Knowledge and social capacity building for sustainable urban transformation

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Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Synthesis and Antimitotic and Tubulin Interaction Profiles of Novel Pinacol Derivatives of Podophyllotoxins

Several pinacol derivatives of podophyllotoxins bearing different side chains and functions at C-7 were synthesized through reductive cross-coupling of podophyllotoxone and several aldehydes and ketones. While possessing a hydroxylated chain at C-7, the compounds retained their respective hydroxyl group with either the 7α (podo) or 7β (epipodo) configuration. Along with pinacols, some C-7 alkylidene and C-7 alkyl derivatives were also prepared. Cytotoxicities against neoplastic cells followed by cell cycle arrest and cellular microtubule disruption were evaluated and mechanistically characterized through tubulin polymerization inhibition and assays of binding to the colchicine site. Compounds of the epipodopinacol (7β-OH) series behaved similarly to podophyllotoxin in all the assays and proved to be the most potent inhibitors. Significantly, 7α-isopropyl-7-deoxypodophyllotoxin (<b>20</b>), without any hydroxyl function, appeared as a promising lead compound for a novel type of tubulin polymerization inhibitors. Experimental results were in overall agreement with modeling and docking studies performed on representative compounds of each series

Secondary Oxide Phosphines to Promote Tandem Acyl–Alkyl Coupling/Hydrogen Transfer to Afford (Hydroxyalkyl)rhodium Complexes. Theoretical and Experimental Studies

Acyl­(σ-norbornenyl)­rhodium­(III) dimer [Rh­(μ-Cl)­(C₉H₆NCO)­(C₇H₉)­L]₂ (<b>1</b>) (C₇H₉ = σ-norbornenyl; L = 4-picoline, isoquinoline) reacts with diphenylphosphine oxide (SPO) to undergo a one-pot reaction involving (i) cleavage of the chloride bridges and coordination of the phosphine, (ii) C–C bond coupling between acyl and norbornenyl in a 18e species, and (iii) ligand-assisted outer-sphere O­(P)-to-O­(C) hydrogen transfer, to afford mononuclear 16e species [RhCl­{(C₉H₆NC­(O)­C₇H₉)­(Ph₂PO)­H}­(L)] (<b>2</b>) containing a quinolinyl-(norbornenylhydroxyalkyl) fragment hydrogen-bonded to a κ¹-<i>P</i>-phosphinite ligand. Pentacoordinated <b>2</b>, which adopt a distorted trigonal bipyramidal structure, are kinetic reaction products that transform into the thermodynamic favored isomers <b>3</b>. Structures <b>3</b> contain an unusual weak η¹-C anagostic interaction involving the rhodium atom and one carbon atom of the olefinic C–H bond of the norbornenyl substituent in the chelating quinolinyl-hydroxyalkyl moiety. Their structure can be described as pseudoctahedral, through a 5 + 1 coordination, with the anagostic interaction in a trans disposition with respect to the phosphorus atom of the phosphinite ligand. Complexes were characterized in solution by NMR spectroscopy and electrospray ionization mass spectrometry. Complex [RhCl­{(C₉H₆NC­(O)­C₇H₉)­(Ph₂PO)­H}­(4-picoline)] (<b>3a</b>) was also identified by X-ray diffraction. Density functional theory calculations confirm the proposed structures by a plausible set of mechanisms that accounts for the <b>1</b> (monomer) → <b>2</b> → <b>3</b> transformation. Lowest-energy pathways involve reductive elimination of quinolinylnorbornenylketone, still coordinated in the rhodium­(I) species thus formed, followed by O-to-O hydrogen transfer from κ¹-<i>P</i>-SPO to the sp³ hybridized carbonyl group (formal alkoxide) avoiding the otherwise expected classical release of ketone. Theoretical ¹³C NMR studies also confirm the experimental spectral data for the considered structures

Fast Electrochemical miRNAs Determination in Cancer Cells and Tumor Tissues with Antibody-Functionalized Magnetic Microcarriers

Microribonucleic acids (miRNAs) have been linked with various regulatory functions and diseases and constitute important targets in future medical diagnostics and prognostics. We report here a novel sensitive and rapid bioelectrochemical strategy for miRNA determination. This strategy involves the development of a sensing approach making use of magnetic beads (MBs) modified with a specific DNA-RNA antibody as capture bioreceptor and amperometric detection implying the H₂O₂/hydroquinone (HQ) system at disposable screen-printed carbon electrodes (SPCEs). The developed biosensor exhibits a dynamic range from 8.2 to 250 pM and a detection limit of 2.4 pM (60 amol) of a synthetic target without any amplification step in 2 h. The usefulness of the approach was evaluated by analyzing total RNA (RNA_t) extracted from metastatic cancer cell lines and human tumor tissues, which demonstrated its potential to perform determination of mature miRNAs in these complex samples. Moreover, the feasibility of the developed methodology to detect simultaneously the expression of two different miRNAs at dual SPCEs (SPdCEs) in one single experiment was also explored. The feasibility to capture and release target miRNAs make the developed methodology also an attractive tool to isolate, purify, and determine target miRNAs with great applicability in the clinical field