Versatile Synthesis of Pyrrole‐2‐acetic Esters and (Pyridine‐2‐one)‐3‐acetic Amides by Palladium‐Catalyzed,Carbon Dioxide‐Promoted Oxidative Carbonylation of (Z)‐(2‐En‐4‐ynyl)amines

The oxidative carbonylation of readily available (Z)‐(2‐en‐4‐ynyl)amines, catalyzed by the PdI₂‐KI system, selectively afforded in satisfactory yields (40–95 %) either pyrrole‐2‐acetic ester or (pyridine‐2‐one)‐3‐acetic amide derivatives, depending on the susbtitution pattern of the substrate and the reaction conditions. The presence of an excess of carbon dioxide proved in most cases to be beneficial to both the reaction rate and product selectivity.     

Blood–Brain Barrier in Brain Tumors: Biology and Clinical Relevance

The presence of barriers, such as the blood–brain barrier (BBB) and brain–tumor barrier (BTB), limits the penetration of antineoplastic drugs into the brain, resulting in poor response to treatments. Many techniques have been developed to overcome the presence of these barriers, including direct injections of substances by intranasal or intrathecal routes, chemical modification of drugs or constituents of BBB, inhibition of efflux pumps, physical disruption of BBB by radiofrequency electromagnetic radiation (EMP), laser-induced thermal therapy (LITT), focused ultrasounds (FUS) combined with microbubbles and convection enhanced delivery (CED). However, most of these strategies have been tested only in preclinical models or in phase 1–2 trials, and none of them have been approved for treatment of brain tumors yet. Concerning the treatment of brain metastases, many molecules have been developed in the last years with a better penetration across BBB (new generation tyrosine kinase inhibitors like osimertinib for non-small-cell lung carcinoma and neratinib/tucatinib for breast cancer), resulting in better progression-free survival and overall survival compared to older molecules. Promising studies concerning neural stem cells, CAR-T (chimeric antigen receptors) strategies and immunotherapy with checkpoint inhibitors are ongoing.     

Influence of O contamination and Au cluster properties on the structural features of Si nanowires

Silicon nanowires (Si NWs) are the emerging nanostructures for future nanodevices. In this work we have prepared them by electron beam evaporation (EBE) through the vapor-liquid-solid (VLS) mechanism. We discuss the growth of epitaxial NWs by EBE and the possibility to control their orientation and length by changing the experimental conditions. Moreover, the effects of the surface contamination and of the Au cluster preparation on the NWs structural properties and density will be discussed. We demonstrate that any O contamination has to be avoided since just a very thin native SiO₂ layer stops ad-atom diffusion on the surface and inhibits the NWs growth. Au cluster preparation has a determinant role too: by varying the procedure for their formation, it is possible to change NWs density and length. In particular, we observed that by evaporating Au on the heated substrate, the droplets active to promote NW growth are immediately formed and a faster growth process starts. The growth rate is about a factor of 4 times higher than in the sample where the Au is evaporated at room temperature and the cluster formed after a subsequent thermal annealing. On the contrary, the slower process allows the atom arrangement and ordering in an epitaxial manner, and a precise control of NW orientation can be achieved.     

Ageing Causes Ultrastructural Modification to Calcium Release Units and Mitochondria in Cardiomyocytes

Ageing is associated with an increase in the incidence of heart failure, even if the existence of a real age-related cardiomyopathy remains controversial. Effective contraction and relaxation of cardiomyocytes depend on efficient production of ATP (handled by mitochondria) and on proper Ca²⁺ supply to myofibrils during excitation–contraction (EC) coupling (handled by Ca²⁺ release units, CRUs). Here, we analyzed mitochondria and CRUs in hearts of adult (4 months old) and aged (≥24 months old) mice. Analysis by confocal and electron microscopy (CM and EM, respectively) revealed an age-related loss of proper organization and disposition of both mitochondria and EC coupling units: (a) mitochondria are improperly disposed and often damaged (percentage of severely damaged mitochondria: adults 3.5 ± 1.1%; aged 16.5 ± 3.5%); (b) CRUs that are often misoriented (longitudinal) and/or misplaced from the correct position at the Z line. Immunolabeling with antibodies that mark either the SR or T-tubules indicates that in aged cardiomyocytes the sarcotubular system displays an extensive disarray. This disarray could be in part caused by the decreased expression of Cav-3 and JP-2 detected by western blot (WB), two proteins involved in formation of T-tubules and in docking SR to T-tubules in dyads. By WB analysis, we also detected increased levels of 3-NT in whole hearts homogenates of aged mice, a product of nitration of protein tyrosine residues, recognized as marker of oxidative stress. Finally, a detailed EM analysis of CRUs (formed by association of SR with T-tubules) points to ultrastructural modifications, i.e., a decrease in their frequency (adult: 5.1 ± 0.5; aged: 3.9 ± 0.4 n./50 μm²) and size (adult: 362 ± 40 nm; aged: 254 ± 60 nm). The changes in morphology and disposition of mitochondria and CRUs highlighted by our results may underlie an inefficient supply of Ca²⁺ ions and ATP to the contractile elements, and possibly contribute to cardiac dysfunction in ageing.     

