Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 188
Filtrar
1.
Front Endocrinol (Lausanne) ; 12: 759338, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795642

RESUMO

Background: The 21-gene assay recurrence score (RS) provides additional information on recurrence risk of breast cancer patients and prediction of chemotherapy benefit. Previous studies that examined the contribution of the individual genes and gene modules of RS were conducted mostly in postmenopausal patients. We aimed to evaluate the gene modules of RS in patients of different ages. Methods: A total of 1,078 estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients diagnosed between January 2009 and March 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were included. All patients were divided into three subgroups: Group A, ≤40 years and premenopausal (n = 97); Group B, >40 years and premenopausal (n = 284); Group C, postmenopausal (n = 697). The estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of the variance tests were conducted for RS and its constituent modules. Results: In patients >40 years, RS had a strong negative correlation with its estrogen module (ρ = -0.76 and -0.79 in Groups B and C) and a weak positive correlation with its invasion module (ρ = 0.29 and 0.25 in Groups B and C). The proliferation module mostly contributed to the variance in young patients (37.3%) while the ER module contributed most in old patients (54.1% and 53.4% in Groups B and C). In the genetic high-risk (RS >25) group, the proliferation module was the leading driver in all patients (ρ = 0.38, 0.53, and 0.52 in Groups A, B, and C) while the estrogen module had a weaker correlation with RS. The impact of ER module on RS was stronger in clinical low-risk patients while the effect of the proliferation module was stronger in clinical high-risk patients. The association between the RS and estrogen module was weaker among younger patients, especially in genetic low-risk patients. Conclusions: RS was primarily driven by the estrogen module regardless of age, but the proliferation module had a stronger impact on RS in younger patients. The impact of modules varied in patients with different genetic and clinical risks.

2.
Int J Biol Macromol ; 191: 1240-1248, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34624378

RESUMO

Developing applicable biosorbents for adsorptive removal of organic pollutants from water is highly demanded. However, most biosorbents suffer poor adsorption capability for anionic organic pollutants due to their negatively charged surface. Herein, we present a facile method to synthesize amine-crosslinked starch (ACS) biosorbent for removing anionic organic pollutants. The adsorption properties of ACS were thoroughly evaluated by selecting anionic brilliant blue (BB), amaranth (ART), diclofenac sodium (DS) as representatives. The results show that the ACS can selectively adsorb anionic molecules with large adsorption capacity and fast removal rate. The adsorption kinetic and isotherm behaviors can be well described by the pseudo-second-order and Langmuir models, respectively. The maximum uptake capacity of ACS for BB, ART and DS is as high as 1287.7, 724.6 and 595.2 mg g-1, respectively. Moreover, the ACS can be easily regenerated and still exhibits favorable adsorption performance even after reusing for five times.

3.
J Adolesc ; 92: 177-188, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34555565

RESUMO

INTRODUCTION: Adolescence to emerging adulthood is a developmental period when individuals experience substantial biological changes and social transitions. In East Asian societies, this period is also marked by high pressure around college entrance exams. However, little is known about how young people's sleep changes over time, or how it is impacted by social institutions in the cultural context. This study fills this gap in the literature by examining sleep trajectories from adolescence to emerging adulthood using a population-based, longitudinal sample from Taiwan. METHODS: Multilevel models were applied to longitudinal data from the Taiwan Youth Project (N = 1,489) to estimate sleep trajectories from age 14 to 22 for total time in bed, bedtime, and wake-up time by gender and by educational pathway, controlling for family background. RESULTS: Analysis revealed that Taiwanese youth sleep less as adolescents than as emerging adults. Gender differences exist in adolescents' sleep trajectories but narrow after age 18. Differences in weekday and weekend time in bed vary by gender and change as individuals emerge into adulthood. Finally, college attendees and high school only attendees display differences in sleep that begin in high school and continue through college. CONCLUSIONS: The findings provide evidence of developmental changes in sleep from adolescence to emerging adulthood and demonstrate that sleep trajectories are gendered and socially patterned. The study is also one of the first to examine the sleep trajectories of East Asian youth and, as such, sheds light on the role of educational and cultural context as an influential factor.

