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1.
Leukemia ; 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39443736

RESUMO

Nucleophosmin (NPM1) is a nucleolar protein and one of the most frequently mutated genes in acute myeloid leukemia (AML). In addition to the commonly detected frameshift mutations in exon12 (NPM1c), previous studies have identified NPM1 gene rearrangements leading to the expression of NPM1-fusion proteins in pediatric AML. However, whether the NPM1-fusions are indeed oncogenic and how the NPM1-fusions cause AML have been largely unknown. In this study, we investigated the subcellular localization and leukemogenic potential of two rare NPM1-fusion proteins, NPM1::MLF1 and NPM1::CCDC28A. NPM1::MLF1 is present in both the nucleus and cytoplasm and occasionally induces AML in the mouse transplantation assay. NPM1::CCDC28A is more localized to the cytoplasm, immortalizes mouse bone marrow cells in vitro and efficiently induces AML in vivo. Mechanistically, both NPM1-fusions bind to the HOX gene cluster and, like NPM1c, cause aberrant upregulation of HOX genes in cooperation with XPO1. The XPO1 inhibitor selinexor suppressed HOX activation and colony formation driven by the NPM1-fusions. NPM1::CCDC28A cells were also sensitive to menin inhibition. Thus, our study provides experimental evidence that both NPM1::MLF1 and NPM1::CCDC28A are oncogenes with functions similar to NPM1c. Inhibition of XPO1 and menin may be a promising strategy for the NPM1-rearranged AML.

2.
Inflammation ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39414673

RESUMO

OBJECTIVE: Patients with rheumatoid arthritis (RA) have increased mortality and morbidity rates owing to cardiovascular diseases (CVD). Timely detection of CVD in RA can greatly improve patient prognosis; however, this technique remains challenging. We aimed to investigate the risk factors for CVD incidence in patients with RA. METHODS: This retrospective study included RA patients without CVD risk factors (n = 402), RA with CVD risk factors (n = 394), and RA with CVD (n = 201). Their data on routine examination indicators, vascular endothelial growth factor (VEGF), and immune cells were obtained from medical records. The characteristic variables between each group were screened using univariate analysis, least absolute shrinkage and selection operator (LASSO), random forest (RF), and logistic regression (LR) models, and individualized nomograms were further established to more conveniently observe the likelihood of CVD in RA. RESULTS: Univariate analysis revealed significantly elevated levels of white blood cells (WBC), blood urea nitrogen (BUN), creatinine, creatine kinase (CK), lactate dehydrogenase (LDH), VEGF, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), apolipoprotein B100 (ApoB100), and apolipoprotein E (ApoE) in RA patients with CVD, whereas apolipoprotein A1 (ApoA1) and high-density lipoprotein/cholesterol (HDL/TC) were decreased. Furthermore, the ratio of regulatory T (Treg) cells exhibiting excellent separation performance in RA patients with CVD was significantly lower than that in other groups, whereas the ratios of Th1/Th2/NK and Treg cells were significantly elevated. The LASSO, RF, and LR models were also used to identify the risk factors for CVD in patients with RA. Through the final selected indicators screened using the three machine learning models and univariate analysis, a convenient nomogram was established to observe the likelihood of CVD in patients with RA. CONCLUSIONS: Serum lipids, lipoproteins, and reduction of Treg cells have been identified as risk factors for CVD in patients with RA. Three nomograms combining various risk factors were constructed to predict CVD occurring in patients with RA (RA with/without CVD risk factors).

