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1.
Phys Rev E ; 109(1-1): 014142, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38366441

RESUMEN

A quantum thermal device based on three nearest-neighbor coupled spin-1/2 systems controlled by the magnetic field is proposed. We systematically study the steady-state thermal behaviors of the system. When the two terminals of our system are in contact with two thermal reservoirs, respectively, the system behaves as a perfect thermal modulator that can manipulate heat current from zero to specific values by adjusting magnetic-field direction over different parameter ranges, since the longitudinal magnetic field can completely block the heat transport. Significantly, the modulator can also be achieved when a third thermal reservoir perturbs the middle spin. We also find that the transverse field can induce the system to separate into two subspaces in which neither steady-state heat current vanishes, thus providing an extra level of control over the heat current through the manipulation of the initial state. In addition, the performance of this device as a transistor can be enhanced by controlling the magnetic field, achieving versatile amplification behaviors, in particular substantial amplification factors.

2.
Phys Rev E ; 109(1-1): 014137, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38366475

RESUMEN

The mechanical strain can control the frequency of two-level atoms in amorphous material. In this work, we would like to employ two coupled two-level atoms to manipulate the magnitude and direction of heat transport by controlling mechanical strain to realize the function of a thermal switch and valve. It is found that a high-performance heat diode can be realized in the wide piezo voltage range at different temperatures. We also discuss the dependence of the rectification factor on temperatures and couplings of heat reservoirs. We find that the higher temperature differences correspond to the larger rectification effect. The asymmetry system-reservoir coupling strength can enhance the magnitude of heat transfer, and the impact of asymmetric and symmetric coupling strength on the performance of the heat diode is complementary. It may provide an efficient way to modulate and control heat transport's magnitude and flow preference. This work may give insight into designing and tuning quantum heat machines.

3.
Front Microbiol ; 14: 1264586, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38075870

RESUMEN

Aspergillus fumigatus, a prevalent saprophytic fungus in the atmosphere, is known to rapidly induce severe invasive aspergillosis (IA) upon inhalation of its conidia by humans or animals. The mortality rate associated with IA exceeds 50%. The misuse of antifungal agents has contributed to the emergence of numerous highly pathogenic drug-resistant strains of A. fumigatus. Our study found that the combination of domiphen and itraconazole had sound synergistic antimicrobial effects against wild-type and itraconazole-resistant A. fumigatus in vivo and in vitro through MIC, FIC, plate inoculation, growth curve experiments, and Galleria mellonella infection model. Drug cytotoxicity and pharmacological tests for acute toxicity assays demonstrated that both itraconazole and domiphen showed minimal cytotoxicity and good biocompatibility. The transcriptome sequencing experiment demonstrated that domiphen exerted a suppressive effect on the expression of various genes, including those involved in drug efflux, redox regulation, and cellular membrane and cell wall remodeling. The present investigation explores the synergistic antimicrobial mechanisms of domiphen and itraconazole, encompassing three key aspects: (i) domiphen inhibited the efflux of itraconazole by reducing the expression of drug efflux-related genes, (ii) the combination has good ability to disrupt the cell membrane and cell wall, (iii) the combination also can remove biofilm more effectively. In summary, the utilization of domiphen as a synergist of itraconazole exhibited disruptive effects on the biofilm, cell wall, and cell membrane of A. fumigatus. This subsequently led to a modified distribution of itraconazole within the fungal organism, ultimately resulting in enhanced antifungal efficacy. The results of this study may provide a new therapeutic strategy for the treatment of IA caused by drug-resistant A. fumigatus.

4.
China CDC Wkly ; 5(45): 1012-1016, 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-38020346

RESUMEN

What is already known about this topic?: Red and processed meat consumption has been positively related to an increased risk of diabetes in Western populations. However, the results remain inconclusive within Asian populations. What is added by this report?: This dose-response meta-analysis of prospective cohort studies conducted in East Asian populations reveals a positive relation between the consumption of processed meat and increased risk of diabetes. Furthermore, a U-shaped association was identified between the consumption of unprocessed red meat and the risk of diabetes. What are the implications for public health practice?: This research presents substantive evidence advocating for the reduction of processed and unprocessed red meat consumption as a viable strategy for mitigating the risk of diabetes in East Asian populations.

