epitope1D: accurate taxonomy-aware B-cell linear epitope prediction.

The ability to identify B-cell epitopes is an essential step in vaccine design, immunodiagnostic tests and antibody production. Several computational approaches have been proposed to identify, from an antigen protein or peptide sequence, which residues are more likely to be part of an epitope, but have limited performance on relatively homogeneous data sets and lack interpretability, limiting biological insights that could otherwise be obtained. To address these limitations, we have developed epitope1D, an explainable machine learning method capable of accurately identifying linear B-cell epitopes, leveraging two new descriptors: a graph-based signature representation of protein sequences, based on our well-established Cutoff Scanning Matrix algorithm and Organism Ontology information. Our model achieved Areas Under the ROC curve of up to 0.935 on cross-validation and blind tests, demonstrating robust performance. A comprehensive comparison to alternative methods using distinct benchmark data sets was also employed, with our model outperforming state-of-the-art tools. epitope1D represents not only a significant advance in predictive performance, but also allows biologically meaningful features to be combined and used for model interpretation. epitope1D has been made available as a user-friendly web server interface and application programming interface at https://biosig.lab.uq.edu.au/epitope1d/.

Oxidative desulfurization pathway for complete catabolism of sulfoquinovose by bacteria.

Catabolism of sulfoquinovose (SQ; 6-deoxy-6-sulfoglucose), the ubiquitous sulfosugar produced by photosynthetic organisms, is an important component of the biogeochemical carbon and sulfur cycles. Here, we describe a pathway for SQ degradation that involves oxidative desulfurization to release sulfite and enable utilization of the entire carbon skeleton of the sugar to support the growth of the plant pathogen Agrobacterium tumefaciens SQ or its glycoside sulfoquinovosyl glycerol are imported into the cell by an ATP-binding cassette transporter system with an associated SQ binding protein. A sulfoquinovosidase hydrolyzes the SQ glycoside and the liberated SQ is acted on by a flavin mononucleotide-dependent sulfoquinovose monooxygenase, in concert with an NADH-dependent flavin reductase, to release sulfite and 6-oxo-glucose. An NAD(P)H-dependent oxidoreductase reduces the 6-oxo-glucose to glucose, enabling entry into primary metabolic pathways. Structural and biochemical studies provide detailed insights into the recognition of key metabolites by proteins in this pathway. Bioinformatic analyses reveal that the sulfoquinovose monooxygenase pathway is distributed across Alpha- and Betaproteobacteria and is especially prevalent within the Rhizobiales order. This strategy for SQ catabolism is distinct from previously described pathways because it enables the complete utilization of all carbons within SQ by a single organism with concomitant production of inorganic sulfite.

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

Serial Mass Screening for Tuberculosis Among Incarcerated Persons in Brazil.

BACKGROUND: An active search for tuberculosis cases through mass screening is widely described as a tool to improve case detection in hyperendemic settings. However, its effectiveness in high-risk populations, such as incarcerated people, is debated. METHODS: Between 2017 and 2021, 3 rounds of mass screening were carried out in 3 Brazilian prisons. Social and health questionnaires, chest X-rays, and Xpert MTB/RIF were performed. RESULTS: More than 80% of the prison population was screened. Overall, 684 cases of pulmonary tuberculosis were diagnosed. Prevalence across screening rounds was not statistically different. Among incarcerated persons with symptoms, the overall prevalence of tuberculosis per 100 000 persons was 8497 (95% confidence interval [CI], 7346-9811), 11 115 (95% CI, 9471-13 082), and 7957 (95% CI, 6380-9882) in screening rounds 1, 2, and 3, respectively. Similar to our overall results, there were no statistical differences between screening rounds and within individual prisons. We found no statistical differences in Computer-Aided Detection for TB version 5 scores across screening rounds among people with tuberculosis-the median scores in rounds 1, 2, and 3 were 82 (interquartile range [IQR], 63-97), 77 (IQR, 60-94), and 81 (IQR, 67-92), respectively. CONCLUSIONS: In this environment with hyperendemic rates of tuberculosis, 3 rounds of mass screening did not reduce the overall tuberculosis burden. In prisons, where a substantial number of tuberculosis cases is undiagnosed annually, a range of complementary interventions and more frequent tuberculosis cases screening may be required.

