More effective therapy for patients with either muscle-invasive or high-risk non-muscle-invasive urothelial carcinoma of the bladder (UCB) is an unmet clinical need. For this, drug repositioning of clinically approved drugs represents an interesting approach. By repurposing existing drugs, alternative anticancer therapies can be introduced in the clinic relatively fast, because the safety and dosing of these clinically approved pharmacological agents are generally well known. Cationic amphiphilic drugs (CADs) dose-dependently decreased the viability of a panel of human UCB lines in vitro. CADs induced lysosomal puncta formation, a hallmark of lysosomal leakage. Intravesical instillation of the CAD penfluridol in an orthotopic mouse xenograft model of human UCB resulted in significantly reduced intravesical tumor growth and metastatic progression. Furthermore, treatment of patient-derived ex vivo cultured human UCB tissue caused significant partial or complete antitumor responses in 97% of the explanted tumor tissues. In conclusion, penfluridol represents a promising treatment option for bladder cancer patients and warrants further clinical evaluation. The Coronavirus disease 2019 (COVID-19) pandemic is straining healthcare resources. Molecular testing turnaround time precludes having results at the point-of-care (POC) thereby exposing COVID-19/Non-COVID-19 patients while awaiting diagnosis. We evaluated the utility of a triage strategy including FebriDx, a 10-minute POC finger-stick blood test that differentiates viral from bacterial acute respiratory infection through detection of Myxovirus-resistance protein A (MxA) and C-reactive protein (CRP), to rapidly isolate viral cases requiring confirmatory testing. This observational, prospective, single-center study enrolled patients presenting to/within an acute care hospital in England with suspected COVID-19 between March and April 2020. Immunocompetent patients≥16years requiring hospitalisation with pneumonia or acute respiratory distress syndrome or influenza-like illness (fever and≥1 respiratory symptom within 7days of enrolment, or inpatients with new respiratory symptoms, fever of unknown cause or pular test was 100% (13/13; 95%CI 70-100 and 13/13; 95%CI 85.4-100, respectively). FebriDx could be deployed as part of a reliable triage strategy for identifying symptomatic cases as possible COVID-19 in the pandemic.FebriDx could be deployed as part of a reliable triage strategy for identifying symptomatic cases as possible COVID-19 in the pandemic.Single atom catalysts (SACs) with the maximized metal atom efficiency have sparked great attention. However, it is challenging to obtain SACs with high metal loading, high catalytic activity, and good stability. Herein, we demonstrate a new strategy to develop a highly active and stable Ag single atom in carbon nitride (Ag-N2 C2 /CN) catalyst with a unique coordination. The Ag atomic dispersion and Ag-N2 C2 configuration have been identified by aberration-correction high-angle-annular-dark-field scanning transmission electron microscopy (AC-HAADF-STEM) and extended X-ray absorption. Experiments and DFT calculations further verify that Ag-N2 C2 can reduce the H2 evolution barrier, expand the light absorption range, and improve the charge transfer of CN. As a result, the Ag-N2 C2 /CN catalyst exhibits much better H2 evolution activity than the N-coordinated Ag single atom in CN (Ag-N4 /CN), and is even superior to the Pt nanoparticle-loaded CN (PtNP /CN). This work provides a new idea for the design and synthesis of SACs with novel configurations and excellent catalytic activity and durability. Varicella zoster virus causes infections of the central nervous system (CNS) manifesting as meningitis or encephalitis. It is not commonly tested in CNS infections when compared to Enterovirus (EV) and Herpes Simplex Virus 1 (HSV-1) and 2 (HSV-2). Cerebrospinal fluid (CSF) findings of viral CNS infections are thought to be comparable. To describe the manifestations of VZV CNS infections and ascertain if there is a predominant syndrome. To compare CSF parameters of VZV with EV, HSV-1 and HSV-2. Retrospective study at two hospitals in Brisbane, reviewing medical notes and laboratory information system for results between January 2001-2019. The following parameters were recorded - disease classification, presence of rash, duration of symptoms prior to hospitalisation, length of admission, duration of antiviral treatment, 30-day mortality. CSF biochemistry, cell count (differential), PCR for VZV, EV, HSV-1 and HSV-2 were recorded. Statistical analysis of CSF parameters included student's t-test and linear regression. Incidence of meningitis was comparable to encephalitis (44 vs 39%) in 52 cases. CSF protein in VZV was significantly elevated compared to EV (median 1121 vs 569 mg/L p<0.001) as was CSF monocytosis (96% vs 61%; p<0.001). CSF parameters between VZV, HSV-1 and HSV-2 were similar. https://www.selleckchem.com/products/asn007.html VZV had a higher incidence than HSV-1 or 2 while it was tested one-third as often. VZV CNS infection cannot be predicted by syndrome. CSF findings are markedly different from EV but like HSV-1 and 2. VZV should be routinely tested with HSV-1 and 2 when viral CNS infection is suspected. This article is protected by copyright. All rights reserved.VZV CNS infection cannot be predicted by syndrome. CSF findings are markedly different from EV but like HSV-1 and 2. VZV should be routinely tested with HSV-1 and 2 when viral CNS infection is suspected. This article is protected by copyright. All rights reserved.Dehydroalanine (Dha) residues are attractive noncanonical amino acids that occur naturally in ribosomally synthesised and post-translationally modified peptides (RiPPs). Dha residues are attractive targets for selective late-stage modification of these complex biomolecules. In this work, we show the selective photocatalytic modification of dehydroalanine residues in the antimicrobial peptide nisin and in the proteins small ubiquitin-like modifier (SUMO) and superfolder green fluorescent protein (sfGFP). For this purpose, a new water-soluble iridium(III) photoredox catalyst was used. The design and synthesis of this new photocatalyst, [Ir(dF(CF3 )ppy)2 (dNMe3 bpy)]Cl3 , is presented. In contrast to commonly used iridium photocatalysts, this complex is highly water soluble and allows peptides and proteins to be modified in water and aqueous solvents under physiologically relevant conditions, with short reaction times and with low reagent and catalyst loadings. This work suggests that photoredox catalysis using this newly designed catalyst is a promising strategy to modify dehydroalanine-containing natural products and thus could have great potential for novel bioconjugation strategies.