5.
Environ Sci Pollut Res Int ; 30(52): 113068-113087, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37848794

RESUMEN

Against the backdrop of China's "double carbon" objective, the exploration of low-carbon land consolidation has become a prominent area of focus for enhancing the development of ecological civilization. In this study, three typical projects at different time points (2016, 2019, and 2022) in Wudi County were selected to measure the carbon effect of land consolidation from four perspectives: artificial and industrial materials, mechanical shift consumption, land use structure, and farmland ecosystem. Based on the calculation of carbon effect of land consolidation by using carbon emission coefficient method, the changes of land use structure and carbon storage of farmland ecosystem before and after land consolidation were corrected by using GIS tools and net ecosystem productivity (NEP) model based on remote sensing technology, and the carbon emission intensity of each land consolidation project was finally obtained. The study summarized the influencing factors of carbon emissions through the above analysis and uses the fuzzy interpretation structure (FISM) model to provide the hierarchy of influencing factors of carbon emissions, thus proposing a low-carbon promotion path for land consolidation. The findings of this study can serve as a useful reference for low-carbon land consolidation efforts. The results showed that (1) the first, second, and third projects emitted 6140.06 t, 1243.78 t, and 17,604.62 t of carbon, respectively. Among them, the largest contributors to these emissions were labor and industrial materials, followed by mechanical shift; land use structure and farmland ecosystem were the main sources of carbon sinks and have a positive impact on the carbon cycle. (2) The carbon emission intensity of project one, project two, and project three after standardization is 0.26, 0.49, and 0.25, respectively, which are all at a high level. (3) According to the FISM model categorized 15 low-carbon upgrading paths, it was recommended that the government take a leading role in Wudi County by developing a scientific and rational construction plan. Additionally, efforts were made to actively protect farmland and forest land from destruction, reduce energy and material consumption, increase carbon storage in the farmland ecosystem, and promote low carbonization of land consolidation to the fullest extent possible.


Asunto(s)
Carbono , Ecosistema , Granjas , Bosques , China
6.
Anal Chem ; 95(34): 12819-12825, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37556314

RESUMEN

Sepsis is a serious medical condition that arises from a runaway response to an infection, which triggers the immune system to release chemicals into the bloodstream. This immune response can result in widespread inflammation throughout the body, which may cause harm to vital organs and, in more severe cases, lead to organ failure and death. Timely and accurate diagnosis of sepsis remains a challenge in analytical diagnostics. In this work, we have developed and validated a sepsis detection device, utilizing 3D printing technology, which incorporates multiple affinity separation zones. Our device requires minimal operator intervention and utilizes CD64, CD69, and CD25 as the biomarker targets for detecting sepsis in liquid biopsies. We assessed the effectiveness of our 3D-printed multizone cell separation device by testing it on clinical samples obtained from both septic patients (n = 35) and healthy volunteers (n = 8) and validated its performance accordingly. Unlike previous devices using poly(dimethyl siloxane), the 3D-printed device had reduced nonspecific binding for anti-CD25 capture, allowing this biomarker to be assayed for the first time in cell separations. Our results showed a statistically significant difference in cell capture between septic and healthy samples (with p values of 0.0001 for CD64, CD69, and CD25), suggesting that 3D-printed multizone cell capture is a reliable method for distinguishing sepsis. A receiver operator characteristic (ROC) analysis was performed to determine the accuracy of the captured cell counts for each antigen in detecting sepsis. The ROC area under the curve (AUC) values for on-chip detection of CD64+, CD69+, and CD25+ leukocytes were 0.96, 0.92, and 0.88, respectively, indicating our diagnostic test matches clinical outcomes. When combined for sepsis diagnosis, the AUC value for CD64, CD69, and CD25 was 0.99, indicating an improved diagnostic performance due to the use of multiple biomarkers.


