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1.
Int J Mol Sci ; 24(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36835140

RESUMO

Transthyretin (TTR) aggregation and amyloid formation are associated with several ATTR diseases, such as senile systemic amyloidosis (SSA) and familial amyloid polyneuropathy (FAP). However, the mechanism that triggers the initial pathologic aggregation process of TTR remains largely elusive. Lately, increasing evidence has suggested that many proteins associated with neurodegenerative diseases undergo liquid-liquid phase separation (LLPS) and subsequent liquid-to-solid phase transition before the formation of amyloid fibrils. Here, we demonstrate that electrostatic interactions mediate LLPS of TTR, followed by a liquid-solid phase transition, and eventually the formation of amyloid fibrils under a mildly acidic pH in vitro. Furthermore, pathogenic mutations (V30M, R34T, and K35T) of TTR and heparin promote the process of phase transition and facilitate the formation of fibrillar aggregates. In addition, S-cysteinylation, which is a kind of post-translational modification of TTR, reduces the kinetic stability of TTR and increases the propensity for aggregation, while another modification, S-sulfonation, stabilizes the TTR tetramer and reduces the aggregation rate. Once TTR was S-cysteinylated or S-sulfonated, they dramatically underwent the process of phase transition, providing a foundation for post-translational modifications that could modulate TTR LLPS in the context of pathological interactions. These novel findings reveal molecular insights into the mechanism of TTR from initial LLPS and subsequent liquid-to-solid phase transition to amyloid fibrils, providing a new dimension for ATTR therapy.


Assuntos
Amiloide , Transição de Fase , Pré-Albumina , Humanos , Amiloide/química , Amiloide/metabolismo , Neuropatias Amiloides Familiares/metabolismo , Proteínas Amiloidogênicas/química , Proteínas Amiloidogênicas/metabolismo , Mutação , Pré-Albumina/química , Pré-Albumina/metabolismo
2.
ACS Appl Mater Interfaces ; 16(1): 943-956, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38146938

RESUMO

All-solid-state batteries (ASSBs) have attracted much attention in the fields of energy storage, electric vehicles, and portable electronic devices due to their safety and high energy density. Ni-rich layered ternary materials (LiNi1-y-zCoyMnzO2, 1 - y - z ≥ 0.7) are considered to be among the most promising candidates for cathode materials in ASSBs due to their unique advantages. Nevertheless, the interfacial chemical reaction between the ternary cathode (NCM) and solid-state electrolytes (SSEs) has become the main issue to limit the long-cycle stability of the cathode. Relative studies have shown that when NCM materials are in direct contact with sulfide-based SSEs, byproducts generated by the interfacial chemical reaction accumulate at the interface, resulting in increasing interfacial impedance. However, up to now, the formation mechanism of the NCM/SSE interfacial chemical reaction, as well as its properties and evolution process, still lacks detailed characterization. In this paper, batteries at different stages during the long-cycling process are characterized to reveal the dynamic evolution process of the chemical reaction from the cathode-electrolyte interface to the interior of the particle and to determine the chemical reaction effect on the irreversible degradation of the battery capacity. On this basis, a surface coating of LiNbO3 is adopted to establish a passivation protection layer at the cathode-electrolyte interface. The coated battery has been subjected to 2000 charge/discharge cycles at a rate of 1 C and achieved a capacity retention rate of up to 82%.

3.
ArXiv ; 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37808091

RESUMO

While significant advancements in artificial intelligence (AI) have catalyzed progress across various domains, its full potential in understanding visual perception remains underexplored. We propose an artificial neural network dubbed VISION, an acronym for "Visual Interface System for Imaging Output of Neural activity," to mimic the human brain and show how it can foster neuroscientific inquiries. Using visual and contextual inputs, this multimodal model predicts the brain's functional magnetic resonance imaging (fMRI) scan response to natural images. VISION successfully predicts human hemodynamic responses as fMRI voxel values to visual inputs with an accuracy exceeding state-of-the-art performance by 45%. We further probe the trained networks to reveal representational biases in different visual areas, generate experimentally testable hypotheses, and formulate an interpretable metric to associate these hypotheses with cortical functions. With both a model and evaluation metric, the cost and time burdens associated with designing and implementing functional analysis on the visual cortex could be reduced. Our work suggests that the evolution of computational models may shed light on our fundamental understanding of the visual cortex and provide a viable approach toward reliable brain-machine interfaces.

