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1.
Stroke ; 55(8): 2113-2125, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38965653

RESUMO

BACKGROUND: Neuronal apoptosis plays an essential role in the pathogenesis of brain injury after subarachnoid hemorrhage (SAH). BAP1 (BRCA1-associated protein 1) is considered to exert pro-apoptotic effects in multiple diseases. However, evidence supporting the effect of BAP1 on the apoptotic response to SAH is lacking. Therefore, we aimed to confirm the role of BAP1 in SAH-induced apoptosis. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect BAP1 expression in the cerebrospinal fluid. Endovascular perforation was performed in mice to induce SAH. Lentiviral short hairpin RNA targeting BAP1 mRNA was transduced into the ipsilateral cortex of mice with SAH to investigate the role of BAP1 in neuronal damage. Luciferase and coimmunoprecipitation assays were performed to investigate the mechanism through which BAP1 participates in hemin-induced SAH. RESULTS: First, BAP1 expression was upregulated in the cerebrospinal fluid of patients with SAH and positively associated with unfavorable outcomes. ATF2 (activating transcription factor-2) then regulated BAP1 expression by binding to the BAP1 promoter. In addition, BAP1 overexpression enhanced P53 activity and stability by reducing P53 proteasome-mediated degradation. Subsequently, elevated P53 promoted neuronal apoptosis via the P53 pathway. Inhibition of the neuronal BAP1/P53 axis significantly reduced neurological deficits and neuronal apoptosis and improved neurological dysfunction in mice after SAH. CONCLUSIONS: Our results suggest that the neuronal ATF2/BAP1 axis exerts a brain-damaging effect by modulating P53 activity and stability and may be a novel therapeutic target for SAH.


Assuntos
Apoptose , Neurônios , Hemorragia Subaracnóidea , Proteína Supressora de Tumor p53 , Proteínas Supressoras de Tumor , Ubiquitina Tiolesterase , Hemorragia Subaracnóidea/metabolismo , Animais , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Apoptose/fisiologia , Camundongos , Neurônios/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Humanos , Masculino , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Fator 2 Ativador da Transcrição/metabolismo , Fator 2 Ativador da Transcrição/genética , Transdução de Sinais/fisiologia , Camundongos Endogâmicos C57BL , Feminino , Pessoa de Meia-Idade
2.
Small ; : e2407204, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39434480

RESUMO

Windows offer the most promising avenue for mitigating energy consumption and reducing greenhouse gas emissions. However, the balance between comfortable natural lighting and all-season energy savings is often neglected in extensive explorations of energy-efficient windows. Herein, a Janus glazing is proposed that enables the switch of passive radiative cooling and heating under the precondition of conveying sufficient natural light. Measurement results indicate that the Janus window maintains a visible transmittance of 0.47, while possesses a near-infrared (NIR) reflectivity/absorptivity of 0.75/0.71 and a mid-infrared (MIR) emissivity of 0.94/0.13 for the cooling and heating modes, respectively. As demonstrated by the outdoor test, the Janus window realizes a reduction of 7.1 °C for room cooling and an increase of 0.4 °C for room heating compared with commercial low-e window, potentially conserving 13%-53% of the total building energy consumption across China. Meanwhile, attributed to the photothermal effect, the Janus window can elevate the surface temperature by 6.1 °C compared with the low-e window, which can effectively reduce fogging occurrences on the window surface for ensuring sunlight entrance in the cold-weather conditions. This strategy offers novel prospects for enhancing energy efficiency in diverse applications, including architectural windows, greenhouse cultivation, photovoltaic generation, etc.

