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1.
J Chem Phys ; 160(22)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38856063

RESUMEN

We performed high-level ab initio quantum chemical calculations, incorporating higher-order excitations, spin-orbit coupling (SOC), and the Gaunt interaction, to calculate the electron affinities (EAs) of alkaline earth (AE) metal atoms (Ca, Sr, Ba, and Ra), which are notably small. The coupled-cluster singles and doubles with perturbative triples [CCSD(T)] method is insufficient to accurately calculate the EAs of AE metal atoms. Higher-order excitations proved crucial, with the coupled-cluster singles, doubles, and triples with perturbative quadruples [CCSDT(2)Q] method effectively capturing dynamic electron correlation effects. The contributions of SOC (ΔESOs) to the EAs calculated using the multireference configuration interaction method with the Davidson correction, including SOC, positively enhance the EAs; however, these contributions are overestimated. The Dirac-Hartree-Fock (DHF)-CCSD(T) method addresses this overestimation and provides reasonable values for ΔESO (ΔESO-D). Employing additional sets of diffuse and core-valence correlation basis sets is critical for accurately calculating the EAs of AE metal atoms. The contributions of the Gaunt interaction (ΔEGaunt) to the EAs of AE metal atoms are negligible. Notably, the CCSDT(2)Q with the complete basis set limit + ΔESO-D + ΔEGaunt produced EA values for Ca, Sr, and Ba that closely aligned with experimental data and achieved accuracy exceeding the chemical accuracy. Based on our findings, the accurately proposed EA for Ra is 9.88 kJ/mol.

2.
Aging Cell ; : e14203, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769776

RESUMEN

The relationship between aging and RNA biogenesis and trafficking is attracting growing interest, yet the precise mechanisms are unknown. The THO complex is crucial for mRNA cotranscriptional maturation and export. Herein, we report that the THO complex is closely linked to the regulation of lifespan. Deficiencies in Hpr1 and Tho2, components of the THO complex, reduced replicative lifespan (RLS) and are linked to a novel Sir2-independent RLS control pathway. Although transcript sequestration in hpr1Δ or tho2Δ mutants was countered by exosome component Rrp6, loss of this failed to mitigate RLS defects in hpr1Δ. However, RLS impairment in hpr1Δ or tho2Δ was counteracted by the additional expression of Nrd1-specific mutants that interacted with Rrp6. This effect relied on the interaction of Nrd1, a transcriptional regulator of aging-related genes, including ribosome biogenesis or RNA metabolism genes, with RNA polymerase II. Nrd1 overexpression reduced RLS in a Tho2-dependent pathway. Intriguingly, Tho2 deletion mirrored Nrd1 overexpression effects by inducing arbitrary Nrd1 chromatin binding. Furthermore, our genome-wide ChIP-seq analysis revealed an increase in the recruitment of Nrd1 to translation-associated genes, known to be related to aging, upon Tho2 loss. Taken together, these findings underscore the importance of Tho2-mediated Nrd1 escorting in the regulation of lifespan pathway through transcriptional regulation of aging-related genes.

3.
ACS Appl Mater Interfaces ; 16(17): 22512-22521, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38651627

RESUMEN

Gold-sulfur interaction has vital importance in nanotechnologies and material chemistry to design functional nanoparticles, self-assembled monolayers, or molecular complexes. In this paper, a mixture of only two basic precursors, such as the chloroauric acid (HAu(III)Cl4) and a thiol molecule (p-fluorothiophenol (p-HSPhF)), are used for the synthesis of gold(I)-thiolate coordination polymers. Under different conditions of synthesis and external stimuli, five different functional materials with different states of [Au(I)(p-SPhF)]n can be afforded. These gold-thiolate compounds are (i) red emissive, flexible, and crystalline fibers; (ii) composite materials made of these red emissive fibers and gold nanoparticles; (iii) amorphous phase; (iv) transparent glass; and (v) amorphous-to-crystalline phase-change material associated with an ON/OFF switch of luminescence. The different functionalities of these materials highlight the great versatility of the gold(I) thiolate coordination polymers with easy synthesis and diverse shaping that may have great potential as sustainable phosphors, smart textiles, sensors, and phase change memories.