4.
Autophagy ; : 1-18, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34436957

RESUMO

TBK1 (TANK-binding kinase 1) is an essential receptor protein required for the innate immune response, but the mechanisms underlying TBK1 stability, especially those regulated via autophagy, remain poorly understood. Here, we demonstrate that USP19 (ubiquitin specific peptidase 19) interacts with and promotes TBK1 lysosomal degradation via chaperone-mediated autophagy (CMA). We observed that TBK1 had a canonical CMA motif, knocking down key proteins involved in CMA (HSPA8/HSC70 or LAMP2A) or inhibiting CMA-prevented USP19-mediated TBK1 degradation. Furthermore, USP19 deficiency in macrophages caused an elevation of TBK1 and the activation of the type-I interferon signaling pathway after vesicular stomatitis virus (VSV) infection. Consistently, macrophage-specific usp19 knockout in mice resulted in attenuated VSV replication and resistance to VSV infection in vivo. Altogether, our results suggest that USP19 is a key regulator of TBK1 and uncovers a previously uncharacterized role for USP19 in CMA-mediated TBK1 degradation and infectious diseases.

5.
Eur J Med Chem ; 223: 113677, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225179

RESUMO

MLL1-WDR5 interaction is essential for the formation of MLL core complex and its H3K4 methyltransferase activity. Disrupting MLL1-WDR5 interaction has been proposed as a potential therapeutic approach in the treatment of leukemia. A "toolkit" of well-characterized chemical probe will allow exploring animal studies. Based on a specific MLL1-WDR5 PPI inhibitor (DDO-2117), which was previously reported by our group, we conducted a bioisosterism approach by click chemistry to discover novel phenyltriazole scaffold MLL1-WDR5 interaction blockers. Here, our efforts resulted in the best inhibitor 24 (DDO-2093) with high binding affinity (Kd = 11.6 nM) and with improved drug-like properties. Both in vitro and in vivo assays revealed 24 could efficiently block the MLL1-WDR5 interaction. Furthermore, 24 significantly suppressed tumor growth in the MV4-11 xenograft mouse model and showed a favorable safety profile. We propose 24 as a chemical probe that is suitable for in vivo pharmacodynamic and biological studies of MLL1-WDR5 interaction.


Assuntos
Antineoplásicos/química , Histona-Lisina N-Metiltransferase/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína de Leucina Linfoide-Mieloide/metabolismo , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Cinética , Camundongos , Camundongos Nus , Simulação de Acoplamento Molecular , Proteína de Leucina Linfoide-Mieloide/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Ligação Proteica , Mapas de Interação de Proteínas/efeitos dos fármacos , Relação Estrutura-Atividade , Transplante Heterólogo , Triazóis/química , Triazóis/metabolismo , Triazóis/farmacologia , Triazóis/uso terapêutico
6.
Clin Breast Cancer ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34244052

RESUMO

BACKGROUND: In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2+ breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2+ early breast cancer. PATIENTS AND METHODS: Nine hundred and nineteen early HER2+ breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR+/HER2+ patients were further divided based on ER level (Low/L: 1%-9%; Median/M: 10%-79%; High/H: 80%-100%) and PR level (Low/L: 0%-19%; High/H: 20%-100%) according to restricted cubic spline (RCS) smoothing curve. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and log rank test. RESULTS: Four hundred and forty two HR+/HER2+ and 477 HR-/HER2+ breast cancer patients were included in our study and 73.2% received target therapy (HR+ 69.7%, HR- 76.5%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 93.0% vs. 86.8%, P < .001), no significant difference was observed between DFS in ER+/PR+ and ER+/PR- subgroup (94.4% vs. 90.4%, P = .22). However, a potential correlation was found between ER/PR levels and DFS in HR+/HER2+ (P = .074) tumors. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR. In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.10 (95%CI 0.01-0.74, P = .024) in all patients and 0.14 (95%CI, 0.02-1.02, P = .053) in patients receiving anti-HER2 therapy. CONCLUSION: ER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.

