Intrinsic Immunity Shapes Viral Resistance of Stem Cells.

Stem cells are highly resistant to viral infection compared to their differentiated progeny; however, the mechanism is mysterious. Here, we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that, conserved across species, stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic, as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner, and many ISGs decrease upon differentiation, at which time cells become IFN responsive, allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly, we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance.

Limited potential for bird migration to disperse plants to cooler latitudes.

Climate change is forcing the redistribution of life on Earth at an unprecedented velocity1,2. Migratory birds are thought to help plants to track climate change through long-distance seed dispersal3,4. However, seeds may be consistently dispersed towards cooler or warmer latitudes depending on whether the fruiting period of a plant species coincides with northward or southward migrations. Here we assess the potential of plant communities to keep pace with climate change through long-distance seed dispersal by migratory birds. To do so, we combine phenological and migration information with data on 949 seed-dispersal interactions between 46 bird and 81 plant species from 13 woodland communities across Europe. Most of the plant species (86%) in these communities are dispersed by birds migrating south, whereas only 35% are dispersed by birds migrating north; the latter subset is phylogenetically clustered in lineages that have fruiting periods that overlap with the spring migration. Moreover, the majority of this critical dispersal service northwards is provided by only a few Palaearctic migrant species. The potential of migratory birds to assist a small, non-random sample of plants to track climate change latitudinally is expected to strongly influence the formation of novel plant communities, and thus affect their ecosystem functions and community assembly at higher trophic levels.

Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA.

MicroRNAs (miRNAs) regulate the levels of translation of messenger RNAs (mRNAs). At present, the major parameter that can explain the selection of the target mRNA and the efficiency of translation repression is the base pairing between the 'seed' region of the miRNA and its counterpart mRNA1. Here we use R1ρ relaxation-dispersion nuclear magnetic resonance2 and molecular simulations3 to reveal a dynamic switch-based on the rearrangement of a single base pair in the miRNA-mRNA duplex-that elongates a weak five-base-pair seed to a complete seven-base-pair seed. This switch also causes coaxial stacking of the seed and supplementary helix fitting into human Argonaute 2 protein (Ago2), reminiscent of an active state in prokaryotic Ago4,5. Stabilizing this transient state leads to enhanced repression of the target mRNA in cells, revealing the importance of this miRNA-mRNA structure. Our observations tie together previous findings regarding the stepwise miRNA targeting process from an initial 'screening' state to an 'active' state, and unveil the role of the RNA duplex beyond the seed in Ago2.

Current European flood-rich period exceptional compared with past 500 years.

There are concerns that recent climate change is altering the frequency and magnitude of river floods in an unprecedented way1. Historical studies have identified flood-rich periods in the past half millennium in various regions of Europe2. However, because of the low temporal resolution of existing datasets and the relatively low number of series, it has remained unclear whether Europe is currently in a flood-rich period from a long-term perspective. Here we analyse how recent decades compare with the flood history of Europe, using a new database composed of more than 100 high-resolution (sub-annual) historical flood series based on documentary evidence covering all major regions of Europe. We show that the past three decades were among the most flood-rich periods in Europe in the past 500 years, and that this period differs from other flood-rich periods in terms of its extent, air temperatures and flood seasonality. We identified nine flood-rich periods and associated regions. Among the periods richest in floods are 1560-1580 (western and central Europe), 1760-1800 (most of Europe), 1840-1870 (western and southern Europe) and 1990-2016 (western and central Europe). In most parts of Europe, previous flood-rich periods occurred during cooler-than-usual phases, but the current flood-rich period has been much warmer. Flood seasonality is also more pronounced in the recent period. For example, during previous flood and interflood periods, 41 per cent and 42 per cent of central European floods occurred in summer, respectively, compared with 55 per cent of floods in the recent period. The exceptional nature of the present-day flood-rich period calls for process-based tools for flood-risk assessment that capture the physical mechanisms involved, and management strategies that can incorporate the recent changes in risk.

A single-cell atlas of de novo ß-cell regeneration reveals the contribution of hybrid ß/δ-cells to diabetes recovery in zebrafish.