4.
Front Bioeng Biotechnol ; 10: 908431, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845395

RESUMO

The recent decline of the international biodiesel industry has led to decreased production and therefore increased the price of glycerol, which is a major by-product of biodiesel but a substrate for production of 3-hydroxypropionic acid (3-HP), that is, glycerol as a feedstock has no advantage over glucose in price. Hence, we engineered glucose to the glycerol pathway and improved 3-HP production by CRISPR interference (CRISPRi). To begin with, we cloned the genes encoding glycerol 3-phosphate dehydrogenase (gpd1) and glycerol 3-phosphatase (gpp2) from Saccharomyces cerevisiae, which jointly catalyze glucose into glycerol. The genes gpd1 and gpp2 were co-expressed in K. pneumoniae with the dCas9 gene integrated in genome, and this recombinant strain produced 2 g/L glycerol in the shake flask. To minimize the glucose consumption by competing pathways including the EMP pathway, glycerol oxidation pathway, and by-products pathways, we developed an CRISPRi system in aforementioned recombinant K. pneumoniae strain to inhibit the expression of the glyceraldehyde-3-phosphate dehydrogenase gene (gapA) and 2,3-butanediol production gene (budA), resulting in a bi-functional strain harboring both glucose-to-glycerol pathway and CRISPRi system. Reverse transcription and quantitative PCR (RT-qPCR) results showed that this engineered CRISPRi system transcriptionally inhibited gapA and budA by 82% and 24%, respectively. In shake flask cultivation, this bi-functional strain produced 2.8 g/L glycerol using glucose as the carbon source, which was 46.6% increase compared to the strain without the engineered CRISPRi system. Moreover, this bi-functional strain produced 0.78 g/L 3-HP using glucose as the sole carbon source. In fed-batch cultivation, this bi-functional strain produced 1.77 g/L 3-HP. This study provides insights for co-utilization of distinct carbon sources.

5.
ACS Appl Mater Interfaces ; 14(50): 55491-55502, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36503239

RESUMO

Developments in electric vehicles and mobile electronic devices are promoting the demand for lithium-ion batteries with higher capacity and longer lifetime. The performances of lithium-ion batteries are crucially affected by cathode materials, among which ternary cathode materials are the most competitive option with the advantages of high capacity, safety, and cost-effectiveness. However, although high-nickel ternary cathode materials can achieve relatively high specific capacity, they generally have unsatisfactory stability during long-term cycling. In this study, the microscopic mechanisms of the cathode failure and the principle of coating modification in lithium-ion batteries have been comprehensively examined. It has been revealed that the irreversible capacity fading is mainly attributed to the interface chemical reaction, which reduces the transition-metal valence states and generates undesired disordered rock-salt phases. This structural phase transformation at the interface induces the dissolution of transition metals and results in irreversible capacity loss of the cathode. To restrain the occurrence of this process, a LiNbO3 coating-modified single-crystal LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode material has been prepared. The electrochemical properties as well as the microstructural evolution of the cathode-electrolyte interface during cycling of both the uncoated and coated samples have been comprehensively characterized and compared through impedance spectroscopy testing, SEM-EDX, STEM, and EELS characterization. Additionally, molecular dynamics simulation results confirmed that LiNbO3 coating can effectively inhibit the dissolution of transition metals while providing stable lithium-ion channels. The experimental results also indicate that the coating modification can effectively improve the cycling stability of the NCM811, with the capacity retention rate for 500 cycles increasing from 19% to 70%. This study is helpful to deepen the understanding of the capacity fading mechanisms, and the coating method is effective at maintaining the structural stability and improving the cycle life of lithium-ion batteries.

6.
Huan Jing Ke Xue ; 40(1): 126-134, 2019 Jan 08.
Artigo em Zh | MEDLINE | ID: mdl-30628267

RESUMO

A 660 MW unit of an ultra-low emission coal-fired power plant in the Beijing-Tianjin-Hebei area was chosen for this study. The particulate matter was sampled with a Dekati low-pressure impactor (DPLI) at the inlet and outlet of flue gas cleaning devices including selective catalytic reduction (SCR), low-low temperature economizer (LLTe), electrostatic precipitator (ESP), wet flue gas desulfurization (WFGD), and wet electrostatic precipitator (WESP). A filter sampling system was also used at the inlet and outlet of the WFGD and WESP. The removal efficiencies of PM1, PM1-2.5, and PM2.5-10 from different flue gas cleaning devices were obtained after ultra-low emission modification. The results show that SCR increases the mass concentration of fine particulates and PM1 by 52.11%. The LLTe improves the removal efficiency of the ESP, especially for particles with a range of 0.1-1 µm. The high-efficiency WFGD removes both SO2 and particulates, but it increases PM1. The mass concentration of PM1 increases by 59.41% and the water-soluble Mg2+, Cl-, and SO42- in PM10 increases. The WESP has a high removal efficiency with respect to PM1, PM1-2.5, and PM2.5-10 and can further reduce the dust concentration. Based on an ultra-low emission reform, the final PM10 emission of this 660 MW unit is 2.04 mg·m-3.

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