3.
J Phys Chem A ; 128(5): 880-894, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38271995

RESUMO

Dye sensitizers with wideband absorption covering the near-IR region have long been of interest because they potentially harvest a wide range of solar energies essential to promote photocurrent power conversion efficiencies. In this study, we used time-dependent density functional theory with spin-orbit (SO) interactions to theoretically explore the long-wavelength absorptions and spin-forbidden triplet transitions activated by SO interactions for terpyridyl ruthenium/osmium complex dyes. These dyes feature a Ru(II) sensitizer coordinated with a phosphine ligand and are exemplified by DX1, denoted as [trans-dichloro-(phenyldimethoxyphosphine)(2,2';6',2″-terpyridyl-4,4',4″-tricarboxylic)Ru]. We found that ancillary ligands significantly affected the longest wavelength spin-allowed absorption, with NCS- ligands yielding longer wavelength S1 transitions than halides. High atomic number halide ligands caused blue shifts in the S1 transition. Os complexes consistently exhibited longer wavelength S1 transitions than Ru complexes with identical ligands. In Ru/Os complexes, ancillary ligands with higher atomic numbers have a more pronounced effect in activating spin-forbidden triplet transitions through spin-orbit coupling (SOC) than those with lower atomic numbers. The absorption wavelength of the SOC-activated transition primarily depended on the energy of lower lying triplet states. Some complexes exhibited T1 states activated by SOC, leading to longer wavelength absorption than that of SOC-activated T2 states. Our study revealed the significance of ancillary ligands and SOC interactions in Ru/Os complexes, offering insights for optimizing materials with enhanced long-wavelength absorption properties, particularly in the near-IR range, for photovoltaic and optoelectronic applications.

4.
Mol Psychiatry ; 27(7): 3034-3046, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35422468

RESUMO

Atherosclerosis (ATH) and Alzheimer's disease (AD) are both age-dependent inflammatory diseases, associated with infiltrated macrophages and vascular pathology and overlapping molecules. C/EBPß, an Aß or inflammatory cytokine-activated transcription factor, and AEP (asparagine endopeptidase) are intimately implicated in both ATH and AD; however, whether C/EBPß/AEP signaling couples ATH to AD pathogenesis remains incompletely understood. Here we show that C/EBPß/AEP pathway mediates ATH pathology and couples ATH to AD. Deletion of C/EBPß or AEP from primary macrophages diminishes cholesterol load, and inactivation of this pathway reduces foam cell formation and lesions in aorta in ApoE-/- mice, fed with HFD (high-fat-diet). Knockout of ApoE from 3xTg AD mouse model augments serum LDL and increases lesion areas in the aorta. Depletion of C/EBPß or AEP from 3xTg/ApoE-/- mice substantially attenuates these effects and elevates cerebral blood flow and vessel length, improving cognitive functions. Strikingly, knockdown of ApoE from the hippocampus of 3xTg mice decreases the cerebral blood flow and vessel length and aggravates AD pathologies, leading to cognitive deficits. Inactivation of C/EBPß/AEP pathway alleviates these events and restores cognitive functions. Hence, our findings demonstrate that C/EBPß/AEP signaling couples ATH to AD via mediating vascular pathology.


Assuntos
Doença de Alzheimer , Aterosclerose , Proteína beta Intensificadora de Ligação a CCAAT , Doença de Alzheimer/metabolismo , Animais , Aterosclerose/complicações , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Knockout para ApoE
5.
Gut ; 71(11): 2233-2252, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017199

RESUMO

OBJECTIVE: This study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer's disease (AD) pathogenesis. DESIGN: We analysed the gut microbiota composition of 3×Tg mice in an age-dependent manner. We generated germ-free 3×Tg mice and recolonisation of germ-free 3×Tg mice with fecal samples from both patients with AD and age-matched healthy donors. RESULTS: Microbial 16S rRNA sequencing revealed Bacteroides enrichment. We found a prominent reduction of cerebral amyloid-ß plaques and neurofibrillary tangles pathology in germ-free 3×Tg mice as compared with specific-pathogen-free mice. And hippocampal RNAseq showed that inflammatory pathway and insulin/IGF-1 signalling in 3×Tg mice brain are aberrantly altered in the absence of gut microbiota. Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. AD patients' gut microbiome exacerbated AD pathologies in 3×Tg mice, associated with C/EBPß/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors' microbiota transplants. CONCLUSIONS: These findings support that a complex gut microbiome is required for behavioural defects, microglia activation and AD pathologies, the gut microbiome contributes to pathologies in an AD mouse model and that dysbiosis of the human microbiome might be a risk factor for AD.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Insulinas , Doença de Alzheimer/metabolismo , Animais , Cognição , Modelos Animais de Doenças , Disbiose , Ácidos Graxos Insaturados , Microbioma Gastrointestinal/fisiologia , Humanos , Inflamação/metabolismo , Fator de Crescimento Insulin-Like I , Camundongos , Doenças Neuroinflamatórias , Placa Amiloide/patologia , RNA Ribossômico 16S
6.
J Enzyme Inhib Med Chem ; 34(1): 1158-1163, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31179772