Regeneration-competent species possess the ability to reverse the progression of severe diseases by restoring the function of the damaged tissue. However, the cellular dynamics underlying this capability remain unexplored. Here, we have used single-cell transcriptomics to map de novo ß-cell regeneration during induction and recovery from diabetes in zebrafish. We show that the zebrafish has evolved two distinct types of somatostatin-producing δ-cells, which we term δ1- and δ2-cells. Moreover, we characterize a small population of glucose-responsive islet cells, which share the hormones and fate-determinants of both ß- and δ1-cells. The transcriptomic analysis of ß-cell regeneration reveals that ß/δ hybrid cells provide a prominent source of insulin expression during diabetes recovery. Using in vivo calcium imaging and cell tracking, we further show that the hybrid cells form de novo and acquire glucose-responsiveness in the course of regeneration. The overexpression of dkk3, a gene enriched in hybrid cells, increases their formation in the absence of ß-cell injury. Finally, interspecies comparison shows that plastic δ1-cells are partially related to PP cells in the human pancreas. Our work provides an atlas of ß-cell regeneration and indicates that the rapid formation of glucose-responsive hybrid cells contributes to the resolution of diabetes in zebrafish.

Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity.

AIMS/HYPOTHESIS: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly connected 'hub' cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility, which we explore here by focusing on the imprinted gene Nnat (encoding neuronatin [NNAT]), which is required for normal insulin synthesis and secretion. METHODS: Single-cell RNA-seq datasets were examined using Seurat 4.0 and ClusterProfiler running under R. Transgenic mice expressing enhanced GFP under the control of the Nnat enhancer/promoter regions were generated for FACS of beta cells and downstream analysis of CpG methylation by bisulphite sequencing and RNA-seq, respectively. Animals deleted for the de novo methyltransferase DNA methyltransferase 3 alpha (DNMT3A) from the pancreatic progenitor stage were used to explore control of promoter methylation. Proteomics was performed using affinity purification mass spectrometry and Ca2+ dynamics explored by rapid confocal imaging of Cal-520 AM and Cal-590 AM. Insulin secretion was measured using homogeneous time-resolved fluorescence imaging. RESULTS: Nnat mRNA was differentially expressed in a discrete beta cell population in a developmental stage- and DNA methylation (DNMT3A)-dependent manner. Thus, pseudo-time analysis of embryonic datasets demonstrated the early establishment of Nnat-positive and -negative subpopulations during embryogenesis. NNAT expression is also restricted to a subset of beta cells across the human islet that is maintained throughout adult life. NNAT+ beta cells also displayed a discrete transcriptome at adult stages, representing a subpopulation specialised for insulin production, and were diminished in db/db mice. 'Hub' cells were less abundant in the NNAT+ population, consistent with epigenetic control of this functional specialisation. CONCLUSIONS/INTERPRETATION: These findings demonstrate that differential DNA methylation at Nnat represents a novel means through which beta cell heterogeneity is established during development. We therefore hypothesise that changes in methylation at this locus may contribute to a loss of beta cell hierarchy and connectivity, potentially contributing to defective insulin secretion in some forms of diabetes. DATA AVAILABILITY: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD048465.

DNA metabarcoding, diversity partitioning and null models reveal mechanisms of seasonal trophic specialization in a Mediterranean warbler.

Optimal Foraging Theory (OFT) predicts that a population's trophic niche expansion should occur in periods of food scarcity as individuals begin to opportunistically exploit sub-optimal food items. However, the Niche Variation Hypothesis (NVH) posits that niche widening may result from increased among-individual differentiation due to food partitioning to avoid competition. We tested these hypotheses through a DNA metabarcoding study of the Sardinian Warbler (Curruca melanocephala) diet over a year. We used null models and the decomposition of beta diversity on among-individual dietary differentiation to infer the mechanisms driving the population's niche variation. Warblers fed frequently on berries, with a peak in late summer and, to a lesser extent, in autumn. Their diet also included a wide range of arthropods, with their prevalence varying among seasons. Consistent with OFT, the population's niche width was narrower in spring/summer when the population was strongly specialized in berries. In winter, the population's niche expanded, possibly reflecting seasonal declines in food abundance. As predicted by NVH, among-individual differentiation tended to be higher in winter, but this was mainly due to increased differences in dietary richness rather than to the partitioning of resources. Overall, our results suggest that within-individual niche does not increase in lean periods, and instead, individuals adopt either a more opportunistic or more specialized foraging strategy. Increased competition in periods of scarcity may help explain such patterns, but instead of showing increased food partitioning as expected from NVH, it may reflect OFT mechanisms on individuals with differential competitive ability to access better food resources.