Identification of eQTLs using different sets of single nucleotide polymorphisms associated with carcass and body composition traits in pigs.

BACKGROUND: Mapping expression quantitative trait loci (eQTLs) in skeletal muscle tissue in pigs is crucial for understanding the relationship between genetic variation and phenotypic expression of carcass traits in meat animals. Therefore, the primary objective of this study was to evaluate the impact of different sets of single nucleotide polymorphisms (SNP), including scenarios removing SNPs pruned for linkage disequilibrium (LD) and SNPs derived from SNP chip arrays and RNA-seq data from liver, brain, and skeletal muscle tissues, on the identification of eQTLs in the Longissimus lumborum tissue, associated with carcass and body composition traits in Large White pigs. The SNPs identified from muscle mRNA were combined with SNPs identified in the brain and liver tissue transcriptomes, as well as SNPs from the GGP Porcine 50 K SNP chip array. Cis- and trans-eQTLs were identified based on the skeletal muscle gene expression level, followed by functional genomic analyses and statistical associations with carcass and body composition traits in Large White pigs. RESULTS: The number of cis- and trans-eQTLs identified across different sets of SNPs (scenarios) ranged from 261 to 2,539 and from 29 to 13,721, respectively. Furthermore, 6,180 genes were modulated by eQTLs in at least one of the scenarios evaluated. The eQTLs identified were not significantly associated with carcass and body composition traits but were significantly enriched for many traits in the "Meat and Carcass" type QTL. The scenarios with the highest number of cis- (n = 304) and trans- (n = 5,993) modulated genes were the unpruned and LD-pruned SNP set scenarios identified from the muscle transcriptome. These genes include 84 transcription factor coding genes. CONCLUSIONS: After LD pruning, the set of SNPs identified based on the transcriptome of the skeletal muscle tissue of pigs resulted in the highest number of genes modulated by eQTLs. Most eQTLs are of the trans type and are associated with genes influencing complex traits in pigs, such as transcription factors and enhancers. Furthermore, the incorporation of SNPs from other genomic regions to the set of SNPs identified in the porcine skeletal muscle transcriptome contributed to the identification of eQTLs that had not been identified based on the porcine skeletal muscle transcriptome alone.

epitope3D: a machine learning method for conformational B-cell epitope prediction.

The ability to identify antigenic determinants of pathogens, or epitopes, is fundamental to guide rational vaccine development and immunotherapies, which are particularly relevant for rapid pandemic response. A range of computational tools has been developed over the past two decades to assist in epitope prediction; however, they have presented limited performance and generalization, particularly for the identification of conformational B-cell epitopes. Here, we present epitope3D, a novel scalable machine learning method capable of accurately identifying conformational epitopes trained and evaluated on the largest curated epitope data set to date. Our method uses the concept of graph-based signatures to model epitope and non-epitope regions as graphs and extract distance patterns that are used as evidence to train and test predictive models. We show epitope3D outperforms available alternative approaches, achieving Mathew's Correlation Coefficient and F1-scores of 0.55 and 0.57 on cross-validation and 0.45 and 0.36 during independent blind tests, respectively.

Synthesis of 6,8-diaminopurines via acid-induced cascade cyclization of 5-aminoimidazole precursors and preliminary anticancer evaluation.

Inspired by the pharmacological interest generated by 6-substituted purine roscovitine for cancer treatment, 5-aminoimidazole-4-carboxamidine precursors containing a cyanamide unit were prepared by condensation of 5-amino-N-cyanoimidazole-4-carbimidoyl cyanides with a wide range of primary amines. When these amidine precursors were combined with acids, a fast cascade cyclization occurred at room temperature, affording new 6,8-diaminopurines with the N-3 and N-6 substituents changed relatively to the original positions they occupied in the amidine and imidazole moieties of precursors. The efficacy and wide scope of this method was well demonstrated by an easy and affordable synthesis of 22 6,8-diaminopurines decorated with a wide diversity of substituents at the N-3 and N-6 positions of the purine ring. Preliminary in silico and in vitro assessments of these 22 compounds were carried out and the results showed that 13 of these tested compounds not only exhibited IC50 values between 1.4 and 7.5 µM against the colorectal cancer cell line HCT116 but also showed better binding energies than known inhibitors in docking studies with different cancer-related target proteins. In addition, good harmonization observed between in silico and in vitro results strengthens and validates this preliminary evaluation, suggesting that these novel entities are good candidates for further studies as new anticancer agents.

