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1.
J Am Chem Soc ; 145(48): 26052-26060, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-37982690

RESUMEN

Engineering the wettability of surfaces with hydrophobic organics has myriad applications in heterogeneous catalysis and the large-scale chemical industry; however, the mechanisms behind may surpass the proverbial hydrophobic kinetic benefits. Herein, the well-studied In2O3 methanol synthesis photocatalyst has been used as an archetype platform for a hydrophobic treatment to enhance its performance. With this strategy, the modified samples facilitated the tuning of a wide range of methanol production rates and selectivity, which were optimized at 1436 µmol gcat-1 h-1 and 61%, respectively. Based on in situ DRIFTS and temperature-programmed desorption-mass spectrometry, the surface-decorated alkylsilane coating on In2O3 not only kinetically enhanced the methanol synthesis by repelling the produced polar molecules but also donated surface active H to facilitate the subsequent hydrogenation reaction. Such a wettability design strategy seems to have universal applicability, judged by its success with other CO2 hydrogenation catalysts, including Fe2O3, CeO2, ZrO2, and Co3O4. Based on the discovered kinetic and mechanistic benefits, the enhanced hydrogenation ability enabled by hydrophobic alkyl groups unleashes the potential of the surface organic chemistry modification strategy for other important catalytic hydrogenation reactions.

2.
J Am Chem Soc ; 145(24): 13134-13146, 2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37278596

RESUMEN

Stable metal nitrides (MN) are promising materials to fit the future "green" ammonia-hydrogen nexus. Either through catalysis or chemical looping, the reductive hydrogenation of MN to MN1-x is a necessary step to generate ammonia. However, encumbered by the formation of kinetically stable M-NH1─3 surface species, this reduction step remains challenging under mild conditions. Herein, we discovered that deleterious Ti-NH1─3 accumulation on TiN can be circumvented photochemically with supported single atoms and clusters of platinum (Pt1-Ptn) under N2-H2 conditions. The photochemistry of TiN selectively promoted Ti-NH formation, while Pt1-Ptn effectively transformed any formed Ti-NH into free ammonia. The generated ammonia was found to originate mainly from TiN reduction with a minor contribution from N2 activation. The knowledge accrued from this fundamental study could serve as a springboard for the development of MN materials for more efficient ammonia production to potentially disrupt the century-old fossil-powered Haber-Bosch process.

3.
Angew Chem Int Ed Engl ; 62(27): e202304470, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37137871

RESUMEN

Cobalt ferrite (CoFe2 O4 ) spinel has been found to produce C2 -C4 hydrocarbons in a single-step, ambient-pressure, photocatalytic hydrogenation of CO2 with a rate of 1.1 mmol g-1 h-1 , selectivity of 29.8 % and conversion yield of 12.9 %. On stream the CoFe2 O4 reconstructs to a CoFe-CoFe2 O4 alloy-spinel nanocomposite which facilitates the light-assisted transformation of CO2 to CO and hydrogenation of the CO to C2 -C4 hydrocarbons. Promising results obtained from a laboratory demonstrator bode well for the development of a solar hydrocarbon pilot refinery.

4.
Dev Growth Differ ; 64(2): 88-97, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34519039

RESUMEN

Plant Rho small GTPases (Rop/Rac) are versatile molecular switches regulating many plant developmental processes. Particularly, their important functions in regulating pollen development have been demonstrated in Arabidopsis. A group of conserved Rop/Rac activators RopGEFs were recently reported to regulate rice (Oryza sativa) pollen tube germination, indicating that rice and Arabidopsis may have a conserved Rop/Rac mediated signaling pathway in regulating pollen tube growth. However, the Rop/Rac activated by the rice pollen specific RopGEFs remains to be identified. Here we demonstrated a Rop/Rac gene, OsRacB, co-expressed with the mature pollen expressed OsRopGEF2/3/6/8. The knockout mutants were normal in anther and pollen development but defective in the pollen grain germination, suggesting a specific and non-redundant role of OsRacB in the mature pollen. We further demonstrated that OsRacB is directly activated by the pollen specific expressing OsRopGEFs in vitro. Together with the previous study, we establish a RopGEF-Rop/Rac regulon which plays essential roles in rice pollen grain germination. Our data encourage further identification of the upstream and downstream players of RopGEF-Rop/Rac signaling in pollen germination and have agricultural implications for breeding robust seed yielding cultivars.


