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1.
Hum Mol Genet ; 31(14): 2424-2437, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35181782

RESUMO

Variants in multiple lysosomal enzymes increase Parkinson's disease (PD) risk, including the genes encoding glucocerebrosidase (GCase), acid sphingomyelinase (ASMase) and galactosylceramidase. Each of these enzymes generates ceramide by hydrolysis of sphingolipids in lysosomes, but the role of this common pathway in PD pathogenesis has not yet been explored. Variations in GBA1, the gene encoding GCase, are the most common genetic risk factor for PD. The lysosomal enzyme cathepsin B has recently been implicated as an important genetic modifier of disease penetrance in individuals harboring GBA1 variants, suggesting a mechanistic link between these enzymes. Here, we found that ceramide activates cathepsin B, and identified a novel role for cathepsin B in mediating prosaposin cleavage to form saposin C, the lysosomal coactivator of GCase. Interestingly, this pathway was disrupted in Parkin-linked PD models, and upon treatment with inhibitor of ASMase which resulted in decreased ceramide production. Conversely, increasing ceramide production by inhibiting acid ceramidase activity was sufficient to upregulate cathepsin B- and saposin C-mediated activation of GCase. These results highlight a mechanistic link between ceramide and cathepsin B in regulating GCase activity and suggest that targeting lysosomal ceramide or cathepsin B represents an important therapeutic strategy for activating GCase in PD and related disorders.


Assuntos
Glucosilceramidase , Doença de Parkinson , Catepsina B/genética , Catepsina B/metabolismo , Ceramidas/metabolismo , Glucosilceramidase/genética , Glucosilceramidase/metabolismo , Humanos , Lisossomos/metabolismo , Doença de Parkinson/metabolismo , Saposinas/genética , Saposinas/metabolismo , alfa-Sinucleína/metabolismo
2.
Small ; 20(1): e2305289, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37649146

RESUMO

Green fuel from water splitting is hardcore for future generations, and the limited source of fresh water (<1%) is a bottleneck. Seawater cannot be used directly as a feedstock in current electrolyzer techniques. Until now single atom catalysts were reported by many synthetic strategies using notorious chemicals and harsh conditions. A cobalt single-atom (CoSA) intruding cobalt oxide ultrasmall nanoparticle (Co3 O4 USNP)-intercalated porous carbon (PC) (CoSA-Co3 O4 @PC) electrocatalyst was synthesized from the waste orange peel as a single feedstock (solvent/template). The extended X-ray absorption fine structure spectroscopy (EXAFS) and theoretical fitting reveal a clear picture of the coordination environment of the CoSA sites (CoSA-Co3 O4 and CoSA-N4 in PC). To impede the direct seawater corrosion and chlorine evolution the seawater has been desalinated (Dseawater) with minimal cost and the obtained PC is used as an adsorbent in this process. CoSA-Co3 O4 @PC shows high oxygen evolution reaction (OER) activity in transitional metal impurity-free (TMIF) 1 M KOH and alkaline Dseawater. CoSA-Co3 O4 @PC exhibits mass activity that is 15 times higher than the commercial RuO2 . Theoretical interpretations suggest that the optimized CoSA sites in Co3 O4 USNPs reduce the energy barrier for alkaline water dissociation and simultaneously trigger an excellent OER followed by an adsorbate evolution mechanism (AEM).

3.
Mol Psychiatry ; 27(8): 3272-3285, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35505090

RESUMO

Despite tremendous effort, the molecular and cellular basis of cognitive deficits in schizophrenia remain poorly understood. Recent progress in elucidating the genetic architecture of schizophrenia has highlighted the association of multiple loci and rare variants that may impact susceptibility. One key example, given their potential etiopathogenic and therapeutic relevance, is a set of genes that encode proteins that regulate excitatory glutamatergic synapses in brain. A critical next step is to delineate specifically how such genetic variation impacts synaptic plasticity and to determine if and how the encoded proteins interact biochemically with one another to control cognitive function in a convergent manner. Towards this goal, here we study the roles of GPCR-kinase interacting protein 1 (GIT1), a synaptic scaffolding and signaling protein with damaging coding variants found in schizophrenia patients, as well as copy number variants found in patients with neurodevelopmental disorders. We generated conditional neural-selective GIT1 knockout mice and found that these mice have deficits in fear conditioning memory recall and spatial memory, as well as reduced cortical neuron dendritic spine density. Using global quantitative phospho-proteomics, we revealed that GIT1 deletion in brain perturbs specific networks of GIT1-interacting synaptic proteins. Importantly, several schizophrenia and neurodevelopmental disorder risk genes are present within these networks. We propose that GIT1 regulates the phosphorylation of a network of synaptic proteins and other critical regulators of neuroplasticity, and that perturbation of these networks may contribute specifically to cognitive deficits observed in schizophrenia and neurodevelopmental disorders.


