Development of α-Tocopherol Acetate Nanoparticles: Influence of Preparative Processes

We studied different methods of preparing α-tocopherol acetate (ATA) nanoparticles, which are to be used in targeting the lungs as aerosols in order to prevent cigarette smoke toxicity. Poly-(lactide) nanoparticles were prepared using nanoprecipitation and solvent evaporation techniques, which produced, respectively, too small and too large nanoparticles to be aerosolized. The emulsification-diffusion method produced 2 months stable nanoparticles with a size between (500–700 nm). Increasing ATA concentration (1–7 mg/mL) induced a decrease in the association rate (97–93%) and in the adsorbed ATA rate (7–4.5%), which was associated with variations of Zeta potentials (?27.5 to ?24.3 mV) and decrease in polymeric wall thickness and density.     

On the effective conductivity and the apparent viscosity of a thin rough polymer interface using PGD-based separated representations

Composite manufacturing processes usually proceed from preimpregnated preforms that are consolidated by simultaneously applying heat and pressure, so as to ensure a perfect contact compulsory for making molecular diffusion possible. However, in practice, the contact is rarely perfect. This results in a rough interface where air could remain entrapped, thus affecting the effective thermal conductivity. Moreover, the interfacial melted polymer is squeezed flowing in the rough gap created by the fibers located on the prepreg surfaces. Because of the typical dimensions of a composite prepreg, with thickness orders of magnitude smaller than its other in-plane dimensions, and its surface roughness having a characteristic size orders of magnitude smaller than the prepreg thickness, high-fidelity numerical simulations for elucidating the impact of surface and interface roughness remain today, despite the impressive advances in computational availabilities, unattainable. This work aims at elucidating roughness impact on heat conduction and the effective viscosity of the interfacial polymer squeeze flow by using an advanced numerical strategy able to reach resolutions never attained until now, a sort of numerical microscope able to attain the scale of the smallest geometrical detail.     

New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune checkpoints, and toll-like receptor 2 (TLR2) are major targets. Magrolimab antagonizes CD47, which is overexpressed by AML and MDS cells, thus inducing macrophage phagocytosis with clinical activity in AML/MDS. Sabatolimab, an inhibitor of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), which disrupts its binding to galectin-9, has shown promising results in AML/MDS, enhancing the effector functions of lymphocytes and triggering tumor cell death. Several other surface molecules, namely CD33, CD123, CD45, and CD70, can be targeted with monoclonal antibodies (mAbs) that exert different mechanisms of action and include naked and conjugated antibodies, bispecific T-cell engagers, trispecific killer engagers, and fusion proteins linked to toxins. These novel mAbs are currently under investigation for use as monotherapy or in combination with hypomethylating agents, BCL2 inhibitors, and chemotherapy in various clinical trials at different phases of development. Here, we review the main molecular targets and modes of action of novel mAb-based immunotherapies, which can represent the future of AML and higher risk MDS treatment.     

White and green tea polyphenols inhibit pancreatic lipase in vitro

Green, white and black teas were assayed for inhibition of pancreatic lipase activity in vitro. White tea proved to be more effective than green tea with black tea showing little inhibition even at 200 μg GAE/ml. The EC₅₀ values for inhibition were 22 μg/ml for white tea and 35 μg/ml for green tea; both easily achievable from normal infusions of tea. Liquid chromatography-mass spectroscopy analysis showed that white and green teas had essentially equal amounts of flavan-3-ols but green tea had higher levels of flavonols. White tea had higher levels of 5-galloyl quinic acid, digalloyl glucose, trigalloyl glucose and the tannin, strictinin.After chromatography on Sephadex LH-20, the main inhibitory fraction was enriched in strictinin and fractions enriched in other components were ineffective. This suggests that strictinin content may be crucial for inhibition of pancreatic lipase. However, the possibility of synergies between the polyphenols cannot be disregarded.     

Microgrids and resilience: Using a systems approach to achieve climate adaptation and mitigation goals

Although energy resource sustainability has been researched extensively, the understanding of how we use and interact with electricity sustainably is less understood. New electrical designs, like microgrids, provide opportunities to better address the immediate needs of electrical sustainability and urban development. This paper analyzes the role of microgrids in urban development and examines how greater systemic thinking between infrastructure planning and energy policymaking can increase a city’s resilience.     

Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.