Dietary metabarcoding reveals the simplification of bird-pest interaction networks across a gradient of agricultural cover.

Agriculture is vital for supporting human populations, but its intensification often leads to landscape homogenization and a decline in non-provisioning ecosystem services. Ecological intensification and multifunctional landscapes are suggested as nature-based alternatives to intensive agriculture, using ecological processes like natural pest regulation to maximize food production. Birds are recognized for their role in increasing crop yields by consuming invertebrate pests in several agroecosystems. However, the understanding of how bird species, their traits and agricultural land cover influence the structure of bird-pest interactions remains limited. We sampled bird-pest interactions monthly for 1 year, at four sites within a multifunctional landscape, following a gradient of increasing agricultural land cover. We analysed 2583 droppings of 55 bird species with DNA metabarcoding and detected 225 pest species in 1139 samples of 42 bird species. As expected, bird-pest interactions were highly variable across bird species. Dietary pest richness was lower in the fully agricultural site, while predation frequency remained consistent across the agricultural land cover gradient. Network analysis revealed a reduction in the complexity of bird-pest interactions as agricultural coverage increased. Bird species abundance affected the bird's contribution to the network structure more than any of the bird traits analysed (weight, phenology, invertebrate frequency in diet and foraging strata), with more common birds being more important to network structure. Overall, our results show that increasing agricultural land cover increases the homogenization of bird-pest interactions. This shows the importance of maintaining natural patches within agricultural landscapes for biodiversity conservation and enhanced biocontrol.

A agricultura é essencial para suportar a população humana, mas a sua intensificação geralmente leva à homogeneização da paisagem e à redução dos serviços do ecossistema que não sejam de provisão. A intensificação ecológica e paisagens multifuncionais são sugeridas como alternativas naturais à agricultura intensiva, utilizando processos ecológicos como a regulação natural de pragas para maximizar a produção de alimentos. As aves são conhecidas pelo seu papel no aumento da produtividade das culturas por consumirem pragas em diversos agroecossistemas. Contudo, o conhecimento de como as espécies de aves, as suas características e a cobertura agrícola influenciam as interações entre aves e pragas são limitados. Nós amostrámos estas interações mensalmente durante um ano, em quatro locais, numa paisagem multifuncional, ao longo um gradiente de aumento da cobertura agrícola. Analisamos 2583 dejetos de 55 espécies de aves com DNA metabarcoding e detetamos 225 espécies praga em 1139 amostras de 42 espécies de aves. Como esperado, as interações entre aves e pragas foram muito distintas entre as várias espécies de aves. A riqueza de pragas na dieta foi menor no local completamente dominado por área agrícola, enquanto a frequência de predação de pragas foi constante ao longo do gradiente de cobertura agrícola. A análise de redes demonstrou uma redução na complexidade das interações entre aves e pragas à medida que a cobertura agrícola aumenta. A abundância das espécies de aves influenciou mais a contribuição das aves para a estrutura da rede do que qualquer uma das características analisadas (peso, fenologia, frequência de invertebrados na dieta e estrato de alimentação), sendo as aves mais comuns as mais importantes na estrutura da rede. De forma geral, os nossos resultados indicam que o aumento da cobertura agrícola aumenta a homogeneização das interações entre aves e pragas. Isto demonstra a importância de preservar áreas naturais em paisagem agrícolas para a conservação de biodiversidade e melhor controlo biológico.

Shedding light on the impacts of Spirulina platensis on gut microbiota and related health benefits.

