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1.
Int J Biol Macromol ; 270(Pt 1): 131968, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704059

RESUMO

Enzymatic degradation of lignocellulosic biomass provides an eco-friendly approach to produce value-added macromolecules, e.g., bioactive polysaccharides. A novel acidophilic GH5 ß-1,4-endoglucanase (termed TaCel5) from Trichoderma asperellum ND-1 was efficiently expressed in Komagataella phaffii (∼1.5-fold increase, 38.42 U/mL). TaCel5 displayed both endoglucanase (486.3 U/mg) and alginate lyase (359.5 U/mg) enzyme activities. It had optimal pH 3.0 and strong pH stability (exceed 86 % activity retained over pH range 3.0-5.0). 80 % activity (both endoglucanase and alginate lyase) was retained in the presence of 15 % ethanol or 3.42 M NaCl. Analysis of action mode revealed that hydrolytic activity of TaCel5 required at least three glucose (cellotriose) residues, yielding mainly cellobiose. Glu241 and Glu352 are essential catalytic residues, while Asp106, Asp277 and Asp317 play auxiliary roles in cellulose degradation. TaCel5 displayed high hydrolysis efficiency for glucan and alginate substrates. ESI-MS analysis indicated that the enzymatic hydrolysates of alginate mainly contained disaccharides and heptasaccharides. This is the first detailed report of a bifunctional GH5 endoglucanase/alginate lyase enzyme from T. asperellum. Thus TaCel5 has strong potential in food and feed industries as a catalyst for bioconversion of cellulose- and alginate-containing waste materials into value-added products oligosaccharides, which was of great benefit both for the economy and environment.


Assuntos
Alginatos , Celulase , Celulose , Oligossacarídeos , Alginatos/metabolismo , Alginatos/química , Celulase/metabolismo , Celulase/química , Oligossacarídeos/metabolismo , Oligossacarídeos/química , Hidrólise , Celulose/metabolismo , Concentração de Íons de Hidrogênio , Hypocreales/enzimologia , Especificidade por Substrato , Polissacarídeo-Liases/metabolismo , Polissacarídeo-Liases/química , Polissacarídeo-Liases/genética
2.
Microvasc Res ; 154: 104685, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38593952

RESUMO

BACKGROUND: Coronary microvascular dysfunction (CMD) is frequently observed in atrial fibrillation (AF), the most commonly sustained arrhythmia. Nevertheless, an in-depth prognostic significance of CMD in AF is lacking. We aimed to provide insight into the predictive impact of CMD assessed by a novel non-invasive coronary angiography-derived index of microcirculatory resistance (caIMR) for major adverse events (MACE) in AF patients. METHOD: This study included patients with AF who underwent invasive coronary angiography due to suspected cardiac ischemia and did not exhibit obstructive epicardial coronary artery disease (≤50 % stenosis). The caIMR was prospectively evaluated, and the optimal cutoff value for predicting MACE was determined through ROC analysis. RESULT: A total of 463 patients with AF were enrolled. During a median of 33 months of follow-up, 111 (23.97 %) patients had MACE endpoints. The best caIMR cutoff value was 39.28. In patients with MACE, both the mean caIMR and the prevalence of elevated caIMR (caIMR>39.28) were significantly higher compared to those without MACE. An elevated caIMR was linked to a higher risk of MACE (log-rank P < 0.001) and emerged as an independent predictor of clinical outcomes (HR: 4.029; 95 % CI: 2.529-6.418; P < 0.001). In addition, the risk of MACE was higher in high caIMR patients with non-paroxysmal AF (log-rank P < 0.001) and no catheter ablation (log-rank P < 0.001). CONCLUSION: Elevated caIMR is common and showed a vital independent prognostic significance in AF patients. In addition to well-known risk factors, assessment of microvascular function can be a feasible approach for early prevention and a therapeutic target in AF patients.