3.
Small ; : e2404638, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240073

RESUMO

The size dependence of metal cluster reactions frequently reveals valuable information on the mechanism of nanometal catalysis. Here, the reactivity of the Ptn + (n = 1-40) clusters with N2O is studied and a significant dependence on the size of these clusters is noticed. Interestingly, the small Ptn + clusters like Pt3 + and Pt4 + are inclined to form N2O complexes; some larger clusters, such as Pt19 +, Pt21 +, and Pt23 +, appear to be unreactive; however, the others such as Pt3 , 9,15 + and Pt18 + are capable of decomposing N2O. While Pt9 + rapidly reacts with N2O to form a stable quasitetrahedron Pt9O+ product, Pt18 + experiences a series of N2O decompositions to produce Pt18O1-7 +. Utilizing high-precision theoretical calculations, it is shown how the atomic structures and active sites of Ptn + clusters play a vital role in determining their reactivity. Cooperative dual Lewis-acid sites (CDLAS) can be achieved on specific metal clusters like Pt18 +, rendering accelerated N2O decomposition via both N- and O-bonding on the neighboring Pt atoms. The influence of CDLAS on the size-dependent reaction of Pt clusters with N2O is illustrated, offering insights into cluster catalysis in reactions that include the donation of electron pairs.

4.
Bioorg Chem ; 152: 107719, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39173226

RESUMO

Glutathione (GSH) exhibits considerable potential in the cosmetic industry for reducing intracellular tyrosinase activity and inhibiting melanin synthesis. However, its efficacy is hindered by limited permeability, restricting its ability to reach the basal layer of the skin where melanin production occurs. The transdermal enhancer peptide TD1 has emerged as a promising strategy to facilitate the transdermal transfer of proteins or peptides by creating intercellular gaps in keratinocytes, providing access to the basal layer. The primary objective of this study is to enhance the transdermal absorption capacity of GSH while augmenting its inhibitory effect on melanin. Two coupling structures were designed for investigation: linear (TD1-linker-GSH) and branched (TD1-GSH). The study examined the impact of the peptide skeleton on melanin inhibition ability. Our findings revealed that the linear structure not only inhibited synthetic melanin production in B16F10 cells through a direct pathway but also through a paracrine pathway, demonstrating a significant tyrosinase inhibition of nearly 70 %, attributed to the paracrine effect of human keratinocyte HaCaT. In pigmentation models of guinea pigs and zebrafish, the application of TD1-linker-GSH significantly reduced pigmentation. Notably, electric two-photon microscopy demonstrated that TD1-linker-GSH exhibited significant transdermal ability, penetrating 158.67 ± 9.28 µm into the skin of living guinea pigs. Molecular docking analysis of the binding activity with tyrosinase revealed that both TD1-linker-GSH and TD1-GSH occupy the same active pocket, with TD1-linker-GSH binding more tightly to tyrosinase. These results provide a potential foundation for therapeutic approaches aimed at enriched pigmentation and advance our understanding of the mechanisms underlying melanogenesis inhibition.


Assuntos
Administração Cutânea , Glutationa , Melaninas , Monofenol Mono-Oxigenase , Peixe-Zebra , Melaninas/metabolismo , Animais , Humanos , Cobaias , Glutationa/metabolismo , Glutationa/química , Monofenol Mono-Oxigenase/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/síntese química , Peptídeos/administração & dosagem , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/administração & dosagem , Melanogênese
5.
Psychol Res Behav Manag ; 17: 1903-1916, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737671

RESUMO

Purpose: To explore the relationship between adolescents' problematic Internet use and loneliness and the mediating roles of social support and family communication. Methods: A questionnaire survey of 2483 adolescents aged 12-17 years in 148 cities in China was conducted using the Problematic Internet Use Scale, the Collaborative Social Support Scale, the Family Communication Scale, and the Loneliness Scale. The data were statistically analyzed by SPSS 26.0 and validated by AMOS 28.0. Structural equation modelling (SEM) was conducted to test the effects of problematic Internet use on adolescents' loneliness and the mediating effects of perceptions of social support and family communication. Results: There was a significant positive effect of adolescents' problematic Internet use on loneliness (B-0.471, P<0.001), and the mediating effects of perceptual social support (0.003, 0.012) and family communication (0.008, 0.019) were found to play a chain effect between adolescents' problematic Internet use and loneliness, respectively. Use and feelings of loneliness played a chain mediating role (0.002, 0.006). Conclusion: This study identified the effects of adolescent problematic Internet use on loneliness and its mechanism of action, emphasized the importance of social support and family communication, and provided practical insights for improving family parenting styles and preventing and intervening in adolescent loneliness problems.

