Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 264
Filtrar
1.
Small ; : e2311086, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459647

RESUMO

Despite the low competitive cost and high theoretical capacity of lithium-sulfur (Li-S) batteries, their practical application is severely hindered by the lithium polysulfide (LiPS) shuttling and low conversion efficiency. Herein, the electronic structure of hollow Titanium dioxide nanospheres is tunned by single Iron atom dopants that can cooperatively enhance LiPS absorption and facilitate desired redox reaction in practical Li-S batteries, further suppressing the notorious shuttle effect, which is consistent with theoretical calculations and in situ UV/vis investigation. The obtained electrode with massive active sites and lower energy barrier for sulfur conversions exhibits exceptional cycling stability after 500 cycles and high capacity under the sulfur loading of 10.53 mg cm-2 . In particular, an Ah-level Li-S pouch cell is fabricated, further demonstrating that the synthetic strategy based on atomic-level design offers a promising route toward practical high-energy-density Li-S batteries.

2.
Nanomicro Lett ; 16(1): 162, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530476

RESUMO

Zinc-air batteries (ZABs) are promising energy storage systems because of high theoretical energy density, safety, low cost, and abundance of zinc. However, the slow multi-step reaction of oxygen and heavy reliance on noble-metal catalysts hinder the practical applications of ZABs. Therefore, feasible and advanced non-noble-metal electrocatalysts for air cathodes need to be identified to promote the oxygen catalytic reaction. In this review, we initially introduced the advancement of ZABs in the past two decades and provided an overview of key developments in this field. Then, we discussed the working mechanism and the design of bifunctional electrocatalysts from the perspective of morphology design, crystal structure tuning, interface strategy, and atomic engineering. We also included theoretical studies, machine learning, and advanced characterization technologies to provide a comprehensive understanding of the structure-performance relationship of electrocatalysts and the reaction pathways of the oxygen redox reactions. Finally, we discussed the challenges and prospects related to designing advanced non-noble-metal bifunctional electrocatalysts for ZABs.

3.
Proc Natl Acad Sci U S A ; 121(8): e2319581121, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38349883

RESUMO

The Tibetan Plateau, recognized as Earth's third pole and among the most responsive regions to climate shifts, profoundly influences regional and even global hydrological processes. Here, we discerned a significant weakening in the influence of temperature on the initiation of surface freeze-thaw cycle (the Start of Thawing, SOT), which can be ascribed to a multitude of climatic variables, with radiation emerging as the most pivotal factor. Additionally, we showed that the diminishing impact of warming on SOT yields amplified soil moisture within the root zone. This, in turn, fosters a greening third pole with increased leaf area index and solar-induced chlorophyll fluorescence. We further showed that current Earth system models failed to reproduce the linkage between weakened sensitivity and productivity under various shared socioeconomic pathways. Our findings highlight the dynamic shifts characterizing the influence of climate warming on spring freeze-thaw process and underscore the profound ecological implications of these changes in the context of future climate scenarios.

4.
Nanoscale Adv ; 6(2): 578-589, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38235078

RESUMO

Lithium-sulfur (Li-S) batteries are attracting tremendous attention owing to their critical advantages, such as high theoretical capacity of sulfur, cost-effectiveness, and environment-friendliness. Nevertheless, the vast commercialisation of Li-S batteries is severely hindered by sharp capacity decay upon operation and shortened cycle life because of the insulating nature of sulfur along with the solubility of intermediate redox products, lithium polysulfides (LiPSs), in electrolytes. This work proposes the use of multifunctional Ni/NiO-embedded carbon nanofibers (Ni/NiO@CNFs) synthesized by an electrospinning technique with the corresponding heat treatment as promising free-standing current collectors to enhance the kinetics of LiPS redox reactions and to provide prolonged cyclability by utilizing more efficient active materials. The electrochemical performance of the Li-S batteries with Ni/NiO@CNFs with ∼2.0 mg cm-2 sulfur loading at 0.5 and 1.0C current densities delivered initial specific capacities of 1335.1 mA h g-1 and 1190.4 mA h g-1, retrieving high-capacity retention of 77% and 70% after 100 and 200 cycles, respectively. The outcomes of this work disclose the beneficial auxiliary effect of metal and metal oxide nanoparticle embedment onto carbon nanofiber mats as being attractively suited up to achieve high-performance Li-S batteries.

