Accumulating evidence implicates oxidative stress in a range of diseases, yet no objective measurement has emerged that characterizes the global nature of oxidative stress. Previously, we reported a ...measurement that employs the moderately strong oxidant iridium (Ir) to probe the oxidative damage in a serum sample and reported that in a small study (N = 15) the Ir-reducing capacity assay could distinguish schizophrenia from healthy control groups based on their levels of oxidative stress. Here, we used a larger sample size to evaluate the Ir-reducing capacity assay to assess its ability to discriminate the schizophrenia (N = 73) and healthy control groups (N = 45). Each serum sample was measured (in triplicate) at three different times that were separated by several weeks. The Intraclass Correlation Coefficient (ICC = 0.69) for these repeated measurements indicates the assay detects stable components in the sample (i.e., it is not detecting transient reactive species or air-oxidizable serum components). Correlations between the Ir-reducing capacity assay and independently-measured total serum protein levels (r = +0.74, p < 2.2 × 10−16) suggest the assay is detecting information in the protein pool. For cross-validation of the discrimination ability, we used machine learning and receiver operating characteristic (ROC) analysis. After adjusting for potential confounders (age and smoking status), an area under the curve (AUC) of ROC curve was calculated to be 0.89 (p = 9.3 × 10−5). In conclusion, this validation indicates the Ir-reducing capacity assay provides a simple global measure of oxidative stress, and further supports the hypothesis that oxidative stress is linked with schizophrenia.
Viable mesenchymal stem cells (MSCs) were efficiently and selectively harvested by near-infrared (NIR) light using the photothermal effect of a conductive polymer nano thin film. The ...poly(3,4-ethylenedioxy thiophene) (PEDOT)-coated cell culture surfaces were prepared via a simple and fast solution-casting polymerization (SCP) technique. The absorption of PEDOT thin films in the NIR region was effectively triggered cell harvesting upon exposure to an NIR source. By controlling the NIR absorption of the PEDOT film through electrochemical doping or growing PEDOT with different thin film thickness from 70 to 300 nm, the proliferation and harvesting of MSCs on the PEDOT surface were controlled quantitatively. This light-induced cell detachment method based on PEDOT films provides the temporal and spatial control of cell harvesting, as well as cell patterning. The harvested stem cells were found to be alive and well proliferated despite the use of temperature increase by NIR. More importantly, the harvested MSCs by this method preserved their intrinsic characteristics as well as multilineage differentiation capacities. This PEDOT surfaces could be used for repetitive culture and detachment of MSCs or for efficient selection or depletion of a specific subset from heterogeneous population during culture of various tissue-derived cells because there were no photodegradation and photobreakage in the PEDOT films by NIR exposure.
The COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool was developed to assist countries to estimate incremental financial costs to roll out COVID-19 vaccines. This article describes ...the purposes, assumptions and methods used in the CVIC tool and presents the estimated financial costs of delivering COVID-19 vaccines in the Lao People's Democratic Republic (Lao PDR).
From March to September 2021, a multidisciplinary team in Lao PDR was involved in the costing exercise of the National Deployment and Vaccination Plan for COVID-19 vaccines to develop potential scenarios and gather inputs using the CVIC tool. Financial costs of introducing COVID-19 vaccines for 3 years from 2021 to 2023 were projected from the government perspective. All costs were collected in 2021 Lao Kip and presented in United States dollar.
From 2021 to 2023, the financial cost required to vaccinate all adults in Lao PDR with primary series of COVID-19 vaccines (1 dose for Ad26.COV2.S (recombinant) vaccine and 2 doses for the other vaccine products) is estimated to be US$6.44 million (excluding vaccine costs) and additionally US$1.44 million and US$1.62 million to include teenagers and children, respectively. These translate to financial costs of US$0.79-0.81 per dose, which decrease to US$0.6 when two boosters are introduced to the population. Capital and operational cold-chain costs contributed 15-34% and 15-24% of the total costs in all scenarios, respectively. 17-26% went to data management, monitoring and evaluation, and oversight, and 13-22% to vaccine delivery.
