Cellular internalisation, bioimaging and dark and photodynamic cytotoxicity of silica nanoparticles doped by {Mo₆I₈}⁴⁺ metal clusters

Silica nanoparticles (SNPs) doped by hexanuclear molybdenum cluster complexes [{Mo₆X₈}L₆]n (X = Cl, Br, or I; L = various inorganic or organic ligands) have been recently suggested as materials with a high potential for biomedical applications due to both the outstanding photoluminescent properties and the ability to efficiently generate singlet oxygen upon photoirradiation. However, no studies were undertaken so far to prove this concept. Therefore, here we examined the potential of photoluminescent SNPs doped by {Mo₆I₈}⁴⁺ for such applications as bioimaging and photodynamic therapy using human epidermoid larynx carcinoma (Hep-2) cell line as a model. Our results demonstrated both: (i) significant luminescence from cells with internalised molybdenum cluster doped SNPs combined with the low cytotoxicity of particles in the darkness and (ii) significant cytotoxicity of the particles upon photoirradiation. Thus, this research provides strong experimental evidence for high potential of molybdenum cluster doped materials in such biomedical applications as optical bioimaging, biolabeling and photodynamic therapy

Luminescent silica mesoparticles for protein transduction

Unlike silica nanoparticles, the potential of silica mesoparticles (SMPs) (i.e. particles of submicron size) for biological applications in particular the in vitro (let alone in vivo) cellular delivery of biological cargo has so far not been sufficiently studied. Here we examine the potential of luminescent (namely, octahedral molybdenum cluster doped) SMPs synthesised by a simple one-pot reaction for the labelling of cells and for protein transduction into larynx carcinoma (Hep-2) cells using GFP as a model protein. Our data demonstrates that the SMPs internalise into the cells within half an hour. This results in cells that detectably luminesce via conventional methods. In addition, the particles are non-toxic both in darkness and upon photo-irradiation. The SMPs were modified to allow their functionalisation by a protein, which then delivered the protein (GFP) efficiently into the cells. Thus, the luminescent SMPs offer a cheap and trackable alternative to existing materials for cellular internalisation of proteins, such as the HIV TAT protein and commercial protein delivery agents (e.g. Pierce™)

Brain imaging of the cortex in ADHD: a coordinated analysis of large-scale clinical and population-based samples

Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. Methods: Cortical thickness and surface area (based on the Desikan–Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen’s d=−0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis

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

Influence Of Precursor Dispersity And Agglomeration On Mechanical Characteristics Of Zro2-Ce2O3 And Zro2-Y2O3-Ce2O3 Ceramics

Powder precursors of ZrO2 - Ce2O3 and ZrO2- Y2O3 - Ce2P3 systems were synthesized by sol-gel method. Dispersity of the powders depended on concentrations of starting reagents and synthesis conditions. To characterize the powder dispersity and aggregated state, electron microscopy and laser scattering particle size distribution analysis were used. Ceramic samples were prepared from these powder precursors; their mechanical characteristics were studied by three points bending method at 1000°C. It was revealed that bending strength - particle size curve for ZrO2- Ce2O3 system has a pronounced maximum. This phenomenon is explained by a change in cerium valence depending on powder precursor agglomerate size. © 2007 Advanced Study Center Co. Ltd

Epidemiological significance of detection of SARS-CoV-2 RNA among different groups of population of Moscow and Moscow Region during the COVID-19 outbreak

The Central Research Institute of Epidemiology of Rospotrebnadzor presents priority data obtained from the largescale population PCR-based study of the changes in the rates of circulation of SARS-CoV-2 among relatively healthy residents of Moscow and Moscow Region

Interglacial History of a Palaeo-lake and Regional Environment: A Multi-proxy Study of a Permafrost Deposit from Bolshoy Lyakhovsky Island, Arctic Siberia

Chironomid, pollen, and rhizopod records from a permafrost sequence at the Bolshoy Lyakhovsky Island (New Siberian Archipelago) document the evolution of a thermokarst palaeo-lake and environmental conditions in the region during the Last Interglacial (MIS 5e, ca. 130120 ka). Open Poaceae and Artemisia associations dominated vegetation at the beginning of the interglacial period, ca. 130 ka. Rare shrub thickets (Salix, Betula nana, Alnus fruticosa) grew in more protected and wetter places as well. Saalian ice wedges started to melt during this time, resulting in the formation of an initial thermokarst water body. The high percentage of semi-aquatic chironomids suggests that a peatland-pool palaeo-biotope existed at the site, when initial water body started to form. A distinct decrease in semi-aquatic chironomid taxa and an increase in lacustrine ones point to a gradual pooling of water in basin, which could in turn create thaw a permanent pond during the subsequent period. The highest relative abundance of Chironomus and Procladius reflects an existence of unfrozen water remaining under the ice throughout the ice-covered period during the later stage of palaeo-lake development. Chironomid record points to three successive stages during the water body evolution: (1) a peatland pool; (2) a pond (i.e., less deep than the maximum ice-cover thickness); and (3) a shallow lake (i.e., more deep than the maximum ice-cover thickness). The evolutionary trend of palaeo-lake points to intensive thermokarst processes occurring in the region during the Last Interglacial. Shrub tundra communities with Alnus fruticosa, Betula nana dominated the vegetation during the interglacial optimum that is evidenced by pollen record. The climate was relatively moist and warm. The results of this study suggest that quantitative chironomid-based temperature reconstructions from the Arctic thermokarst ponds/lakes may be problematic owing to other key environmental factors, such as prolonged periods of winter anoxia and local hydrological/geomorphological processes, controlling the chironomid assemblage

Langmuir Monolayers and Thin Films of Amphifilic Thiacalix[4]arenes. Properties and Matrix for the Immobilization of Cytochrome <i>c</i>

Formation and properties of Langmuir films of thiacalix[4]­arene (TCA) derivatives containing N-donor groups on the lower rim (YO­(CH₂)₃CN; OCH₂CN; NH₂; OCH₂ArCN-<i>p</i>) in <i>1</i>,<i>3</i>-<i>alternate</i> conformation on aqueous subphase and solid substrates have been studied. Only <i>tetra</i>-cyanopropoxy-<i>p</i>-<i>tert</i>-butylthiacalix­[4]­arene <b>1</b> forms a typical monomolecular layer with perpendicular orientation of the macrocycle relative to the water–air interface that is able to immobilize cytochrome <i>c</i> in the entire range of the surface pressure. Obtained monolayers were transferred by Langmuir–Schaefer technique onto quartz, indium–tin oxide (ITO), and silicon. It was demonstrated that protein activity is retained after immobilization on the substrate

Hybrid Molecules of Azithromycin with Chloramphenicol and Metronidazole: Synthesis and Study of Antibacterial Properties

The sustained rise of antimicrobial resistance (AMR) causes a strong need to develop new antibacterial agents. One of the methods for addressing the problem of antibiotic resistance is through the design of hybrid antibiotics. In this work, we proposed a synthetic route for the conjugation of an azithromycin derivative with chloramphenicol and metronidazole hemisuccinates and synthesized two series of new hybrid molecules 4a–g and 5a–g. While a conjugation did not result in tangible synergy for wild-type bacterial strains, new compounds were able to overcome AMR associated with the inducible expression of the ermC gene on a model E. coli strain resistant to macrolide antibiotics. The newly developed hybrids demonstrated a tendency to induce premature ribosome stalling, which might be crucial since they will not induce a macrolide-resistant phenotype in a number of pathogenic bacterial strains. In summary, the designed structures are considered as a promising direction for the further development of hybrid molecules that can effectively circumvent AMR mechanisms to macrolide antibiotics