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1.
J Am Chem Soc ; 146(23): 16194-16202, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38832699

RESUMEN

Although progress has been made in enantioselective hydroboration of di- and trisubstituted alkenes over the past decades, enantioselective hydroboration of tetrasubstituted alkenes with high diastereo- and enantioselectivities continues as an unmet challenge since the 1950s due to its extremely low reactivity and the difficulties to simultaneously control the regio- and stereoselectivity of a tetrasubstituted alkene. Here, we report highly regio-, diastereo-, and enantioselective catalytic hydroboration of diverse acyclic tetrasubstituted alkenes. The delicate interplay of an electron-rich rhodium complex and coordination-assistance forms a highly adaptive catalyst that effectively overcomes the low reactivity and controls the stereoselectivity. The generality of the catalyst system is exemplified by its efficacy across various tetrasubstituted alkenes with diverse steric and electronic properties.

2.
Acc Chem Res ; 56(3): 308-321, 2023 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-36628651

RESUMEN

ConspectusAlkenes are versatile compounds that are readily available on a large scale from industry or through organic synthesis. The widespread occurrence of alkenes provides the continuous impetus for the development of catalytic asymmetric alkene hydrofunctionalizations, which enables expeditious construction of complex chiral molecules from readily available starting materials. Catalytic asymmetric hydrofunctionalization of internal alkenes presents a notable challenge, due to their low reactivity, many potential side reactions, and the simultaneous control of the regio-, diastereo-, and enantioselectivities.Dehydroamino acids and enamides are among the first substrates that provide notable enantioselectivities in catalytic asymmetric hydrogenation. The crucial importance of an amide coordinating group is established by a series of classical mechanistic studies. This initial success greatly stimulated further development for catalytic hydrogenation and hydrofunctionalization. Building on these pioneering works in asymmetric hydrogenation as well as related hydrofunctionalizations, we have adopted coordination assistance as a powerful tool to address the challenges associated with the asymmetric hydrofunctionalization of internal alkenes. Using a functional group on the alkene substrate as a native coordinating group, a two-point binding mode of the substrate to the metal center effectively enhances the reactivity and facilitates the control of regio-, diastereo- and enantioselectivities. Through this strategy, we have developed a number of alkene hydrofunctionalization methods with excellent regio-, diastereo-, and enantiocontrols.In this Account, we summarize the recent advance in our lab using coordination assistance as a key element to achieve regio- and enantioselective hydroalkynylation of internal alkenes. First, we describe our early work aimed at controlling the regio- and enantioselectivity of hydroalkynylation using disubstituted enamide as the substrate. Both α- and ß-alkynylation were achieved by channeling the reaction pathway into a Chalk-Harrod or modified Chalk-Harrod mechanism. Next, we discuss the further development of catalysts to achieve regiodivergent and enantioselective hydroalkynylation of trisubstituted enamide to access vicinal stereocenters and quaternary carbon stereocenters. We also discuss the hydroalkynylation of α,ß-unsaturated amides to achieve unconventional site-selectivity through a combination of alkene isomerization and regioselective hydroalkynylation. This provides the basis for the construction of a remote quaternary carbon stereocenter through catalytic hydroalkynylation of trisubstituted ß,γ-unsaturated amides. We further show that this controlling principle is applicable to terminal alkene with a coordinating group as well. A ligand-controlled mechanism shift is discussed for the enantioselective alkynylation at the terminal and internal position of 1,1,-disubstituted alkenes. Finally, we briefly mention the application of coordination assistance to other hydrofunctionalizations such as hydroboration and hydrosilylation, where previously inaccessible reactivity and selectivity were achieved. Collectively, these catalytic methods demonstrate the power of coordination assistance for enantioselective hydrofunctionalizations. We anticipate that this strategy will create a platform to enable diverse enantioselective alkene transformations.

