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1.
Artículo en Inglés | MEDLINE | ID: mdl-38690838

RESUMEN

In the past decade, perovskite solar cell (PSC) photoelectric conversion efficiency has advanced significantly, and tin dioxide (SnO2) has been extensively used as the electron transport layer (ETL). Due to its high electron mobility, strong chemical stability, energy level matching with perovskite, and easy low-temperature fabrication, SnO2 is one of the most effective ETL materials. However, the SnO2 material as an ETL has its limitations. For example, SnO2 films prepared by low-temperature spin-coating contain a large number of oxygen vacancies, resulting in energy loss and high open-circuit voltage (VOC) loss. In addition, the crystal quality of perovskites is closely related to the substrate, and the disordered crystal orientation will lead to ion migration, resulting in a large number of uncoordinated Pb2+ defects. Therefore, interface optimization is essential to improve the efficiency and stability of the PSC. In this work, 2-(5-chloro-2-benzotriazolyl)-6-tert-butyl-p-cresol (CBTBC) was introduced for ETL modification. On the one hand, the hydroxyl group of CBTBC forms a Lewis mixture with the Sn atom, which reduces the oxygen vacancy defect and prevents nonradiative recombination. On the other hand, the SnO2/CBTBC interface can effectively improve the crystal orientation of perovskite by influencing the crystallization kinetics of perovskite, and the nitrogen element in CBTBC can effectively passivate the uncoordinated Pb2+ defects at the SnO2/perovskite interface. Finally, the prevailing PCE of PSC (1.68 eV) modified by CBTBC was 20.34% (VOC = 1.214 V, JSC = 20.49 mA/cm2, FF = 82.49%).

2.
Adv Healthc Mater ; : e2400819, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38722289

RESUMEN

Mild photothermal therapy (PTT) is a spatiotemporally controllable method that utilizes the photothermal effect at relatively low temperatures (40-45 °C) to especially eliminate tumor tissues with negligible side effects on the surrounding normal tissues. However, the overexpression of heat shock protein 70 (HSP70) and limited effect of single treatment drastically impeded the therapeutic efficacy. Herein, the constructed multifunctional core-shell structured Ag-Cu@SiO2-PDA/GOx nanoreactors (APG NRs) that provide a dual inhibition of HSP70 strategy for the second near-infrared photoacoustic (NIR-II PA) imaging-guided combined mild PTT/chemodynamic therapy (CDT). The Ag-Cu cores can convert endogenous H2O2 to hydroxyl radical (•OH), which could induce lipid peroxidation (LPO) and further degrade HSP70. The polydopamine (PDA)/glucose oxidase (GOx) shells were utilized as the NIR-II photothermal agent to generate low temperature, and the GOx could reduce the energy supplies and inhibit energy-dependent HSP70 expression. Furthermore, both the generation of •OH and GOx-mediated energy shortage can reduce HSP70 expression to sensitize mild PTT under 1064 nm laser, and in turn, GOx and laser self-amplify the catalytic reactions of APG NRs for more production of •OH. The multifunctional nanoreactors will provide more potential possibilities for the clinical employment of mild PTT and the advancement of tumor combination therapies. This article is protected by copyright. All rights reserved.

3.
Sci Adv ; 10(18): eadl4450, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701202

RESUMEN

Caulobacter crescentus Tad (tight adherence) pili, part of the type IV pili family, are crucial for mechanosensing, surface adherence, bacteriophage (phage) adsorption, and cell-cycle regulation. Unlike other type IV pilins, Tad pilins lack the typical globular ß sheet domain responsible for pilus assembly and phage binding. The mechanisms of Tad pilus assembly and its interaction with phage ΦCb5 have been elusive. Using cryo-electron microscopy, we unveiled the Tad pilus assembly mechanism, featuring a unique network of hydrogen bonds at its core. We then identified the Tad pilus binding to the ΦCb5 maturation protein (Mat) through its ß region. Notably, the amino terminus of ΦCb5 Mat is exposed outside the capsid and phage/pilus interface, enabling the attachment of fluorescent and affinity tags. These engineered ΦCb5 virions can be efficiently assembled and purified in Escherichia coli, maintaining infectivity against C. crescentus, which presents promising applications, including RNA delivery and phage display.


