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Microbiota-Mediated Crosstalk Between the Gut and the Vascular System: Protective Effects of Novel Postbiotic Formulations on Human Endothelial and Vascular Smooth Muscle Cells
No full textThe close connections between the intestine and distal systems, known as axes, are a growing focus of scientific research; however, the gut–vascular axis, particularly as a target of microbial metabolites, remains underexplored. In this study, three supernatants derived from probiotic formulations composed of Lactobacillus and Bifidobacterium strains (MIX-1, MIX-2, and MIX-3) were evaluated in counteracting vascular alterations associated with dysbiosis. Human aortic smooth muscle (HASMCs) and endothelial (HAECs) cells were exposed to pro-oxidative (H2O2) and pro-inflammatory (TMAO) stimuli. Concentrations up to 5–10% (v/v) were tolerated in both cell lines, with MIX-1 and MIX-3 showing the greatest protective efficacy. These formulations exerted antioxidant effects by reducing H2O2-induced ROS production and cell viability loss, and anti-inflammatory effects by limiting TMAO-induced IL-1β release. MIX-1 also attenuated TMAO-induced IL-6 release. Further analyses indicated a partial involvement of the SIRT1-pathway in its vascular antioxidant effects. Chromatographic profiling revealed comparable qualitative metabolites among the probiotic supernatants, while quantitative differences were observed, with higher lactate levels in MIX-1 and MIX-3 compared to MIX-2. Finally, we have determined that Limosilactobacillus reuteri-PBS072 is mainly responsible for the antioxidant effect of MIX-1 and MIX-3. Overall, these findings highlight the potential of probiotic-derived metabolites in modulating the gut–vascular axis and promoting vascular protection
Terrorismo
No full textIl contributo si sofferma sul termine terrorismo e lo analizza nella sua complessa genealogia storic
Transnational Shelley(s): Metamorphoses and Reconfigurations
No full textThis special issue celebrates the multifaceted afterlives of Percy Bysshe Shelley and Mary Shelley, exploring the many echoes their oeuvre has generated throughout the history of modern and contemporary literature. Beginning with Mary Shelley’s immediate editorial and critical efforts, and moving through late nineteenth-century Victorian celebrations and Modernist (apparent) rejection, the history of the Shelleys’ critical fortune stands as one of the most compelling trajectories in modern literary culture. It offers a privileged point of observation from which to ponder the nature of their poetic and philosophical legacy. As the various contributions to this issue demonstrate, that legacy has reverberated across literary traditions from across the globe, extending well beyond the boundaries of the anglophone canon. the process
Plasmonic Metamaterial’s Light Trapping Enhancement of Ultrathin PbS-CQD Solar Thermal PV Cells
No full textEnhancing photon absorptance in ultrathin solar/thermophotovoltaic (STPV) cells is crucial for low-cost highly efficient cells. A complete study of power conversion enhancement, in a proposed ultrathin STPV cell, is presented here. It involves lead sulfide colloidal quantum dots (PbS-CQDs), a silver (Ag)-nano-pyramid design, aluminum nitride (AlN) crossed prisms as front texturization, with embedded Ag nanospheres, and a tantalum (Ta) film as a back reflector. By combining the three mechanisms of surface plasmon polariton (SPP), localized plasmons (LSPR), and magnetic polariton (MP) in the same structure, photon absorptance in the active PbS-CQDs layer is greatly improved. The suggested structure attained a highly active absorptance of over 80%, covering visible and near-infrared (0.30–1.77 μm). The short circuit current density is also evaluated under AM 1.5 solar illumination and various blackbody temperatures (TB), with values of 48.90 mA cm−2 and 6.93 mA cm−2, respectively, corresponding to unprecedented power conversion efficiencies (PCEs) of 20.20% and 15.58%. The effects of metamaterial light management on PCE enhancement are discussed. Collectively, the findings show that the proposed hybrid cell is potentially useful in high-performance hybrid thermal and solar cells. Graphical Abstract: (Figure presented.
Synthesis and biological investigation of peptidomimetic SARS-CoV-2 main protease inhibitors bearing quinoline-based heterocycles at P3
No full textIn the last few years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the cause of a worldwide pandemic, highlighting the need for novel antiviral agents. The main protease (Mpro) of SARS-CoV-2 was immediately identified as a crucial enzyme for viral replication and has been validated as a drug target. Here, we present the design and synthesis of peptidomimetic Mpro covalent inhibitors characterized by quinoline-based P3 moieties. Structure–activity relationships (SARs) were also investigated at P1 and P2, as well as for different warheads. The binding modes of the designed inhibitors were assessed using X-ray crystallographic and molecular docking studies. The identified Mpro inhibitors were tested for their antiviral activities in cell-based assays, and the results were encouraging. The SAR studies presented here can contribute to the future design of improved inhibitors by addressing some of the current or prospective issues regarding Mpro inhibitors currently used in therapy
Error analysis for a fully-discrete finite element approximation of the unsteady p(.,.)-Stokes equations
No full textn this paper, we examine a fully-discrete finite element approximation of the unsteady p(.,.)-Stokes equations ({i.e.}, p(.,.) is time- and space-dependent), employing a backward Euler step in time and conforming discretely inf-sup stable finite elements in space, for error decay rates for the velocity vector field.