3.
Toxicology ; 503: 153757, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364893

RESUMO

Doxorubicin (DOX) is a widely used antitumor agent; however, its clinical application is limited by dose-related organ damage. Because organic cation/carnitine transporters (OCTN1 and OCTN2), which are critical for DOX uptake, are highly expressed in hepatocytes, we aimed to elucidate the role of these transporters in hepatic DOX uptake. The results indicated that inhibitors and RNA interference both significantly reduced DOX accumulation in HepG2 and HepaRG cells, suggesting that OCTN1/2 contribute substantially to DOX uptake by hepatocytes. To determine whether metformin (MET, an inhibitor of OCTN1 and OCTN2) ameliorates DOX-induced hepatotoxicity, we conducted in vitro and in vivo studies. MET (1-100 µM) inhibited DOX (500 nM) accumulation and cytotoxicity in vitro in a concentration-dependent manner. Furthermore, intravenous MET administration at 250 or 500 mg/kg or by gavage at 50, 100, or 200 mg/kg reduced DOX (8 mg/kg) accumulation in a dose-dependent manner in the mouse liver and attenuated the release of alanine aminotransferase, aspartate aminotransferase, and carboxylesterase 1. Additionally, MET reduced the distribution of DOX in the heart, liver, and kidney and enhanced the urinary elimination of DOX; however, it did not increase the nephric toxicity of DOX. In conclusion, our study demonstrated that MET alleviates DOX hepatotoxicity by inhibiting OCTN1- and OCTN2-mediated DOX uptake in vitro (mouse hepatocytes and HepaRG or HepG2 cells) and in mice.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Metformina , Simportadores , Camundongos , Animais , Proteínas de Transporte de Cátions Orgânicos/genética , Membro 5 da Família 22 de Carreadores de Soluto , Metformina/farmacologia , Doxorrubicina/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
4.
Adv Sci (Weinh) ; 11(7): e2306504, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38064198

RESUMO

Seeking new cathode chemistry with high onset potential and compatibility with electrolytes has become a challenge for aqueous Zn ion batteries. Anion intercalation in graphite (4.5 V vs Li+ /Li) possesses the potentiality but usually shows a competitive relationship with oxygen evolution reaction (OER) in aqueous solutions. Herein, a decoupled design is proposed to optimize a full utilization of perchlorate ion intercalation in graphite cathode by pH adjustment. Benefiting from the decoupled design, high Coulombic efficiency is obtained by decelerating the kinetic of OER in acidic media. The decoupled Zn-graphite battery exhibits a wide potential window of 2.01 V, as well as an attractive energy density of 231 Wh kg-1 . In addition, a Zn-graphite battery with SO 4 2 - ${\mathrm{SO}}_4^{2 - }$ insertion is assembled, which demonstrates the capability of the proposed decoupled strategy to integrate novel electrode chemistries for high-performance aqueous Zn-based energy storage systems.

5.
Natl Sci Rev ; 11(1): nwad102, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38116087

RESUMO

Precisely acquiring the timing information of individual X-ray photons is important in both fundamental research and practical applications. The timing precision of commonly used X-ray single-photon detectors remains in the range of one hundred picoseconds to microseconds. In this work, we report on high-timing-precision detection of single X-ray photons through the fast transition to the normal state from the superconductive state of superconducting nanowires. We successfully demonstrate a free-running X-ray single-photon detector with a timing resolution of 20.1 ps made of 100-nm-thick niobium nitride film with an active area of 50 µm by 50 µm. By using a repeated differential timing measurement on two adjacent X-ray single-photon detectors, we demonstrate a precision of 0.87 ps in the arrival-time difference of X-ray photon measurements. Therefore, our work significantly enhances the timing precision in X-ray photon counting, opening a new niche for ultrafast X-ray photonics and many associated applications.

