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Based on two perfect metal cluster models with atomic-precis i on structure, this work reveals that clusteroluminescence induced by specific metal atom aggregations could be a critical approach for enhancing photoluminescence from metal clusters at room temperature. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.INTRODUCTION Prophylaxis with factor VIII (FVIII) concentrates in children with haemophilia A (HA) is current standard of care. The benefit of prophylactic treatment for adult HA patients is not commonly accepted. AIM To investigate the benefit of prophylaxis over on-demand treatment in adult and elderly patients with severe or non-severe HA in a real-life setting. METHODS Data from 163 patients comprising 1202 patient-years were evaluated for 7.5 (±5.3) years. The effects on the annual bleeding rate (ABR, including spontaneous and traumatic bleeds) of treatment with a plasma-derived FVIII concentrate, the patient's age and disease severity were investigated. The effect of changing the treatment from on demand to continuous prophylaxis on the patients' ABRs was further analysed. RESULTS Prophylaxis had the greatest effect on the ABRs of patients of any age with severe or non-severe HA. The difference in ABR of all patients treated on demand (median 31.4; interquartile range (IQR) 27.6; N = 83) compared with those treated prophylactically (median 1.3; IQR 3.6; N = 122) was statistically significant (P  less then  .05), even for patients with non-severe HA (median 8.4; IQR 15.5; N = 11) vs median 1.5; IQR 4.2 (N = 17), P  less then  .05). Patients, aged up to 88 years, switching from on demand to continuous prophylaxis showed the lowest median ABR (1.1; N = 51) after their regimen change. CONCLUSION Any (even low-frequency) prophylaxis results in lower ABR than on-demand treatment. Patients switching to prophylaxis benefitted the most, irrespective of age or HA severity. Prophylactic treatment-even tertiary-is the regimen of choice for patients of any age, including elderly patients, with severe or non-severe HA. © 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.Radiation therapy is one of the core components of multidisciplinary cancer care. Although approximately 50% of all European cancer patients have an indication for radiotherapy at least once in the course of their disease, more than one out of four cancer patients in Europe do not receive the radiotherapy they need. There are multiple reasons for this underutilisation, with limited availability of the necessary resources - in terms of both trained personnel and equipment - being a major underlying cause of suboptimal access to radiotherapy. Moreover, large variations across European countries are observed, not only in available radiotherapy equipment and personnel per inhabitant or per cancer patient, but also in workload. This variation is in part determined by the country's gross national income. Radiation therapy and technology are advancing quickly, hence recommendations supporting resource planning and investment should reflect this dynamic environment and account for evolving treatment complexity and fractionation schedules. The forecasted increase in cancer incidence, the rapid introduction of innovative cancer treatments and the more active involvement of patients in the healthcare discussion are all factors that should be taken under consideration. In this continuously changing oncology landscape, reliable data on the actual provision and use of radiotherapy, the optimal evidence-based demand and the future needs are crucial to inform cancer care planning and address and overcome the current inequalities in access to radiotherapy in Europe. This article is protected by copyright. All rights reserved.Recent experimental results have shown that the detection of cues in behavioral attention tasks relies on transient increases of acetylcholine (ACh) release in frontal cortex and cholinergically-driven oscillatory activity in the gamma frequency band(Howe et al., 2017).The cue-induced gamma rhythmic activity requires stimulation of M1 muscarinic receptors.Usingbiophysical computational modeling, we show that a network of excitatory (E) and inhibitory (I) neurons, that initially displays asynchronous firing, can generate transient gamma oscillatory activity in response to simulated brief pulses of ACh. ACh effects are simulated astransient modulation of the conductance of an M-type K+ current which is blocked by activation of muscarinic receptors and has significant effects on neuronal excitability. TheACh-induced effects on the M-current conductance, gks , change network dynamics to promote the emergence of network gamma rhythmicity through a PING mechanism. Depending on connectivity strengths between and among E and I cells, gamma activity decays with the simulated gks transient modulation or is sustained in the network after the gks transient has completely dissipated. We investigated the sensitivity of the emergent gamma activity to synaptic strengths, external noise and simulated levels of gks modulation. To address recent experimental findings that cholinergic signaling is likely spatially focused and dynamic, we show that localized gks modulation can induce transient changes of cellular excitability in local subnetworks, subsequently causing population-specific gamma oscillations. These results highlight dynamical mechanisms underlying localization of ACh-driven attentional responses and the emergence of dominance of ACh-driven cell populationswithin a network. This article is protected by copyright. All rights reserved.Graphdiyne (GDY), a new kind of 2D material, is combined here with micromotor technology for "on-the-fly" operations in complex biomedia. Microtubular structures are prepared by template deposition on membrane templates, resulting in functional structures