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This paper presents a method for designing low carbon bio-based building materials, also named bio-concretes, produced with wood wastes in shavings form (WS) and cementitious pastes. As the aggregates phase of bio-concretes is composed of plant-based particles, known as porous and high water-absorbing materials, the bio-concretes cannot be designed by using the traditional design rules used for conventional mortar or concrete. Then, the method used in the current paper is an adaptation of a previous one that has been developed in a recent paper where bio-concretes were produced with a cement matrix, three types of bio-aggregates, and a proposal of a design abacus. However, when that abacus is used for designing WBC with low cement content in the matrix, the target compressive strength is not reached. In the present paper, the method is extended to low cement content matrix (up to 70% of cement substitution) and also considering the greenhouse gas (GHG) emission of the WBC. To obtain data for proposing a new design abacus, an experimental program was carried out by producing nine workable WBCs, varying wood volumetric fractions (40–45–50%), and water-to-binder ratios. The bio-concretes produced presented adequate consistency, lightness (density between 715 and 1207 kg/m3), and compressive strength ranging from 0.64 to 12.27 MPa. In addition, the GHG emissions of the WBC were analysed through the Life Cycle Assessment methodology. From the relationships obtained between density, compressive strength, water-to-binder ratio, cement consumption, and GHG emissions of the WBC, calibration constants were proposed for developing the updated and more complete abacus regarding an integrated mix design methodology. [ABSTRACT FROM AUTHOR]

Embolization of de novo pulmonary arteriovenous malformations (PAVMs) using high-volume detachable non-fibered (HVDNF) coils was compared to traditional non-HVDNF coils. Persistent-occlusion rates were evaluated. A total of 272 de novo (previously untreated) PAVM treatments were retrospectively stratified into those treated with non-HVDNF coils only (n = 192) and those treated with HVDNF coils with or without other coils (n = 80). Propensity score matching, followed by survival analysis and cost analysis, was performed. The overall persistent-occlusion rate was 86.0% (234/272). Persistent occlusion was achieved in 81.8% of PAVMs using non-HVDNF coils, compared with 96.3% using HVDNF coils (p = 0.0017). The mean follow-up was 30.7 ± 31.9 months versus 14.7 ± 13.4 months, respectively (p < 0.0001). Propensity-matched survival analysis demonstrated PAVMs treated with HVDNF coils recurred significantly less frequently than PAVMs treated with non-HVNDF coils (p = 0.023). The use of HVDNF coils was more expensive than standard coils, however not significantly different for the treatment of complex PAVMs. The use of high-volume detachable non-fibered coils was associated with higher persistent-occlusion rates when compared with non-HVDNF coils. HVDNF coils were more expensive on average; however, cost was similar between groups for the treatment of complex PAVMs. [ABSTRACT FROM AUTHOR]

New disease targets and medicinal chemistry approaches are urgently needed to develop novel therapeutic strategies for treating pulmonary diseases. Emerging evidence suggests that reduced activity of protein phosphatase 2A (PP2A), a complex heterotrimeric enzyme that regulates dephosphorylation of serine and threonine residues from many proteins, is observed in multiple pulmonary diseases, including lung cancer, smoke-induced chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, asthma, and idiopathic pulmonary fibrosis. Loss of PP2A responses is linked to many mechanisms associated with disease progressions, such as senescence, proliferation, inflammation, corticosteroid resistance, enhanced protease responses, and mRNA stability. Therefore, chemical restoration of PP2A may represent a novel treatment for these diseases. This review outlines the potential impact of reduced PP2A activity in pulmonary diseases, endogenous and exogenous inhibitors of PP2A, details the possible PP2A-dependent mechanisms observed in these conditions, and outlines potential therapeutic strategies for treatment. Substantial medicinal chemistry efforts are underway to develop therapeutics targeting PP2A activity. The development of specific activators of PP2A that selectively target PP2A holoenzymes could improve our understanding of the function of PP2A in pulmonary diseases. This may lead to the development of therapeutics for restoring normal PP2A responses within the lung. [ABSTRACT FROM AUTHOR]

Digital breast tomosynthesis (DBT) reconstructions introduce out-of-plane artifacts and false-tissue boundaries impacting the dense/adipose and breast outline (convex hull) segmentations. A virtual clinical trial method was proposed to segment both the breast tissues and the breast outline in DBT reconstructions. The DBT images of a representative population were simulated using three acquisition geometries: a left–right scan (conventional, I), a two-directional scan in the shape of a "T" (II), and an extra-wide range (XWR, III) left–right scan at a six-times higher dose than I. The nnU-Net was modified including two losses for segmentation: (1) tissues and (2) breast outline. The impact of loss (1) and the combination of loss (1) and (2) was evaluated using models trained with data simulating geometry I. The impact of the geometry was evaluated using the combined loss (1&2). The loss (1&2) improved the convex hull estimates, resolving 22.2% of the false classification of air voxels. Geometry II was superior to I and III, resolving 99.1% and 96.8% of the false classification of air voxels. Geometry III (Dice = (0.98, 0.94)) was superior to I (0.92, 0.78) and II (0.93, 0.74) for the tissue segmentation (adipose, dense, respectively). Thus, the loss (1&2) provided better segmentation, and geometries T and XWR improved the dense/adipose and breast outline segmentations relative to the conventional scan. [ABSTRACT FROM AUTHOR]

In recent years, polymeric materials have been gaining prominence in studies of controlled release systems to obtain improvements in drug administration. These systems present several advantages compared with conventional release systems, such as constant maintenance in the blood concentration of a given drug, greater bioavailability, reduction of adverse effects, and fewer dosages required, thus providing a higher patient compliance to treatment. Given the above, the present work aimed to synthesize polymeric matrices derived from polyethylene glycol (PEG) capable of promoting the controlled release of the drug ketoconazole in order to minimize its adverse effects. PEG 4000 is a widely used polymer due to its excellent properties such as hydrophilicity, biocompatibility, and non-toxic effects. In this work, PEG 4000 and derivatives were incorporated with ketoconazole. The morphology of polymeric films was observed by AFM and showed changes on the film organization after drug incorporation. In SEM, it was possible to notice spheres that formed in some incorporated polymers. The zeta potential of PEG 4000 and its derivatives was determined and suggested that the microparticle surfaces showed a low electrostatic charge. Regarding the controlled release, all the incorporated polymers obtained a controlled release profile at pH 7.3. The release kinetics of ketoconazole in the samples of PEG 4000 and its derivatives followed first order for PEG 4000 HYDR INCORP and Higuchi for the other samples. Cytotoxicity was determined and PEG 4000 and its derivatives were not cytotoxic. [ABSTRACT FROM AUTHOR]