Spirulina (S.) platensis is a blue-green algae with reported nutritional and health-promoting properties, such as immunomodulating, antioxidant, cholesterol-lowering properties, and beneficial effects on inflammatory diseases. Spirulina platensis can improve the function and composition of the gut microbiota and exert systemic beneficial effects. Gut dysbiosis is characterized by an imbalance in the composition and function of gut microbiota and is associated with several diseases. Some dietary bioactive compounds can restore the composition, diversity, and function of the gut microbiota and improve health-related parameters. This review proposes to gather relevant information on the effects of S. platensis supplementation on the modulation of the function and composition of gut microbiota and local and systemic measures related to gut health, such as inflammation, oxidative stress, and glucose and lipid metabolism. The body of evidence conducted with animals and clinical studies shows that S. platensis supplementation increased gut microbiota diversity and improved gut microbiota composition, as reported by a decrease in the Firmicutes/Bacteroides ratio, increase in the relative abundance of Prevotella and Lactobacillaceae, increase in short-chain fatty acid production and decrease of gut permeability. Improvements in gut microbiota have been associated with host health benefits such as anti-obesity, anti-diabetic, anti-hypertensive, anti-lipemic, anti-inflammatory, and antioxidant effects.

Molecular characterization of Chikungunya virus recovered from patients in the Maranhão state, Brazil.

BACKGROUND: Chikungunya virus (CHIKV) is an arbovirus from the Togaviridae family which has four genotypes: West African (WA), East/Central/South African (ECSA) and Asian/Caribbean lineage (AL) and Indian Ocean Lineage (IOL). The ECSA genotype was first registered in Brazil in Feira de Santana and spread to all Brazilian regions. This study reports the characterization of CHIKV isolates recovered from sera samples of fifty patients from seventeen cities in Maranhão, a state from Brazilian northeast region and part of the Legal Amazon area. METHODS AND RESULTS: Primers were developed to amplify the partial regions coding structural proteins (E1, E3, E2, 6 K, and Capsid C). The consensus sequences have 2871 bp, covering approximately 24% of the genome. The isolates were highly similar (> 99%) to the ECSA isolate from Feira de Santana (BHI3734/H804698), presenting 30 non-synonymous mutations in E1 (5.95%), 18 in E2 (4.46%), and 1 in E3 (3.03%), taking the BHI3734/H804698 isolate as standard. Although the mutations described have not previously been related to increased infectivity or transmissibility of CHIKV, in silico analysis showed changes in physicochemical characteristics, antigenicity, and B cell epitopes of E1 and E2. CONCLUSIONS: These findings demonstrate the importance of molecular approaches for monitoring the viral adaptations undergone by CHIKV and its geographic distribution.

Estimating the heritability of nitrogen and carbon isotopes in the tail hair of beef cattle.

BACKGROUND: The natural abundance of nitrogen (δ15N) and carbon (δ13C) isotopes in animal tissues are used to estimate an animal's efficiency in nitrogen utilization, and their feed conversion efficiency, especially in tropical grazing systems with prolonged protein restriction. It is postulated that selection for improving these two characteristics (δ15N and δ13C) would assist the optimisation of the adaptation in ever-changing environments, particularly in response to climate change. The aim of this study was to determine the heritability of δ15N and δ13C in the tail hair of tropically adapted beef cattle to validate their inclusion in genetic breeding programs. METHODS: In total, 492 steers from two breeds, Brahman (n = 268) and Droughtmaster (n = 224) were used in this study. These steers were managed in two mixed breed contemporary groups across two years (year of weaning): steers weaned in 2019 (n = 250) and 2020 (n = 242). Samples of tail switch hair representing hair segments grown during the dry season were collected and analysed for δ15N and δ13C with isotope-ratio mass spectrometry. Heritability and variance components were estimated in a univariate multibreed (and single breed) animal model in WOMBAT and ASReml using three generations of full pedigree. RESULTS: The estimated heritability of both traits was significantly different from 0, i.e. 0.43 ± 0.14 and 0.41 ± 0.15 for δ15N and δ13C, respectively. These traits had favourable moderate to high genetic and phenotypic correlations (- 0.78 ± 0.16 and - 0.40 ± 0.04, respectively). The study also provides informative single-breed results in spite of the limited sample size, with estimated heritability values of 0.37 ± 0.19 and 0.19 ± 0.17 for δ15N and δ13C in Brahman, and 0.36 ± 0.21 and 0.46 ± 0.22 for δ15N and δ13C in Droughtmaster, respectively. CONCLUSIONS: The findings of this study show, for the first time, that the natural abundances of both nitrogen and carbon isotopes in the tail hair in cattle may be moderately heritable. With further research and validation, tail hair isotopes can become a practical tool for the large-scale selection of more efficient cattle.

Comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine.

