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Duration of surgical general anaesthesia is associated with severe brain injury and neurological deficits. The specific mechanisms underlying post-general anaesthesia brain injury, however, still remain to be elucidated. Herein, we explore the role of microRNA-214 (miR-214) in the occurrence of brain injury after general anaesthesia and its underlying mechanism. Hippocampal tissues and neurons were isolated from rats exposed to 2% sevoflurane. TUNEL stains reflect hippocampal neuron apoptosis. Cultured hippocampal neurons stained with JC-1 and MitoTracker dyes were imaged by fluorescence microscope to visualize changes of mitochondrial membrane potential and mitochondrial fusion. Mitochondrial function was evaluated. Mitofusin 2 (Mfn2) binding to miR-214 or pyruvate kinase M2 (Pkm2) was confirmed by co-immunoprecipitation, immunofluorescence, dual luciferase reporter gene and RNA immunoprecipitation assays. After exposure to 2% sevoflurane, up-regulated miR-214 expression and impaired interaction between Mfn2 and Pkm2 were found in rat hippocampal tissues. Rats exposed to 2% sevoflurane also experienced neuronal injury, mitochondrial defects and deficits in the brain-derived neurotrophic factor (Bdnf) signalling. miR-214 was shown to target Mfn2 by impairing its binding with Pkm2. Inhibiting miR-214 expression using its specific inhibitor improved mitochondrial membrane potential, enhanced mitochondrial fusion, maintained mitochondrial function, restored interaction between Mfn2 and Pkm2, and activated the Bdnf signalling in cultured hippocampal neurons. Adenovirus infection of miR-214 inhibitor reduced neuron apoptosis and maintained mitochondrial function in the hippocampus of rats exposed to 2% sevoflurane. Taken together, the study demonstrates inhibition of miR-214 is cerebral protective against brain injury following general anaesthesia.
Assuntos
Anestesia Geral/efeitos adversos , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , GTP Fosfo-Hidrolases/metabolismo , MicroRNAs/genética , Dinâmica Mitocondrial , Proteínas Mitocondriais/metabolismo , Piruvato Quinase/metabolismo , Anestesia Geral/métodos , Animais , Lesões Encefálicas/prevenção & controle , Respiração Celular , Modelos Animais de Doenças , GTP Fosfo-Hidrolases/genética , Expressão Gênica , Regulação da Expressão Gênica , Hipocampo/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Oxirredução , Fosforilação Oxidativa , Ligação Proteica , Interferência de RNA , RatosRESUMO
The performance of perovskite nanocrystals (NCs) in optoelectronics and photocatalysis is severely limited by the presence of large amounts of crystal boundaries in NCs film that greatly restricts energy transfer. Creating heterostructures based on perovskite NCs and 2D materials is a common approach to improve the energy transport at the perovskite/2D materials interface. Herein, methylamine lead bromide (MAPbBr3 , MA: CH3 NH3 + ) perovskite NCs are homogeneously deposited on highly conductive few-layer MXene (Ti3 C2 Tx ) nanosheets to form heterostructures through an in situ solution growth method. An optimal mixed solvent ratio is essential to realize the growth of perovskite NCs on Ti3 C2 Tx nanosheets. Time-resolved photoluminescence spectroscopy, transient absorption spectroscopy, and the photoresponse of electron- and hole-only photoelectric conversion devices reveal the interfacial energy transfer behavior within MAPbBr3 /Ti3 C2 Tx heterostructures. The present investigation may provide a useful guide toward use of halide perovskite/2D material heterostructures in applications such as photocatalysis as well as optoelectronics.