Assuntos
Proteínas de Ciclo Celular , Proteínas Ativadoras de GTPase , Esquizofrenia , Animais , Camundongos , Encéfalo/metabolismo , Proteínas de Ciclo Celular/genética , Cognição , Proteínas Ativadoras de GTPase/genética , Camundongos Knockout , Fosforilação , Esquizofrenia/genética , Sinapses/metabolismo
4.
Nano Lett ; 22(1): 286-293, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34978186

RESUMO

Self-assembled alkane layers are introduced between graphene layers to physically block nanometer size defects in graphene and lateral gas pathways between graphene layers. A well-defined hexatriacontane (HTC) monolayer on graphene could cover nanometer-size defects because of the flexible nature and strong intermolecular van der Waals interactions of alkane, despite the roughness of graphene. In addition, HTC multilayers between graphene layers greatly improve their adhesion. This indicates that HTC multilayers between graphene layers can effectively block the lateral pathway between graphene layers by filling open space with close-packed self-assembled alkanes. By these mechanisms, alternately stacked composites of graphene and self-assembled alkane layers greatly increase the gas-barrier property to a water vapor transmission rate (WVTR) as low as 1.2 × 10-3 g/(m2 day), whereas stacked graphene layers generally show a WVTR < 0.5 g/(m2 day). Furthermore, the self-assembled alkane layers have superior crystallinity and wide bandgap, so they have little effect on the transmittance.

5.
Nanotechnology ; 33(5)2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34673562

RESUMO

In this work, we synthesized a monolayer of graphene and hexagonal boron nitride (hBN) using chemical vapor deposition. The physicochemical and electrochemical properties of the materials were evaluated to determine their morphology. High-purity materials and their atomic-scale coating on copper (Cu) foil were employed to prevent fast degradation rate. The hexagonal two-dimensional (2D) atomic structures of the as-prepared materials were assessed to derive their best anti-corrosion behavior. The material prepared under optimized conditions included edge-defect-free graphene nanosheets (∼0.0034µm2) and hBN (∼0.0038µm2) per unit area of 1µm2. The coating of each material on the Cu surface significantly reduced the corrosion rate, which was âˆ¼2.44 × 10-2/year and 6.57 × 10-3/year for graphene/Cu and hBN/Cu, respectively. Importantly, the corrosion rate of Cu was approximately 3-fold lower after coating with hBN relative to that of graphene/Cu. This approach suggests that the surface coating of Cu using cost-effective, eco-friendly, and the most abundant materials in nature is of interest for developing marine anti-corrosion micro-electronic devices and achieving surface modification of pure metals in industrial applications.

6.
Hum Mol Genet ; 27(11): 1972-1988, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29579237

RESUMO

GBA1 encodes the lysosomal enzyme ß-glucocerebrosidase (GCase) which converts glucosylceramide into ceramide and glucose. Mutations in GBA1 lead to Gaucher's disease and are a major risk factor for Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), synucleinopathies characterized by accumulation of intracellular α-synuclein. In this study, we examined whether decreased ceramide that is observed in GCase-deficient cells contributes to α-synuclein accumulation. We demonstrated that deficiency of GCase leads to a reduction of C18-ceramide species and altered intracellular localization of Rab8a, a small GTPase implicated in secretory autophagy, that contributed to impaired secretion of α-synuclein and accumulation of intracellular α-synuclein. This secretory defect was rescued by exogenous C18-ceramide or chemical inhibition of lysosomal enzyme acid ceramidase that converts lysosomal ceramide into sphingosine. Inhibition of acid ceramidase by carmofur resulted in increased ceramide levels and decreased glucosylsphingosine levels in GCase-deficient cells, and also reduced oxidized α-synuclein and levels of ubiquitinated proteins in GBA1-PD patient-derived dopaminergic neurons. Together, these results suggest that decreased ceramide generation via the catabolic lysosomal salvage pathway in GCase mutant cells contributes to α-synuclein accumulation, potentially due to impaired secretory autophagy. We thus propose that acid ceramidase inhibition which restores ceramide levels may be a potential therapeutic strategy to target synucleinopathies linked to GBA1 mutations including PD and DLB.