RESUMO

Even though phenazines have been extensively reported as anticancer molecules, the molecular target of these compounds is severely lagging behind. Our study consequently focuses on the anticancer target of a phenazine analogue (CPUL1) for its potently antitumor activities in initial stage. Along with redox status courses of Hep G2 cells, thioredoxin reductase I (TrxR1) was speculated as anticancer target of CPUL1. By virtue of zymologic, immunological and molecular biological experiments, we demonstrated that TrxR1 could be the anticancer target of CPUL1. The knowledge on phenazine targeting to TrxR1 have not been reported previously. Thus, it can provide valuable information for further development of the TrxR1 inhibitors.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Fenazinas/química , Fenazinas/farmacologia , Tiorredoxina Redutase 1/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Células Hep G2 , Humanos , Modelos Moleculares , Estrutura Molecular , Fenazinas/síntese química , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Tiorredoxina Redutase 1/metabolismo
7.
Neuropsychopharmacology ; 49(3): 620-630, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38030711

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease with cognitive dysfunction as its major clinical symptom. However, there is no disease-modifying small molecular medicine to effectively slow down progression of the disease. Here, we show an optimized asparagine endopeptidase (AEP, also known as δ-secretase) inhibitor, #11 A, that displays an orderly in vivo pharmacokinetics/pharmacodynamics (PK/PD) relationship and robustly attenuates AD pathologies in a sporadic AD mouse model. #11 A is brain permeable with great oral bioavailability. It blocks AEP cleavage of APP and Tau dose-dependently, and significantly decreases Aß40 and Aß42 and p-Tau levels in APP/PS1 and Tau P301S mice after oral administration. Notably, #11 A strongly inhibits AEP and prevents mouse APP and Tau fragmentation by AEP, leading to reduction of mouse Aß42 (mAß42), mAß40 and mouse p-Tau181 levels in Thy1-ApoE4/C/EBPß transgenic mice in a dose-dependent manner. Repeated oral administration of #11 A substantially decreases mAß aggregation as validated by Aß PET assay, Tau pathology, neurodegeneration and brain volume reduction, resulting in alleviation of cognitive impairment. Therefore, our results support that #11 A is a disease-modifying preclinical candidate for pharmacologically treating AD.


Assuntos
Doença de Alzheimer , Cisteína Endopeptidases , Doenças Neurodegenerativas , Camundongos , Animais , Doença de Alzheimer/patologia , Proteínas tau , Camundongos Transgênicos , Peptídeos beta-Amiloides , Modelos Animais de Doenças
8.
Polymers (Basel) ; 16(18)2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39339111

RESUMO

There is a growing trend in incorporating biomass-based engineered nanomaterials into food products to enhance their quality and functionality. The zeta potential, droplet size, microstructure, and content of free fatty acid (FFA) release were determined to investigate the influence of a plant-derived particle stabilizer, i.e., lignin-containing cellulose nanofibrils (LCNFs). Remarkable differences were observed during digestion stages, which were found to be correlated with the concentrations of LCNFs. The gradual FFA release in the small intestine stage from LCNF-coated lipid droplets was monitored over time, with a final lowest release of FFAs amounting to 26.3% in the emulsion containing 20.0% (v/v) of the dispersed phase stabilized by 3 mg/mL of LCNFs. This release can be attributed to the physical barrier at lipid droplet surfaces and the network effect created by the free LCNFs in the continuous phase. This work provides a foundation for the potential application of nature-derived LCNF materials in reducing fat absorbance.

