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1.
ACS Appl Mater Interfaces ; 16(13): 16573-16579, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38511295

RESUMO

The intrinsic stability of the acceptor is a crucial component of the photovoltaic device stability. In this study, we investigated the efficiency and stability of the nonfused-ring acceptors LC8 and BC8 under indoor light conditions. Interestingly, we found that devices based on BC8 with terminal side chains exhibited a higher indoor efficiency and stability. Through accelerated aging experiments, we discovered that the acceptors generate singlet oxygen under light exposure with BC8 demonstrating lower levels of ROS compared to LC8. We attribute this difference to the modulation of the acceptor aggregation orientation. Furthermore, the generated reactive oxygen species (ROS) further deteriorate the acceptor structure, and this phenomenon is also observed in high-efficiency acceptor structures, such as Y6. Our research reveals important mechanisms of acceptor photo-oxidation processes, providing a theoretical basis for enhancing the intrinsic stability of acceptors.

2.
Inorg Chem ; 63(9): 4328-4336, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38367216

RESUMO

The study of structural reconstruction is vital for the understanding of the real active sites in heterogeneous catalysis and guiding the improved catalyst design. Herein, we applied a copper nitride precatalyst in the nitroarene reductive coupling reaction and made a systematic investigation on the dynamic structural evolution behaviors and catalytic performance. This Cu3N precatalyst undergoes a rapid phase transition to nanostructured Cu with rich defective sites, which act as the actual catalytic sites for the coupling process. The nitride-derived defective Cu is very active and selective for azo formation, with 99.6% conversion of nitrobenzene and 97.1% selectivity to azobenzene obtained under mild reaction conditions. Density functional theory calculations suggest that the defective Cu sites play a role for the preferential adsorption of nitrosobenzene intermediates and significantly lowered the activation energy of the key coupling step. This work not only proposes a highly efficient noble-metal-free catalyst for nitroarenes coupling to valuable azo products but also may inspire more scientific interest in the study of the dynamic evolution of metal nitrides in different catalytic reactions.

3.
Nat Commun ; 14(1): 8255, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38086803

RESUMO

The hypothesis of N-methyl-D-aspartate receptor (NMDAR) dysfunction for cognitive impairment in schizophrenia constitutes the theoretical basis for the translational application of NMDAR co-agonist D-serine or its analogs. However, the cellular mechanism underlying the therapeutic effect of D-serine remains unclear. In this study, we utilize a mouse neurodevelopmental model for schizophrenia that mimics prenatal pathogenesis and exhibits hypoexcitability of parvalbumin-positive (PV) neurons, as well as PV-preferential NMDAR dysfunction. We find that D-serine restores excitation/inhibition balance by reconstituting both synaptic and intrinsic inhibitory control of cingulate pyramidal neurons through facilitating PV excitability and activating small-conductance Ca2+-activated K+ (SK) channels in pyramidal neurons, respectively. Either amplifying inhibitory drive via directly strengthening PV neuron activity or inhibiting pyramidal excitability via activating SK channels is sufficient to improve cognitive function in this model. These findings unveil a dual mechanism for how D-serine improves cognitive function in this model.


Assuntos
Esquizofrenia , Camundongos , Animais , Gravidez , Feminino , Esquizofrenia/tratamento farmacológico , Serina/farmacologia , Células Piramidais/fisiologia , Neurônios/metabolismo , Transmissão Sináptica , Receptores de N-Metil-D-Aspartato/metabolismo
4.
Anal Chem ; 95(15): 6287-6294, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37014332

RESUMO

Mitochondrial membrane potential (MMP) and sulfur dioxide (SO2) significantly affect the mitochondrial state. In this work, TC-2 and TC-8 were constructed through side-chain engineering, in which TC-2 bearing the poorer hydrophobicity could localize on mitochondria better. Interestingly, short-wave emission was captured due to the sensitive response of TC-2 to SO2 (LOD = 13.8 nM). Meanwhile, the probe could bind with DNA, presenting enhanced long-wave emission. Encouragingly, TC-2 could migrate from mitochondria to the nucleus when MMP was decreased, accompanied by the increase of fluorescence lifetime (9-fold). Hence, TC-2 could be used for dual-channel monitoring of mitochondrial SO2 and MMP, which showed a completely different pathway from the commercial MMP detectors JC-1/JC-10. The cellular experiments showed that MMP was gradually decreased due to reactive oxygen species-triggered oxidative stress, and the SO2 level was up-regulated simultaneously. Overall, this work proposed a new method to investigate and diagnose the mitochondrial-related diseases.