Assuntos
Glucosilceramidase/genética , Doença de Parkinson/genética , alfa-Sinucleína/genética , Proteínas rab de Ligação ao GTP/genética , Autofagia/genética , Sistemas CRISPR-Cas/genética , Linhagem Celular , Ceramidas/genética , Ceramidas/metabolismo , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Edição de Genes , Expressão Gênica/genética , Glucosilceramidase/farmacocinética , Humanos , Doença por Corpos de Lewy/genética , Doença por Corpos de Lewy/patologia , Lisossomos/genética , Lisossomos/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Isoformas de Proteínas/genética
7.
Langmuir ; 36(20): 5563-5570, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32345023

RESUMO

Boron nitride (BN) nanofiller-based polymer composites have been considered promising candidates for efficient heat-dissipating packaging materials because of their superior thermal conductivity, mechanical strength, and chemical resistance. However, strong aggregation of the BN nanofillers in the composite matrix as well as the difficulty in the modification of the chemically inert surface prevents their effective use in polymer composites. Herein, we report an effective method by using in situ stabilizers to achieve homogeneous dispersion of boron nitride (BN) nanofillers in an epoxy-based polymeric matrix and demonstrate their use as efficient heat-dissipating materials. Poly(4-vinylpyridine) (P4VP) is designed and added into the epoxy resin to produce in situ stabilizers during preparation of hexagonal BNs (h-BNs) and BN nanotubes (BNNTs) dispersion. In-depth experimental and theoretical studies indicated that the homogeneous distribution of BN nanofillers in epoxy composites achieved by using the in situ stabilizer enhanced the thermal conductivity of the composite by ∼27% at the same concentration of the BN nanofillers. In addition, the thermal conductivity of the h-BN/epoxy composite (∼3.3 W/mK) was dramatically improved by ∼48% (4.9 W/mK) when the homogeneously dispersed BNNTs (∼1.8 vol %) were added. The concept of the proposed in situ stabilizer can be further utilized to prepare the epoxy composites with the homogeneous distribution of BN nanofillers, which is critical for reproducible and position-independent composite properties.

8.
Int J Mol Sci ; 21(4)2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32102322

RESUMO

Commercially available boron nitride nanotubes (BNNTs) and their purified form (pBNNTs) were dispersed in aqueous solutions with various dispersants, and their cytotoxicity and drug encapsulation capacity were monitored. Our data suggest that pBNNTs showed an average increase in dispersibility of 37.3% in aqueous solution in the presence of 10 different dispersants. In addition, 100 µg of pBNNTs induced an average decrease in cytotoxicity of 27.4% compared to same amount of BNNTs in normal cell lines. The same amount of pBNNTs can encapsulate 10.4-fold more drug (camptothecin) compared to BNNTs. These data suggest that the purification of BNNTs improves several of their properties, which can be applied to biological experiments and are thus essential in the biological application of BNNTs.


