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1.
Materials (Basel) ; 17(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38893991

RESUMO

This study investigates the effect of a high-temperature annealing process on the characteristics and performance of a memristor based on a Ag/Ga2O3/Pt structure. Through X-ray diffraction analysis, successful phase conversion from amorphous Ga2O3 to ß-Ga2O3 is confirmed, attributed to an increase in grain size and recrystallization induced by annealing. X-ray photoelectron spectroscopy analysis revealed a higher oxygen vacancy in annealed Ga2O3 thin films, which is crucial for conductive filament formation and charge transport in memristors. Films with abundant oxygen vacancies exhibit decreased set voltages and increased capacitance in a low-resistive state, enabling easy capacitance control depending on channel presence. In addition, an excellent memory device with a high on/off ratio can be implemented due to the reduction of leakage current due to recrystallization. Therefore, it is possible to manufacture a thin film suitable for a memristor by increasing the oxygen vacancy in the Ga2O3 film while improving the overall crystallinity through the annealing process. This study highlights the significance of annealing in modulating capacitance and high-resistive/low-resistive state properties of Ga2O3 memristors, contributing to optimizing device design and performance. This study underscores the significance of high-temperature annealing in improving the channel-switching characteristics of Ga2O3-based memristors, which is crucial for the development of low-power, high-efficiency memory device.

2.
J Rehabil Med ; 56: jrm35279, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898678

RESUMO

OBJECTIVE: To examine the association between physical activity, neck circumference, and cardiovascular disease risk in older wheelchair users. DESIGN: A cross-sectional study. SUBJECTS/PATIENTS: Sixty-one Korean wheelchair users aged 50 years and older. METHODS: Physical activity was assessed using a self-administered questionnaire. Neck circumference was measured with a tape ruler. Cardiovascular disease risk was evaluated by calculating the Framingham risk score (FRS) for estimating 10-year cardiovascular disease risk, which was classified as low-moderate (19% or less) or high risk (20% or more). RESULTS: The FRS for 10-year cardiovascular disease risk was inversely related to physical activity (beta [SE] = -0.213 (0.103), p = 0.043) and positively related to neck circumference (beta [SE] = 1.331 ± 0.419, p = 0.003). Binary logistic regression showed that those with low physical activity (odds ratio [95% confidence interval] = 4.256 (1.188~15.243), p = 0.026) or a large neck circumference (odds ratio [95% confidence interval] = 3.645 (1.172~11.338), p = 0.025) had a higher risk for high cardiovascular disease risk compared with those with high physical activity or normal neck circumference. CONCLUSION: The current study findings suggest that an intervention targeting physical inactivity and upper-body obesity should be implemented to reduce cardiovascular disease risk in older wheelchair users.


Assuntos
Doenças Cardiovasculares , Pescoço , Cadeiras de Rodas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Doenças Cardiovasculares/etiologia , Atividade Motora/fisiologia , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Exercício Físico/fisiologia , Inquéritos e Questionários , Pessoas com Deficiência
3.
Small Methods ; : e2301251, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308408

RESUMO

The 1T phase of MoS2 exhibits much higher electrocatalytic activity and better stability than the 2H phase. However, the harsh conditions of 1T phase synthesis remain a significant challenge for various extensions and applications of MoS2 . In this work, a simple hydrothermal-based synthesis method for the phase transition of MoS2 is being developed. For this, the NH2 -MIL-125(Ti) (Ti MOF) is successfully utilized to induce the phase transition of MoS2 from 2H to 1T, achieving a high conversion ratio of ≈78.3%. The optimum phase-induced MoS2 /Ti MOF heterostructure demonstrates enhanced oxygen evolution reaction (OER) performance, showing an overpotential of 290 mV at a current density of 10 mA cm-2 . The density functional theory (DFT) calculations are demonstrating the benefits of this phase transition, determining the electronic properties and OER performance of MoS2 .

4.
Mar Drugs ; 22(2)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38393059

RESUMO

Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.