7.
Pharmaceuticals (Basel) ; 14(6)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207271

RESUMO

Lipoteichoic acid (LTA) stimulates pleural mesothelial cell (PMC) to overproduce plasminogen activator inhibitor-1 (PAI-1), and thus may promote pleural fibrosis in Gram-positive bacteria (GPB) parapneumonic effusion (PPE). Histone deacetylase inhibitor (HDACi) was found to possess anti-fibrotic properties. However, the effects of HDACi on pleural fibrosis remain unclear. The effusion PAI-1 was measured among 64 patients with GPB PPE. Pleural fibrosis was measured as radiographical residual pleural thickening (RPT) and opacity at a 12-month follow-up. The LTA-stimulated human PMCs and intrapleural doxycycline-injected rats were pretreated with or without the pan-HDACi, m-carboxycinnamic acid bis-hydroxamide (CBHA), then PAI-1 and collagen expression and activated signalings in PMCs, and morphologic pleural changes in rats were measured. Effusion PAI-1 levels were significantly higher in GPB PPE patients with RPT > 10 mm (n = 26) than those without (n = 38), and had positive correlation with pleural fibrosis shadowing. CBHA significantly reduced LTA-induced PAI-1 and collagen expression via inhibition of JNK, and decreased PAI-1 promoter activity and mRNA levels in PMCs. Furthermore, in doxycycline-treated rats, CBHA substantially repressed PAI-1 and collagen synthesis in pleural mesothelium and minimized pleural fibrosis. Conclusively, CBHA abrogates LTA-induced PAI-1 and collagen expression in PMCs and attenuates experimental pleural fibrosis. PAI-1 inhibition by HDACi may confer potential therapy for pleural fibrosis.

8.
Biomed Pharmacother ; 138: 111543, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311538

RESUMO

Acute lung injury (ALI) is a severe lung disease with limited therapeutic strategies. Munronoid I, a limonoid, which is extracted and purified from Munronia sinica, exhibits effective anti-neoplastic activities. In this study, we attempted to determine the anti-inflammatory effects of Munronoid I using both the lipopolysaccharide (LPS)-induced in vivo murine ALI models and in vitro assays. Our results demonstrated that Munronoid I treatment ameliorated LPS-induced ALI and inflammation in mice. Moreover, it also significantly inhibited LPS-induced pathological injuries, infiltration of inflammatory cells, and production of IL-1ß and IL-6. Furthermore, the in vitro assay showed that Munronoid I could inhibit the LPS-induced expression of inflammatory mediators such as iNOS, COX2, and production of pro-inflammatory cytokines by suppressing the activation of NF-κB signaling pathway in mouse peritoneal macrophages. Munronoid I reduced the LPS-, tumor necrosis factor alpha (TNF-α)- or interleukin 1 beta (IL-1ß)-induced transforming growth factor beta-activated kinase 1 (TAK1) phosphorylation and protein expression. Furthermore, the Munronoid I also promoted K48-linked ubiquitination and proteasomal degradation of TAK1. Taken together, these results demonstrated that Munronoid I exhibited anti-inflammatory activities both in vitro and in vivo, which might be a potential therapeutic candidate for the treatment of ALI and pulmonary inflammation.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/farmacologia , Limoninas/farmacologia , Pulmão/efeitos dos fármacos , MAP Quinase Quinase Quinases/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/enzimologia , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/isolamento & purificação , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Mediadores da Inflamação/metabolismo , Limoninas/isolamento & purificação , Lipopolissacarídeos , Pulmão/enzimologia , Pulmão/patologia , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/patologia , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação , Proteólise , Ubiquitinação
9.
Chemistry ; 27(39): 10115-10122, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34101277

RESUMO

The development of high-performance and low-cost durable triboelectric nanogenerators (TENGs) is essential for converting mechanical energy into electrical energy. Many organic polymer friction materials used widely have thermal stability problems, which makes TENGs with semiconductors as friction materials stand out. Here, we report a semi-flexible TENG based on metal and TiO2 modified by polyoxometalates (POMs) as pure inorganic friction materials. Six different POMs are firstly selected to modify the friction materials of TENGs, and the output performance of TENGs with different POMs-modified semiconductors and different metals as friction materials are tested. Compared with the unmodified TENGs, the open-circuit voltage (VOC ) of the optimal Ag-K6 P2 Mo18 O62 (P2 Mo18 )/TiO2 TENG device is increased by more than 4 times, which is mainly attributed to the strong electron-accepting and storage capabilities of POMs. This study has demonstrated that TENGs modified by POMs have potential application prospects and provided a new method for increasing the electrical output of TENGs.

10.
J Med Chem ; 64(12): 8221-8245, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34105966

RESUMO

WD repeat-containing protein 5 (WDR5) is essential for the stability and methyltransferase activity of the mixed lineage leukemia 1 (MLL1) complex. Dysregulation of the MLL1 gene is associated with human acute leukemias, and the direct disruption of the WDR5-MLL1 protein-protein interaction (PPI) is emerging as an alternative strategy for MLL-rearranged cancers. Here, we represent a new aniline pyrimidine scaffold for WDR5-MLL1 inhibitors. A comprehensive structure-activity analysis identified a potent inhibitor 63 (DDO-2213), with an IC50 of 29 nM in a competitive fluorescence polarization assay and a Kd value of 72.9 nM for the WDR5 protein. Compound 63 selectively inhibited MLL histone methyltransferase activity and the proliferation of MLL translocation-harboring cells. Furthermore, 63 displayed good pharmacokinetic properties and suppressed the growth of MV4-11 xenograft tumors in mice after oral administration, first verifying the in vivo efficacy of targeting the WDR5-MLL1 PPI by small molecules.


