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1.
ACS Nano ; 18(16): 10688-10725, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38600721

RESUMO

Metal-halide perovskite solar cells (PSCs), an emerging technology for transforming solar energy into a clean source of electricity, have reached efficiency levels comparable to those of commercial silicon cells. Compared with other types of PSCs, inverted perovskite solar cells (IPSCs) have shown promise with regard to commercialization due to their facile fabrication and excellent optoelectronic properties. The interlayer interfaces play an important role in the performance of perovskite cells, not only affecting charge transfer and transport, but also acting as a barrier against oxygen and moisture permeation. Herein, we describe and summarize the last three years of studies that summarize the advantages of interface engineering-based advances for the commercialization of IPSCs. This review includes a brief introduction of the structure and working principle of IPSCs, and analyzes how interfaces affect the performance of IPSC devices from the perspective of photovoltaic performance and device lifetime. In addition, a comprehensive summary of various interface engineering approaches to solving these problems and challenges in IPSCs, including the use of interlayers, interface modification, defect passivation, and others, is summarized. Moreover, based upon current developments and breakthroughs, fundamental and engineering perspectives on future commercialization pathways are provided for the innovation and design of next-generation IPSCs.

2.
J Med Chem ; 67(2): 1168-1183, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38227770

RESUMO

Tropomyosin receptor kinase (TRK) fusion, an oncogenic form of kinase with pan-tumor occurrence, is a clinically validated important antitumor target. In this study, we screened our in-house kinase inhibitor library against TRK and identified a promising hit compound 4 with a novel pyridin-2(1H)-one scaffold. Through a combination of structure-based drug design and structure-activity relationship (SAR) study, compound 14q was identified as a potent TRK inhibitor with good kinase selectivity. It also blocked cellular TRK signaling, thereby inhibiting TRK-dependent cell viability. Additionally, 14q displayed acceptable pharmacokinetic properties with 37.8% oral bioavailability in mice. Strong in vivo tumor growth inhibition of 14q was observed in subcutaneous M091 and KM12 tumor xenograft models with TRK fusion, causing significant tumor inhibition or even complete tumor regression.


Assuntos
Antineoplásicos , Neoplasias , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacocinética , Receptor trkA , Transdução de Sinais , Relação Estrutura-Atividade , Piridonas/química , Piridonas/farmacologia
3.
Br J Pharmacol ; 181(9): 1474-1493, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38129941

RESUMO

BACKGROUND AND PURPOSE: We evaluated the hypothesis that central orexin application could counteract motion sickness responses through regulating neural activity in target brain areas. EXPERIMENTAL APPROACH: Thec effects of intracerebroventricular (i.c.v.) injection of orexin-A and SB-334867 (OX1 antagonist) on motion sickness-induced anorexia, nausea-like behaviour (conditioned gaping), hypoactivity and hypothermia were investigated in rats subjected to Ferris wheel-like rotation. Orexin-A responsive brain areas were identified using Fos immunolabelling and were verified via motion sickness responses after intranucleus injection of orexin-A, SB-334867 and TCS-OX2-29 (OX2 antagonist). The efficacy of intranasal application of orexin-A versus scopolamine on motion sickness symptoms in cats was also investigated. KEY RESULTS: Orexin-A (i.c.v.) dose-dependently attenuated motion sickness-related behavioural responses and hypothermia. Fos expression was inhibited in the ventral part of the dorsomedial hypothalamus (DMV) and the paraventricular nucleus (PVN), but was enhanced in the ventral part of the premammillary nucleus ventral part (PMV) by orexin-A (20 µg) in rotated animals. Motion sickness responses were differentially inhibited by orexin-A injection into the DMV (anorexia and hypoactivity), the PVN (conditioned gaping) and the PMV (hypothermia). SB-334867 and TCS-OX2-29 (i.c.v. and intranucleus injection) inhibited behavioural and thermal effects of orexin-A. Orexin-A (60 µg·kg-1) and scopolamine inhibited rotation-induced emesis and non-retching/vomiting symptoms, while orexin-A also attenuated anorexia with mild salivation in motion sickness cats. CONCLUSION AND IMPLICATIONS: Orexin-A might relieve motion sickness through acting on OX1 and OX2 receptors in various hypothalamus nuclei. Intranasal orexin-A could be a potential strategy against motion sickness.


Assuntos
Benzoxazóis , Hipotermia , Enjoo devido ao Movimento , Naftiridinas , Ureia/análogos & derivados , Ratos , Gatos , Animais , Orexinas/farmacologia , Receptores de Orexina/metabolismo , Anorexia/metabolismo , Hipotálamo/metabolismo , Enjoo devido ao Movimento/tratamento farmacológico , Enjoo devido ao Movimento/metabolismo , Escopolamina/metabolismo , Escopolamina/farmacologia , Antagonistas dos Receptores de Orexina/metabolismo , Antagonistas dos Receptores de Orexina/farmacologia
4.
Chemosphere ; 308(Pt 3): 136439, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36115474

RESUMO

Iron minerals, which exert excellent biocompatibility and reactivity with redox-active microorganisms, have attracted attention as a precursor to synthesizing composite materials with higher catalytic efficiency in driving redox-active microorganisms to reduce Cr(VI). However, researches on the effective preparation method of composites, the interaction between bacteria and composite materials and the mechanism of electron transfer are still scarce. In this work, Fe-complex@BC prepared by a one-step method using goethite was used for chromium treatment together with soil microorganisms. The composite was the best-performing in promoting Cr(VI) bioreduction (up to 3.48 mg (L·h)-1) than Fe-complex (2.26 mg (L·h)-1) and biochar (0.5 mg (L·h)-1), even about 19 times higher than that of bioreduction without materials. Specifically, Fe-complex@BC shortened the electron transfer distance due to its excellent adsorption properties for bacteria and Cr(VI). Its high redox activity also promoted Cr(VI) bioreduction by directly enhancing electron transfer. In addition, the presence of the Fe(III)/Fe(II) cycle proved that the active sites of composite could be regenerated to reduce Cr(VI) persistently by receiving extracellular electrons from bacteria. High-throughput 16 S rDNA gene sequencing indicated the composite could promote the proliferation of electrochemically active bacteria, which directly enhanced bioreduction. This study developed the low-cost Fe@BC material prepared by a one-step co-pyrolysis method, which exerts a synergistic effect with soil microorganisms and presents a promising potential for chromium pollution treatment.


Assuntos
Elétrons , Compostos Férricos , Adsorção , Carvão Vegetal/química , Cromo/química , DNA Ribossômico , Compostos Férricos/química , Compostos Ferrosos , Ferro/química , Minerais/química , Solo
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