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One of comics' wildest writers takes on the symbiotic super hero! Flash Thompson, the Secret Avenger called Agent Venom, faces Daimon Hellstrom and the Monsters of Evil in a battle to save his soul! But when Venom's psychopathic off spring targets the Microverse, Flash and the new Scarlet Spider must put their rivalries aside to handle the madness of Carnage! Venom says farewell to New York and heads to Philadelphia - but Toxin follows soon after. And the pair of lethal symbiotes may unwittingly unleash something even more deadly! Can Flash battle side-by-side with the original Venom, Eddie Brock, to save the City of Brotherly Love? Plus underworld boss Lord Ogre! The killer called Crossbones! And...a symbiotic sidekick?! Cullen Bunn's explosive Venom run is collected in full!

2´-fucosyllactose (2´-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits.

Background Corynebacterium diphtheriae , the causative agent of diphtheria, remains a public health concern, especially in regions with low vaccination coverage. While advances in genomic typing, such as core-genome Multi-Locus Sequence Typing (cgMLST), have improved our ability for strain identification, a standardized and stable genomic taxonomy is still lacking. This study aimed to establish a consistent taxonomic classification and nomenclature for C. diphtheriae strains using cgMLST-based Life Identification Number (LIN) codes. Methods Comparing 1,665 genomes from C. diphtheriae and closely related species C. belfantii and C. rouxii , we observed population-level genetic discontinuities in cgMLST profiles dissimilarities, and established hierarchical taxonomic levels based on optimal allelic difference thresholds. Ten-level LIN codes were defined, encompassing broad population structure subdivisions and fine-scale epidemiological levels. The LIN code system was implemented into the BIGSdb-Pasteur platform, and nicknames derived from the 7-loci MLST sequence types were given to sublineages and clonal groups. Results cgMLST genetic thresholds were first defined at species and lineage levels (minimum of 1,240 and 1,035 allelic differences, respectively). Sublineages (SL), clonal groups (ClG), and genetic clusters (GC) were next defined with progressively finer allelic mismatch thresholds (500, 55, and 25 differences, respectively). A broad population diversity of C. diphtheriae was uncovered, with the distinction of > 400 SLs and > 1,000 GCs. For epidemiological purposes, five shallow-level thresholds (8, 4, 2,1, and 0 allelic mismatches) were defined, completing the 10-level LIN code taxonomy. We illustrate LIN codes applicability to investigate the genetic diversity and transmission chains of relevant clusters, such as SL8 (the 1990s ex-USSR outbreak) or SL384 (involved in outbreaks in Yemen and Europe). Conclusions The cgMLST-based LIN code system provides a stable genomic taxonomy for strains of C. diphtheriae, C. rouxii and C. belfantii . By defining ten hierarchical levels of resolution, this system effectively captures its phylogenetic diversity, facilitating population biology research and epidemiological surveillance. The public availability of this system in the BIGSdb-Pasteur platform provides a standardized framework for diphtheria genomic epidemiology with potential to harmonize global surveillance of diphtheria resurgence.

Serotonin (5-HT) deficiency occurs in a number of brain disorders that affect cognitive function. However, a direct causal relationship between 5-HT hypo-transmission and memory and underlying mechanisms has not been established. We used mice with a constitutive depletion of 5-HT brain levels (Pet1KO mice) to analyze the contribution of 5-HT to different forms of learning and memory. Pet1KO mice exhibited a striking deficit in novel object recognition memory, a hippocampal-dependent task. No alterations were found in tasks for social recognition, procedural learning, or fear memory. Viral delivery of designer receptors exclusively activated by designer drugs was used to selectively silence the activity of 5-HT neurons in the raphe. Inhibition of 5-HT neurons in the median raphe, but not the dorsal raphe, was sufficient to impair object recognition in adult mice. In vivo electrophysiology in behaving mice showed that long-term potentiation in the hippocampus of 5-HT-deficient mice was altered, and administration of the 5-HT1A agonist 8-OHDPAT rescued the memory deficits. Our data suggest that hyposerotonergia selectively affects declarative hippocampal-dependent memory. Serotonergic projections from the median raphe are necessary to regulate object memory and hippocampal synaptic plasticity processes, through an inhibitory control mediated by 5-HT1A receptors.