Assuntos
Neoplasias , Streptomyces , Humanos , Linhagem Celular Tumoral , Células CACO-2 , Streptomyces/metabolismo , Células A549 , Proteínas rho de Ligação ao GTP/metabolismo , Movimento Celular , Transição Epitelial-Mesenquimal
5.
Arch Virol ; 169(3): 41, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326489

RESUMO

Despite significant improvements in vaccines and chemotherapeutic drugs, pathogenic RNA viruses continue to have a profound impact on the global economy and pose a serious threat to animal and human health through emerging and re-emerging outbreaks of diseases. To overcome the challenge of viral adaptation and evolution, increased vigilance is required. Particularly, antiviral drugs derived from new, natural sources provide an attractive strategy for controlling problematic viral diseases. In this antiviral study, we discovered a previously unknown bacterium, Mameliella sp. M20D2D8, by conducting an antiviral screening of marine microorganisms. An extract from M20D2D8 exhibited antiviral activity with low cytotoxicity and was found to be effective in vitro against multiple influenza virus strains: A/PR8 (IC50 = 2.93 µg/mL, SI = 294.85), A/Phil82 (IC50 = 1.42 µg/mL, SI = 608.38), and B/Yamagata (IC50 = 1.59 µg/mL, SI = 543.33). The antiviral action was found to occur in the post-entry stages of viral replication and to suppress viral replication by inducing apoptosis in infected cells. Moreover, it efficiently suppressed viral genome replication, protein synthesis, and infectivity in MDCK and A549 cells. Our findings highlight the antiviral capabilities of a novel marine bacterium, which could potentially be useful in the development of drugs for controlling viral diseases.


Assuntos
Herpesvirus Cercopitecino 1 , Influenza Humana , Viroses , Animais , Humanos , Influenza Humana/tratamento farmacológico , Antivirais/farmacologia , Extratos Vegetais/farmacologia , Replicação Viral
6.
Nutrients ; 16(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38257121

RESUMO

Caffeine is present in various foods and medicines and is highly accessible through various routes, regardless of age. However, most studies on caffeine have focused on the effects of high-dose caffeine ingestion based on the recommended daily amount for adults. In this study, we examined the physiological changes in the central and peripheral vessels that may occur when ingesting low-dose caffeine due to its high accessibility, with the aim of creating an environment of safe caffeine ingestion. This study included 26 healthy participants in their 20s. Peak systolic velocity (PSV), heart rate (HR), and pulse wave velocity (PWV) for vascular stiffness assessment were measured at 0, 30, and 60 min after caffeine ingestion using diagnostic ultrasound to determine the physiological changes in the blood vessels, common carotid artery (CCA) and radial artery (RA). In addition, percutaneous oxygen saturation (SpO2), blood pressure (BP), and accelerated photoplethysmography (APG) were measured. In comparison with before ingestion, the HR tended to decrease and showed a significant difference at 30 and 60 min (p = 0.014 and p = 0.031, respectively). PSV significantly decreased in both vessels at 30 and 60 min (p < 0.001 and p < 0.001, respectively). APG showed a decreasing trend until 60 min after ingestion, with a significant difference at 30 and 60 min (p = 0.003 and p = 0.012, respectively). No significant difference was observed in SpO2, BP, or PWV; however, they showed a tendency to increase after ingestion. Decreased HR may occur because of the baroreflex caused by an increase in BP. The RA has many branches and a smaller diameter; therefore, the PSV was lower in the RA than that in the CCA. This effect can occur because of the difficulty in the smooth expansion of blood vessels, which leads to a decrease in blood flow. In addition, an increase in intracellular calcium concentration can prevent vasodilation and increase the propagation velocity of pulse waves. The reflected waves can increase systolic blood pressure but reduce PWV and vascular elasticity. These results suggest that even low-dose caffeine can improve blood vessel health by providing temporary stimulation to the blood vessels; however, it can also cause changes in blood flow and blood vessel elasticity, which can lead to serious diseases such as stroke and high blood pressure. Therefore, caution should be exercised when caffeine consumption is indiscriminate.


Assuntos
Cafeína , Análise de Onda de Pulso , Adulto , Humanos , Ultrassonografia , Artéria Radial , Ingestão de Alimentos
7.
Small ; 20(1): e2305289, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37649146

RESUMO

Green fuel from water splitting is hardcore for future generations, and the limited source of fresh water (<1%) is a bottleneck. Seawater cannot be used directly as a feedstock in current electrolyzer techniques. Until now single atom catalysts were reported by many synthetic strategies using notorious chemicals and harsh conditions. A cobalt single-atom (CoSA) intruding cobalt oxide ultrasmall nanoparticle (Co3 O4 USNP)-intercalated porous carbon (PC) (CoSA-Co3 O4 @PC) electrocatalyst was synthesized from the waste orange peel as a single feedstock (solvent/template). The extended X-ray absorption fine structure spectroscopy (EXAFS) and theoretical fitting reveal a clear picture of the coordination environment of the CoSA sites (CoSA-Co3 O4 and CoSA-N4 in PC). To impede the direct seawater corrosion and chlorine evolution the seawater has been desalinated (Dseawater) with minimal cost and the obtained PC is used as an adsorbent in this process. CoSA-Co3 O4 @PC shows high oxygen evolution reaction (OER) activity in transitional metal impurity-free (TMIF) 1 M KOH and alkaline Dseawater. CoSA-Co3 O4 @PC exhibits mass activity that is 15 times higher than the commercial RuO2 . Theoretical interpretations suggest that the optimized CoSA sites in Co3 O4 USNPs reduce the energy barrier for alkaline water dissociation and simultaneously trigger an excellent OER followed by an adsorbate evolution mechanism (AEM).