3.
Prehosp Emerg Care ; 27(5): 669-686, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35579544

RESUMEN

INTRODUCTION: There is limited research available on safe medication management practices in emergency medical services (EMS) practice, with most evidence-based medication safety guidelines based on research in nursing, operating theater and pharmacy settings. Prevention of errors requires recognition of contributing factors across the spectrum from the organizational level to procedural elements and patient characteristics. Evidence is inconsistent regarding the incidence of medication errors and multiple sources also state that errors are under-reported, making the true magnitude of the problem difficult to quantify. Definitions of error also vary, with the specific context of medication errors in prehospital practice yet to be established. The objective of this review is to identify the factors influencing the occurrence of medication errors by EMS personnel in the prehospital environment. METHODS AND ANALYSIS: The review included both qualitative and quantitative research involving interventions or phenomena related to medication safety or medication error by EMS personnel in the prehospital environment. A search of multiple databases was conducted to identify studies meeting these inclusion criteria. All studies selected were assessed for methodological quality; however, this was not used as a basis for exclusion. Each stage of study selection, appraisal and data extraction was conducted by two independent reviewers, with a third reviewer deciding any unresolved conflicts. The review follows a convergent integrated approach, conducting a single qualitative synthesis of qualitative and "qualitized" quantitative data. RESULTS: Fifty-six articles were included in the review, with case reports and qualitative studies being the most frequent study types. Qualitative analysis revealed seven major themes: organizational factors (with reporting as a sub-theme), equipment/medications, environmental factors, procedure-related factors, communication, patient-related factors (with pediatrics as a sub-theme) and cognitive factors. Both contributing factors and protective factors were identified. DISCUSSION: The body of evidence regarding medication errors is heterogenous and limited in both quantity and quality. Multiple factors influence medication error occurrence; knowledge of these is necessary to mitigate the risk of errors. Medication error incidence is difficult to quantify due to inconsistent measure, definitions and contexts of research conducted to date. Further research is required to quantify the prevalence of identified factors in specific practice settings.


Asunto(s)
Servicios Médicos de Urgencia , Auxiliares de Urgencia , Humanos , Niño , Paramédico , Errores de Medicación/prevención & control , Investigación Cualitativa
4.
Arch Pharm (Weinheim) ; 356(8): e2300110, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37328442

RESUMEN

Four series of novel pyrazole derivatives (compounds 17a-m, 18a-m, 19a-g, and 20a-g) were synthesized, and their antibacterial and antifungal activities were evaluated. Most of the target compounds (17a-m, 18k-m, and 19b-g) showed strong antifungal activity and high selectivity relative to both Gram-positive and Gram-negative bacteria. Among them, compounds 17l (minimum inhibitory concentration [MIC] = 0.25 µg/mL) and 17m (MIC = 0.25 µg/mL) showed the strongest antifungal activity, being 2- and 4-fold more active than the positive controls gatifloxacin and fluconazole, respectively. In particular, compound 17l showed little cytotoxicity against human LO2 cells and did not exhibit hemolysis at ultrahigh concentrations, as did the positive control compounds gatifloxacin and fluconazole. These results indicate that these compounds are valuable for further development as antifungal agents.


Asunto(s)
Antibacterianos , Tiadiazoles , Humanos , Antibacterianos/farmacología , Antifúngicos/farmacología , Gatifloxacina , Tiadiazoles/farmacología , Fluconazol/farmacología , Relación Estructura-Actividad , Bacterias Gramnegativas , Bacterias Grampositivas , Pruebas de Sensibilidad Microbiana , Pirazoles/farmacología
5.
Psychol Health Med ; 28(8): 2156-2168, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35477332

RESUMEN

A range of studies have shown that prenatal maternal stress (PNMS) exposure is associated with offspring autistic-like behaviors, however the potential pathways remain unexplored. This study aimed to evaluate the mediating role of parent-child interactions in early life in the association between PNMS exposure and preschoolers' autistic-like behaviors. Data from 65,928 child-parent dyads were obtained via a primary caregiver-reported questionnaire administered as part of the Longhua Child Cohort Study. To strengthen confidence in the reliability of the results, the analyses were initially conducted on a random selection of 70% of the total sample, and then validated on the remaining 30% of the sample. Analysis of covariance and multiple linear models were employed to estimate the associations between PNMS exposure, parent-child interactions in early life, and children's autistic-like behaviors. The results showed that PNMS exposure was positively associated with the presence of autistic-like behaviors at preschool age. The total indirect effect of the frequency of positive parent-child interactions in early life accounted for 9.69% or 8.99% of the variance of the association. Our findings indicate that parent-child interactions in early life might function as potential mediators of the association between PNMS and the increased risk of offspring autistic-like behaviors.

