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1.
Foods ; 13(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731658

RESUMO

Parkinson's disease (PD), the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Despite no specific drug being available for its treatment, curcumin, from the spice turmeric, shows promise. However, its application in PD is limited by a lack of understanding of its anti-amyloidogenic mechanisms. In this study, we first reconstructed the liquid-liquid phase separation (LLPS) of α-Syn in vitro under different conditions, which may be an initial step in entraining the pathogenic aggregation. Subsequently, we evaluated the effects of curcumin on the formation of droplets, oligomers, and aggregated fibers during the LLPS of α-synuclein, as well as its impact on the toxicity of aggregated α-synuclein to cultured cells. Importantly, we found that curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. Finally, the molecular dynamic simulations of interactions between α-Syn decamer fibrils and curcumin showed that van der Waal's interactions make the largest contribution to the anti-aggregation effect of curcumin. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of PD.

2.
ACS Appl Mater Interfaces ; 16(19): 24863-24870, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38706443

RESUMO

Water evaporation-induced electricity generators (WEGs) have drawn widespread attention in the field of hydrovoltaic technology, which can convert atmospheric thermal energy into sustainable electric power. However, it is restricted in the wide application of WEGs due to the low power output, complex fabrication process, and high cost. Herein, we present a simple and effective approach to fabricate TiO2-carbon black film-based WEGs (TC-WEGs). A single TC-WEG device can sustainably output an open-circuit voltage of 1.9 V and a maximum power density of 40.9 µW/cm2. Moreover, it has been shown that TC-WEGs exhibit stable electrical energy output when operating in seawater, which can yield a short-circuit current of 1.2 µA. The superior electricity generation performance can be attributed to the intrinsic characteristics of the TC-WEGs, including hydrophilicity, porous structure, and electrical conductivity. This work provides an important reference for the constant harvesting of clean energy.

3.
Small ; : e2401972, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770749

RESUMO

Due to the chemical stability of graphene, synthesis of carboxylated graphene still remains challenging during the electrochemical exfoliation of graphite. In this work, a spatially confined radical addition reaction which occurs in the sub-nanometer scaled interlayers of the expanded graphene sheets for the electrochemical synthesis of highly stable carboxylated graphene is reported. Here, formate anions act as both intercalation ions and co-reactant acid for the confinement of electro-generated carboxylic radical (●COOH) in the sub-nanometer scaled interlayers, which facilitates the radical addition reaction on graphene sheets. The controllable carboxylation of graphene is realized by tuning the concentration of formate anions in the electrolyte solution. The high crystallinity of the obtained product indicates the occurrence of spatially confined ●COOH addition reaction between the sub-nanometer interlayers of expanded graphite. In addition, the carboxylated graphene have been used for water desalination and hydrogen/oxygen reduction reaction. Therefore, this work provides a new method for the in situ preparation of functionalized graphene through the electrolysis and its applications in water desalination and hydrogen/oxygen reduction reactions.

4.
Anal Chem ; 96(17): 6784-6793, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38632870

RESUMO

Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma, with HBV surface antigen (HBsAg) being a crucial marker in the clinical detection of HBV. Due to the significant harm and ease of transmission associated with HBV, HBsAg testing has become an essential part of preoperative assessments, particularly for emergency surgeries where healthcare professionals face exposure risks. Therefore, a timely and accurate detection method for HBsAg is urgently needed. In this study, a surface-enhanced Raman scattering (SERS) sensor with a sandwich structure was developed for HBsAg detection. Leveraging the ultrasensitive and rapid detection capabilities of SERS, this sensor enables quick detection results, significantly reducing waiting times. By systematically optimizing critical factors in the detection process, such as the composition and concentration of the incubation solution as well as the modification conditions and amount of probe particles, the sensitivity of the SERS immune assay system was improved. Ultimately, the sensor achieved a sensitivity of 0.00576 IU/mL within 12 min, surpassing the clinical requirement of 0.05 IU/mL by an order of magnitude. In clinical serum assay validation, the issue of false positives was effectively addressed by adding a blocker. The final sensor demonstrated 100% specificity and sensitivity at the threshold of 0.05 IU/mL. Therefore, this study not only designed an ultrasensitive SERS sensor for detecting HBsAg in actual clinical serum samples but also provided theoretical support for similar systems, filling the knowledge gap in existing literature.


