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Herein we report the preparation of C4‐functionalized proline‐derived azabicycloalkane (Aba) amino acids by exploiting a direct ring closing enyne metathesis reaction of readily accessible dipeptide precursors. The reverse‐turn inducing properties of the newly synthesized constrained dipeptide mimics were assessed by computational studies. Furthermore, the desired Aba derivatives, carrying a synthetically versatile diene moiety, were subjected to post‐functionalization reactions to validate their potential application in peptide/peptidomimetic chemistry and drug discovery. [ABSTRACT FROM AUTHOR]

Adherence to positive airway pressure treatment is crucial in managing obstructive sleep apnoea (OSA). However, the need for continuous usage poses a significant challenge. Introducing AI-supported educational programs offers a unique opportunity. These programs can facilitate the creation of interactive learning paths for patients, providing personalized information and practical advice based on their health conditions. The goal is to develop a personalized educational platform leveraging AI to improve adherence, therapeutic efficacy, and quality of life for patients with OSA. [ABSTRACT FROM AUTHOR]

IntroductionExposure to environmental contaminants during pregnancy is one of the determinants of child’s future health outcomes. The effect of environmental pollution on pregnant women living in heavily polluted areas is of special interest and, in this context, the Neonatal Environment and Health Outcomes (NEHO) cohort will focus on the investigation of (1) toxicants transferred from the environment to the mother and from the mother to the developing fetus and (2) the influence of toxicants on pregnancy outcomes, fetal development and health status during infancy. Because the human placenta is positioned at the interface between the maternal/external environment and the embryo, it can be considered a highly informative matrix regarding many key pregnancy events that can shape infant’s future health.Methods and analysisThe NEHO cohort will enrol an estimated total of 800 pregnant women in three selected National Priority Contaminated Sites in southern Italy. Epidemiological data, concerning maternal health status, lifestyle and pregnancy, are obtained through questionnaires provided to the mother starting from the last 2 months of pregnancy. At delivery, maternal blood, umbilical cord blood and placenta tissue are collected to assess contaminant levels and to clarify how toxicants interact with the placental domain. Furthermore, placental transcriptome is studied in order to explore the interferences of toxicants on the role of the placenta in maternal/fetal interplay. Regular follow-up is planned at 6, 12 and 24 months.Ethics and disseminationThe study has been approved by all the Ethics Committees of the three National Priority Contaminated Sites involved: the Ethics Committee of the University Hospitals of Messina (18 September 2017, n. 9/2017); the Ethics Committee ‘Catania 2’ (11 July 2017, n. 38/2017/CECT2); the Ethics Committee of the Region of Calabria (20 July 2017, n. 173). Findings will be disseminated in the scientific community and on a regional basis for appropriate policy actions.

Simple Summary: For many types of cancer, chemotherapy is still widely used, but it can cause serious side effects because it kills all rapidly growing cells, not just the cancerous ones. In this paper, a nanoparticle-based drug delivery system has been designed to selectively deliver a highly cytotoxic drug to tumor cells. The nanoparticles, obtained from a protein called silk fibroin, have been loaded with a naphthalene diimide derivative, namely NDI-1, which kills cells by affecting their DNA. The surface of the silk fibroin nanoparticles has been decorated with cyclopentapeptides incorporating the Arg-Gly-Asp sequence (cRGDs) to specifically target the tumor cells, thus reducing the harm to healthy cells and minimizing side effects. Developing drug delivery systems to target cytotoxic drugs directly into tumor cells is still a compelling need with regard to reducing side effects and improving the efficacy of cancer chemotherapy. In this work, silk fibroin nanoparticles (SFNs) have been designed to load a previously described cytotoxic compound (NDI-1) that disrupts the cell cycle by specifically interacting with non-canonical secondary structures of DNA. SFNs were then functionalized on their surface with cyclic pentapeptides incorporating the Arg-Gly-Asp sequence (cRGDs) to provide active targeting toward glioma cell lines that abundantly express ανβ3 and ανβ5 integrin receptors. Cytotoxicity and selective targeting were assessed by in vitro tests on human glioma cell lines U373 (highly-expressing integrin subunits) and D384 cell lines (low-expressing integrin subunits in comparison to U373). SFNs were of nanometric size (d50 less than 100 nm), round shaped with a smooth surface, and with a negative surface charge; overall, these characteristics made them very likely to be taken up by cells. The active NDI-1 was loaded into SFNs with high encapsulation efficiency and was not released before the internalization and degradation by cells. Functionalization with cRGDs provided selectivity in cell uptake and thus cytotoxicity, with a significantly higher cytotoxic effect of NDI-1 delivered by cRGD-SFNs on U373 cells than on D384 cells. This manuscript provides an in vitro proof-of-concept of cRGD-silk fibroin nanoparticles' active site-specific targeting of tumors, paving the way for further in vivo efficacy tests. [ABSTRACT FROM AUTHOR]