6.
J Clin Lab Anal ; 38(8): e25033, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563457

RESUMO

BACKGROUND: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc. METHODS: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820). CONCLUSIONS: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice.


Assuntos
Imunoglobulina G , Medições Luminescentes , Humanos , Imunoglobulina G/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Imunoensaio/métodos , Medições Luminescentes/métodos , Adulto , Curva ROC , Nefelometria e Turbidimetria/métodos , Estudos de Casos e Controles , China , Idoso , Síndrome de Sjogren/sangue , Síndrome de Sjogren/diagnóstico , Povo Asiático , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/diagnóstico , População do Leste Asiático
7.
J Am Chem Soc ; 146(13): 9302-9310, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38506150

RESUMO

Tailoring materials with prescribed properties and regular structures is a critical and challenging research topic. Early transition metals were found to form supermagic M8C12 metallocarbohedrenes (Met-Cars); however, stable metal carbides are not limited to this common stoichiometry. Utilizing self-developed deep-ultraviolet laser ionization mass spectrometry, here, we report a strategy to generate new titanium carbides by reacting pure Tin clusters with acetylene. Interestingly, two products corresponding to Ti17C2 and Ti19C10 exhibit superior abundances in addition to the Ti8C12 Met-Cars. Using global-minimum search, the structures of Ti17C2 and Ti19C10 are determined to be an ellipsoidal D4d and a rod-shaped D5h geometry, respectively, both with carbon-capped Ti4C moieties and superatomic features. We illustrate the electronic structures and bonding nature in these carbon-doped superatoms concerning their enhanced stability and local aromaticity, shedding light on a new class of metal-carbide nanomaterials with atomic precision.

8.
J Phys Chem A ; 128(7): 1274-1279, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38334079

RESUMO

Iodomethane and bromomethane (CH3I/CH3Br) are common chemicals, but their chemistry on nanometals is not fully understood. Here, we analyze the reactivity of Rhn+ (n = 3-30) clusters with halomethanes and unveil the spin effect and concentration dependence in the C-H and C-X bond activation. It is found that the reactions under halomethane-rich conditions differ from those under metal-rich conditions. Both CH3I and CH3Br undergo similar dehydrogenation on the Rhn+ clusters in the presence of small quantity reactants; however, different reactions are observed in the presence of sufficient CH3I/CH3Br, showing dominant Rh(CH3Br)x+ (x = 1-4) products but a series of RhnCxHyIz+ species (x = 1-4, y = 1-12, and z = 1-5) pertaining to H2, HI, or CH4 removal. Density functional theory calculations reveal that the dehydrogenation and demethanation of CH3Br are relatively less exothermic and will be deactivated by sufficient gas collisions if helium cooling takes away energy immediately; instead, the successive adsorption of CH3Br gives rise to a series of Rh(CH3Br)x+ species with accidental C-Br bond dissociation.

9.
Mol Immunol ; 168: 25-37, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382243

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) is one of the most common pulmonary complications in patients with primary Sjögren's syndrome (pSS). This study was performed to identify immunological risk factors of pSS-associated ILD (pSS-ILD) and to further establish and evaluate of nomograms predicting the risk of ILD in patients with pSS. METHODS: A total of 622 patients with pSS (117 with ILD and 505 without lung involvement) and 166 healthy control subjects (HCs) were ultimately recruited to this retrospective study. Routine examination indicators, tumour markers and lymphocyte (LYMP) subpopulations were extracted. Simple and multiple logistic regressions analyses were performed to screen for independent predictors. Restricted cubic splines were used to examine associations of independent predictors with ILD, and a risk assessment model was constructed. A nomogram prediction model was developed, and receiver operating characteristic (ROC) curve analysis was performed to assess its performance. RESULTS: Univariate and multivariate logistic regression analyses showed that the older age, white blood cell (WBC) count, haemoglobin (HB) level, albumin (ALB) level, CA242 level, and the C-reactive protein (CRP)/LYMP ratio (CLR) were independent predictors of pSS-ILD in a linear manner, these factors were integrated and used to construct a nomogram prediction model. The model had clinical predictive value. In addition, the elevated Th2 cells proportion in pSS patients was significantly positively correlated with lung involvement, while it was negatively correlated with HB and ALB levels. Remarkably, the numbers of Th2 cells were correlated with the CLR in both pSS patients and those with pSS-ILD. CONCLUSIONS: Our novel ILD nomogram could be used to assess the risk of ILD in pSS patients with good discrimination ability. As well as, elevated peripheral blood Th2 cell levels may be related to ILD in patients with pSS.