9.
ACS Omega ; 9(27): 29379-29390, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39005832

RESUMO

Herein, we explored the oxidative coupling reactions of carbazole-based polycyclic aromatic hydrocarbons using traditional Scholl reactions and electrochemical oxidation. Our findings indicate that the oxidation predominantly occurs at the carbazole functional group. The underlying reaction mechanisms were also clarified through theoretical investigations, highlighting that the primary oxidation pathway involves the 3,6-positions of the carbazole moiety, which is attributable to its high electron density.

10.
Chemosphere ; 352: 141351, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340997

RESUMO

The efficient and ecofriendly removal of pharmaceutical antibiotics and heavy metal Cr(VI) from water sources is a crucial challenge in current environmental management. Photocatalysis presents a viable environmentally friendly solution for eliminating organic contaminants and heavy-metal ions. In this study, a novel S-scheme CuInS2/ZnIn2S4 (CIS/ZIS) heterojunction was developed using a one-pot solvothermal method. The optimized CIS/ZIS heterojunction exhibited considerably improved photocatalytic activity for the removal of antibiotics and Cr(VI), achieving over 90% removal for both tetracycline hydrochloride (TC) (20 mg/L) and Cr(VI) (20 mg/L) under visible light irradiation. The study also delved into the effect of coexisting inorganic anions and assessed the cyclic stability of the composite photocatalysts. This enhancement mechanism can be delineated into three key elements. First, the incorporation of the narrow-gap semiconductor CuInS2 effectively augmented the photoabsorption capacity. Second, the inclusion of ZnIn2S4 caused an increase in surface active sites. Most importantly, the internal electric field at the interface between CuInS2 and ZnIn2S4 expedited the separation of photogenerated carriers. Furthermore, the results revealed that superoxide radical and photogenerated holes are the primary active substance responsible for TC removal, while photogenerated electrons play a central role in the photoreduction of Cr(VI). To gain insights into the transport pathways of photogenerated carriers, we conducted experiments with nitrotetrazolium blue chloride (NBT) and photodeposited gold. This study offers an innovative approach to enhancing the photocatalytic performance of ternary In-based materials by constructing S-scheme heterojunctions.


Assuntos
Antibacterianos , Cromo , Eletricidade , Elétrons
11.
Front Mol Neurosci ; 17: 1459858, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39498265

RESUMO

Depression is one of the most common affective disorders in people's life. Women are susceptibility to depression during puberty, peripartum and menopause transition, when they are suffering from sex hormone fluctuation. A lot of studies have demonstrated the neuroprotective effect of estrogen on depression in women, however, the effect of FSH on depression is unclear. In this study, we investigated the role of FSH on depression in mice. Our study demonstrated that FSH induced depression-like behaviors in mice in a dose-dependent manner. This induction was associated with elevated levels of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α in both serum and hippocampal tissues. Additionally, FSH treatment resulted in impaired synaptic plasticity and a reduction in the expression of key synaptic proteins. It is noteworthy that the depression-like behaviors, inflammatory cytokines expression and synaptic plasticity impairment induced by FSH could be alleviated by knocking down the expression of FSH receptor (FSHR) in the hippocampus of the mice. Therefore, our findings reveal that FSH may play an important role in the pathogenesis of depression and targeting FSH may be a potential therapeutic strategy for depression during hormone fluctuation in women.

