The contamination of ground and surface waters with per- and polyfluoroalkyl substances (PFASs) is of major concern due to their potential adverse effects on human health. The carbon-fluorine bond makes these compounds extremely stable and hardly degradable by natural processes. Therefore, methods for PFAS removal from water are desperately needed.
View Article and Find Full Text PDFRegular wave patterns were created by a 2 kV gallium ion on Si(111) monocrystals at incidence angles between 60° and 80° with respect to the surface normal. The characteristic wavelength and surface roughness of the structured surfaces were determined to be between 35-75 nm and 0.5-2.
View Article and Find Full Text PDFIn communication technologies such as digital watermarking, wireless sensor networks (WSNs), and visual light communication (VLC), error-correcting codes are crucial. The Enhanced Hadamard Error-Correcting Code (EHC), which is based on 2D Hadamard Basis Images, is a novel error correction technique that is presented in this study. This technique is used to evaluate the effectiveness of the video watermarking scheme.
View Article and Find Full Text PDFp75 neurotrophin receptor (p75) signaling pathways substantially overlap with degenerative networks active in Alzheimer disease (AD). Modulation of p75 with the first-in-class small molecule LM11A-31 mitigates amyloid-induced and pathological tau-induced synaptic loss in preclinical models. Here we conducted a 26-week randomized, placebo-controlled, double-blinded phase 2a safety and exploratory endpoint trial of LM11A-31 in 242 participants with mild to moderate AD with three arms: placebo, 200 mg LM11A-31 and 400 mg LM11A-31, administered twice daily by oral capsules.
View Article and Find Full Text PDFBackground: () uses various strategies that attenuate mucosal immunity to ensure its persistence in the stomach. We recently found evidence that might modulate the natural killer group 2, member 2 (NKG2D) system. The NKG2D receptor and its ligands are a major activation system of natural killer and cytotoxic T cells, which are important for mucosal immunity and tumor immunosurveillance.
View Article and Find Full Text PDFBackground And Aims: HCV infection can be successfully managed with antiviral therapies; however, progression to chronic liver disease states, including NAFLD, is common. There is currently no reliable in vitro model for investigating host-viral interactions underlying the link between HCV and NAFLD; although liver organoids (LOs) show promise, they currently lack nonparenchymal cells, which are key to modeling disease progression.
Approach And Results: Here, we present a novel, multicellular LO model using a coculture system of macrophages and LOs differentiated from the same human pluripotent stem cells (PSCs).
Zika virus (ZIKV) is a mosquito-borne human flavivirus responsible that causing emergency outbreaks in Brazil. ZIKV is suspected of causing Guillain-Barre syndrome in adults and microcephaly. The NS2B-NS3 protease and NS5 RNA-dependent RNA polymerase (RdRp), central to ZIKV multiplication, have been identified as attractive molecular targets for drugs.
View Article and Find Full Text PDFTransformation pathways for the land sector in line with the Paris Agreement depend on the assumption of globally implemented greenhouse gas (GHG) emission pricing, and in some cases also on inclusive socio-economic development and sustainable land-use practices. In such pathways, the majority of GHG emission reductions in the land system is expected to come from low- and middle-income countries, which currently account for a large share of emissions from agriculture, forestry and other land use (AFOLU). However, in low- and middle-income countries the economic, financial and institutional barriers for such transformative changes are high.
View Article and Find Full Text PDFGinsenosides are a class of natural steroid glycosides and triterpene saponins found in . After screening of a commercial ginsenoside compound library for low cellular cytotoxicity and the ability to mediate efficient reductions in hepatitis B virus (HBV) mRNA expression levels in HepG2.2.
View Article and Find Full Text PDFBioluminescence resonance energy transfer (BRET) saturation is a method of studying protein-protein interaction (PPI) upon quantification of the dependence of the BRET signal on the acceptor/donor (A:D) expression ratio. In this study, using the very bright Nluc/YFP BRET pair acquired respectively with microplate reader and automated confocal microscopy, we significantly improved BRET saturation assay by extending A:D expression detection range and normalizing A:D expression with a new BRET-free probe. We next found that upon using variable instead of fixed amount of donor molecules co-expressed with increasing acceptor concentrations, BRET saturation assay robustness can be further improved when studying cytosolic protein, although the relative amounts of dimers (BRETmax) and the relative dimer affinity (BRET50) remain similar.
View Article and Find Full Text PDFBroadly effective antiviral therapies must be developed to be ready for clinical trials, which should begin soon after the emergence of new life-threatening viruses. Here, we pave the way towards this goal by reviewing conserved druggable virus-host interactions, mechanisms of action, immunomodulatory properties of available broad-spectrum antivirals (BSAs), routes of BSA delivery, and interactions of BSAs with other antivirals. Based on the review, we concluded that the range of indications of BSAs can be expanded, and new pan- and cross-viral mono- and combinational therapies can be developed.
