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BACKGROUND: Colitis caused by checkpoint inhibitors (CPI) is frequent and is treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear. METHODS: Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations. RESULTS: CPI colitis biopsies showed enrichment of CD4+resident memory (RM) T cells in addition to CD8+ RM and cytotoxic CD8+ T cells. Matching T cell receptor (TCR) clonotypes suggested that both RMs are progenitors that yield cytotoxic effectors. Activated, CD38+ HLA-DR+ CD4+ RM and cytotoxic CD8+ T cells were enriched in steroid-experienced and a validation data set of steroid-naïve CPI colitis, underscoring their pathogenic potential across steroid exposure. Distinct from ulcerative colitis, CPI colitis exhibited perturbed stromal metabolism (NAD+, tryptophan) impacting epithelial survival and inflammation. Endothelial cells in CPI colitis after anti-TNF and anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) upregulated the integrin α4β7 ligand molecular vascular addressin cell adhesion molecule 1 (MAdCAM-1), which may preferentially respond to vedolizumab (anti-α4β7). CONCLUSIONS: These findings nominate CD4+ RM and MAdCAM-1+ endothelial cells for targeting in specific subsets of CPI colitis patients.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

Ecuador is some country rich in agricultural biomass that is not used at all. But this type of biomass has an ecological value that can impact the diet of the Ecuadorian population. What is viable is the use of urban biomass as a raw material to produce sustainable green hydrogen. The methodology is based on qualitative research (qualitative exegetical content) and quantitative research (elementary analysis of the substrate). The sample was 296 homes whose organic bio-waste was analyzed to determine the theoretical percentage of CH4. The results allowed us to obtain the stoichiometric equations of CH4, in which a value of 49,6% was found, and a PCI of 3878.77 kcal/kg. It is concluded that the intra-domestic urban biomass generated in Guayaquil homes can be replaced with an 80.74% possibility of being used to produce green hydrogen by applying biological technology (dark fermentation). Combining both technologies (hydrogen and biomass) contribute to reducing energy dependence on fossil fuels and water to generate electricity and reducing the carbon footprint by promoting circular, sustainable and sustainable energy production.

Historically, Chinese societies have been characterized by patriarchal structures (Confucianism and filial piety) that assign distinct roles to men and women within the family unit. These norms typically dictate that women take on the primary responsibility for childcare and household duties, while men are expected to be the primary breadwinners. As the authors observe the second generation of Chinese immigrants settling in Portugal, the immigrants grapple with the significant challenge of striving to preserve cultural heritage with the adaptation to Western norms. Therefore, there is a growing recognition of the need to reassess these traditional gender norms. Women in these families are increasingly participating in the workforce, challenging the notion that childcare should be solely to their domain. This study focuses on the experiences of Chinese immigrants, including both married couples and single individuals residing in Portugal. Through qualitative research methods such as interviews (involving 25 participants) and observations, the research aims to gain a nuanced understanding of the attitude and engagement toward childcare, and the ways it differs between men and women in these immigrant families. Participants’ responses indicate that men’s anticipation of women dedicating more time to childcare is notably influenced by educational attainment and financial circumstances. Conversely, women generally believe that being exempt from labor is not a viable alternative irrespective of their educational qualifications. The traditional distribution of caregiving duties does not consistently apply to Chinese female immigrants. By exploring the influence of traditional Confucian culture on migrants’ perspectives and challenges in assuming parental responsibilities, this study highlights gender disparities among Chinese immigrants and propose solutions to address this gender conflict on division.

We present an assessment of the tropical peatlands in the upper-Ucayali Valley in central Peru—an Amazonian region that has been largely ignored in ecological and wetlands research. We focused on groundtruthing and identifying the strongest landscape-level predictors of peat depth. The 2015 product from the Peruvian Ministry of the Environment (MINAM) appears to be a sufficient proxy, primarily due to its inclusion of the aguajal category, identified as bosque inundable de palmeras (Bi-pal) or palm swamp, which are typically associated with Amazonian peatlands. Aberrations in the MINAM product are also present in attempted updates addressing aguajales, wetlands, and conservation threats, regardless of the varied geographic methodologies employed by previous studies. Our analysis of the CIFOR Global Wetlands Map lends credence to these methodologies, although our results are inconsistent with the depth predictions contained within the product. The predictive strength of factors contained with the MIANM classification is explored, most notably contact segments indicative of transitions from high-terrace terra firma forests (bosque de terraza alta) directly to low-lying inundated and wetland zones. The potential of factors related to elevation (slope, rise, steepness) is likewise questioned based on their performance in multiple linear regression analyses. Future studies are needed to enhance our understanding of the hydrogeologic settings and associated geochemical attributes of palm swamps and peatlands in The Amazon.