4.
ACS Omega ; 9(13): 15493-15501, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38585131

RESUMEN

Glucose oxidase (GOx) activity assays are vital for various applications, including glucose metabolism estimation and fungal testing. However, conventional methods involve time-consuming and complex procedures. In this study, we present a colorimetric platform for in situ GOx activity measurement utilizing redox-sensitive electrochromic nanoparticles based on polyaniline (PAni). The glucose-adsorbed colorimetric paper sensor, herein termed Glu@CPS, is created by immobilizing ferrocene and glucose onto paper substrates that have been functionalized with PAni nanoparticles. Glu@CPS not only demonstrated rapid detection (within 5 min) but also exhibited remarkable selectivity for GOx and a limit of detection as low as 1.25 µM. Moreover, Glu@CPS demonstrated consistent accuracy in the measurement of GOx activity, exhibiting no deviations even after being stored at ambient temperature for a duration of one month. To further corroborate the effectiveness of this method, we applied Glu@CPS in the detection of GOx activity in a moldy red wine. The results highlight the promising potential of Glu@CPS as a convenient and precise platform for GOx activity measurement in diverse applications including food quality control, environmental monitoring, and early detection of fungal contamination.

5.
Adv Sci (Weinh) ; 11(19): e2306684, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38482992

RESUMEN

Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor-suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy. Here, a cold-responsive nanoplatform composed of upconversion nanoparticles coated with silica - chlorin e6 - hyaluronic acid (UCNPs@SiO2-Ce6-HA) is designed. This nanoplatform is employed to integrate cryotherapy with photodynamic therapy (PDT) in order to improve skin cancer treatment efficacy in a synergistic manner. The cryotherapy appeared to enhance the upconversion brightness by suppressing the thermal quenching. The low-temperature treatment afforded a 2.45-fold enhancement in the luminescence of UCNPs and a 3.15-fold increase in the photodynamic efficacy of UCNPs@SiO2-Ce6-HA nanoplatforms. Ex vivo tests with porcine skins and the subsequent validation in mouse tumor tissues revealed the effective HA-mediated transdermal delivery of designed nanoplatforms to deep tumor tissues. After transdermal delivery, in vivo photodynamic therapy using the UCNPs@SiO2-Ce6-HA nanoplatforms resulted in the optimized efficacy of 79% in combination with cryotherapy. These findings underscore the Cryo-PDT as a truly promising integrated treatment paradigm and warrant further exploring the synergistic interplay between cryotherapy and PDT with bright upconversion to unlock their full potential in cancer therapy.


Asunto(s)
Ácido Hialurónico , Nanopartículas , Fotoquimioterapia , Animales , Fotoquimioterapia/métodos , Ratones , Ácido Hialurónico/química , Nanopartículas/química , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/tratamiento farmacológico , Crioterapia/métodos , Clorofilidas , Porfirinas/química , Porfirinas/administración & dosificación , Modelos Animales de Enfermedad , Fármacos Fotosensibilizantes/administración & dosificación , Administración Cutánea , Dióxido de Silicio/química , Porcinos
6.
J Phys Chem Lett ; 15(5): 1390-1396, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38289254

RESUMEN

The post-encapsulation method (such as single-layered encapsulation) is a promising strategy to synthesize yolk-shell structures that protect functional nanoparticles by the molecular sieving effect. However, this method exhibited limited loading capacity and nonuniform encapsulation during the co-encapsulation of various nanoparticles owing to the insufficient surface area for nanoparticle attachment. To address these limitations, we proposed a double-layered encapsulation method comprising an increased number of silica template layers and separate attachment of multifarious nanoparticles to different layers. Compared with conventional methods, this strategy can precisely adjust the ratio of encapsulated nanoparticles and increase the loading amount, which improves the functionality of yolk-shell structures, such as the photothermal properties of gold nanoparticle-encapsulated yolk-shell structures (∼69%). We describe, for the first time, the precise control of the ratio of encapsulated nanoparticles and the loading of numerous nanoparticles. Consequently, this strategy has significant potential for various applications of yolk-shell structures.