The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain–Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that immunization of mice with a single dose of the nanoparticle vaccine candidate (zDIII-F) resulted in the robust induction of neutralizing antibody responses that protected the animals from the lethal ZIKV challenge. The antibodies neutralized infectivity of other ZIKV lineages indicating that the zDIII-F can confer heterologous protection. The vaccine candidate also induced a significantly higher frequency of interferon (IFN)-γ positive CD4 T cells and CD8 T cells suggesting that both humoral and cell-mediated immune responses were induced by the vaccine candidate. Although our studies showed that a soluble DIII vaccine candidate could also induce humoral and cell-mediated immunity and protect from lethal ZIKV challenge, the immune responses and protection conferred by the nanoparticle vaccine candidate were superior. Further, passive transfer of neutralizing antibodies from the vaccinated animals to naïve animals protected against lethal ZIKV challenge. Since previous studies have shown that antibodies directed at the DIII region of the E protein do not to induce antibody-dependent enhancement (ADE) of ZIKV or other related flavivirus infections, our studies support the use of the zDIII-F nanoparticle vaccine candidate for safe and enhanced immunological responses against ZIKV. [ABSTRACT FROM AUTHOR]

Despite numerous efforts over the last three decades, nucleic acid-based therapeutics still lack delivery platforms in the clinical stage. Cell-penetrating peptides (CPPs) may offer solutions as potential delivery vectors. We have previously shown that designing a "kinked" structure in the peptide backbone resulted in a CPP with efficient in vitro transfection properties. Further optimization of the charge distribution in the C-terminal part of the peptide led to potent in vivo activity with the resultant CPP NickFect55 (NF55). Currently, the impact of the linker amino acid was further investigated in the CPP NF55, with the aim to discover potential transfection reagents for in vivo application. Taking into account the expression of the delivered reporter in the lung tissue of mice, and the cell transfection in the human lung adenocarcinoma cell line, the new peptides NF55-Dap and NF55-Dab* have a high potential for delivering nucleic acid-based therapeutics to treat lung associated diseases, such as adenocarcinoma. [ABSTRACT FROM AUTHOR]

Bone marrow transplantation is a treatment for a variety of hematological and non-hematological diseases. For the transplant success, it is mandatory to have a thriving engraftment of transplanted cells, which directly depends on their homing. The present study proposes an alternative method to evaluate the homing and engraftment of hematopoietic stem cells using bioluminescence imaging and inductively coupled plasma mass spectrometry (ICP-MS) associated with superparamagnetic iron oxide nanoparticles. We have identified an enriched population of hematopoietic stem cells in the bone marrow following the administration of Fluorouracil (5-FU). Lately, the cell labeling with nanoparticles displayed the greatest internalization status when treated with 30 µg Fe/mL. The quantification by ICP-MS evaluate the stem cells homing by identifying 3.95 ± 0.37 µg Fe/mL in the control and 6.61 ± 0.84 µg Fe/mL in the bone marrow of transplanted animals. In addition, 2.14 ± 0.66 mg Fe/g in the spleen of the control group and 2.17 ± 0.59 mg Fe/g in the spleen of the experimental group was also measured. Moreover, the bioluminescence imaging provided the follow up on the hematopoietic stem cells behavior by monitoring their distribution by the bioluminescence signal. Lastly, the blood count enabled the monitoring of animal hematopoietic reconstitution and ensured the transplantation effectiveness. [ABSTRACT FROM AUTHOR]

The recent advances in unmanned aerial vehicle (UAV)-based remote sensing systems have broadened the remote sensing applications for agriculture. Despite the great possibilities of using UAVs to monitor agricultural fields, specific problems related to missing parts in UAV orthomosaics due to drone flight restrictions are common in agricultural monitoring, especially in large areas. In this study, we propose a methodological framework to impute missing parts of UAV orthomosaics using PlanetScope (PS) and Sentinel-2 (S2) data and the random forest (RF) algorithm of an integrated crop–livestock system (ICLS) covered by grass at the time. We validated the proposed framework by simulating and imputing artificial missing parts in a UAV orthomosaic and then comparing the original data with the model predictions. Spectral bands and the normalized difference vegetation index (NDVI) derived from PS, as well as S2 images (separately and combined), were used as predictor variables of the UAV spectral bands and NDVI in developing the RF-based imputation models. The proposed framework produces highly accurate results (RMSE = 6.77–17.33%) with a computationally efficient and robust machine-learning algorithm that leverages the wealth of empirical information present in optical satellite imagery (PS and S2) to impute up to 50% of missing parts in a UAV orthomosaic. [ABSTRACT FROM AUTHOR]

(1) Background: COVID-19 vaccination in Brazil has been performed mostly with CoronaVac (Sinovac), ChAdOx1-S (AstraZeneca-University of Oxford) and BNT162b2 (Pfizer-BioNTech) vaccines. The titers of IgG antibodies reactive to the SARS-CoV-2 spike protein correlate with vaccine efficacy. Studies comparing vaccine immunogenicity in a real-world scenario are lacking. (2) Methods: We performed a population-based study to analyze the immunoglobulin G response to different COVID-19 vaccines. Citizens older than 18 years (n = 2376) provided personal data, a self-declaration of any previous COVID-19 positive tests and information regarding COVID-19 vaccination: the vaccine popular name and the date of each dose. Blood samples were collected and the levels of IgG reactive to SARS-CoV-2 antigens were determined and compared between different vaccine groups. (3) Results: The seroconversion for anti-spike IgG achieved > 95% by February 2022 and maintained stable until June 2022. Higher anti-spike IgG titers were detected in individuals vaccinated with BNT162b2, followed by ChAdOx1-S and CoronaVac. The anti-spike IgG response was negatively correlated with age and interval after the second dose for the BNT162b2 vaccine. Natural infections boosted anti-spike IgG in those individuals who completed primary vaccination with ChAdOx1-S and CoronaVac, but not with BNT162b2. The levels of anti-spike IgG increased with the number of vaccine doses administered. The application of BNT162b2 as a 3rd booster dose resulted in high anti-spike IgG antibody titers, despite the type of vaccine used during primary vaccination. (4) Conclusions: Our data confirmed the effectiveness of the Brazilian vaccination program. Of the vaccines used in Brazil, BNT162b2 performed better to elicit anti-spike protein IgG after primary vaccination and as a booster dose and thus should be recommended as a booster whenever available. A continuous COVID-19 vaccination program will be required to sustain anti-spike IgG antibodies in the population. [ABSTRACT FROM AUTHOR]

Simple Summary: Magnetic nanoparticles can render therapeutics or drugs magnetically guidable, which enables their targeted transport to the diseased tissue in the patient's body. Before its translation into patients, the efficacy of magnetic accumulation must be tested in cell culture systems. To analyze magnetic enrichment under conditions similar to blood flow, we established an experimental in vitro setup with a tumor spheroid placed in a perfused chamber: with this, we showed that it is possible to accumulate cells or chemotherapeutics at the tumor, increasing their therapeutic efficacy. Superparamagnetic iron oxide nanoparticles (SPIONs) are used in nanomedicine as transporter systems for therapeutic cargos, or to magnetize cells to make them magnetically guidable. In cancer treatment, the site-directed delivery of chemotherapeutics or immune effector cells to the tumor can increase the therapeutic efficacy in the target region, and simultaneously reduce toxic side-effects in the rest of the body. To enable the transfer of new methods, such as the nanoparticle-mediated transport from bench to bedside, suitable experimental setups must be developed. In vivo, the SPIONs or SPION-loaded cells must be applied into the blood stream, to finally reach the tumor: consequently, targeting and treatment efficacy should be analyzed under conditions which are as close to in vivo as possible. Here, we established an in vitro method, including tumor spheroids placed in a chamber system under the influence of a magnetic field, and adapted to a peristaltic pump, to mimic the blood flow. This enabled us to analyze the magnetic capture and antitumor effects of magnetically targeted mitoxantrone and immune cells under dynamic conditions. We showed that the magnetic nanoparticle-mediated accumulation increased the anti-tumor effects, and reduced the unspecific distribution of both mitoxantrone and cells. Especially for nanomedical research, investigation of the site-specific targeting of particles, cells or drugs under circulation is important. We conclude that our in vitro setup improves the screening process of nanomedical candidates for cancer treatment. [ABSTRACT FROM AUTHOR]