Assuntos
Doenças Pulmonares Intersticiais , Síndrome de Sjogren , Humanos , Estudos Retrospectivos , Nomogramas , Células Th2 , Síndrome de Sjogren/complicações , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Fatores de Risco
10.
Eur J Med Res ; 28(1): 586, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093395

RESUMO

INTRODUCTION: Cervical cancer threatens women's health seriously. In recent years, the incidence of cervical cancer is on the rise, and the age of onset tends to be younger. Prevention, early diagnosis and specific treatment have become the main means to change the prognosis of cervical cancer patients. Metabolomics research can directly reflect the changes of biochemical processes and microenvironment in the body, which can provide a comprehensive understanding of the changes of metabolites in the process of disease occurrence and development, and provide new ways for the prevention and diagnosis of diseases. OBJECTIVES: The aim of this study is to review the metabolic changes in cervical cancer and the application of metabolomics in the diagnosis and treatment. METHODS: PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2022. RESULTS: With the emergence of metabolomics, metabolic regulation and cancer research are further becoming a focus of attention. By directly reflecting the changes in the microenvironment of the body, metabolomics research can provide a comprehensive understanding of the patterns of metabolites in the occurrence and development of diseases, thus providing new ideas for disease prevention and diagnosis. CONCLUSION: With the continuous, in-depth research on metabolomics research technology, it will bring more benefits in the screening, diagnosis and treatment of cervical cancer with its advantages of holistic and dynamic nature.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Metabolômica , Prognóstico , Microambiente Tumoral
11.
Sci Adv ; 9(33): eadi0214, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37585530

RESUMO

Probing atomic clusters with magic numbers is of supreme importance but challenging in cluster science. Pronounced stability of a metal cluster often arises from coincident geometric and electronic shell closures. However, transition metal clusters do not simply abide by this constraint. Here, we report the finding of a magic-number cluster Rh19- with prominent inertness in the sufficient gas-collision reactions. Photoelectron spectroscopy experiments and global-minimum structure search have determined the geometry of Rh19- to be a regular Oh­[Rh@Rh12@Rh6]- with unusual high-spin electronic configuration. The distinct stability of such a strongly magnetic cluster Rh19- consisting of a nonmagnetic element is fully unveiled on the basis of its unique bonding nature and superatomic states. The 1-nanometer-sized Oh-Rh19- cluster corresponds to a fragment of the face-centered cubic lattice of bulk rhodium but with altered magnetism and electronic property. This cluster features exceptional electron-spin state isomers confirmed in photoelectron spectra and suggests potential applications in atomically precise manufacturing involving spintronics and quantum computing.