Land subsidence in urban environments is an increasingly prominent aspect in the monitoring and maintenance of urban infrastructures. In this study we update the subsidence information over Rome and its surroundings (already the subject of past research with other sensors) for the first time using Copernicus Sentinel-1 data and open source tools. With this aim, we have developed a fully automatic processing chain for land deformation monitoring using the European Space Agency (ESA) SentiNel Application Platform (SNAP) and Stanford Method for Persistent Scatterers (StaMPS). We have applied this automatic processing chain to more than 160 Sentinel-1A images over ascending and descending orbits to depict primarily the Line-Of-Sight ground deformation rates. Results of both geometries were then combined to compute the actual vertical motion component, which resulted in more than 2 million point targets, over their common area. Deformation measurements are in agreement with past studies over the city of Rome, identifying main subsidence areas in: (i) Fiumicino; (ii) along the Tiber River; (iii) Ostia and coastal area; (iv) Ostiense quarter; and (v) Tivoli area. Finally, post-processing of Persistent Scatterer Inteferometry (PSI) results, in a Geographical Information System (GIS) environment, for the extraction of ground displacements on urban infrastructures (including road networks, buildings and bridges) is considered.

Intratumoral injections often lack visibility, leading to unpredictable outcomes such as incomplete tumor coverage, off-target drug delivery and systemic toxicities. This study investigated an ultrasound (US) and x-ray imageable thermosensitive hydrogel based on poloxamer 407 (POL) percutaneously delivered in a healthy swine model. The primary objective was to assess the 2D and 3D distribution of the hydrogel within tissue across three different needle devices and injection sites: liver, kidney, and intercostal muscle region. Secondly, pharmacokinetics of POL loaded with doxorubicin (POLDOX) were evaluated and compared to free doxorubicin injection (DOXSoln) with a Single End Hole Needle. Utilizing 2D and 3D morphometrics from US and x-ray imaging techniques such as Computed Tomography (CT) and Cone Beam CT (CBCT), we monitored the localization and leakage of POLDOX over time. Relative iodine concentrations measured with CBCT following incorporation of an iodinated contrast agent in POL indicated potential drug diffusion and advection transport. Furthermore, US imaging revealed temporal changes, suggesting variations in acoustic intensity, heterogeneity, and echotextures. Notably, 3D reconstruction of the distribution of POL and POLDOX from 2D ultrasound frames was achieved and morphometric data obtained. Pharmacokinetic analysis revealed lower systemic exposure of the drug in various organs with POLDOX formulation compared to DOXSoln formulation. This was demonstrated by a lower area under the curve (852.1 ± 409.1 ng/mL·h vs 2283.4 ± 377.2 ng/mL·h) in the plasma profile, suggesting a potential reduction in systemic toxicity. Overall, the use of POL formulation offers a promising strategy for precise and localized drug delivery, that may minimize adverse effects. Dual modality POL imaging enabled analysis of patterns of gel distribution and morphology, alongside of pharmacokinetics of local delivery. Incorporating hydrogels into drug delivery systems holds significant promise for improving the predictability of the delivered drug and enhancing spatial conformability. These advancements can potentially enhance the safety and precision of anticancer therapy.

Food systems must become more sustainable and equitable, a transformation which requires the transdisciplinary co-production of knowledge. We present a framework of food sustainability that was co-created by academic and non-academic actors and comprises five dimensions: food security, right to food, environmental performance, poverty and inequality, and social-ecological resilience. For each dimension, an interdisciplinary research team—together with actors from different food systems—defined key indicators and empirically applied them to six case studies in Kenya and Bolivia. Food sustainability scores were analysed for the food systems as a whole, for the five dimensions, and for food system activities. We then identified the indicators with the greatest influence on sustainability scores. While all food systems displayed strengths and weaknesses, local and agroecological food systems scored comparatively highly across all dimensions. Agro-industrial food systems scored lowest in environmental performance and food security, while their resilience scores were medium to high. The lowest-scoring dimensions were right to food, poverty and inequality, with particularly low scores obtained for the indicators women’s access to land and credit, agrobiodiversity, local food traditions, social protection, and remedies for violations of the right to food. This qualifies them as key levers for policy interventions towards food sustainability.