Aging results in a decline in neural stem cells (NSCs), neurogenesis, and cognitive function, and evidence is emerging to demonstrate disrupted adult neurogenesis in the hippocampus of patients with several neurodegenerative disorders. Here, single-cell RNA sequencing of the dentate gyrus of young and old mice shows that the mitochondrial protein folding stress is prominent in activated NSCs/neural progenitors (NPCs) among the neurogenic niche, and it increases with aging accompanying dysregulated cell cycle and mitochondrial activity in activated NSCs/NPCs in the dentate gyrus. Increasing mitochondrial protein folding stress results in compromised NSC maintenance and reduced neurogenesis in the dentate gyrus, neural hyperactivity, and impaired cognitive function. Reducing mitochondrial protein folding stress in the dentate gyrus of old mice improves neurogenesis and cognitive function. These results establish the mitochondrial protein folding stress as a driver of NSC aging and suggest approaches to improve aging-associated cognitive decline.

Abstract Background Breast cancer (BC) is a heterogeneous neoplasm characterized by several subtypes. One of the most aggressive with high metastasis rates presents overexpression of the human epidermal growth factor receptor 2 (HER2). A quantitative evaluation of HER2 levels is essential for a correct diagnosis, selection of the most appropriate therapeutic strategy and monitoring the response to therapy. Results In this paper, we propose the synergistic use of SERS and Raman technologies for the identification of HER2 expressing cells and its accurate assessment. To this end, we selected SKBR3 and MDA-MB-468 breast cancer cell lines, which have the highest and lowest HER2 expression, respectively, and MCF10A, a non-tumorigenic cell line from normal breast epithelium for comparison. The combined approach provides a quantitative estimate of HER2 expression and visualization of its distribution on the membrane at single cell level, clearly identifying cancer cells. Moreover, it provides a more comprehensive picture of the investigated cells disclosing a metabolic signature represented by an elevated content of proteins and aromatic amino acids. We further support these data by silencing the HER2 gene in SKBR3 cells, using the RNA interference technology, generating stable clones further analysed with the same combined methodology. Significant changes in HER2 expression are detected at single cell level before and after HER2 silencing and the HER2 status correlates with variations of fatty acids and downstream signalling molecule contents in the context of the general metabolic rewiring occurring in cancer cells. Specifically, HER2 silencing does reduce the growth ability but not the lipid metabolism that, instead, increases, suggesting that higher fatty acids biosynthesis and metabolism can occur independently of the proliferating potential tied to HER2 overexpression. Conclusions Our results clearly demonstrate the efficacy of the combined SERS and Raman approach to definitely pose a correct diagnosis, further supported by the data obtained by the HER2 gene silencing. Furthermore, they pave the way to a new approach to monitor the efficacy of pharmacologic treatments with the aim to tailor personalized therapies and optimize patients’ outcome.

Abstract This study examines the convergence between traditional and scientific knowledge regarding the use of fire and its potential to trigger wildfires, with possible impacts on ecosystems and human well-being. The research encompasses three distinct natural regions of Ecuador: the coast, the highlands, and the Amazon. Data on traditional fire use were collected through semi-structured interviews with 791 members from five local communities. These data were compared with climatic variables (rainfall (mm), relative humidity (%), wind speed (km/h), and wind direction) to understand the climatic conditions conducive to wildfires and their relationship with human perceptions. Furthermore, the severity of fires over the past 4 years (2019–2022) was assessed using remote sensing methods, employing the Normalized Burn Ratio (NBR) and the difference between pre-fire and post-fire conditions (NBR Pre-fire–NBR Post-fire). The results revealed a significant alignment between traditional knowledge, climatic data, and many fires, which were of low severity, suggesting potential benefits for ecosystems. These findings not only enable the identification of optimal techniques and timing for traditional burns but also contribute to human well-being by maintaining a harmonious balance between communities and their environment. Additionally, they provide valuable insights for the development of more inclusive and effective integrated fire management strategies in these natural areas of Ecuador.

