| 1. |
- Du, Mulong, et al.
(författare)
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Cyp2a6 activity and cigarette consumption interact in smoking-related lung cancer susceptibility
- 2024
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 84:4, s. 616-625
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Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen–metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke–exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers (OR = 0.88, 95% confidence interval = 0.85–0.91, P = 2.18 X 10-16), which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor helicase-like transcription factor. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis.
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| 2. |
- Molinero-Fernandez, Águeda, et al.
(författare)
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Demonstrating the Analytical Potential of a Wearable Microneedle-Based Device for Intradermal CO2 Detection
- 2024
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Ingår i: ACS Sensors. - : American Chemical Society (ACS). - 2379-3694. ; 9:1, s. 361-370
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Tidskriftsartikel (refereegranskat)abstract
- Monitoring of carbon dioxide (CO2) body levels is crucial under several clinical conditions (e.g., human intensive care and acid–base disorders). To date, painful and risky arterial blood punctures have been performed to obtain discrete CO2 measurements needed in clinical setups. Although noninvasive alternatives have been proposed to assess CO2, these are currently limited to benchtop devices, requiring trained personnel, being tedious, and providing punctual information, among other disadvantages. To the best of our knowledge, the literature and market lack a wearable device for real-time, on-body monitoring of CO2. Accordingly, we have developed a microneedle (MN)-based sensor array, labeled as CO2–MN, comprising a combination of potentiometric pH- and carbonate (CO32–)-selective electrodes together with the reference electrode. The CO2–MN is built on an epidermal patch that allows it to reach the stratum corneum of the skin, measuring pH and CO32– concentrations directly into the interstitial fluid (ISF). The levels for the pH–CO32– tandem are then used to estimate the PCO2 in the ISF. Assessing the response of each individual MN, we found adequate response time (t95 < 5s), sensitivity (50.4 and −24.6 mV dec–1 for pH and CO32–, respectively), and stability (1.6 mV h–1 for pH and 2.1 mV h–1 for CO32–). We validated the intradermal measurements of CO2 at the ex vivo level, using pieces of rat skin, and then, with in vivo assays in anesthetized rats, showing the suitability of the CO2–MN wearable device for on-body measurements. A good correlation between ISF and blood CO2 concentrations was observed, demonstrating the high potential of the developed MN sensing technology as an alternative to blood-based analysis in the near future. Moreover, these results open new horizons in the noninvasive, real-time monitoring of CO2 as well as other clinically relevant gases.
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| 3. |
- Molinero Fernandez, Agueda, et al.
(författare)
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In Vivo Transdermal Multi-Ion Monitoring with a Potentiometric Microneedle-Based Sensor Patch
- 2023
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Ingår i: ACS Sensors. - : American Chemical Society (ACS). - 2379-3694. ; 8:1, s. 158-166
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Tidskriftsartikel (refereegranskat)abstract
- Microneedle sensor technology offers exciting opportunities for decentralized clinical analyses. A novel issue puts forward herein is to demonstrate the uniqueness of membrane-based microneedles to accomplish real-time, on-body monitoring of multiple ions simultaneously. The use of multi-ion detection is clinically relevant since it is expected to provide a more complete and reliable assessment of the clinical status of a subject concerning electrolyte disorders and others. We present a microneedle system for transdermal multiplexed tracing of pH, Na+, K+, Ca2+, Li+, and Cl-. The device consists of an array of seven solid microneedles externally modified to provide six indicator electrodes, each selective for a different ion, and a common reference electrode, all integrated into a wearable patch read in a potentiometric mode. We show in vitro measurements at the expected clinical levels, resulting in a fast response time, excellent reversibility and repeatability, and adequate selectivity. Close-to-Nernstian sensitivity, sufficient stability and resiliency to skin penetration guarantee the sensor's success in transdermal measurements, which we demonstrate through ex vivo (with pieces of rat skin) and in vivo (on-body measurements in rats) tests. Accuracy is evaluated by comparison with gold standard techniques to characterize collected dermal fluid, blood, and serum. In the past, interstitial fluid (ISF) analysis has been challenging due to difficult sample collection and analysis. For ions, this has resulted in extrapolations from blood concentrations (invasive tests) rather than pure measurements in ISF. The developed microneedle patch is a relevant analytical tool to address this information gap.
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| 4. |
- Pérez Ràfols, Clara, et al.
(författare)
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Why Not Glycine Electrochemical Biosensors?
- 2020
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Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 20:14
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Tidskriftsartikel (refereegranskat)abstract
- Glycine monitoring is gaining importance as a biomarker in clinical analysis due to its involvement in multiple physiological functions, which results in glycine being one of the most analyzed biomolecules for diagnostics. This growing demand requires faster and more reliable, while affordable, analytical methods that can replace the current gold standard for glycine detection, which is based on sample extraction with subsequent use of liquid chromatography or fluorometric kits for its quantification in centralized laboratories. This work discusses electrochemical sensors and biosensors as an alternative option, focusing on their potential application for glycine determination in blood, urine, and cerebrospinal fluid, the three most widely used matrices for glycine analysis with clinical meaning. For electrochemical sensors, voltammetry/amperometry is the preferred readout (10 of the 13 papers collected in this review) and metal-based redox mediator modification is the predominant approach for electrode fabrication (11 of the 13 papers). However, none of the reported electrochemical sensors fulfill the requirements for direct analysis of biological fluids, most of them lacking appropriate selectivity, linear range of response, and/or capability of measuring at physiological conditions. Enhanced selectivity has been recently reported using biosensors (with an enzyme element in the electrode design), although this is still a very incipient approach. Currently, despite the benefits of electrochemistry, only optical biosensors have been successfully reported for glycine detection and, from all the inspected works, it is clear that bioengineering efforts will play a key role in the embellishment of selectivity and storage stability of the sensing element in the sensor.