5.
FASEB J ; 38(1): e23365, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38069862

RESUMO

CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily and expressed in both normal and malignant lymphoid cells. However, the role of CD30 in lymphopoiesis is not known. In this study, we showed CD30 was expressed both in T and B cells, but its deficiency in mice had no effect on T- and B-cell development. In fact, CD30 deficiency attenuated B-cell response to T-cell-dependent antigens. The impaired B cell response in CD30-deficient mice is caused by the reduction of activation-induced cytidine deaminase (AID) expression. Moreover, CD30-deficient mice exhibited decreased TCR-mediated T cell proliferation and slightly impaired TCR signaling. High-throughput RNA sequencing analysis revealed that CD30 deficiency led to a decrease of FOXO-autophagy axis in T cells upon TCR stimulation. Thus, CD30 positively regulates T-cell-dependent immune response and T cell proliferation.


Assuntos
Antígeno Ki-1 , Ativação Linfocitária , Linfócitos T , Animais , Camundongos , Proliferação de Células , Antígeno Ki-1/genética , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia
6.
Materials (Basel) ; 16(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37959577

RESUMO

Due to its extremely high theoretical mass specific capacity, silicon is considered to be the most promising anode material for lithium-ion batteries (LIBs). However, serious volume expansion and poor conductivity limit its commercial application. Herein, dealloying treatments of spray dryed Al-Si-Cu-Ni particles are performed to obtain a Cu/Ni co-doped Si-based anode material with a porous nanowire network structure. The porous structure enables the material to adapt to the volume changes in the cycle process. Moreover, the density functional theory (DFT) calculations show that the co-doping of Cu and Ni can improve the capture ability towards Li, which can accelerate the electron migration rate of the material. Based on the above advantages, the as-prepared material presents excellent electrochemical performance, delivering a reversible capacity of 1092.4 mAh g-1 after 100 cycles at 100 mA g-1. Even after 500 cycles, it still retains 818.7 mAh g-1 at 500 mA g-1. This study is expected to provide ideas for the preparation and optimization of Si-based anodes with good electrochemical performance.

7.
Molecules ; 28(21)2023 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-37959744

RESUMO

Aldehyde dehydrogenase-2 (ALDH2) is a crucial enzyme participating in intracellular aldehyde metabolism and is acknowledged as a potential therapeutic target for the treatment of alcohol use disorder and other addictive behaviors. Using previously reported ALDH2 inhibitors of Daidzin, CVT-10216, and CHEMBL114083 as reference molecules, here we perform a ligand-based virtual screening of world-approved drugs via 2D/3D similarity search methods, followed by the assessments of molecular docking, toxicity prediction, molecular simulation, and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis. The 2D molecular fingerprinting of ECFP4 and FCFP4 and 3D molecule-shape-based USRCAT methods show good performances in selecting compounds with a strong binding behavior with ALDH2. Three compounds of Zeaxanthin (q = 0), Troglitazone (q = 0), and Sequinavir (q = +1 e) are singled out as potential inhibitors; Zeaxanthin can only be hit via USRCAT. These drugs displayed a stronger binding strength compared to the reported potent inhibitor CVT-10216. Sarizotan (q = +1 e) and Netarsudil (q = 0/+1 e) displayed a strong binding strength with ALDH2 as well, whereas they displayed a shallow penetration into the substrate-binding tunnel of ALDH2 and could not fully occupy it. This likely left a space for substrate binding, and thus they were not ideal inhibitors. The MM-PBSA results indicate that the selected negatively charged compounds from the similarity search and Vina scoring are thermodynamically unfavorable, mainly due to electrostatic repulsion with the receptor (q = -6 e for ALDH2). The electrostatic attraction with positively charged compounds, however, yielded very strong binding results with ALDH2. These findings reveal a deficiency in the modeling of electrostatic interactions (in particular, between charged moieties) in the virtual screening via the 2D/3D similarity search and molecular docking with the Vina scoring system.