6.
Opt Lett ; 47(11): 2858-2861, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35648948

RESUMEN

In this Letter, GaN-based green resonant-cavity light-emitting diodes (RCLEDs) with a low-cost aluminum (Al) metal bottom mirror, a dielectric top mirror, and a copper (Cu) supporting plate were fabricated. The green-emitting epitaxial wafer was grown on a patterned sapphire substrate (PSS) to ensure high crystal quality (CQ). Laser lift-off (LLO) of the PSS and electrical plating of a Cu supporting plate were then carried out to realize the vertical device structure. The emission wavelength and full width at half maximum (FWHM) of the main emission peak of the device are ∼518 nm and 14 nm, respectively. Under the current density of 50 A/cm2, a relatively high light output power (LOP) of 11.1 mW can be obtained from the green RCLED. Moreover, when the current injection is 20 mA (8 A/cm2), the corresponding forward bias voltage is as low as ∼2.46 V. The reasons for the low operating voltage and high LOP can be attributed to the improvement of CQ, the release of residual compressive stress of the GaN-based epilayer due to the removal of PSS, and better heat dissipation properties of the Cu supporting plate.

7.
Exp Eye Res ; 224: 109264, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36162459

RESUMEN

Diabetic retinopathy (DR) is one of the common systemic complications of diabetes. Epithelial-mesenchymal transition (EMT) is required for DR progression. Previous studies have explored that circular RNAs (circRNAs) are crucial for DR development. Herein, we focused on the biological functions of circSCMH1 in DR. RT-qPCR determined the expression of circSCMH1, miR-200a-3p and ZEB1. EMT-related proteins were measured by Western blot. Gene combinations were validated by RIP and dual luciferase reporter assays. CCK-8, EdU, TUNEL staining and Transwell analysis were used to assess the cellular function. FISH analysis assessed the localization of circSCMH1 and miR-200a-3p. HE staining was used to detect retinal structures in a mouse DR model. High-glucose (HG) significantly increased circSCMH1 expression in ARPE-19 cells. Additionally, circSCMH1 silencing repressed proliferation, migration, and EMT in HG cells. Mechanistically, circSCMH1 positively regulated ZEB1 expression via targeting miR-200a-3p. Furthermore, circSCMH1 was observed to induce HG cell growth and EMT by regulating the miR-200a-3p/ZEB1 axis. Finally, we verified that downregulation of circSCMH1 or ZEB1 alleviated EMT in the retina of diabetic mice. These findings have implications for new therapeutic targets for DR.


Asunto(s)
Diabetes Mellitus Experimental , Retinopatía Diabética , MicroARNs , ARN Circular , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , Animales , Ratones , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Diabetes Mellitus Experimental/genética , Retinopatía Diabética/genética , Transición Epitelial-Mesenquimal/genética , Glucosa , MicroARNs/genética , MicroARNs/metabolismo , Retina/metabolismo , ARN Circular/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética
8.
Public Health ; 206: 20-28, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35313129