Assuntos
Corantes Fluorescentes , Mitocôndrias , Humanos , Corantes Fluorescentes/metabolismo , Potenciais da Membrana , Mitocôndrias/metabolismo , Dióxido de Enxofre/metabolismo , Células HeLa , Potencial da Membrana Mitocondrial
5.
Psychopharmacology (Berl) ; 240(6): 1275-1285, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37071130

RESUMO

RATIONALE: Serotonergic psychedelics show promise in the treatment of psychiatric disorders, including obsessive-compulsive disorder. Dysfunction of the orbitofrontal cortex (OFc) has been implicated in the pathophysiology of compulsive behavior, which might be a key region for the efficacy of psychedelics. However, the effects of psychedelics on the neural activities and local excitation/inhibition (E/I) balance in the OFc are unclear. OBJECTIVES: This study aimed to investigate how 25C-NBOMe, a substituted phenethylamine psychedelic, regulated the synaptic and intrinsic properties of neurons in layer II/III of the OFc. METHODS: Acute brain slices containing the OFc of adult male Sprague Dawley rats were used for ex vivo whole-cell recording. The synaptic and intrinsic properties of neurons were monitored using voltage and current clamps, respectively. Electrically evoked action potential (eAP) was used to measure synaptic-driven pyramidal activity. RESULTS: 25C-NBOMe enhanced spontaneous neurotransmission at glutamatergic synapses but diminished that in GABAergic synapses through the 5-HT2A receptor. 25C-NBOMe also increased both evoked excitatory currents and evoked action potentials. Moreover, 25C-NBOMe promoted the excitability of pyramidal neurons but not fast-spiking neurons. Either inhibiting G protein-gated inwardly rectifying potassium channels or activating protein kinase C significantly obstructed the facilitative effect of 25C-NBOMe on the intrinsic excitability of pyramidal neurons. CONCLUSIONS: This work reveals the multiple roles of 25C-NBOMe in modulating synaptic and neuronal function in the OFc, which collectively promotes local E/I ratios.


Assuntos
Alucinógenos , Ratos , Animais , Masculino , Alucinógenos/farmacologia , Ratos Sprague-Dawley , Neurônios , Transmissão Sináptica/fisiologia , Córtex Pré-Frontal , Células Piramidais
6.
Neuropharmacology ; 227: 109452, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36724866

RESUMO

Serotoninergic psychedelics induced extensive alterations in perception and cognition, which has been attributable to its disruptive effect on oscillatory rhythms of prefrontal cortex. However, there is a lack of information how serotoninergic psychedelics affect the intra-prefrontal network, which intrinsically interact to accomplish perceptual processing. Uncovering the altered neural network caused by psychedelics helps to understand the mechanisms of their psychoactive effects and contribute to develop biological markers of psychedelic effects. In present study, we investigated the effects of substituted phenethylamine psychedelic 25C-NBOMe on neural oscillations in the intra-prefrontal and hippocampal-prefrontal network. The effective dose of 25C-NBOMe (0.1 mg/kg) disrupting sensorimotor gating in male Sprague-Dawley rats was used to observe its effects on neural oscillations in the prelimbic cortex, anterior cingulate cortex, orbitofrontal cortex (OFC) and hippocampus CA1. The power of high frequency oscillation (HFO, 120-150 Hz) was potentiated by 25C-NBOMe selectively in the OFC, with peaking at 20-30 min after treatment. 25C-NBOMe strengthened HFO coherence within the intra-prefrontal, rather than hippocampal-prefrontal network. Potentiated HFO in the OFC had a strong positive correlation with the strengthened inter-prefrontal HFO coherence by 25C-NBOMe. The 25C-NBOMe-induced alterations of rhythmic patterns were prevented by pre-treatment with selective serotonin 2A receptor antagonist MDL100,907. These results demonstrate that OFC rhythmic activity in HFO is relatively susceptible to substituted phenethylamine and potentially drives drug-induced rhythmic coherence within intra-prefrontal regions. Our findings provide additional insight into the neuropathophysiology of the psychoactive effects of psychedelics and indicate that the altered HFO might be applied as a potential biological marker of psychedelic effect.