Cancer is still one of the most challenging diseases to treat, making the pursuit for novel molecules with potential anticancer activity an important research topic. Herein, we have performed a comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine. The former is a well-known bioluminescent substrate, while the latter is a metabolic product of the resulting bioluminescent reaction. While both types of analogs showed anticancer activity toward lung and gastric cancer cell lines, we have obtained data that highlight relevant differences between the activity of these two types of compounds. More specifically, we observed relevant differences in structure-activity relationships between these types of compounds. Also, coelenteramine analogs showed time-dependent activity, while coelenterazine-based compounds usually present time-independent activity. Coelenterazine analogs also appear to be relatively safer toward noncancer cells than coelenteramine analogs. There was also seen a correlation between the activity of the coelenterazine-based compounds and their light-emission properties. Thus, these results further indicate the potential of the marine coelenterazine chemi-/bioluminescent system as a source of new molecules with anticancer activity, while providing more insight into their modes of action.

Two pathways drive meiotic chromosome axis assembly in Saccharomyces cerevisiae.

Successful meiotic recombination, and thus fertility, depends on conserved axis proteins that organize chromosomes into arrays of anchored chromatin loops and provide a protected environment for DNA exchange. Here, we show that the stereotypic chromosomal distribution of axis proteins in Saccharomyces cerevisiae is the additive result of two independent pathways: a cohesin-dependent pathway, which was previously identified and mediates focal enrichment of axis proteins at gene ends, and a parallel cohesin-independent pathway that recruits axis proteins to broad genomic islands with high gene density. These islands exhibit elevated markers of crossover recombination as well as increased nucleosome density, which we show is a direct consequence of the underlying DNA sequence. A predicted PHD domain in the center of the axis factor Hop1 specifically mediates cohesin-independent axis recruitment. Intriguingly, other chromosome organizers, including cohesin, condensin, and topoisomerases, are differentially depleted from the same regions even in non-meiotic cells, indicating that these DNA sequence-defined chromatin islands exert a general influence on the patterning of chromosome structure.

Walk or be walked by the dog? The attachment role.

BACKGROUND: The human-animal bond has been recognized as having positive effects on the health and well-being of both humans and pets. The present study aims to explore the influence of attachment on physical activity (PA), lifestyle, and health outcomes of dog owners (DO), highlighting the mutual benefits resulting from the relationship between DO and dogs. METHODS: Thirty-eight DO and their dogs participated in this study. Socio-demographic data, the Self-Rated Health (SRH), FANTASTICO Lifestyle Scale, and the Lexington Attachment Pet Scale (LAPS) were assessed. PA was measured in both the DO and the dogs, using an ActiGraph GT3X accelerometer in the context of daily routine. Descriptive statistics and Spearman rank correlation analyses were performed to examine the associations between LAPS, PA levels, socio-demographic variables, lifestyle behaviors, and SRH. RESULTS: Significant correlations were found between the dog owners' light-level PA and the pets' vigorous level of PA (rho = 0.445, p = 0.01). Furthermore, the importance of the pets' health (rho = -0.785, p = 0.02) and the LAPS subscales, namely proximity (rho = 0.358, p = 0.03), and attachment (rho = 0.392, p = 0.01), were related to taking the pet for a walk. Regarding lifestyle, DO with a healthier lifestyle had a better self-assessment of their health using the SRH (rho = 0.39, p = 0.02). Moreover, DO with better lifestyles also exhibited greater concern for their pet's health (rho = 0.398, p = 0.01). CONCLUSIONS: This study emphasizes that individuals who adopt healthier habits tend to perceive themselves as healthier and exhibit greater concern for their pets' health. The attachment between DO and dogs is important in promoting healthy lifestyle behaviors and engagement in PA. Our results highlight that the presence of a dog is associated with a higher level of PA in DO, depending on the strength of the human-animal bond.

Neurococcidiomycosis in children with hydrocephalus: assessment of functional outcome, quality of life and survival in relation to neuroimaging findings.