Assuntos
Antineoplásicos/uso terapêutico , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Leucemia/tratamento farmacológico , Proteína de Leucina Linfoide-Mieloide/antagonistas & inibidores , Ligação Proteica/efeitos dos fármacos , Compostos de Anilina/síntese química , Compostos de Anilina/metabolismo , Compostos de Anilina/farmacocinética , Compostos de Anilina/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Proliferação de Células/efeitos dos fármacos , Estabilidade de Medicamentos , Feminino , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Microssomos Hepáticos/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteína de Leucina Linfoide-Mieloide/metabolismo , Pirimidinas/síntese química , Pirimidinas/metabolismo , Pirimidinas/farmacocinética , Pirimidinas/uso terapêutico , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
11.
ACS Appl Mater Interfaces ; 13(21): 25010-25023, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34008956

RESUMO

High-performance triiodide reduction reaction (IRR) catalysts in dye-sensitized solar cells (DSSCs) and hydrogen evolution reaction (HER) catalysts in electrochemical water splitting are extremely compelling for renewable energy conversion and storage. The best IRR and HER catalysts generally rely on the use of noble metal platinum (Pt), which suffers obstacles in real-world implementation. The rational design of efficient bifunctional IRR and HER catalysts based on inexpensive and earth-abundant elements to replace scarce Pt could enable low-cost photoelectric conversion and hydrogen production but is challenging and rarely reported. Herein, we present a bifunctional NiFeCoW@NC hybrid with the unique architecture of WC loaded on the in situ formed carbon nanotubes embedded with Co-doped FeNi3 nanoparticles based on the anisotropic integration design principle, which operates efficiently for DSSCs and hydrogen evolution. The assembled DSSCs using the designed multimetal-based NiFeCoW@NC counter electrode delivered a high power conversion efficiency of 6.92% and long-term stability superior to bimetal-based NiFe@NC, CoW@NC, and Pt counterparts. It also exhibited eminent hydrogen evolution performance with a low overpotential of 127.8 mV to drive a 10 mA cm-2 current density, a Tafel slope of 60.4 mV dec-1, and satisfactory durable stability in 0.5 M H2SO4. This work provides a design principle for low-cost and highly active bifunctional catalysts to replace Pt for DSSCs and hydrogen evolution.

12.
Front Public Health ; 9: 598302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046381

RESUMO

This study attempts to compare the impacts of the coronavirus (COVID-19) pandemic on college students' lifestyles and mental health conditions in South Korea and Taiwan. As the COVID-19 outbreak has spread across the globe, it has brought significant changes to college campuses worldwide. College students have been heavily affected by the closure, as online learning has become increasingly common in higher education institutions. Using data collected from college students in South Korea and Taiwan in the spring of 2020, this study examines the effects of pandemic-related lifestyle changes on mental health conditions for college students in the two countries. The results were 3-fold. First, compared to college students in Taiwan, college students in South Korea reported greater decreases in time spent traveling, being with friends, eating at restaurants, and engaging in part-time employment, and greater increases in online shopping and ordering food for delivery. Second, college students in South Korea reported a higher level of worry, a greater possibility of contact with a person with COVID-19, and a lower level of happiness than did college students in Taiwan. Third, our findings indicate that social activities, including spending time with friends, were positively correlated with mental health conditions in South Korea and Taiwan. Comparing Korean and Taiwanese students' lifestyle changes and mental health conditions amid the pandemic, the study argues that the decrease in socialization and interaction under these new circumstances may be a significant factor that explains an increase in mental health issues in Korean college students compared to Taiwanese students, given the increase in confirmed COVID-19 cases in South Korea and the corresponding greater use of online teaching platforms there than in Taiwan.


Assuntos
COVID-19 , Pandemias , Humanos , República da Coreia/epidemiologia , SARS-CoV-2 , Estudantes , Taiwan/epidemiologia
13.
J Res Adolesc ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957002

RESUMO

A Positive Youth Development (PYD) perspective emphasizes adolescents' potential for healthy, successful development. Researchers have introduced a variety of constructs that may promote PYD. For example, Intentional Self-Regulation (ISR) enables youth to seek out and use resources in the environment; purpose can help youth navigate and overcome obstacles. We examine connections between ISR, purpose and two PYD outcomes: confidence and connection. Data come from 763 Scottish youth (ages 12-14). We estimated fixed-effects regression models predicting confidence and connection from both ISR and purpose, confirming outcomes were independently associated with one or both predictors. Our findings are especially salient to the field of youth purpose, linking purpose with specific PYD outcomes.

