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Titanium dioxide (TiO 2 ) is one of the most commonly used nanomaterials in the world. Additive E171, which is used in the food industry, contains a nanometric particle fraction of TiO 2 . Oral exposure of humans to these nanoparticles (NPs) is intensive, leading to the question of their impact on health. Daily oral intake by rats of amounts of E171 that are relevant to human intake has been associated with an increased risk of chronic intestinal inflammation and carcinogenesis. Due to their food preferences, children are very exposed to this NP. Furthermore, maternal-foetal transfer of TiO 2 NPs during pregnancy, as well as exposure of the offspring by breastfeeding , have been recently described. In France, the use of E171 in the production of foodstuffs was suspended in January 2020 as a precautionary measure. To provide some answers to this public health problem and help global regulatory agencies finalize their decisions, we reviewed in vitro and in vivo studies that address the effects of TiO 2 NPs through oral exposure, especially their effects on the gastrointestinal tract, one of the most exposed tissues. Our review also highlights the effects of exposure on the offspring during pregnancy and by breastfeeding .

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting millions worldwide and imposing a significant social and economic burden. Despite extensive research, there is still no effective cure for this disease. AD is multifactorial and involves multiple etiopathogenic mechanisms, one of which is oxidative stress. Consequently, the Nrf2/ARE pathway, which regulates the expression of cellular defense genes, including those for antioxidant enzymes, is considered to be a prospective therapeutic target for AD. Meanwhile, multitarget-directed ligands (MTDLs) are a promising approach for developing effective AD medications. In this regard, we evaluated the antioxidant potential of eight chromone-containing MTDLs in vitro, including Nrf2 transcriptional activation potencies, Nrf2/ARE downstream genes activation, and antioxidant effects in vitro. All tested compounds effectively activated the Nrf2/ARE pathway. Notably, compounds 4b, 4c, 4f, and 4h demonstrated the highest Nrf2 activation potencies, while compounds 4b, 4c, 4d, and 4g significantly induced the expression of Nrf2-target antioxidant genes, specifically NQO1 and HO1. Additionally, compound 4d exhibited a significant antioxidant effect in vitro. These findings encourage further investigation of the studied compounds, with particular emphasis on compound 4d as the most promising candidate.

Interspecies hybrids often show some advantages over parents but also frequently suffer from reduced fertility, which can sometimes be overcome through sexual reproduction that sorts out genetic incompatibilities. Sex is however inefficient due to the low viability or fertility of hybrid offspring and thus limits their evolutionary potential. Mitotic cell division could be an alternative to fertility recovery in species such as fungi that can also propagate asexually. Here, to test this, we evolve in parallel and under relaxed selection more than 600 diploid yeast inter-specific hybrids that span from 100,000 to 15 M years of divergence. We find that hybrids can recover fertility spontaneously and rapidly through whole-genome duplication. These events occur in both hybrids between young and well-established species. Our results show that the instability of ploidy in hybrid is an accessible path to spontaneous fertility recovery. Hybridization across species can lead to offspring with reduced fertility. Here, the authors experimentally evolve yeast and show that whole-genome duplication during asexual reproduction can restore fertility in hybrids over a relatively short evolutionary timespan.

Background Epigenetic variations, particularly in response to environmental factors, play a crucial role in shaping immune identity and function in hematopoietic cells. This study investigates interindividual differences in DNA methylation among dairy cows, with the aim of enhancing our understanding of the adaptive capacity essential for sustainable animal production. We conducted whole-genome sequencing and DNA methylation analysis using enzymatic methyl-seq on whole blood from 60 Holstein cows. The study included five phenotype groups: mastitis, lameness, infertility, metabolic disorders and healthy controls. Results Among the 50 million CpG sites, 5.1% were identified as variable methylated cytosines (VMCs) and 94.9% as conserved methylated cytosines (CMCs). VMCs displayed variability in distal promoter regions, suggesting potential plasticity in the associated genes, while CMCs exhibited a bimodal methylation pattern near the transcription start site, indicative of tissue-specific functions. Notably, we identified motif enrichments related to genes potentially expressed in blood. An age-related analysis revealed a 1.4% faster decline in CMCs methylation compared to VMCs. Additionally, disease risk assessment may be achievable using as few as 586 methylation biomarkers, which could be used to select which cows to keep in the herd for additional lactation. Conclusion Our results suggest a dual role for VMCs and CMCs: while the stability of conserved sites is potentially associated with essential functions in cell development and homeostasis, variable sites may be involved in dynamically regulating gene transcription in response to internal or external stimuli. These insights underscore the epigenome’s role in immune regulation and adaptive resilience in cattle.

Due to their unique physicochemical properties, engineered nanoparticles (NPs) are used in numerous skin products as sunscreen, texture agents, colorant, and drug delivery systems. While the skin is considered the first line of defense against xenobiotic entrance, the small size of NPs could promote the interaction with cutaneous cells. This review investigates the fate and the toxicological effects of organic and inorganic NPs used in cosmetic and dermatology. After direct exposure to skin cells, cytotoxicity, oxidative stress, inflammatory response, and genotoxicity were reported in a dose and time-dependent manner, especially for inorganic NPs. Despite these findings, the toxicity of nanoparticles applied to a healthy skin could be questioned due to their inability, for most of them, to reach the viable epidermis. Advanced skin models and toxicity tests validated for nanomaterials should be required for a better prediction of the dermal nanotoxicity.