Insufficient invasion of conceptus-derived trophoblast cells in the maternal decidua is a key event in the development of early-onset preeclampsia (PE), a subtype of PE associated with high maternal and fetal morbidity and mortality. Kisspeptins, a family of peptides previously shown to inhibit trophoblast cell invasion, have been implicated in the pathogenesis of early-onset PE. However, a role of kisspeptin signaling during the genesis of this syndrome has not been elucidated. Herein, we used the preeclamptic-like BPH/5 mouse model to investigate kisspeptin expression and potential upstream regulatory mechanisms in a PE-like syndrome. Expression of the kisspeptin encoding gene, Kiss1, and the 10-amino-acid kisspeptide (Kp-10), are upregulated in the non-pregnant uterus of BPH/5 females during diestrus and in the maternal-fetal interface during embryonic implantation and decidualization. Correspondingly, the dysregulation of molecular pathways downstream to kisspeptins also occurs in this mouse model. BPH/5 females have abnormal sex steroid hormone profiles during early gestation. In this study, the normalization of circulating concentrations of 17β-estradiol (E2) and progesterone (P4) in pregnant BPH/5 females not only mitigated Kiss1 upregulation, but also rescued the expression of multiple molecules downstream to kisspeptin and ameliorated adverse fetoplacental outcomes. Those findings suggest that uterine Kiss1 upregulation occurs pre-pregnancy and persists during early gestation in a PE-like mouse model. Moreover, this study highlights the role of sex steroid hormones in uteroplacental Kiss1 dysregulation and the improvement of placentation by normalization of E2, P4 and Kiss1. [ABSTRACT FROM AUTHOR]

The techniques and analyses employed by remote sensing provide key information about atmospheric particle properties at regional and global scales. However, limitations in optical spectral models used to represent the different types of aerosols in the atmosphere and their effects (direct and indirect) are still one of the major causes of sources of uncertainties and substantial impacts in climate prediction. There are no studies yet in South America, especially in the Amazon Basin, that have evaluated the advantages, disadvantages, inconsistencies, applicability, and suitability of the MODIS sensor (Moderate Resolution Imaging Spectroradiometer) destined for monitoring the ambient aerosol optical thickness over rivers and continents. In this study, the results of the DT (Dark Target) algorithm for products with 3 km and 10 km resolutions were systematically evaluated for six sites in the Amazon rainforest. The comparisons between the products were carried out with the AERONET (Aerosol Robotic Network) measurements, which were used as reference. Statistical parameters between AERONET vs. MODIS were also evaluated based on biomass burning records in the site regions. Here, the DT 10 km product showed satisfactory performance for the Amazon region, with observations between the expected error (EE) limits above 66%, in addition to R > 0.8 and RMSE < 0.3. However, the regional analysis for the two sites in the central and southern regions of the Amazon basin did not have the same performance, where the results showed an EE of 24 and 47%, respectively. The DT 3 km product did not perform well in any site, with an EE below 50%. Both products overestimated the AOD, but the 3 km product overestimated it approximately four times more due to its algorithm setup. Thus, we recommend the 10 km product for general analysis in Amazonia. Regional biomass burning records showed a direct relationship with the AERONET vs. MODIS DT with overestimation of both products. All variations between products and sites were justified based on the difficulty of retrieving surface reflectance and the model selected for local aerosols. Improvements in the optical spectral model currently implemented in the algorithms, with more realistic representations of the main types of the aerosol present in the Amazon Basin, may contribute to better performance among the evaluated products. [ABSTRACT FROM AUTHOR]

Health is influenced by how the gut microbiome develops as a result of external and internal factors, such as nutrition, the environment, medication use, age, sex, and genetics. Alpha and beta diversity metrics and (enterotype) clustering methods are commonly employed to perform population studies and to analyse the effects of various treatments, yet, with the continuous development of (new) sequencing technologies, and as various omics fields as a result become more accessible for investigation, increasingly sophisticated methodologies are needed and indeed being developed in order to disentangle the complex ways in which the gut microbiome and health are intertwined. Diseases of affluence, such as type 2 diabetes (T2D) and cardiovascular diseases (CVD), are commonly linked to species associated with the Bacteroides enterotype(s) and a decline of various (beneficial) complex microbial trophic networks, which are in turn linked to the aforementioned factors. In this review, we (1) explore the effects that some of the most common internal and external factors have on the gut microbiome composition and how these in turn relate to T2D and CVD, and (2) discuss research opportunities enabled by and the limitations of some of the latest technical developments in the microbiome sector, including the use of artificial intelligence (AI), strain tracking, and peak to trough ratios. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a degenerative genetic myopathy characterized by complete absence of dystrophin. Although the mdx mouse lacks dystrophin, its phenotype is milder compared to DMD patients. The incorporation of a null mutation in the Cmah gene led to a more DMD-like phenotype (i.e., more fibrosis). Although fibrosis is thought to be the major determinant of 'structural weakness', intracellular remodeling of myofibrillar geometry was shown to be a major cellular determinant thereof. To dissect the respective contribution to muscle weakness, we assessed biomechanics and extra- and intracellular architecture of whole muscle and single fibers from extensor digitorum longus (EDL) and diaphragm. Despite increased collagen contents in both muscles, passive stiffness in mdx Cmah − / − diaphragm was similar to wt mice (EDL muscles were twice as stiff). Isometric twitch and tetanic stresses were 50% reduced in mdx Cmah − / − diaphragm (15% in EDL). Myofibrillar architecture was severely compromised in mdx Cmah − / − single fibers of both muscle types, but more pronounced in diaphragm. Our results show that the mdx Cmah − / − genotype reproduces DMD-like fibrosis but is not associated with changes in passive visco-elastic muscle stiffness. Furthermore, detriments in active isometric force are compatible with the pronounced myofibrillar disarray of the dystrophic background. [ABSTRACT FROM AUTHOR]