Asunto(s)
Sepsis , Humanos , Biomarcadores/metabolismo , Separación Celular , Sepsis/diagnóstico , Sepsis/metabolismo , Neutrófilos/metabolismo , Leucocitos/química , Receptores de IgG/metabolismo , Curva ROC
7.
Phys Rev E ; 107(6-1): 064125, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37464716

RESUMEN

A quantum thermal diode is designed based on three pairwise coupled qubits, two connected to a common reservoir and the other to an independent reservoir. It is found that the internal couplings between qubits can enhance heat currents. If the two identical qubits uniformly couple with the common reservoir, the crossing dissipation will occur, leading to the initial-state-dependent steady state, which can be decomposed into the mixture of two particular steady states: the heat-conducting state generating maximum heat current and the heat-resisting state not transporting heat. However, the rectification factor doesn't depend on the initial state. In particular, we find that neither quantum entanglement nor quantum discord is present in the steady state, but the pure classical correlation shows a remarkably consistent behavior as the heat rectification factor, which reveals the vital role of classical correlation in the system.

8.
Methods Mol Biol ; 2679: 233-240, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37300620

RESUMEN

Liquid biopsies are examination procedures for deciding the grouping of malignant growth cells tracked down in samples of blood and other body fluids. Liquid biopsies are likewise significantly less intrusive than tissue biopsies as they just require small amount of blood or body fluids from the patient. With the utilization of microfluidics, cancer cells can be isolated from the fluid biopsy and achieve early diagnosis. 3D printing is turning out to be progressively well known for microfluidic devices creation. 3D printing has shown multiple advantages compared to traditional microfluidic devices production, including effortless large-scale manufacturing of precise copies, the fuse of new materials, and execution of additional complicated or drawn-out plans that are hard to execute in conventional microfluidic devices. Combining 3D printing with microfluidics makes for a relatively inexpensive analysis of liquid biopsies with a chip that can be more advantageous to use over traditional microfluidic chips. In this chapter, a method for affinity-based separation of cancer cells in a liquid biopsy using a 3D microfluidic chip will be discussed, along with the rationale behind the method.


Asunto(s)
Microfluídica , Neoplasias , Humanos , Microfluídica/métodos , Dispositivos Laboratorio en un Chip , Impresión Tridimensional , Biopsia Líquida , Neoplasias/diagnóstico
9.
Phys Rev E ; 107(4-1): 044121, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37198796

RESUMEN

Precisely controlling heat transfer in a quantum mechanical system is particularly significant for designing quantum thermodynamical devices. With the technology of experiment advances, circuit quantum electrodynamics (circuit QED) has become a promising system due to controllable light-matter interactions as well as flexible coupling strengths. In this paper, we design a thermal diode in terms of the two-photon Rabi model of the circuit QED system. We find that the thermal diode can not only be realized in the resonant coupling but also achieve better performance, especially for the detuned qubit-photon ultrastrong coupling. We also study the photonic detection rates and their nonreciprocity, which indicate similar behaviors with the nonreciprocal heat transport. This provides the potential to understand thermal diode behavior from the quantum optical perspective and could shed new insight into the relevant research on thermodynamical devices.

10.
J Environ Manage ; 340: 117929, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37086561

RESUMEN

As an important means to address global climate change and land-use/land-cover (LULC) change, ecological restoration projects (ERPs) have a large effect on carbon storage functions and eco-environmental quality. However, the various ERPs carried out in the Yellow River Delta region have important implications for ecological security strategies in China. Therefore, based on land-use data and remote sensing image data, with the help of ArcGIS and Google Earth Engine (GEE) platforms, this study uses the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model, an improved remote sensing ecological index (RSEI) model and other methods to deeply examine the evolutionary trends of eco-environmental quality and carbon storage during the implementation of ERPs in the Yellow River Delta and selects key implementation areas for in-depth analysis to determine the implementation effects of ERPs. Our findings suggested that the RSEI and carbon storage levels in the study area had opposite evolutionary trends from 2001 to 2020. Among them, the RSEI showed a fluctuating upwards trend (0.4461 (2001) and 0.5185 (2020)), while the total carbon stock showed a fluctuating downwards trend (30.67 Tg (2001) and 26.40 Tg (2020)). However, from 2015 to 2020, the RSEI and carbon storage were at a relatively stable level, which indirectly indicated that the ERPs carried out during the period from 2015 to 2020 had achieved a good comprehensive implementation effect. In addition, the areas with better improvement effects from 2015 to 2020 were primarily located in the mouth of the Yellow River Delta (Areas C and D), and their RSEI and the total carbon stock showed a certain upwards trend. This research can promote the formulation of the management strategy of ERPs in the Yellow River Delta, which is of tremendous importance to the ecological environmental preservation and high-quality development of the Yellow River Basin.