Assuntos
Antígenos de Superfície da Hepatite B , Análise Espectral Raman , Antígenos de Superfície da Hepatite B/sangue , Análise Espectral Raman/métodos , Humanos , Vírus da Hepatite B/isolamento & purificação , Nanopartículas Metálicas/química , Hepatite B/sangue , Hepatite B/diagnóstico , Propriedades de Superfície , Limite de Detecção
5.
J Am Chem Soc ; 146(18): 12538-12546, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38656110

RESUMO

There is growing acknowledgment that the properties of the electrochemical interfaces play an increasingly pivotal role in improving the performance of the hydrogen evolution reaction (HER). Here, we present, for the first time, direct dynamic spectral evidence illustrating the impact of the interaction between interfacial water molecules and adsorbed hydroxyl species (OHad) on the HER properties of Ni(OH)2 using Au/core-Ni(OH)2/shell nanoparticle-enhanced Raman spectroscopy. Notably, our findings highlight that the interaction between OHad and interfacial water molecules promotes the formation of weakly hydrogen-bonded water, fostering an environment conducive to improving the HER performance. Furthermore, the participation of OHad in the reaction is substantiated by the observed deprotonation step of Au@2 nm Ni(OH)2 during the HER process. This phenomenon is corroborated by the phase transition of Ni(OH)2 to NiO, as verified through Raman and X-ray photoelectron spectroscopy. The significant redshift in the OH-stretching frequency of water molecules during the phase transition confirms that surface OHad disrupts the hydrogen-bond network of interfacial water molecules. Through manipulation of the shell thickness of Au@Ni(OH)2, we additionally validate the interaction between OHad and interfacial water molecules. In summary, our insights emphasize the potential of electrochemical interfacial engineering as a potent approach to enhance electrocatalytic performance.

6.
Nat Mater ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589543

RESUMO

Unconventional 1T'-phase transition metal dichalcogenides (TMDs) have aroused tremendous research interest due to their unique phase-dependent physicochemical properties and applications. However, due to the metastable nature of 1T'-TMDs, the controlled synthesis of 1T'-TMD monolayers (MLs) with high phase purity and stability still remains a challenge. Here we report that 4H-Au nanowires (NWs), when used as templates, can induce the quasi-epitaxial growth of high-phase-purity and stable 1T'-TMD MLs, including WS2, WSe2, MoS2 and MoSe2, via a facile and rapid wet-chemical method. The as-synthesized 4H-Au@1T'-TMD core-shell NWs can be used for ultrasensitive surface-enhanced Raman scattering (SERS) detection. For instance, the 4H-Au@1T'-WS2 NWs have achieved attomole-level SERS detections of Rhodamine 6G and a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins. This work provides insights into the preparation of high-phase-purity and stable 1T'-TMD MLs on metal substrates or templates, showing great potential in various promising applications.

7.
Plant Physiol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478589

RESUMO

Manipulation of gene expression is central to understanding gene function, engineering cell behavior, and altering biological traits according to production demands. Nuclease-dead Cas9 (dCas9), a variant of active Cas9, offers a versatile platform for the precise control of genome function without DNA cleavage. Notably, however, an effective and universal dCas9-based transcriptional repression system remains unavailable in plants. The non-canonical histone acetyltransferase TENDRIL-LESS (CsTEN) is responsible for chromatin loosening and histone modification in cucumber (Cucumis sativus). In this study, we engineered a gene regulation tool by fusing TEN and its truncated proteins with dCas9. The full-length dCas9-TEN protein substantially repressed gene expression, with the N-terminal domain identified as the core repression domain. We subsequently validated the specificity and efficacy of this system through both transient infection and genetic transformation in cucumber and Arabidopsis (Arabidopsis thaliana). Electrophoretic mobility shift assay (EMSA) revealed the ability of the N-terminal domain of TEN to bind to chromatin, which may promote target binding of the dCas9 complex and enhance the transcriptional repression effect. Our tool enriches the arsenal of genetic regulation tools available for precision breeding in crops.