Synthesis and Biological Evaluation of New Geiparvarin Derivatives

New geiparvarin derivatives modified at the alkenyloxy bridge, where the 3′‐methyl group was replaced by a hydrogen atom, were synthesized and evaluated against a panel of human tumor cell lines in vitro. Compounds (R)‐ 4 and (R)‐ 5 show greater inhibitory activity toward cell growth than the parent geiparvarin.

     

Mesoporous multifunctional upconversion luminescent and magnetic "nanorattle" materials for targeted chemotherapy

Nanorattles consisting of hydrophilic, rare-earth-doped NaYF(4) shells each containing a loose magnetic nanoparticle were fabricated through an ion-exchange process. The inner magnetic Fe(3)O(4) nanoparticles are coated with a SiO(2) layer to avoid iron leaching in acidic biological environments. This multifunctional mesoporous nanostructure with both upconversion luminescent and magnetic properties has excellent water dispersibility and a high drug-loading capacity. The material emits visible luminescence upon NIR excitation and can be directed by an external magnetic field to a specific target, making it an attractive system for a variety of biological applications. Measurements on cells incubated with the nanorattles show them to have low cytotoxicity and excellent cell imaging properties. In vivo experiments yield highly encouraging tumor shrinkage with the antitumor drug doxorubicin (DOX) and significantly enhanced tumor targeting in the presence of an applied magnetic field.     

Encapsulating Eu3+ complex doped layers to improve Si‐based solar cell efficiency

This paper reports the electrical characterization of commercially available crystalline silicon solar cells encapsulated with poly‐vinylacetate doped with different Eu³⁺ organic complexes. The inclusion of these complexes in the encapsulating matrix allows down‐shifting of the solar spectrum components below 420 nm toward the maximum quantum efficiency of the solar cells. This effect has been proven under Air Mass 1·5 conditions (simulating terrestrial applications) where an increase of the total power delivered by the encapsulated cells has been observed. Moreover, this enhancement has been obtained using very low percentage by weight of organolanthanide dopants, allowing a reduction in the Watt peak price. At higher concentrations a strong quenching of the energy transfer from the organic antenna to the lanthanide ion has been observed. Copyright © 2009 John Wiley & Sons, Ltd.     

Sex and HDAC4 Differently Affect the Pathophysiology of Amyotrophic Lateral Sclerosis in SOD1-G93A Mice

Amyotrophic Lateral Sclerosis (ALS) is a devastating adult-onset neurodegenerative disease, with ineffective therapeutic options. ALS incidence and prevalence depend on the sex of the patient. Histone deacetylase 4 (HDAC4) expression in skeletal muscle directly correlates with the progression of ALS, pointing to the use of HDAC4 inhibitors for its treatment. Contrarily, we have found that deletion of HDAC4 in skeletal muscle worsened the pathological features of ALS, accelerating and exacerbating skeletal muscle loss and negatively affecting muscle innervations in male SOD1-G93A (SOD1) mice. In the present work, we compared SOD1 mice of both sexes with the aim to characterize ALS onset and progression as a function of sex differences. We found a global sex-dependent effects on disease onset and mouse lifespan. We further investigated the role of HDAC4 in SOD1 females with a genetic approach, and discovered morpho-functional effects on skeletal muscle, even in the early phase of the diseases. The deletion of HDAC4 decreased muscle function and exacerbated muscle atrophy in SOD1 females, and had an even more dramatic effect in males. Therefore, the two sexes must be considered separately when studying ALS.