Hydrogels are a great ally in the pharmaceutical and biomedical areas. They have a three-dimensional polymeric structure that allows the swelling of aqueous fluids, acting as an absorbent, or encapsulating bioactive agents for controlled drug release. Interestingly, plants are a source of biogels, specifically polysaccharides, composed of sugar monomers. The crosslinking of these polymeric chains forms an architecture similar to the extracellular matrix, enhancing the biocompatibility of such materials. Moreover, the rich hydroxyl monomers promote a hydrophilic behavior for these plant-derived polysaccharide gels, enabling their biodegradability and antimicrobial effects. From an economic point of view, such biogels help the circular economy, as a green material can be obtained with a low cost of production. As regards the bio aspect, it is astonishingly attractive since the raw materials (polysaccharides from plants-cellulose, hemicelluloses, lignin, inulin, pectin, starch, guar, and cashew gums, etc.) might be produced sustainably. Such properties make viable the applications of these biogels in contact with the human body, especially incorporating drugs for controlled release. In this context, this review describes some sources of plant-derived polysaccharide gels, their biological function, main methods for extraction, remarkable applications, and properties in the health field. [ABSTRACT FROM AUTHOR]

Natural polysaccharides are structures composed of highly diversified biological macromolecules whose properties have been exploited by a diversity of industries. Until 2018, the polysaccharides market raised more than US $ 12 billion worldwide, while an annual growth forecast of 4.8% is expected by 2026. The food industry is largely responsible for the consumption of this plant-source material, produced by microbiological fermentation. Among the used polysaccharides, gums are hydrocolloids obtained from a variety of sources and in different forms, being composed of salts of calcium, potassium, magnesium and sugar monomers. Their non-toxicity, hydrophilicity, viscosity, biodegradability, biocompatibility and sustainable production are among their main advantages. Although Brazil is amongst the largest producers of cashew gum, reaching 50 tons per year, the polysaccharide is not being used to its full potential, in particular, with regard to its uses in pharmaceuticals. Cashew gum (CG), obtained from Anacardium occidentale L., caught the attention of the industry only in 1970; in 1990, its production started to grow. Within the Brazilian academy, the groups from the Federal University of Ceará and Piauí are devoting the most efforts to the study of cashew gum, with a total of 31 articles already published. The number of patents in the country for innovations containing cashew tree gum has reached 14, including the technological process for the purification of cashew tree gum, comparison of physical and chemical methods for physicochemical characterizations, and optimum purification methodology. This scenario opens a range of opportunities for the use of cashew gum, mainly in the development of new pharmaceutical products, with a special interest in nanoparticles. [ABSTRACT FROM AUTHOR]

Simple Summary: It is often mentioned that calf stress is reduced when a two-stage weaning method is adopted. However, is this always the case? Here, we describe the occurrence of negative effects on the nostrils of calves from the use of nose-flap devices to aid weaning, which can lead to health and welfare impoverishment. Commercial nose-flap devices were fitted in the nostrils of 21 pure and 20 crossbred Nellore calves for five days. Nose-flap retention was 73.2%. Without exception, all calves showed open wounds in the nasal septum, including those that lost the device before day five. Almost half of the calves showed weight loss during the period wearing the nose-flap devices. Due to the incidence of nasal-septum injuries, it is imperative that more studies be done to assess these overlooked effects of the two-stage weaning method, which is referred to as a low-stress practice for beef calves. This case report aims to describe the occurrence of negative impacts of wearing nose-flap devices on beef calves subjected to the two-stage weaning method. Forty-one calves, twenty-one pure Nellore and twenty F1 Angus-Nellore, were weaned on average at 236 days of age. Commercial nose-flap devices were fitted in the nostrils of the calves (d0) to prevent suckling and removed five days later (d5). Individual body weights were assessed at d0 and d5, and average daily gain (ADG) was calculated. At d5, during nose-flap device removal, it was noted that 26.8% of the calves lost the nose-flap device; however, all of them had wounds in their nostrils (no injuries in the nostrils had been observed on d0). To assess the severity of these injuries, an impairment score was assigned to each calf, ranging from 1 = no lesions to 5 = injured with purulent discharge. A logistic regression model was fitted to evaluate the effect of sex and genetic group on nose-flap retention (kept or lost). The retention rate did not differ (p > 0.05) between sex and genetic groups. All calves showed at least open wounds of the nasal septum (score 2), including those that lost the nose-flaps before d5. Almost half of the calves showed weight loss during this period. We conclude that there is a considerable risk of the two-stage weaning method compromising the physical integrity of the nostrils of beef calves through the use of these devices, and due to this, it should not be referred to as a low-stress weaning practice for beef calves. [ABSTRACT FROM AUTHOR]

The integration and analysis of multi-omics modalities is an important challenge in bioinformatics and data science in general. A standard approach is to conduct a series of univariate tests to determine the significance for each parameter, but this underestimates the connected nature of biological data and thus increases the number of false-negative errors. To mitigate this issue and to understand how different omics' data domains are jointly affected, we used the Stacked Regularization model with Bayesian optimization over its full parameter space. We applied this approach to a multi-omics data set consisting of microbiota, metabolites and clinical data from two recent clinical studies aimed at detecting the impact of replacing part of the vegetable fat in infant formula with bovine milk fat on healthy term infants. We demonstrate how our model achieves a high discriminative performance, show the advantages of univariate testing and discuss the detected outcome in its biological context. [ABSTRACT FROM AUTHOR]

In continental countries, building materials are often moved over long distances from factories to building sites. This is especially important when quality and performance certification systems are required for the building materials' acquisition. In this scenario, the transportation phase tends to have a great contribution to building materials' environmental impacts. Taking into consideration that countries such as China, India, and Brazil, i.e., continental countries, are expecting the largest future housing demand, the issue of transportation will have a crucial role in environmental impacts. Through a Brazilian case study, the present work investigates the potential environmental impacts of structural masonry made of concrete and ceramic blocks certified by the Brazilian Quality Program. A cradle-to-site Life-Cycle Assessment (LCA) is carried out while considering a country-level approach using data from the literature and Ecoinvent. The results show that ceramic blocks are preferable for most states and scenarios. Human Health and Ecosystem Quality are the two categories most affected by transportation, and they can reach more than 96% and 99%, respectively. The efficiency of the building material transportation system plays an important role in reducing greenhouse gas emissions. A shift in building components from concrete to ceramic blocks has the potential to mitigate between 154 and 229 Mt CO2-eq between 2020 and 2050. The methodological approach used in this work can be applied to other building materials and other countries, especially those of continental dimensions that are expected to have a significant future housing demand. [ABSTRACT FROM AUTHOR]

This study describes the use of a smartphone for monitoring acid-base titrations on wax printed paper microzones. An array of twelve microzones of 5 mm diameter each was wax printed on filter paper. The analytical performance of the proposed devices was explored with acid-base titrations examples, where jaboticaba peel extract was used as a natural pH indicator. The color intensity was captured using a smartphone and analyzed through a free App named Photometrix®. Before titrations, color intensity versus pH was calibrated to be used as a reference in titrations as (i) strong acid versus strong base; (ii) strong base versus strong acid; and (iii) weak acid versus strong base. In all examples, images were obtained after the addition of each aliquot of titrant solutions. The obtained titration curves showed the same behavior as the conventional titration curves. After evaluating the feasibility of the proposed methodology, the concentration level of acetic acid was obtained in three vinegar samples. Although the obtained values ranged from 5% to 8% compared to the concentrations on the conventional method, the proposed methodology presented high analytical reliability. The calculated concentrations of acetic acid in three samples ranged from 3.87% to 3.93%, and the proposed methodology did not significantly differ from classic acid-base titration at a confidence level of 95%. The acid-base titration on paper-based devices is outstanding, since any titration can be completed within 5 min using 20 μL volumes. Besides, the use of a smartphone to capture images followed by analysis in a free app offers simplicity to all users. The proposed methodology arises as a new strand to be exploited in the diffusion of the analytical chemistry education field as well as an alternative for quantitative analysis with extremely simplified instrumentation. [ABSTRACT FROM AUTHOR]