Asunto(s)
Ecosistema , Monitoreo del Ambiente , Carbono , Tecnología de Sensores Remotos , China , Conservación de los Recursos Naturales
11.
Analyst ; 147(20): 4536-4546, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36098233

RESUMEN

Inertial microfluidic devices continue to show promise for label-free separation of cells from liquid biopsies and other biological samples. Serpentine-channel microfluidic devices capitalizing on inertial forces such as Dean flow have been demonstrated for cell separation, but are limited in performance due to the magnitude of the inertial lift and drag force gradients across the separation channel. We have developed a new flow design that uses periodic channel contractions to enhance the magnitude of the force gradient. Separation recover was 97% with the final sorter output consisting of 78% target cells. Separation efficiency was 87% for whole blood, which could be increased to 97% if the sample was diluted prior to sorting. The enrichment of cancer cells was over 1000-fold, and sorted cancer cells maintained a viability of 93.8% for 96 hours after sorting. In the analysis of blood plasma, breast cancer cells from a clinical patient were enriched 20×. The incorporation of periodic channel contractions in a Dean flow circuit resulted in an increase in Dean flow gradient according to simulation, resulting in sorting of small-diameter cancer cells in blood samples.


Asunto(s)
Técnicas Analíticas Microfluídicas , Neoplasias , Movimiento Celular , Separación Celular/métodos , Diseño de Equipo , Humanos , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/métodos
12.
Environ Res ; 214(Pt 4): 114151, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36037923

RESUMEN

Comprehensive and accurate grasp of land-use carbon emissions (LCE) level and its driving mechanism is key to success in China's pursuit of low-carbon development, and it is also the scientific basis for the formulation and implementation of regional carbon emissions strategies. Based on fossil fuel carbon emissions raster data (published by the Open-Data Inventory for Anthropogenic Carbon dioxide (ODIAC) platform) and land use data, this manuscript selects the Yellow River Delta as the study area and uses an improved LCE measurement model, exploratory spatial data analysis, multiscale geographical weighting regression (MGWR), and other models to explore the spatiotemporal heterogeneity and driving mechanisms of LCE at the grid level. The results showed the following: ① The total amount of LCE in the study area continued to increase from 2000 to 2019, the growth rate decreased, but the peak of LCE had not yet been reached. ② The LCE of the study area showed a significant positive global autocorrelation. The H-H aggregation region showed a relatively stable spatial distribution range; the L-L aggregation region showed wide distribution characteristics that covered the entire study area; and the aggregation regions of H-L and L-H, which have not yet reached the scale. ③ At the global dimension, the mean correlation coefficients between LCE and driving factors (net primary productivity (NPP), nighttime light (NTL), and population density (PD)) from 2000 to 2019 were -0.11, 0.28, and 0.12; at the local dimension, the strength (from strong to weak) of the effect of each factor on LCE was PD, NTL, NPP (2000) and NTL, PD, NPP (2019). The research results provide a scientific basis and basic guarantee for the development, and implementation of regional carbon emission strategies.


Asunto(s)
Combustibles Fósiles , Ríos , Dióxido de Carbono/análisis , China , Desarrollo Económico , Densidad de Población , Análisis Espacial
13.
Antioxidants (Basel) ; 11(4)2022 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-35453395

