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Alzheimer’s disease (AD) causes a great socioeconomic burden because of its increasing prevalence and the lack of effective therapies. The multifactorial nature of AD prompts researchers to search for new strategies for discovering disease-modifying therapeutics. To this extent, the multitarget approach holds the potential of synergic or cooperative activities arising from compounds that are properly designed to address two or more pathogenetic mechanisms. As a privileged and nature-friendly scaffold, coumarin has successfully been enrolled as the heterocyclic core in the design of multipotent anti-Alzheimer’s agents. Herein, we comprehensively summarize the most recent literature (2018–2023), covering the rational design and the discovery of coumarin-containing multitarget directed ligands (MTDLs) whose anti-AD profile encompassed at least two different biological activities relevant for disease onset and progression. To enhance the clarity of presentation, synthetic coumarin-based MTDLs are categorized into four clusters based on their substitution pattern and reported bioactivities: (i) mono-, (ii) di-, and (iii) polysubstituted coumarins directed at protein targets, and (iv) coumarins directed at protein targets with additional metal-chelating features. Before discussing multimodal coumarins, the rationale for addressing each biological target is briefly presented.

L’articolo indaga le ragioni del profondo impatto che le “rivoluzioni colorate” dei primi anni Duemila hanno avuto sulle percezioni politico-strategiche della Russia. Lo scopo del lavoro è quello di mettere in evidenza alcuni aspetti delle “rivoluzioni colorate” suscettibili di rafforzare la tendenza della Russia ad attribuire alle potenze occidentali intenzioni ostili nei suoi confronti, in particolare l’attivismo in Georgia e Ucraina di ONG occidentali già coinvolte nel political warfare condotto dagli Stati Uniti in Polonia negli anni di Reagan (sostegno a Solidarnošc) e ancora in Serbia nel dopo-Guerra fredda (aiuti alle opposizioni attive nel rovesciamento di Slobodan Miloševic nel 2000). L’articolo mostra come le locuzioni “rivoluzione colorata” e “guerra ibrida” siano diventate sinonimi nel recente discorso strategico russo, e come il political warfare statunitense in Polonia e il rovesciamento di Miloševic in Serbia vengano considerati dai russi come dei precedenti delle “rivoluzioni colorate”.

Abstract A plethora of different electronic and optoelectronic devices have been developed lately, for biosensing applications (e.g., label‐free, fast, and easier to operate) based on a detecting interface accommodating the biorecognition elements, anchored by thiolate self‐assembled monolayers (SAMs) on a gold surface. Here, a surface plasmon resonance (SPR) characterization of anti‐p24 anchored on different SAMs is performed to investigate the effect of the SAM structure on the antibodies’ packing efficiency and the sensors’ analytical figures of merit. Notably, the mixed SAM deposited from a solution 10:1 of 3‐mercaptopropionic acid and 11‐mercaptoundecanoic acid (11MUA) is compared to that resulting from a solution 10:1 of ad hoc synthesized N‐(2‐hydroxyethyl)‐3‐mercaptopropanamide (NMPA)/11MUA. Despite the improvement in the anti‐p24 surface coverage registered using the 11MUA/NMPA SAM, the latter produces a significant decrease in the antibodies’ binding efficiency against human immunodeficiency virus p24 protein. To provide a molecular rationale behind the SPR data, density functional theory calculations are also undertaken. A comprehensive physical view of the main competing phenomena affecting the biorecognition events at a biofunctionalized gold detecting interface is represented here.

The coumarin core (i.e., 1-benzopyran-2 (2H)-one) is a structural motif highly recurrent in both natural products and bioactive molecules. Indeed, depending on the substituents and branching positions around the byciclic core, coumarin-containing compounds have shown diverse pharmacological activities, ranging from anticoagulant activities to anti-inflammatory, antimicrobial, anti-HIV and antitumor effects. In this survey, we have reported the main scientific results of the 20-years investigation on the coumarin core, exploited by the research group headed by Prof. Angelo Carotti (Bari, Italy) either as a scaffold or a pharmacophore moiety in designing novel biologically active small molecules.

