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1.
Front Oncol ; 14: 1314301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651148

RESUMO

Background: The epidermal growth factor receptor (EGFR) ex20ins mutation, as a rare subtype of mutation, has gradually attracted attention. Its heterogeneity is high, its prognosis is extremely poor, and the efficacy of existing traditional treatment plans is limited. In this study, we aimed to evaluate efficacy of high dose furmonertinib as a first-line treatment for EGFR ex20ins-positive NSCLC. Methods: This is a retrospective, multi-center, non-interventional study. From May 2021 to March 2023, 9 NSCLC patients with EGFR ex20ins were enrolled. Efficacy and safety of 160 mg furmonertinib were evaluated. Objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and treatment related adverse events (TRAEs) were assessed. Results: Of the evaluated patients, six patients experienced partial remission (PR), two patients experienced stable disease (SD) and one patient experienced progress disease (PD). Data indicated 66.7% ORR and 88.9% DCR. The median progression free survival (PFS) was 7.2 months (95% CI: 6.616 - 7.784). Besides, a longgest PFS with 18 months was found in one patient with p.H773_V774insGTNPH mutation. No ≥ level 3 adverse events have been found. Conclusions: The study proved the potential efficacy of 160mg furmonertinib in patients with advanced NSCLC with EGFR ex20ins. Meanwhile, 160mg furmonertinib had a good safety profile.

2.
PLoS One ; 19(4): e0301390, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558102

RESUMO

How to evaluate the resilience level and change trend of supply chain is an important research direction in current supply chain management practice. This paper proposes a new method of supply chain resilience assessment based on hesitant fuzzy linguistic term set (HFLTS) and matter element extension theory. Firstly, based on the research status quo at home and abroad, a low-carbon enterprise supply chain resilience assessment index system is established, which includes six first-level indicators and corresponding 21 second-level indicators of product supply resilience, resource resilience, partner resilience, information response resilience, financial resilience and knowledge resilience. Secondly, HFLTS was used to collect expert opinions and Ordered Weighted Arithmetic (OWA) to calculate the expert composite language, by which the fuzzy evaluation matrix of supply chain resilience assessment indicators was obtained. Once again, the resilience indicator weights are determined based on a game-theoretic portfolio assignment method combining the best-worst method (BWM) and the CRITIC method. Finally, the nearness degree function is combined with the extension comprehensive evaluation method to improve the matter element extension model, and the supply chain resilience assessment model of low-carbon enterprises based on the game theory combination assignment-improved matter element extension is established. Taking X low-carbon enterprise as an example, the evaluation results show that the supply chain resilience level of this enterprise is II, and the eigenvalue of the grade variable is 2.69, and the supply chain resilience is shifting to III, and the supply chain resilience is shifting to III, which indicates that the supply chain resilience of this enterprise is being enhanced. Therefore, the improved matter element extension not only ensures the accuracy of the evaluation results, but also has higher prediction accuracy.


Assuntos
Lógica Fuzzy , Resiliência Psicológica , Linguística
3.
Cell Metab ; 36(4): 857-876.e10, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569472

RESUMO

Leptin resistance during excess weight gain significantly contributes to the recidivism of obesity to leptin-based pharmacological therapies. The mechanisms underlying the inhibition of leptin receptor (LepR) signaling during obesity are still elusive. Here, we report that histone deacetylase 6 (HDAC6) interacts with LepR, reducing the latter's activity, and that pharmacological inhibition of HDAC6 activity disrupts this interaction and augments leptin signaling. Treatment of diet-induced obese mice with blood-brain barrier (BBB)-permeable HDAC6 inhibitors profoundly reduces food intake and leads to potent weight loss without affecting the muscle mass. Genetic depletion of Hdac6 in Agouti-related protein (AgRP)-expressing neurons or administration with BBB-impermeable HDAC6 inhibitors results in a lack of such anti-obesity effect. Together, these findings represent the first report describing a mechanistically validated and pharmaceutically tractable therapeutic approach to directly increase LepR activity as well as identifying centrally but not peripherally acting HDAC6 inhibitors as potent leptin sensitizers and anti-obesity agents.


