COVID-19 has spread globally since its discovery in Hubei province, China in December 2019. A combination of computed tomography imaging, whole genome sequencing, and electron microscopy were ...initially used to screen and identify SARS-CoV-2, the viral etiology of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.
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IJS, KILJ, NUK, PNG, UL, UM
Diagnostic assays are commonly performed in multiple steps, where reagents are added at specific times and concentrations into a reaction chamber. The reagents require storage, preparation, and ...addition in the correct sequence and amount. These steps rely on trained technicians and instrumentation to perform each task. The reliance on such resources hinders the use of these diagnostic assays by lay users. We developed a tablet that can sequentially introduce prequantified lyophilized diagnostic reagents at specific time points for a multistep assay. We designed the tablet to have multiple layers using cellulose-grade polymers, such as microcrystalline cellulose and hydroxypropyl cellulose. Our formulation allows each layer to dissolve at a controlled rate to introduce reagents into the solution sequentially. The release rate is controlled by modulating the compression force or chemical formulation of the layer. Controlling the reagent release time is important because different assays have specific times when reagents need to be added. As proof of concept, we demonstrated two different assays with our tablet system. Our tablet detected nucleic acid target (tpp47 gene from Treponema pallidum) and nitrite ions in an aqueous sample without user intervention. Our multilayer tablets can simplify multistep assay processes.
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IJS, KILJ, NUK, PNG, UL, UM
Detecting nucleic acids at ultralow concentrations is critical for research and clinical applications. Particle-based assays are commonly used to detect nucleic acids. However, DNA hybridization on ...particle surfaces is inefficient due to the instability of tethered sequences, which negatively influences the assay’s detection sensitivity. Here, we report a method to stabilize sequences on particle surfaces using a double-stranded linker at the 5′ end of the tethered sequence. We termed this method Rigid Double Stranded Genomic Linkers for Improved DNA Analysis (RIGID-DNA). Our method led to a 3- and 100-fold improvement of the assays’ clinical and analytical sensitivity, respectively. Our approach can enhance the hybridization efficiency of particle-based assays without altering existing assay workflows. This approach can be adapted to other platforms and surfaces to enhance the detection sensitivity.
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Designing diagnostic assays to genotype rapidly mutating viruses remains a challenge despite the overall improvements in nucleic acid detection technologies. RT-PCR and next-generation sequencing are ...unsuitable for genotyping during outbreaks or in point-of-care detection due to their infrastructure requirements and longer turnaround times. We developed a quantum dot barcode multiplexing system to genotype mutated viruses. We designed multiple quantum dot barcodes to target conserved, wildtype, and mutated regions of SARS-CoV-2. We calculated ratios of the signal output from different barcodes that enabled SARS-CoV-2 detection and identified SARS-CoV-2 variant strains from a sample. We detected different sequence types, including conserved genes, nucleotide deletions, and single nucleotide substitutions. Our system detected SARS-CoV-2 patient specimens with 98% sensitivity and 94% specificity across 91 patient samples. Further, we leveraged our barcoding and ratio system to track the emergence of the N501Y SARS-CoV-2 mutation from December 2020 to May 2021 and demonstrated that the more transmissible N501Y mutation started to dominate infections by April 2021. Our barcoding and signal ratio approach can genotype viruses and track the emergence of viral mutations in a single diagnostic test. This technology can be extended to tracking other viruses. Combined with smartphone detection technologies, this assay can be adapted for point-of-care tracking of viral mutations in real time.
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IJS, KILJ, NUK, PNG, UL, UM
Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from ...optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (n = 46) with those of community-acquired pneumonia (CAP) patients (n = 30) and controls without active infection (n = 30) using ultrahigh-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate and univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid 12(R)-HETE, ceramide (d18:1/16:0), cholesterol sulfate, and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, were identified and found to have significantly higher levels in TB patients than those in CAP patients and controls. In a comparison of TB patients and controls, the four metabolites demonstrated area under the receiver operating characteristic curve (AUC) values of 0.914, 0.912, 0.905, and 0.856, sensitivities of 84.8%, 84.8%, 87.0%, and 89.1%, specificities of 90.0%, 86.7%, 86.7%, and 80.0%, and fold changes of 4.19, 26.15, 6.09, and 1.83, respectively. In a comparison of TB and CAP patients, the four metabolites demonstrated AUC values of 0.793, 0.717, 0.802, and 0.894, sensitivities of 89.1%, 71.7%, 80.4%, and 84.8%, specificities of 63.3%, 66.7%, 70.0%, and 83.3%, and fold changes of 4.69, 3.82, 3.75, and 2.16, respectively. 4α-Formyl-4β-methyl-5α-cholesta-8-en-3β-ol combined with 12(R)-HETE or cholesterol sulfate offered ≥70% sensitivity and ≥90% specificity for differentiating TB patients from controls or CAP patients. These novel plasma biomarkers, especially 12(R)-HETE and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, alone or in combination, are potentially useful for rapid and noninvasive diagnosis of TB. The present findings may offer insights into the pathogenesis and host response in TB.