12.
BMC Psychiatry ; 23(1): 616, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608360

RESUMO

BACKGROUND: Mixed results have been found regarding the relationship between media use degree and depressive symptoms. The purpose of this study is to explore the relationship between media use degree, big five personality and depressive symptoms with a mediation model. METHOD: This was a cross-sectional study. With 9-item Patient Health Questionnaire (PHQ-9), 10-item Big Five Inventory (BFI-10) and self-designed media usage scale, 11,031 participants aged 12 and above in 120 cities in China were collected. Pearson correlation analysis and regression analysis were performed on the data. The Process plug-in was used to construct the mediation model and explore the relationship among media use degree, big five personality and depressive symptoms. The nonparametric percentile Bootstrap method was used to test the mediating effect of personality traits. RESULTS: The degree of media use was positively correlated with depressive symptoms (r = 0.20, P < 0.001), and big five personality played a mediating role between the degree of media use and depressive symptoms. Among five traits, extroversion (r=-0.12, P < 0.001), conscientiousness (r=-0.23, P < 0.001), openness (r=-0.03, P < 0.01) and agreeableness (r=-0.22, P < 0.001) were negatively correlated with depressive symptoms, and neuroticism (r = 0.25, P < 0.001) were positively correlated with depressive symptoms. In addition, extraversion (-0.004, -0.001), conscientiousness (-0.015, -0.008), agreeableness (-0.008, -0.001) and neuroticism (-0.015, -0.007) in big five personality played a mediating role between media use and depressive symptoms. CONCLUSION: The degree of media use positively predicted depressive symptoms, and excessive media use may bring risks to mental health. People with high neuroticism, low agreeableness, low conscientiousness and low extroversion are more likely to suffer from depressive symptoms.


Assuntos
Depressão , Personalidade , Humanos , Estudos Transversais , Transtornos da Personalidade , Neuroticismo
13.
Curr Pharm Des ; 29(12): 947-956, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37013424

RESUMO

INTRODUCTION: This paper aims to reveal the molecular mechanism of resveratrol against oxidative stress and cell injury. The ovarian granulosa-lutein cell injury and apoptosis induced by oxidative stress may be responsible for female luteal phase deficiency. The antioxidant function of resveratrol has been confirmed; however, its effect on the expression of antioxidant enzymes and regulatory mechanisms in ovarian granulosa-lutein cells remains unclear. OBJECTIVE: This study aimed to investigate the role of the SIRT1/Nrf2/ARE signaling pathway in the effect of resveratrol on the hydrogen peroxide-induced injury of rat ovarian granulosa-lutein cells. METHODS: In this study, ovarian granulosa-lutein cells extracted from 3-week female SD rats were treated with 200 µM H2O2 in the presence or absence of 20 µM resveratrol. siRNA-SIRT1 and siRNA-Nrf2 were used to inhibit the expression of SIRT1 and Nrf2, respectively. Cell counting kit 8 (CCK-8), cellular morphology, progesterone secretion, and estradiol were used to evaluate cell injury. Hoechst 33258 staining was used to measure cell apoptosis. DHE staining, DCFH-DA staining, malondialdehyde content, protein carbonyl content, total antioxidant capacity and SOD viability were used to estimate the levels of oxidative stress. Western blot analysis was used to detect the levels of apoptosis-related proteins, and SIRT1/Nrf2/ARE signaling pathway-related proteins. RESULTS: The H2O2 treatment-induced rat ovarian granulosa-lutein cells injury was shown as decreased cell viability, impaired cellular morphology, and decreased levels of progesterone and estradiol. The H2O2 treatment also exacerbated cell apoptosis demonstrated as more apoptotic cells stained by Hoechst staining, decreased level of anti-apoptosis protein Bcl-2 and increased level of pro-apoptosis protein Bax. These effects of cell injury and apoptosis induced by H2O2 can be ameliorated by resveratrol. Resveratrol also alleviated oxidative stress induced by H2O2, supported by decreased superoxide anion and cellular total ROS, decreased malondialdehyde and protein carbonyl levels, and increased total antioxidant capacity and SOD viability. Western blot results demonstrated resveratrol reversed the H2O2-induced decrease in levels of antioxidant enzymes containing ARE sequences and activated SIRT1/Nrf2 pathway. Further treatment by siRNA-Nrf2 suggested resveratrol could not activate the expression of antioxidant enzymes under a condition of inhibition of Nrf2. CONCLUSION: This study demonstrates that resveratrol attenuated oxidative stress to protect H2O2-induced rat ovarian granulosa-lutein cell injury and apoptosis via SIRT1/Nrf2/ARE signaling pathway.