Precision agriculture is crucial for increasing food output without expanding the cultivable area, which requires sensors to be deployed for controlling the level of nutrients in the soil. In this paper, we report on a microfluidic electronic tongue (e-tongue) based on impedance measurements which is capable of distinguishing soil samples enriched with plant macronutrients. The e-tongue setup consisted of an array of sensing units made with layer-by-layer films deposited onto gold interdigitated electrodes. Significantly, the sensing units could be reused with adequate reproducibility after a simple washing procedure, thus indicating that there is no cross-contamination in three independent sets of measurements. A high performance was achieved by treating the capacitance data with the multidimensional projection techniques Principal Component Analysis (PCA), Interactive Document Map (IDMAP), and Sammon's Mapping. While an optimized performance was demonstrated with IDMAP and feature selection, during which data of a limited frequency range were used, the distinction of all soil samples was also possible with the well-established PCA analysis for measurements at a single frequency. The successful use of a simple microfluidic e-tongue for soil analysis paves the way for enhanced tools to support precision agriculture. [ABSTRACT FROM AUTHOR]

Poor linear growth is common in children with cystic fibrosis (CF) and predicts pulmonary status and mortality. Growth impairment develops in infancy, prior to pulmonary decline and despite aggressive nutritional measures. We hypothesized that growth restriction during early childhood in CF is associated with reduced adult height. We used the Cystic Fibrosis Foundation (CFF) patient registry to identify CF adults between 2011 and 2015 (ages 18–19 y, n = 3655) and had height for age (HFA) records between ages 2 and 4 y. We found that only 26% CF adults were ≥median HFA and 25% were <10th percentile. Between 2 and 4 years, those with height < 10th percentile had increased odds of being <10th percentile in adulthood compared to children ≥ 10th percentile (OR = 7.7). Of HFA measured between the 10th and 25th percentiles at ages 2–4, 58% were <25th percentile as adults. Only 13% between the 10th and 25th percentile HFA at age 2–4 years were >50th percentile as adults. Maximum height between ages 2 and 4 highly correlated with adult height. These results demonstrate that low early childhood CF height correlates with height in adulthood. Since linear growth correlates with lung growth, identifying both risk factors and interventions for growth failure (nutritional support, confounders of clinical care, and potential endocrine involvement) could lead to improved overall health. [ABSTRACT FROM AUTHOR]

Robotic devices can be used for motor control and learning research. In this work, we present the construction, modeling and experimental validation of a bimanual robotic device. We tested some hypotheses that may help to better understand the motor learning processes involved in the interlimb coordination function. The system emulates a bicycle handlebar with rotational motion, thus requiring bilateral upper limb control and a coordinated sequence of joint sub-movements. The robotic handlebar is compact and portable and can register in a fast rate both position and forces independently from arms, including prehension forces. An impedance control system was implemented in order to promote a safer environment for human interaction and the system is able to generate force fields, suitable for implementing motor learning paradigms. The novelty of the system is the decoupling of prehension and manipulation forces of each hand, thus paving the way for the investigation of hand dominance function in a bimanual task. Experiments were conducted with ten healthy subjects, kinematic and dynamic variables were measured during a rotational set of movements. Statistical analyses showed that movement velocity decreased with practice along with an increase in reaction time. This suggests an increase of the task planning time. Prehension force decreased with practice. However, an unexpected result was that the dominant hand did not lead the bimanual task, but helped to correct the movement, suggesting different roles for each hand during a cooperative bimanual task. [ABSTRACT FROM AUTHOR]

Micro-blade design is an important factor in the cutting of single cells and other biological structures. This paper describes the fabrication process of three-dimensional (3D) micro-blades for the cutting of single cells in a microfluidic "guillotine" intended for fundamental wound repair and regeneration studies. Our microfluidic guillotine consists of a fixed 3D micro-blade centered in a microchannel to bisect cells flowing through. We show that the Nanoscribe two-photon polymerization direct laser writing system is capable of fabricating complex 3D micro-blade geometries. However, structures made of the Nanoscribe IP-S resin have low adhesion to silicon, and they tend to peel off from the substrate after at most two times of replica molding in poly(dimethylsiloxane) (PDMS). Our work demonstrates that the use of a secondary mold replicates Nanoscribe-printed features faithfully for at least 10 iterations. Finally, we show that complex micro-blade features can generate different degrees of cell wounding and cell survival rates compared with simple blades possessing a vertical cutting edge fabricated with conventional 2.5D photolithography. Our work lays the foundation for future applications in single cell analyses, wound repair and regeneration studies, as well as investigations of the physics of cutting and the interaction between the micro-blade and biological structures. [ABSTRACT FROM AUTHOR]

Multi-Walled Carbon Nanotubes (MWCNT) have been functionalized with rutin through three steps (i. reaction step; ii. purification step; iii. drying step) and their physicochemical properties investigated with respect to morphological structure, thermal analysis, Fourier Transform Infrared Spectroscopy (FTIR), and cytotoxicity. The molecular docking suggested the rutin-functionalized MWCNT occurred by hydrogen bonds, which was confirmed by FTIR assays, corroborating the results obtained by thermal analyses. A tubular shape, arranged in a three-dimensional structure, could be observed. Mild cytotoxicity observed in 3T3 fibroblasts suggested a dose–effect relationship after exposure. These findings suggest the formation of aggregates of filamentous structures on the cells favoring the cell penetration. [ABSTRACT FROM AUTHOR]