Assuntos
Leptina , Obesidade , Animais , Camundongos , Desacetilase 6 de Histona , Leptina/metabolismo , Obesidade/metabolismo , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Aumento de Peso , Redução de Peso
4.
Syst Parasitol ; 101(3): 33, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647718

RESUMO

The mitochondrial (mt) genome can provide data for phylogenetic analyses and evolutionary biology. Herein, we sequenced and annotated the complete mt genome of Ergasilus anchoratus. This mt genome was 13852 bp long and comprised 13 protein-coding genes (PCGs), 22 tRNAs and 2 rRNAs. All PCGs used the standard ATN start codons and complete TAA/TAG termination codons. A majority of tRNA genes exhibited standard cloverleaf secondary structures, with the exception of one tRNA that lacked the TψC arm (trnC), and three tRNAs that lacked the DHU arm (trnR, trnS1 and trnS2). Phylogenetic analyses conducted using Bayesian inference (BI) and maximum likelihood (ML) methods both supported Ergasilidae as a monophyletic family forming a sister group to Lernaea cyprinacea and Paracyclopina nana. It also supported the monophyly of orders Calanoida, Cyclopoida, and Siphonostomatoida; and the monophyly of families Harpacticidae, Ergasilidae, Diaptomidae, and Calanidae. The gene orders of E. anchoratus and Sinergasilus undulatus were identical, which represents the first instance of two identical gene orders in copepods. More mt genomes are needed to better understand the phylogenetic relationships within Copepoda in the future.

5.
Korean Circ J ; 54(4): 172-186, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38654563

RESUMO

BACKGROUND AND OBJECTIVES: Long-term pathological myocardial hypertrophy (MH) seriously affects the normal function of the heart. Dronedarone was reported to attenuate left ventricular hypertrophy of mice. However, the molecular regulatory mechanism of dronedarone in MH is unclear. METHODS: Angiotensin II (Ang II) was used to induce cell hypertrophy of H9C2 cells. Transverse aortic constriction (TAC) surgery was performed to establish a rat model of MH. Cell size was evaluated using crystal violet staining and rhodamine phalloidin staining. Reverse transcription quantitative polymerase chain reaction and western blot were performed to detect the mRNA and protein expressions of genes. JASPAR and luciferase activity were conducted to predict and validate interaction between forkhead box O3 (FOXO3) and protein kinase inhibitor alpha (PKIA) promoter. RESULTS: Ang II treatment induced cell hypertrophy and inhibited sirtuin 1 (SIRT1) expression, which were reversed by dronedarone. SIRT1 overexpression or PKIA overexpression enhanced dronedarone-mediated suppression of cell hypertrophy in Ang II-induced H9C2 cells. Mechanistically, SIRT1 elevated FOXO3 expression through SIRT1-mediated deacetylation of FOXO3 and FOXO3 upregulated PKIA expression through interacting with PKIA promoter. Moreover, SIRT1 silencing compromised dronedarone-mediated suppression of cell hypertrophy, while PKIA upregulation abolished the influences of SIRT1 silencing. More importantly, dronedarone improved TAC surgery-induced MH and impairment of cardiac function of rats via affecting SIRT1/FOXO3/PKIA axis. CONCLUSIONS: Dronedarone alleviated MH through mediating SIRT1/FOXO3/PKIA axis, which provide more evidences for dronedarone against MH.