6.
J Cardiovasc Med (Hagerstown) ; 24(12): 891-899, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37942790

RESUMO

BACKGROUND: Patients with aortic valve stenosis have been postulated to have coronary microvascular dysfunction (CMD) contributing to the clinical symptoms and adverse outcomes. The coronary angiography (CAG)-derived index of microcirculatory resistance (caIMR) is proposed as a novel, less invasive and pressure-wire-free index to assess CMD. This study aimed to quantify CMD assessed by caIMR and investigate its prognostic impact in patients with aortic valve stenosis. METHODS: This study included 77 moderate or severe aortic valve stenosis patients with no obstructive coronary disease (defined as having no stenosis more than 50% in diameter) who underwent caIMR measurement. CMD was defined by caIMR at least 25. Major adverse cardiovascular events (MACE) were the clinical outcomes during the median 40 months of follow-up. RESULTS: The incidence of CMD was 47.7%. Seventeen MACE occurred during the follow-up duration. CMD was associated with an increased risk of MACE (log-rank P < 0.001) and an independent predictor of clinical outcomes [hazard ratio 5.467, 95% confidence interval (CI) 1.393-21.458; P = 0.015]. The receiver-operating characteristic (ROC) curve analysis demonstrated that caIMR could provide a significant predictive value for MACE in aortic valve stenosis patients (AUC 0.785, 95% CI 0.609-0.961, P < 0.001). In addition, the risk of MACE was higher in CMD patients with severe aortic valve stenosis (log-rank P < 0.001) and no aortic valve replacement (log-rank P = 0.003) than in other groups. CONCLUSION: Aortic valve stenosis patients demonstrated markedly impaired caIMR. CMD assessed by caIMR increases the risk of MACE and is an independent predictor of adverse outcomes in aortic valve stenosis patients. This finding suggests that using caIMR in the clinical assessment may help identify high-risk groups and stimulate earlier intervention.


Assuntos
Estenose da Valva Aórtica , Doença da Artéria Coronariana , Estenose Coronária , Humanos , Prognóstico , Microcirculação , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Doença da Artéria Coronariana/complicações , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/terapia , Estenose Coronária/complicações
7.
Chem Biol Interact ; 382: 110627, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37453608

RESUMO

Doxorubicin (DOX) has been widely used to treat various tumors; however, DOX-induced cardiotoxicity limits its utilization. Since high accumulation of DOX in cardiomyocytes/mitochondria is the key reason, we aimed to clarify the mechanisms of DOX uptake and explore whether selectively inhibiting DOX uptake transporters would attenuate DOX accumulation and cardiotoxicity. Our results demonstrated that OCTN1/OCTN2/PMAT (organic cation/carnitine transporter 1/2 or plasma membrane monoamine transporter), especially OCTN2, played crucial roles in DOX uptake in cardiomyocytes, while OCTN2 and OCTN1 contributed to DOX transmembrane transport in mitochondria. Metformin (1-100 µM) concentration-dependently reduced DOX (5 µM for accumulation, 500 nM for cytotoxicity) concentration and toxicity in cardiomyocytes/mitochondria via inhibition of OCTN1-, OCTN2- and PMAT-mediated DOX uptake but did not affect its efflux. Furthermore, metformin (iv: 250 and 500 mg/kg or ig: 50, 100 and 200 mg/kg) could dose-dependently reduce DOX (8 mg/kg) accumulation in mouse myocardium and attenuated its cardiotoxicity. In addition, metformin (1-100 µM) did not impair DOX efficacy in breast cancer or leukemia cells. In conclusion, our study clarified the role of multiple transporters, especially OCTN2, in DOX uptake in cardiomyocytes/mitochondria; metformin alleviated DOX-induced cardiotoxicity without compromising its antitumor efficacy by selective inhibition of multiple transporters mediated DOX accumulation in myocardium/mitochondria.


Assuntos
Metformina , Miócitos Cardíacos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Membro 5 da Família 22 de Carreadores de Soluto/metabolismo , Doxorrubicina/farmacologia , Mitocôndrias , Metformina/farmacologia , Metformina/metabolismo
8.
Physiol Plant ; 175(3): e13939, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37243848

RESUMO

The floral coloration of tulip flowers is one of the most prominent traits contributing to its high ornamental value. The molecular mechanisms of petal coloration remain elusive in tulip species. In this study, we performed comparative metabolome and transcriptome analyses using four tulip cultivars with distinguished petal colors. Four types of anthocyanins were identified, including cyanidin derivatives and pelargonidin derivatives. Comparative transcriptome analysis identified 22,303 differential expressed genes (DEGs) from the four cultivars, and 2589 DEGs were commonly regulated in three comparison groups (colored vs. white cultivar), including anthocyanins biosynthesis-related genes and regulatory transcription factors. Two basic helix-loop-helix (bHLH) transcription factors, TgbHLH42-1 and TgbHLH42-2, with differential expression levels among cultivars and petal developmental stages, have high homology to TRANSPARENT TESTA 8 (AtTT8) of Arabidopsis. The anthocyanins accumulation in TgbHLH42-1 overexpressing (OE) seedlings was markedly greater than that in wild-type seedlings in the presence of methyl jasmonate (MeJA), but not for TgbHLH42-2 OE seedlings. Both TgbHLH42-1 and TgbHLH42-2 restored pigmentation defects in tt8 mutant seeds after complementation assay. TgbHLH42-1 could interact with MYB protein AtPAP1 to synergistically activate the transcription of AtDFR, whereas TgbHLH42-2 failed to. Silencing TgbHLH42-1 or TgbHLH42-2 individually could not, but simultaneously silencing both TgbHLH42 could reduce the anthocyanin in tulip petals. These results indicate that TgbHLH42-1 and TgbHLH42-2 function partially redundantly to positively regulate anthocyanin biosynthesis during tulip petal coloration.