The continued emergence of SARS-CoV-2 variants is one of several factors that may cause false-negative viral PCR test results. Such tests are also susceptible to false-positive results due to trace contamination from high viral titer samples. Host immune response markers provide an orthogonal indication of infection that can mitigate these concerns when combined with direct viral detection. Here, we leverage nasopharyngeal swab RNA-seq data from patients with COVID-19, other viral acute respiratory illnesses, and nonviral conditions (n = 318) to develop support vector machine classifiers that rely on a parsimonious 2-gene host signature to diagnose COVID-19. We find that optimal classifiers include an interferon-stimulated gene that is strongly induced in COVID-19 compared with nonviral conditions, such as IFI6, and a second immune-response gene that is more strongly induced in other viral infections, such as GBP5. The IFI6+GBP5 classifier achieves an area under the receiver operating characteristic curve (AUC) greater than 0.9 when evaluated on an independent RNA-seq cohort (n = 553). We further provide proof-of-concept demonstration that the classifier can be implemented in a clinically relevant RT-qPCR assay. Finally, we show that its performance is robust across common SARS-CoV-2 variants and is unaffected by cross-contamination, demonstrating its utility for improved accuracy of COVID-19 diagnostics. IMPORTANCE In this work, we study upper respiratory tract gene expression to develop and validate a 2-gene host-based COVID-19 diagnostic classifier and then demonstrate its implementation in a clinically practical qPCR assay. We find that the host classifier has utility for mitigating false-negative results, for example due to SARS-CoV-2 variants harboring mutations at primer target sites, and for mitigating false-positive viral PCR results due to laboratory cross-contamination. Both types of error carry serious consequences of either unrecognized viral transmission or unnecessary isolation and contact tracing. This work is directly relevant to the ongoing COVID-19 pandemic given the continued emergence of viral variants and the continued challenges of false-positive PCR assays. It also suggests the feasibility of pan-respiratory virus host-based diagnostics that would have value in congregate settings, such as hospitals and nursing homes, where unrecognized respiratory viral transmission is of particular concern.

BackgroundInfection by coronavirus SARS-CoV2 is a severe and often deadly disease that has implications for the respiratory system and multiple organs across the human body. While the effects in the lung have been extensively studied, less is known about the impact COVID-19 has across other organs.MethodsHere, we contribute a single-nuclei RNA-sequencing atlas comprising six human organs across 20 autopsies where we analyzed the transcriptional changes due to COVID-19 in multiple cell types. The integration of data from multiple organs enabled the identification of systemic transcriptional changes.ResultsComputational cross-organ analysis for endothelial cells and macrophages identified systemic transcriptional changes in these cell types in COVID-19 samples. In addition, analysis of gene modules showed enrichment of specific signaling pathways across multiple organs in COVID-19 autopsies.ConclusionsAltogether, the COVID Tissue Atlas enables the investigation of both cell type-specific and cross-organ transcriptional responses to COVID-19, providing insights into the molecular networks affected by the disease and highlighting novel potential targets for therapies and drug development.FundingThe Chan-Zuckerberg Initiative, The Chan-Zuckerberg Biohub.

Spatial transcriptomics extends single-cell RNA sequencing (scRNA-seq) by providing spatial context for cell type identification and analysis. Imaging-based spatial technologies such as multiplexed error-robust fluorescence in situ hybridization (MERFISH) can achieve single-cell resolution, directly mapping single-cell identities to spatial positions. MERFISH produces a different data type than scRNA-seq, and a technical comparison between the two modalities is necessary to ascertain how to best integrate them. We performed MERFISH on the mouse liver and kidney and compared the resulting bulk and single-cell RNA statistics with those from the Tabula Muris Senis cell atlas and from two Visium datasets. MERFISH quantitatively reproduced the bulk RNA-seq and scRNA-seq results with improvements in overall dropout rates and sensitivity. Finally, we found that MERFISH independently resolved distinct cell types and spatial structure in both the liver and kidney. Computational integration with the Tabula Muris Senis atlas did not enhance these results. We conclude that MERFISH provides a quantitatively comparable method for single-cell gene expression and can identify cell types without the need for computational integration with scRNA-seq atlases.