RESUMEN

OBJECTIVES: This study aimed to explore the association of visual, hearing, or dual sensory impairment with healthcare use and costs. STUDY DESIGN: This is a cohort study. METHODS: These research data were from the China Health and Retirement Longitudinal Study spanning 2011-2018 and included 8982 community-dwelling middle-aged and older adults (aged ≥45 years at baseline). Sensory impairment was measured according to self-reported assessment of visual and hearing functions, and healthcare use and costs were ascertained via self-report. The associations of sensory impairment with healthcare use and costs were estimated using the mixed-effects regression models. RESULTS: Of the 8982 respondents, 4346 (48.39%) were females and their mean (standard deviation) age at baseline was 57.03 (8.26) years. Individuals with hearing impairment (HI) only, visual impairment (VI) only, and dual sensory impairment (DSI) were all at significantly higher risks of healthcare use and catastrophic health expenditure than those without sensory impairment (all P < 0.05), except that VI only non-significantly prolonged inpatient days. Compared with no impairment, DSI was associated with increases in outpatient (ß = 50.67, 95% confidence interval [CI] = 17.47-83.86) and inpatient out-of-pocket costs (ß = 40.35, 95% CI = 5.94-74.76), while VI only or HI only did not show significant effects. Further stratification analyses indicated that the associations between sensory impairment and outpatient use were more pronounced among males than among females but that age group did not moderate the associations with any healthcare outcomes. CONCLUSIONS: HI and VI were independently and together associated with higher risks of healthcare use and catastrophic health expenditure. Dual sensory impairment was the only category consistently associated with increased outpatient and inpatient costs.


Asunto(s)
Pérdida Auditiva , Trastornos de la Visión , Anciano , China/epidemiología , Estudios de Cohortes , Atención a la Salud , Femenino , Pérdida Auditiva/epidemiología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Trastornos de la Visión/epidemiología
9.
BMC Med Educ ; 22(1): 219, 2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-35354454

RESUMEN

BACKGROUND: Overseas study trips can enhance healthcare students' intercultural communication competence. An opportunity to immerse in the new culture enables them to develop their ability to offer services to people from different countries. However, the role that open-mindedness (i.e., a personality trait) can play in this process has not been explored. METHODS: The present study adopted a mixed-method design to identify how open-mindedness trait affected this overseas learning process. Thirty-two undergraduate healthcare students in Australia took part in the study. Questionnaires, which measured socio-demographic information, intercultural communication competence and open-mindedness trait were administered to the participants before and after their overseas trip. Half of the participants (n = 16) were interviewed after the overseas trip. RESULTS: The correlational analysis showed that the open-mindedness trait was correlated with cultural skills, a component of intercultural communication competence, but not significant with the other three components. Three themes emerging from the qualitative data indicated that the open-mindedness trait affected students' cultural exposure. This trait enabled participants to be actively involved in the immersion in the local culture. They were willing to learn from peer fellows, and keen to embrace novel challenges. CONCLUSION: It is concluded that open-mindedness trait is vital for increasing cultural immersion, and hence promote intercultural communication skills.


Asunto(s)
Competencia Cultural , Atención a la Salud , Australia , Comunicación , Humanos , Encuestas y Cuestionarios
10.
Nanotechnology ; 31(42): 424007, 2020 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-32599566

RESUMEN

The separation of processing and memory units in von Neumann architecture creates issues with energy consumption and speed mismatches, which is a huge obstacle on the road of integrated-circuit development. Potentially, the excellent performance of two-dimensional materials field-effect transistors controlled by organic ferroelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) polymer could clear the path for the development of next-generation microelectronics. Here, we combined P(VDF-TrFE) polymer and molybdenum disulfide (MoS2) nanoflakes to fabricate a horizontal dual-gate ferroelectric field-effect transistor (HDG-FeFET) device. This device can provide in-situ memory of logic results while processing the AND logic function. During the logic operations, the logic output state-1/state-0 current ratio approached 105. After 900 s, the corresponding non-volatile memory state-1/state-0 current ratio remains at 104. This type of transistor is expected to provide a promising in-memory computing solution for next-generation computing architecture.

11.
Phys Chem Chem Phys ; 22(35): 20043-20049, 2020 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-32936150

RESUMEN

Computational evidence is reported on a boron-based ternary Rb6Be2B6 cluster as the "Big Mac" sandwich on a subnanoscale with thickness of 0.58 nm. The core hexagonal B6 ring, occurring in the naked form due to double 6π/6σ aromaticity, is capped by two tetrahedral BeRb3 ligands. Such a B6 motif is scarce in boron clusters. The sandwich cluster has four-fold 2σ/6π/6σ/2σ aromaticity and its tetrahedral BeRb3 ligand is the simplest case of three-dimensional aromaticity (or spherical aromaticity). The sandwich can be formulated as a charge-transfer complex, [Rb3Be]3+[B6]6-[BeRb3]3+, whose components are held together by robust electrostatics, facilitating dual-mode dynamic fluxionality.