Assuntos
Antocianinas , Tulipa , Antocianinas/metabolismo , Tulipa/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Pigmentação , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo
9.
Sci Rep ; 13(1): 7370, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147325

RESUMO

To reveal the mechanical properties of rocks under stress disturbance and unloading confining pressure, conventional triaxial compression tests, triaxial compression tests on unloading damaged sandstone, and cyclic loading and unloading tests on unloading damaged sandstone were conducted. Then, the evolutionary characteristics of dissipated energy in sandstone under cyclic loading and unloading were explored, and damage variables were proposed. The crack development characteristics were analyzed from a microscopic perspective. The study results reveal that: (1) the sandstone exhibits obvious brittle failure under different stress paths, and the macroscopic failure mode is dominated by shear failure. As the number of cycles increases, the load-bearing capacity, elastic modulus, and deformation modulus of the sandstone will be significantly reduced if it suffers greater unloading damage. (2) The cyclic action in the early stage inhibits the development of the internal fracture. However, the inhibitory effect is significantly reduced for specimens with larger unloading quantities. The damage variable in the cyclic loading and unloading is about 50.00% of that in the unloading, indicating that unloading confining pressure is the dominant factor for specimen failure. (3) The extension of microcracks within the sandstone is dominated by intergranular cracks, and the number of cracks increases with the increase of unloading quantity. After cyclic loading and unloading, the structure becomes looser. The test results deepen the understanding of rock mechanical behavior and fracture evolution under cyclic loading and can provide a basis for structural stability improvement under stress disturbance and unloading confining pressure.

10.
Eur J Intern Med ; 108: 74-80, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36464551

RESUMO

BACKGROUND: Coronary slow flow (CSF) is common and linked to worse cardiovascular events and life-threatening arrhythmias. However, the clinical implication of CSF among myocardial infarction with the non-obstructive coronary artery (MINOCA) has never been studied. We aimed to evaluate the impact of CSF on the MINOCA population. METHODS: Patients diagnosed with MINOCA were consecutively selected. The corrected TIMI frame count (cTFC) was used to evaluate the coronary flow. CSF was defined as cTFC greater than 27 frames per second (FPS) in any of the three coronary arteries. Major adverse cardiovascular events (MACE) are the primary endpoint. Cox regression analysis was used to evaluate the association between CSF and MACE. RESULTS: A total of 158 patients with MINOCA were enrolled, of which 54 (34.2%) patients had CSF. Forty incidents of MACE occurred during the median 28 months of follow-up. The MACE incidence was higher among patients who presented with CSF than the normal coronary flow patients (35.2% vs. 20.2%, p = 0.040). In the Kaplan-Meier analysis, CSF patients had significantly higher rates of MACE (log-rank P = 0.034). Multivariate Cox regression analysis showed that CSF was an independent predictor linked to an increased hazard of MACE (adjusted HR, 2.76; 95% CI, 1.34-5.67; P = 0.006). CONCLUSION: The presence of CSF is associated with a higher risk of adverse events and is an independent predictor of clinical outcomes among patients with MINOCA. This result suggests that CSF might serve as a robust tool to stratify MINOCA patients.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Humanos , Prognóstico , Vasos Coronários/diagnóstico por imagem , MINOCA , Angiografia Coronária , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Fatores de Risco , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem
11.
Clin Cardiol ; 46(2): 204-213, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36567512