Assuntos
Alucinógenos , Ratos , Masculino , Animais , Alucinógenos/farmacologia , Ratos Sprague-Dawley , Fenetilaminas/farmacologia , Suscetibilidade a Doenças , Córtex Pré-Frontal
7.
Chem Sci ; 14(2): 323-330, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36687347

RESUMO

Photo-induced reactive oxygen species (ROS) generation by organic photosensitizers (PSs), which show potential in significant fields such as photodynamic therapy (PDT), are highly dependent on the formation of the excited triplet state through intersystem crossing (ISC). The current research on ISC of organic PSs generally focuses on molecular structure optimization. In this manuscript, the influence of aggregation patterns on ISC was investigated by constructing homologous monomers (S-TPA-PI and L-TPA-PI) and their homologous dimers (S-2TPA-2PI and L-2TPA-2PI). In contrast to J-aggregated S-TPA-PI, S-2TPA-2PI-aggregate forming "end-to-end" stacking through π-π interaction could generate ROS more efficiently, due to a prolonged exciton lifetime and enhanced ISC rate constant (k ISC), which were revealed by femtosecond transient absorption spectroscopy and theoretical calculations. This finding was further validated by the regulation of aggregation patterns induced by host-guest interaction. Moreover, S-2TPA-2PI could target mitochondria and achieve rapid mitophagy to cause more significant cancer cell suppression. Overall, the delicate supramolecular dimerization tactics not only revealed the structure-property relationship of organic PSs but also shed light on the development of a universal strategy in future PDT and photocatalysis fields.

8.
Anal Chem ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626816

RESUMO

Development of an activated ratiometric indicator that is specific to plasma membrane (PM) viscosity exhibits great application prospects in disease diagnosis and treatment but remains a great challenge. Herein, a photo-activated fluorescent probe (CQ-IC) was designed and prepared tactfully, which could analyze and real-time monitor the microenvironmental homeostasis of the PM based on a two-channel ratiometric imaging model. Interestingly, upon light irradiation, CQ-IC generates reactive oxygen species and thus increases the cellular viscosity, which increases two emission peaks at 480 and 610 nm. This work would propose a new strategy to sensor PM homeostasis and effectively guide the treatment of viscosity-related diseases among various physiological and pathological processes.

9.
Anal Chem ; 94(39): 13396-13403, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36136967

RESUMO

Intracellular lipid storage and regulation occur in lipid droplets, which are of great significance to the physiological activities of cells. Herein, a lipid droplet-specific fluorescence probe (lip-YB) with a high quantum yield (QYlip-YB = 73.28%), excellent photostability, and quickly polarity sensitivity was constructed successfully. Interestingly, lip-YB exhibited remarkable two-photon (TP) characteristics, which first realized real-time monitoring of the lipid droplet multidynamics process, diagnosing nonalcoholic fatty liver disease (NAFLD) and inflammation in living mice via TP fluorescence imaging. It is found that the as-prepared lip-YB provides a new avenue to design lipid droplet-specific imaging probes, clarifies its roles and mechanisms in cell metabolism, and can timely intervene in lipid droplet-related diseases during various physiological and pathological processes.