More precisely, we derive error decay rates that are optimal with respect to natural fractional regularity assumptions on the velocity vector field and the kinematic pressure. The optimality of the derived error decay rates is confirmed via numerical experiments
The relationship between primate distal fibula trabecular architecture and arboreality, phylogeny and size
No full textThe fibula, despite being traditionally overlooked compared to the femur and the tibia, has recently received attention in primate functional morphology due to its correlation with the degree of arboreality (DOA). Highlighting further fibular features that are associated with arboreal habits would be key to improving palaeobiological inferences in fossil specimens. Here we present the first investigation on the trabecular bone structure of the primate fibula, focusing on the distal epiphysis, across a vast array of species. We collected μCT data on the distal fibula for 21 species of primates, with representatives from most of the orders, and we employed a recently developed approach implemented in the R package 'indianaBones' to isolate the entire trabecular bone underlying an epiphysis or articular facet. After extracting both traditional trabecular parameters and novel topological indices, we tested for the posited relationship between trabecular bone and DOA. To disentangle this effect from others related to body size and phylogenetic relationship, we included a body mass proxy as covariate and employed phylogenetic comparative methods. We ran univariate/multivariate and exploratory/inferential statistical analyses. The trabecular structure of the fibular distal epiphysis in primates does not appear to be associated with the DOA. Instead, it is strongly affected by body mass and phylogenetic relationships. Although we identified some minor trends related to human bipedalism, our findings overall discourage, at this stage, the study of distal fibula trabecular bone to infer arboreal behaviors in extinct primates. We further found that body size distribution is strongly related to phylogeny, an issue preventing us from unravelling the influence of the two factors and that we believe can potentially affect future comparative analyses of primates. Overall, our results add to previous evidence of how trabecular traits show variable correlation with locomotor aspects, size and phylogenetic history across the primate skeleton, thus outlining a complex scenario in which a network of interconnected factors affects the morphological evolution of primates. This work may represent a starting point for future studies, for example, focusing on the effect of human bipedalism on distal fibula trabecular bone, or aiming to better understand the effects of body size and phylogenetic history on primate morphological evolution
Artificial Intelligence-Guided Lung Ultrasound by Nonexperts
No full textImportance: Lung ultrasound (LUS) aids in the diagnosis of patients with dyspnea, including those with cardiogenic pulmonary edema, but requires technical proficiency for image acquisition. Previous research has demonstrated the effectiveness of artificial intelligence (AI) in guiding novice users to acquire high-quality cardiac ultrasound images, suggesting its potential for broader use in LUS. Objective: To evaluate the ability of AI to guide acquisition of diagnostic-quality LUS images by trained health care professionals (THCPs). Design, setting, and participants: In this multicenter diagnostic validation study conducted between July 2023 and December 2023, participants aged 21 years or older with shortness of breath recruited from 4 clinical sites underwent 2 ultrasound examinations: 1 examination by a THCP operator using Lung Guidance AI and the other by a trained LUS expert without AI. The THCPs (including medical assistants, respiratory therapists, and nurses) underwent standardized AI training for LUS acquisition before participation. Interventions: Lung Guidance AI software uses deep learning algorithms guiding LUS image acquisition and B-line annotation. Using an 8-zone LUS protocol, the AI software automatically captures images of diagnostic quality. Main outcomes and measures: The primary end point was the proportion of THCP-acquired examinations of diagnostic quality according to a panel of 5 masked expert LUS readers, who provided remote review and ground truth validation. Results: The intention-to-treat analysis included 176 participants (81 female participants [46.0%]; mean [SD] age, 63 [14] years; mean [SD] body mass index, 31 [8]). Overall, 98.3% (95% CI, 95.1%-99.4%) of THCP-acquired studies were of diagnostic quality, with no statistically significant difference in quality compared to LUS expert-acquired studies (difference, 1.7%; 95% CI, -1.6% to 5.0%). Conclusions and relevance: In this multicenter validation study, THCPs with AI assistance achieved LUS images meeting diagnostic standards compared with LUS experts without AI. This technology could extend access to LUS to underserved areas lacking expert personnel. Trial registration: ClinicalTrials.gov Identifier: NCT05992324