Assuntos
Antioxidantes , Células Lúteas , Ratos , Feminino , Animais , Resveratrol/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Peróxido de Hidrogênio/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Células Lúteas/metabolismo , Progesterona/metabolismo , Progesterona/farmacologia , Sirtuína 1/metabolismo , Carbonilação Proteica , Ratos Sprague-Dawley , Estresse Oxidativo , Transdução de Sinais , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/farmacologia , RNA Interferente Pequeno/farmacologia , Estradiol/farmacologia , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Malondialdeído/metabolismo , Malondialdeído/farmacologia , Espécies Reativas de Oxigênio/metabolismo
14.
J Phys Chem A ; 127(13): 2912-2920, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36976294

RESUMO

Well-resolved Nbn- clusters are produced and reacted with ethene and propene via a downstream flow tube reactor. Interestingly, the Nbn- clusters readily react with ethene and propene to form dehydrogenation products; however, Nb15- shows up in the mass spectra with prominent mass abundance indicating its inertness to react with olefins. For this cluster, we conduct photoelectron velocity map imaging (VMI) experiments and verify the stability of Nb15- within a highly symmetrical rhombic dodecahedron structure. Theoretical studies show that the stability of the Nb15- cluster is correlated with its superatomic nature pertaining to both geometric and electronic shell closures. Notably, the superatomic 1s orbital is dominated by the 5s electron of the central Nb atom, while the other superatomic orbitals are contributed by s-d hybridization, especially a remarkable contribution of s-dz2 hybridization. Apart from the closed shells, the highly symmetric geometry of Nb15- is associated with a regular polyhedral structure directed by all rhombus facets, embodying a magic number for body-centered dodecahedra, indicative of enhanced stability as a double magic cluster free of olefin adsorption.

15.
EMBO Mol Med ; 15(1): e15631, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36453131

RESUMO

Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in de novo guanine nucleotide synthesis pathway. Although IMPDH inhibitors are widely used as effective immunosuppressants, their antitumor effects have not been proven in the clinical setting. Here, we found that acute myeloid leukemias (AMLs) with MLL-fusions are susceptible to IMPDH inhibitors in vitro. We also showed that alternate-day administration of IMPDH inhibitors suppressed the development of MLL-AF9-driven AML in vivo without having a devastating effect on immune function. Mechanistically, IMPDH inhibition induced overactivation of Toll-like receptor (TLR)-TRAF6-NF-κB signaling and upregulation of an adhesion molecule VCAM1, which contribute to the antileukemia effect of IMPDH inhibitors. Consequently, combined treatment with IMPDH inhibitors and the TLR1/2 agonist effectively inhibited the development of MLL-fusion AML. These findings provide a rational basis for clinical testing of IMPDH inhibitors against MLL-fusion AMLs and potentially other aggressive tumors with active TLR signaling.


Assuntos
Leucemia Mieloide Aguda , Proteína de Leucina Linfoide-Mieloide , Humanos , Proteína de Leucina Linfoide-Mieloide/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Inibidores Enzimáticos/farmacologia , NF-kappa B , Imunossupressores/uso terapêutico
16.
Am J Transl Res ; 14(11): 8031-8048, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505274

RESUMO

Low back pain (LBP) caused by intervertebral disc (IVD) generation (IVDD) has always been an important problem that cannot be ignored. Traditional therapies have many deep-rooted and intractable complications that promote their treatment mode transfer to new therapies. This article mainly summarizes the shortcomings of traditional treatment methods and analyzes the research status and future development direction of IVDD treatment. We outlined the most promising IVDD therapies, including cell, exosome, gene, and tissue engineering therapy, especially tissue engineering therapy, which runs through the whole process of other therapies. In addition, the article focuses on the cellular, animal, and preclinical challenges faced by each therapeutic approach, as well as their respective advantages and disadvantages, to provide better ideas for relieving the IVDD patients' pain through new treatment methods.