Asunto(s)
Caulobacter crescentus , Fimbrias Bacterianas , Caulobacter crescentus/virología , Caulobacter crescentus/metabolismo , Fimbrias Bacterianas/metabolismo , Fimbrias Bacterianas/química , Fimbrias Bacterianas/ultraestructura , Unión Proteica , Microscopía por Crioelectrón , Proteínas Fimbrias/metabolismo , Proteínas Fimbrias/química , Proteínas Fimbrias/genética , Fagos ARN/metabolismo , Fagos ARN/química , Modelos Moleculares
4.
Food Chem ; 449: 139277, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38608607

RESUMEN

Mogrosides are low-calorie, biologically active sweeteners that face high production costs due to strict cultivation requirements and the low yield of monk fruit. The rapid advancement in synthetic biology holds the potential to overcome this challenge. This review presents mogrosides exhibiting antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and liver protective activities, with their efficacy in diabetes treatment surpassing that of Xiaoke pills (a Chinese diabetes medication). It also discusses the latest elucidated biosynthesis pathways of mogrosides, highlighting the challenges and research gaps in this field. The critical and most challenging step in this pathway is the transformation of mogrol into a variety of mogrosides by different UDP-glucosyltransferases (UGTs), primarily hindered by the poor substrate selectivity, product specificity, and low catalytic efficiency of current UGTs. Finally, the applications of mogrosides in the current food industry and the challenges they face are discussed.


Asunto(s)
Biología Sintética , Humanos , Industria de Alimentos , Animales , Antioxidantes/química , Antioxidantes/metabolismo , Cucurbitaceae/química , Cucurbitaceae/metabolismo , Edulcorantes/metabolismo
5.
Cell Death Dis ; 15(4): 238, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561367

RESUMEN

Macrophages, as pivotal cells within the tumour microenvironment, significantly influence the impact of and reactions to treatments for solid tumours. The rapid evolution of bioengineering technology has revealed the vast potential of engineered macrophages in immunotherapy, disease diagnosis, and tissue engineering. Given this landscape, the goal of harnessing and innovating macrophages as a novel strategy for solid tumour immunotherapy cannot be overstated. The diverse strategies for engineered macrophages in the realm of cancer immunotherapy, encompassing macrophage drug delivery systems, chimeric antigen receptor macrophage therapy, and synergistic treatment approaches involving bacterial outer membrane vesicles and macrophages, are meticulously examined in this review. These methodologies are designed to enhance the therapeutic efficacy of macrophages against solid tumours, particularly those that are drug-resistant and metastatic. Collectively, these immunotherapies are poised to supplement and refine current solid tumour treatment paradigms, thus heralding a new frontier in the fight against malignant tumours.


Asunto(s)
Inmunoterapia , Neoplasias , Humanos , Inmunoterapia/métodos , Neoplasias/patología , Macrófagos/patología , Inmunoterapia Adoptiva , Sistemas de Liberación de Medicamentos , Microambiente Tumoral
6.
Cells ; 13(7)2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38607004

RESUMEN

Leucine-rich repeat kinase 2 (LRRK2) is a serine-threonine protein kinase belonging to the ROCO protein family. Within the kinase domain of LRRK2, a point mutation known as LRRK2 G2019S has emerged as the most prevalent variant associated with Parkinson's disease. Recent clinical studies have indicated that G2019S carriers have an elevated risk of cancers, including colon cancer. Despite this observation, the underlying mechanisms linking LRRK2 G2019S to colon cancer remain elusive. In this study, employing a colitis-associated cancer (CAC) model and LRRK2 G2019S knock-in (KI) mouse model, we demonstrate that LRRK2 G2019S promotes the pathogenesis of colon cancer, characterized by increased tumor number and size in KI mice. Furthermore, LRRK2 G2019S enhances intestinal epithelial cell proliferation and inflammation within the tumor microenvironment. Mechanistically, KI mice exhibit heightened susceptibility to DSS-induced colitis, with inhibition of LRRK2 kinase activity ameliorating colitis severity and CAC progression. Our investigation also reveals that LRRK2 G2019S promotes inflammasome activation and exacerbates gut epithelium necrosis in the colitis model. Notably, GSDMD inhibitors attenuate colitis in LRRK2 G2019S KI mice. Taken together, our findings offer experimental evidence indicating that the gain-of-kinase activity in LRRK2 promotes colorectal tumorigenesis, suggesting LRRK2 as a potential therapeutic target in colon cancer patients exhibiting hyper LRRK2 kinase activity.