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The cell-autonomous circadian clock regulates IgE- and IL-33-mediated mast cell activation, both of which are key events in the development of allergic diseases. Accordingly, clock modifiers could be used to treat allergic diseases, as well as many other circadian-related diseases, such as sleep and metabolic disorders. The nuclear receptors REV-ERB-α and -ß (REV-ERBs) are crucial components of the circadian clockwork. Efforts to pharmacologically target REV-ERBs using putatively specific synthetic agonists, particularly SR9009, have yielded beneficial effects on sleep and metabolism. Here, we sought to determine whether REV-ERBs are functional in the circadian clockwork in mast cells and, if so, whether SR9009 affects IgE- and IL-33-mediated mast cell activation. Bone marrow-derived mast cells (BMMCs) obtained from wild-type mice expressed REV-ERBs, and SR9009 or other synthetic REV-ERBs agonists affected the mast cell clockwork. SR9009 inhibited IgE- and IL-33-mediated mast cell activation in wild-type BMMCs in association with inhibition of Gab2/PI3K and NF-κB activation. Unexpectedly, these suppressive effects of SR9009 were observed in BMMCs following mutation of the core circadian gene Clock. These findings suggest that SR9009 inhibits IgE- and IL-33-mediated mast cell activation independently of the functional circadian clock activity. Thus, SR9009 or other synthetic REV-ERB agonists may have potential for anti-allergic agents.
Assuntos
Imunoglobulina E/metabolismo , Interleucina-33/antagonistas & inibidores , Mastócitos/efeitos dos fármacos , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/agonistas , Pirrolidinas/farmacologia , Receptores Citoplasmáticos e Nucleares/agonistas , Tiofenos/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Antialérgicos/farmacologia , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Relógios Circadianos/efeitos dos fármacos , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/metabolismo , Masculino , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sono/efeitos dos fármacosRESUMO
Despite the concerted efforts to directly probe the electron-electron (e-e) scattering mediated relaxation process in graphene using transient absorption spectroscopy, the initial sub-10 fs photoexcited carrier relaxation dynamics has remained elusive. Herein, we utilize a simple z-scan approach to elucidate this process and discern its mechanisms in CVD grown single layer graphene using femtosecond laser pulses with temporal pulse widths far longer than the relaxation time. We report the first experimental observation of e-e scattering lifetime shortening with increasing fluence, which had been theoretically predicted. Analysis from two-body Coulombic scattering suggests that Auger processes are essential relaxation channels in single layer graphene. Importantly, our straightforward approach on the graphene model system is applicable to the family of emergent layered materials.
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Nutrition and light-dark cycle influence rat testicular development. With 9% casein diet (low protein diet) under normal 12 h-12 h lighting cycles (9P), juvenile rat testes undergo normal growth. On the other hand, a low protein diet with constant darkness (D9P) results in a growth arrest of rat testes. Supplementation of cystine to the low protein diet under constant darkness (D9PC) had a tendency to increase testes weight, suggesting an improvement in growth suppression. Whether the growth suppression of testes in D9P is associated with suppression of spermatogenesis has not yet been shown. We aimed to determine the effect of a low protein diet and constant darkness with or without dietary cystine in testes using a histological technique. In the histological assessment, D9P testes showed a decreased number of seminiferous tubules with elongated spermatids, indicating a functional testicular defect in this group. However, cystine supplementation resulted in enhanced spermatogenesis versus control animals (D9PC vs. D9P) implying the importance of cystine to testicular development in this condition. Furthermore, serum testosterone concentration was increased in D9PC suggesting contribution of testosterone to ameliorate spermatogenesis. From these results, we conclude that cystine supplementation to a low protein diet under constant darkness promoted an increase in testosterone which in turn benefitted spermatogenesis.