7.
Sci Adv ; 9(49): eadi6681, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-38055811

RESUMEN

Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that are reversible but can be trapped by TOP2 poisons. Trapped TOP2ccs block transactions on DNA and generate genotoxic stress, which are the mechanisms of action of TOP2 poisons. How cells avoid TOP2cc accumulation remains largely unknown. In this study, we uncovered RAD54 like 2 (RAD54L2) as a key factor that mediates a TOP2-specific DNA damage avoidance pathway. RAD54L2 deficiency conferred unique sensitivity to treatment with TOP2 poisons. RAD54L2 interacted with TOP2A/TOP2B and ZATT/ZNF451 and promoted the turnover of TOP2 from DNA with or without TOP2 poisons. Additionally, inhibition of proteasome activity enhanced the chromatin binding of RAD54L2, which in turn led to the removal of TOP2 from chromatin. In conclusion, we propose that RAD54L2-mediated TOP2 turnover is critically important for the avoidance of potential TOP2-linked DNA damage under physiological conditions and in response to TOP2 poisons.


Asunto(s)
Venenos , ADN-Topoisomerasas de Tipo II/genética , Daño del ADN , Reparación del ADN , ADN/química , Cromatina/genética
8.
Int J Biochem Cell Biol ; 162: 106454, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37574041

RESUMEN

Cisplatin, a widely prescribed chemotherapeutic agent for treating solid tumors, induces DNA adducts and activates cellular defense mechanisms, including DNA repair, cell cycle checkpoint control, and apoptosis. Considering the circadian rhythmicity displayed by most chemotherapeutic agents and their varying therapeutic efficacy based on treatment timing, our study aimed to investigate whether the circadian clock system influences the DNA damage responses triggered by cisplatin in synchronized cells. We examined the DNA damage responses in circadian-synchronized wild-type mouse embryonic fibroblasts (WT-MEF; clock-proficient cells), cryptochrome1 and 2 double knock-out MEF (CRYDKO; clock-deficient cells), and mouse hepatocarcinoma Hepa1c1c7 cells. Varying the treatment time resulted in a significant difference in the rate of platinum-DNA adduct removal specifically in circadian-synchronized WT-MEF, while CRYDKO did not exhibit such variation. Moreover, diurnal variation in other DNA damage responses, such as cell cycle checkpoint activity indicated by p53 phosphorylation status and apoptosis measured by DNA break frequency, was observed only in circadian-synchronized WT-MEF, not in CRYDKO or mouse hepatocarcinoma Hepa1c1c7 cells. These findings highlight that the DNA damage responses triggered by cisplatin are indeed governed by circadian control exclusively in clock-proficient cells. This outcome bears potential implications for enhancing or devising chronotherapy approaches for cancer patients.


Asunto(s)
Relojes Circadianos , Neoplasias , Animales , Ratones , Cisplatino/farmacología , Cisplatino/uso terapéutico , Aductos de ADN/uso terapéutico , Daño del ADN , Fibroblastos/metabolismo , Reparación del ADN , Relojes Circadianos/genética , Neoplasias/genética , Apoptosis
9.
J Phys Chem A ; 127(28): 5815-5822, 2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37432658