Amorphous silica nanoparticles are widely used as pharmaceutical excipients and food additive (E551). Despite the potential human health risks of mineral nanoparticles, very few data regarding their oral toxicity are currently available. This study aims to evaluate and to understand the interactions of silica particles at 1 and 10 mg mL−1 with the intestinal barrier using a Caco-2 monolayer and a Caco-2/HT29-MTX co-culture. A size- and concentration-dependent reversible increase of the paracellular permeability is identified after a short-term exposure to silica nanoparticles. Nanoparticles of 30 nm induce the highest transepithelial electrical resistance drop whereas no effect is observed with 200 nm particles. Additive E551 affect the Caco-2 monolayer permeability. Mucus layer reduces the permeability modulation by limiting the cellular uptake of silica. After nanoparticle exposure, tight junction expression including Zonula occludens 1 (ZO-1) and Claudin 2 is not affected, whereas the actin cytoskeleton disruption of enterocytes and the widening of ZO-1 staining bands are observed. A complete permeability recovery is concomitant with the de novo filament actin assembly and the reduction of ZO-1 bands. These findings suggest the paracellular modulation by small silica particles is directly correlated to the alteration of the ZO-actin binding strongly involved in the stability of the tight junction network.

Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, prompting the exploration of adjunctive therapies to mitigate vascular complications. This study investigated the vascular effects of local ice cryotherapy in the adjuvant-induced arthritis (AIA) rat model, with a focus on vascular inflammation, immune cell infiltration, and arthritis severity. AIA rats received local ice application twice daily to inflamed joints for 14 days. Arthritis severity and joint damage were assessed clinically and radiographically. Aortic mRNA expression of endothelial activation (CXCL-1, CCL-2, CCL-3, ICAM-1, VCAM-1) and dysfunction markers (COX-2, Arginase-2, p22 and p47phox) were assessed by RT-qPCR. Circulating and aortic leukocyte populations (including CD4 + , CD8 + , Tc17, Th17 T lymphocytes, neutrophils and monocytes) were determined by flow cytometry. Plasma levels of sclerostin (SOST) and osteoprotegerin (OPG) were measured using Multiplex. Ice cryotherapy significantly reduced arthritis severity and joint damage, decreased aortic COX-2 and p47phox expression, but increased VCAM-1 expression, and markedly reduced aortic infiltration by CD4 + , CD8 + T cells, and Tc17 cells, without affecting circulating leukocyte counts or plasma OPG and SOST. Decrease in arthritis score correlated positively with reduced vascular immune infiltration. These findings suggest potential anti-inflammatory and vasculoprotective benefits from local ice cryotherapy, supporting its use as a well-tolerated RA adjunct therapy.

Background Chronic pain (CP) and psychiatric disorders (PD) are common in older adults, and they both may significantly impact patients’ functioning and quality of life. However, research on the prevalence and impact of CP in people with PD remains limited– especially in older adults– and psychiatric care often neglects somatic comorbidities. Objectives The main objective of the DoCPPA study is to determine the prevalence and characteristics of CP in older adults with PD followed-up in psychiatric services. Our secondary objective is to estimate associations between CP and various clinical indicators related to physical, cognitive, and mental health, as well as quality of life. Setting Department of Aging Psychiatry of Le Vinatier Hospital Center (France, Bron), inpatient and outpatient psychiatric services. Method/design Cross-sectional monocentric study with 430 patients with PD under psychiatric care. The inclusion period will be 36 months. The patients will be evaluated using validated scales and neuropsychological assessments. Discussion This study aims to contribute to improving care in aging psychiatry, a field where a major challenge lies in the management of multiple chronic conditions.

About 15,000 angiosperm species (∼6%) have separate sexes, a phenomenon known as dioecy. Why dioecious taxa are so rare is still an open question. Early work reported lower species richness in dioecious compared with nondioecious sister clades, raising the hypothesis that dioecy may be an evolutionary dead-end. This hypothesis has been recently challenged by macroevolutionary analyses that detected no or even positive effect of dioecy on diversification. However, the possible genetic consequences of dioecy at the population level, which could drive the long-term fate of dioecious lineages, have not been tested so far. Here, we used a population genomics approach in the Silene genus to look for possible effects of dioecy, especially for potential evidence of evolutionary handicaps of dioecy underlying the dead-end hypothesis. We collected individual-based RNA-seq data from several populations in 13 closely related species with different sexual systems: seven dioecious, three hermaphroditic, and three gynodioecious species. We show that dioecy is associated with increased genetic diversity, as well as higher selection efficacy both against deleterious mutations and for beneficial mutations. The results hold after controlling for phylogenetic inertia, differences in species census population sizes and geographic ranges. We conclude that dioecious Silene species neither show signs of increased mutational load nor genetic evidence for extinction risk. We discuss these observations in the light of the possible demographic differences between dioecious and self-compatible hermaphroditic species and how this could be related to alternatives to the dead-end hypothesis to explain the rarity of dioecy.

Novel multitarget-directed ligands BIGI 4a-d and BIGI 5a-d were designed and synthesized with a simple and cost-efficient procedure via a one-pot three-component Biginelli reaction targeting acetyl-/butyrylcholinesterases inhibition, calcium channel antagonism, and antioxidant ability. Among these multitarget-directed ligands, BIGI 4b, BIGI 4d, and BIGI 5b were identified as promising new hit compounds showing in vitro balanced activities toward the recognized AD targets. In addition, these compounds showed suitable physicochemical properties and a good druglikeness score predicted by Data Warrior software.