Assuntos
Cistina , Escuridão/efeitos adversos , Dieta com Restrição de Proteínas/efeitos adversos , Espermatogênese/efeitos dos fármacos , Testosterona/metabolismo , Animais , Cistina/administração & dosagem , Cistina/farmacologia , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/farmacologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Testículo/efeitos dos fármacosRESUMO
Interleukin-33 (IL-33)/ST2-mediated mast cell activation plays important roles in the pathophysiology of allergic diseases. Hence, pharmacologically targeting the IL-33/ST2 pathway in mast cells could help to treat such diseases. We found that resveratrol inhibits IL-33/ST2-mediated mast cell activation. Resveratrol suppressed IL-33-induced IL-6, IL-13, and TNF-α production in mouse bone marrow-derived mast cells (BMMCs), mouse fetal skin-derived mast cells, and human basophils. Resveratrol also attenuated cytokine expression induced by intranasal administration of IL-33 in mouse lung. IL-33-mediated cytokine production in mast cells requires activation of the NF-κB and MAPK p38-MAPK-activated protein kinase-2/3 (MK2/3)-PI3K/Akt pathway, and resveratrol clearly inhibited IL-33-induced activation of the MK2/3-PI3K/Akt pathway, but not the NF-κB pathway, without affecting p38 in BMMCs. Importantly, resveratrol inhibited the kinase activity of MK2, and an MK2/3 inhibitor recapitulated the suppressive effects of resveratrol. Resveratrol and an MK2/3 inhibitor also inhibited IgE-dependent degranulation and cytokine production in BMMCs, concomitant with suppression of the MK2/3-PI3K/Akt pathway. These findings indicate that resveratrol inhibits both IL-33/ST2-mediated and IgE-dependent mast cell activation principally by targeting the MK2/3-PI3K/Akt axis downstream of p38. Thus, resveratrol may have potential for the prevention and treatment of broad ranges of allergic diseases.
Assuntos
Hipersensibilidade/tratamento farmacológico , Interleucina-33/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Resveratrol/farmacologia , Administração Intranasal , Animais , Basófilos/efeitos dos fármacos , Basófilos/imunologia , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Células Cultivadas , Modelos Animais de Doenças , Humanos , Hipersensibilidade/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/antagonistas & inibidores , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/administração & dosagem , Interleucina-33/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Pulmão/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Masculino , Mastócitos/imunologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Cultura Primária de Células , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resveratrol/uso terapêuticoRESUMO
In this work, 0-dimensional (0D) CsPbBr3 QDs were integrated with 2D bismuthene having ultrafast carrier mobility, to obtain a 0D/2D nanohybrid. Moreover, an excellent charge transfer efficiency (0.53) and an appreciable quenching constant of 2.3 × 105 M-1 were observed. Tuning the ratio of bismuthene in the Bi/perovskite nanohybrid achieved the quantified control of charge transfer efficiency and quenching performance at the interface.
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Although all-inorganic perovskite light emitting diodes (PeLED) have satisfactory stability under an ambient atmosphere, producing devices with high performance is challenging. A device architecture with a reduced energy barrier between adjacent layers and optimized energy level alignment in the PeLED is critical to achieve high electroluminescence efficiency. In this study, we report the optimization of a CsPbBr3-based PeLED device structure with Li-doped TiO2 nanoparticles as the electron transport layer (ETL). Optimal Li doping balances charge carrier injection between the hole transport layer (HTL) and ETL, leading to superior performance in both devices. The turn-on voltages for devices with Li-doped TiO2 nanoparticles were significantly reduced from 7.7 V to 4.9 V and from 3 V to 2 V in the direct and inverted PeLED structures, respectively. The low turn-on voltage for green emission is one of the lowest values among the reported CsPbBr3-based PeLEDs. Further investigations show that the device with an inverted structure is superior to the device with a direct structure because the energy barrier for carrier injection was minimized. The inverted structure devices exhibited a current efficiency of 5.6 cd A-1 for the pristine TiO2 ETL, while it was 15.2 cd A-1 for the Li-doped TiO2 ETL, a factor of â¼2.7 enhancement at 5000 cd m-2.