12.
Acta Pharmacol Sin ; 41(6): 843-851, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31913347

RESUMEN

An increasing number of drugs are metabolized by aldehyde oxidase (AOX), but AOX-mediated drug interactions are seldom reported due to the lack of appropriate inhibitors and inducers. A recent study reported that nimesulide (NIM) could increase the liver injury risk of methotrexate. The latter was mainly metabolized by AOX to form hepatotoxic 7-hydroxymethotrexate (7-OH MTX). Thus, we speculated that NIM could induce AOX. In this study, we investigated the potential induction of AOX activity by NIM using methotrexate as the probe substrate. Treatment of primary human and rat hepatocytes with NIM (20 µM) for 24 h caused a 2.0- and 3.1-fold, respectively, increase in 7-OH MTX formation. Oral administration of NIM (100 mg·kg-1·d-1, for 5 days) to rats significantly increased the systematic exposure (6.5-fold), liver distribution (2.5-fold), and excretion (5.2-fold for urinary excretion and 2.1-fold for fecal excretion) of 7-OH MTX. The 7-OH MTX formation in liver cytosol from rats pretreated with 20, 50, and 100 mg·kg-1·d-1 NIM for 5 days increased by 1.9-, 3.2-, and 3.7-fold, respectively, compared with that of rats pretreated with the vehicle. We revealed that the elevation of AOX activity was accompanied by an increase in AOX1 protein levels but not the corresponding mRNA levels. Collectively, our results demonstrate for the first time that NIM can increase the AOX activity of humans and rats, and may raise concerns regarding the risk of drug interactions between NIM and AOX substrates in clinical practice.


Asunto(s)
Aldehído Oxidasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Sulfonamidas/farmacología , Administración Oral , Animales , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Relación Dosis-Respuesta a Droga , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Masculino , Metotrexato/administración & dosificación , Ratas , Ratas Wistar , Sulfonamidas/administración & dosificación
13.
Environ Res ; 183: 109190, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32311903

RESUMEN

OBJECTIVE: To investigate the relationship between climate variables, East Asian summer monsoon (EASM) and large outbreaks of dengue in China. METHODS: We constructed ecological niche models (ENMs) to analyse the influence of climate factors on dengue occurrence and predict dengue outbreak areas in China. Furthermore, we formulated a generalised additive model (GAM) to quantify the impact of the EASM on dengue occurrence in mainland China from 1980 to 2016. RESULTS: Mean Temperature of Coldest Quarter had a 62.6% contribution to dengue outbreaks. Southern China including Guangdong, Guangxi, Fujian and Yunnan provinces are more vulnerable to dengue emergence and resurgence. In addition, we found population density had a 68.7% contribution to dengue widely distribution in China using ENMs. Statistical analysis indicated a dome-shaped association between EASM and dengue outbreak using GAM, with the greatest impact in the South-East of China. Besides, there was a positive nonlinear association between monthly average temperature and dengue occurrence. CONCLUSION: We demonstrated the influence of climate factors and East Asian summer monsoon on dengue outbreaks, providing a framework for future studies on the association between climate change and vector-borne diseases.


Asunto(s)
Cambio Climático , Dengue , Estaciones del Año , China/epidemiología , Dengue/epidemiología , Brotes de Enfermedades , Humanos , Lluvia
14.
J Am Chem Soc ; 141(11): 4670-4677, 2019 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-30807127