RESUMEN

We re-examined the existence of planar tetracoordinate F (ptF) atoms, which was proposed recently by using high-level ab initio methods such as coupled-cluster singles and doubles with perturbative triples (CCSD(T)) with large basis sets. Our calculations indicate that the planar structures of FIn4+ (D4h), FTl4+ (D4h), FGaIn3+ (C2V), FIn2Tl2+ (D2h), FIn3Tl+ (C2V), and FInTl3+ (C2V) are not the minimum energy states; by contrast, they are transition states. Density functional theory calculations overestimate the size of the cavity formed by the four peripheral atoms, leading to erroneous conclusions regarding the existence of ptF atoms. Our analysis suggests that the preference for non-planar structures in the six cations studied is not due to the pseudo Jahn-Teller effect. Additionally, spin-orbit coupling does not alter the main conclusion that the ptF atom does not exist. If sufficiently large cavity formation by group 13 elements to accommodate the central F- ion is guaranteed, then the existence of ptF atoms is plausible.

10.
Nurs Health Sci ; 25(3): 402-410, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37519187

RESUMEN

This study aimed to examine the association of COVID-19-related stress, anxiety, access to public healthcare services, and the presence of secondary caregivers (CGs) on the burden of caregiving and health-related quality of life (HRQoL) for CGs of people with dementia (PwD). A cross-sectional survey with 218 family CGs for PwD was completed in various settings between August and September 2021. The CGs had moderate and severe stress (42.7%) and reported having difficulty accessing public healthcare services (51.8%) and receiving help from secondary CGs (42.7%). In the multivariable linear regression, the stress and anxiety levels related to COVID-19 had a positive association with caregiver burden (ß = 4.25, p < 0.001, and ß = 5.73, p = 0.032, respectively), with no statistically significant association to HRQoL. Unexpectedly, accessing public healthcare services and supporting the secondary CGs were unrelated to the caregiving burden and HRQoL. Therefore, interventions aiming to alleviate family CGs' stress and anxiety levels should be provided to ensure PwD live in their homes in terms of continuity of public health service delivery.


Asunto(s)
COVID-19 , Carga del Cuidador , Cuidadores , Demencia , Humanos , COVID-19/epidemiología , Pandemias , Calidad de Vida , Cuidadores/psicología , Estudios Transversales , Accesibilidad a los Servicios de Salud , Masculino , Femenino , Persona de Mediana Edad
11.
Exp Mol Med ; 55(7): 1492-1505, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37394593

RESUMEN

Hepatic glucose production by glucagon is crucial for glucose homeostasis during fasting, yet the underlying mechanisms remain incompletely delineated. Although CD38 has been detected in the nucleus, its function in this compartment is unknown. Here, we demonstrate that nuclear CD38 (nCD38) controls glucagon-induced gluconeogenesis in primary hepatocytes and liver in a manner distinct from CD38 occurring in the cytoplasm and lysosomal compartments. We found that the localization of CD38 in the nucleus is required for glucose production by glucagon and that nCD38 activation requires NAD+ supplied by PKCδ-phosphorylated connexin 43. In fasting and diabetes, nCD38 promotes sustained Ca2+ signals via transient receptor potential melastatin 2 (TRPM2) activation by ADP-ribose, which enhances the transcription of glucose-6 phosphatase and phosphoenolpyruvate carboxykinase 1. These findings shed light on the role of nCD38 in glucagon-induced gluconeogenesis and provide insight into nuclear Ca2+ signals that mediate the transcription of key genes in gluconeogenesis under physiological conditions.


Asunto(s)
Diabetes Mellitus , Canales Catiónicos TRPM , Humanos , Gluconeogénesis/fisiología , Glucagón , Adenosina Difosfato Ribosa/metabolismo , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Hígado/metabolismo , Glucosa/metabolismo , Hepatocitos/metabolismo , Ayuno , Diabetes Mellitus/metabolismo
12.
PeerJ Comput Sci ; 9: e1355, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37346503