RESUMO

BACKGROUND: Ischemic pain with no-obstructive coronary artery (INOCA) is clinically significant and defined by nonobstructive coronary stenosis <50%. Coronary microvascular dysfunction (CMD) is a relevant cause associated with adverse outcomes. OBJECTIVES: Investigated the effect of no-stenosis (0% stenosis) and non-obstructive (0% < stenosis < 50%) on the prognostic impact of CMD in INOCA. METHOD: A retrospective study assessed the coronary microvascular function in 151 INOCA patients who underwent invasive angiography by the coronary angiography-derived index of microcirculation-resistance (caIMR). CZT-SPECT was performed to evaluate myocardial perfusion imaging (MPI) abnormalities. Chi-square test/Fisher exact test, Student t-test, Kaplan-Meier curve, and Uni-multivariable Cox proportional models were used for analysis. Clinical outcomes were major adverse cardiovascular events (MACE) during a median follow-up of 35 months. RESULT: No-stenosis was present in 71 (47%) INOCA patients, and 80 (53%) were with nonobstructive. CMD (caIMR ≥ 25) was more prevalent in patients with no-stenosis than nonobstructive (76.1% vs. 48.8%, p = .001), along with abnormal MPI (39.4% vs. 22.5%, p = .024). The MACE rates were not different between no-stenosis and nonobstructive stenosis. CMD showed an increased risk of MACE for all INOCA. No-stenosis with CMD had the worst prognosis. Cox regression analysis identified CMD and abnormal MPI as predictors of MACE in all INOCA and patients with no-stenosis. However, no-stenosis and nonobstructive stenosis were not predictors of MACE in INOCA. CONCLUSION: CMD was more frequently present in INOCA with no-stenosis. However, there was no difference in long-term clinical outcomes between no-stenosis and nonobstructive stenosis. CMD could independently predict poor outcomes in INOCA, particularly in patients with no-stenosis.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Isquemia Miocárdica , Humanos , Vasos Coronários , Estudos Retrospectivos , Fatores de Risco , Isquemia Miocárdica/complicações , Estenose Coronária/diagnóstico , Estenose Coronária/diagnóstico por imagem , Angiografia Coronária/métodos , Prognóstico , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico
12.
Int J Mol Sci ; 23(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36142739

RESUMO

With global warming and regional decreases in precipitation, drought has become a problem worldwide. As the number of arid regions in the world is increasing, drought has become a major factor leading to significant crop yield reductions and food crises. Soybean is a crop that is relatively sensitive to drought. It is also a crop that requires more water during growth and development. The aim of this study was to identify the quantitative trait locus (QTL) that affects drought tolerance in soybean by using a recombinant inbred line (RIL) population from a cross between the drought-tolerant cultivar 'Jindou21' and the drought-sensitive cultivar 'Zhongdou33'. Nine agronomic and physiological traits were identified under drought and well-watered conditions. Genetic maps were constructed with 923,420 polymorphic single nucleotide polymorphism (SNP) markers distributed on 20 chromosomes at an average genetic distance of 0.57 centimorgan (cM) between markers. A total of five QTLs with a logarithm of odds (LOD) value of 4.035-8.681 were identified on five chromosomes. Under well-watered conditions and drought-stress conditions, one QTL related to the main stem node number was located on chromosome 16, accounting for 17.177% of the phenotypic variation. Nine candidate genes for drought resistance were screened from this QTL, namely Glyma.16G036700, Glyma.16G036400, Glyma.16G036600, Glyma.16G036800, Glyma.13G312700, Glyma.13G312800, Glyma.16G042900, Glyma.16G043200, and Glyma.15G100700. These genes were annotated as NAC transport factor, GATA transport factor, and BTB/POZ-MATH proteins. This result can be used for molecular marker-assisted selection and provide a reference for breeding for drought tolerance in soybean.


Assuntos
Glycine max , Locos de Características Quantitativas , Mapeamento Cromossômico , Secas , Fatores de Transcrição GATA/genética , Fenótipo , Melhoramento Vegetal , Glycine max/genética , Água
13.
Toxicol Lett ; 363: 1-10, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35589016