Assuntos
Reposicionamento de Medicamentos , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Ligantes , Zeaxantinas
8.
Leukemia ; 37(11): 2261-2275, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37670087

RESUMO

The highly conserved MicroRNA-9 (miR-9) family consists of three members. We discovered that miR-9-1 deletion reduced mature miR-9 expression, causing 43% of the mice to display smaller size and postweaning lethality. MiR-9-1-deficient mice with growth defects experienced severe lymphopenia, but other blood cells were unaffected. The lymphopenia wasn't due to defects in hematopoietic progenitors, as mutant bone marrow (BM) cells underwent normal lymphopoiesis after transplantation into wild-type recipients. Additionally, miR-9-1-deficient mice exhibited impaired osteoblastic bone formation, as mutant mesenchymal stem cells (MSCs) failed to differentiate into osteoblastic cells (OBs). RNA sequencing revealed reduced expression of master transcription factors for osteoblastic differentiation, Runt-related transcription factor 2 (Runx2) and Osterix (Osx), and genes related to collagen formation, extracellular matrix organization, and cell adhesion, in miR-9-1-deficient MSCs. Follistatin (Fst), an antagonist of bone morphogenetic proteins (BMPs), was found to be a direct target of miR-9-1. Its deficiency led to the up-regulation of Fst, inhibiting BMP signaling in MSCs, and reducing IL-7 and IGF-1. Thus, miR-9-1 controls osteoblastic regulation of lymphopoiesis by targeting the Fst/BMP/Smad signaling axis.


Assuntos
Linfopenia , MicroRNAs , Animais , Camundongos , Linfopoese/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular , MicroRNAs/genética , MicroRNAs/metabolismo , Osteogênese/genética , Osteoblastos/metabolismo
9.
Clin Anat ; 2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37596915

RESUMO

Several reports have shown a coincidence relationship between perforators and acupoints. However, there have been few previous reports of objective experimental methods to verify the reliability of the accuracy of acupoint location (APL) with nearby perforators. This research aimed to determine the internal agreement of the APL of five acupuncturists and to analyze the coincidence rate of acupoints with nearby perforators. Three two healthy volunteers were recruited with the inclusion and exclusion criteria. Three TCM clinical physicians determined acupoints in areas of the lower limb of participants. Two microsurgeons sketched corresponding regions based on the most common skin flap operation sites, located bone markers, and drew the skin flap axis. Doppler ultrasound was used to mark the perforator point and the distances measured for both points. There is no significant difference in the distance between the acupoints and perforators localization in different groups, and there are significant differences between the angle formed by acupoints and penetrators in all groups. All the points located by the traditional Chinese medicine (TCM) therapists are distributed around the dot. The distance between the coordinate point (A-B) of Wenliu (LI7) localization is the largest, reaching 16.6 mm. The accuracy of the acupoint location of each physician is limited by the clinical experience of physicians, and the difference among them is significant. There is a certain correspondence between the location of acupoints and perforators, which needs further studies to confirm.

10.
Angew Chem Int Ed Engl ; 62(42): e202306901, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37302981

RESUMO

The sluggish sulfur redox kinetics and shuttle effect of lithium polysulfides (LiPSs) are recognized as the main obstacles to the practical applications of the lithium-sulfur (Li-S) batteries. Accelerated conversion by catalysis can mitigate these issues, leading to enhanced Li-S performance. However, a catalyst with single active site cannot simultaneously accelerate multiple LiPSs conversion. Herein, we developed a novel dual-defect (missing linker and missing cluster defects) metal-organic framework (MOF) as a new type of catalyst to achieve synergistic catalysis for the multi-step conversion reaction of LiPSs. Electrochemical tests and first-principle density functional theory (DFT) calculations revealed that different defects can realize targeted acceleration of stepwise reaction kinetics for LiPSs. Specifically, the missing linker defects can selectively accelerate the conversion of S8 →Li2 S4 , while the missing cluster defects can catalyze the reaction of Li2 S4 →Li2 S, so as to effectively inhibit the shuttle effect. Hence, the Li-S battery with an electrolyte to sulfur (E/S) ratio of 8.9 mL g-1 delivers a capacity of 1087 mAh g-1 at 0.2 C after 100 cycles. Even at high sulfur loading of 12.9 mg cm-2 and E/S=3.9 mL g-1 , an areal capacity of 10.4 mAh cm-2 for 45 cycles can still be obtained.