8.
Hortic Res ; 11(3): uhae035, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38544552

RESUMO

Tomato (Solanum lycopersicum) is a globally cultivated crop with great economic value. The exocarp determines the appearance of tomato fruit and protects it from various biotic and abiotic challenges at both pre-harvest and post-harvest stages. However, no tomato exocarp-specific promoter is currently available, which hinders exocarp-based genetic engineering. Here, we identified by RNA sequencing and reverse transcription-quantitative PCR analyses that the tomato gene SlPR10 (PATHOGENESIS RELATED 10) was abundantly and predominantly expressed in the exocarp. A fluorescent reporter expressed by a 2087-bp SlPR10 promoter (pSlPR10) was mainly detected in the exocarp of transgenic tomato plants of both Ailsa Craig and Micro-Tom cultivars. This promoter was further utilized for transgenic expression of SlANT1 and SlMYB31 in tomato, which are master regulators of anthocyanin and cuticular wax biosynthesis, respectively. pSlPR10-driven SlANT1 expression resulted in anthocyanin accumulation in the exocarp, conferring gray mold resistance and extended shelf life to the fruit, while SlMYB31 expression led to waxy thickening in the fruit skin, delaying water loss and also extending fruit shelf life. Intriguingly, pSlPR10 and two other weaker tomato exocarp-preferential promoters exhibited coincided expression specificities in the gynophore of transgenic Arabidopsis (Arabidopsis thaliana) plants, providing not only an inkling of evolutionary homology between tomato exocarp and Arabidopsis gynophore but also useful promoters for studying gynophore biology in Arabidopsis. Collectively, this work reports a desirable promoter enabling targeted gene expression in tomato exocarp and Arabidopsis gynophore and demonstrates its usefulness in genetic improvement of tomato fruit quality.

9.
Nanoscale ; 16(11): 5706-5714, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38407467

RESUMO

N2 molecules with the NN triple bond structure are difficult to cleave under mild conditions to achieve the nitrogen fixation reaction. Photoelectrochemical (PEC) catalysis technology combining the advantages of photocatalysis and electrocatalysis provides the possibility of the nitrogen reduction reaction under ambient conditions. Herein, an SnO2/TiO2 photoelectrode was first fabricated through depositing SnO2 quantum dots on TiO2 nanorod arrays via a simple hydrothermal method. The oxygen vacancy (Vo) content was then induced in SnO2 through annealing SnO2/TiO2 at high temperature under an inert atmosphere. The heterogeneous structure of Vo-SnO2 quantum dots and TiO2 nanorods boosted the separation of photocarriers. The photoelectrons generated by photoexcitation were transferred from the conduction band of TiO2 to the conduction band of Vo-SnO2 and trapped by Vo. Vo activates N2 molecules adsorbed on the catalyst surface, and reacts with H+ in the electrolyte to generate NH3. The nitrogen fixation yield of PEC catalysis and its faradaic efficiency can reach 19.41 µg cm-2 h-1, and 59.6% at -0.2 V bias potential, respectively. The heterogeneous structure of Vo-SnO2/TiO2, introduction of Vo and synergistic effect between light and electricity greatly promotes the PEC nitrogen reduction to NH3.

10.
ACS Appl Mater Interfaces ; 16(10): 12149-12160, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38412551

RESUMO

Photocatalysis driven by plasmon-induced hot carriers has been gaining increasing attention. Recent studies have demonstrated that plasmon-induced hot carriers can directly participate in photocatalytic reactions, leading to great enhancement in solar energy conversion efficiency, by improving the catalytic activity or changing selectivity. Nevertheless, the utilization efficiency of hot carriers remains unsatisfactory. Therefore, how to correctly understand the generation and transfer process of hot carriers, as well as accurately differentiate between the possible mechanisms, have become a key point of attention. In this review, we overview the fundamental processes and mechanisms underlying hot carrier generation and transport, followed by highlighting the importance of hot carrier monitoring methods and related photocatalytic reactions. Furthermore, possible strategies for the further characterization of plasmon-induced hot carriers and boosting their utilization efficiency have been proposed. We hope that a comprehensive understanding of the fundamental behaviors of hot carriers can aid in designing more efficient photocatalysts for plasmon-induced photocatalytic reactions.

11.
Proc Natl Acad Sci U S A ; 121(10): e2319366121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38422020

RESUMO

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Idoso , Humanos , Masculino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Envelhecimento/genética , Mutação , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Prognóstico
12.
Anal Chem ; 96(10): 4275-4281, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38409670