RESUMEN

Piperlongumine, a natural alkaloid substance extracted from the fruit of the long pepper (Piper longum Linn.), is known to inhibit the cytosolic thioredoxin reductase (TXNRD1 or TrxR1) and selectively kill cancer cells. However, the details and mechanism of the inhibition by piperlongumine against TXNRD1 remain unclear. In this study, based on the classical DTNB reducing assay, irreversible inhibition of recombinant TXNRD1 by piperlongumine was found and showed an apparent kinact value of 0.206 × 10-3 µM-1 min-1. Meanwhile, compared with the wild-type TXNRD1 (-GCUG), the UGA-truncated form (-GC) of TXNRD1 was resistant to piperlongumine, suggesting the preferential target of piperlongumine is the selenol (-SeH) at the C-terminal redox motif of the enzyme. Interestingly, the high concentration of piperlongumine-inhibited TXNRD1 showed that its Sec-dependent activity is decayed but its intrinsic NADPH oxidase activity is retained. Furthermore, piperlongumine did not induce ferroptosis in HCT116 cells at 10 µM, whereas significantly promoted erastin-induced lipid oxidation, which could be alleviated by supplying glutathione (GSH) or N-acetyl L-cysteine (NAC). However, restricting GSH synthesis by inhibiting glutaminase (GLS) using the small molecule inhibitor CB-839 only slightly enhanced erastin-induced cell death. Taken together, this study elucidates the molecular mechanism of the antitumor capacity of piperlongumine by targeting TXNRD1 and reveals the potential possibility of inhibiting TXNRD1 to strengthen cancer cells' ferroptosis.

14.
Biosens Bioelectron X ; 10: 100109, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35075447

RESUMEN

Since the outbreak of the coronavirus disease 2019 (COVID-19), countries around the world have suffered heavy losses of life and property. The global pandemic poses a challenge to the global public health system, and public health organizations around the world are actively looking for ways to quickly and efficiently screen for viruses. Point-of-care testing (POCT), as a fast, portable, and instant detection method, is of great significance in infectious disease detection, disease screening, pre-disease prevention, postoperative treatment, and other fields. Microfluidic technology is a comprehensive technology that involves various interdisciplinary disciplines. It is also known as a lab-on-a-chip (LOC), and can concentrate biological and chemical experiments in traditional laboratories on a chip of several square centimeters with high integration. Therefore, microfluidic devices have become the primary implementation platform of POCT technology. POCT devices based on microfluidic technology combine the advantages of both POCT and microfluids, and are expected to shine in the biomedical field. This review introduces microfluidic technology and its applications in combination with other technologies.

15.
Free Radic Biol Med ; 180: 52-62, 2022 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-34973363

RESUMEN

Shikonin, a naturally occurring naphthoquinone with potent anti-tumor activity, has been reported to induce cancer cell death via targeting selenoenzyme thioredoxin reductase 1 (TrxR1; TXNRD1). However, the interaction between shikonin and TrxR1 remains unclear, and the roles of the cellular antioxidant system in shikonin induced cell death are obscure. Here, we found that shikonin modified the Sec498 residue of TrxR1 to fully inhibit its antioxidant activity, however, the shikonin-modified TrxR1 still remained intrinsic NADPH oxidase activity, which promotes superoxide anions production. Besides, TrxR1 efficiently reduced shikonin in both selenocysteine dependent and selenocysteine independent manners, and the oxygen-coupled redox cycling of shikonin also generates excessive superoxide anions. The inhibitory effects and the redox cycling of shikonin towards TrxR1 caused cancer cell ROS-dependent necroptosis. Interestingly, as we evaluated, some cancer cell lines were insensitive to shikonin, especially kelch-like ECH associated protein 1 (KEAP1)-mutant non-small cell lung cancer (NSCLC) cells, which harbor constitutive activation of the nuclear factor-erythroid 2-related factor 2 (NRF2). NADPH bankruptcy caused by glucose starvation or glucose limitation (inhibiting glucose transporter 1 by BAY-876) could efficiently overcome the resistance of KEAP1-mutant NSCLC cells to shikonin. Glucose-6-phosphate dehydrogenase (G6PD), was known as a rate-limiting enzyme in the pentose phosphate pathway, however, the pharmacological inhibition of G6PD by 6-aminonicotinamide (6-AN), enhanced the shikonin-induced cytotoxicity but has no selectivity on KEAP1-mutant NSCLC cells. This study will be helpful in applying shikonin for potential chemotherapy, and in combinational treatment of KEAP1-mutant NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Naftoquinonas , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Naftoquinonas/farmacología , Necroptosis , Oxidación-Reducción , Oxígeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tiorredoxina Reductasa 1 , Reductasa de Tiorredoxina-Disulfuro/genética , Reductasa de Tiorredoxina-Disulfuro/metabolismo
16.
Int J Gynaecol Obstet ; 157(2): 375-382, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34368966