Simple Summary: The usage of forage cactus is essential for the maintenance of livestock activity in semiarid regions as an alternative to conventional crops. Cactaceae have adaptive characteristics that ensure their development progress under drought conditions. Four genotypes of forage cactus (Gigante, Miúda, IPA Sertânia, and Orelha de Elefante Mexicana) were fed to lactating dairy cows and the diets were then evaluated based on animal performance, milk fatty acid profile, and microbial protein synthesis. Miúda forage cactus led to a higher nutrient intake and milk yield, as well as greater microbial protein synthesis. Higher saturated fatty acids were observed when the Gigante and IPA Sertânia forage cactus genotypes were fed to dairy cows. Orelha de Elefante Mexicana forage cactus caused lower milk yield along with protein yields and content; however, it improved the milk fatty acid profile by promoting a higher ratio of unsaturated to saturated fatty acids and desirable fatty acids. It is concluded that the Miúda forage cactus is the genotype most suitable for the diets of lactating dairy cows. This study aimed to investigate the effects on nutrient intake and digestibility, milk yield (MY) and composition, milk fatty acids profile, and microbial protein synthesis caused by feeding lactating dairy cows four different forage cactus genotypes. Eight Girolando cows (5/8 Holstein × 3/8 Gyr), weighing 490 ± 69.0 kg (means ± standard deviation), and producing 15.5 ± 1.0 kg/d of milk during pretrial were distributed to two contemporaneous 4 × 4 Latin squares. The cows were fed a total mixed ration composed of sorghum silage (385 g/kg of dry matter (DM)), concentrated mix (175 g/kg DM), and forage cactus (440 g/kg DM). The experimental treatments consisted of different cactus genotypes, such as Gigante cactus (GC), Miúda cactus (MC), IPA Sertânia cactus (SC), and Orelha de Elefante Mexicana cactus (OEMC). The feeding of MC provided a higher intake of DM, organic matter (OM), and total digestible nutrients, as well as higher MY, energy-corrected milk, and microbial protein synthesis in comparison with those resulting from the other genotypes tested. The GC promoted lower DM and OM, and the apparent digestibility of neutral detergent fiber. The cows fed with OEMC showed lower MY and milk protein yield and content, and higher unsaturated over saturated fatty acid ratio in milk. Miúda forage cactus increased nutrient intake, digestibility of DM and OM, and microbial synthesis without impairing the milk fatty acid profile. [ABSTRACT FROM AUTHOR]

In Brazil, the correct measurement of the individual firm energy of a plant is important, since it influences directly the determination of its assured energy which is used to establish contracts between power plants and distribution companies, free consumers, and traders. With increasing technological development and greater reliability in the use of automated techniques for monitoring, the use of the Acoustic Doppler Current Profiler (ADCP), has become a reality in Brazil. The ADCP has many advantages over the traditional techniques used for monitoring flows in gage stations of the national hydrometeorological network. In this context, the purpose of this work is to evaluate the impact of the streamflow rating curve measurement on the evaluation of the firm energy of a hydropower plant. A linear optimization model based on dynamic programming was used to calculate the firm energy and it was considered possible measurement errors in the plant's inflow values and in the parameters of its polynomials that defines the upward and downward elevation. The results pointed that the two considerations had an impact on the calculated firm energy: the inflow measurements and the streamflow rating curve. Therefore, it is shown the importance of an accurate measurement of inflows for the evaluation of the plant's firm energy. [ABSTRACT FROM AUTHOR]

Presently, there is no FDA- or EMA-approved antiviral for the treatment of human adenovirus (HAdV) ocular infections. This study determined the antiviral activity of filociclovir (FCV) against ocular HAdV isolates in vitro and in the Ad5/NZW rabbit ocular model. The 50% effective concentrations (EC50) of FCV and cidofovir (CDV) were determined for several ocular HAdV types using standard plaque reduction assays. Rabbits were topically inoculated in both eyes with HAdV5. On day 1, the rabbits were divided into four topical treatment groups: (1) 0.5% FCV 4x/day × 10 d; (2) 0.1% FCV 4x/day × 10 d; (3) 0.5% CDV 2x/day × 7 d; (4) vehicle 4x/day × 10 d. Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. The resulting viral eye titers were determined using standard plaque assays. The mean in vitro EC50 for FCV against tested HAdV types ranged from 0.50 to 4.68 µM, whereas those treated with CDV ranged from 0.49 to 30.3 µM. In vivo, compared to vehicle, 0.5% FCV, 0.1% FCV, and 0.5% CDV produced lower eye titers, fewer numbers of positive eye cultures, and shorter durations of eye infection. FCV demonstrated anti-adenovirus activity in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Serine peptidases (SPs) are responsible for most primary protein digestion in Lepidoptera species. An expansion of the number of genes encoding trypsin and chymotrypsin enzymes and the ability to upregulate the expression of some of these genes in response to peptidase inhibitor (PI) ingestion have been associated with the adaptation of Noctuidae moths to herbivory. To investigate whether these gene family expansion events are common to other Lepidoptera groups, we searched for all genes encoding putative trypsin and chymotrypsin enzymes in 23 publicly available genomes from this taxon. Phylogenetic analysis showed that several gene family expansion events may have occurred in the taxon's evolutionary history and that these events gave rise to a very diverse group of enzymes, including proteins lacking the canonical SP catalytic triad. The expression profile of these enzymes along the midgut and the secretion mechanisms by which these enzymes enter the luminal content were also analyzed in Spodoptera frugiperda larvae using RNA-seq and proteomics. These results support the proposal of a midgut countercurrent flux responsible for the direction of these proteins to the anterior portion of the midgut and show that these enzymes reach the midgut lumen via both exocytosis and microapocrine secretion mechanisms. [ABSTRACT FROM AUTHOR]

Change detection methods are often incapable of accurately detecting changes within time series that are heavily influenced by seasonal variations. Techniques for de-seasoning time series or methods that apply the spatial context have been used to improve the results of change detection. However, few studies have explored Landsat's shortwave infrared channel (SWIR 2) to discriminate between seasonal changes and land use/land cover changes (LULCC). Here, we explored the effectiveness of Operational Land Imager (OLI) spectral bands and vegetation indices for detecting deforestation in highly seasonal areas of Brazilian savannas. We adopted object-based image analysis (OBIA), applying a multidate segmentation to an OLI time series to generate input data for discrimination of deforestation from seasonal changes using the Random Forest (RF) algorithm. We found adequate separability between deforested objects and seasonal changes using SWIR 2. Using spectral indices computed from SWIR 2, the RF algorithm generated a change map with an overall accuracy of 88.3%. For deforestation, the producer's accuracy was 88.0% and the user's accuracy was 84.6%. The SWIR 2 channel as well as the mid-infrared burn index presented the highest importance among spectral variables computed by the RF average impurity decrease measure. Our results give support to further change detection studies regarding to suitable spectral channels and provided a useful foundation for savanna change detection using an object-based method applied to Landsat time series. [ABSTRACT FROM AUTHOR]

This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU), grew within a colloidal solution of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers A and E, respectively). This method, applied for the first time in Semi-Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a 20-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. Monomer E-based PHU exhibited higher Mw¯ than monomer A-based PHU (34.1 kDa and 16.4 kDa, respectively). Applying the enhanced methodology to prepare 10 multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating monomer E enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when monomer A was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and, as such, provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may result in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn 2+ . Members of this HDAC group are involved in epigenetic regulation primarily by modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extranuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases, and we will discuss the potential of their inhibitors for lung injury prevention.