RESUMO

Surface-enhanced Raman scattering (SERS) can overcome the existing technological limitations, such as complex processes and harsh conditions in gaseous small-molecule detection, and advance the development of real-time gas sensing at room temperature. In this study, a SERS-based hydrogen bonding induction strategy for capturing and sensing gaseous acetic acid is proposed for the detection demands of gaseous acetic acid. This addresses the challenges of low adsorption of gaseous small molecules on SERS substrates and small Raman scattering cross sections and enables the first SERS-based detection of gaseous acetic acid by a portable Raman spectrometer. To provide abundant hydrogen bond donors and acceptors, 4-mercaptobenzoic acid (4-MBA) was used as a ligand molecule modified on the SERS substrate. Furthermore, a sensing chip with a low relative standard deviation (RSD) of 4.15% was constructed, ensuring highly sensitive and reliable detection. The hydrogen bond-induced acetic acid trapping was confirmed by experimental spectroscopy and density functional theory (DFT). In addition, to achieve superior accuracy compared to conventional methods, an innovative analytical method based on direct response hydrogen bond formation (IO-H/Iref) was proposed, enabling the detection of gaseous acetic acid at concentrations as low as 60 ppb. The strategy demonstrated a superior anti-interference capability in simulated breath and wine detection systems. Moreover, the high reusability of the chip highlights the significant potential for real-time sensing of gaseous acetic acid.

13.
Biosens Bioelectron ; 251: 116101, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324971

RESUMO

Abnormal levels of uric acid (UA) in urine serve as warning signs for gout and metabolic cardiovascular diseases, necessitating the monitoring of UA levels for early prevention. However, the current analytical methods employed suffer from limitations in terms of inadequate suitability for home-based applications and the requirement of non-invasive procedures. In this approach, creatinine, a metabolite with a constant excretion rate, was incorporated as an endogenous internal standard (e-IS) for calibration, presenting a rapid, pretreatment-free, and accurate strategy for quantitative determination of UA concentrations. By utilizing urine creatinine as an internal reference value to calibrate the signal fluctuation of surface-enhanced Raman spectroscopy (SERS) of UA, the quantitative accuracy can be significantly improved without the need for an external internal standard. Due to the influence of the medium, UA, which carries a negative charge, is selectively adsorbed by Au@Ag nanoparticles functionalized with hexadecyltrimethylammonium chloride (CTAC) in this system. Furthermore, a highly convenient detection method was developed, which eliminates the need for pre-processing and minimizes matrix interference by simple dilution. The method was applied to the urine detection of different volunteers, and the results were highly consistent with those obtained using the UA colorimetric kit (UACK). The detection time of SERS was only 30 s, which is 50 times faster than UACK. This quantitative strategy of using urinary creatinine as an internal standard to correct the SERS intensity of uric acid is also expected to be extended to the quantitative detection needs of other biomarkers in urine.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Ácido Úrico/urina , Creatinina/urina , Análise Espectral Raman/métodos , Nanopartículas Metálicas/química , Prata/química
14.
Proc Natl Acad Sci U S A ; 121(8): e2319364121, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38359296

RESUMO

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.


Assuntos
Hematopoiese Clonal , Hematopoese , Humanos , Idoso , Hematopoiese Clonal/genética , Hematopoese/genética , Envelhecimento/genética , Mutação , Biomarcadores
15.
J Am Chem Soc ; 146(8): 5532-5542, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38362877

RESUMO

The electrochemical carbon dioxide reduction reaction (CO2RR) toward C2 products is a promising way for the clean energy economy. Modulating the structure of the electric double layer (EDL), especially the interfacial water and cation type, is a useful strategy to promote C-C coupling, but atomic understanding lags far behind the experimental observations. Herein, we investigate the combined effect of interfacial water and alkali metal cations on the C-C coupling at the Cu(100) electrode/electrolyte interface using ab initio molecular dynamics (AIMD) simulations with a constrained MD and slow-growth approach. We observe a linear correlation between the water-adsorbate stabilization effect, which manifests as hydrogen bonds, and the corresponding alleviation in the C-C coupling free energy. The role of a larger cation, compared to a smaller cation (e.g., K+ vs Li+), lies in its ability to approach the interface through desolvation and coordinates with the *CO+*CO moiety, partially substituting the hydrogen-bonding stabilizing effect of interfacial water. Although this only results in a marginal reduction of the energy barrier for C-C coupling, it creates a local hydrophobic environment with a scarcity of hydrogen bonds owing to its great ionic radius, impeding the hydrogen of surrounding interfacial water to approach the oxygen of the adsorbed *CO. This skillfully circumvents the further hydrogenation of *CO toward the C1 pathway, serving as the predominant factor through which a larger cation facilitates C-C coupling. This study unveils a comprehensive atomic mechanism of the cation-water-adsorbate interactions that can facilitate the further optimization of the electrolyte and EDL for efficient C-C coupling in CO2RR.