Asunto(s)
Arabidopsis , Proteínas de Unión al GTP Monoméricas , Oryza , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Unión al GTP Monoméricas/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polen/genética , Polen/metabolismo , Proteínas de Unión al GTP rho/genética , Proteínas de Unión al GTP rho/metabolismo
5.
Langmuir ; 38(49): 15156-15164, 2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36442080

RESUMEN

Photocatalytic hydrogen production technology from water is a more effective and promising method to solve energy and environmental crises. In this work, flowerlike CaMoO4 microspheres were successfully synthesized by an ultrasonic precipitation method and modified with variable concentrations of CdSe NCs. CdSe/CaMoO4 microspheres showed increased light absorption ability, larger relative surface area, lower electrochemical impedance, and longer fluorescence lifetime. The photocatalytic hydrogen production rate of CdSe/CaMoO4 microspheres could reach up to 10 162.33 µmol g-1 h-1. The constructed type-I heterostructure improved the separation of photogenerated electrons and inhibited the rapid recombination of photogenerated electrons and holes, thus enhancing the photocatalytic hydrogen production performance. CdSe/CaMoO4 with high hydrogen production activity would be an efficient photocatalyst for hydrogen production applications.

6.
BMC Musculoskelet Disord ; 23(1): 1119, 2022 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-36550505

RESUMEN

BACKGROUND: Work-related neck pain (WRNP) is a leading cause of disability and absenteeism. Patients with neck pain often have neck muscle tenderness and decreased cervical mobility, which are sometimes combined with psychosocial issues, such as pain catastrophising, thereby reducing their work ability. Whilst multidisciplinary treatments, including pharmacological interventions, manual therapy and specific neck exercises, have produced positive outcomes, effective personalised treatment modalities are still needed. Furthermore, manual therapies using the hands can bring fatigue to therapist. Occiflex is a computerised device that can provide personalised segmental joint mobilisation based on symptoms and injury of the patient and then provide a medium range of joint activities to improve range of cervical motion. This study aims to compare the effect of computerised mobilisation performed with Occiflex with that of traditional manual therapy on WRNP. METHODS: We will conduct a prospective randomised controlled trial including 150 patients with WRNP. These patients will be randomly assigned to one of three groups: (i) home exercise (TE), (ii) home exercise plus Occiflex therapy and (iii) home exercise plus manual therapy delivered by a physical therapist. Ten treatment sessions will be performed in four weeks. During the trial, these patients will receive only the assigned treatment and the standard patient education and will be asked not to use any analgesics unless strictly necessary. Assessments by trained evaluators will occur at baseline, week 4 and week 12. The primary outcome measures will include visual analogue scale (VAS) for pain and neck disability index (NDI) at each time point. Secondary outcome measures will include cervical range of motion (CROM), pressure pain threshold (PPT), global perceived effect (GPE) and sick leave. Group by time differences will be analysed using linear mixed models with repeated measures. DISCUSSION: This protocol describes the methods for a randomised controlled trial to compare the effectiveness of computerised versus manual mobilisation techniques in treating WRNP. The results will provide an alternative method (Occiflex) that is possibly effective for treating neck pain whilst minimising the manual work done by therapists. TRIAL REGISTRATION: The study protocol was retrospectively registered at http://www.chictr.org.cn (registration number: ChiCTR2100053076) on November 10, 2021.


Asunto(s)
Manipulaciones Musculoesqueléticas , Dolor de Cuello , Humanos , Dolor de Cuello/terapia , Dolor de Cuello/diagnóstico , Estudios Prospectivos , Modalidades de Fisioterapia , Manipulaciones Musculoesqueléticas/métodos , Cuello , Terapia por Ejercicio/métodos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Angew Chem Int Ed Engl ; 61(1): e202110158, 2022 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-34734453