6.
Front Med (Lausanne) ; 11: 1334524, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585148

RESUMO

Background: Vitamin D is a crucial fat-soluble vitamin that has garnered significant attention due to its potential impact on respiratory health. It is noteworthy that many patients with chronic obstructive pulmonary disease (COPD) often experience deficiencies or insufficiencies of vitamin D. To address this issue, our retrospective study aimed to explore the potential association between serum 25-hydroxyvitamin D concentration and the prognoses of COPD patients in the Intensive Care Unit (ICU). Methods: This study utilised data from the Medical Information Marketplace in Intensive Care IV (MIMIC-IV), a database of patients admitted to the Intensive Care Unit at Beth Israel Deaconess Medical Center (BIDMC) in the United States of America, with a focus on patients with a diagnosis of COPD. These patients were categorized into two groups: those who received vitamin D supplementation during their ICU stay and those who did not. We assessed in-hospital mortality and ICU mortality outcomes. Our analysis involved various analytical tools, including Kaplan-Meier survival curves, Cox proportional risk regression models, and subgroup analyses, to investigate the relationship between vitamin D supplementation and these outcomes. Additionally, we employed propensity-score matching (PSM) to enhance the reliability of our findings. Results: The study included a total of 3,203 COPD patients, with 587 in the vitamin D group and 2,616 in the no-vitamin D group. The Kaplan-Meier survival curve demonstrated a significant difference in survival probability between the two groups. After adjusting for potential confounders using Cox regression models, the vitamin D group exhibited a substantially lower risk of in-hospital and ICU mortalities compared to the no-vitamin D group. The hazard ratios for in-hospital and ICU mortalities in the vitamin D group were 1.7 (95% CI: 1.3, 2.3) and 1.8 (95% CI: 1.2, 2.6), respectively. Propensity-score matching (PSM) estimation yielded consistent results. Furthermore, in the subgroup analysis, female patients who received vitamin D supplementation showed a reduced risk of in-hospital mortality. Conclusion: The study suggests that vitamin D supplementation may be linked to a reduction in in-hospital and ICU mortalities among COPD patients in the ICU. Of particular note is the potential benefit observed in terms of in-hospital mortality, especially for female patients.

7.
Oncol Lett ; 27(5): 227, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38586208

RESUMO

Lung cancer is associated with high morbidity and mortality rates. Forkhead box P2 (FOXP2) functions as an antitumor gene in various cancers. However, its role in lung cancer remains to be elucidated. The present study explored the potential role of FOXP2 in lung cancer. mRNA levels and protein expression were determined using RT-qPCR and western blotting, respectively. Functional analysis was performed using the CCK-8, Transwell and TUNEL assays. FOXP2 expression was downregulated in lung cancer. Notably, FOXP2 suppressed the proliferative, migratory and invasive abilities of lung cancer cells and promoted tumor cell apoptosis. In addition, FOXP2 blocked TGFß signaling. However, SRI-011381-stimulated activation of TGFß signaling reversed the effects of overexpressed FOXP2 and promoted the aggressiveness of lung cancer cells. FOXP2 functions as an antitumor gene in lung cancer cells. FOXP2 suppressed the malignant behavior of lung cancer by inactivating TGFß signaling.

8.
Mikrochim Acta ; 191(5): 248, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587676

RESUMO

Tumor-associated antigen (TAA)-based diagnosis has gained prominence for early tumor screening, treatment monitoring, prognostic assessment, and minimal residual disease detection. However, limitations such as low sensitivity and difficulty in extracting non-specific binding membrane proteins still exist in traditional detection methods. Upconversion luminescence (UCL) exhibits unique physical and chemical properties under wavelength near-infrared light excitation. Rolling circle amplification (RCA) is an efficient DNA amplification technique with amplification factors as high as 105. Therefore, the above two excellent techniques can be employed for highly accurate imaging analysis of tumor cells. Herein, we developed a novel nanoplatform for TAA-specific cell imaging based on UCL and RCA technology. An aptamer-primer complex selectively binds to Mucin 1 (MUC1), one of TAA on cell surface, to trigger RCA reaction, generating a large number of repetitive sequences. These sequences provide lots of binding sites for complementary signal probes, producing UCL from lanthanide-doped upconversion nanoparticles (UCNPs) after releasing quencher group. The experimental results demonstrate the specific attachment of upconversion nanomaterials to cancer cells which express a high level of MUC1, indicating the potential of UCNPs and RCA in tumor imaging.


Assuntos
Luminescência , Ácidos Nucleicos , Diagnóstico por Imagem , Membrana Celular , Técnicas de Amplificação de Ácido Nucleico
9.
Biomed Environ Sci ; 37(2): 146-156, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582977

RESUMO

Objective: This study aimed to explore the association of single nucleotide polymorphisms (SNP) in the matrix metalloproteinase 2 (MMP-2) signaling pathway and the risk of vascular senescence (VS). Methods: In this cross-sectional study, between May and November 2022, peripheral venous blood of 151 VS patients (case group) and 233 volunteers (control group) were collected. Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway, assessed through carotid-femoral pulse wave velocity (cfPWV), and analyzed using multivariate logistic regression. The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality regression (GMDR) modeling. Results: Within the multivariate logistic regression models, four SNPs were screened to have significant associations with VS: chemokine (C-C motif) ligand 2 (CCL2) rs4586, MMP2 rs14070, MMP2 rs7201, and MMP2 rs1053605. Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype, and those of the T/T genotype had a 19.375-fold increased risk. CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions. Conclusion: CCL2 rs4586, MMP-2 rs14070, MMP-2 rs7201, and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.