12.
Adv Sci (Weinh) ; : e2407235, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316380

RESUMO

Accurately predicting the power conversion efficiency (PCE) in dye-sensitized solar cells (DSSCs) represents a crucial challenge, one that is pivotal for the high throughput rational design and screening of promising dye sensitizers. This study presents precise, predictive, and interpretable machine learning (ML) models specifically designed for Zn-porphyrin-sensitized solar cells. The model leverages theoretically computable, effective, and reusable molecular descriptors (MDs) to address this challenge. The models achieve excellent performance on a "blind test" of 17 newly designed cells, with a mean absolute error (MAE) of 1.02%. Notably, 10 dyes are predicted within a 1% error margin. These results validate the ML models and their importance in exploring uncharted chemical spaces of Zn-porphyrins. SHAP analysis identifies crucial MDs that align well with experimental observations, providing valuable chemical guidelines for the rational design of dyes in DSSCs. These predictive ML models enable efficient in silico screening, significantly reducing analysis time for photovoltaic cells. Promising Zn-porphyrin-based dyes with exceptional PCE are identified, facilitating high-throughput virtual screening. The prediction tool is publicly accessible at https://ai-meta.chem.ncu.edu.tw/dsc-meta.

13.
RSC Adv ; 13(4): 2501-2513, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36741182

RESUMO

A series of π-extended salophen-type Schiff-base zinc(ii) complexes, e.g., zinc-salophen complexes (ZSC), were investigated toward potential applications for dye-sensitized solar cells. The ZSC dyes adopt linear-, X-, or π-shaped geometries either with the functionalization of 1 donor/1 acceptor or 2 donors/2 acceptors to achieve a push-pull type molecular structure. The frontier molecular orbitals, light-harvesting properties as well as charge transfer characters against regio-specific substitution of donor/acceptor groups were studied by using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results reveal that all ZSC dyes of D-ZnS-π-A geometry (where D, S, and A denote to donor, salophen ligand, and acceptor, respectively) exhibit relatively lower HOMO energy compared to the structurally resembled porphyrin dye YD2-o-C8. Natural transition orbital (NTO) and electron-hole separation (EHS) approaches clearly differentiate the linear type YD-series dyes from CL-, AJ1-, and AJ2-series dyes because of poor charge transfer (CT) properties. In contrast, the π-shaped AJ2-series and X-shaped AJ1-series dyes outperform the others in a manner of stronger CT characteristics, broadened UV-vis absorption as well as tunable bandgap simply via substitution of p-ethynylbenzoic acids (EBAs) and arylamine donors at salophen 7,8- and 2,3,12,13-positions, respectively. Both EHS and calculated exciton binding energies suggest the strength of CT character for ZSC dyes with an amino donor in the trend TPA > AN > DPA. This work has provided clear illustration toward molecular design of efficient dyes featuring a zinc-salophen backbone.

14.
ACS Appl Mater Interfaces ; 15(13): 16953-16962, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36867759

RESUMO

Artificial camouflage has garnered long-standing interest in both academia and industry. The metasurface-based cloak has attracted much attention due to the powerful capability of manipulating the electromagnetic wave, convenient multifunctional integration design, and easy fabrication. However, existing metasurface-based cloaks tend to be passive and of single function and monopolarization, which cannot meet the requirement of applications in ever-changing environments. So far, it is still challenging to realize a reconfigurable full-polarization metasurface cloak with multifunctional integration. Herein, we proposed an innovative metasurface cloak, which can simultaneously realize dynamic illusion effects at lower frequencies (e.g., 4.35 GHz) and specific microwave transparency at higher frequencies (e.g., X band) for communication with the outside environment. These electromagnetic functionalities are demonstrated by both numerical simulations and experimental measurements. The simulation and measurement results agree well with each other, indicating that our metasurface cloak can generate various electromagnetic illusions for full polarizations as well as a polarization-insensitive transparent window for the signal transmission to enable the communication between the cloaked device and the outside environment. It is believed that our design can offer powerful camouflage tactics to address the stealth problem in ever-changing environments.