RESUMEN

Urea, an agricultural fertilizer, nourishes humanity. The century-old Bosch-Meiser process provides the world's urea. It is multi-step, consumes enormous amounts of non-renewable energy, and has a large CO2 footprint. Thus, developing an eco-friendly synthesis for urea is a priority. Herein we report a single-step Pd/LTA-3A catalyzed synthesis of urea from CO2 and NH3 under ambient conditions powered solely by solar energy. Pd nanoparticles serve the dual function of catalyzing the dissociation of NH3 and providing the photothermal driving force for urea formation, while the absorption capacity of LTA-3A removes by-product H2 O to shift the equilibrium towards urea production. The solar urea conversion rate from NH3 and CO2 is 87 µmol g-1 h-1 . This advance represents a first step towards the use of solar energy in urea production. It provides insights into green fertilizer production, and inspires the vision of sustainable, modular plants for distributed production of urea on farms.

8.
Acc Chem Res ; 52(3): 633-644, 2019 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-30668116

RESUMEN

The utilization of solar energy and the development of its related optoelectronic devices have become more important than ever. Solar cells or photoelectrochemical (PEC) cells that require the design of light harvesting assemblies for efficiently converting solar light into electricity or solar fuels are of particular interest. Semiconductor TiO2, serving as the photoelectrode for photovoltaic devices (e.g., dye- or quantum dot-sensitized solar cells (DSSCs/QDSSCs) or perovskite solar cells (PSCs)) and PEC cells, has aroused intense research interest owing to its inherent characteristics of wide band gap and promising optical and electrical properties. TiO2 nanowires (TNWs) have been widely used in optoelectronic devices due to their unique 1D geometry and salient optical and electrical properties. However, the insufficient surface area resulting from the relatively large diameter of NWs and considerable free space between adjacent NWs restricts their optoelectronic performance. Hence, it is desirable to explore every feasible aspect of TNWs in terms of structural design and optical management, aiming to further improve the performance of optoelectronic devices. In this Account, we present a brief survey of strategies for designing branched or hyperbranched TNW-based photoelectrodes and their applications in solar cells and PEC cells. The general strategies (e.g., alkaline/acid hydrothermal method, lift-off transfer, and self-assembly approach) are discussed to address the challenges associated with fabricating TNWs on transparent conducting oxide (TCO) substrates. A series of strategies to fabricate judiciously designed 3D branched array architectures, including length tuning and sequential surface branched or hyperbranched modification, are proposed. The versatile implantation of the TNWs onto other backbones (nanosheets, nanotubes, hollow spheres, or multilayered electrodes) and substrates (fiber-shaped metal wire or mesh, flexible metal foil, or plastic sheet) is demonstrated to construct a new class of the TNW-embedded composite electrode materials with desired morphological characteristics and optoelectronic properties, for example, favorable energy level alignment for cascade charge transfer and rational homogeneous/heterogeneous interfacial engineering. The functionalities of TNW-based electrodes include enlarged surface area and superior light scattering for maximized light harvesting, as well as facilitated charge transport and suppressed charge recombination for enhanced charge collection, which are promising in optoelectronic fields such as solar cells, photocatalysis, and PEC cells. Beyond TNWs, one can also integrate other types of semiconductor (e.g., Fe2O3 or WO3) NWs into rationally designed structures for preparing novel photocatalytic materials with panchromatic absorption, efficient charge transfer, and excellent catalytic properties. Finally, an insightful perspective for rational design of advanced NW-based materials is provided.