Assuntos
Metaloproteinase 2 da Matriz , Polimorfismo de Nucleotídeo Único , Humanos , Estudos de Casos e Controles , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Análise de Onda de Pulso , Transdução de Sinais
10.
Opt Express ; 32(4): 5301-5322, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439261

RESUMO

Source and mask optimization (SMO) technology is increasingly relied upon for resolution enhancement of photolithography as critical dimension (CD) shrinks. In advanced CD technology nodes, little process variation can impose a huge impact on the fidelity of lithography. However, traditional source and mask optimization (SMO) methods only evaluate the imaging quality in the focal plane, neglecting the process window (PW) that reflects the robustness of the lithography process. PW includes depth of focus (DOF) and exposure latitude (EL), which are computationally intensive and unfriendly to gradient-based SMO algorithms. In this study, we propose what we believe to be a novel process window enhancement SMO method based on the Nondominated Sorting Genetic Algorithm II (NSGA-II), which is a multi-objective optimization algorithm that can provide multiple solutions. By employing the variational lithography model (VLIM), a fast focus-variation aerial image model, our method, NSGA-SMO, can directly optimize the PW performance and improve the robustness of SMO results while maintaining the in-focus image quality. Referring to the simulations of two typical patterns, NSGA-SMO showcases an improvement of more than 20% in terms of DOF and EL compared to conventional multi-objective SMO, and even four times superior to single-objective SMO for complicated patterns.

11.
Cell Rep ; 43(4): 113975, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38507411

RESUMO

The intestine is a highly metabolic tissue, but the metabolic programs that influence intestinal crypt proliferation, differentiation, and regeneration are still emerging. Here, we investigate how mitochondrial sirtuin 4 (SIRT4) affects intestinal homeostasis. Intestinal SIRT4 loss promotes cell proliferation in the intestine following ionizing radiation (IR). SIRT4 functions as a tumor suppressor in a mouse model of intestinal cancer, and SIRT4 loss drives dysregulated glutamine and nucleotide metabolism in intestinal adenomas. Intestinal organoids lacking SIRT4 display increased proliferation after IR stress, along with increased glutamine uptake and a shift toward de novo nucleotide biosynthesis over salvage pathways. Inhibition of de novo nucleotide biosynthesis diminishes the growth advantage of SIRT4-deficient organoids after IR stress. This work establishes SIRT4 as a modulator of intestinal metabolism and homeostasis in the setting of DNA-damaging stress.


Assuntos
Proliferação de Células , Homeostase , Proteínas Mitocondriais , Nucleotídeos , Sirtuínas , Animais , Sirtuínas/metabolismo , Camundongos , Nucleotídeos/metabolismo , Intestinos/patologia , Organoides/metabolismo , Mucosa Intestinal/metabolismo , Glutamina/metabolismo , Humanos , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/patologia , Neoplasias Intestinais/genética , Camundongos Endogâmicos C57BL
12.
Materials (Basel) ; 17(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38541411

RESUMO

Ce-doped gadolinium gallium aluminum oxide (Ce: GGAG) precursors were first prepared by the microwave-assisted homogeneous precipitation method (MAHP). Thermal gravity-differential thermal analysis (TG-DTA), X-ray diffraction (XRD), specific surface area analysis (BET) and field emission scanning electron microscopy (FE-SEM) were employed to investigate the crystal structure, phase evolution and morphologies of the Ce: GGAG precursors and powders. The influence of Ga ion concentration in the salt solution on the properties of Ce: GGAG powders was investigated. All the precursors were transformed into single-phase GGAG after being calcined at 950 °C in a furnace for 3 h. Monodispersed Ce: GGAG powders were obtained as the Ga ion concentration was lower than 0.06 mol/L. Single-phase and dense Ce: GGAG ceramics were obtained after sintering at 1600 °C in a flowing oxygen atmosphere for 10 h. Specifically, the Ce: GGAG ceramic reached its maximum density of ~6.68 g/cm3, which was close to its theoretical density of 6.70 g/cm3, and exhibited the highest optical transmittance of 65.2% at 800 nm after hot isostatic pressing sintering (HIP) as the Ga ion concentration was 0.02 mol/L. The decay time and light yield of the GGAG ceramic were 35 ns and 35,000 ± 1250 ph/MeV, respectively, suggesting that Ce: GGAG ceramics prepared using MAHP-synthesized nanopowders are promising for scintillation applications.