Asunto(s)
Colitis , Neoplasias del Colon , Gasderminas , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Animales , Ratones , Colitis/inducido químicamente , Colitis/complicaciones , Colitis/genética , Neoplasias del Colon/genética , Inflamación/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/metabolismo , Microambiente Tumoral
7.
Front Immunol ; 15: 1366096, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38596689

RESUMEN

Background: The tumor microenvironment (TME) plays a pivotal role in the progression and metastasis of lung adenocarcinoma (LUAD). However, the detailed characteristics of LUAD and its associated microenvironment are yet to be extensively explored. This study aims to delineate a comprehensive profile of the immune cells within the LUAD microenvironment, including CD8+ T cells, CD4+ T cells, and myeloid cells. Subsequently, based on marker genes of exhausted CD8+ T cells, we aim to establish a prognostic model for LUAD. Method: Utilizing the Seurat and Scanpy packages, we successfully constructed an immune microenvironment atlas for LUAD. The Monocle3 and PAGA algorithms were employed for pseudotime analysis, pySCENIC for transcription factor analysis, and CellChat for analyzing intercellular communication. Following this, a prognostic model for LUAD was developed, based on the marker genes of exhausted CD8+ T cells, enabling effective risk stratification in LUAD patients. Our study included a thorough analysis to identify differences in TME, mutation landscape, and enrichment across varying risk groups. Moreover, by integrating risk scores with clinical features, we developed a new nomogram. The expression of model genes was validated via RT-PCR, and a series of cellular experiments were conducted, elucidating the potential oncogenic mechanisms of GALNT2. Results: Our study developed a single-cell atlas for LUAD from scRNA-seq data of 19 patients, examining crucial immune cells in LUAD's microenvironment. We underscored pDCs' role in antigen processing and established a Cox regression model based on CD8_Tex-LAYN genes for risk assessment. Additionally, we contrasted prognosis and tumor environments across risk groups, constructed a new nomogram integrating clinical features, validated the expression of model genes via RT-PCR, and confirmed GALNT2's function in LUAD through cellular experiments, thereby enhancing our understanding and approach to LUAD treatment. Conclusion: The creation of a LUAD single-cell atlas in our study offered new insights into its tumor microenvironment and immune cell interactions, highlighting the importance of key genes associated with exhausted CD8+ T cells. These discoveries have enabled the development of an effective prognostic model for LUAD and identified GALNT2 as a potential therapeutic target, significantly contributing to the improvement of LUAD diagnosis and treatment strategies.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Pronóstico , Linfocitos T CD8-positivos , Nomogramas , Neoplasias Pulmonares/genética , Microambiente Tumoral , Lectinas Tipo C
8.
Infect Drug Resist ; 17: 1259-1266, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562404