Acute monoblastic/monocytic leukemia (AMoL), previously defined as M5 according to FAB classification, is one of the most common subtypes of Acute Myeloid Leukemia (AML) in children, representing ~15–24% of all pediatric AMLs. Currently, the characterization of monocytic-lineage neoplasia at diagnosis includes cytomorphology, cytochemistry, immunophenotyping by multiparametric flow cytometry, cytogenetics, and molecular biology. Moreover, measurable residual disease (MRD) detection is critical in recognizing residual blasts refractory to chemotherapy. Nonetheless, diagnosis and MRD detection may still be challenging in pediatric AMoL since the morphological and immunophenotypic features of leukemic cells potentially overlap with those of normal mature monocytic compartment, as well as differential diagnosis can be troublesome, particularly with Juvenile Myelomonocytic Leukemia and reactive monocytosis in infants and young children. A failure or delay in diagnosis and inaccuracy in MRD assessment may worsen the AMoL prognosis. Therefore, improving diagnosis and monitoring techniques is mandatory to stratify and tailor therapies to the risk profile. This Mini Review aims to provide an updated revision of the scientific evidence on pediatric AMoL diagnostic tools.

In the recent years, scholars of International Relations have increasingly highlighted the blurring of boundaries between war and peace, identifying this as a major trend in contemporary international politics. Notably, many of the concepts coined after the Cold War to capture the transformation of warfare (i.e. «asymmetric war», «unrestricted warfare», «hybrid war», «gray zone strategies») center on the growing ambiguity between war and peace. This article examines these concepts, arguing that the «transformations» they describe often, and somewhat ironically, underscore the enduring centrality of political warfare in global politics. [ABSTRACT FROM AUTHOR]

This comprehensive review, covering 2021-2023, explores the multifaceted chemical and pharmacological potential of coumarins, emphasizing their significance as versatile natural derivatives in medicinal chemistry. The synthesis and functionalization of coumarins have advanced with innovative strategies. This enabled the incorporation of diverse functional fragments or the construction of supplementary cyclic architectures, thereby the biological and physico-chemical properties of the compounds obtained were enhanced. The unique chemical structure of coumarine facilitates binding to various targets through hydrophobic interactions pi-stacking, hydrogen bonding, and dipole-dipole interactions. Therefore, this important scaffold exhibits promising applications in uncountable fields of medicinal chemistry (e.g., neurodegenerative diseases, cancer, inflammation). [ABSTRACT FROM AUTHOR]

Objective: This study was aimed to test the agreement between a manual and an automatic technique in measuring fetal brain volume (FBV) from three‐dimensional (3D) fetal head datasets. Methods: FBV were acquired independently by two operators from low risk singleton pregnancies at a gestational age between 19 and 34 weeks. FBV measurements were obtained using an automatic software (Smart ICV™) and manually by Virtual Organ Computer‐aided AnaLysis (VOCAL™). Intraclass correlation coefficient (ICC) were calculated to assess reliability, while bias and agreement were evaluate by examining Bland–Altman plots. The time spent in measuring volumes was calculated and values obtained compared. Results: Sixty‐three volumes were considered for the study. In all the included volumes successful volume analysis were obtained with both techniques. Smart ICV™ showed a high intra‐observer (0.996; 95% CI 0.994–0.998) and inter‐observer (ICC 0.995; 95% CI 0.991–0.997). An excellent degree of reliability was found when the two techniques were compared (ICC 0.995; 95% CI 0.987–0.998). The time required to perform FBV was significantly lower for Smart ICV™ than VOCAL™ (8.2 ± 4.5 vs. 121.3 ± 19.0 s; p < 0.0001). Conclusions: The measurement of FBV is feasible with both manual and automatic techniques. Smart ICV™ showed an excellent intra‐ and inter‐observer reliability associated with a valuable agreement with volume measurements obtained manually with VOCAL™. Volumes may be measured significantly faster with smart ICV™ than manually and this automatic software has the potential to become the preferred methods for the assessment of FBV. [ABSTRACT FROM AUTHOR]

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