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. The pore-forming cholesterol-dependent cytolysin (CDC) pneumolysin (PLY) and the physiological metabolite hydrogen peroxide (H 2 O 2 ) can greatly increase the virulence of pneumococci. Although most studies have focused on the contribution of both virulence factors to the course of pneumococcal infection, it is unknown whether or how H 2 O 2 can affect PLY activity. Of note, S. pneumoniae exploits endogenous H 2 O 2 as an intracellular signalling molecule to modulate the activity of several proteins. Here, we demonstrate that H 2 O 2 negatively affects the haemolytic activity of PLY in a concentration-dependent manner. Prevention of cysteine-dependent sulfenylation upon substitution of the unique and highly conserved cysteine residue to serine in PLY significantly reduces the toxin's susceptibility to H 2 O 2 treatment and completely abolishes the ability of DTT to activate PLY. We also detect a clear gradual correlation between endogenous H 2 O 2 generation and PLY release, with decreased H 2 O 2 production causing a decline in the release of PLY. Comparative transcriptome sequencing analysis of the wild-type S. pneumoniae strain and three mutants impaired in H 2 O 2 production indicates enhanced expression of several genes involved in peptidoglycan (PG) synthesis and in the production of choline-binding proteins (CPBs). One explanation for the impact of H 2 O 2 on PLY release is the observed upregulation of the PG bridge formation alanyltransferases MurM and MurN, which evidentially negatively affect the PLY release. Our findings shed light on the significance of endogenous pneumococcal H 2 O 2 in controlling PLY activity and release.

Digital breast tomosynthesis (DBT) reconstructions introduce out-of-plane artifacts and false-tissue boundaries impacting the dense/adipose and breast outline (convex hull) segmentations. A virtual clinical trial method was proposed to segment both the breast tissues and the breast outline in DBT reconstructions. The DBT images of a representative population were simulated using three acquisition geometries: a left-right scan (conventional, I), a two-directional scan in the shape of a "T" (II), and an extra-wide range (XWR, III) left-right scan at a six-times higher dose than I. The nnU-Net was modified including two losses for segmentation: (1) tissues and (2) breast outline. The impact of loss (1) and the combination of loss (1) and (2) was evaluated using models trained with data simulating geometry I. The impact of the geometry was evaluated using the combined loss (1&2). The loss (1&2) improved the convex hull estimates, resolving 22.2% of the false classification of air voxels. Geometry II was superior to I and III, resolving 99.1% and 96.8% of the false classification of air voxels. Geometry III (Dice = (0.98, 0.94)) was superior to I (0.92, 0.78) and II (0.93, 0.74) for the tissue segmentation (adipose, dense, respectively). Thus, the loss (1&2) provided better segmentation, and geometries T and XWR improved the dense/adipose and breast outline segmentations relative to the conventional scan.

Superparamagnetic iron oxide nanoparticles (SPIONs) have their use approved for the diagnosis/treatment of malignant tumors and can be metabolized by the organism. To prevent embolism caused by these nanoparticles, they need to be coated with biocompatible and non-cytotoxic materials. Here, we synthesized an unsaturated and biocompatible copolyester, poly (globalide- co -ε-caprolactone) (PGlCL), and modified it with the amino acid cysteine (Cys) via a thiol-ene reaction (PGlCLCys). The Cys-modified copolymer presented reduced crystallinity and increased hydrophilicity in comparison to PGlCL, thus being used for the coating of SPIONS (SPION@PGlCLCys). Additionally, cysteine pendant groups at the particle's surface allowed the direct conjugation of (bio)molecules that establish specific interactions with tumor cells (MDA-MB 231). The conjugation of either folic acid (FA) or the anti-cancer drug methotrexate (MTX) was carried out directly on the amine groups of cysteine molecules present in the SPION@PGlCLCys surface (SPION@PGlCLCys&#95;FA and SPION@PGlCLCys&#95;MTX) by carbodiimide-mediated coupling, leading to the formation of amide bonds, with conjugation efficiencies of 62% for FA and 60% for MTX. Then, the release of MTX from the nanoparticle surface was evaluated using a protease at 37 °C in phosphate buffer pH~5.3. It was found that 45% of MTX conjugated to the SPIONs were released after 72 h. Cell viability was measured by MTT assay, and after 72 h, 25% reduction in cell viability of tumor cells was observed. Thus, after a successful conjugation and subsequent triggered release of MTX, we understand that SPION@PGlCLCys has a strong potential to be treated as a model nanoplatform for the development of treatments and diagnosis techniques (or theranostic applications) that can be less aggressive to patients.

The aim of this research work was the comparative study of the different properties of interest in the case of plastic materials for food use before and after being subjected to treatment by high hydrostatic pressure (HHP) as well as the impact of additivation with antimicrobials. This method of food preservation is currently on the rise and is of great interest because it is possible to extend the shelf life of many foods without the need for the use of additives or thermal processing, as is the case with other preservation methods currently used. The effects of HHP treatment (680 MPa for 8 min) on plastic materials commonly used in the food industry were studied. These materials, in sheet or film form, were polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), multilayer polyethylene terephthalate-ethylene-vinyl alcohol copolymer-polyethylene (PET-EVOH-PE), multilayer polyethylene-polyethylene terephthalate (PE-PET), polyvinyl chloride aluminum (PVC-AL), and polylactic acid (PLA), which were provided by manufacturing companies in the sector. PE, PP, and PLA activated with tyrosol, zinc oxide, or zinc acetate were also tested. The phenomena and properties, such as overall migration, thermal behavior, oxygen barrier, and physical properties were analyzed before and after the process. The results show that the HHP process only slightly affected the properties of the materials. After pressurization, oxygen permeability increased greatly in PVC-AL (from 7.69 to 51.90) and decreased in PLA (from 8.77 to 3.60). The additivation of the materials caused a change in color and an increase in oxygen permeability. The additivated PE and PP showed migration values above the legal limit for certain simulants. The HHP treatment did not greatly affect the mechanical properties of the additivated materials. The main increases in the migration after HHP treatment were observed for PE activated with tyrosol or zinc oxide and for PS activated with zinc oxide. Activated PLA performed the best in the migration studies, irrespective of the HHP treatment. The results suggest that activated PLA could be used in HHP food processing as an inner antimicrobial layer in contact with the food packed in a container with the desired oxygen permeability barrier.

Wounds result from different causes (e.g., trauma, surgeries, and diabetic ulcers), requiring even extended periods of intensive care for healing, according to the patient's organism and treatment. Currently, wound dressings generated by polymeric fibers at micro and nanometric scales are promising for healing the injured area. They offer great surface area and porosity, mimicking the fibrous extracellular matrix structure, facilitating cell adhesion, migration, and proliferation, and accelerating the wound healing process. Such properties resulted in countless applications of these materials in biomedical and tissue engineering, also as drug delivery systems for bioactive molecules to help tissue regeneration. The techniques used to engineer these fibers include spinning methods (electro-, rotary jet-), airbrushing, and 3D printing. These techniques have important advantages, such as easy-handle procedure and process parameters variability (type of polymer), but encounter some scalability problems. RJS is described as a simple and low-cost technique resulting in high efficiency and yield for fiber production, also capable of bioactive agents' incorporation to improve the healing potential of RJS wound dressings. This review addresses the use of RJS to produce polymeric fibers, describing the concept, type of configuration, comparison to other spinning techniques, most commonly used polymers, and the relevant parameters that influence the manufacture of the fibers, for the ultimate use in the development of wound dressings.