16.
Nano Lett ; 24(9): 2681-2688, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38408023

RESUMO

Perovskite light-emitting diodes (PeLEDs) have emerged as promising candidates for lighting and display technologies owing to their high photoluminescence quantum efficiency and high carrier mobility. However, the performance of planar PeLEDs is limited by the out-coupling efficiency, predominantly governed by photonic losses at device interfaces. Most notably, the plasmonic loss at the metal electrode interfaces can account for up to 60% of the total loss. Here, we investigate the use of plasmonic nanostructures to improve the light out-coupling in PeLEDs. By integrating these nanostructures with PeLEDs, we have demonstrated an effectively reduced plasmonic loss and enhanced light out-coupling. As a result, the nanostructured PeLEDs exhibit an average 1.5-fold increase in external quantum efficiency and an ∼20-fold improvement in device lifetime. This finding offers a generic approach for enhancing light out-coupling, promising great potential to go beyond existing performance limitations.

17.
Chem Sci ; 15(8): 2697-2711, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38404398

RESUMO

Plasmonic nanocavities exhibit exceptional capabilities in visualizing the internal structure of a single molecule at sub-nanometer resolution. Among these, an easily manufacturable nanoparticle-on-mirror (NPoM) nanocavity is a successful and powerful platform for demonstrating various optical phenomena. Exciting advances in surface-enhanced spectroscopy using NPoM nanocavities have been developed and explored, including enhanced Raman, fluorescence, phosphorescence, upconversion, etc. This perspective emphasizes the construction of NPoM nanocavities and their applications in achieving higher enhancement capabilities or spatial resolution in dark-field scattering spectroscopy and plasmon-enhanced spectroscopy. We describe a systematic framework that elucidates how to meet the requirements for studying light-matter interactions through the creation of well-designed NPoM nanocavities. Additionally, it provides an outlook on the challenges, future development directions, and practical applications in the field of plasmon-enhanced spectroscopy.

18.
Angew Chem Int Ed Engl ; 63(14): e202317922, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38366167

RESUMO

Carbon coating layers have been found to improve the catalytic performance of transition metals, which is usually explained as an outcome of electronic synergistic effect. Herein we reveal that the defective graphitic carbon, with a unique interlayer gap of 0.342 nm, can be a highly selective natural molecular sieve. It allows efficient diffusion of hydrogen molecules or radicals both along the in-plane and out-of-plane direction, but sterically hinders the diffusion of molecules with larger kinetic diameter (e.g., CO and O2) along the in-plane direction. As a result, poisonous species lager than 0.342 nm are sieved out, even when their adsorption on the metal is thermodynamically strong; at the same time, the interaction between H2 and the metal is not affected. This natural molecular sieve provides a very chance for constructing robust metal catalysts for hydrogen-relevant processes, which are more tolerant to chemical or electrochemical oxidation or CO-relevant poisoning.

19.
Int J Mol Sci ; 25(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38203794

RESUMO

Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.


Assuntos
Genes myc , Simulação de Acoplamento Molecular , Peptídeos/farmacologia , Tiazóis/farmacologia
20.
Small ; : e2311393, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287737

RESUMO

Electrolyte plays a crucial role in ensuring stable operation of lithium metal batteries (LMBs). Localized high-concentration electrolytes (LHCEs) have the potential to form a robust solid-electrolyte interphase (SEI) and mitigate Li dendrite growth, making them a highly promising electrolyte option. However, the principles governing the selection of diluents, a crucial component in LHCE, have not been clearly determined, hampering the advancement of such a type of electrolyte systems. Herein, the diluents from the perspective of molecular polarity are rationally designed and developed. A moderately fluorinated solvent, 1-(1,1,2,2-tetrafluoroethoxy)propane (TNE), is employed as a diluent to create a novel LHCE. The unique molecular structure of TNE enhances the intrinsic dipole moment, thereby altering solvent interactions and the coordination environment of Li-ions in LHCE. The achieved solvation structure not only enhances the bulk properties of LHCE, but also facilitates the formation of more stable anion-derived SEIs featured with a higher proportion of inorganic species. Consequently, the corresponding full cells of both Li||LiFePO4 and Li||LiNi0.8 Co0.1 Mn0.1 O2 cells utilizing Li thin-film anodes exhibit extended long-term stability with significantly improved average Coulombic efficiency. This work offers new insights into the functions of diluents in LHCEs and provides direction for further optimizing the LHCEs for LMBs.

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