Glutamate imbalance in key structure of the default mode network in adults with attention-deficit/hyperactivity disorder.

The default mode network (DMN) is atypically active in patients with ADHD, likely contributing to the inattention patterns observed in patients with the disorder. Nonetheless, magnetic resonance spectroscopy (MRS) studies have rarely targeted the posterior cingulate cortex, a key DMN region, and little is known about the biochemical setting within this network in patients with ADHD. We aimed to assess the differences in metabolite profiles of the posterior cingulate cortex-a key region of the DMN-between patients with ADHD and controls. Five brain metabolites-glutamate, inositol, N-acetyl aspartate, choline, and creatine-were measured through MRS in the posterior cingulate cortex of patients and controls in a 3.0 T scanner. Between-group comparison of neurometabolite concentrations in PCC was performed using multivariate analysis of covariance. A total of 88 patients and 44 controls were included in the analysis. Patients with ADHD showed lower levels of glutamate in the posterior cingulate cortex compared to controls (p = 0.003). Lower concentrations of glutamate in the posterior cingulate cortex suggest that a glutamatergic imbalance within the posterior cingulate cortex might play a role in the pathogenesis of ADHD. Further understanding of the causes and consequences of such glutamate decrease might help explain how some glutamate-related drug effects impact on ADHD symptomatology.

The symptomatology of Attention-Deficit/Hyperactivity Disorder and the genetic control of vitamin D levels.

OBJECTIVES: Vitamin D deficiency has been associated with psychiatric disorders and behavioral phenotypes such as Attention-Deficit/Hyperactivity Disorder (ADHD). Considering that vitamin D levels are polygenic, we aim to evaluate the overall effects of its genetic architecture on symptoms of inattention, hyperactivity, and impulsivity and on the serum levels of vitamin D in two independent samples of adults, as well as the specific effects of five relevant polymorphisms in vitamin D-related genes. METHODS: We evaluated 870 subjects from an ADHD sample (407 cases and 463 controls) and 319 subjects from an academic community (nutrigenetic sample). Vitamin D serum levels were obtained through Elisa test and genetic data by TaqMan™ allelic discrimination and Infinium PsychArray-24 BeadChip genotyping. Polygenic Scores (PGS) were calculated on PRSice2 based on the latest GWAS for Vitamin D and statistical analyses were conducted at Plink and SPSS software. RESULTS: Vitamin D PGSs were associated with inattention in the ADHD sample and with hyperactivity when inattention symptoms were included as covariates. In the nutrigenetic sample, CYP2R1 rs10741657 and DHCR7 rs12785878 were nominally associated with impulsivity and hyperactivity, respectively, and both with vitamin D levels. In the clinical sample, RXRG rs2134095 was associated with impulsivity. DISCUSSION: Our findings suggest a shared genetic architecture between vitamin D levels and ADHD symptoms, as evidenced by the associations observed with PGS and specific genes related to vitamin D levels. Interestingly, differential effects for vitamin D PGS were found in inattention and hyperactivity, which should be considered in further studies involving ADHD.

A Review on 3D Scanners Studies for Producing Customized Orthoses.