Assuntos
Compostos de Boro/química , Nanotecnologia/métodos , Nanotubos/química , Água/química , Células 3T3-L1 , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Compostos de Boro/isolamento & purificação , Compostos de Boro/farmacologia , Células CHO , Células CACO-2 , Camptotecina/química , Camptotecina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Composição de Medicamentos/métodos , Humanos , Camundongos
9.
Hum Mol Genet ; 26(4): 729-741, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28115417

RESUMO

TMEM230 is a newly identified Parkinson's disease (PD) gene encoding a transmembrane protein whose cellular and pathogenic roles remain largely unknown. Here, we demonstrate that loss of TMEM230 disrupts retromer cargo CI-M6PR (cation-independent mannose 6-phosphate receptor) trafficking and autophagic cargo degradation rates. TMEM230 depletion further inhibits extracellular secretion of the autophagic cargo p62 and immature lysosomal hydrolases in Golgi-derived vesicles leading to their intracellular accumulation, and is specifically mediated by loss of the small GTPase Rab8a. Importantly, PD-linked TMEM230 variants also induce retromer mislocalization, defective cargo trafficking, and impaired autophagy. Finally, we show that knockdown of another PD gene, LRRK2, which phosphorylates Rab8a, similarly impairs retromer trafficking, secretory autophagy and Golgi-derived vesicle secretion, thus demonstrating converging roles of two PD genes TMEM230 and LRRK2 on Rab8a function, and suggesting that retromer and secretory dysfunction play an important role in PD pathogenesis.


Assuntos
Complexo de Golgi/metabolismo , Proteínas de Membrana/metabolismo , Doença de Parkinson/metabolismo , Vesículas Secretórias/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Células COS , Chlorocebus aethiops , Complexo de Golgi/genética , Células HEK293 , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Proteínas de Membrana/genética , Doença de Parkinson/genética , Fosforilação/genética , Vesículas Secretórias/genética , Extratos do Timo , Proteínas rab de Ligação ao GTP/genética
10.
Sensors (Basel) ; 19(16)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31443298

RESUMO

N-containing gaseous compounds, such as trimethylamine (TMA), triethylamine (TEA), ammonia (NH3), nitrogen monoxide (NO), and nitrogen dioxide (NO2) exude irritating odors and are harmful to the human respiratory system at high concentrations. In this study, we investigated the sensing responses of five sensor materials-Al-doped ZnO (AZO) nanoparticles (NPs), Pt-loaded AZO NPs, a Pt-loaded WO3 (Pt-WO3) thin film, an Au-loaded WO3 (Au-WO3) thin film, and N-doped graphene-to the five aforementioned gases at a concentration of 10 parts per million (ppm). The ZnO- and WO3-based materials exhibited n-type semiconducting behavior, and their responses to tertiary amines were significantly higher than those of nitric oxides. The N-doped graphene exhibited p-type semiconducting behavior and responded only to nitric oxides. The Au- and Pt-WO3 thin films exhibited extremely high responses of approximately 100,000 for 10 ppm of triethylamine (TEA) and approximately -2700 for 10 ppm of NO2, respectively. These sensing responses are superior to those of previously reported sensors based on semiconducting metal oxides. On the basis of the sensing response results, we drew radar plots, which indicated that selective pattern recognition could be achieved by using the five sensing materials together. Thus, we demonstrated the possibility to distinguish each type of gas by applying the patterns to recognition techniques.

11.
J Anesth ; 32(6): 886-892, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30374890

RESUMO

PURPOSE: The purpose of this study was to determine whether intraoperative infusion of remifentanil induces acute tolerance to opioids, and compare the postoperative pain and opioid consumption by the effect site concentrations of remifentanil. METHODS: One hundred and ninety-eight patients undergoing gastrectomy were randomly assigned to maintain target effect site concentrations of remifentanil at 0 (Group 1, n = 39), 2 (Group 2, n = 40), 4 (Group 3, n = 39), 8 (Group 4, n = 40), or 12 ng/ml (Group 5, n = 40) during operation. Postoperative pain intensities and fentanyl requirement were recorded at postoperative 2, 6, 24, and 48 h. RESULTS: Fentanyl requirement for postoperative 2 h was significantly greater in Group 5 compared to Group 1 (376 ± 116 vs. 283 ± 129 µg, P = 0.03). However, there were no differences in fentanyl requirements among the groups after postoperative 2 h. Also, total fentanyl consumption for 48 h was similar in all groups (Group 1; 3106 ± 629, Group 2; 2970 ± 705, Group 3; 3017 ± 555, Group 4; 3151 ± 606, and Group 5; 2984 ± 443 µg, P = 0.717). Pain scores at rest and during deep breathing were comparable in all groups at the time of each examination. CONCLUSION: Intraoperative infusion of remifentanil with 12 ng/ml of effect site concentration in patients undergoing gastrectomy increases early postoperative fentanyl requirement. Acute opioid tolerance would be developed by higher concentration of remifentanil than dosage of common anesthetic practice.