11.
Plant Phenomics ; 5: 0047, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228514

RESUMO

Enhancing the photosynthetic rate is one of the effective ways to increase rice yield, given that photosynthesis is the basis of crop productivity. At the leaf level, crops' photosynthetic rate is mainly determined by photosynthetic functional traits including the maximum carboxylation rate (Vcmax) and stomatal conductance (gs). Accurate quantification of these functional traits is important to simulate and predict the growth status of rice. In recent studies, the emerging sun-induced chlorophyll fluorescence (SIF) provides us an unprecedented opportunity to estimate crops' photosynthetic traits, owing to its direct and mechanistic links to photosynthesis. Therefore, in this study, we proposed a practical semimechanistic model to estimate the seasonal Vcmax and gs time-series based on SIF. We firstly generated the coupling relationship between the open ratio of photosystem II (qL) and photosynthetically active radiation (PAR), then estimate the electron transport rate (ETR) based on the proposed mechanistic relationship between SIF and ETR. Finally, Vcmax and gs were estimated by linking to ETR based on the principle of evolutionary optimality and the photosynthetic pathway. Validation with field observations showed that our proposed model can estimate Vcmax and gs with high accuracy (R2 > 0.8). Compared to simple linear regression model, the proposed model could increase the accuracy of Vcmax estimates by >40%. Therefore, the proposed method effectively enhanced the estimation accuracy of crops' functional traits, which sheds new light on developing high-throughput monitoring techniques to estimate plant functional traits, and also can improve our understating of crops' physiological response to climate change.

12.
Sci Adv ; 9(21): eabq4974, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37235657

RESUMO

Photosynthesis and evapotranspiration in Amazonian forests are major contributors to the global carbon and water cycles. However, their diurnal patterns and responses to atmospheric warming and drying at regional scale remain unclear, hindering the understanding of global carbon and water cycles. Here, we used proxies of photosynthesis and evapotranspiration from the International Space Station to reveal a strong depression of dry season afternoon photosynthesis (by 6.7 ± 2.4%) and evapotranspiration (by 6.1 ± 3.1%). Photosynthesis positively responds to vapor pressure deficit (VPD) in the morning, but negatively in the afternoon. Furthermore, we projected that the regionally depressed afternoon photosynthesis will be compensated by their increases in the morning in future dry seasons. These results shed new light on the complex interplay of climate with carbon and water fluxes in Amazonian forests and provide evidence on the emerging environmental constraints of primary productivity that may improve the robustness of future projections.


Assuntos
Clima , Florestas , Estações do Ano , Fotossíntese , Carbono , Árvores , Água
13.
Glob Chang Biol ; 29(16): 4556-4568, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37120816

RESUMO

The soil freeze-thaw cycle in the permafrost regions has a significant impact on regional surface energy and water balance. Although increasing efforts have been made to understand the responses of spring thawing to climate change, the mechanisms controlling the global interannual variability of the start date of permafrost frozen (SOF) remain unclear. Using long-term SOF from the combinations of multiple satellite microwave sensors between 1979 and 2020, and analytical techniques, including partial correlation, ridge regression, path analysis, and machine learning, we explored the responses of SOF to multiple climate change factors, including warming (surface and air temperature), start date of permafrost thawing (SOT), soil properties (soil temperature and volume of water), and the snow depth water equivalent (SDWE). Overall, climate warming exhibited the maximum control on SOF, but SOT in spring was also an important driver of SOF variability; among the 65.9% significant SOT and SOF correlations, 79.3% were positive, indicating an overall earlier thawing would contribute to an earlier frozen in winter. The machine learning analysis also suggested that apart from warming, SOT ranked as the second most important determinant of SOF. Therefore, we identified the mechanism responsible for the SOT-SOF relationship using the SEM analysis, which revealed that soil temperature change exhibited the maximum effect on this relationship, irrespective of the permafrost type. Finally, we analyzed the temporal changes in these responses using the moving window approach and found increased effect of soil warming on SOF. In conclusion, these results provide important insights into understanding and predicting SOF variations with future climate change.