9.
Drug Metab Dispos ; 48(1): 52-62, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31704713

RESUMEN

Glutathione (GSH) has been reported to be closely related to various diseases of the central nervous system, yet its authentic active ingredients and action sites remain unclear. In the present study, oral exogenous GSH significantly alleviated ischemic brain injury, but this result was inconsistent with its low bioavailability and blood-brain barrier (BBB) permeability. To ascertain the exposure of GSH-derived ingredients, including GSH, cysteine (CYS), glutamate (Glu), glycine (GLY), CYS-GLY, and γ-glutamylcysteine (γ-GC) were systematically studied both in vitro and in vivo. The outcomes demonstrated that oral GSH not only increases the GSH and CYS levels in rat striatum and cortex, but it also can decrease the rise of intracerebral Glu concentration caused by ischemia/reperfusion surgery. Then the influence of GSH on the BBB was investigated via measuring IgG leakage, intracerebral endotoxin, and tight-junction proteins. All indicators showed that GSH dosing can repair the destroyed BBB. Oral GSH greatly enhances the exposure of GSH, CYS, CYS-GLY, and γ-GC in rat duodenum, jejunum, ileum, and colon. Accumulating evidence reveals a close link between brain injury and gastrointestinal dysfunction. Our findings further suggest that oral GSH significantly improves intestinal inflammatory damage and barrier disruptions. In conclusion, oral GSH can have a direct therapeutic role in brain injury by stabilizing intracerebral levels of GSH, CYS, and Glu. It can also play an indirect therapeutic role by enhancing the intestinal exposure of GSH, CYS, CYS-GLY, and γ-GC and improving intestinal barrier disruptions. SIGNIFICANCE STATEMENT: The authentic active ingredients and action sites of exogenous glutathione (GSH) in the treatment of ischemic brain injury are unclear. We have shown that oral exogenous GSH not only stabilizes intracerebral levels of GSH, cysteine (CYS), and glutamate (Glu) to act directly on brain injury, but it can also exert an indirect therapeutic role by improving intestinal barrier disruptions. These findings have great significance for revealing the therapeutic effect of GSH on ischemic brain injury and for promoting its further development and clinical application.


Asunto(s)
Barrera Hematoencefálica/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Glutatión/farmacocinética , Glutatión/uso terapéutico , Modelos Biológicos , Daño por Reperfusión/tratamiento farmacológico , Administración Oral , Animales , Sitios de Unión , Biotransformación , Barrera Hematoencefálica/metabolismo , Isquemia Encefálica/metabolismo , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Glutatión/administración & dosificación , Humanos , Íleon/efectos de los fármacos , Íleon/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo
10.
Eur J Clin Microbiol Infect Dis ; 39(9): 1771-1779, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32242313

RESUMEN

Pentamidine sensitizes FDA-approved antibiotics to combat Gram-negative pathogens. We screened 1374 FDA-approved non-antibiotics for their ability to be sensitized by pentamidine against Escherichia coli. We identified mitomycin C and mefloquine as potent hits effective against multiple drug-resistant, Gram-negative bacteria. Killing kinetics and an in vivo model with Caenorhabditis elegans (C. elegans) revealed that such combinations produced synergy against colistin-resistant Enterobacter cloacae (E. cloacae). These findings suggest combinations of FDA-approved non-antibiotics, and pentamidine can be repurposed into new antimicrobial agents.


Asunto(s)
Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Pentamidina/farmacología , Animales , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Caenorhabditis elegans/efectos de los fármacos , Reposicionamiento de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Sinergismo Farmacológico , Quimioterapia Combinada , Enterobacter cloacae/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Modelos Animales , Pentamidina/administración & dosificación , Pentamidina/uso terapéutico , Estados Unidos , United States Food and Drug Administration
11.
Mol Ther ; 27(12): 2182-2194, 2019 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-31451355

RESUMEN

Long noncoding RNAs (lncRNAs) are an important class of pervasive noncoding RNA involved in a variety of biological functions. Numerous studies have demonstrated their important regulatory role in human disease, especially cancer. However, the mechanism underlying the transcription of lncRNAs is not fully elucidated. Here, a comparison of local chromatin structure of the ROR lncRNA locus revealed a cohesin-complex-mediated intrachromosomal loop that is juxtaposed with an upstream enhancer to the ROR promoter, enabling activation of endogenous ROR lncRNA in tumor cells. This chromosomal interaction was not observed in normal control cells. Knockdown of SMC1 by RNAi or deletion of the enhancer DNA by CRISPR/Cas9 abolished the intrachromosomal interaction, resulting in ROR lncRNA silencing and inhibition of the tumor progression in animals carrying tumor xenografts. Our results reveal a novel mechanism by which the cohesin-orchestrated intrachromosomal looping may serve as a critical epigenetic driver to activate transcription of ROR lncRNA, subsequently inducing tumorigenesis. Our data represent a novel chromosomal folding pattern of lncRNA regulation, thereby providing a novel alternative concept of chromosomal interaction in lncRNA-triggered tumorigenesis.