8.
Maturitas ; 180: 107891, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38006815

RESUMO

The effects of normal-weight obesity, which is defined as having a high level of body fat despite a normal body mass index, on the health of bones in older adults are poorly understood. This cross-sectional study examined the relationship between normal-weight obesity and bone mineral density in Korean adults aged 50 years or more (2815 men and 2744 women) from the 2008-2011 Korea National Health and Nutrition Examination Surveys. Between the ages of 50 and 69 years, individuals with normal-weight obesity had a higher risk of low bone mineral density (odds ratio = 1.596, 95 % confidence interval = 1.189-2.141, p = 0.002) compared with individuals with normal-weight non-obesity. However, no significant association between normal-weight obesity and bone mineral density was observed among people between the ages of 70 and 89 years. The study findings support the clinical significance of normal-weight obesity as a proxy biomarker to identify in primary care settings people who are at increased risk of developing osteoporosis at an early stage of aging.


Assuntos
Densidade Óssea , Osteoporose , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Obesidade/complicações , Osteoporose/etiologia , Osteoporose/complicações , Inquéritos Nutricionais , República da Coreia/epidemiologia
9.
Front Bioeng Biotechnol ; 11: 1296832, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38116201

RESUMO

Conventional swabs have been used as a non-invasive method to obtain samples for DNA analysis from the buccal and the nasal mucosa. However, swabs may not always collect pure enough genetic material. In this study, buccal and nasal microneedle swab is developed to improve the accuracy and reliability of genomic analysis. A cytotoxicity test, a skin sensitivity test, and a skin irritation test are conducted with microneedle swabs. Polymer microneedle swabs meet the safety requirements for clinical research and commercial use. When buccal and nasal microneedle swabs are used, the amount of genetic material obtained is greater than that from commercially available swabs, and DNA purity is also high. The comparatively short microneedle swab (250 µm long) cause almost no pain to all 25 participants. All participants also report that the microneedle swabs are very easy to use. When genotypes are compared at five SNP loci from blood of a participant and from that person's buccal or nasal microneedle swab, the buccal and nasal microneedle swabs show 100% concordance for all five SNP genotypes. Microneedle swabs can be effectively used for genomic analysis and prevention through genomic analysis, so the utilization of microneedle swabs is expected to be high.

10.
Heliyon ; 9(12): e23157, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144313

RESUMO

We studied on the bipolar resistive switching (RS)-dependent capacitance of Ga2O3 memristors, grown using controlled oxygen flow via a radio frequency sputtering process. The Ag/Ga2O3/Pt memristor structure was employed to investigate the capacitance changes associated with RS behavior and oxygen concentration. In the low-resistance state (LRS), capacitance increased by over 60 times compared to the high-resistance state (HRS). Furthermore, in the HRS state, increasing the oxygen flow from 0 to 0.3 sccm resulted in an 80 % decrease in capacitance, while in the LRS state, capacitance increased by 128 %. These results indicate that RS-dependent capacitance in Ga2O3 memristors is influenced by the density of oxygen vacancies. The presence of oxygen vacancies affects charge storage capacity and capacitance, with higher oxygen concentrations leading to reduced capacitance in HRS and increased capacitance in LRS. The results contribute to the understanding of the capacitance behavior in Ga2O3 memristors and highlight the significance of oxygen vacancies in their operation.