When a limb suffers a fracture, rupture, or dislocation, it is traditionally immobilized with plaster. This may induce discomfort in the patient, as well as excessive itching and sweating, which creates the growth of bacteria, leading to an unhygienic environment and difficulty in keeping the injury clean during treatment. Furthermore, if the plaster remains for a long period, it may cause lesions in the joints and ligaments. To overcome all of these disadvantages, orthoses have emerged as important medical devices to help patients in rehabilitation, as well as for self-care of deficiencies in clinics and daily life. Traditionally, these devices are produced manually, which is a time-consuming and error-prone method. From another point of view, it is possible to use imageology (X-ray or computed tomography) to scan the human body; a process that may help orthoses manufacturing but which induces radiation to the patient. To overcome this great disadvantage, several types of 3D scanners, without any kind of radiation, have emerged. This article describes the use of various types of scanners capable of digitizing the human body to produce custom orthoses. Studies have shown that photogrammetry is the most used and most suitable 3D scanner for the acquisition of the human body in 3D. With this evolution of technology, it is possible to decrease the scanning time and it will be possible to introduce this technology into clinical environment.

Implications of converting native forest areas to agricultural systems on the dynamics of CO2 emission and carbon stock in a Cerrado soil, Brazil.

The conversion of native vegetation to agricultural areas leads to a natural process of carbon loss but these systems can stabilize in terms of carbon dynamics depending on the management and conversion time, presenting potential to both store and stabilize this carbon in the soil, resulting in lower soil respiration rates. In this context, this study aimed to investigate the effect of converting native Cerrado forest areas to agricultural systems with a forest planted with Eucalyptus camaldulensis and silvopastoral systems on the dynamics of CO2 emission and carbon stock at different soil depths. The experimental sites are located in the Midwest of Brazil, in the coordinates 20°22'31″ S and 51°24'12″ W. Were evaluated soil CO2 emission (FCO2), soil organic carbon, the degree of humification of soil organic matter (HLIFS), soil temperature, soil moisture, and soil chemical and physical attributes. The soil of the area is classified as an Oxisol (Haplic Acrustox). Soil samples were collected at depths of 0.00-0.10, 0.10-0.20, 0.20-0.30, and 0.30-0.40 m. The lowest FCO2 values were found in the silvopastoral system (1.05 µmol m-2 s-1), followed by the native forest (1.65 µmol m-2 s-1) and the eucalyptus system (1.96 µmol m-2 s-1), indicating a 36% reduction in FCO2 compared to the conversion of the native forest to the silvopastoral system and an increase of 19% when converting the native forest to the eucalyptus system. The soil chemical attributes (N, K+, Ca2+, H++Al3+, CEC, and organic carbon) showed a decrease along the profile. The shallowest depths (0.00-0.10 and 0.10-0.20 m) presented no differences between systems but the subsequent depths (0.20-0.30 and 0.30-0.40 m) had a difference (95% confidence interval), relative to N, Ca2+, H++Al3, CEC, and organic carbon stock (OCS), and the soil under silvopastoral system showed a higher concentration of these attributes than the native forest. The multivariate analysis showed that the eucalyptus and silvopastoral systems did not differ from the forest in the shallowest soil layer but differed from each other. This behavior changed from the second assessed depth (0.10-0.20 m), in which the silvopastoral system stands out, differing both from the eucalyptus system and from the native forest, and this behavior is maintained at the following depths (0.20-0.30 and 0.30-0.40 m). OCS, H++Al3, CEC, and nitrogen are strongly related to land use change for silvopastoral system. Regarding the behavior/relationship of attributes as a function of depth, the silvopastoral system contributed to soil carbon accumulation and stability over consecutive years.

Exploring the Feasibility of a Cancer Awareness Program for High School Students in a Brazilian School: A Pilot Study.

Cancer is a leading cause of mortality globally and is projected to be the primary cause of death in Brazil by 2030. Yet, for high school students, information and understanding about cancer are primarily offered through standard biology lessons. This study aimed to assess the feasibility of a brief educational intervention related to cancer among high school students in a Brazilian private school. Participants attended a 1-h online session regarding different aspects of cancer. A self-reported questionnaire about the main topics addressed in the session was filled out before [pre] and after [post] the educational intervention and the results were compared by McNemar's chi-square test. From 900 parents invited, 44 (4.9%) responded to the invitation and agreed with their children's participation, and 24 students attended the activity. The questionnaire was easy to fill out for the students and allowed us to measure differences after the educational intervention. The high school students considered the most interesting topics cancer myths and protective/risk factors. The project was feasible and showed easy application and better knowledge after the educational intervention. The main challenge is related to the access to parents to authorize their children's participation. Designing interventions that focus on cancer education might be a viable way to increase prevention and early diagnosis with implications for students, their families, and the community.