Asunto(s)
Carcinogénesis/patología , Proteínas de Ciclo Celular/genética , Proteínas Cromosómicas no Histona/genética , Cromosomas Humanos , Complejo Mediador/genética , Neoplasias/patología , ARN Largo no Codificante/genética , ARN Interferente Pequeño/genética , Animales , Apoptosis , Carcinogénesis/genética , Carcinogénesis/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proliferación Celular , Proteínas Cromosómicas no Histona/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Complejo Mediador/antagonistas & inhibidores , Ratones , Ratones Desnudos , Neoplasias/genética , Neoplasias/metabolismo , Regiones Promotoras Genéticas , ARN Largo no Codificante/antagonistas & inhibidores , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
12.
J Sci Food Agric ; 100(13): 4849-4857, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32476141

RESUMEN

BACKGROUND: Natural plant essential oils have antimicrobial properties; however, essential oils are difficult to maintain in a system because of their volatile nature. First, we prepared microcapsules from ß-cyclodextrin and oregano essential oil and characterized their properties. Second, the effect of microcapsules on the preservation of freshly cut purple yam was studied using an edible coating technique. Purple yams immersed in distilled water were used as control, and their characteristics were compared with yams coated with citric acid, citric acid + sodium alginate, and citric acid + sodium alginate + ß-cyclodextrin-oregano essential oil microcapsules (CA-SA-MC) and stored at 4 °C for 5 days. RESULTS: Microcapsules of oregano essential oil and ß-cyclodextrin solution were successfully prepared via the inclusion method, with an optimal encapsulation efficiency of 55.14%. Scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis showed strong bonds between ß-cyclodextrin and oregano essential oil. All edible coatings, particularly CA-SA-MC, significantly (P ≤ 0.05) maintained firmness, total soluble solids, ascorbic acid content, and anthocyanin content compared with control treatment. This treatment also prevented browning and extended the shelf life of purple yam. CONCLUSION: Oregano essential oil can be successfully encapsulated into cyclodextrin microcapsules. It has a great impact on the shelf life extension of purple yam and could be successfully applied to other fresh produce. © 2020 Society of Chemical Industry.


Asunto(s)
Dioscorea/química , Conservación de Alimentos/métodos , Aceites Volátiles/farmacología , Origanum/química , beta-Ciclodextrinas/química , Conservación de Alimentos/instrumentación , Conservantes de Alimentos/química , Conservantes de Alimentos/farmacología , Almacenamiento de Alimentos , Aceites Volátiles/química , Tubérculos de la Planta/química
13.
Angew Chem Int Ed Engl ; 59(47): 20980-20987, 2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-32716141

RESUMEN

The performances of electron-transport-layer (ETL)-free perovskite solar cells (PSCs) are still inferior to ETL-containing devices. This is mainly due to severe interfacial charge recombination occurring at the transparent conducting oxide (TCO)/perovskite interface, where the photo-injected electrons in the TCO can travel back to recombine with holes in the perovskite layer. Herein, we demonstrate for the first time that a non-annealed, insulating, amorphous metal oxyhydroxide, atomic-scale thin interlayer (ca. 3 nm) between the TCO and perovskite facilitates electron tunneling and suppresses the interfacial charge recombination. This largely reduced the interfacial charge recombination loss and achieved a record efficiency of 21.1 % for n-i-p structured ETL-free PSCs, outperforming their ETL-containing metal oxide counterparts (18.7 %), as well as narrowing the efficiency gap with high-efficiency PSCs employing highly crystalline TiO2 ETLs.