View Article and Find Full Text PDFThe repurposing of marketed drugs for new indications is an elegant strategy to quickly and cost-efficiently address unmet medical needs. The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) has been shown to be a valid drug target. We performed structure-based virtual screening to assess the off-label utilization of existing drugs as novel HCV inhibitors.
View Article and Find Full Text PDFZika virus (ZIKV), an RNA virus, rapidly spreads mosquito-borne sickness. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. In this study, to address these unmet medical needs, we aimed to design B- and T-cell candidate multi-epitope-based subunit against ZIKV using an approach.
View Article and Find Full Text PDFBackground: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects.
Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro.
Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective.
The quantification of infectious virus particles is fundamental to perform in vitro virology studies. To determine the number of hepatitis B virus (HBV) genome-containing particles in vitro, the genome equivalents (GEq) are measured using quantitative PCR (qPCR). However, in addition to infectious virions, HBV DNA-containing, non-infectious HBV particles are also produced in vitro, which can lead to an over-estimation of the number of infectious HBV particles when analyzed by qPCR.
View Article and Find Full Text PDFBackground & Aims: Chronic hepatitis B is an incurable disease. Addressing the unmet medical need for therapies has been hampered by a lack of suitable cell culture models to investigate the HBV life cycle in a single experimental setup. We sought to develop a platform suitable to investigate all aspects of the entire HBV life cycle.
View Article and Find Full Text PDFTherapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs.
View Article and Find Full Text PDFMaterials (Basel)
February 2021
The present investigation is directed to phase transitions in the equimolar NiCoFeCrGa high entropy alloy, which is a mixture of face-centered cubic (FCC) and body-centered cubic (BCC) crystalline phases. The microstructure of the samples was investigated by using scanning electron microscopy (SEM), time-of-flight secondary ion mass spectroscopy (TOF-SIMS), transmission electron microscopy-based energy-dispersive spectroscopy (EDS) and electron energy loss spectroscopy (EELS), as well as X-ray diffraction (XRD) measurements. Based on the phases observed in different temperature ranges, a sequence of the phase transitions can be established, showing that in a realistic process, when freely cooling the sample with the furnace from high to room temperature, a microstructure having spinodal-like decomposition can also be expected.
View Article and Find Full Text PDFOver 5 million Americans and 50 million individuals worldwide are living with Alzheimer's disease (AD). The progressive dementia associated with AD currently has no cure. Although clinical trials in patients are ultimately required to find safe and effective drugs, animal models of AD permit the integration of brain pathologies with learning and memory deficits that are the first step in developing these new drugs.
View Article and Find Full Text PDFJ Enzyme Inhib Med Chem
December 2021
To develop unique small-molecule inhibitors of hepatitis C virus (HCV), thiophen urea (TU) derivatives were synthesised and screened for HCV entry inhibitory activities. Among them, seven TU compounds exhibited portent anti-viral activities against genotypes 1/2 (EC < 30 nM) and subsequently, they were further investigated; based on the pharmacological, metabolic, pharmacokinetic, and safety profiles, was selected as the optimised lead compound as an HCV entry inhibitor. possesses effective multi-genotypic antiviral activity.
View Article and Find Full Text PDFInteractions between the hepatitis B virus core protein (HBc) and host cell proteins are poorly understood, although they may be essential for the propagation of the virus and its pathogenicity. HBc has a C-terminal PDZ (PSD-95, Dlg1, ZO-1)-binding motif (PBM) that is responsible for interactions with host PDZ domain-containing proteins. In this work, we focused on the human protein tyrosine phosphatase non-receptor type 3 (PTPN3) and its interaction with HBc.
View Article and Find Full Text PDFThe ongoing coronavirus disease 19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become fatal for the world with affected population crossing over 25 million in more than 217 countries, consequently declared a global pandemic by the World Health Organization. Unfortunately, neither specific prophylactic or therapeutic drugs nor vaccines are available. To address the unmet medical needs, we explored a strategy identifying new compounds targeting the main protease (M) of SARS-CoV-2.
View Article and Find Full Text PDFCoronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). This virus is capable of human-to-human transmission, and is spreading rapidly round the globe, with markedly high fatality rates. Unfortunately, there are neither vaccines nor specific therapies available to combat it, and the developments of such approaches depend on pursuing multiple avenues in biomedical science.
View Article and Find Full Text PDFCombination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), echovirus 1 (EV1), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1) in vitro.
View Article and Find Full Text PDFThe management of chronic hepatitis B virus (CHB) infection is an area of massive unmet clinical need worldwide. In spite of the development of powerful nucleoside/nucleotide analogue (NUC) drugs, and the widespread use of immune stimulators such as interferon-alpha (IFNα) or PEGylated interferon-alpha (PEG-IFNα), substantial improvements in CHB standards of care are still required. We believe that the future for CHB treatment now rests with advanced therapeutics, vaccination, and precision medicine, if all are to bring under control this most resilient of virus infections.
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