15.
Quant Imaging Med Surg ; 13(1): 293-308, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36620177

RESUMO

Background: Moyamoya disease (MMD) is a teratogenic and lethal disease. However, existing studies do not sufficiently indicate the impact factors. Therefore, we investigated the different impact factors on cerebral hemodynamics after revascularization in patients with MMD. Methods: We retrospectively collected the clinical data of 233 adult patients with MMD who underwent revascularization surgery in the Department of Neurosurgery, Renmin Hospital of Wuhan University, from January 2015 to June 2021 for this retrospective cohort study. We analyzed the effects on hemodynamic improvement of age, sex, stroke type, early symptoms, Suzuki stage, history of hypertension, history of diabetes, and history of hyperlipidemia in patients with MMD. We also evaluated the efficacy of different revascularization strategies and we verified the effect of computed tomography perfusion (CTP) in evaluating cerebral hemodynamics. Results: The CTP values demonstrated that δ cerebral blood volume (CBV) values were significantly higher in the combined group [1.01 (0.87-1.75)] relative to those in the indirect group [1.34 (1.01-1.63); P=0.027]. There was no statistical significance in the improvement of clinical symptoms and clinical prognosis between the indirect and combined groups. Patients with MMD with diabetes [δ mean transit time (MTT), 0.49 (0.35-0.70) vs. 0.72 (0.52-0.87); P<0.001] or calcium channel blocker (CCB) [δCBV, 1.46 (1.10-1.83) vs. 1.12 (0.93-1.54); P=0.001] had better cerebral hemodynamics than patients in non-diabetic group or non-CCB group after revascularization. Conclusions: We didn't find differences in clinical outcome between indirect and combined revascularization in patients with MMD. we demonstrated that CTP values can be used as a way to detect postoperative cerebral hemodynamic changes in MMD patients. Interestingly, we found that MMD patients with diabetes or CCB showed better cerebral perfusion after revascularization.

16.
Nat Commun ; 14(1): 6577, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37852961

RESUMO

Alzheimer's disease (AD) is the most common dementia. It is known that women with one ApoE4 allele display greater risk and earlier onset of AD compared with men. In mice, we previously showed that follicle-stimulating hormone (FSH), a gonadotropin that rises in post-menopausal females, activates its receptor FSHR in the hippocampus, to drive AD-like pathology and cognitive impairment. Here we show in mice that ApoE4 and FSH jointly trigger AD-like pathogenesis by activating C/EBPß/δ-secretase signaling. ApoE4 and FSH additively activate C/EBPß/δ-secretase pathway that mediates APP and Tau proteolytic fragmentation, stimulating Aß and neurofibrillary tangles. Ovariectomy-provoked AD-like pathologies and cognitive defects in female ApoE4-TR mice are ameliorated by anti-FSH antibody treatment. FSH administration facilitates AD-like pathologies in both young male and female ApoE4-TR mice. Furthermore, FSH stimulates AD-like pathologies and cognitive defects in ApoE4-TR mice, but not ApoE3-TR mice. Our findings suggest that in mice, augmented FSH in females with ApoE4 but not ApoE3 genotype increases vulnerability to AD-like process by activating C/EBPß/δ-secretase signalling.


Assuntos
Doença de Alzheimer , Animais , Feminino , Masculino , Camundongos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Apolipoproteína E3/genética , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Hormônio Foliculoestimulante , Camundongos Transgênicos
17.
Nat Commun ; 13(1): 4820, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35973996

RESUMO

Brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B receptor (TrkB) are expressed in human osteoblasts and mediate fracture healing. BDNF/TrkB signaling activates Akt that phosphorylates and inhibits asparagine endopeptidase (AEP), which regulates the differentiation fate of human bone marrow stromal cells (hBMSC) and is altered in postmenopausal osteoporosis. Here we show that R13, a small molecular TrkB receptor agonist prodrug, inhibits AEP and promotes bone formation. Though both receptor activator of nuclear factor kappa-Β ligand (RANK-L) and osteoprotegerin (OPG) induced by ovariectomy (OVX) remain comparable between WT and BDNF+/- mice, R13 treatment significantly elevates OPG in both mice without altering RANKL, blocking trabecular bone loss. Strikingly, both R13 and anti-RANK-L exhibit equivalent therapeutic efficacy. Moreover, OVX increases RANK-L and OPG in WT and AEP KO mice with RANK-L/OPG ratio lower in the latter than the former, attenuating bone turnover. 7,8-DHF, released from R13, activates TrkB and its downstream effector CREB, which is critical for OPG augmentation. Consequently, 7,8-DHF represses C/EBPß/AEP pathway, inhibiting RANK-L-induced RAW264.7 osteoclastogenesis. Therefore, our findings support that R13 exerts its therapeutic efficacy toward osteoporosis via inhibiting AEP and escalating OPG.