14.
Mol Cancer ; 18(1): 161, 2019 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-31722709

RESUMEN

BACKGROUND: Dynamic N6-methyladenosine (m6A) RNA modification generated and erased by N6-methyltransferases and demethylases regulates gene expression, alternative splicing and cell fate. Ocular melanoma, comprising uveal melanoma (UM) and conjunctival melanoma (CM), is the most common primary eye tumor in adults and the 2nd most common melanoma. However, the functional role of m6A modification in ocular melanoma remains unclear. METHODS: m6A assays and survival analysis were used to explore decreased global m6A levels, indicating a late stage of ocular melanoma and a poor prognosis. Multiomic analysis of miCLIP-seq, RNA-seq and Label-free MS data revealed that m6A RNA modification posttranscriptionally promoted HINT2 expression. RNA immunoprecipitation (RIP)-qPCR and dual luciferase assays revealed that HINT2 mRNA specifically interacted with YTHDF1. Furthermore, polysome profiling analysis indicated a greater amount of HINT2 mRNA in the translation pool in ocular melanoma cells with higher m6A methylation. RESULTS: Here, we show that RNA methylation significantly inhibits the progression of UM and CM. Ocular melanoma samples showed decreased m6A levels, indicating a poor prognosis. Changes in global m6A modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of methylated HINT2 mRNA, a tumor suppressor in ocular melanoma. CONCLUSIONS: Our work uncovers a critical function for m6A methylation in ocular melanoma and provides additional insight into the understanding of m6A modification.


Asunto(s)
Adenosina/análogos & derivados , Neoplasias del Ojo/genética , Melanoma/genética , Proteínas Mitocondriales/genética , Procesamiento Postranscripcional del ARN , ARN Mensajero/genética , Adenosina/metabolismo , Apoptosis , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Neoplasias del Ojo/metabolismo , Neoplasias del Ojo/mortalidad , Neoplasias del Ojo/patología , Perfilación de la Expresión Génica , Humanos , Melanoma/metabolismo , Melanoma/mortalidad , Melanoma/patología , Metilación , Proteínas Mitocondriales/metabolismo , Pronóstico , ARN Mensajero/metabolismo
15.
Exp Eye Res ; 184: 64-71, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30898556

RESUMEN

Neovascularization during ocular tissue repair can cause severe visual loss in the optical axis and is therefore an issue of considerable concern to ophthalmologists. Here, we introduced a cholesterol-modified siRNA delivery system targeting stromal cell-derived factor 1 (SDF-1) to treat ocular angiogenesis in vivo. SDF-1 expression was analyzed in rat endothelial progenitor cells (EPCs) and bone marrow mesenchymal stem cells (BMSCs) using quantitative PCR (qPCR). Migration ability of BMSC and HUVEC were assessed through transwell assay. The proliferation effect of chol-siSDF1 on HUVEC was measured by colony formation assay. In vivo anti-angiogenic effects of chol-siSDF1 were tested in a cornea alkali burn model and the area of cornea neovascularization was measured using computer-imaging analysis system. Then phosphorylated Akt and total Akt protein levels were measured through western blot. Results turned out that rat EPCs and BMSCs showed high SDF-1 mRNA expression, which can be down-regulated by using chol-siSDF-1. Chol-siSDF-1 could significantly inhibit migration of BMSC and HUVEC. In addition, chol-siSDF1 also could inhibit HUVEC proliferation and exert a significant anti-angiogenic effect in corneal alkali burn model. As for the mechanism, chol-siSDF1 may inhibit the neovascularization, proliferation and metastasis through inhibiting the Akt signaling pathway. Thus, cholesterol modification of siRNA targeting SDF-1 displays an effective inhibition of migration and angiogenesis, with a much longer duration of inhibition effect.


Asunto(s)
Quemaduras Químicas/terapia , Quimiocina CXCL12/genética , Colesterol/química , Neovascularización de la Córnea/terapia , Quemaduras Oculares/inducido químicamente , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , ARN Interferente Pequeño/uso terapéutico , Inhibidores de la Angiogénesis , Animales , Western Blotting , Movimiento Celular/fisiología , Células Cultivadas , Neovascularización de la Córnea/metabolismo , Células Progenitoras Endoteliales/metabolismo , Ensayo de Inmunoadsorción Enzimática , Técnicas de Silenciamiento del Gen , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Masculino , Células Madre Mesenquimatosas/metabolismo , Fosforilación , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Hidróxido de Sodio
16.
Anal Bioanal Chem ; 411(5): 1041-1052, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30613842

