Parkinson’s disease (PD) has been attributed to a combination of genetic and nongenetic factors. We studied a set of monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA ...N370S) but clinically discordant for PD. We applied induced pluripotent stem cell (iPSC) technology for PD disease modeling using the twins’ fibroblasts to evaluate and dissect the genetic and nongenetic contributions. Utilizing fluorescence-activated cell sorting, we obtained a homogenous population of “footprint-free” iPSC-derived midbrain dopaminergic (mDA) neurons. The mDA neurons from both twins had ∼50% GBA enzymatic activity, ∼3-fold elevated α-synuclein protein levels, and a reduced capacity to synthesize and release dopamine. Interestingly, the affected twin’s neurons showed an even lower dopamine level, increased monoamine oxidase B (MAO-B) expression, and impaired intrinsic network activity. Overexpression of wild-type GBA and treatment with MAO-B inhibitors normalized α-synuclein and dopamine levels, suggesting a combination therapy for the affected twin.
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•GBA N370S results in elevated α-synuclein, and high MAO-B increases DA metabolism•iPSC-derived mDA neurons reveal differences between MZ twins discordant for PD•Neuronal purification offers a relatively pure population of mDA neurons•Footprint-free iPSCs, high-throughput MEA, and NanoString are utilized
Woodard et al. studied a set of identical twins harboring GBA N370S mutation but clinically discordant for Parkinson's disease (PD). Using iPSC technology, they found that enzymes GBA and MAO-B could be therapeutic targets in PD. These findings shed light into future studies using iPSCs to model idiopathic PD cases.
•A self-driving bead-based bioassay.•High temporal stability and reproducibility (<1.2%).•Free from background fluctuations with the use of reference particles.•Dose-dependent measurement of ...microorganisms, as low as 106 cfu/mL.•Detection of live microorganisms, including motile bacterium, P. aeruginosa, and nonmotile bacterium, S. aureus.
A self-driving, thermal-diffusion-based bioassay for the detection of microorganisms in a liquid medium is presented in this paper. In the bioassay, each particle functions as an individual sensing probe. Thus, the representative Brownian velocity of microparticles can be obtained by analyzing the velocity histogram of each particle. The ensemble average was used to enhance peak Brownian velocity. Relative error was reduced to 0.5% when the number of counted particles exceeded 60. The experimentally measured and theoretically derived Brownian velocities and diameters of the particles were in good agreement. The relative standard deviations of the temporal stability and reproducibility of the bioassay were maintained below 1.2%. A calibration curve was constructed and used to distinguish two mixed colloidal suspensions to provide proof that the bioassay can be used in practical applications. The particles were functionalized with antibodies to enable the real biological application of the bioassay in the capture and detection of motile Pseudomonas aeruginosa and nonmotile Staphylococcus aureus. The diffusivity values of both bacterial growth media decreased as bacterial concentration increased. Given that the viscosity of the growth media varied as bacteria proliferated, additional bacteria-free reference particles were added to the medium to provide dynamic background information. The diffusion-based bioassay presented here is easy to use, robust, and highly reliable. In contrast to most existing biosensors, it does not require an external power source and is thus ideal for use in resource-limited areas.
Rapid diagnosis and screening of diseases have become increasingly important in predictive and preventive medicine as they improve patient treatment strategies and reduce cost as well as burden on ...our healthcare system. In this regard, wearable devices are emerging as effective and reliable point-of-care diagnostics that can allow users to monitor their health at home. These wrist-worn, head-mounted, smart-textile, or smart-patches devices can offer valuable information on the conditions of patients as a non-invasive form of monitoring. However, they are significantly limited in monitoring physiological signals and biomechanics, and, mostly, rely on the physical attributes. Recently, developed wearable devices utilize body fluids, such as sweat, saliva, or skin interstitial fluid, and electrochemical interactions to allow continuous physiological condition and disease monitoring for users. Among them, tear fluid has been widely utilized in the investigation of ocular diseases, diabetes, and even cancers, because of its easy accessibility, lower complexity, and minimal invasiveness. By determining the concentration change of analytes within the tear fluid, it would be possible to identify disease progression and allow patient-oriented therapies. Considering the emerging trend of tear-based biosensing technology, this review article aims to focus on an overview of the tear fluid as a detection medium for certain diseases, such as ocular disorders, diabetes, and cancer. In addition, the rise and application of minimally invasive detection and monitoring via integrated contact lens biosensors will also be addressed, in regards to their practicality and current developmental progress.