PURPOSE: Coccidioidal meningitis (CM) is an uncommon disease frequently misdiagnosed. Neuroimaging and mortality are not considered in detail in previous pediatric CM series. Our objective is to evaluate outcome of pediatric neurococcidiomycosis in relation to neuroimaging findings. METHODS: We performed a prospective, observational, cross-sectional study in children with hydrocephalus and CM treated at Specialties Hospital in Torreon, Mexico (between 2015 and 2020). The outcome was evaluated by Hydrocephalus Outcome Questionnaire (HOQ) and the modified Rankin Scale (mRS). Follow-up was established at the first shunt surgery and survival since CM diagnosis confirmation. Neuroimaging was analyzed in relation to clinical data, outcome and survival. Kaplan-Meier analysis was performed with IBM-SPSS-25. RESULTS: Ten pediatric cases with CM and hydrocephalus were reported. Aged 6-228 months, 60% were female. Mean number of surgeries was 4.3 SD ± 3 (range 1-15). Asymmetric hydrocephalus was the most common neuroimaging finding (70%), followed by cerebral vasculitis (20%) and isolated fourth ventricle (IFV) (20%). The mean HOQ overall score was 0.338 SD ± 0.35. A minimum follow-up of 18 months was reported. Mean survival was 13.9 SD ± 6.15 months (range 3-24). Poor survival was correlated with asymmetric hydrocephalus (p = 0.335), cerebral vasculitis (p = 0.176), IFV (p < 0.001), bacterial superinfection (p = 0.017), lower mRS scores at hospital discharge (p = 0.017) and during follow-up (p = 0.004). The mortality rate was 20%. CONCLUSIONS: We report the largest series in Latin America of pediatric CM and hydrocephalus. Asymmetric hydrocephalus, IFV and cerebral vasculitis are complications that increase mortality and must be early diagnosed for a timely surgical and medical treatment. HOQ and mRS could be alternative scales to evaluate outcome in these patients. After a long follow-up (18 months), survival remained poor after diagnosis confirmation in our series.

Automated treatment planning for whole breast irradiation with individualized tangential IMRT fields.

PURPOSES: This study aimed to develop and validate algorithms for automating intensity modulated radiation therapy (IMRT) planning in breast cancer patients, with a focus on patient anatomical characteristics. MATERIAL AND METHODS: We retrospectively selected 400 breast cancer patients without lymph node involvement for automated treatment planning. Automation was achieved using the Eclipse Scripting Application Programming Interface (ESAPI) integrated into the Eclipse Treatment Planning System. We employed three beam insertion geometries and three optimization strategies, resulting in 3600 plans, each delivering a 40.05 Gy dose in 15 fractions. Gantry angles in the tangent fields were selected based on a criterion involving the minimum intersection area between the Planning Target Volume (PTV) and the ipsilateral lung in the Beam's Eye View projection. ESAPI was also used to gather patient anatomical data, serving as input for Random Forest models to select the optimal plan. The Random Forest classification considered both beam insertion geometry and optimization strategy. Dosimetric data were evaluated in accordance with the Radiation Therapy Oncology Group (RTOG) 1005 protocol. RESULTS: Overall, all approaches generated high-quality plans, with approximately 94% meeting the acceptable dose criteria for organs at risk and/or target coverage as defined by RTOG guidelines. Average automated plan generation time ranged from 6 min and 37 s to 9 min and 22 s, with the mean time increasing with additional fields. The Random Forest approach did not successfully enable automatic planning strategy selection. Instead, our automated planning system allows users to choose from the tested geometry and strategy options. CONCLUSIONS: Although our attempt to correlate patient anatomical features with planning strategy using machine learning tools was unsuccessful, the resulting dosimetric outcomes proved satisfactory. Our algorithm consistently produced high-quality plans, offering significant time and efficiency advantages.

A Review of Natural Polysaccharides: Sources, Characteristics, Properties, Food, and Pharmaceutical Applications.

Natural polysaccharides, which are described in this study, are some of the most extensively used biopolymers in food, pharmaceutical, and medical applications, because they are renewable and have a high level of biocompatibility and biodegradability. The fundamental understanding required to properly exploit polysaccharides potential in the biocomposite, nanoconjugate, and pharmaceutical industries depends on detailed research of these molecules. Polysaccharides are preferred over other polymers because of their biocompatibility, bioactivity, homogeneity, and bioadhesive properties. Natural polysaccharides have also been discovered to have excellent rheological and biomucoadhesive properties, which may be used to design and create a variety of useful and cost-effective drug delivery systems. Polysaccharide-based composites derived from natural sources have been widely exploited due to their multifunctional properties, particularly in drug delivery systems and biomedical applications. These materials have achieved global attention and are in great demand because to their biochemical properties, which mimic both human and animal cells. Although synthetic polymers account for a substantial amount of organic chemistry, natural polymers play a vital role in a range of industries, including biomedical, pharmaceutical, and construction. As a consequence, the current study will provide information on natural polymers, their biological uses, and food and pharmaceutical applications.

