Highly bright and photostable cyanine dye-doped silica nanoparticles for optical imaging: Photophysical characterization and cell tests

Spherical silica nanoparticles containing fluorescent trimethine indocyanine dyes (λ_abs = 547 nm, λ_em = 570 nm) were prepared using a water-in-oil microemulsion method. The nanoparticles were of 50 nm diameter and were almost monodispersed in aqueous solution at pH 5.5. Entrapment of dye molecules in the silica matrix stabilised photoemission over several hours of continuous irradiation. The photoemission intensity of the indocyanine was increased 13-fold over that recorded in solution. As each nanoparticle contained 110 dye molecules, the photoemission brightness of each particle was enhanced by three orders of magnitude. The fluorescent nanoparticles have been tested as imaging tools in in vitro tests. As an example of non-macrophagic cells, a highly differentiated neuronal cell line (GT1-7) was used and the results showed that the prepared nanoparticles can be incorporated into these cells with no apparent toxicity for up to three days.     

High Mobility Group Box 1 Protein in Cerebral Thromboemboli

High-mobility group box 1 protein (HMGB1) is a damage-associated molecular pattern (DAMP) involved in neutrophil extracellular trap (NET) formation and thrombosis. NETs are regularly found in cerebral thromboemboli. We here analyzed associated HMGB1 expression in human thromboemboli retrieved via mechanical thrombectomy from 37 stroke patients with large vessel occlusion. HMGB1 was detected in all thromboemboli, accounting for 1.7% (IQR 0.6–6.2%) of the total thromboemboli area and was found to be colocalized with neutrophils and NETs and in spatial proximity to platelets. Correlation analysis revealed that the detection of HMGB1 was strongly related to the number of neutrophils (r = 0.58, p = 0.0002) and platelets (r = 0.51, p = 0.001). Our results demonstrate that HMGB1 is a substantial constituent of thromboemboli causing large vessel occlusion stroke.     

A priori performance assessment of line-less mobile assembly systems

Present assembly systems are often based on rigid, line-based approaches and are hindered in their reconfiguration capability. Line-less Mobile Assembly Systems (LMAS) are a novel approach for assembly organization. They improve flexibility through mobile resources, permitting spatiotemporal freedom in scheduling and resource assignment. This paper presents a method for a priori assessment of LMAS during the early stages of the assembly system design process. The method applies a modified, extended mean value analysis to a closed queuing network representation of LMAS to estimate performance. The method is validated model analysis and comparison on two use cases indicating plausible model behavior.     

Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca²⁺ release from the sarcoplasmic reticulum (0 mM Ca²⁺), but it reduced the subsequent tonic phase characterised by Ca²⁺ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca²⁺ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K⁺ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.     

Pt–Ba–Al2O3 for NOx storage and reduction: Characterization of the dispersed species

Pt–Ba–Al₂O₃ active and selective for NO_x storage and selective reduction to N₂ has been prepared and tested. Characterization of the parent Al₂O₃, Pt–Al₂O₃ and Ba–Al₂O₃ materials, as well as of Pt–Ba–Al₂O₃ catalyst in the oxidized, reduced and sulphated state has been performed by FT-IR spectroscopy of low-temperature adsorbed carbon monoxide and of adsorbed acetonitrile. XRD, TEM and XPS analyses have also been performed. Evidence for the predominance of Ba species, which are highly dispersed on the alumina support surface, and may be carbonated or sulphated, has been provided. Competitive interaction of Pt and Ba species with the surface sites of alumina has also been found.     

Enabling Electrocatalytic Fischer–Tropsch Synthesis from Carbon Dioxide Over Copper-based Electrodes

We report on the discovery that paraffins and olefins up to C₆ hydrocarbons can be obtained in CO₂ electroreduction at room temperature and atmospheric pressure by application of a commercially available Cu-electrode (Eurofysica), provided pretreatment by electropolishing is avoided. The product distribution follows the Schultz–Flory distribution and, depending on the applied potential, the chain growth probability (α) ranges from 0.23 to 0.31, values lower than those obtained in Fischer–Tropsch synthesis over heterogeneous Co- or Fe-based catalysts.     

The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.     

Graphene nanoplatelets composite membranes for thermal comfort enhancement in performance textiles

The advent of 2D nanostructured materials as advanced fillers for polymer matrix composites has opened the doors to a plethora of new industrial applications requiring both electric and thermal management. Unique properties, in fact, can arise from accurate selection and processing of 2D fillers and their matrix. Here, we report an innovative family of nanocomposite membranes based on polyurethane (PU) and graphene nanoplatelets (GNPs), designed to improve thermal comfort in functional textiles. GNP particles were thoroughly characterized (through Raman, atomic force microscopy, high-resolution TEM, scanning electron microscope), and showed high crystallinity (I_D/I_G = 0.127), low thickness (D50 < 6–8 layers), and high lateral dimensions (D50 ≈ 3 μm). When GNPs were loaded (up to 10% wt/wt) into the PU matrix, their homogeneous dispersion resulted in an increase of the in-plane thermal conductivity of composite membranes up to 471%. The thermal dissipation of membranes, alone or coupled with cotton fabric, was further evaluated by means of an ad hoc system designed to simulate a human forearm. The results obtained provide a new strategy for the preparation of membranes suitable for technical textiles, with improved thermal comfort.     

Novel KCND3 Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt KV4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties

KCND3 encodes the voltage-gated potassium channel K_V4.3 that is highly expressed in the cerebellum, where it regulates dendritic excitability and calcium influx. Loss-of-function K_V4.3 mutations have been associated with dominant spinocerebellar ataxia (SCA19/22). By targeted NGS sequencing, we identified two novel KCND3 missense variants of the K_V4.3 channel: p.S347W identified in a patient with adult-onset pure cerebellar syndrome and p.W359G detected in a child with congenital nonprogressive ataxia. Neuroimaging showed mild cerebellar atrophy in both patients. We performed a two-electrode voltage-clamp recording of K_V4.3 currents in Xenopus oocytes: both the p.G345V (previously reported in a SCA19/22 family) and p.S347W mutants exhibited reduced peak currents by 50%, while no K+ current was detectable for the p.W359G mutant. We assessed the effect of the mutations on channel gating by measuring steady-state voltage-dependent activation and inactivation properties: no significant alterations were detected in p.G345V and p.S347W disease-associated variants, compared to controls. K_V4.3 expression studies in HEK293T cells showed 53% (p.G345V), 45% (p.S347W) and 75% (p.W359G) reductions in mutant protein levels compared with the wildtype. The present study broadens the spectrum of the known phenotypes and identifies additional variants for KCND3-related disorders, outlining the importance of SCA gene screening in early-onset and congenital ataxia.