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Thanks to their tunability and versatility, the colloidal quantum dots (CQDs) made of II-VI semiconductor compound offer the potential to bridge the "green gap" in conventional semiconductors. However, when the CQDs are pumped to much higher initial excitonic states compared to their bandgap, multiexciton interaction is enhanced, leading to a much higher stimulated emission threshold. Here, to circumvent this drawback, for the first time, we show a fully colloidal gain in green enabled by a partially indirect pumping approach assisted by Förster resonance energy transfer process. By introducing the blue CQDs as exciton donors, the lasing threshold of the green CQDs, is reduced dramatically. The blue CQDs thus serve as an energy-transferring buffer medium to reduce excitation energy from pumping photons in a controlled way by injecting photoinduced excitons into green CQDs. Our newly developed colloidal pumping scheme could enable efficient CQD lasers of full visible colors by a single pump source and cascaded exciton transfer. This would potentially pave the way for an efficient multicolor laser for lighting and display applications.
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The performance of a photovoltaic device is strongly dependent on the light harvesting properties of the absorber layer as well as the charge separation at the donor/acceptor interfaces. Atomically thin two-dimensional transition metal dichalcogenides (2-D TMDCs) exhibit strong light-matter interaction, large optical conductivity, and high electron mobility; thus they can be highly promising materials for next-generation ultrathin solar cells and optoelectronics. However, the short optical absorption path inherent in such atomically thin layers limits practical applications. A heterostructure geometry comprising 2-D TMDCs (e.g., MoS2) and a strongly absorbing material with long electron-hole diffusion lengths such as methylammonium lead halide perovskites (CH3NH3PbI3) may overcome this constraint to some extent, provided the charge transfer at the heterostructure interface is not hampered by their band offsets. Herein, we demonstrate that the intrinsic band offset at the CH3NH3PbI3/MoS2 interface can be overcome by creating sulfur vacancies in MoS2 using a mild plasma treatment; ultrafast hole transfer from CH3NH3PbI3 to MoS2 occurs within 320 fs with 83% efficiency following photoexcitation. Importantly, our work highlights the feasibility of applying defect-engineered 2-D TMDCs as charge-extraction layers in perovskite-based optoelectronic devices.
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BACKGROUND: Estrogen plays an important role in the progression of ovarian cancer in humans. FOXP1 belongs to the forkhead/winged-helix transcription factor family, and previous research indicated that FOXP1 functioned as a tumor suppressor gene. FOXP1 may be similar to FOXA1 and is closely related to steroid hormone receptors, but the relationship between FOXP1 and ER currently remains unclear. METHODS: Ovarian tumors (60 malignant cases, 26 borderline cases, and 13 benign cases) and 14 normal ovarian tissues were collected retrospectively. Immunohistochemistry, western blotting and real-time PCR were used to characterize the expression patterns of FOXP1, ERα, and ERß both at the mRNA and protein levels. We also used co-immunoprecipitation and immunofluorescent colocalization to investigate whether a correlation exists between FOXP1 and ERα/ERß in ovarian cancer tissues. RESULTS: The mRNA level for FOXP1 and ERß in ovarian carcinoma tissues decreased, while the expression level of ERα mRNA increased compared with normal ovarian tissues. With an increase in the degree of ovarian carcinoma malignancy, the ERα expression level also increased. The expression pattern of ERß in ovarian neoplasms was similar to that of the FOXP1 protein; presenting nuclear staining decreased, while cytoplasmic expression increased. Colocalization of FOXP1, ERα, and ERß was present in the cytoplasm, with ERß specific co-localization with FOXP1 in the perinuclear area. While immunoprecipitates created with FOXP1 mouse anti-human monoclonal antibody showed a positive reaction to an anti-ER antibody, immunoprecipitates containing anti-ER antibody and react to anti-FOXP1 antibody. CONCLUSION: Interactions between FOXP1 and ER may play a pivotal role in the progression of ovarian cancer, and the activation or induction of FOXP1 and ERß expression in cancer cells may inhibit tumor proliferation.