14.
Cell Discov ; 10(1): 17, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38346975

RESUMO

Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced ß-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy. The KD ameliorated pentetrazol-induced epilepsy in mice. Mechanistically, KD-produced BHB, but not other ketone bodies, inhibited HDAC1/HDAC2, increased H3K27 acetylation, and transcriptionally upregulated SIRT4 and glutamate decarboxylase 1 (GAD1). BHB-induced SIRT4 de-carbamylated and inactivated glutamate dehydrogenase to preserve glutamate for GABA synthesis, and GAD1 upregulation increased mouse brain GABA/glutamate ratio to inhibit neuron excitation. BHB administration in mice inhibited epilepsy induced by pentetrazol. BHB-mediated relief of epilepsy required high GABA level and GABA/glutamate ratio. These results identified BHB as the major antiepileptic metabolite of the KD and suggested that BHB may serve as an alternative and less toxic antiepileptic agent than KD.

15.
bioRxiv ; 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38352486

RESUMO

Introduction: Reduced brain energy metabolism, mTOR dysregulation, and extracellular amyloid-ß oligomer (xcAßO) buildup characterize AD; how they collectively promote neurodegeneration is poorly understood. We previously reported that xcAßOs inhibit N utrient-induced M itochondrial A ctivity (NiMA) in cultured neurons. We now report NiMA disruption in vivo . Methods: Brain energy metabolism and oxygen consumption were recorded in APP SAA/+ mice using two-photon fluorescence lifetime imaging and multiparametric photoacoustic microscopy. Results: NiMA is inhibited in APP SAA/+ mice before other defects are detected in these amyloid-ß-producing animals that do not overexpress APP or contain foreign DNA inserts into genomic DNA. GSK3ß signals through mTORC1 to regulate NiMA independently of mitochondrial biogenesis. Inhibition of GSK3ß with lithium or TWS119 stimulates NiMA in cultured human neurons, and mitochondrial activity and oxygen consumption in APP SAA mice. Conclusion: NiMA disruption in vivo occurs before histopathological changes and cognitive decline in APP SAA mice, and may represent an early stage in human AD.

16.
Sci Total Environ ; 921: 171145, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38395167

RESUMO

Ubiquitous humic substances usually exhibit strong interfering effects on target pollutant removal in advanced water purification. This work aims to develop a photochemical conversion system on the nonstoichiometric TiO2 for pollutant removal in environmentally relevant matrices. In this synergistic reaction system, the redox-reactive humic substances and defective oxygen vacancies can serve as the organic electron transfer mediator and the key surface reactive sites, respectively. This system achieves a superior pollutant degradation in real surface water at low oxidant concentrations. Reactive oxygen vacancies on the TiO2 surface and sub-surface are of considerable interest for this photochemical reaction system. By engineering defective oxygen vacancies on high-energy {001} polar facet, the surface and electronic interactions between tailored TiO2 and humic substances are greatly strengthened for the promoted electron transfer and oxidant activation. Rendered by the strong surface affinity and molecular activation, defective oxygen vacancies thermodynamically and dynamically promote reactive chain reactions for free radical formation, including the selective O2 reduction to ·O2- and the H2O2 activation to ·OH. Our findings take new insights into environmental geochemistry, and provide an effective strategy to in-situ boost the humic substances-mediated water purification without secondary pollution. ENVIRONMENTAL IMPLICATION: Humic substances are widely distributed in aquatic environment, thus playing important roles in environmental geochemistry. For example, humic substances can achieve good surface adsorption through electrostatic adsorption, ligand exchange and electronic interactions with typical TiO2 to form reactive ligand-metal charge transfer complexes for pollutant degradation. Inspired by the unique properties of surface and sub-surface oxygen vacancies, the defective TiO2 was designed to refine the humic substances-mediated photochemical reactions. A superior reactivity was measured for pollutant degradation. Our findings provide an effective strategy to boost naturally photochemical decontamination in environmentally relevant matrices.