Duchenne muscular dystrophy (DMD) is a degenerative genetic myopathy characterized by complete absence of dystrophin. Although the mdx mouse lacks dystrophin, its phenotype is milder compared to DMD patients. The incorporation of a null mutation in the Cmah gene led to a more DMD-like phenotype (i.e., more fibrosis). Although fibrosis is thought to be the major determinant of 'structural weakness', intracellular remodeling of myofibrillar geometry was shown to be a major cellular determinant thereof. To dissect the respective contribution to muscle weakness, we assessed biomechanics and extra- and intracellular architecture of whole muscle and single fibers from extensor digitorum longus (EDL) and diaphragm. Despite increased collagen contents in both muscles, passive stiffness in mdx Cmah-/- diaphragm was similar to wt mice (EDL muscles were twice as stiff). Isometric twitch and tetanic stresses were 50% reduced in mdx Cmah-/- diaphragm (15% in EDL). Myofibrillar architecture was severely compromised in mdx Cmah-/- single fibers of both muscle types, but more pronounced in diaphragm. Our results show that the mdx Cmah-/- genotype reproduces DMD-like fibrosis but is not associated with changes in passive visco-elastic muscle stiffness. Furthermore, detriments in active isometric force are compatible with the pronounced myofibrillar disarray of the dystrophic background.

The mechanical and physical properties of zirconium carbide (ZrC) are limited to its ability to deteriorate in oxidizing environments. Low refractory oxides are typically formed as layers on ZrC surfaces when exposed to the slightest concentrations of oxygen. However, this carbide has a wide range of applications in nuclear reactor lines and nozzle flaps in the aerospace industry, just to name a few. To develop mechanically strong and oxygen-resistant ZrC materials, the need for studying and characterizing the oxidized layers, with emphasis on the interfacial structure between ZrC and the oxidized phases, cannot be understated. In this paper, the ZrC(111)// c -ZrO 2 (111) interface was studied by both finite temperature molecular dynamic simulation and DFT. The interfacial mechanical properties were characterized by the work of adhesion which revealed a Zr|OO|Zr|OO//ZrC(111) interface model as the most stable with an oxygen layer from ZrO 2 being deposited on the ZrC(111) surface. Further structural analysis at the interface showed a crack in the first ZrO 2 layer at the interfacial region. Investigations of the electronic structure using the density of state calculations and Bader charge analysis revealed the interfacial properties as local effects with no significant impacts in the bulk regions of the interface slab.

In the field of non-oxide ceramic composites, and by using the polymer-derived ceramic route, understanding the relationship between the thermal behaviour of the preceramic polymers and their structure, leading to the mechanisms involved, is crucial. To investigate the role of Zr on the fabrication of ZrC-SiC composites, linear or hyperbranched polycarbosilanes and polyzirconocarbosilanes were synthesised through either "click-chemistry" or hydrosilylation reactions. Then, the thermal behaviours of these polymeric structures were considered, notably to understand the impact of Zr on the thermal path going to the composites. The inorganic materials were characterised by thermogravimetry-mass spectrometry (TG-MS), X-ray diffraction (XRD), and scanning electron microscopy (SEM). To link the macromolecular structure to the organisation involved during the ceramisation process, eight temperature domains were highlighted on the TG analyses, and a four-step mechanism was proposed for the polymers synthesised by a hydrosilylation reaction, as they displayed better ceramic yields. Globally, the introduction of Zr in the polymer had several effects on the temperature fragmentation mechanisms of the organometallic polymeric structures: (i) instead of stepwise mass losses, continuous fragment release prevailed; (ii) the stability of preceramic polymers was impacted, with relatively good ceramic yields; (iii) it modulated the chemical composition of the generated composites as it led, inter alia, to the consumption of free carbon.

Sickle cell disease (SCD) is one of the most common autosomal recessive disorders in the world. Due to functional asplenia, a dysfunctional antibody response, antibiotic drug resistance and poor response to immunization, SCD patients have impaired immunity. A leading cause of hospitalization and death in SCD patients is the acute chest syndrome (ACS). This complication is especially manifested upon infection of SCD patients with Streptococcus pneumoniae ( Spn )-a facultative anaerobic Gram-positive bacterium that causes lower respiratory tract infections. Spn has developed increased rates of antibiotics resistance and is particularly virulent in SCD patients. The primary defense against Spn is the generation of reactive oxygen species (ROS) during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn itself produces high levels of the ROS hydrogen peroxide (H 2 O 2 ) as a virulence strategy. Apart from H 2 O 2 , Spn also secretes another virulence factor, i.e., the pore-forming exotoxin pneumolysin (PLY), a potent mediator of lung injury in patients with pneumonia in general and particularly in those with SCD. PLY is released early on in infection either by autolysis or bacterial lysis following the treatment with antibiotics and has a broad range of biological activities. This review will discuss recent findings on the role of pneumococci in ACS pathogenesis and on strategies to counteract the devastating effects of its virulence factors on the lungs in SCD patients.

The extensive use of oral dosage forms for the treatment of diseases may be linked to deficient pharmacokinetic properties. In some cases the drug is barely soluble; in others, the rapid transit of the formulation through the gastrointestinal tract (GIT) makes it difficult to achieve therapeutic levels in the organism; moreover, some drugs must act locally due to a gastric pathology, but the time they remain in the stomach is short. The use of formulations capable of improving all these parameters, as well as increasing the resident time in the stomach, has been the target of numerous research works, with low-density systems being the most promising and widely explored, however, there is further scope to improve these systems. There are a vast variety of polymeric materials used in low-density gastroretentive systems and a number of methods to improve the bioavailability of the drugs. This works aims to expedite the development of breakthrough approaches by providing an in-depth understanding of the polymeric materials currently used, both natural and synthetic, their properties, advantages, and drawbacks.

Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate lung barrier function and to impair host defense in order to promote infection. Although in general, these toxins target common cellular signaling pathways and host compartments, toxin- and cell-specific effects have also been reported. Toxins can affect resident pulmonary cells involved in alveolar fluid clearance (AFC) and barrier function through impairing vectorial Na + transport and through cytoskeletal collapse, as such, destroying cell-cell adhesions. The resulting loss of alveolar-capillary barrier integrity and fluid clearance capacity will induce capillary leak and foster edema formation, which will in turn impair gas exchange and endanger the survival of the host. Toxins modulate or neutralize protective host cell mechanisms of both the innate and adaptive immunity response during chronic infection. In particular, toxins can either recruit or kill central players of the lung's innate immune responses to pathogenic attacks, i.e., alveolar macrophages (AMs) and neutrophils. Pulmonary disorders resulting from these toxin actions include, e.g., acute lung injury (ALI), the acute respiratory syndrome (ARDS), and severe pneumonia. When acute infection converts to persistence, i.e., colonization and chronic infection, lung diseases, such as bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) can arise. The aim of this review is to discuss the impact of bacterial toxins in the lungs and the resulting outcomes for pathogenesis, their roles in promoting bacterial dissemination, and bacterial survival in disease progression., Competing Interests: The authors declare no conflict of interest