Assuntos
Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Fatores de Transcrição Forkhead/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Proteínas Repressoras/genética , Western Blotting , Carcinoma Epitelial do Ovário , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Imunofluorescência , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunoprecipitação , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/metabolismo , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Semiconductor nanostructures (e.g., nanowires and nanobelts) hold great promise as subwavelength coherent light sources, nonlinear optical frequency converters, and all-optical signal processors for optoelectronic applications. However, at such small scales, optical second-harmonic generation (SHG) is generally inefficient. Herein, we report on a straightforward strategy using a thin Au layer to enhance the SHG from a single CdS nanobelt by 3 orders of magnitude. Through detailed experimental and theoretical analysis, we validate that the augmented SHG originates from the mutual intensification of the local fields induced by the plasmonic nanocavity and by the reflections within the CdS Fabry-Pérot resonant cavity in this hybrid semiconductor-metal system. Polarization-dependent SHG measurements can be employed to determine and distinguish the contributions of SH signals from the CdS nanobelt and gold film, respectively. When the thickness of gold film becomes comparable to the skin depth, SHG from the gold film can be clearly observed. Our work demonstrates a facile approach for tuning the nonlinear optical properties of mesoscopic, nanostructured, and layered semiconductor materials.
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The origins of performance enhancement in hybrid plasmonic organic photovoltaic devices are often embroiled in a complex interaction of light scattering, localized surface plasmon resonances, exciton-plasmon energy transfer and even nonplasmonic effects. To clearly deconvolve the plasmonic contributions from a single nanostructure, we herein investigate the influence of a single silver nanowire (NW) on the charge carriers in bulk heterojunction polymer solar cells using spatially resolved optical spectroscopy, and correlate to electrical device characterization. Polarization-dependent photocurrent enhancements with a maximum of â¼ 36% over the reference are observed when the transverse mode of the plasmonic excitations in the Ag NW is activated. The ensuing higher absorbance and light scattering induced by the electronic motion perpendicular to the NW long axis lead to increased exciton and polaron densities instead of direct surface plasmon-exciton energy transfer. Finite-difference time-domain simulations also validate these findings. Importantly, our study at the single nanostructure level explores the fundamental limits of plasmonic enhancement achievable in organic solar cells with a single plasmonic nanostructure.
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BACKGROUND: Induced pluripotent stem (iPS) cells efficiently generated from accessible tissues have the potential for clinical applications. Oral gingiva, which is often resected during general dental treatments and treated as biomedical waste, is an easily obtainable tissue, and cells can be isolated from patients with minimal discomfort. METHODOLOGY/PRINCIPAL FINDINGS: We herein demonstrate iPS cell generation from adult wild-type mouse gingival fibroblasts (GFs) via introduction of four factors (Oct3/4, Sox2, Klf4 and c-Myc; GF-iPS-4F cells) or three factors (the same as GF-iPS-4F cells, but without the c-Myc oncogene; GF-iPS-3F cells) without drug selection. iPS cells were also generated from primary human gingival fibroblasts via four-factor transduction. These cells exhibited the morphology and growth properties of embryonic stem (ES) cells and expressed ES cell marker genes, with a decreased CpG methylation ratio in promoter regions of Nanog and Oct3/4. Additionally, teratoma formation assays showed ES cell-like derivation of cells and tissues representative of all three germ layers. In comparison to mouse GF-iPS-4F cells, GF-iPS-3F cells showed consistently more ES cell-like characteristics in terms of DNA methylation status and gene expression, although the reprogramming process was substantially delayed and the overall efficiency was also reduced. When transplanted into blastocysts, GF-iPS-3F cells gave rise to chimeras and contributed to the development of the germline. Notably, the four-factor reprogramming efficiency of mouse GFs was more than 7-fold higher than that of fibroblasts from tail-tips, possibly because of their high proliferative capacity. CONCLUSIONS/SIGNIFICANCE: These results suggest that GFs from the easily obtainable gingival tissues can be readily reprogrammed into iPS cells, thus making them a promising cell source for investigating the basis of cellular reprogramming and pluripotency for future clinical applications. In addition, high-quality iPS cells were generated from mouse GFs without Myc transduction or a specific system for reprogrammed cell selection.