Transcranial direct-current stimulation (tDCS) is a noninvasive brain stimulation technique that has been successfully applied for modulation of cortical excitability. tDCS is capable of inducing changes in neuronal membrane potentials in a polarity-dependent manner. When tDCS is of sufficient length, synaptically driven after-effects are induced. The mechanisms underlying these after-effects are largely unknown, and there is a compelling need for animal models to test the immediate effects and after-effects induced by tDCS in different cortical areas and evaluate the implications in complex cerebral processes. Here we show in behaving rabbits that tDCS applied over the somatosensory cortex modulates cortical processes consequent to localized stimulation of the whisker pad or of the corresponding area of the ventroposterior medial (VPM) thalamic nucleus. With longer stimulation periods, poststimulation effects were observed in the somatosensory cortex only after cathodal tDCS. Consistent with the polarity-specific effects, the acquisition of classical eyeblink conditioning was potentiated or depressed by the simultaneous application of anodal or cathodal tDCS, respectively, when stimulation of the whisker pad was used as conditioned stimulus, suggesting that tDCS modulates the sensory perception process necessary for associative learning. We also studied the putative mechanisms underlying immediate effects and after-effects of tDCS observed in the somatosensory cortex. Results when pairs of pulses applied to the thalamic VPM nucleus (mediating sensory input) during anodal and cathodal tDCS suggest that tDCS modifies thalamocortical synapses at presynaptic sites. Finally, we show that blocking the activation of adenosine A1 receptors prevents the long-term depression (LTD) evoked in the somatosensory cortex after cathodal tDCS.

Nanosized fertilizers are the new frontier of nanotechnology towards a sustainable agriculture. Here, an efficient N-nanofertilizer is obtained by post-synthetic modification (PSM) of nitrate-doped amorphous calcium phosphate (ACP) nanoparticles (NPs) with urea. The unwasteful PSM protocol leads to N-payloads as large as 8.1 w/w%, is well replicated by using inexpensive technical-grade reagents for cost-effective up-scaling and moderately favours urea release slowdown. Using the PSM approach, the N amount is ca. 3 times larger than that obtained in an equivalent one-pot synthesis where urea and nitrate are jointly added during the NPs preparation. In vivo tests on cucumber plants in hydroponic conditions show that N-doped ACP NPs, with half absolute N-content than in conventional urea treatment, promote the formation of an equivalent amount of root and shoot biomass, without nitrogen depletion. The high nitrogen use efficiency (up to 69%) and a cost-effective preparation method support the sustainable real usage of N-doped ACP as a nanofertilizer.

Demineralization of dental hard tissue is a widespread problem and the main responsible for dental caries and dentin hypersensitivity. The most promising strategies to induce the precipitation of new mineral phase are the application of materials releasing gradually Ca 2+ and PO 4 3− ions or mimicking the mineral phase of the host tissue. However, the design of formulations covering both processes is so far a challenge in preventive dentistry. In this work, we have synthesized innovative biomimetic amorphous calcium phosphate (ACP), which has been, for the first time, doped with fluoride ions (FACP) to obtain materials with enhanced anti-caries and remineralizing properties. Significantly, the doping with fluoride (F) did not vary the physico-chemical features of ACP but resulted in a faster conversion to the crystalline apatite phase in water, as observed by in-situ time-dependent Raman experiments. The efficacy of the as synthesized ACP and FACP samples to occlude dentinal tubules and induce enamel remineralization has been tested in vitro in human molar teeth. The samples showed good ability to partially occlude the tubules of acid-etched dentin and to restore demineralized enamel into its native structure. Results demonstrate that ACP and FACP are promising biomimetic materials in preventive dentistry to hinder demineralization of dental hard tissues.