RESUMEN

OBJECTIVE: To improve perinatal management for hypertensive disorders in pregnancy (HDP) using checklists. METHODS: A pre-post evaluation of the implementation of checklists was performed. The checklist for HDP was adapted for the local context through expert consultations and had been used within peripartum since September 2017. Data of 763 women with singleton pregnancies diagnosed with HDP were collected between April 2016 and March 2019 at the Obstetrics & Gynecology Hospital of Fudan University. The monitoring and control groups consisted of 394 and 369 cases, respectively. Analysis was carried out by intention-to-treat with respect to maternal and fetal complications and delivery outcomes. RESULTS: After the implementation of the checklists, patients had a significant reduction in anti-hypertensive treatment both orally (P = 0.028) and intravenously (P = 0.003), and increased utilization rate of MgSO4 management (P < 0.001). Gestation was prolonged in the expectant treatment (P = 0.012) and the rate of elective and intrapartum cesarean delivery decreased (P < 0.001 and P = 0.001, respectively). The neonates of these patients had a low rate of admission to the neonatal intensive care unit (P < 0.001). CONCLUSION: National clinical guidelines complied critically after the implementation of the checklists. These checklists could be used for improving the quality of the clinical strategy and treatment, which benefitted perinatal management.


Asunto(s)
Hipertensión , Resultado del Embarazo , Cesárea , Lista de Verificación , Femenino , Edad Gestacional , Humanos , Recién Nacido , Embarazo , Mejoramiento de la Calidad
17.
Biomed Pharmacother ; 146: 112546, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34954641

RESUMEN

Thioredoxin reductase 1 (TrxR1 or TXNRD1) is a major enzyme in cellular redox regulation and is considered as a drug target for cancer therapy. Previous studies have reported that plumbagin caused reactive oxygen species (ROS)-dependent apoptosis via inhibiting TrxR1 activity or being reduced by TrxR1, leading to selectively cancer cell death. However, the mechanism of TrxR1-mediated redox cycling of plumbagin is obscure and the evidence for plumbagin targeting TrxR1 is still lacking. Herein, we demonstrated that TrxR1 catalyzed plumbagin reduction in both selenocysteine (Sec)-dependent and independent manners, and its activity relied on the intact N-terminal motif of TrxR1, but a high-efficiency reduction was supported by the C-terminal thiols. During the redox cycling of plumbagin, excessive ROS production was observed coupled with oxygen. Using LC-MS and TrxR1 mutants, we found that the Sec residue of TrxR1 was modified by plumbagin, which converted the enzyme from antioxidant to pro-oxidant. Furthermore, we evaluated the therapeutic potential of plumbagin in non-small cell lung cancer (NSCLC), and found that Kelch-like ECH-associated protein 1 (KEAP1)-mutant NSCLC cells, which possess constitutive nuclear factor erythroid 2-related factor 2 (NRF2) activity, were insensitive to plumbagin; however, inhibition of glucose transporter 1 (GLUT1) by small-molecule BAY-876 or inhibiting glucose-6-phosphate dehydrogenase (G6PD) by 6-aminonicotinamide (6-AN) overcame the plumbagin-resistance of KEAP1-mutant NSCLC cells. Taken together, this study elucidated the pharmacological mechanism of plumbagin by targeting TrxR1 and revealed the synergy effect of plumbagin and BAY-876, which may be helpful for applying naphthoquinone compounds to chemotherapy, particularly for treating KEAP1-mutant NSCLC cells.


Asunto(s)
Transportador de Glucosa de Tipo 1/antagonistas & inhibidores , Proteína 1 Asociada A ECH Tipo Kelch/genética , Naftoquinonas/farmacología , Pirazoles/farmacología , Quinolinas/farmacología , Tiorredoxina Reductasa 1/farmacología , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Selenocisteína/metabolismo
18.
Free Radic Biol Med ; 172: 482-489, 2021 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-34186208