11.
Healthcare (Basel) ; 11(16)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37628501

RESUMO

BACKGROUND: The disadvantage of using body mass index (BMI) as an obesity diagnostic tool is that it cannot distinguish between fat mass and lean mass, which may understate the impact of obesity on metabolic complications. This population-based cross-sectional study aimed to investigate the relationship between normal-weight obesity (NWO) and metabolic syndrome in Korean adults aged 20 years (5962 males and 6558 females) who took part in the Korea National Health and Nutrition Examination Surveys from 2008 to 2011. METHODS: NWO was defined as having a BMI of 18.5 to 24.9 kg/m2 and a body fat percentage of 26.0% in males or 36.0% in females. Metabolic syndrome (MetS) was defined using the revised National Cholesterol Education Program definition, with a Korean-specific waist circumference threshold of >90 cm for males and >85 cm for females. RESULTS: NWO males and females were 2.7 times (p < 0.001) and 1.9 times (p < 0.001) more likely to develop metabolic syndrome than normal-weight non-obese males and females, respectively. Additionally, NWO females were 1.3 times (p = 0.027) more likely to develop MetS even after adjustments for all measured covariates. CONCLUSIONS: The current findings of the study show that NWO is a proxy biomarker of MetS to be considered for early intervention.

12.
Mol Cell ; 83(15): 2753-2767.e10, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37478846

RESUMO

Nuclear hormone receptors (NRs) are ligand-binding transcription factors that are widely targeted therapeutically. Agonist binding triggers NR activation and subsequent degradation by unknown ligand-dependent ubiquitin ligase machinery. NR degradation is critical for therapeutic efficacy in malignancies that are driven by retinoic acid and estrogen receptors. Here, we demonstrate the ubiquitin ligase UBR5 drives degradation of multiple agonist-bound NRs, including the retinoic acid receptor alpha (RARA), retinoid x receptor alpha (RXRA), glucocorticoid, estrogen, liver-X, progesterone, and vitamin D receptors. We present the high-resolution cryo-EMstructure of full-length human UBR5 and a negative stain model representing its interaction with RARA/RXRA. Agonist ligands induce sequential, mutually exclusive recruitment of nuclear coactivators (NCOAs) and UBR5 to chromatin to regulate transcriptional networks. Other pharmacological ligands such as selective estrogen receptor degraders (SERDs) degrade their receptors through differential recruitment of UBR5 or RNF111. We establish the UBR5 transcriptional regulatory hub as a common mediator and regulator of NR-induced transcription.


Assuntos
Cromatina , Fatores de Transcrição , Humanos , Ligantes , Cromatina/genética , Fatores de Transcrição/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Ubiquitinas , Ubiquitina-Proteína Ligases/genética
13.
ACS Appl Mater Interfaces ; 15(15): 19307-19318, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37016485

RESUMO

A new nonfullerene acceptor (NFA), BTA-ERh, was synthesized and integrated into a PM6:Y7:PC71BM ternary system to regulate the blend film morphology for enhanced device performance. Due to BTA-ERh's good miscibility with host active blend films, an optimized film morphology was obtained with appropriate phase separation and fine-tuning of film crystallinity, which ultimately resulted in efficient exciton dissociation, charge transport, lower recombination loss, and decreased trap-state density. The resulting additive-free quaternary devices achieved a remarkable efficiency of 18.90%, with a high voltage, fill factor, and current density of 0.87 V, 76.32%, and 28.60 mA cm-2, respectively. By adding less of a new small molecule with high crystallinity, the favorable nanomorphology shape of blend films containing NFAs might be adjusted. Consequently, this strategy can enhance photovoltaic device performance for cutting-edge NFA-based organic solar cells (OSCs). In contrast, the additive-free OSCs exhibited good operational stability. More importantly, large-area modules with the quaternary device showed a remarkable efficiency of 12.20%, with an area as high as 55 cm2 (substrate size, 100 cm2) in an air atmosphere via D-bar coating. These results highlight the enormous research potential for a multicomponent strategy for future additive-free OSC applications.

14.
Molecules ; 28(6)2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36985832

RESUMO

Understanding the behavior of surfactants at interfaces is crucial for many applications in materials science and chemistry. Optical tweezers combined with trajectory analysis can become a powerful tool for investigating surfactant characteristics. In this study, we perform trap-and-track analysis to compare the behavior of cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC) at water-glass interfaces. We use optical tweezers to trap a gold nanoparticle and statistically analyze the particle's movement in response to various surfactant concentrations, evidencing the rearrangement of surfactants adsorbed on glass surfaces. Our results show that counterions have a significant effect on surfactant behavior at the interface. The greater binding affinity of bromide ions to CTA+ micelle surfaces reduces the repulsion among surfactant head groups and enhances the mobility of micelles adsorbed on the interface. Our study provides valuable insights into the behavior of surfactants at interfaces and highlights the potential of optical tweezers for surfactant research. The development of this trap-and-track approach can have important implications for various applications, including drug delivery and nanomaterials.