14.
Nat Commun ; 12(1): 1984, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790277

RESUMO

Polymer memristors with light weight and mechanical flexibility are preeminent candidates for low-power edge computing paradigms. However, the structural inhomogeneity of most polymers usually leads to random resistive switching characteristics, which lowers the production yield and reliability of nanoscale devices. In this contribution, we report that by adopting the two-dimensional conjugation strategy, a record high 90% production yield of polymer memristors has been achieved with miniaturization and low power potentials. By constructing coplanar macromolecules with 2D conjugated thiophene derivatives to enhance the π-π stacking and crystallinity of the thin film, homogeneous switching takes place across the entire polymer layer, with fast responses in 32 ns, D2D variation down to 3.16% ~ 8.29%, production yield approaching 90%, and scalability into 100 nm scale with tiny power consumption of ~ 10-15 J/bit. The polymer memristor array is capable of acting as both the arithmetic-logic element and multiply-accumulate accelerator for neuromorphic computing tasks.

15.
Front Pharmacol ; 12: 643520, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897433

RESUMO

Rheumatic diseases are a group of chronic autoimmune disorders that involve multiple organs or systems and have high mortality. The mechanisms of these diseases are still ill-defined, and targeted therapeutic strategies are still challenging for physicians. Recent research indicates that cell metabolism plays important roles in the pathogenesis of rheumatic diseases. In this review, we mainly focus on lipid metabolism profiles (dyslipidaemia, fatty acid metabolism) and mechanisms in rheumatic diseases and discuss potential clinical applications based on lipid metabolism profiles.

16.
Mol Oncol ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811456

RESUMO

Glioma cells are characterized by high migration and invasion ability; however, the molecular mechanism behind both processes still remains to be investigated. Several studies have demonstrated that ubiquitin-specific protease 39 (USP39) plays an oncogenic role in various cancer types. Here, we investigated the expression and function of USP39 in patients with glioma. Oncomine database analysis revealed that high USP39 expression was significantly correlated with poor overall survival in patients with glioma. Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro. Gene expression profiling of glioma cells transduced with short hairpin RNA (shRNA) against USP39 revealed that disintegrin and metalloproteinase domain-containing protein 9 (ADAM9), a molecule previously related to tumor cell migration and invasion, was significantly downregulated. Furthermore, USP39 induced ADAM9 messenger RNA (mRNA) maturation and decreased the expression of integrin ß1. Additionally, overexpression of ADAM9 inhibited the migration and invasion of glioma cells caused by USP39 depletion in vitro. USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice. Altogether, our data show that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered potential target for treating patients with glioma.

17.
Appl Opt ; 60(5): 1420-1427, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690586

RESUMO

Fundus examination plays an important part in a medical setting. The fundus camera is one of the detection instruments used in obtaining fundus images, which can reflect information about disease and other conditions. However, traditional fundus cameras have many disadvantages in regard to data sharing, image recognition, and processing, as well as doctor-patient communication. In recent years, mobile medical systems have gradually become more prevalent in medical and health system environments. In this paper, we propose a design method for a smartphone fundus camera consisting of an illumination system and an imaging system. The end of the system can be combined with a smartphone to take the fundus images directly. We manufactured a prototype, designed an artificial eye model, and carried out a series of experiments. The results show that we can get fundus images clearly, and the imaging system will be able to correct refractive errors ranging from -8D∼+8D. The spatial resolution of the system is up to 15 µm. This is a portable device with an overall size of 160mm×160mm×80mm and a weight of 540 g. It has the advantages of lower price, simple operation, high resolution, and compact size, making it suitable as a portable ocular monitoring device.