With the CVIC tool, costs of five scenarios were estimated with different target population and booster dose use. These facilitated Lao PDR to refine their strategic planning for COVID-19 vaccine rollout and to decide on the level of external resources needed to mobilize and support outreach services. The results may further inform inputs in cost-effectiveness or cost-benefit analyses and potentially be applied and adjusted in similar low- and middle-income settings.
••Ascorbate has been proposed for severe paraquat poisoning.••Spectroelectrochemical studies indicate ascorbate cannot quench the paraquat radical.••Oxidized ascorbate (e.g., dehydroascorbate) can ...quench the paraquat radical.
The toxicity of paraquat is believed to involve a redox-cycling mechanism that can disrupt cellular redox homeostasis and, also, generate damaging free radicals. It has been suggested that for cases of severe paraquat poisoning the administration of ascorbate (i.e., vitamin C) can confer benefit by quenching the paraquat free radical (PQ+·). Here, we used an electrochemical approach that abstracts-away many of the (bio)chemical complexities and isolates the redox-interactions between paraquat and ascorbate. Specifically, we used a series of experiments that coupled electrochemical measurements of electron flow with optical measurements of paraquat's redox-state switching. Our results demonstrate that the reduced absorbate cannot quench the PQ+·-radical because they are both reductants. However, oxidation of ascorbate does allow PQ+·-radical scavenging. More broadly, we believe this study demonstrates the potential for developing electrochemical approaches to complement existing experimental methods in redox biology.
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It is well-established that redox-reactions are integral to biology for energy harvesting (oxidative phosphorylation), immune defense (oxidative burst) and drug metabolism (phase I reactions), yet ...there is emerging evidence that redox may play broader roles in biology (e.g., redox signaling). A critical challenge is the need for tools that can probe biologically-relevant redox interactions simply, rapidly and without the need for a comprehensive suite of analytical methods. We propose that electrochemistry may provide such a tool. In this tutorial review, we describe recent studies with a redox-capacitor film that can serve as a bio-electrode interface that can accept, store and donate electrons from mediators commonly used in electrochemistry and also in biology. Specifically, we (i) describe the fabrication of this redox-capacitor from catechols and the polysaccharide chitosan, (ii) discuss the mechanistic basis for electron exchange, (iii) illustrate the properties of this redox-capacitor and its capabilities for promoting redox-communication between biology and electrodes, and (iv) suggest the potential for enlisting signal processing strategies to "extract" redox information. We believe these initial studies indicate broad possibilities for enlisting electrochemistry and signal processing to acquire "systems level" redox information from biology.
Human adipose-derived stem cells (hADSCs) formed robust cell sheets by engineering the cells with soluble cell adhesive molecules (CAMs), which enabled unique approaches to harvest large area hADSC ...sheets. As a soluble CAM, fibronectin (FN) (100 pg/ml) enhanced the cell proliferation rate and control both cell-to-cell and cell-to-substrate interactions. Through this engineering of FN, a transferrable hADSC sheet was obtained as a free-stranding sheet (122.6 mm
) by a photothermal method. During the harvesting of hADSC sheets by the photothermal method, a collagen layer in-between cells and conductive polymer film (CP) was dissociated, to protect cells from direct exposure to a near infrared (NIR) source. The hADSC sheets were applied to chronic wound of genetically diabetic db/db mice in vivo, to accelerate 30% faster wound closure with a high closure effect (ε
) than that of control groups. These results indicated that the engineering of CAM and collagens allow hADSC sheet harvesting, which could be extended to engineer various stem cell sheets for efficient therapies.