Assuntos
Analgésicos Opioides/administração & dosagem , Gastrectomia/métodos , Dor Pós-Operatória/tratamento farmacológico , Remifentanil/administração & dosagem , Adulto , Idoso , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Fentanila/uso terapêutico , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos
12.
Nanotechnology ; 27(27): 275602, 2016 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-27232210

RESUMO

Using single-walled carbon nanotubes (SWCNTs) as nanomasks on an undoped GaN template, a significant biaxial stress relaxation was achieved in the subsequently-grown Si-doped n-GaN layer. Enhanced near band edge (NBE) emission intensity, similar free carrier concentrations, and the reduced peak width of the asymmetric (102) crystallographic plane all confirmed the suppression of threading dislocations due to the nanoepitaxial growth process. Temperature-dependent photoluminescence (PL) revealed improved internal quantum efficiency (IQE) of InGaN/GaN multi-quantum wells (MQWs) grown on this n-GaN layer. Furthermore, enhanced light output power and a remarkable reduction in efficiency droop were observed for the blue light-emitting diodes (LEDs), especially at higher injection currents. Our results emphasize the strong potential for SWCNTs as nanomasks in the heteroepitaxy of GaN-based devices without the exploitation of complicated lithography or etching processes.

13.
J Neurosci ; 33(29): 12122-35, 2013 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-23864697

RESUMO

Activity of glycogen synthase kinase-3ß (GSK-3ß) is required for long-term depression (LTD) via molecular mechanisms that are incompletely understood. Here, we report that PSD-95, a major scaffold protein of the postsynaptic density (PSD) that promotes synaptic strength, is phosphorylated on threonine-19 (T19) by GSK-3ß. In cultured rat hippocampal neurons, phosphorylation of T19 increases rapidly with chemical LTD and is attenuated by pharmacologic or genetic suppression of GSK-3ß. In organotypic rat hippocampal slices, we find that a nonphosphorylatable PSD-95 mutant (T19A) tagged with photoactivatable green fluorescent protein (PAGFP) shows enhanced stability in dendritic spines versus wild-type PSD-95, whereas the phosphomimetic mutant (PSD-95-T19D) is more readily dispersed. Further, overexpression of PSD-95-T19A, but not WT-PSD-95, impairs AMPA receptor internalization and the induction of LTD. These data indicate that phosphorylation on T19 by GSK-3ß destabilizes PSD-95 within the PSD and is a critical step for AMPA receptor mobilization and LTD.


Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Depressão Sináptica de Longo Prazo/fisiologia , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Sinapses/metabolismo , Treonina/metabolismo , Animais , Proteína 4 Homóloga a Disks-Large , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta , Células HEK293 , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Indóis/farmacologia , Cloreto de Lítio/farmacologia , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Maleimidas/farmacologia , Neurônios/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos , Receptores de AMPA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sinapses/efeitos dos fármacos
14.
Nanotechnology ; 25(44): 445601, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-25319609

RESUMO

Nitrogen-doped graphene synthesis with ∼g scale has been accomplished using the arc discharge method. The defects formed in the synthesis process were reduced by adding various metal catalysts, among which Bi2O3 was found to be the most effective. Adding dopants to the starting materials increased the electrical conductivity of the graphene product, and the doping concentration in graphene was tuned by adjusting the amount of nitrogen dopants. A step-wise technique to fabricate graphene thin films was developed, including dispersion, separation, and filtering processes. The arc graphene can also find its potential application in supercapacitors, taking advantage of its large surface area and improved conductivity by doping.