Assuntos
Pergelissolo , Solo , Congelamento , Água , Mudança Climática
14.
RSC Adv ; 13(14): 9428-9440, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36968061

RESUMO

Although lithium-sulfur batteries possess the highest theoretical capacity and lowest cost among all known rechargeable batteries, their commercialization is still hampered by the intrinsic disadvantages of low conductivity of sulfur and polysulfide shuttle effect, which is most critical. Considerable research efforts have been dedicated to solving these difficulties for every part of Li-S batteries. Separator modification with metal electrocatalysts is a promising approach to overcome the major part of these disadvantages. This work focuses on the development of Ni nanoparticles encapsulated in a few-layer nitrogen-doped graphene supported by nitrogen-doped graphitic carbon (Ni@NGC) with different metal loadings as separator modifications. The effect of metal loading on the Li-S electrochemical reaction kinetics and performance of Li-S batteries was investigated. Controlling the Ni loading allowed for the modulation of the surface area-to-metal content ratio, which influenced the reaction kinetics and cycling performance of Li-S cells. Among the separators with different Ni loadings, the one with 9 wt% Ni exhibited the most efficient acceleration of the polysulfide redox reaction and minimized the polysulfide shuttling effect. Batteries with this separator retained 77.2% capacity after 200 cycles at 0.5C, with a high sulfur loading of ∼4.0 mg cm-2, while a bare separator showed 51.3% capacity retention after 200 cycles under the same conditions. This work reveals that there is a vast utility space for carbon-encapsulated Ni nanoparticles in electrochemical energy storage devices with optimal selection and rational design.

15.
FASEB J ; 37(4): e22862, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36906291

RESUMO

The paraspeckle protein NONO is a multifunctional nuclear protein participating in the regulation of transcriptional regulation, mRNA splicing and DNA repair. However, whether NONO plays a role in lymphopoiesis is not known. In this study, we generated mice with global deletion of NONO and bone marrow (BM) chimeric mice in which NONO is deleted in all of mature B cells. We found that the global deletion of NONO in mice did not affect T-cell development but impaired early B-cell development in BM at pro- to pre-B-cell transition stage and B-cell maturation in the spleen. Studies of BM chimeric mice demonstrated that the impaired B-cell development in NONO-deficient mice is B-cell-intrinsic. NONO-deficient B cells displayed normal BCR-induced cell proliferation but increased BCR-induced cell apoptosis. Moreover, we found that NONO deficiency impaired BCR-induced activation of ERK, AKT, and NF-κB pathways in B cells, and altered BCR-induced gene expression profile. Thus, NONO plays a critical role in B-cell development and BCR-induced B-cell activation.


Assuntos
NF-kappa B , Transdução de Sinais , Camundongos , Animais , Camundongos Knockout , NF-kappa B/metabolismo , Linfócitos B/metabolismo , Receptores de Antígenos de Linfócitos B , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a RNA/metabolismo
16.
Nanomaterials (Basel) ; 13(4)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36839145

RESUMO

Lithium-sulfur batteries (LSBs), with their high theoretical specific capacity and energy density, have great potential to be a candidate for secondary batteries in the future. However, Li-S batteries suffer from multiple issues and challenges, for example, uneven growth of lithium dendrites, low utilization of the active material (sulfur), and low specific capacity. This paper reports a low-cost and anodic oxidation method to produce niobium pentoxide with a porous structure (P-Nb2O5). A simple one-step process was used to synthesize P-Nb2O5 with porous structures by anodizing niobium at 40 V in fluorinated glycerol. The porous Nb2O5 showed excellent rate capability and good capacity retention by maintaining its structural integrity, allowing us to determine the advantages of its porous structure. As a result of the highly porous structure, the sulfur was not only provided with adequate storage space and abundant adsorption points, but it was also utilized more effectively. The initial discharge capacity with the P-Nb2O5 cathode rose to 1106.8 mAh·g-1 and dropped to 810.7 mAh·g-1 after 100 cycles, which demonstrated the good cycling performance of the battery. This work demonstrated that the P-Nb2O5 prepared by the oxidation method has strong adsorption properties and good chemical affinity.