RESUMEN

Innovative technology and improvements in intelligent machinery, transportation facilities, emergency systems, and educational services define the modern era. It is difficult to comprehend the scenario, do crowd analysis, and observe persons. For e-learning-based multiobject tracking and predication framework for crowd data via multilayer perceptron, this article recommends an organized method that takes e-learning crowd-based type data as input, based on usual and abnormal actions and activities. After that, super pixel and fuzzy c mean, for features extraction, we used fused dense optical flow and gradient patches, and for multiobject tracking, we applied a compressive tracking algorithm and Taylor series predictive tracking approach. The next step is to find the mean, variance, speed, and frame occupancy utilized for trajectory extraction. To reduce data complexity and optimization, we applied T-distributed stochastic neighbor embedding (t-SNE). For predicting normal and abnormal action in e-learning-based crowd data, we used multilayer perceptron (MLP) to classify numerous classes. We used the three-crowd activity University of California San Diego, Department of Pediatrics (USCD-Ped), Shanghai tech, and Indian Institute of Technology Bombay (IITB) corridor datasets for experimental estimation based on human and nonhuman-based videos. We achieve a mean accuracy of 87.00%, USCD-Ped, Shanghai tech for 85.75%, and IITB corridor of 88.00% datasets.

13.
Int J Mol Sci ; 24(7)2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37047518

RESUMEN

Etoposide (ETO) is an anticancer drug that targets topoisomerase II (TOP2). It stabilizes a normally transient TOP2-DNA covalent complex (TOP2cc), thus leading to DNA double-strand breaks (DSBs). Tyrosyl-DNA phosphodiesterases two (TDP2) is directly involved in the repair of TOP2cc by removing phosphotyrosyl peptides from 5'-termini of DSBs. Recent studies suggest that additional factors are required for TOP2cc repair, which include the proteasome and the zinc finger protein associated with TDP2 and TOP2, named ZATT. ZATT may alter the conformation of TOP2cc in a way that renders the accessibility of TDP2 for TOP2cc removal. In this study, our genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens revealed that ZATT also has a TDP2-independent role in promoting cell survival following ETO treatment. ZATT KO cells showed relatively higher ETO sensitivity than TDP2-KO cells, and ZATT/TDP2 DKO cells displayed additive hypersensitivity to ETO treatment. The study using a series of deletion mutants of ZATT determined that the N-terminal 1-168 residues of ZATT are required for interaction with TOP2 and this interaction is critical to ETO sensitivity. Moreover, depletion of ZATT resulted in accelerated TOP2 degradation after ETO or cycloheximide (CHX) treatment, suggesting that ZATT may increase TOP2 stability and likely participate in TOP2 turnover. Taken together, this study suggests that ZATT is a critical determinant that dictates responses to ETO treatment and targeting. ZATT is a promising strategy to increase ETO efficacy for cancer therapy.


Asunto(s)
Proteínas de Unión al ADN , Venenos , Etopósido/farmacología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , ADN-Topoisomerasas de Tipo II/genética , ADN-Topoisomerasas de Tipo II/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , ADN/metabolismo
14.
Chemphyschem ; 24(13): e202300048, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37040088

RESUMEN

The photochemical reaction mechanism underlying the intramolecular H-transfer of the H2 C3 O+ ⋅ radical cation to the H2 CCCO+ ⋅ methylene ketene cation was elucidated using time-dependent density functional theory and high-level ab initio methods. Once the D1 state of H2 C3 O+ ⋅ is populated, the reaction proceeds to form an intermediate (IM) in the D1 state (IM4D1 ). The molecular structure of the conical intersection (CI) was optimized using a multiconfigurational ab initio method. The CI is readily accessible because it lies slightly above the IM4D1 in energy. In addition, the gradient difference vector of the CI is almost parallel to the intramolecular H-transfer reaction coordinate. Once the vibration mode of IM4D1 which is parallel to the reaction coordinate is populated, the degeneracy of the CI is readily lifted and H2 CCCO+ ⋅ was formed via a relaxation pathway in the D0 state. Our calculated results clearly describe the photochemical intramolecular H transfer reaction reported in a recent study.