RESUMO

Glucocorticoids such as dexamethasone (DEX) are widely prescribed to treat numerous conditions and diseases. However, glucocorticoid-induced liver lipid metabolism disorder, even nonalcoholic fatty liver disease, has caused extensive attention. Since fatty acid transporters such as CD36 and FATP play crucial roles in hepatic fatty acid uptake, this work examined their potential involvement in DEX-induced liver lipid accumulation. Chronic DEX administration (1-5 mg/kg/day over 28 days) induced hepatic lipid accumulation in mice. Fatty acid uptake in HepG2 cells and mouse primary hepatocytes was also stimulated after incubation with 0.5-2 µM DEX. Meanwhile, qPCR and western blotting demonstrated dose-dependent upregulation of CD36 expression by DEX in the mouse liver and in cultured hepatocytes. Glucocorticoid receptor (GR) inhibition with mifepristone (RU486) and siRNA-mediated GR knockdown attenuated lipid accumulation in hepatocytes by inhibiting DEX-induced CD36 upregulation, and direct binding of GR to the CD36 promoter was demonstrated by luciferase reporter and chromatin immunoprecipitation assays. These results indicate that DEX promotes free fatty acid uptake leading to hepatic steatosis by upregulating CD36 expression via activation of GR. Thus, strategies aimed at inhibiting GR/CD36 expression or activity might help prevent or reduce the onset and progression of hepatic lipid metabolism disorders induced by glucocorticoid drugs.


Assuntos
Transtornos do Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Animais , Antígenos CD36/genética , Dexametasona/toxicidade , Ácidos Graxos/metabolismo , Glucocorticoides/metabolismo , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/metabolismo , Fígado/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de Glucocorticoides/metabolismo , Regulação para Cima
14.
Toxicology ; 459: 152853, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34252480

RESUMO

Oxaliplatin (OXA) is a third-generation platinum drug; however, its application is greatly limited due to the severe peripheral neurotoxicity. This study aims to confirm the transport mechanism of OXA and to explore whether L-tetrahydropalmatine (L-THP) would alleviate OXA-induced peripheral neurotoxicity by selectively inhibiting these uptake transporters in vitro and in vivo. Our results revealed that organic cation transporter 2 (OCT2), organic cation/carnitine transporter 1 (OCTN1) and organic cation/carnitine transporter 2 (OCTN2) were involved in the uptake of OXA in dorsal root ganglion (DRG) neurons and mitochondria, respectively. L-THP (1-100 µM) reduced OXA (40 µM) induced cytotoxicity in MDCK-hOCT2 (Madin-Darby canine kidney, MDCK), MDCK-hOCTN1, MDCK-hOCTN2, and rat primary DRG cells, and decreased the accumulation of OXA in above cells and rat DRG mitochondria, but did not affect its efflux from MDCK-hMRP2 cells. Furthermore, Co-administration of L-THP (5-20 mg/kg for mice, 10-40 mg/kg for rats; twice a week, iv or ig) attenuated OXA (8 mg/kg for mice, 4 mg/kg for rats; twice a week, iv) induced peripheral neurotoxicity and reduced the platinum concentration in the DRG. Whereas, L-THP (1-100 µM for cells; 10-20 mg/kg for mice) did not impair the antitumour efficacy of OXA (40 µM for cells; 8 mg/kg for mice) in HT29 tumour-bearing nude mice nor in tumour cells (HT29 and SW620 cells). In conclusion, OCT2, OCTN1 and OCTN2 contribute to OXA uptake in the DRG and mitochondria. L-THP attenuates OXA-induced peripheral neurotoxicity via inhibiting OXA uptake but without impairing the antitumour efficacy of OXA. L-THP is a potential candidate drug to attenuate OXA-induced peripheral neurotoxicity.


Assuntos
Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Alcaloides de Berberina/farmacologia , Proteínas de Transporte/antagonistas & inibidores , Gânglios Espinais/metabolismo , Mitocôndrias/metabolismo , Oxaliplatina/farmacocinética , Oxaliplatina/toxicidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Animais , Comportamento Animal/efeitos dos fármacos , Cães , Gânglios Espinais/efeitos dos fármacos , Células HEK293 , Células HT29 , Humanos , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico/antagonistas & inibidores , Ratos , Membro 5 da Família 22 de Carreadores de Soluto/antagonistas & inibidores , Membro 5 da Família 22 de Carreadores de Soluto/metabolismo , Simportadores/antagonistas & inibidores , Simportadores/metabolismo
15.
Exp Ther Med ; 20(5): 101, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32973950