Global DNA methylation patterns in Alcohol Use Disorder.

Alcohol Use Disorder (AUD) is a highly prevalent condition worldwide that produces a wide range of pathophysiological consequences, with a critical impact on health and social issues. Alcohol influences gene expression through epigenetic changes mainly through DNA methylation. In this sense, levels of 5-methylcytosine (5-mC), namely Global DNA methylation (GMe), which can be influenced by environmental and hormonal effects, represent a putative biological mechanism underlying alcohol effects. Our aim was to investigate the influence of AUD diagnosis and alcohol patterns (i.e., years of addiction, use in the last 30 days, and alcohol severity) on GMe levels. The sample consisted of 256 men diagnosed with AUD and 361 men without AUD. DNA samples from peripheral blood were used to assess GMe levels, measured through the levels of 5-mC using high-performance liquid chromatography. Results from multiple linear regression analysis indicated that the presence of AUD was associated with lower GMe levels (beta=-0.155, p=0.011). Other alcohol-related outcomes were not associated with DNA methylation. Our findings are consistent with the hypothesis that the impact of chronic and heavy alcohol use in GMe could be a potential mechanism mediating the multiple organ damages related to AUD.

CASP4/11 Contributes to NLRP3 Activation and COVID-19 Exacerbation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers activation of the NLRP3 inflammasome, which promotes inflammation and aggravates severe COVID-19. Here, we report that SARS-CoV-2 induces upregulation and activation of human caspase-4/CASP4 (mouse caspase-11/CASP11), and this process contributes to NLRP3 activation. In vivo infections performed in transgenic hACE2 humanized mice, deficient or sufficient for Casp11, indicate that hACE2 Casp11-/- mice were protected from disease development, with the increased pulmonary parenchymal area, reduced clinical score of the disease, and reduced mortality. Assessing human samples from fatal cases of COVID-19, we found that CASP4 was expressed in patient lungs and correlated with the expression of inflammasome components and inflammatory mediators, including CASP1, IL1B, IL18, and IL6. Collectively, our data establish that CASP4/11 promotes NLRP3 activation and disease pathology, revealing a possible target for therapeutic interventions for COVID-19.

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.

CLINICAL EFFICACY OF PHOTODYNAMIC THERAPY IN MANAGEMENT OF ORAL POTENTIALLY MALIGNANT DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Despite phototherapy (in the form of photodynamic therapy (PDT)-mediated oxidative stress) being utilized in the management of oral potentially malignant disorders (OPMDs), the evidence of certainty remains unclear. Hence, this systematic review and meta-analysis (PROSPERO # CRD42021218748) is aimed to evaluate the clinical efficacy of PDT-induced oxidative stress in OPMDs METHODS: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched without restriction of language or year of publication. In addition, gray literature was searched and a manual search was performed. Two independent reviewers screened all the studies, assessing data extraction, risk of bias and certainty of evidence. A narrative synthesis was carried out. For the meta-analysis, random effects were considered to determine the prevalence of a total and a partial remission (PR) of oral potentially malignant disorders (OPMDs). The certainty of evidence was explored using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-three studies were included in the qualitative and quantitative syntheses. A total of 880 patients were included (564 males; 218 females) with an age range between 24 and 89-years-old. The results showed the prevalence of the total and partial remissions respectively for the following OPMLs: actinic cheilitis (AC): 69.9% and 2.4%; oral leukoplakia (OL): 44% and 36.9%; oral verrucous hyperplasia (OVH): 98.5%; oral erythroleukoplakia (OEL): 92.1% and 7.9%. The prevalence of no remission of OL was 18.8%. CONCLUSIONS: PDT demonstrated significant results in clinical remission of OPMDs and most of the eligible studies have shown a total or a partial remission of the included lesions, but at a low or a very low certainty of evidence. Hence, further clinical studies with robust methodology are warranted to offer further validated data. Also, further evidence is required to understand further the mechanism of PDT-induced oxidative stress.