15.
J Chem Phys ; 158(15)2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37094019

RESUMEN

Discovery of a new oxidation state for an element expands its chemistry. A high oxidation state, such as +7, is rare for sp-block elements except for halogens. In this study, we determined that Te can attain a +7 oxidation state through the existence of a distorted octahedron (DOH) structure of TeCl6+ based on coupled cluster singles and doubles with perturbative triples calculations. We propose a new type of isomerization that resembles pseudorotation. The octahedron structure of TeF6+ bearing one elongated axial bond isomerizes to a DOH via an associated pseudorotation.

16.
Aging Dis ; 14(2): 484-501, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37008056

RESUMEN

Aging can increase the risk of various hepatic diseases, especially non-alcoholic fatty liver disease (NAFLD). Although the mechanisms underlying the pathogenesis of age-related disorders such as NAFLD remain incompletely understood, recent studies have implicated the accumulation of senescent cells as a contributing factor. Here, we show that tristetraprolin (TTP) deficiency accelerates NAFLD during aging by enhancing the senescence-associated secretory phenotype (SASP) as well as several hallmarks of senescence. The sequestration of plasminogen activator inhibitor (PAI)-1, a mediator of cellular senescence, in stress granules, (SGs) inhibits cellular senescence. In our previous report, we have shown that carbon monoxide (CO), a small gaseous mediator, can induce the assembly of SGs via an integrated stress response. Here, we show that CO treatment promotes the assembly of SGs which can sequester PAI-1, resulting in the inhibition of etoposide (ETO)-induced cellular senescence. Notably, CO-induced TTP activation enhances PAI-1 degradation, leading to protection against ETO-induced cellular senescence. CO-dependent Sirt1 activation promotes the inclusion of TTP into SGs, leading to decreased PAI-1 levels. Therefore, our findings highlight the importance of TTP as a therapeutic target in age-related NAFLD and offer a potential new strategy to reduce the detrimental effects of senescent cells in hepatic disorders.

17.
J Nutr Biochem ; 118: 109325, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36958418

RESUMEN

The molecular mechanisms underlying the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD), and Huntington's disease remain enigmatic, resulting in an unmet need for therapeutics development. Here, we suggest that filbertone, a key flavor compound found in the fruits of hazel trees of the genus Corylus, can ameliorate PD via lowering the abundance of aggregated α-synuclein. We previously reported that inhibition of hypothalamic inflammation by filbertone is mediated by suppression of nuclear factor kappa-B. Here, we report that filbertone activates PERK through mitochondrial reactive oxygen species production, resulting in the increased nuclear translocation of transcription factor-EB in SH-SY5Y human neuroblastoma cells. TFEB activation by filbertone promotes the autophagy-lysosomal pathway, which in turn alleviates the accumulation of α-synuclein. We also demonstrate that filbertone prevented the loss of dopaminergic neurons in the substantia nigra and striatum of mice on high-fat diet. Filbertone treatment also reduced high-fat diet-induced α-synuclein accumulation through upregulation of the autophagy-lysosomal pathway. In addition, filbertone improved behavioral abnormalities (i.e., latency time to fall and decrease of running distance) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD murine model. In conclusion, filbertone may show promise as a potential therapeutic for neurodegenerative disease.


Asunto(s)
Neuroblastoma , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Ratones , Animales , alfa-Sinucleína/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neuroblastoma/patología , Enfermedad de Parkinson/tratamiento farmacológico , Autofagia/fisiología , Neuronas Dopaminérgicas/metabolismo , Lisosomas/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo
18.
Metabolism ; 141: 155516, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36773805