17.
Micromachines (Basel) ; 15(2)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38399017

RESUMO

Microlens arrays, as typical micro-optical elements, effectively enhance the integration and performance of optical systems. The surface shape errors and surface roughness of microlens arrays are the main indicators of their optical characteristics and determine their optical performance. In this study, a mask-moving-projection-lithography-based high-precision surface fabrication method for microlens arrays is proposed, which effectively reduces the surface shape errors and surface roughness of microlens arrays. The pre-exposure technology is used to reduce the development threshold of the photoresist, thus eliminating the impact of the exposure threshold on the surface shape of the microlens. After development, the inverted air bath reflux method is used to bring the microlens array surface to a molten state, effectively eliminating surface protrusions. Experimental results show that the microlens arrays fabricated using this method had a root mean square error of less than 2.8%, and their surface roughness could reach the nanometer level, which effectively improves the fabrication precision for microlens arrays.

18.
J Nutr Biochem ; 126: 109578, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38216066

RESUMO

Alginate oligosaccharide (AOS) may delay aging by decreasing oxidative stress, but the effects on vascular aging remain unclear. Here, we evaluate the effect of AOS on vascular aging and investigate the underlying mechanisms. Twenty-month-old rats acted as the natural aging model in vivo. Senescence of human aortic vascular smooth muscle cells (HA-VSMCs) was induced in vitro using angiotensin II (AngII). The aging rats and senescent cells were treated with AOS, followed by assessment of aging makers, oxidative stress, and aging-induced vascular remodeling. AOS treatment alleviated vascular aging and HA-VSMC senescence and decreased the levels of oxidative stress and vascular remodeling-associated indicators. AOS upregulated the expression of glutathione peroxidase 7 (GPX7) in aging rats and GPX7 depletion disrupted the geroprotective effect of AOS. AOS increased the nuclear translocation of nuclear factor erythroid-2-related factor (Nrf2) protein, which interacts with GPX7 protein to induce its expression. In conclusion, AOS alleviates vascular aging and HA-VSMC senescence and reduces aging-related vascular remodeling via the GPX7 antioxidant pathway, which may provide new avenues for treating aging-associated diseases.


Assuntos
Alginatos , Remodelação Vascular , Ratos , Humanos , Animais , Lactente , Alginatos/farmacologia , Alginatos/metabolismo , Envelhecimento/metabolismo , Estresse Oxidativo , Glutationa Peroxidase/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/metabolismo , Miócitos de Músculo Liso
19.
Cell Mol Life Sci ; 81(1): 25, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38212570

RESUMO

Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IRW-K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Camundongos , Animais , Insulina/metabolismo , Receptor de Insulina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Triptofano/metabolismo , Fosforilação , Glucose/metabolismo
20.
Materials (Basel) ; 17(2)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38255570

RESUMO

Highly transparent Ho:Y2O3 ceramics for laser diode lighting were prepared using the vacuum sintering method with 0.3 at.% Nb2O5 as a sintering additive. The microstructures, transmittance, and luminescence properties of the Ho:Y2O3 ceramic samples were investigated in detail. The transmittance levels of all samples with various Ho3+ concentrations reached ~81.5% (2 mm thick) at 1100 nm. Under the excitation of 363 nm (ultraviolet) or 448 nm (blue) light, Ho:Y2O3 transparent ceramic samples showed that green emission peaked at 550 nm. The emission intensity was strongly affected by the concentration of Ho3+ ions, reaching its highest level in the sample doped with 1 at.% Ho3+. The CIE coordinates of the luminescence were in the green region (i.e., the CIE coordinates of the sample doped with 1 at.% Ho3+ were [0.27, 0.53] and [0.30, 0.69], under the excitation of 363 nm and 448 nm light, respectively). The possibility of its application as laser diode lighting was reported. Under the excitation of 450 nm blue laser, the sample doped with 0.5 at.% Ho3+ had the best performance: the saturated luminous flux, lumen efficiency, and the luminescence saturation power densities were 800 lm, 57.7 lm/W, and 17.6 W/mm2, respectively. Furthermore, the materials have high thermal conductivity and mechanical strength due to their host of rare-earth sesquioxide. Thus, Ho:Y2O3 transparent ceramics are expected to be a promising candidate for green-light-emitting devices for solid-state lighting, such as laser diode lighting.

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