Assuntos
Osteoprotegerina , Pró-Fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo , Proteínas de Transporte , Cisteína Endopeptidases , Feminino , Humanos , Camundongos , NF-kappa B , Osteoclastos/fisiologia , Pró-Fármacos/farmacologia , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Receptor trkB
18.
Adv Sci (Weinh) ; 9(22): e2201054, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35666027

RESUMO

With rapid development of radar and infrared (IR) surveillance technologies, the need for microwave-IR compatible camouflage is now more than ever. Here, a novel multispectral metadevice is proposed to simultaneously achieve microwave scattering reduction, dynamic IR camouflage, and low IR reflection. This metadevice is constructed by the coding thermoelectric elements with the properly designed phase arrangement, and the incident microwave energy can be redirected to the nonthreatening directions for specular reflection reduction. The dynamic IR camouflage with low IR reflection is realized by using the thermoelectric cooling and heating effect and high-IR-absorptivity surface. The above three functionalities are demonstrated by experimental measurement. The 10 dB scattering reduction can be realized at the microwave band of 10-16.1 GHz. In the IR region, the designed metadevice can not only dynamically modulate the surface temperature for matching different background temperatures, but also realize the pixel temperature control for adapting to a spatially varying thermal background. In addition, it reflects almost no surrounding thermal signals compared with the traditional low-emissivity IR stealth material. This study paves an effective way to achieve microwave-IR compatible camouflage, which may inspire the future researches and applications in multispectral camouflage and stealth fields.

19.
Environ Pollut ; 306: 119450, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35561800

RESUMO

Biodegradable cellulosic pulp foams with robustness and water resistance are urgently needed in nowadays to replace petroleum-based plastic foams for environmental sustainability. In this work, a facile protocol to fabricate robust poly-lactic acid (PLA) coated cellulose foams (PCCF) was developed through a combined water-based foaming and PLA melt-coating process using pulp as the raw material. In the synthesis, the so-called PLA coating was realized through melting PLA powders dispersed between fibers by an in-situ heating and post cooling process. Performance tests revealed that the incorporation of PLA coating significantly enhances mechanical strength, water stability, and biodegradability of the synthesized PCCF samples compared with conventional cellulosic foams. Specifically, the low-density PCCF were observed with mechanical strength up to 81.24 kPa, high water stability, and more than 95% degradation in 56 days. As the fabrication process is simple and pulp is highly cost competitive, our proposed synthesis strategy makes the PCCF a promising substitute for petroleum-based plastic foams at large-scale production.


Assuntos
Petróleo , Plásticos , Ácido Láctico , Poliésteres , Temperatura , Água
20.
Polymers (Basel) ; 14(8)2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35458333

RESUMO

In this work, two novel tetra-substituted X-shaped molecules X1 and X2 that were constructed with anthracene as the central core and arylamine as the donor groups have been synthesized. The HTMs X1 and X2 were synthesized in two steps from industrially accessible and moderately reasonable beginning reagents. These new HTMs are described in terms of utilization of light absorption, energy level, thermal properties, hole mobility (µh), and film-forming property. The photovoltaic performances of these HTMs were effectively assessed in perovskite solar cells (PSCs). The devices based on these HTMs accomplished an overall efficiency of 16.10% for X1 and 10.25% for X2 under standard conditions (AM 1.5 G and 100 mW cm-2). This precise investigation provides another perspective on the use of HTMs in PSCs with various device configurations.

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