RESUMEN

The great hurdles related with matrix-assisted laser desorption/ionization (MALDI) analysis are inhomogeneous crystallization, poor reproducibility, and low sensitivity. To effectively improve the performance of MALDI mass spectrometry (MS), graphene oxide (GO) was first utilized as an auxiliary matrix of the conventional matrices, including 2,5-dihydroxybenzoic acid (DHB), α-cyano-4-hydoxycyanocinnamic acid (CHCA), 2,4,6-trihydroxyacetophenone (THAP), and 3,5-dimethoxy-4-hydroxycinnamic acid (SA), for the analysis of small molecules and biological macromolecules on different MALDI MS systems. The results revealed that the DHB-GO composite matrix could provide much superior crystal homogenization, better reproducibility, higher sensitivity, and more excellent linearity for the statins' tissue imaging on iMScope than the single-use DHB matrix. Moreover, the DHB-GO dramatically improved the spot-to-spot and shot-to-shot reproducibility, crystal homogenization, sensitivity, and linearity of MALDI-TOF MS for statins' analysis in dried droplet. The capability of THAP on the analysis of lipids, similarly, could be greatly enhanced by the combined use of GO. THAP-GO composite matrix was expected to be widely used in the MALDI MS-based liposome studies. It was also found that CHCA-GO could provide superior analytical performance for peptides. The sensitivity and reproducibility of intact proteins could be greatly improved by SA-GO composite matrix. More importantly, the better reproducibility produced by the composite matrices sufficiently indicated that low concentration (0.1 mg mL-1) of GO almost did not cause contamination to MALDI MS system. Thus, GO was proved to be a versatile auxiliary matrix for the MALDI MS-based routine analysis of small molecules and biological macromolecules. Graphical abstract ᅟ.


Asunto(s)
Grafito/química , Lípidos/análisis , Péptidos/análisis , Proteínas/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Acetofenonas/química , Animales , Ácidos Cumáricos/química , Cristalización , Gentisatos/química , Hígado/química , Masculino , Ratones Endogámicos BALB C , Somatostatina/análisis
17.
Acta Pharmacol Sin ; 40(5): 699-709, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30218071

RESUMEN

The combinational administration of antioxidants and chemotherapeutic agents during conventional cancer treatment is among one of the most controversial areas in oncology. Although the data on the combinational usage of doxorubicin (DOX) and glutathione (GSH) agents have been explored for over 20 years, the duration, administration route, and authentic rationality have not yet been fully understood yet. In the current study, we systematically investigated the pharmacokinetics (PK) and pharmacodynamics (PD) with both in vivo and in vitro models to elucidate the influence of GSH on the toxicity and efficacy of DOX. We first studied the cardioprotective and hepatoprotective effects of GSH in Balb/c mice, H9c2, and HL7702 cells. We showed that coadministration of exogenous GSH (5, 50, and 500 mg/kg per day, intragastric) significantly attenuated DOX-induced cardiotoxicity and hepatotoxicity by increasing intracellular GSH levels, whereas the elevated GSH concentrations did not affect the exposure of DOX in mouse heart and liver. From PK and PD perspectives, then the influences of GSH on the chemotherapeutic efficacy of DOX were investigated in xenografted nude mice and cancer cell models, including MCF-7, HepG2, and Caco-2 cells, which revealed that administration of exogenous GSH dose-dependently attenuated the anticancer efficacy of DOX in vivo and in vitro, although the elevated GSH levels neither influenced the concentration of DOX in tumors in vivo, nor the uptake of DOX in MCF-7 tumor cells in vitro. Based on the results we suggest that the combined administration of GSH and DOX should be contraindicated during chemotherapy unless DOX has caused serious hepatotoxicity and cardiotoxicity.


Asunto(s)
Antineoplásicos/uso terapéutico , Antioxidantes/uso terapéutico , Cardiotónicos/uso terapéutico , Cardiotoxicidad/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Doxorrubicina/uso terapéutico , Glutatión/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidad , Antioxidantes/administración & dosificación , Antioxidantes/farmacocinética , Cardiotónicos/administración & dosificación , Cardiotónicos/farmacocinética , Línea Celular Tumoral , Contraindicaciones de los Medicamentos , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Doxorrubicina/toxicidad , Quimioterapia Combinada , Glutatión/administración & dosificación , Glutatión/farmacocinética , Xenoinjertos , Humanos , Hígado/metabolismo , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Miocardio/metabolismo , Ratas , Distribución Tisular
18.
Small ; 14(11): e1703762, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29380522