18.
Int J Mol Sci ; 23(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36361683

RESUMO

More research is required to understand how melatonin protects neurons. The study aimed to find out if and how long non-coding RNA (lncRNA) contributes to melatonin's ability to defend the hippocampus from H2O2-induced oxidative injury. LncRNAs related to oxidative injury were predicted by bioinformatics methods. Mouse hippocampus-derived neuronal HT22 cells were treated with H2O2 with or without melatonin. Viability and apoptosis were detected by Cell Counting Kit-8 and Hoechst33258. RNA and protein levels were measured by quantitative real-time PCR, Western blot, and immunofluorescence. Bioinformatics predicted that 38 lncRNAs were associated with oxidative injury in mouse neurons. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was related to H2O2-induced oxidative injury and up-regulated by melatonin in HT22 cells. The knockdown of NEAT1 exacerbated H2O2-induced oxidative injury, weakened the moderating effect of melatonin, and abolished the increasing effect of melatonin on the mRNA and protein level of Slc38a2. Taken together, melatonin attenuates H2O2-induced oxidative injury by upregulating lncRNA NEAT1, which is essential for melatonin stabilizing the mRNA and protein level of Slc38a2 for the survival of HT22 cells. The research may assist in the treatment of oxidative injury-induced hippocampal degeneration associated with aging using melatonin and its target lncRNA NEAT1.


Assuntos
Melatonina , MicroRNAs , RNA Longo não Codificante , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Melatonina/farmacologia , Peróxido de Hidrogênio/toxicidade , Hipocampo/metabolismo , Apoptose/genética , Estresse Oxidativo , RNA Mensageiro/metabolismo , MicroRNAs/genética
19.
Front Public Health ; 10: 1000158, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324440

RESUMO

Background: Previous studies have paid attention to media as an important channel for understanding organ donation knowledge and have not divided groups according to the degree of media use to study their differences in organ donation. Therefore, the purpose of this study is to explore the influence of media use on organ donation willingness and the influencing factors of organ donation willingness of people with different media use levels. Methods: A cross-sectional study of residents from 120 cities in China was conducted by questionnaire survey. Using Mplus 8.3 software, the latent profile analysis of seven media usage related items was made, and multiple linear regression was performed to analyze the influence of varying levels of media use on organ donation willingness of different population. Results: All the interviewees were divided into three groups, namely, "Occluded media use" (9.7%), "Ordinary media use" (67.1%) and "High-frequency media use" (23.2%). Compared with ordinary media use, high-frequency media population (ß = 0.06, P < 0.001) were positively correlated with their willingness to accept organ donation, residents who used media occlusion (ß = -0.02, P < 0.001) were negatively correlated with their willingness to accept organ donation. The influencing factors of residents' accept willingness to organ donation were different among the types of occluded media use, ordinary media use and high-frequency media use. Conclusion: It is necessary to formulate personalized and targeted dissemination strategies of organ donation health information for different media users.


Assuntos
Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Humanos , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , China
20.
Chemphyschem ; 23(17): e202200288, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35689533

RESUMO

We have performed a study on the accommodation of nitrogen doping toward superatomic states of transition metal clusters. By reacting cobalt clusters with N2 in the presence of plasma radiation, a large number of odd-nitrogen clusters were observed, typically Co3 N2m-1 + (m=1-5) and Co4 N2m-1 + (m=1-6) series, showing N≡N bond cleavage in the mild plasma atmosphere. Interestingly, the Co3 N7 + , Co4 N9 + , and Co5 N9 + clusters exhibit prominent mass abundances. First-principles calculation results elucidate the stability of the diverse cobalt nitride clusters and find unique stability of Co4 N9 + with a swallow-kite structure of which four coordinated N2 molecules causes a significantly enlarged HOMO-LUMO gap, while the single N atom doping gives rise to superatomic states of 1S2 1P3 ||1D0 . We reveal an efficient dinitrogen activation strategy by reacting multiple N2 molecules with cobalt clusters under a plasma atmosphere.


Assuntos
Cobalto , Nitrogênio , Cobalto/química , Nitrogênio/química
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