RESUMO

Hyponatremia is a risk factor associated with poor prognosis in patients with heart failure (HF) with reduced ejection fraction. However, whether hyponatremia has a similar role in patients with HF with preserved ejection fraction (HFpEF) has remained controversial. Therefore, the present study aimed to investigate the clinical characteristics and 24-month prognostic profile of a cohort of patients with HFpEF in China. From a registered observational cohort study on 1,027 subjects with HF, 496 patients with HFpEF were included. The association between baseline hyponatremia on admission and 24-month adverse outcomes (including all-cause mortality, re-hospitalization for HF and stroke) was analyzed using logistic regression with the Cox proportional hazards model. Of the 496 patients with HFpEF with a mean age of 72.8 years and proportion of males of 53.0%, 71 patients were diagnosed with hyponatremia. Furthermore, 29 patients (5.8%) were lost to follow-up. The hyponatremia group had lower blood pressure and serum hemoglobin, higher N-terminal pro B-type natriuretic peptide (NT-proBNP) and D-dimer, more patients with a history of atrial fibrillation and a higher proportion of spironolactone and loop diuretic use. According to a multivariate regression analysis, New York Heart Association functional classes III-IV and a serum NT-proBNP level above the median were risk factors for hyponatremia, while higher systolic blood pressure and ß-blocker use were protective factors against hyponatremia. In the Kaplan-Meier analysis, hyponatremia was associated with all-causes of mortality, re-hospitalization for HF and a poor prognosis for patients suffering from strokes (log-rank P<0.05 for all 3 endpoints). On multivariate logistic regression analysis with the Cox proportional hazard model, hyponatremia was an independent predictor of three adverse outcomes [all-cause mortality: Hazard ratio (HR)=1.54, 95% CI=1.07-2.91, P=0.034; re-hospitalization for heart failure: HR=1.28, 95% CI=1.16-2.47, P=0.013; stroke: HR=1.78, 95% CI=1.04-2.89, P=0.016]. Collectively, the present results suggested that hyponatremia on admission was significantly associated with all-cause mortality, re-hospitalization and stroke within 24 months in a cohort of hospitalized patients with HFpEF in China. Thus, hyponatremia should be carefully monitored and frequently adjusted in patients with HFpEF (NCT04062500).

16.
Sci Rep ; 10(1): 9057, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32494024

RESUMO

The niobium nitride (NbN) nanowires fabricated with the high-quality ultra-thin NbN film with a thickness of 3 nm-6 nm were widely used for single photon detectors. These nanowires had a low aspect ratio, less than 1:20. However, increasing the thickness and the aspect ratio of highly-uniformed NbN nanowires without reducing the superconductivity is crucial for the device in detecting high-energy photons. In this paper, a high-quality superconducting nanowire with aspect ratio of 1:1 was fabricated with optimized process, which produced a superconducting critical current of 550 µA and a hysteresis of 36 µA at 2.2 K. With the optimization of the electron beam lithography process of AR-P6200.13 and the adjustion of the chamber pressure, the discharge power, as well as the auxiliary gas in the process of reactive ion etching (RIE), the meandered NbN nanowire structure with the minimum width of 80 nm, the duty cycle of 1:1 and the depth of 100 nm were finally obtained on the silicon nitride substrate. Simultaneously, the sidewall of nanowire was vertical and smooth, and the corresponding depth-width ratio was more than 1:1. The fabricated NbN nanowire will be applied to the detection of soft X-ray photon emitted from pulsars with a sub-10 ps time resolution.

17.
Opt Express ; 28(11): 16696-16707, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32549486

RESUMO

Superconducting nanowire-based single-photon detectors (SNSPDs) are promising devices, especially with unrivalled timing jitter ability. However, the intrinsic physical mechanism and the ultimate limit of the timing jitter are still unknown. Here, we investigated the timing jitter of the SNSPD response to different excitation wavelengths from visible to near-infrared (NIR) as a function of the relative bias currents and the substrate temperature. We established a physical model based on a 1D electrothermal model to describe the hotspot evolution and thermal diffusion process after a single photon irradiated the nanowire. The simulations are in good agreement with the experimental results and reveal the other influencing factors and potential ways to further improve the timing jitter of SNSPDs. Finally, we introduce a new time-resolved approach, where by collecting the instrument response function (IRF) of SNSPDs, the wavelength of the incident photons can be easily discriminated with a resolution below 80 nm.