Assuntos
Gotículas Lipídicas , Hepatopatia Gordurosa não Alcoólica , Animais , Corantes Fluorescentes/metabolismo , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Gotículas Lipídicas/metabolismo , Lipídeos , Camundongos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/metabolismo
10.
ACS Appl Bio Mater ; 5(7): 3554-3562, 2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35797702

RESUMO

The real-time and differentiated visualization of the organelles is favorable for exploring the distribution and interaction. However, most visual probes emit monochromatic fluorescence and target a single organelle, which impedes the in-depth study of their interplay. To overcome this obstacle, we tactfully conceived a polarity-sensitive fluorescent DPDO-C that could accurately discriminate polarity changes in the cellular environment, exhibiting distinct fluorescence in lipid droplets (LDs) and mitochondria. Remarkably, the probe DPDO-C could migrate from mitochondria to LDs with the assistance of reactive oxygen species, which was conducive to further monitoring of the number and size of LDs as well as the interactions between LDs and other organelles. Moreover, the nuanced difference between normal and fatty liver tissues was also distinguished by two-color fluorescence imaging, which could act as a promising candidate for the early diagnosis of fatty liver.


Assuntos
Fígado Gorduroso , Gotículas Lipídicas , Fígado Gorduroso/diagnóstico por imagem , Humanos , Microscopia de Fluorescência/métodos , Imagem Óptica , Espécies Reativas de Oxigênio
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 271: 120881, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35042042

RESUMO

Precise design of organic photosensitizers (PSs) promoted the technological innovation for multimodal imaging-guided synergistic therapy. Nonetheless, various group substitution could not only optimize the basic photophysical behavior, but possibly change the aggregate, which handicaps the deep understanding of the "Formula-Aggergete-Property" relationship. Bearing this in mind, herein two isomers, named 6-TDE and 7-TDE, were prepared via substituting position modification. Among them, 6-TDE exhibited the grid-like structure, while 7-TDE presented wavy-like structure. Despite the aggregates were different, 6-TDE and 7-TDE shared common features including partly twisted backbone and non-overlapped-orbit, hence resulting in similar optical physical behavior such as decent extinction coefficient, near-IR emission, large stockes shifts, etc. Meanwhile, though two PSs could both generated Type-I and Type-II ROS, 7-TDE possessed smaller singlet-triplet splitting (ΔEST), which exhibited favorable ROS as well as outstanding mitochondrial targeting, achieving efficient photodynamic therapy (PDT) effect. During this process, mitochondrial autophagy could be tracked and observed effectively and in real-time. Moreover, 7-TDE presented outstanding performance in multimodal imaging, including fluorescence imaging (FLI), photoacousticimaging (PAI) and photothermal imaging (PTI). This study enriches the strategy of precise molecular engineering to optimize theranostic agents.


Assuntos
Fotoquimioterapia , Nanomedicina Teranóstica , Imagem Óptica/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Medicina de Precisão , Nanomedicina Teranóstica/métodos
12.
Small ; 18(6): e2104857, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34850563

RESUMO

Photodynamic therapy (PDT) with organic photosensitizers generally goes through the oxygen-dependent process, generating singlet oxygen and/or superoxide anion. However, the generation of reactive oxygen species is often suppressed as a result of hypoxia, one of the common features in tumors, therefore limiting the effectiveness of the tumor treatments. Consequently, it is urgent and significant to develop an oxygen-independent hydroxyl radical photogenerator and unveil the mechanism. In this work, a hydroxyl radical (·OH) photogenerator originating from the electron transfer process is engineered. Detailed mechanism studies reveal that the optimized photosensitizer, WS2D, which contains a bithiophene unit, could both promote charge carrier generation and accelerate reaction efficiency, resulting in the efficient production of ·OH. In addition, WS2D nanoparticles are constructed to improve the polydispersity and stability in aqueous solution, which exhibit excellent biocompatibility and mitochondrial targeting. Bearing the above advantages, WS2D is employed in phototheranostics, which could release ·OH effectively and damage mitochondria precisely, achieving high PDT efficiency in vitro and in vivo. Overall, this work successfully provides valuable insights into the structural design of a hydroxyl radicals (·OH) photogenerator with great practical perspectives.