Assuntos
Fundo de Olho , Fotografação/instrumentação , Smartphone/instrumentação , Humanos , Processamento de Imagem Assistida por Computador , Oftalmoscopia , Reprodutibilidade dos Testes
18.
Inorg Chem ; 60(8): 5829-5839, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33779146

RESUMO

The establishment of a heterojunction is a crucial strategy to design highly effective nonnoble metal nanocatalysts for the photocatalytic nitrogen reduction reaction (PNRR). Heteropoly blues (r-POMs) can act as electron-transfer mediators in PNRR, but its agglomeration limits the further promotion of PNRR productivity. In this work, we construct a protonation-modified surface of N-vacancy g-C3N4 (HV-C3N4), achieving the high dispersion of r-POMs via the surface modification strategy. Enlightened by the synergy effect of the nitrogenase, r-POMs were anchored onto HV-C3N4 nanosheets through an electrostatic self-assembly method for preparing r-POMs-based protonation-defective graphitic carbonitride (HV-C3N4/r-POMs). As an electron donor, r-PW12 can match with the energy level of HV-C3N4 to build a heterojunction. The electron redistribution of the heterojunction facilitates the optimization of the electronic structure for enhancing the performance of PNRR. HV-C3N4/r-PW12 exhibits the best PNRR efficiency of 171.4 µmol L-1 h-1, which is boosted by 94.39% (HV-C3N4) and 86.98% (r-PW12). The isotope 15NH4+ experiment proves that ammonia is derived from N2, not carbon nitride. This study opens up a crucial view to achieve the high dispersion of r-POMs nanoparticles and develop high-efficiency nonnoble metal photocatalysts for the PNRR.

19.
iScience ; 24(2): 102034, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33554057

RESUMO

Human mitochondrial NAD(P)+-dependent malic enzyme (ME2) is well recognized to associate with cancer cell metabolism, and the single nucleotide variants (SNVs) of ME2 may play a role in enzyme regulation. Here we reported that the SNVs of ME2 occurring in the allosteric sites lead to inactivation or overactivation of ME2. Two ME2-SNVs, ME2_R67Q and ME2-R484W, that demonstrated inactivating or overactivating enzyme activities of ME2, respectively, have different impact toward the cells. The cells with overactivating SNV enzyme, ME2_R484W, grow more rapidly and are more resistant to cellular senescence than the cells with wild-type or inactivating SNV enzyme, ME2_R67Q. Crystal structures of these two ME2-SNVs reveal that ME2_R67Q was an inactivating "dead form," and ME2_R484W was an overactivating "closed form" of the enzyme. The resolved ME2-SNV structures provide a molecular basis to explain the abnormal kinetic properties of these SNV enzymes.

20.
Rheumatology (Oxford) ; 60(5): 2177-2189, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33165604

RESUMO

OBJECTIVES: Muscle cell necrosis is the most common pathological manifestation of idiopathic inflammatory myopathies. Evidence suggests that glycolysis might participate in it. However, the mechanism is unclear. This study aimed to determine the role of glycolysis in the muscle damage that occurs in DM/PM. METHODS: Mass spectrometry was performed on muscle lesions from DM/PM and control subjects. The expression levels of pyruvate kinase isozyme M2 (PKM2), the nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and pyroptosis-related genes in muscle tissues or plasma were determined by real-time PCR, western blot analysis, IF and ELISA. In addition, IFNγ was used to stimulate myotubes, and the relationships among PMK2 expression, NLRP3 inflammasome activation and pyroptosis were investigated. RESULTS: Mass spectrometry and bioinformatics analysis suggested that multiple glycolysis processes, the NLRP3 inflammasome and programmed cell death pathway-related proteins were dysregulated in the muscle tissues of DM/PM. PKM2 and the NLRP3 inflammasome were upregulated and positively correlated in the muscle fibres of DM/PM. Moreover, the pyroptosis-related proteins were increased in muscle tissues of DM/PM and were further increased in PM. The levels of PKM2 in muscle tissues and IL-1ß in plasma were high in patients with anti-signal recognition particle autoantibody expression. The pharmacological inhibition of PKM2 in IFNγ-stimulated myotubes attenuated NLRP3 inflammasome activation and subsequently inhibited pyroptosis. CONCLUSION: Our study revealed upregulated glycolysis in the lesioned muscle tissues of DM/PM, which activated the NLRP3 inflammasome and leaded to pyroptosis in muscle cells. The levels of PKM2 and IL-1ß were high in patients with anti-signal recognition particle autoantibody expression. These proteins might be used as new biomarkers for muscle damage.


Assuntos
Proteínas de Transporte/metabolismo , Dermatomiosite/metabolismo , Glicólise/fisiologia , Inflamassomos/metabolismo , Proteínas de Membrana/metabolismo , Músculo Esquelético/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Hormônios Tireóideos/metabolismo , Biologia Computacional , Humanos , Espectrometria de Massas , Mioblastos/metabolismo , Regulação para Cima
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...