RESUMEN

The control of chemo-, regio-, diastereo-, and enantioselectivity is a central theme in organic synthesis. The capability to obtain the full set of stereoisomers of a molecule would significantly enhance the efficiency for the synthesis of natural product analogues and creation of chiral compound libraries for drug discovery. Despite the tremendous progress achieved in the field of asymmetric synthesis in the past decades, the precise control of both relative and absolute configurations in catalyst-controlled reactions that create multiple stereocenters remains a significant synthetic challenge. We report here the development of a catalyst-controlled hydroboration with hitherto unattainable selectivity. The Rh-catalyzed hydroboration of α, ß-unsaturated carbonyl compounds with pinacolborane proceeds with high levels of regio-, diastereo-, and enantioselectivities to provide a hydroboration product with two vicinal stereocenters. Through the appropriate choice of substrate geometry ( E or Z) and ligand enantiomer ( S or R), all the possible diastereoisomers are readily accessible. The boron-containing products underwent many stereospecific transformations, thus providing a strategy for collective stereodivergent synthesis of diverse valuable chiral building blocks.

15.
Small ; 15(5): e1803876, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30624032

RESUMEN

Due to their advantages compared with planar structures, rolled-up tubes have been applied in many fields, such as field-effect transistors, compact capacitors, inductors, and integrative sensors. On the other hand, because of its perfect insulating nature, ultrahigh mechanical strength and atomic thickness property, 2D hexagonal boron nitride (h-BN) is a very suitable material for rolled-up memory applications. In this work, a tubular 3D resistive random access memory (RRAM) device based on rolled-up h-BN tube is realized, which is achieved by self-rolled-up technology. The tubular RRAM device exhibits bipolar resistive switching behavior, nonvolatile data storage ability, and satisfactorily low programming current compared with other 2D material-based RRAM devices. Moreover, by releasing from the substrate, the footprint area of the tubular device is reduced by six times. This tubular RRAM device has great potential for increasing the data storage density, lowering the power consumption, and may be applied in the fields of rolled-up systems and sensing-storage integration.

16.
Circ J ; 83(4): 809-817, 2019 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-30799311

RESUMEN

BACKGROUND: Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P<0.001). The diagnostic sensitivity of TRS 2°P for the primary composite endpoint was 76.3% (95% CI: 72.1-80.5%). Similar associations were also observed between TRS 2°P and CV death and non-fatal MI, but not non-fatal ischemic stroke. CONCLUSIONS: TRS 2°P reliably stratified post-MI patients for risk of future CV events.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Infarto del Miocardio/diagnóstico , Medición de Riesgo/métodos , Prevención Secundaria/métodos , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Accidente Cerebrovascular , Terapia Trombolítica
17.
Biochem J ; 475(3): 621-642, 2018 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-29321244

RESUMEN

Macrophage foam cells store excess cholesterol as cholesteryl esters, which need to be hydrolyzed for cholesterol efflux. We recently reported that silencing expression of carboxylesterase 1 (CES1) in human THP-1 macrophages [CES1KD (THP-1 cells with CES1 expression knocked down) macrophages] reduced cholesterol uptake and decreased expression of CD36 and scavenger receptor-A in cells loaded with acetylated low-density lipoprotein (acLDL). Here, we report that CES1KD macrophages exhibit reduced transcription of cytochrome P45027A1 (CYP27A1) in nonloaded and acLDL-loaded cells. Moreover, levels of CYP27A1 protein and its enzymatic product, 27-hydroxycholesterol, were markedly reduced in CES1KD macrophages. Transcription of LXRα (liver X receptor α) and ABCA1 (ATP-binding cassette transporter A1) was also decreased in acLDL-loaded CES1KD macrophages, suggesting reduced signaling through PPARγ-CYP27A1-LXRα. Consistent with this, treatment of CES1KD macrophages with agonists for PPARγ, RAR, and/or RAR/RXR partially restored transcription of CYP27A1 and LXRα, and repaired cholesterol influx. Conversely, treatment of control macrophages with antagonists for PPARγ and/or RXR decreased transcription of CYP27A1 and LXRα Pharmacologic inhibition of CES1 in both wild-type THP-1 cells and primary human macrophages also decreased CYP27A1 transcription. CES1 silencing did not affect transcript levels of PPARγ and RXR in acLDL-loaded macrophages, whereas it did reduce the catabolism of the endocannabinoid 2-arachidonoylglycerol. Finally, the gene expression profile of CES1KD macrophages was similar to that of PPARγ knockdown cells following acLDL exposures, further suggesting a mechanistic link between CES1 and PPARγ. These results are consistent with a model in which abrogation of CES1 function attenuates the CYP27A1-LXRα-ABCA1 signaling axis by depleting endogenous ligands for the nuclear receptors PPARγ, RAR, and/or RXR that regulate cholesterol homeostasis.