Graphene oxide was encapsulated into environmentally benign sodium alginate to prepare composite hydrogel beads, and then used as adsorbents to remove ciprofloxacin. Display omitted
Graphene oxide ...(GO) was encapsulated into environmentally benign sodium alginate (SA) to prepare a GO-SA composite hydrogel and an aerogel, which were then used as adsorbents to remove ciprofloxacin from aqueous solutions. The characteristics of these materials were investigated using scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis, Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). The characterizations demonstrated that the incorporation of GO improved the pore uniformity of the gels and decreased the pore sizes. Kinetic studies showed that the adsorption capacity of SA composite gels increased approximately seven to nine times after the incorporation of GO, matching with pseudo-second-order models. Non-linear fitting parameters of adsorption isotherm studies indicated that a Langmuir model could precisely represent the adsorption behavior. GO-SA aerogels exhibited high tolerance to changes in pH and ionic strength; changes in these parameters minimally influenced the adsorption capacity of the GO-SA aerogels for ciprofloxacin. This work is especially relevant for environmental applications. These graphene-based composites are environmentally benign adsorbents and can remove organic contaminants from aqueous solutions.
Development of specific antiviral agents is an urgent unmet need for SARS-coronavirus 2 (SARS-CoV-2) infection. This study focuses on host proteases that proteolytically activate the SARS-CoV-2 spike ...protein, critical for its fusion after binding to angiotensin-converting enzyme 2 (ACE2), as antiviral targets. We first validate cleavage at a putative furin substrate motif at SARS-CoV-2 spikes by expressing it in VeroE6 cells and find prominent syncytium formation. Cleavage and the syncytium are abolished by treatment with the furin inhibitors decanoyl-RVKR-chloromethylketone (CMK) and naphthofluorescein, but not by the transmembrane protease serine 2 (TMPRSS2) inhibitor camostat. CMK and naphthofluorescein show antiviral effects on SARS-CoV-2-infected cells by decreasing virus production and cytopathic effects. Further analysis reveals that, similar to camostat, CMK blocks virus entry, but it further suppresses cleavage of spikes and the syncytium. Naphthofluorescein acts primarily by suppressing viral RNA transcription. Therefore, furin inhibitors may be promising antiviral agents for prevention and treatment of SARS-CoV-2 infection.
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•The furin cleavage site in the SARS-CoV-2 spike protein mediates syncytium formation•The SARS-CoV-2 spike-mediated syncytium is suppressed by specific furin inhibitors•Furin inhibitors block SARS-CoV-2 virus entry and virus replication•Furin inhibitors are potential antiviral agents for SARS-CoV-2 infection and pathogenesis
Development of effective antiviral agents is an urgent unmet need for SARS-CoV-2 infection. Cheng et al. find that cleavage of the furin substrate site in the viral spike protein is critical for virus production and cytopathic effects. Two inhibitors targeting furin are potential antiviral agents to control SARS-CoV-2 infection and pathogenesis.
Combining the advantages from both porous materials and graphene, porous graphene materials have attracted vast interests due to their large surface areas, unique porous structures, diversified ...compositions and excellent electronic conductivity. These unordinary features enable porous graphene materials to serve as key components in high‐performance electrochemical energy storage and conversion devices such as lithium ion batteries, supercapacitors, and fuel cells. This progress report summarizes the typical fabrication methods for porous graphene materials with micro‐, meso‐, and macro‐porous structures. The structure–property relationships of these materials and their application in advanced electrochemical devices are also discussed.
This Progress Report summarizes the typical fabrication methods for porous graphene materials with micro‐, meso‐, and macro‐porous structures. The structure–property relationships of these materials and their application in advanced electrochemical devices, such as lithium ion batteries, supercapacitors, and fuel cells are also discussed.
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