17.
Virology ; 578: 180-189, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36586181

RESUMO

Porcine deltacoronavirus is an evolving coronavirus that primarily infects the intestine and may lead to intestinal disease in piglets. Up to now, no commercial vaccination is readily accessible to protect against the spread of PDCoV. Lactococcus lactis has been shown to have good immune efficacy and safety and can be used as a genetically engineered vaccine to deliver antigens. In this research, we utilized L. lactis NZ9000 to provide the S1 protein orally and improved the delivery efficiency by connecting the M cell targeting ligand Co1 with the S1 protein of PDCoV in tandem to obtain the recombinant protein S1-Co1. We successfully constructed two recombinant strains capable of expressing PDCoV-S1 and PDCoV-S1-Co1 proteins (i.e., L. lactis NZ9000-S1 and L. lactis NZ9000-S1-Co1), and their immunogenic capacity was evaluated in mice. Our study shows that Lactococcus is an advantageous bacterial live vector vaccine and is anticipated as a potential PDCoV vaccination option.


Assuntos
Lactococcus lactis , Animais , Camundongos , Suínos , Lactococcus lactis/genética , Lactococcus lactis/metabolismo , Imunidade nas Mucosas , Vacinação , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Administração Oral
18.
Adv Mater ; 35(6): e2208470, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36469454

RESUMO

Single-atom catalysts (SACs) pave new possibilities to improve the utilization efficiency of sulfur electrodes arising from polysulfide shuttle effects and sluggish kinetics due to their excellent applicability in atomic-scale reaction mechanisms and structure-activity relationships. Herein, nitrogen (N)-anchored SACs on the highly ordered N-doped carbon nanotube arrays are reported as the sulfur host for fast redox conversion in lithium-sulfur (Li-S) batteries. The cube structure of the aligned carbon nanotubes can promote the rapid mass transfer under high sulfur loadings, and abundant single-atom active sites further accelerate the conversion of lithium polysulfides (LiPSs). The synergistic enhancement effect induced by adjacent single atoms with interatomic distances <1 nm further accelerates the rapid multi-step reaction of sulfur at high sulfur loadings. As a result, the obtained Li-S batteries exhibit outstanding cycle stability with a high areal capacity of 5.6 mAh cm-2 after 100 cycles under a high sulfur loading of 7.2 mg cm-2 (electrolyte to sulfur ratio is ≈3.7 mL g-1 ). Even assembled into a pouch cell, it still delivers a high capacity of 953.4 mAh g-1 after 100 cycles at 0.1 C, contributing to the development of the practically viable Li-S batteries.

19.
Molecules ; 27(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36557906

RESUMO

Mitochondrial aldehyde dehydrogenase (ALDH2) is a potential target for the treatment of substance use disorders such as alcohol addiction. Here, we adopted computational methods of molecular dynamics (MD) simulation, docking, and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis to perform a virtual screening of FDA-approved drugs, hitting potent inhibitors against ALDH2. Using MD-derived conformations as receptors, butenafine (net charge q = +1 e) and olaparib (q = 0) were selected as promising compounds with a low toxicity and a binding strength equal to or stronger than previously reported potent inhibitors of daidzin and CVT-10216. A few negatively charged compounds were also hit from the docking with the Autodock Vina software, while the MM-PBSA analysis yielded positive binding energies (unfavorable binding) for these compounds, mainly owing to electrostatic repulsion in association with a negatively charged receptor (q = -6 e for ALDH2 plus the cofactor NAD+). This revealed a deficiency of the Vina scoring in dealing with strong charge-charge interactions between binding partners, due to its built-in protocol of not using atomic charges for electrostatic interactions. These observations indicated a requirement of further verification using MD and/or MM-PBSA after docking prediction. The identification of key residues for the binding implied that the receptor residues at the bottom and entrance of the substrate-binding hydrophobic tunnel were able to offer additional interactions with different inhibitors such as π-π, π-alkyl, van der Waals contacts, and polar interactions, and that the rational use of these interactions is beneficial to the design of potent inhibitors against ALDH2.


Assuntos
Simulação de Dinâmica Molecular , Aldeído-Desidrogenase Mitocondrial , Simulação de Acoplamento Molecular
20.
Environ Sci Ecotechnol ; 12: 100210, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36338337

RESUMO

Sudden mega natural gas leaks of two Nord Stream pipelines in the Baltic Sea (Denmark) occurred from late September to early October 2022, releasing large amounts of methane into the atmosphere. We inferred the methane emissions of this event based on surface in situ observations using two inversion methods and two meteorological reanalysis datasets, supplemented with satellite-based observations. We conclude that approximately 220 ± 30 Gg of methane was released from September 26 to October 1, 2022.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...