15.
Nanoscale ; 16(8): 3817-3837, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38327235

RESUMO

This review provides a comprehensive overview of the growth methodologies and neutron shielding applications of Boron Nitride Nanotubes (BNNTs). BNNTs have garnered significant attention because of their unique combination of high thermal stability, mechanical strength, and exceptional neutron absorption properties. Synthesis methods for BNNTs, including laser ablation, thermal plasma treatment, chemical vapour deposition (CVD), and ball milling have been thoroughly examined, highlighting their mechanisms, advantages, and challenges. Each method contributes uniquely to the quality and applicability of BNNTs in terms of scalability and production efficiency. This study focused on the applications of BNNTs in neutron absorption, particularly in aerospace engineering. BNNTs have shown promising potential in enhancing the safety and longevity of space missions by providing effective radiation protection. Furthermore, their potential in medical applications, particularly in Boron Neutron Capture Therapy (BNCT) for cancer treatment, has been explored. BNCT offers a targeted approach to cancer therapy by utilizing the high boron-10 content of BNNTs for precise and localized treatment. This review also provides an outlook on the future of BNNT research, emphasizing the need for more efficient growth methods to facilitate wider adoption and commercialization. The versatility of BNNTs across various fields, from space exploration to medical science, underscores their potential as materials of significant scientific and technological importance. As research progresses, BNNTs are expected to play a pivotal role in advancing materials science and offer innovative solutions to complex challenges.

16.
JCI Insight ; 9(3)2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329128

RESUMO

The glucocerebrosidase (GCase) encoded by the GBA1 gene hydrolyzes glucosylceramide (GluCer) to ceramide and glucose in lysosomes. Homozygous or compound heterozygous GBA1 mutations cause the lysosomal storage disease Gaucher disease (GD) due to severe loss of GCase activity. Loss-of-function variants in the GBA1 gene are also the most common genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Restoring lysosomal GCase activity represents an important therapeutic approach for GBA1-associated diseases. We hypothesized that increasing the stability of lysosomal GCase protein could correct deficient GCase activity in these conditions. However, it remains unknown how GCase stability is regulated in the lysosome. We found that cathepsin L, a lysosomal cysteine protease, cleaves GCase and regulates its stability. In support of these data, GCase protein was elevated in the brain of cathepsin L-KO mice. Chemical inhibition of cathepsin L increased both GCase levels and activity in fibroblasts from patients with GD. Importantly, inhibition of cathepsin L in dopaminergic neurons from a patient GBA1-PD led to increased GCase levels and activity as well as reduced phosphorylated α-synuclein. These results suggest that targeting cathepsin L-mediated GCase degradation represents a potential therapeutic strategy for GCase deficiency in PD and related disorders that exhibit decreased GCase activity.


Assuntos
Cisteína Proteases , Doença de Parkinson , Humanos , Animais , Camundongos , Glucosilceramidase/genética , Catepsina L/genética , Catepsina L/metabolismo , Catepsinas/metabolismo , Catepsinas/uso terapêutico , Cisteína Proteases/metabolismo , Cisteína Proteases/uso terapêutico , Doença de Parkinson/metabolismo , Lisossomos/metabolismo
17.
ACS Omega ; 8(24): 21514-21521, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37360428

RESUMO

Highly crystalline double-walled boron nitride nanotubes (DWBNNTs ∼60%) were synthesized from ammonia borane (AB; H3B-NH3) precursors using a high-temperature thermal plasma method. The differences between the synthesized BNNTs using the hexagonal boron nitride (h-BN) precursor and AB precursor were compared using various techniques such as thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, and in situ optical emission spectroscopy (OES). The synthesized BNNTs were longer and had fewer walls when the AB precursor was used than when the conventional method was used (with the h-BN precursor). The production rate significantly improved from ∼20 g/h (h-BN precursor) to ∼50 g/h (AB precursor), and the content of amorphous boron impurities was significantly reduced, implying a self-assembly mechanism of BN radicals rather than the conventional mechanism involving boron nanoballs. Through this mechanism, the BNNT growth, which was accompanied by an increased length, a decreased diameter, and a high growth rate, could be understood. The findings were also supported by in situ OES data. Considering the increased production yield, this synthesis method using AB precursors is expected to make an innovative contribution to the commercialization of BNNTs.