Macromolecular phenolics are among the most abundant organic molecules in nature, yet their biological activities are largely unresolved because of their structural complexity and because of an ...inability to probe their functionality experimentally. We developed thin film and electrochemical methodologies to probe the redox properties of melanin, lignin, and humic acid, three of the most abundant phenolic materials. We observed that all three phenolic matrixes possess redox activity and can be repeatedly switched between oxidized and reduced states. Furthermore, we observed that melanin possesses pro-oxidant activities exemplified by the uncatalyzed generation of reactive oxygen species (ROS) upon exposure to air; however, this pro-oxidant activity is observed only for melanin films that are poised in their reduced state. Conversely, melanin’s antioxidant radical-scavenging activities are insensitive to its redox state. These results demonstrate that natural phenolic matrixes are not inert but rather serve as open-source redox media with significant potential for impacting redox signaling and redox biology.
Bipyridazines were modified with heterocyclic amines such as piperazine to give symmetric quadrupolar (SPBP) and asymmetric dipolar (APBP) bipyridazine. The fluorescence of SPBP and APBP was highly ...sensitive to solvent polarity, giving a synthetic rainbow of emission in different organic solvents. The solvent-induced changes in the Stokes shift of the bipyridazines resulted in positive solvatochromism. The symmetric bipyridazine showed higher solvatochromic sensitivity than that of the asymmetric bipyridazine and diazines. The positive solvatochromic fluorescence properties were reproduced in a binary system of toluene/dimethyl sulfoxide (DMSO) mixture, which showed a synthetic rainbow of emission by varying the DMSO content in toluene. An organic sensitive poly(methyl methacrylate) film containing SPBP exhibited a visible sensitivity for the detection of solvents by their polarity upon exposure to organic solvent molecules.
Growing evidence implicates an association between psychosocial stress and oxidative stress (OxSt) although there are not yet reliable biomarkers to study this association. We used a Trier Social ...Stress Test (TSST) and compared the response of a healthy control group (HC; N=10) against the response of a schizophrenia group (SCZ; N=10) that is expected to have higher levels of OxSt. Because our previous study showed inconsistent changes in conventional molecular markers for stress responses in the neuroendocrine and immune systems, we analyzed the same serum samples using a separate reducing capacity assay that provides a more global measurement of OxSt. This assay uses the moderately strong oxidizing agent iridium (Ir) to probe a sample's reducing capacity. Specifically, we characterized OxSt by this Ir-reducing capacity assay (Ir-RCA) using two measurement modalities (optical and electrochemical) and we tuned this assay by imposing an input voltage sequence that generates multiple output metrics for data-driven analysis. We defined five OxSt metrics (one optical and four electrochemical metrics) and showed: (i) internal consistency among each metric in the measurements of all 40 samples (baseline and post TSST for N=20); (ii) all five metrics were consistent with expectations of higher levels of OxSt for the SCZ group (three individual metrics showed statistically significant differences); and (iii) all five metrics showed higher levels of OxSt Post-TSST (one metric showed statistically significant difference). Using multivariant analysis, we showed that combinations of OxSt metrics could discern statistically significant increases in OxSt for both the SCZ and HC groups 90 min after the imposed acute psychosocial stress.
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•Ir-reducing capacity assay (Ir-RCA) provides a robust global measure of oxidative stress in serum.•The multiple oxidative stress (OxSt) output metrics of this Ir-RCA are useful for data-driven analysis.•The combination of OxSt metrics can discern significant increases in OxStwithin 90 mins of an imposed psychosocial stress.
A series of new electrofluorescent switches was prepared using electroactive fluorescent tetrazines, an original family of molecules featuring both highly stable reduced anion-radicals and ...fluorescence in the neutral state. The cells were prepared with four layers: the tetrazine polymer film, a photo cured polymer electrolyte film, and two indium-tin oxide films as the two contact electrodes. When externally biased, the fluorescence of the tetrazine fluorophore can be switched on and off reversibly, according to its redox state through scanning the potential between two transparent ITO electrodes. Electrochromism of a tetrazine containing conducting polymer has also been examined.
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