κB p65 in cytoplasmic fractions without corresponding increase in nuclear fractions, indicating that this regulation is independent of p65 translocation process. MiR-520b mimics attenuated the activity of VCAM-1 promoter, whereas miR-520b inhibitor activated its activity. However, miR-520b inhibitor had no effect on promoter activity containing the mutated NF-κB p65 binding sites, strongly demonstrating that the impact of miR-520b on VCAM1 gene is mediated by NF-κB p65. Thus, we concluded that miR-520b suppressed EC inflammation and the cross-talk between monocytes and ECs by down-regulating NF-κB p65-ICAM1/VCAM1 axis and might serve as a potential therapeutic target for EC dysfunction and atherosclerosis.


Assuntos
Células Endoteliais/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição RelA/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia , Sequência de Bases , Células HeLa , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , NF-kappa B/antagonistas & inibidores , Células THP-1 , Fator de Transcrição RelA/antagonistas & inibidores , Molécula 1 de Adesão de Célula Vascular/antagonistas & inibidores
18.
Epigenomics ; 13(10): 793-808, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33876670

RESUMO

Aim: To reveal transcriptome-wide N6-methyladenosine (m6A) methylome of coronary artery disease (CAD). Materials & methods: The m6A levels of RNA from peripheral blood mononuclear cells measured by colorimetry were significantly decreased in CAD cases. Transcriptome-wide m6A methylome profiled by methylated RNA immunoprecipitation sequencing (MeRIP-seq) identified differentially methylated m6A sites within both mRNAs and lncRNAs between CAD and control group. Results: Bioinformatic analysis indicated that differentially methylated genes were involved in the pathogenesis of atherosclerosis. MeRIP-quantitative real-time PCR assay confirmed the reliability of MeRIP-seq data. Finally, the rat carotid artery balloon injury model was performed to confirm the role of m6A demethylase FTO in neointima formation. Conclusion: Our study provided a resource of differentially methylated m6A profile for uncovering m6A biological functions in the pathogenesis of CAD.


Assuntos
Adenosina/análogos & derivados , Doença da Artéria Coronariana/genética , Adenosina/genética , Animais , Biologia Computacional , Humanos , Masculino , Metilação , Ratos Sprague-Dawley , Transcriptoma
19.
Adv Mater ; 31(49): e1902962, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31618496

RESUMO

The minimization of the subthreshold swing (SS) in transistors is essential for low-voltage operation and lower power consumption, both critical for mobile devices and internet of things (IoT) devices. The conventional metal-oxide-semiconductor field-effect transistor requires sophisticated dielectric engineering to achieve nearly ideal SS (60 mV dec-1 at room temperature). However, another type of transistor, the junction field-effect transistor (JFET) is free of dielectric layer and can reach the theoretical SS limit without complicated dielectric engineering. The construction of a 2D SnSe/MoS2 van der Waals (vdW) heterostructure-based JFET with nearly ideal SS is reported. It is shown that the SnSe/MoS2 vdW heterostructure exhibits excellent p-n diode rectifying characteristics with low saturate current. Using the SnSe as the gate and MoS2 as the channel, the SnSe/MoS2 vdW heterostructure exhibit well-behavioured n-channel JFET characteristics with a small pinch-off voltage VP of -0.25 V, nearly ideal subthreshold swing SS of 60.3 mV dec-1 and high ON/OFF ratio over 106 , demonstrating excellent electronic performance especially in the subthreshold regime.

20.
Atherosclerosis ; 286: 88-96, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31103880

RESUMO

BACKGROUND AND AIMS: The role of circular RNAs (circRNAs) in coronary artery disease (CAD) remains elusive. The aim of the present study was to profile circRNAs expression in CAD patients and assess diagnostics biomarkers for CAD. METHODS: The circRNA profiles of 24 CAD patients and 7 controls were assessed by microarray. The expression levels of candidate circRNAs were further verified by qRT-PCR in large cohorts. Logistic regression analysis and receiver operating characteristic were conducted to assess the diagnostic value. Gain-of-function approach was used to determine the functional significance of validated circRNA in THP-1-derived macrophages. RESULTS: A total of 624 circRNAs and 171 circRNAs were significantly upregulated and downregulated, respectively, in CAD patients relative to controls. Hsa_circ_0001879 and hsa_circ_0004104 were validated to be significantly upregulated in large cohorts. The receiver operating characteristics analysis of hsa_circ_0001879 and hsa_circ_0004104 in CAD patients and controls showed that the area under curve was 0.703 (95% confidence interval: 0.656-0.750; p < 0.001) and 0.700 (95% confidence interval: 0.646-0.755; p < 0.001), respectively. The combination of hsa_circ_0001879 and hsa_circ_0004104, together with CAD risk factors, had the better performance to discriminate CAD patients from healthy controls. Overexpression of hsa_circ_0004104 resulted in dysregulation of atherosclerosis-related genes in THP-1-derived macrophages. CONCLUSIONS: We offered a transcriptome-wide overview of aberrantly expressed circRNAs in CAD patients and identified two novel circRNA biomarkers to diagnose CAD. Upregulation of hsa_circ_0004104 might contribute to the pathogenesis of CAD.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/genética , RNA Circular/isolamento & purificação , Transcriptoma , Biomarcadores , Células Cultivadas , Estudos de Coortes , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/metabolismo , Regulação para Baixo , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , RNA Circular/biossíntese , Regulação para Cima
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