18.
ACS Appl Mater Interfaces ; 15(20): 24681-24692, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37163756

RESUMO

Microfiber fabrication via wet-spinning of lyotropic liquid crystals (LCs) with anisotropic nanomaterials has gained increased attention due to the microfibers' excellent physical/chemical properties originating from the unidirectional alignment of anisotropic nanomaterials along the fiber axis with high packing density. For wet-spinning of the microfibers, however, preparing lyotropic LCs by achieving high colloidal stability of anisotropic nanomaterials, even at high concentrations, has been a critically unmet prerequisite, especially for recently emerging nanomaterials. Here, we propose a cationically charged polymeric stabilizer that can efficiently be adsorbed on the surface of boron nitride nanotubes (BNNTs), which provide steric hindrance in combination with Coulombic repulsion leading to high colloidal stability of BNNTs up to 22 wt %. The BNNT LCs prepared from the dispersions with various stabilizers were systematically compared using optical and rheological analysis to optimize the phase behavior and rheological properties for wet-spinning of the BNNT LCs. Systematic optical and mechanical characterizations of the BNNT microfibers with aligned BNNTs along the fiber axis revealed that properties of the microfibers, such as their tensile strength, packing density, and degree of BNNT alignment, were highly dependent on the quality of BNNT LCs directly related to the types of stabilizers.

19.
Chemosphere ; 286(Pt 2): 131673, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34358889

RESUMO

In the field of nanotechnology, nanoadsorbents have emerged as a powerful tool for the purification of contaminated aqueous environments. Among the variety of nanoadsorbents developed so far, magnetite (Fe3O4) nanoparticles have drawn particular interest because of their quick separation, low cost, flexibility, reproducibility, and environmentally benign nature. Herein, we describe a new strategy for the synthesis of Fe3O4 nanoclusters, which is based on the use of naturally available edible mushrooms (Pleurotus eryngii) and environmentally benign propylene glycol as a solvent medium. By tuning the temperature, we successfully convert Fe3O4 nanoparticles into Fe3O4 nanoclusters via hydrothermal treatment, as evidenced by transmission electron microscopy. The Fe3O4 nanoclusters are functionalized with an organic molecule linker (dihydrolipoic acid, DHLA) to remove hazardous Hg(II) ions selectively. Batch adsorption experiments demonstrate that Hg(II) ions are strongly adsorbed on the material surface, and X-ray photoelectron and Fourier transform infrared spectroscopy techniques reveal the Hg(II) removal mechanism. The DHLA@Fe3O4 nanoclusters show a high removal efficiency of 99.2 % with a maximum Hg(II) removal capacity of 140.84 mg g-1. A kinetic study shows that the adsorption equilibrium is rapidly reached within 60 min and follows a pseudo second-order kinetic model. The adsorption and separation system can be readily recycled using an external magnet when the separation occurs within 10 s. We have studied the effect of various factors on the adsorption process, including pH, concentration, dosage, and temperature. The newly synthesized superparamagnetic DHLA@Fe3O4 nanoclusters open a new path for further development of the medical, catalysis, and environmental fields.


Assuntos
Nanopartículas de Magnetita , Mercúrio , Nanopartículas , Poluentes Químicos da Água , Purificação da Água , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Mercúrio/análise , Pleurotus , Reprodutibilidade dos Testes , Poluentes Químicos da Água/análise
20.
Nano Converg ; 9(1): 20, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35552898

RESUMO

Highly crystalline and few-walled boron nitride nanotubes (BNNTs) had been synthesized by laser ablation using only ammonia borane as a precursor. As a molecular precursor, ammonia borane supplied both B and N atoms with a ratio of 1:1, and BNNTs were formed via the homogeneous nucleation of BN radicals, not the growth from boron nano-droplets, which is a generally accepted growth mechanism of the laser-grown BNNTs. Owing to the absence of amorphous boron impurities, the van der Waals interaction among BNNTs became effective and thus a BNNT fibers was formed spontaneously during the BNNT synthesis. The BNNT growth and the subsequent fiber formation are found to occur only at high pressures of a surrounding gas. The mechanism behind the critical role of pressure was elucidated from the perspective of reaction kinetics and thermal fluid behaviors. A polarized Raman study confirmed that the BNNT fiber formed exhibits a good alignment of BNNTs, which implies great potential for continuous production of high-quality BNNT fibers for various applications.

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