Genome-wide association studies: utility and limitations for research in physiology.

Physiological systems are subject to interindividual variation encoded by genetics. Genome-wide association studies (GWAS) operate by surveying thousands of genetic variants from a substantial number of individuals and assessing their association to a trait of interest, be it a physiological variable, a molecular phenotype (e.g. gene expression), or even a disease or condition. Through a myriad of methods, GWAS downstream analyses then explore the functional consequences of each variant and attempt to ascertain a causal relationship to the phenotype of interest, as well as to delve into its links to other traits. This type of investigation allows mechanistic insights into physiological functions, pathological disturbances and shared biological processes between traits (i.e. pleiotropy). An exciting example is the discovery of a new thyroid hormone transporter (SLC17A4) and hormone metabolising enzyme (AADAT) from a GWAS on free thyroxine levels. Therefore, GWAS have substantially contributed with insights into physiology and have been shown to be useful in unveiling the genetic control underlying complex traits and pathological conditions; they will continue to do so with global collaborations and advances in genotyping technology. Finally, the increasing number of trans-ancestry GWAS and initiatives to include ancestry diversity in genomics will boost the power for discoveries, making them also applicable to non-European populations.

Brain fatty acid and transcriptome profiles of pig fed diets with different levels of soybean oil.

BACKGROUND: The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs' brain tissue. RESULTS: Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from - 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change - 1.489), CALB1 (log2 fold change - 3.431) and CAST (log2 fold change + 0.421) genes. A "calcium transport" network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. CONCLUSION: The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.

Transcriptome profile of skeletal muscle using different sources of dietary fatty acids in male pigs.

Pork is of great importance in world trade and represents the largest source of fatty acids in the human diet. Lipid sources such as soybean oil (SOY), canola (CO), and fish oil (FO) are used in pig diets and influence blood parameters and the ratio of deposited fatty acids. In this study, the main objective was to evaluate changes in gene expression in porcine skeletal muscle tissue resulting from the dietary oil sources and to identify metabolic pathways and biological process networks through RNA-Seq. The addition of FO in the diet of pigs led to intramuscular lipid with a higher FA profile composition of C20:5 n-3, C22:6 n-3, and SFA (C16:0 and C18:0). Blood parameters for the FO group showed lower cholesterol and HDL content compared with CO and SOY groups. Skeletal muscle transcriptome analyses revealed 65 differentially expressed genes (DEG, FDR 10%) between CO vs SOY, and 32 DEG for CO vs FO, and 531 DEG for SOY vs FO comparison. Several genes, including AZGP1, PDE3B, APOE, PLIN1, and LIPS, were found to be down-regulated in the diet of the SOY group compared to the FO group. The enrichment analysis revealed DEG involved in lipid metabolism, metabolic diseases, and inflammation between the oil groups, with specific gene functions in each group and altered blood parameters. The results provide mechanisms to help us understand the behavior of genes according to fatty acids.

Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model.

BACKGROUND: COVID-19 is characterized by severe acute lung injury, which is associated with neutrophil infiltration and the release of neutrophil extracellular traps (NETs). COVID-19 treatment options are scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment. METHODS: Here, we report the efficacy of NET-degrading DNase I treatment in a murine model of COVID-19. SARS-CoV-2-infected K18-hACE2 mice were performed for clinical sickness scores and lung pathology. Moreover, the levels of NETs were assessed and lung injuries were by histopathology and TUNEL assay. Finally, the injury in the heart and kidney was assessed by histopathology and biochemical-specific markers. RESULTS: DNase I decreased detectable levels of NETs, improved clinical disease, and reduced lung, heart, and kidney injuries in SARS-CoV-2-infected K18-hACE2 mice. Furthermore, our findings indicate a potentially deleterious role for NETs lung tissue in vivo and lung epithelial (A549) cells in vitro, which might explain part of the pathophysiology of severe COVID-19. This deleterious effect was diminished by the treatment with DNase I. CONCLUSIONS: Together, our results support the role of NETs in COVID-19 immunopathology and highlight NETs disruption pharmacological approaches as a potential strategy to ameliorate COVID-19 clinical outcomes.