15.
Polymers (Basel) ; 15(6)2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36987184

RESUMO

With the International Maritime Organization (IMO) reinforcing environmental regulations on the shipbuilding industry, the demand for fuels, such as liquefied natural gas (LNG) and liquefied petroleum gas (LPG), has soared. Therefore, the demand for a Liquefied Gas Carrier for such LNG and LPG also increases. Recently, CCS carrier volume has been increasing, and damage to the lower CCS panel has occurred. To withstand liquefied gas loads, the CCSs should be fabricated using a material with improved mechanical strength and thermal performance compared with the conventional material. This study proposes a polyvinyl chloride (PVC)-type foam as an alternative to commercial polyurethane foam (PUF). The former material functions as both insulation and a support structure primarily for the LNG-carrier CCS. To investigate the effectiveness of the PVC-type foam for a low-temperature liquefied gas storage system, various cryogenic tests, namely tensile, compressive, impact, and thermal conductivity, are conducted. The results illustrate that the PVC-type foam proves stronger than PUF in mechanical performance (compressive, impact) across all temperatures. In the tensile test, there are reductions in strength with PVC-type foam but it meets CCS requirements. Therefore, it can serve as insulation and improve the overall CCS mechanical strength against increased loads under cryogenic temperatures. Additionally, PVC-type foam can serve as an alternative to other materials in various cryogenic applications.

16.
Int J Mol Sci ; 24(6)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36982727

RESUMO

The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 inflammasome activation. In this study, we aimed to investigate the inhibitory activity of ethanolic extracts of seeds of Cornus officinalis (CO), a herb and food plant used in traditional medicine, on AIM2-inflammasome activation. We found that CO inhibited the release of IL-1ß induced by dsDNA in both BMDMs and HaCaT cells, but that it showed no effect on the release of IL-1ß induced by NLRP3 inflammasome triggers, such as nigericin and silica, or the NLRC4 inflammasome trigger flagellin. Furthermore, we demonstrated that CO inhibited the cleavage of caspase-1, an inflammasome activation marker, and an upstream event, the translocation and speck formation of ASC. In addition, further experiments and mechanistic investigations revealed that CO can inhibit AIM2 speck formation induced by dsDNA in AIM2-overexpressing HEK293T cells. To verify the correlation in vivo, we investigated the efficacy of CO in an imiquimod (IMQ)-induced psoriasis model, which has reported associations with the AIM2 inflammasome. We found that topical application of CO alleviated psoriasis-like symptoms, such as erythema, scaling, and epidermal thickening, in a dose-dependent manner. Moreover, CO also significantly decreased IMQ-induced expression of AIM2 inflammasome components, including AIM2, ASC, and caspase-1, and led to the elevation of serum IL-17A. In conclusion, our results suggest that CO may be a valuable candidate for the discovery of AIM2 inhibitors and the regulation of AIM2-related diseases.


Assuntos
Cornus , Dermatite , Psoríase , Humanos , Inflamassomos/metabolismo , Imiquimode/efeitos adversos , Células HEK293 , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Inflamação , Extratos Vegetais/efeitos adversos , Sementes/metabolismo , Caspases , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-1beta/metabolismo , Caspase 1/metabolismo , Proteínas de Ligação a DNA/metabolismo
17.
Nature ; 615(7954): 913-919, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36922589

RESUMO

Chromatin-binding proteins are critical regulators of cell state in haematopoiesis1,2. Acute leukaemias driven by rearrangement of the mixed lineage leukaemia 1 gene (KMT2Ar) or mutation of the nucleophosmin gene (NPM1) require the chromatin adapter protein menin, encoded by the MEN1 gene, to sustain aberrant leukaemogenic gene expression programs3-5. In a phase 1 first-in-human clinical trial, the menin inhibitor revumenib, which is designed to disrupt the menin-MLL1 interaction, induced clinical responses in patients with leukaemia with KMT2Ar or mutated NPM1 (ref. 6). Here we identified somatic mutations in MEN1 at the revumenib-menin interface in patients with acquired resistance to menin inhibition. Consistent with the genetic data in patients, inhibitor-menin interface mutations represent a conserved mechanism of therapeutic resistance in xenograft models and in an unbiased base-editor screen. These mutants attenuate drug-target binding by generating structural perturbations that impact small-molecule binding but not the interaction with the natural ligand MLL1, and prevent inhibitor-induced eviction of menin and MLL1 from chromatin. To our knowledge, this study is the first to demonstrate that a chromatin-targeting therapeutic drug exerts sufficient selection pressure in patients to drive the evolution of escape mutants that lead to sustained chromatin occupancy, suggesting a common mechanism of therapeutic resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Leucemia , Mutação , Proteínas Proto-Oncogênicas , Animais , Humanos , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/genética , Cromatina/genética , Cromatina/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia/tratamento farmacológico , Leucemia/genética , Leucemia/metabolismo , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo
18.
Nanoscale ; 15(12): 5816-5824, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36857715