RESUMEN

Objective: Pseudomonas aeruginosa (PA) often displays drug resistance and biofilm-mediated adaptability. Here, we aimed to evaluate the antibiofilm efficacy of azithromycin-based combination regimens. Methods: Minimum inhibitory concentrations (MICs), minimal biofilm eradication concentrations (MBECs), and MBEC-combination of azithromycin, colistin, amikacin, and levofloxacin to bioluminescent strain PAO1 and carbapenem-resistant PAO1 (CRPAO1) were assessed. An animal biofilm infection model was established and detected using a live animal bio-photonic imaging system. Results: In vitro, PAO1 and CRPAO1 were susceptible to colistin, amikacin, and levofloxacin, while they were unsusceptible to azithromycin. The combinations based on azithromycin have no synergistic effect on biofilm in vitro. In vivo, azithromycin plus colistin or levofloxacin could shorten the PAO1 biofilm eradication time, which totally eradicates the biofilm in all mice on the 8th or 6th day, while monotherapy only eradicate biofilm in 70% or 80% mice on the 8th day. For CRPAO1 biofilm, only azithromycin-colistin combination and colistin monotherapy eradicated the bacteria in 60% and 40% of mice at the 6th day. Conclusion: Azithromycin-based combinations containing levofloxacin or colistin had no synergistic effect in vitro, and they are promising for clinical applications due to the good synergistic activity against PAO1 biofilms in vivo.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38683422

RESUMEN

BACKGROUND: In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties. METHODS: In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI. RESULTS: Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65 years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics. CONCLUSIONS: Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics.

10.
Front Biosci (Landmark Ed) ; 29(4): 144, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38682183

RESUMEN

BACKGROUND: Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. METHODS: A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. RESULTS: Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. CONCLUSION: Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Encefálicas , Glioma , Enzimas Activadoras de Ubiquitina , Humanos , Glioma/genética , Glioma/metabolismo , Glioma/patología , Enzimas Activadoras de Ubiquitina/genética , Enzimas Activadoras de Ubiquitina/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Femenino , Masculino , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Estimación de Kaplan-Meier , Biología Computacional/métodos
12.
Clin Transl Med ; 14(3): e1599, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38450975

RESUMEN

BACKGROUND: Cancer is a thorny problem which cannot be conquered by mankind at present and recent researchers have put their focus on tumor microenviroment. Neutrophils, the prominent leukocytes in peripheral blood that accumulate in tumours, serves as frontline cells in response to tumour progression owing to the rapid development of micro biotechnology. Hence, targeted therapy with these neutrophils has made targeting treatment a promising field in cancer therapy. MAIN BODY: We broadly summarise some studies on the phenotypes and functions of tumour-associated neutrophils as well as the unique web-like products of neutrophils that play a role in cancer progression-neutrophil extracellular traps-and the interactions between neutrophils and the tumour microenvironment. Moreover, several targeted neutrophils therapeutic studies have made some progress and provided potential strategies for the treatment of cancer. CONCLUSION: This review aims to offer a holistic perspective on therapeutic interventions targeting neutrophils to further inspire more researches on cancer therapies.


Asunto(s)
Trampas Extracelulares , Neoplasias , Humanos , Neutrófilos , Leucocitos , Fenotipo , Neoplasias/tratamiento farmacológico , Microambiente Tumoral
13.
Electrophoresis ; 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528332

RESUMEN

Chemically active droplets display complex self-propulsion behavior in homogeneous surfactant solutions, often influenced by the interplay between diffusiophoresis and Marangoni effects. Previous studies have primarily considered these effects separately or assumed axisymmetric motion. To understand the full hydrodynamics, we investigate the motion of a two-dimensional active droplet under their combined influences using weakly nonlinear analysis and numerical simulations. The impact of two key factors, the Péclet number ( P e $Pe$ ) and the mobility ratio between diffusiophoretic and Marangoni effects ( m $m$ ), on droplet motion is explored. We establish a phase diagram in the P e - m $Pe-m$ space, categorizing the boundaries between four types of droplet states: stationary, steady motion, periodic/quasi-periodic motion, and chaotic motion. We find that the mobility ratio does not affect the critical P e $Pe$ for the onset of self-propulsion, but it significantly influences the stability of high-wavenumber modes as well as the droplet's velocity and trajectory. Scaling analysis reveals that in the high P e $Pe$ regime, the Marangoni and diffusiophoresis effects lead to distinct velocity scaling laws: U ∼ P e - 1 / 2 $U\sim Pe^{-1/2}$ and U ∼ P e - 1 / 3 $U\sim Pe^{-1/3}$ , respectively. When these effects are combined, the velocity scaling depends on the sign of the mobility ratio. In cases with a positive mobility ratio, the Marangoni effect dominates the scaling, whereas the negative diffusiophoretic effect leads to an increased thickness of the concentration boundary layer and a flattened scaling of the droplet velocity.