Remediation through the coordinated use of local rice husk residues for the selective adsorption of iron and nickel in real landfill leachate.

Herein, we demonstrate the prospects of tackling several environmental problems by transforming a local rice husk residue into an effective adsorbent, which was then applied for the treatment of real landfill leachate (LL). The study focused on establishing (i) the effect of simple washing on morphological aspects, (ii) evaluating target adsorption capacity for total iron (Fe) and nickel (Ni), (iii) determining regeneration and reuse potential of the adsorbent and (iv) complying to the requirements of worldwide legislations for reuse of treated LL wastewater. The adsorbent was prepared by employing a simple yet effective purification process that can be performed in situ. The LL was collected post-membrane treatment, and the characterizations revealed high concentrations of Fe, Ni, and organic matter content. The simple washing affected the crystallinity, resulting in structural alterations of the adsorbents, also increasing the porosity and specific surface. The adsorption process for Ni occurred naturally at pH 6, but adjusting the pH to 3 significantly improved removal efficiency and adsorption capacity for total Fe. The kinetics were accurately described by the pseudo-second-order model, while the Langmuir model provided a better fit for the isotherms. The adsorbent was stable for 5 reuses, and the metals adsorbed were recovered through basic leaching. The removal capacities achieved underscore the remarkable effectiveness of the process, ensuring the treated LL wastewater meets rigorous global environmental legislations for safe use in irrigation. Thus, by employing the compelling methods herein optimized it is possible to refer to the of solving three environmental problems at once.

Histological biomarkers and microbiological parameters of an estuarine fish from the Brazilian Amazon coast as potential indicators of risk to human health.

This study aimed to isolate and identify pathogenic bacteria in the intestinal tract, skin, and muscles of Sciades herzbergii; detect histopathological changes in the gill and liver; and use these biomarkers for the assessment of potential risks to human health. Fish were sampled during the rainy and dry seasons at two points in São Marcos Bay, Maranhão, Brazil: Ilha dos Caranguejos (IC) and Porto Grande (PG). Isolation and quantification were carried out using COLItest®. Colonies were subjected to identification and phenotypic investigation of antimicrobial resistance using Vitek®. Gill and liver samples were subjected to routine histological examination. The results indicated the presence of Klebsiella pneumoniae and Escherichia coli, the latter of which showed phenotypic resistance to norfloxacin and gentamicin. Fish caught at PG exhibited more extensive gill and liver damage than fish caught at IC. The findings suggest that histological changes in target organs of S. herzbergii may be influenced by infection with pathogenic bacteria.

Neutrophil virucidal activity against SARS-CoV-2 is mediated by NETs.

BACKGROUND: The inflammation in the lungs and other vital organs in COVID-19 are characterized by the presence of neutrophils and high concentration of neutrophil extracellular traps (NETs), which also seems to mediate host tissue damage. However, it is not known whether NETs could have virucidal activity against SARS-CoV-2. METHODS: We investigated whether NETs could prevent SARS-CoV-2 replication in neutrophils and epithelial cells, and what the consequence of NETs degradation in K18-humanized ACE2 transgenic mice infected with SARS-CoV-2. RESULTS: Here, by immunofluorescence microscopy we observed that viral particles co-localize with NETs in neutrophils isolated from COVID-19 patients or from healthy individuals and infected in vitro. The inhibition of NETs production increased virus replication in neutrophils. In parallel, we observed that NETs inhibited virus abilities to infect and replicate in epithelial cells after 24 h of infection. Degradation of NETs with DNase I prevented their virucidal effect in vitro. Using K18-humanized ACE2 transgenic mice we observed a higher viral load in animals treated with DNase I. On the other hand, the virucidal effect of NETs was not dependent on neutrophil elastase or myeloperoxidase activity. CONCLUSION: Our results provide evidence of the role of NETosis as a mechanism of SARS-CoV-2 viral capture and inhibition.