Abstract
A need for multi-functional assessment tools evaluating trade-offs and co-benefits for various types of Nature-Based Solutions (NBS) has been increasingly identified in recent years. ...Methodologically, concepts for a tool are presented which include quantifying the demand and potential for NBS to enhance ecosystem service (ES) provision, and linking ESs to readily quantifiable and legislatively-relevant environmental quality indicators (EQIs). The objective of tool application is to identify optimal NBS placement across a diverse set of socio-environmental indicators, whilst also incorporating issues of relative location of areas of implementation and benefit accrual. Embedded within the tool is the importance of evaluating outcomes in terms of economic benefits and of sustainable development goals. The concepts are illustrated with simplified examples, relating to the case of implementing urban forestry as an exemplar NBS. By summarising the knowledge base it is demonstrated that benefits of NBS are substantially scale-dependent in two main respects; those of extent and proximity to receptors. Evaluation tools should be capable of quantifying scale-dependence. The substantive importance of these considerations and how their dynamics vary between indicators and services is illustrated graphically through schematic functions. When developed, the tool should be used as a focus for consultation and co-design to pinpoint the size of NBS necessary to achieve a sufficient level of benefit for a particular receptor. This could be measured against target levels of benefit for each indicator, distinguishing between primary intended outcomes and those co-benefits or trade-offs that are secondary or unintended.
Ordered mesoporous CeZrO2 synthesized via colloidal solution combustion synthesis exhibits superior performance for CO oxidation as Diesel Particulate Filter.
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•Ordered mesoporous ...CexZr1-xO2 are synthesized via colloidal solution combustion synthesis method.•High surface area and pore volume are beneficial for CO oxidation.•Mesoporous CexZr1-xO2 catalyst is active, durable and thermally stable under accelerated ageing at 800 °C.•600 g catalysts can be produced in 6 h by the scale-up synthesis.•T50 and T90 of CexZr1-xO2 catalyst as diesel particulate filters can be achieved below 100 °C for CO oxidation in simulated vehicle gas environment.
The scale-up synthesis of mesoporous binary metal oxides with uniform porosity for practical application is still challenging. Here we report an ordered mesoporous CexZr1-xO2 catalyst synthesized by a scalable colloidal solution combustion method, and tested for CO oxidation. The mesoporous CexZr1-xO2 catalyst is durable and demonstrates superior CO oxidation activity with a full conversion at ∼ 400 °C due to its high surface area of about 141 m2/g and pore volumes of 0.55 mL/g. The CexZr1-xO2 catalyst is also active and thermally stable up to 800 °C. Its structure is robust with uniform Zr distribution and nano-cavities even after accelerated ageing. We have also realized the practical feasibility by scale-up synthesis of 600 g mesoporous CexZr1-xO2 catalyst. It is then effectively applied as diesel oxidation catalysts in a Diesel Particulate Filter (DPF) in simulated vehicle gas environment. Our DPF prototype allows nearly a full CO to CO2 conversion below 100 °C. The synthesis is simple and scalable, allowing full control of composition and porosity to effectively design binary oxides for enhanced catalytic applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death ...mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
The abnormal accumulation of β‐amyloid peptide (Aβ) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aβ‐mediated neurotoxicity remain elusive, Aβ ...has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione‐derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors. This study investigates ET’s potential to counteract Aβ‐toxicity in transgenic Caenorhabditis elegans overexpressing a human Aβ peptide. The accumulation of Aβ in this model leads to paralysis and premature death. We show that ET dose‐dependently reduces Aβ‐oligomerization and extends the lifespan and healthspan of the nematodes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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