Assuntos
Radical Hidroxila , Fotoquimioterapia , Radical Hidroxila/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/química , Oxigênio Singlete
13.
Nat Commun ; 12(1): 3049, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031410

RESUMO

Photo-degradation of organic semiconductors remains as an obstacle preventing their durable practice in optoelectronics. Herein, we disclose that volume-conserving photoisomerization of a unique series of acceptor-donor-acceptor (A-D-A) non-fullerene acceptors (NFAs) acts as a surrogate towards their subsequent photochemical reaction. Among A-D-A NFAs with fused, semi-fused and non-fused backbones, fully non-fused PTIC, representing one of rare existing samples, exhibits not only excellent photochemical tolerance in aerobic condition, but also efficient performance in solar cells. Along with a series of in-depth investigations, we identify that the structural confinement to inhibit photoisomerization of these unique A-D-A NFAs from molecular level to macroscopic condensed solid helps enhancing the photochemical stabilities of molecules, as well as the corresponding OSCs. Although other reasons associating with the photostabilities of molecules and devices should not excluded, we believe this work provides helpful structure-property information toward new design of stable and efficient photovoltaic molecules and solar cells.

14.
Neuropsychopharmacology ; 46(5): 970-981, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33514875

RESUMO

Impaired glutamate homeostasis is a key characteristic of the neurobiology of drug addiction in rodent models and contributes to the vulnerability to relapse to drug seeking. Although disrupted astrocytic and presynaptic regulation of glutamate release has been considered to constitute with impaired glutamate homeostasis in rodent model of drug relapse, the involvement of endocannabinoids (eCBs) in this neurobiological process has remained largely unknown. Here, using cocaine self-administration in rats, we investigated the role of endocannabinoids in impaired glutamate homeostasis in the core of nucleus accumbens (NAcore), which was indicated by augmentation of spontaneous synaptic glutamate release, downregulation of metabotropic glutamate receptor 2/3 (mGluR2/3), and mGluR5-mediated astrocytic glutamate release. We found that the endocannabinoid, anandamide (AEA), rather than 2-arachidonoylglycerol elicited glutamate release through presynaptic transient receptor potential vanilloid 1 (TRPV1) and astrocytic cannabinoid type-1 receptors (CB1Rs) in the NAcore of saline-yoked rats. In rats with a history of cocaine self-administration and extinction training, AEA failed to alter synaptic glutamate release in the NAcore, whereas CB1R-mediated astrocytic glutamate release by AEA remained functional. In order to induce increased astrocytic glutamate release via exogenous AEA, (R)-methanandamide (methAEA, a metabolically stable form of AEA) was chronically infused in the NAcore via osmotic pumps during extinction training. Restoration of mGluR2/3 function and mGluR5-mediated astrocytic glutamate release was observed after chronic methAEA infusion. Additionally, priming or cue-induced reinstatement of cocaine seeking was inhibited in methAEA-infused rats. These results demonstrate that enhancing endocannabinoid signaling is a potential pathway to restore glutamate homeostasis and may represent a promising therapeutic strategy for preventing cocaine relapse.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Preparações Farmacêuticas , Animais , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Endocanabinoides , Extinção Psicológica , Ácido Glutâmico , Homeostase , Núcleo Accumbens , Ratos , Ratos Sprague-Dawley , Recidiva , Autoadministração
15.
ACS Appl Bio Mater ; 4(5): 4507-4521, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35006787

RESUMO

Chemodynamic therapy (CDT), as the emerging modality of cancer therapy based on Fenton or Fenton-like reactions, still suffers from low efficacy of hydroxyl radical generation, which requires full exposure of reaction sites of CDT nanoagents to intracellular H2O2. However, the amount of exposed reaction sites is severely restrained by the controlled size (<200 nm) and the limited specific surface area of nanoagents. Herein, we highlight the in-situ bloomed micrometer-scale CoMn-based layered double hydroxide (CoMn-LDH) ultrathin nanosheets, which are derived from CoMn boride-based CMB@ss-SF nanospheres in response to overexpressed glutathione (GSH) and dissolved oxygen in tumor microenvironment (TME), accomplishing intensive photothermal-enhanced CDT. The micrometer-scale CoMn-LDH ultrathin nanosheets would provide abundant reactive sites to accelerate heterogeneous Fenton-like reaction as well as GSH depletion, eliciting quick release of metal ions and further realizing intensive homogeneous Fenton-like reactions for ·OH generation. Moreover, the nanoagent can harvest 808 nm light into heat, which can be utilized to promote the CDT efficacy and realize photoacoustic imaging (PAI). Because of acidity and overexpressed GSH in TME, the nanoagent exhibited superior biodegradability. Benefiting from the synergistic advantages, CMB@ss-SF with negligible cytotoxicity completely eradicated the tumors in mouse. This work provides avenue for developing CDT nanoagents.


Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Terapia Fototérmica , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Feminino , Neoplasias Hepáticas/patologia , Teste de Materiais , Camundongos , Camundongos Endogâmicos ICR , Tamanho da Partícula , Técnicas Fotoacústicas , Microambiente Tumoral/efeitos dos fármacos
16.
Psychother Psychosom ; 90(2): 127-136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33152729

RESUMO

BACKGROUND: As the fight against the COVID-19 epidemic continues, medical workers may have allostatic load. OBJECTIVE: During the reopening of society, medical and nonmedical workers were compared in terms of allostatic load. METHODS: An online study was performed; 3,590 Chinese subjects were analyzed. Socio-demographic variables, allostatic load, stress, abnormal illness behavior, global well-being, mental status, and social support were assessed. RESULTS: There was no difference in allostatic load in medical workers compared to nonmedical workers (15.8 vs. 17.8%; p = 0.22). Multivariate conditional logistic regression revealed that anxiety (OR = 1.24; 95% CI 1.18-1.31; p < 0.01), depression (OR = 1.23; 95% CI 1.17-1.29; p < 0.01), somatization (OR = 1.20; 95% CI 1.14-1.25; p < 0.01), hostility (OR = 1.24; 95% CI 1.18-1.30; p < 0.01), and abnormal illness behavior (OR = 1.49; 95% CI 1.34-1.66; p < 0.01) were positively associated with allostatic load, while objective support (OR = 0.84; 95% CI 0.78-0.89; p < 0.01), subjective support (OR = 0.84; 95% CI 0.80-0.88; p < 0.01), utilization of support (OR = 0.80; 95% CI 0.72-0.88; p < 0.01), social support (OR = 0.90; 95% CI 0.87-0.93; p < 0.01), and global well-being (OR = 0.30; 95% CI 0.22-0.41; p < 0.01) were negatively associated. CONCLUSIONS: In the post-COVID-19 epidemic time, medical and nonmedical workers had similar allostatic load. Psychological distress and abnormal illness behavior were risk factors for it, while social support could relieve it.


Assuntos
Alostase/fisiologia , Ansiedade/fisiopatologia , COVID-19 , Depressão/fisiopatologia , Pessoal de Saúde , Comportamento de Doença/fisiologia , Satisfação Pessoal , Apoio Social , Estresse Psicológico/fisiopatologia , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ocupações
17.
Neuropharmacology ; 177: 108231, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32693006

RESUMO

Juvenile social isolation (SI) and neglect have a negative impact on neurodevelopment persistently, which is associated with cognitive dysfunction in neurodevelopmental disorders. Given the critical role of metabotropic glutamate receptors (mGluRs) in synaptic homeostasis of the prefrontal cortex (PFC), pharmacological intervention on mGluRs has been attempted in order to improve cognitive dysfunction in animal models of neurodevelopmental disorder, as well as in clinical trials. Here we examined the effects of the mGluR2/3 antagonist LY341495 on prefrontal synaptic transmission, spatial working memory, and recognition memory in adult C57BL/6J mice that experienced juvenile SI. We found that SI-reared mice exhibited working memory impairment and decreased excitatory presynaptic release probability of pyramidal neurons in the medial PFC compared with group-reared mice. The positive effect of LY341495 on excitatory synaptic transmission in SI-reared mice was more prominent than the effect in group-reared mice. A single treatment with mGluR2/3 antagonist LY341495 significantly improved the performance of SI-reared mice in the Y-maze test but not in the novel object recognition (NOR) test, while repeated treatments were effective in both tasks. These findings suggest that enhancing glutamatergic transmission via inhibition of mGluR2/3 signaling might represent a promising strategy for improving cognitive function in neurodevelopmental disorders.