RESUMEN

OBJECTIVE: Emerging evidence suggests that crosstalk between Kupffer cells (KCs) and hepatocytes protects against non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms that lead to the reduction of steatosis in NAFLD remain obscure. METHODS: Ttp+/+ and Ttp-/- mice were fed with a high-fat diet. Hepatic steatosis was analyzed by Nile Red staining and measurement of inflammatory cytokines. Lipid accumulation and cell death were evaluated in co-culture systems with primary hepatocytes and KCs derived from either Ttp+/+ or Ttp-/- mice. RESULTS: Tristetraprolin (TTP), an mRNA binding protein, was essential for the protective effects of metformin in NAFLD. Metformin activated TTP via the AMPK-Sirt1 pathway in hepatocytes and KCs. TTP inhibited TNF-α production in KCs, which in turn decreased hepatocyte necroptosis. Downregulation of Rheb expression by TTP promoted hepatocyte lipophagy via mTORC1 inhibition and increased nuclear translocation of transcription factor-EB (TFEB). Consistently, TTP-deficient NAFLD mice failed to respond to metformin with respect to alleviation of hepatic steatosis, protection of hepatocyte necroptosis, or induction of lipophagy. CONCLUSIONS: TTP, which is essential for the protective effects of metformin, may represent a novel primary therapeutic target in NAFLD.


Asunto(s)
Metformina , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hígado/metabolismo , Macrófagos del Hígado , Metformina/farmacología , Necroptosis , Hepatocitos/metabolismo , Comunicación , Autofagia , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Metabolismo de los Lípidos
19.
Nurs Open ; 10(2): 579-590, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36631728

RESUMEN

AIM: The study aimed to assess the validity and reliability of the short-form Nurse Professional Competence Scale-Korean version (NPC-K) among Korean nursing students at the point of graduation. DESIGN: This was a cross-sectional survey. METHODS: The Nurse Professional Competence scale was translated into Korean using the World Health Organization (WHO) translation method. A total of 195 graduating nursing students participated. Exploratory factor analysis for validity and Cronbach's alpha coefficients for reliability were examined. RESULTS: Factor analysis showed that five NPC-K factors accounted for 68.38% of the total variance. Cronbach's alpha for the total scale was 0.97. The NPC-K has high internal reliability and acceptable construct validity. The content of the scale reflected nursing students' confidence in formal competence requirements based on Korean cultural and educational backgrounds. An accurate assessment of nurse professional competence using the NPC-K may help nursing academics enhance the quality of education and training.


Asunto(s)
Estudiantes de Enfermería , Humanos , Estudios Transversales , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Competencia Profesional , Análisis Factorial , República de Corea
20.
ACS Appl Mater Interfaces ; 14(48): 53999-54011, 2022 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-36444765

RESUMEN

It has been challenging to synthesize p-type SnOx (1 < x < 2) and engineer the electrical properties such as carrier density and mobility due to the narrow processing window and the localized oxygen 2p orbitals near the valence band. Herein, we report on the multifunctional encapsulation of p-SnOx to limit the surface adsorption of oxygen and selectively permeate hydrogen into the p-SnOx channel for thin-film transistor (TFT) applications. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) measurements identified that ultrathin SiO2 as a multifunctional encapsulation layer effectively suppressed the oxygen adsorption on the back channel surface of p-SnOx and selectively diffused hydrogen across the entire thickness of the channel. Encapsulated p-SnOx-based TFTs demonstrated much enhanced channel conductance modulation in response to the gate bias applied, featuring higher on-state current and lower off-state current (on/off ratio > 103), field effect mobility of 3.41 cm2/(V s), and threshold voltages of ∼5-10 V. The fabricated devices show minimal deviations as small as ±6% in the TFT performance parameters, which demonstrates good reproducibility of the fabrication process. The relevance between the TFT performance and the effects of hydrogen permeation is discussed in regard to the intrinsic and extrinsic doping mechanisms. Density functional theory calculations reveal that hydrogen-related impurity complexes are in charge of the enhanced channel conductance with gate biases, which further supports the selective permeation of hydrogen through a thin SiO2 encapsulation.

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