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| 5. |
- Wang, Qianyu, et al.
(författare)
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Electrochemical biosensor for glycine detection in biological fluids
- 2021
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 182
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Tidskriftsartikel (refereegranskat)abstract
- We present herein the very first amperometric biosensor for the quantitative determination of glycine in diverse biological fluids. The biosensor is based on a novel quinoprotein that catalyzes the oxidation of glycine with high specificity. This process is coupled to the redox conversion of Prussian blue in the presence of hydrogen peroxide originating from the enzymatic reaction. The optimized tailoring of the biosensor design consists of the effective encapsulation of the quinoprotein in a chitosan matrix with the posterior addition of an outer Nafion layer, which is here demonstrated to suppress matrix interference. This is particularly important in the case of ascorbic acid, which is known to influence the redox behavior of the Prussian blue. The analytical performance of the biosensor demonstrates fast response time (<7 s), acceptable reversibility, reproducibility, and stability (<6% variation) as well as a wide linear range of response (25?500 ?M) that covers healthy (and even most unhealthy) physiological levels of glycine in blood/serum, urine and sweat. A total of 6 real samples from healthy patients and animals were analyzed: two serum, two urine and two sweat samples. The results were validated via commercially available fluorescence kit, displaying discrepancy of less than 9% in all the samples. The unique analytical features and effortless preparation of the new glycine biosensor position it at the forefront of current technologies towards decentralized clinical applications and sport performance monitoring.
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| 6. |
- Wang, Qianyu, et al.
(författare)
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Intradermal Glycine Detection with a Wearable Microneedle Biosensor : The First In Vivo Assay
- 2022
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:34, s. 11856-11864
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Tidskriftsartikel (refereegranskat)abstract
- Glycine (GLY) is gaining importance in medical diagnoses due to its relationship with multiple physiological functions. Today, GLY is exclusively analyzed using instrumentation centralized in clinical labs, and a tangible point-of-care tool that gathers real-time data from the patient for effective and fast evaluations is lacking. Relevant clinical advances are expected as soon as the rapid provision of both punctual and continuous measurements is possible. In that context, this work presents a microneedle (MN)-based biosensor for intradermal GLY detection in interstitial fluid (ISF). The MN tip is externally tailored to detect GLY levels through the hydrogen peroxide formed in its reaction with a quinoprotein-based GLY oxidase enzyme. The analytical performance of the MN biosensor indicates a fast response time (<7 s); acceptable reversibility, reproducibility, and stability; as well as a wide linear range of response (25-600 μM) that covers the physiological levels of GLY in ISF. The MN biosensor conveniently exhibits high selectivity for GLY over other compounds commonly found in ISF, and the response is not influenced by temperature, pH, or skin insertions. Validated intradermal measurements of GLY were obtained at the in vitro (with pieces of rat skin), ex vivo (on-body tests of euthanized rats) and in vivo (on-body tests of anesthetized rats) levels, demonstrating its ability to produce accurate physiological data. The developed GLY MN biosensor is skin-wearable and provides reliable, real-time intradermal GLY measurements in ISF by means of a minimally invasive approach.
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| 7. |
- Zhou, Sha, et al.
(författare)
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Sources of uncertainty in modeled land carbon storage within and across three MIPs : Diagnosis with three new techniques
- 2018
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Ingår i: Journal of Climate. - 0894-8755. ; 31:7, s. 2833-2851
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Tidskriftsartikel (refereegranskat)abstract
- Terrestrial carbon cycle models have incorporated increasingly more processes as a means to achieve more-realistic representations of ecosystem carbon cycling. Despite this, there are large across-model variations in the simulation and projection of carbon cycling. Several model intercomparison projects (MIPs), for example, the fifth phase of the Coupled Model Intercomparison Project (CMIP5) (historical simulations), Trends in Net Land-Atmosphere Carbon Exchange (TRENDY), and Multiscale Synthesis and Terrestrial Model Intercomparison Project (MsTMIP), have sought to understand intermodel differences. In this study, the authors developed a suite of new techniques to conduct post-MIP analysis to gain insights into uncertainty sources across 25 models in the three MIPs. First, terrestrial carbon storage dynamics were characterized by a three-dimensional (3D) model output space with coordinates of carbon residence time, net primary productivity (NPP), and carbon storage potential. The latter represents the potential of an ecosystem to lose or gain carbon. This space can be used to measure how and why model output differs. Models with a nitrogen cycle generally exhibit lower annual NPP in comparison with other models, and mostly negative carbon storage potential. Second, a transient traceability framework was used to decompose any given carbon cycle model into traceable components and identify the sources of model differences. The carbon residence time (or NPP) was traced to baseline carbon residence time (or baseline NPP related to the maximum carbon input), environmental scalars, and climate forcing. Third, by applying a variance decomposition method, the authors show that the intermodel differences in carbon storage can be mainly attributed to the baseline carbon residence time and baseline NPP (>90% in the three MIPs). The three techniques developed in this study offer a novel approach to gain more insight from existing MIPs and can point out directions for future MIPs. Since this study is conducted at the global scale for an overview on intermodel differences, future studies should focus more on regional analysis to identify the sources of uncertainties and improve models at the specified mechanism level.
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