Assuntos
Aminoácidos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Memória de Curto Prazo/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Isolamento Social/psicologia , Xantenos/farmacologia , Fatores Etários , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Glutamato Metabotrópico/metabolismo
18.
ACS Appl Mater Interfaces ; 12(14): 16700-16706, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32180394

RESUMO

The absorption of nonfullerene acceptors (NFAs) at near-infrared (NIR) regions is crucial for obtaining high current densities in organic solar cells (OSCs). Herein, two narrow-band gap NFAs with unfused backbones possessing broad (600-900 nm) and strong absorption are developed by the conjugation of a benzothiadiazole core to halogenated end groups through a cyclopentadithiophene bridge. Compared with the fluorinated counterpart BCDT-4F, the chlorinated NFA BCDT-4Cl shows stronger J-aggregation and closer molecular packing, leading to an optimized blend morphology when paired with the polymer donor, PBDB-T. Thus, an obvious improvement in external quantum efficiency response was obtained for BCDT-4Cl-based OSCs, presenting a higher efficiency of 12.10% than those (9.65%) based on BCDT-4F. This work provides a design strategy for NIR acceptors in the combination of electron-deficient core and halogenated terminal in unfused backbones, which results in not only fine-tuning the optoelectronic properties but also simplifying the synthetic complexities of molecules.

19.
Psychopharmacology (Berl) ; 236(11): 3281-3289, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31197434

RESUMO

RATIONALE: Juvenile social isolation (SI) and neglect is associated with a wide range of psychiatric disorders. While dysfunction of the corticolimbic pathway is considered to link various abnormal behaviors in SI models of schizophrenia, the enduring effects of early social deprivation on physiological properties of medium spiny neurons (MSNs) in nucleus accumbens (NAc) are not well understood. OBJECTIVES: This study investigated the impacts of juvenile SI on locomotor activity to methamphetamine (METH) and neurophysiological characteristics of MSNs in the core of NAc. METHODS: Socially isolated C57BL/6 mice experienced single housing for 4 weeks on postnatal day (PND) 21. The locomotor response to METH (1.0 mg/kg) was observed in both socially isolated and group-housed mice at PND 56. The effects of juvenile SI on the excitatory synaptic events in MSNs and the intrinsic excitability of MSNs in NAc core were investigated in other batches during PND 63-70. RESULTS: Socially isolated mice showed locomotor hypersensitivity to METH, although the expression of locomotor sensitization to METH in socially isolated mice was not different from group-housed mice. The recordings from MSNs of SI-reared mice exhibited higher frequency and smaller amplitude of miniature/spontaneous excitatory postsynaptic current than those from group-reared mice. Moreover, SI resulted in increased intrinsic excitability of MSNs in adult mice. CONCLUSIONS: These results demonstrate neuronal hyperactivity in the NAc of socially isolated mice, which could contribute to locomotor hypersensitivity to METH. Furthermore, the findings indicate a biological link between early negative life events and the vulnerability to psychostimulant-induced psychosis in adulthood.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Neurônios/efeitos dos fármacos , Núcleo Accumbens/citologia , Núcleo Accumbens/efeitos dos fármacos , Isolamento Social/psicologia , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Metanfetamina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neuritos/efeitos dos fármacos , Neuritos/fisiologia , Neurônios/fisiologia , Núcleo Accumbens/fisiologia , Gravidez
20.
Nat Commun ; 10(1): 2152, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31089140

RESUMO

The flexibility in structural design of organic semiconductors endows organic solar cells (OSCs) not only great function-tunabilities, but also high potential toward practical application. In this work, simple non-fused-ring electron acceptors are developed through two-step synthesis from single aromatic units for constructing efficient OSCs. With the assistance of non-covalent interactions, these rotatable non-fused acceptors (in solution) allow transiting into planar and stackable conformation in condensed solid, promoting acceptors not only feasible solution-processability, but also excellent film characteristics. As results, decent power conversion efficiencies of 10.27% and 13.97% can be achieved in single and tandem OSCs consisting of simple solution-cast blends, in which the fully unfused acceptors exhibit exceptionally low synthetic complexity index. In addition, the unfused acceptor and its based OSCs exhibit promising stabilities under continuous illumination. Overall, this work reveals valuable insights on the structural design of simple and effective electron acceptors with great practical perspectives.

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