14.
Micromachines (Basel) ; 15(3)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38542604

RESUMEN

In this work, the major methods for implementing flexible sensing technology-flexible surface acoustic wave (SAW) sensors-are summarized; the working principles and device characteristics of the flexible SAW sensors are introduced; and the latest achievements of the flexible SAW sensors in the selection of the substrate materials, the development of the piezoelectric thin films, and the structural design of the interdigital transducers are discussed. This paper focuses on analyzing the research status of physical flexible SAW sensors such as temperature, humidity, and ultraviolet radiation, including the sensing mechanism, bending strain performance, device performance parameters, advantages and disadvantages, etc. It also looks forward to the development of future chemical flexible SAW sensors for gases, the optimization of the direction of the overall device design, and systematic research on acoustic sensing theory under strain. This will enable the manufacturing of multifunctional and diverse sensors that better meet human needs.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124182, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38522376

RESUMEN

Inflammation is a key factor leading to the occurrence and development of many diseases, both lipid droplets (LDs) and hypochlorous acid (HClO/ClO-) are regarded as the important biomarkers of inflammation. Therefore, it is of great significance to develop an efficient single chemical sensor that can simultaneously detect these two biomarkers. To achieve the goal, we developed a dual-locked fluorescence probe (TPA-DNP) by fusing two targets activated reporting system, its implementation was achieved by turning-on the fluorescence of TPA-DNP through LDs and HClO/ClO- simultaneously. In simulated LDs environment, TPA-DNP displayed excellent selectivity to HClO/ClO-, high sensitivity (LOD = 0.527 µM) and strong anti-interference ability. In addition, cell and zebrafish imaging experiments showed that TPA-DNP could be utilized to visualize exogenous/endogenous HClO/ClO- in LDs environment, and could also be used to observe the impact of LDs changes on the HClO/ClO- detection. On the basis, TPA-DNP served as a favorable tool to achieve visualization of inflammatory dynamic changes.


Asunto(s)
Ácido Hipocloroso , Gotas Lipídicas , Animales , Pez Cebra , Inflamación , Colorantes Fluorescentes , Biomarcadores
16.
Org Lett ; 26(15): 3164-3168, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38553426

RESUMEN

The catalyst-dependent intermolecular carbonyl-alkyne metathesis (CAM) reaction of 1H-indene-1,2,3-triones with internal alkynes was realized using Ru and Co catalysts. 2-(2-Oxo-1,2-diphenylethylidene)-1H-indene-1,3(2H)-dione derivatives were obtained using a Ru catalyst, whereas S-alkyl 2-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)-2-phenylethanethioates were prepared using a Co catalyst. These transformations led to the synthesis of α,ß-unsaturated carbonyl compounds with a broad substrate scope, excellent regiocontrol, and gram-scale amenability. This catalytic strategy using a Co or Ru catalyst has rarely been described for other established CAM catalysts.

17.
Langmuir ; 40(13): 7049-7059, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38520349

RESUMEN

In this study, the gas-sensitive response of metal (Ag, Au, Pt)-modified SnS2 toward SF6 decomposition gases (SOF2, SO2F2, SO2, H2S) in gas-insulated switchgear was studied by analyzing the adsorption structure, band structure, charge transfer, and density of states based on density functional theory. The results show that the adsorption of the four target gases on pristine SnS2 belongs to weak physical adsorption. Compared with the pristine SnS2, the adsorption energy of the transition metal atom-modified SnS2 monolayer has been improved to a certain extent and the adsorption capacity of these four gases on the transition metal atom-modified SnS2 monolayer has obviously improved. Moreover, the recovery time of Ag-SnS2/SOF2, Ag-SnS2/SO2F2, Au-SnS2/SOF2, Au-SnS2/SO2F2, and Pt-SnS2/SO2F2 is too short, indicating that these conditions have poor adsorption capacity and sensitivity to SF6 decomposition gases and are not suitable as detection materials for these gases. According to the different changes in conductivity during adsorption, it provides a feasible solution to detect each SF6 decomposition gas. This theoretical study effectively explained the adsorption and sensing properties between the metal-modified monolayers and gases.