RESUMEN

The selenoprotein thioredoxin reductase 1 (TrxR1; TXNRD1) participates in multiple cellular processes and is regarded as a cellular target in anti-tumor drug discovery and development. TrxR1 has been reported to reduce menadione to menadiol and to produce superoxide anion radicals. However, the details of TrxR1-mediated menadione reduction have rarely been studied. In this study, we found that wild-type TrxR1 could reduce menadione in a less efficient way, but the U498C mutant variant supported high-efficiency menadione reduction in a Sec-independent manner. Meanwhile, the site-directed mutagenesis results showed that Cys64 mutant increased the Km values and decreased the catalytic efficiency, which was associated with a charge-transfer complex between FAD-Cys64. Mass spectrometry (MS) revealed that in NADPH pre-reduced TrxR1 but not oxidized TrxR1, the highly active Sec498 of wild-type TrxR1 was arylated by menadione and strongly impaired the DTNB reducing activity in a dose-dependent manner. TrxR1 reduced menadione more efficiently than glutathione reductase (GR), and interestingly menadione did not inhibit the GSSG reducing activity of GR. In summary, our results demonstrate that TrxR1 catalyzes the reduction of menadione in a Sec-independent manner, which highly depend on Cys498 instead of N-terminal redox motif, and the Sec498 of TrxR1 is the primary target of menadione. The interaction between menadione and TrxR1 revealed in this study may provide a valuable reference for the development of anticancer drugs targeting selenoprotein TrxR1.


Asunto(s)
Tiorredoxina Reductasa 1 , Vitamina K 3 , NADP , Oxidación-Reducción , Superóxidos , Tiorredoxina Reductasa 1/genética , Tiorredoxina Reductasa 1/metabolismo , Reductasa de Tiorredoxina-Disulfuro/genética , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Vitamina K 3/farmacología
19.
Methods Mol Biol ; 2321: 207-219, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34048019

RESUMEN

This chapter discusses two microfluidic-based approaches for early sepsis detection that achieve a higher accuracy than traditional blood culture analysis. Patient blood samples were included in this work to validate the performance of our chips in diagnosing sepsis. The single-parameter chip demonstrated the increased accuracy if using CD64 as a biomarker for sepsis detection compared with C-reactive protein (CRP) and procalcitonin (PCT) when applied alone. In addition, a multiparameter chip measuring a combined panel of CD25, CD64, and CD69, and achieved a high accuracy with an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.978. The combined panel was also able to detect culture-negative patients and provided a faster diagnosis. Besides, microfluidics has advantages of less time consuming, easier to manufacture, less sample loading, less complex, and portable. Therefore, our approach is of great potential to become a bedside sepsis detection method.


Asunto(s)
Microfluídica/instrumentación , Microfluídica/métodos , Sepsis/diagnóstico , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Área Bajo la Curva , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Diagnóstico Precoz , Humanos , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Lectinas Tipo C/metabolismo , Polipéptido alfa Relacionado con Calcitonina/metabolismo , Curva ROC , Receptores de IgG/metabolismo , Sepsis/metabolismo
20.
Medicine (Baltimore) ; 100(20): e25739, 2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34011031

RESUMEN

BACKGROUND: Nocturia is a common and highly troubled lower urinary tract symptom, which has a wide range of effects. About 33% of patients with lower urinary tract symptoms have been affected by nocturia. Nocturia is mainly manifested as the increase of urination frequency and urine volume at night. It has been proved that acupuncture can reduce the symptoms of nocturia and regulate bladder function in Western countries. Acupuncture may be a promising choice for the treatment of nocturia. METHODS: RCTs of acupuncture for nocturia will be searched in the relevant database, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Wanfang Database, Chinese Biomedical Literature Database, and Chinese Scientific Journal Database. The studies of electronic searches will be exported to EndNote V.9.1 software. We will run meta-analyses using the Review Manager (RevMan) V.5.3 software. Any disagreement will be solved in consultation with a third reviewer. RESULTS: Our study aims to explore the efficacy of acupuncture for nocturia and to provide up-to-date evidence for clinical of nocturia. CONCLUSION: The conclusion of this study will provide evidence for the efficacy of acupuncture treatment of nocturia. INPLASY REGISTRATION NUMBER: INPLASY202130100.


Asunto(s)
Terapia por Acupuntura/métodos , Nocturia/terapia , Terapia por Acupuntura/efectos adversos , Humanos , Metaanálisis como Asunto , Nocturia/diagnóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
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