RESUMO

Rational design of electrocatalysts, including an increased catalytic surface area, a unique surface structure, and improved conductivity, for facilitating the hydrogen evolution reaction (HER) is emerging as an important issue. In this work, we consider the engineering of catalyst surfaces as an effective and feasible way to accelerate the HER kinetics. By etching the surface Fe of FeRu alloy nanoparticles (NPs) using hydrofluoric acid (HF), a distorted catalytic surface of FeRu NPs was formed. The distorted surface of the HF-treated FeRu NPs was successfully analyzed by X-ray absorption spectroscopy, high-resolution photoemission spectroscopy, and electrochemical absorption/desorption experiments. The electrocatalytic HER activity of the HF-treated FeRu NPs demonstrated that surface distortion enhances the water dissociation reaction and the electron transfer rate. As a result, the surface-distorted FeRu NPs improved HER performances in alkaline media compared to the pristine FeRu alloy NP/C, commercial Ru/C, and the state-of-the-art Pt/C catalysts.

19.
Cancers (Basel) ; 15(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36672439

RESUMO

Colorectal cancer (CRC) is the third most deadly type of cancer in the world and continuous investigations are required to discover novel therapeutics for CRC. Induction of apoptosis is one of the promising strategies to inhibit cancers. Here, we have identified a novel compound, Libertellenone T (B), isolated from crude extracts of the endolichenic fungus from Pseudoplectania sp. (EL000327) and investigated the mechanism of action. CRC cells treated by B were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that B induced CRC cell death via multiple mechanisms including G2/M phase arrest caused by microtubule stabilization and caspase-dependent apoptosis. Further studies revealed that B induced the generation of reactive oxygen species (ROS) attributed to activating the JNK signaling pathway by which apoptosis and autophagy was induced in Caco2 cells. Moreover, B exhibited good synergistic effects when combined with the well-known anticancer drug, 5-FU, and another cytotoxic novel compound D, which was isolated from the same crude extract of EL000327. Overall, Libertellenone T induces G2/M phase arrest, apoptosis, and autophagy via activating the ROS/JNK pathway in CRC. Thus, B may be a potential anticancer therapeutic against CRC that is suitable for clinical applications.

20.
Cancers (Basel) ; 14(24)2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36551553

RESUMO

Background: Uncertainty exists regarding the associations between physical activity (PA), relative handgrip strength (RHGS), and health-related quality of life (HRQoL) among elderly Korean cancer survivors. This study investigated the moderating effect of RHGS on the relationship between PA and HRQoL in 308 cancer survivors aged ≥65 years using the data from the Korean National Health and Nutrition Examination Survey in 2014−2019. Methods: HRQoL was evaluated with the EuroQol-5-dimension instrument. PA and handgrip strength were assessed with the Global Physical Activity Questionnaire and a hand dynamometer, respectively. Age, sex, body mass index, income, marital status, educational background, heavy alcohol consumption, smoking status, multimorbidity, and hemoglobin were included as covariates. Results: Bivariate logistic regression showed that insufficient PA and no PA were associated with higher odds of a low HRQoL (odds ratio, OR = 2.6, 95% confidence interval, CI = 1.3~5.1, p = 0.005; OR = 2.4, 95% CI = 1.1~5.0, p = 0.024, respectively), compared with sufficient PA (OR = 1). Weak RHGS was associated with high odds of a low HRQoL (OR = 2.6, 95%= 1.530~4.6, p < 0.001) compared with normal RHGS (OR = 1). Particularly, RHGS (ß = −0.0573, 95% CI = −0.1033~−0.0112) had a significant moderating effect on the relationship between PA and HRQoL even after adjustments for all the covariates. The negative influence of physical inactivity on HRQoL was observed in cancer survivors with weak RHGS but not in cancer survivors with normal RHGS. Conclusions: The current findings suggest that maintaining or promoting muscular strength through regular exercise is critical for the HRQoL of elderly Korean cancer survivors.

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