Introduction Exposure to environmental contaminants during pregnancy is one of the determinants of child's future health outcomes. The effect of environmental pollution on pregnant women living in heavily polluted areas is of special interest and, in this context, the Neonatal Environment and Health Outcomes (NEHO) cohort will focus on the investigation of (1) toxicants transferred from the environment to the mother and from the mother to the developing fetus and (2) the influence of toxicants on pregnancy outcomes, fetal development and health status during infancy. Because the human placenta is positioned at the interface between the maternal/external environment and the embryo, it can be considered a highly informative matrix regarding many key pregnancy events that can shape infant's future health. Methods and analysis The NEHO cohort will enrol an estimated total of 800 pregnant women in three selected National Priority Contaminated Sites in southern Italy. Epidemiological data, concerning maternal health status, lifestyle and pregnancy, are obtained through questionnaires provided to the mother starting from the last 2 months of pregnancy. At delivery, maternal blood, umbilical cord blood and placenta tissue are collected to assess contaminant levels and to clarify how toxicants interact with the placental domain. Furthermore, placental transcriptome is studied in order to explore the interferences of toxicants on the role of the placenta in maternal/fetal interplay. Regular follow-up is planned at 6, 12 and 24 months. Ethics and dissemination The study has been approved by all the Ethics Committees of the three National Priority Contaminated Sites involved: the Ethics Committee of the University Hospitals of Messina (18 September 2017, n. 9/2017); the Ethics Committee 'Catania 2' (11 July 2017, n. 38/2017/CECT2); the Ethics Committee of the Region of Calabria (20 July 2017, n. 173). Findings will be disseminated in the scientific community and on a regional basis for appropriate policy actions. [ABSTRACT FROM AUTHOR]

On a subfreezing surface, nucleating embryos usually form as supercooled condensate that later freezes into ice, as opposed to desublimation. Ice nucleating proteins (INPs) have been widely used to quickly freeze existing supercooled water; however, nobody has studied how they might affect the initial mode of embryo formation. We show that INPs deposited on a substrate can switch the mode of embryo nucleation to desublimation, rather than supercooled condensation, beneath a critical temperature. By patterning a hydrophobic surface with an array of hydrophilic stripes, the INPs can be selectively deposited by evaporating water that exclusively spreads along the hydrophilic regions. The resulting array of desublimating ice stripes created dry zones free of condensation or frost in the intermediate areas, as the hygroscopic ice stripes served as overlapping humidity sinks. [ABSTRACT FROM AUTHOR]

Simple Summary: Many tumor cell types overexpress integrins, a glycoprotein, on their cell membranes. The tripeptide motif Arg-Gly-Asp (RGD) is well-known for being recognized by the integrin superfamily members and can thus be used to actively target nanoparticles containing cytotoxic drugs directly to the tumor cells. According to this strategy, the antitumor activity is boosted, and healthy organs are spared. In this paper, silk fibroin, a naturally derived protein, has been used to prepare nanoparticles (SFNs) functionalized on their surface with RGD. In vitro experiments revealed that functionalization of SFNs with RGD provided active internalization by tumor cells overexpressing integrin receptors. Therefore, RGD-SFNs may be used for tumor-specific delivery of anticancer drugs. Arg-Gly-Asp (RGD)-based cyclopentapeptides (cRGDs) have a high affinity towards integrin αvβ3 and αvβ5, which are overexpressed by many tumor cells. Here, curcumin-loaded silk fibroin nanoparticles (SFNs) have been functionalized on the surface with cRGD to provide active targeting towards tumor cells; a "click reaction" between the RGD-based cyclopentapeptide carrying an azide group and triple-bond-functionalized nanoparticles has been exploited. Both naked and functionalized SFNs were less than 200 nm in diameter and showed a round-shaped morphology but, after functionalization, SFNs increased in size and protein molecular weight. The functionalization of SFNs' surfaces with cRGD provided active internalization by cells overexpressing integrin receptors. At the lowest concentration tested (0.01 mg/mL), functionalized SFNs showed more effective uptake with respect to the naked by tumor cells that overexpress integrin receptors (but not for non-overexpressing ones). In contrast, at higher concentrations, the non-specific cell membrane protein–particle interactions are promoted and coupled to specific and target mediated uptake. Visual observations by fluorescence microscopy suggested that SFNs bind to integrin receptors on the cell surface and are then internalized by endocytosis. Overall, SFN functionalization provided in vitro active targeting for site-specific delivery of anticancer drugs, boosting activity and sparing healthy organs. [ABSTRACT FROM AUTHOR]