RESUMEN

Lead halide perovskite nanocrystals (NCs) have demonstrated great potential as appealing candidates for advanced optoelectronic applications. However, the toxicity of lead and the intrinsic instability toward moisture hinder their mass production and commercialization. Herein, to solve such thorny problems, novel lead-free Cs2 AgBiBr6 double perovskite NCs fabricated via a simple hot-injection method are reported, which exhibit impressive stability in moisture, light, and temperature. Such materials are then applied into photocatalytic CO2 reduction, achieving a total electron consumption of 105 µmol g-1 under AM 1.5G illumination for 6 h. This study offers a reliable avenue for Cs2 AgBiBr6 perovskite nanocrystals preparation, which holds a great potential in the further photochemical applications.

19.
Acta Pharmacol Sin ; 39(8): 1373-1385, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29188801

RESUMEN

Among the somatostatin analogues, octreotide (OCT) is the most commonly used in clinic via intravenous or subcutaneous injection to treat various diseases caused by increased secretion of growth hormone, gastrin or insulin. In order to assesse the feasibility of developing oral formulations of OCT, we conducted systematical pharmacokinetic and pharmacodynamic analyses of OCT in several animal models. The pharmacokinetic studies in rats showed that intragastric administration of OCT had extremely low bioavailability (<0.5%), but it could specifically distribute to the gastric mucosa due to the high expression of somatostatin receptor 2 (SSTR2) in the rat stomach. The pharmacodynamic studies revealed that intragastric administration of OCT dose-dependently protected against gastric mucosal injury (GMI) in mice with WIRS-induced mouse gastric ulcers, which were comparable to those achieved by intravenous injection of OCT, and this effect was markedly attenuated by co-administration of CYN-154806, an antagonist of SSTR2. In pyloric ligation-induced ulcer mice, we further demonstrated that OCT significantly reduced the secretion of gastric acid via down-regulating the level of gastrin, which was responsible for the protective effect of OCT against GMI. Overall, we have provided pharmacokinetic and pharmacodynamic evidence for the feasibility of developing an oral formulation of OCT. Most importantly, the influence of SSTR2 on the pharmacokinetics and pharmacodynamics of OCT suggested that an oral formulation of OCT might be applicable for other clinical indications, including neuroendocrine neoplasms and pituitary adenoma due to the overexpression of SSTR2 on these tumor cells.


Asunto(s)
Antiulcerosos/farmacocinética , Antiulcerosos/uso terapéutico , Mucosa Gástrica/efectos de los fármacos , Octreótido/farmacocinética , Octreótido/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Administración Intravenosa , Administración Oral , Animales , Antiulcerosos/administración & dosificación , Antiulcerosos/metabolismo , Células CACO-2 , Perros , Mucosa Gástrica/patología , Células HCT116 , Humanos , Células de Riñón Canino Madin Darby , Masculino , Ratones Endogámicos BALB C , Octreótido/administración & dosificación , Octreótido/metabolismo , Oligopéptidos/farmacología , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/metabolismo , Sustancias Protectoras/farmacocinética , Sustancias Protectoras/uso terapéutico , Ratas Sprague-Dawley , Receptores de Somatostatina/antagonistas & inhibidores , Distribución Tisular
20.
J Am Chem Soc ; 139(16): 5660-5663, 2017 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-28385017

RESUMEN

Halide perovskite quantum dots (QDs), primarily regarded as optoelectronic materials for LED and photovoltaic devices, have not been applied for photochemical conversion (e.g., water splitting or CO2 reduction) applications because of their insufficient stability in the presence of moisture or polar solvents. Herein, we report the use of CsPbBr3 QDs as novel photocatalysts to convert CO2 into solar fuels in nonaqueous media. Under AM 1.5G simulated illumination, the CsPbBr3 QDs steadily generated and injected electrons into CO2, catalyzing CO2 reduction at a rate of 23.7 µmol/g h with a selectivity over 99.3%. Additionally, through the construction of a CsPbBr3 QD/graphene oxide (CsPbBr3 QD/GO) composite, the rate of electron consumption increased 25.5% because of improved electron extraction and transport. This study is anticipated to provide new opportunities to utilize halide perovskite QD materials in photocatalytic applications.

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