18.
Plant Mol Biol ; 102(1-2): 109-122, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31820285

RESUMO

KEY MESSAGE: Drought tolerance level of 136 soybean genotypes, the correlations among traits were evaluated, and several important drought-tolerant genotypes, traits, SNPs and genes were possibly useful for soybean genetic breeding. Drought is an adverse environmental factor affecting crops growth, development, and yield. Promising genotypes and genes with improved tolerance to drought are probably effective ways to alleviate the situation. In this study, our main task was to determine drought tolerance level of 136 soybean genotypes, the correlations among physiological and agronomic traits under drought, and drought-tolerant single nucleotide polymorphism (SNPs) and genes. In this study, twenty-six varieties were identified as excellent tolerant genotypes to stress among which S14, S93 and S135 with high drought-tolerant index (DTI > 1.3) and yield (Y > 300 kg). Fourteen varieties were identified as drought-sensitive genotypes, such as S25, S45 and S58, with low drought-tolerant index (DTI < 0.5). 422 SNPs and 302 genes correlated with seed number per plant (SNPP), maturity (M), number of seeds per pod (NSPP), node number of main stem (NNMS), Stem diameter (SD) and pull stem (PS) were detected under well-watered and drought conditions by genome-wide association study (GWAS). Among them, we found SNPs (Chr 3:1758920-1958934) between drought-tolerant and sensitive genotypes. 13 genes (Glyma.03G017800, Glyma.03G018000, Glyma.03G018200, Glyma.03G018400, Glyma.03G018500, Glyma.03G018600, Glyma.03G018700, Glyma.03G018800, Glyma.03G018900, Glyma.03G019000, Glyma.03G019100, Glyma.03G019200, Glyma.03G019300) correlated with NNMS were detected. By qRT-PCR, the expression level of Glyma.03G018000 and Glyma.03G018900 in drought-tolerant varieties was significantly increased, but low or no expression in sensitive varieties under drought stress. This study provides important drought-tolerant genotypes, traits, SNPs and potential genes, possibly useful for soybean genetic breeding.


Assuntos
Secas , Genótipo , Glycine max/fisiologia , Fenótipo , Melhoramento Vegetal , Adaptação Fisiológica/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Genoma de Planta/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sementes , Alinhamento de Sequência , Glycine max/genética
19.
J Colloid Interface Sci ; 561: 629-637, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31771869

RESUMO

All-in-one supercapacitors constitute an indispensable part in adapting to the rapid development of flexible energy storage equipment. Herein, an all-in-one configured PANI supercapacitor with a dynamic electrode/electrolyte interface was designed through hydrogen bonds and metal coordination bonds. The supercapacitor exhibits remarkable electrochemical capacitance (162 F g-1 at 0.5 A g-1, 137.4 mF cm-2 at 0.5 A cm-2) and excellent structural stabilities (almost no degradation in performance and structural damage in the cases of bending, folding, stretching and self-healing process). Besides, the hydrogel electrode can be efficiently recycled through a convenient method without virtual loss of electrochemical performance. Construction of the dynamic interface inside the supercapacitor provides a practical guidance for large-scale preparation of flexible energy storage devices, electronic skin and stretchable sensors.

20.
Nanotechnology ; 31(10): 105402, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31751956

RESUMO

Clarifying the interaction between active materials and current collectors of the same electrode is crucial for understanding the electrochemical energy storage mechanism and designing high-performance supercapacitors. The interaction mechanism is mainly due to the evolution of chemical bonding. Here, we explore the chemical bonding evolution between cobalt-nickel layered double hydroxide and carbon fiber paper by using ex situ x-ray photoelectron spectroscopy during redox reaction. The results reveal that chemical bonding corresponds to more ionic states at the lowest potential and more covalent states at the highest potential. Attributed to the formation of C-O-Metal (Co, Ni) chemical bonds, high capacitance with enhanced stability and rate capability is obtained. The Co-Ni layered double hydroxide electrode exhibits a high areal and mass specific capacitance of 0.55 and 952 F g-1 at a low mass loading of 0.58 mg cm-2. At a high mass loading of 3.59 mg cm-2, high areal and mass specific capacitance of 3.24 F cm-2 and 811 F g-1 are obtained. Based on this, a hybrid supercapacitor is fabricated with high-mass-loading Co-Ni layered double hydroxide and active carbon as positive and negative electrodes, respectively. As a result, this device delivers a prominent energy density of 20.9 Wh cm-3 at a power density of 0.12 W cm-3.

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