rich in sp and sp2 carbons with high conjugated π network. This results in a highly increased surface area for a higher loading of anticancer drugs or enhanced quenching ability over other 2D based micromotors such as GO or smooth tubular micromotors. High biocompatibility with almost 100 % cell viability is observed in cytotoxicity assays with moving micromotors in the presence of HeLa cells. On a first example, GDY micromotors loaded with doxorubicin (DOX) are used for pH responsive release and HeLa cancer cells killing. The use of affinity peptide engineered GDY micromotors is also illustrated for highly sensitive and selective fluorescent "OFF-ON" detection of Cholera B toxin via specific recognition of the Subunit A region of the target toxin. The novel developments illustrated here offer considerable promise for the use of GDY on board of micromotors in living biosystems. MitoTEMPO © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Owing to the electron donating and accepting nature of corroles (Corr) and phthalocyanines (Pc), respectively, we designed and developed two novel covalently linked Corr-Pc conjugates. The synthetic route allows the preparation of the target conjugates in satisfying yields. Comprehensive steady-state absorption, fluorescence, and electrochemical assays enabled insights onto energy and electron transfer processes upon photoexcitation. Coordinating a pyridine-appended subphthalocyanine (SubPc) to the Pc of the conjugate sets up the ways and means to realize the first example of an array composed by three different porphyrinoids, which drives a cascade of energy and charge transfer processes occur. Importantly, the SubPc assists in stabilizing the charge-separated state, that is, one-electron oxidized Corr and the one electron reduced Pc, upon photoexcitation by means of a reductive charge transfer to the SubPc. To the best of our knowledge, this is the first case of an intramolecular oxidation of a Corr within electron donor-acceptor conjugates by means of just photoexcitation. Moreover, the combination of Corr, Pc, and SubPc guarantees panchromatic absorption across the visible range of the solar spectrum, with the SubPc covering the "green gap" that usually affects porphyrinoids. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The intracellular molecular pathways involved in radiation-induced nephropathy are still poorly understood. Glomerular endothelial cells are key components of the structure and function of the glomerular filtration barrier but little is known about the mechanisms implicated in their injury and repair. The current study establishes the response of immortalized human glomerular endothelial cells (GEnC) to ionizing radiation (IR). We investigated the role of sphingolipids and the lipid-modifying enzyme sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) in radiation-induced GEnC damage. After delivering a single dose of radiation, long and very-long-chain ceramide species, and the expression levels of SMPDL3b were elevated. In contrast, levels of ceramide-1-phosphate (C1P) dropped in a time-dependent manner although mRNA and protein levels of ceramide kinase (CERK) remained stable. Treatment with C1P or knocking down SMPDL3b partially restored cell survival and conferred radioprotection. We also report a novel role for the NADPH oxidase enzymes (NOXs), namely NOX1, and NOX-derived reactive oxygen species (ROS) in radiation-induced GEnC damage. Subjecting cultured endothelial cells to radiation was associated with increased NOX activity and superoxide anion generation. Silencing NOX1 using NOX1-specific siRNA mitigated radiation-induced oxidative stress and cellular injury. In addition, we report a novel connection between NOX and SMPDL3b. Treatment with the NOX inhibitor, GKT, decreased radiation-induced cellular injury and restored SMPDL3b basal levels of expression. Our findings indicate the importance of SMPDL3b as a potential therapeutic target in radiation-induced kidney damage. © 2020 Federation of American Societies for Experimental Biology.While urine has been considered as a useful bio-fluid for health monitoring, its dynamic changes to physical activity are not well understood. We examined urine's possible antitumor capability in response to medium-level, loading-driven physical activity. Urine was collected from mice subjected to 5-minute skeletal loading and human individuals before and after 30-minute step aerobics. Six cancer cell lines (breast, prostate, and pancreas) and a mouse model of the mammary tumor were employed to evaluate the effect of urine. Compared to urine collected prior to loading, urine collected post-activity decreased the cellular viability, proliferation, migration, and invasion of tumor cells, as well as tumor weight in the mammary fat pad. Detection of urinary volatile organic compounds and ELISA assays showed that the loading-conditioned urine reduced cholesterol and elevated dopamine and melatonin. Immunohistochemical fluorescent images presented upregulation of the rate-limiting enzymes for the production of dopamine and melatonin in the brain. Molecular analysis revealed that the antitumor effect was linked to the reduction in molecular vinculin-linked molecular force as well as the downregulation of the Lrp5-CSF1-CD105 regulatory axis. Notably, the survival rate for the high expression levels of Lrp5, CSF1, and CD105 in tumor tissues was significantly lowered in the Cancer Genome Atlas database. Collectively, this study revealed that 5- or 10-minute loading-driven physical activity was sufficient to induce the striking antitumor effect by activating the neuronal signaling and repressing cholesterol synthesis. The result supported the dual role of loading-conditioned urine as a potential tumor suppressor and a source of diagnostic biomarkers. © 2020 Federation of American Societies for Experimental Biology.