Asunto(s)
Transportador 1 de Casete de Unión a ATP/genética , Hidrolasas de Éster Carboxílico/genética , Colestanotriol 26-Monooxigenasa/genética , Colesterol/metabolismo , Receptores X del Hígado/genética , Antígenos CD36/genética , Hidrolasas de Éster Carboxílico/antagonistas & inhibidores , Línea Celular , Células Espumosas/metabolismo , Regulación de la Expresión Génica , Silenciador del Gen , Humanos , Macrófagos/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Receptor alfa de Ácido Retinoico/genética , Receptor alfa X Retinoide/genética , Receptores Depuradores de Clase A/genética
18.
Angew Chem Int Ed Engl ; 58(47): 17068-17073, 2019 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-31538388

RESUMEN

We report the development of palladium(0)-catalyzed syn-selective 1,2-carboboration and -silylation reactions of alkenes containing cleavable directing groups. With B2 pin2 or PhMe2 Si-Bpin as nucleophiles and aryl/alkenyl triflates as electrophiles, a broad range of mono-, di-, tri- and tetrasubstituted alkenes are compatible in these transformations. We further describe a directed dearomative 1,2-carboboration of electron-rich heteroarenes by employing this approach. Through use of a removable chiral directing group, we demonstrate the viability of achieving stereoinduction in Heck-type alkene 1,2-difunctionalization. This work introduces new avenues to access highly functionalized boronates and silanes with precise regio- and stereocontrol.


Asunto(s)
Alquenos/química , Compuestos Heterocíclicos/química , Paladio/química , Silanos/química , Catálisis , Ciclización , Estructura Molecular
19.
Small ; 14(20): e1800319, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29665261

RESUMEN

Recently, layered ultrathin 2D semiconductors, such as MoS2 and WSe2 are widely studied in nonvolatile memories because of their excellent electronic properties. Additionally, discrete 0D metallic nanocrystals and quantum dots (QDs) are considered to be outstanding charge-trap materials. Here, a charge-trap memory device based on a hybrid 0D CdSe QD-2D WSe2 structure is demonstrated. Specifically, ultrathin WSe2 is employed as the channel of the memory, and the QDs serve as the charge-trap layer. This device shows a large memory window exceeding 18 V, a high erase/program current ratio (reaching up to 104 ), four-level data storage ability, stable retention property, and high endurance of more than 400 cycles. Moreover, comparative experiments are carried out to prove that the charges are trapped by the QDs embedded in the Al2 O3 . The combination of 2D semiconductors with 0D QDs opens up a novelty field of charge-trap memory devices.

20.
Small ; 14(12): e1703667, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29457377

RESUMEN

Recently, organic-inorganic hybrid perovskites (OIHP) are studied in memory devices, but ternary resistive memory with three states based on OIHP is not achieved yet. In this work, ternary resistive memory based on hybrid perovskite is achieved with a high device yield (75%), much higher than most organic ternary resistive memories. The pseudohalide-induced 2D (CH3 NH3 )2 PbI2 (SCN)2 perovskite thin film is prepared by using a one-step solution method and fabricated into Al/perovskite film/indium-tin oxide (glass substrate as well as flexible polyethylene terephthalate substrate) random resistive access memory (RRAM) devices. The three states have a conductivity ratio of 1:103 :107 , long retention over 10 000 s, and good endurance properties. The electrode area variation, impedance test, and current-voltage plotting show that the two resistance switches are attributable to the charge trap filling due to the effect of unscreened defect in 2D nanosheets and the formation of conductive filaments, respectively. This work paves way for stable perovskite multilevel RRAMs in ambient atmosphere.

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