18.
Nat Commun ; 15(1): 2772, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555290

RESUMEN

The voltage-gated calcium channel CaV1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II, S6III, and S6IV helices and forms extensive hydrophobic interactions with CaV1.2. Our structure elucidates that benidipine is located in the DIII-DIV fenestration site. Its hydrophobic sidechain, phenylpiperidine, is positioned at the exterior of the pore domain and cradled within a hydrophobic pocket formed by S5DIII, S6DIII, and S6DIV helices, providing additional interactions to exert inhibitory effects on both L-type and T-type voltage gated calcium channels. These findings provide the structural foundation for the rational design and optimization of therapeutic inhibitors of voltage-gated calcium channels.


Asunto(s)
Canales de Calcio Tipo L , Canales de Calcio Tipo L/metabolismo , Estructura Secundaria de Proteína
19.
J Colloid Interface Sci ; 664: 1-12, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38458050

RESUMEN

The electrochemical conversion of nitrogen to ammonia provides an encouraging method to substitute the traditional Haber-Bosch process, owing to its high efficiency and mild reaction conditions. The search for high-performance catalysts and comprehension of catalytic mechanisms remains significant challenges. Herein, we conduct a systematic theoretical calculation of the NRR performance and mechanism of 24 Ti2XT2 (X = B, C, N; T = F, Cl, Br, I, O, S, Se, Te) MXenes with a T-vacancy to explore the influence of surface functional terminations and non-metallic center elements. Our findings demonstrate that surface functionalization significantly reduces the limiting potential by altering the rate-determining step. This change ranges from -1.24 V (Ti2NF2) to -0.21 V (Ti2BSe2), signifying the remarkable efficacy of modification of the surrounding environment of the exposed transition metal active center in promoting electrocatalytic performance. Detailed investigation of the charge density difference and orbital interaction reveals that the different NRR performance originates from the surface termination and non-metallic atoms regulate the electronic properties of the active Ti atoms. We also introduce the free energy change of *NNH2 (ΔG*NNH2) as a descriptor to predict the performance of NRR, which exhibits satisfactory linear relationship with free energy change of different intermediates and displays favourable volcano plot with limiting potential. Moreover, we highlight the pivotal role of work function in tuning the energy barrier of the rate-determining step, which can be regulated through the surface modification of MXenes. Our study not only offers a comprehensive understanding of the crucial impact of surface modification on the catalytic activities of defective MXenes, but also provides a rational perspective for designing efficient NRR catalysts.

20.
ChemSusChem ; : e202400150, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472126

RESUMEN

Cu-catalyzed electrochemical CO2 reduction reaction (CO2RR) produces multi-carbon (C2+) chemicals with considerable selectivities and activities, yet required high overpotentials impede its practical application. Here, we design interfaces with abrupt coordination number (CN) changes that greatly reduce the applied potential for achieving high C2+ Faradaic efficiency (FE). Encouraged by the mechanistic finding that the coupling between *CO and *CO(H) is the most probable C-C bond formation path, we use Cu2O- and Cu-phthalocyanine-derived Cu (OD-Cu and PD-Cu) to build the interface. Using operando X-ray absorption spectroscopy (XAS), we find that the Cu CN of OD-Cu is ~11, favoring CO* adsorption, while the PD-Cu has a COH*-favorable CN of ~4. Operando Raman spectroscopy revealed that the interfaces with abrupt CN changes promote *OCCOH formation. As a result, the designed catalyst achieves a C2+ FE of 85±2 % at 220 mA cm-2 in a zero-gap CO2 electrolyzer. An improvement of C2+ FE by 3 times is confirmed at the low potential regime where the current density is 60-140 mA cm-2, compared to bare OD-Cu. We report a 45-h stable CO2RR operation at 220 mA cm-2, producing a C2+ product FE of ~80 %.

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