Introduction Metastases account for the vast majority of cancer-related deaths (1), however, why some cancers metastasize while others do not is poorly understood. Specific genetic alterations do not define metastatic [...], Metastasis is the leading cause of cancer-related deaths. It is unclear how intratumor heterogeneity (ITH) contributes to metastasis and how metastatic cells adapt to distant tissue environments. The study of these adaptations is challenged by the limited access to patient material and a lack of experimental models that appropriately recapitulate ITH. To investigate metastatic cell adaptations and the contribution of ITH to metastasis, we analyzed single-cell transcriptomes of matched primary tumors and metastases from patient-derived xenograft models of breast cancer. We found profound transcriptional differences between the primary tumor and metastatic cells. Primary tumors upregulated several metabolic genes, whereas motility pathway genes were upregulated in micrometastases, and stress response signaling was upregulated during progression. Additionally, we identified primary tumor gene signatures that were associated with increased metastatic potential and correlated with patient outcomes. Immune-regulatory control pathways were enriched in poorly metastatic primary tumors, whereas genes involved in epithelial-mesenchymal transition were upregulated in highly metastatic tumors. We found that ITH was dominated by epithelial-mesenchymal plasticity (EMP), which presented as a dynamic continuum with intermediate EMP cell states characterized by specific genes such as CRYAB and S100A2. Elevated expression of an intermediate EMP signature correlated with worse patient outcomes. Our findings identified inhibition of the intermediate EMP cell state as a potential therapeutic target to block metastasis.

La harina obtenida de granos amaranto es considerada una fuente rica en compuestos bioactivos por lo que ha llamado el interés en industrias como la alimentaria. Este trabajo tuvo como objetivo evaluar el efecto de la incorporación de harina de Amaranthu spp y chocolate en las características sensoriales y bromatológicas de galletas. Para lo cual, se empleó un Diseño Completamente al Azar (DCA) con un arreglo factorial A*B, donde el factor A = Porcentaje de sustitución de harina de amaranto y B = Adición de chocolate, se evaluaron los perfiles sensoriales mediante una escala hedónica y características bromatólogicas (humedad, cenizas, fibra, grasas y proteínas). Además, al tratamiento que presentó mejor caracterización bromatológica se analizó la presencia de Aerobeos mesófilos, mohos y levaduras. En cuanto a la caracterización sensorial, se demostró que los tratamientos T1, T3 y T7 presentaron la mayor intensidad en los perfiles evaluados. Sin embargo, en el T7 (20 % de HA +0 % de chocolate) se observó una mayor concentración de proteína (8.37 %); fibra (4.69 %); y ceniza (2.31 %); así como también, un bajo contenido de grasa (17.84 %) y humedad (2.94 %), también se evidenció una presencia de 0,31𝑥103 A. mesófilos y ausencia de mohos y levaduras. Con esto se concluye que la harina de amaranto puede ser utilizadas en la elaboración de galletas en concentraciones del 20 % y permite obtener un producto con buena calidad nutricional. DOI: https://doi.org/10.54167/tch.v18i2.1484

Introdução: compreender o sentido e o significado de conforto para a pessoa em situação paliativa pode apresentar-se como um desafio para o enfermeiro na definição dos cuidados. Objetivo: mapear a evidência científica disponível sobre os cuidados de enfermagem que promovem o conforto na pessoa em situação paliativa. Materiais e método: revisão da literatura segundo as recomendações do Joanna Briggs Institute e do Prisma-ScR. Pesquisa completa nas bases de dados Medline Complete, Cinhal Complete, Scopus, Web of Science, Repositório Científico de Acesso Aberto de Portugal e OpenGrey. Incluídos estudos primários, com metodologia quantitativa, qualitativa ou métodos mistos, publicados entre janeiro de 2014 e março de 2023, em português, inglês ou espanhol. Sintaxe de pesquisa ajustada a cada base de dados. Combinação de MeSH, palavras de texto e de termos de indexação através dos operadores booleanos AND e OR. A truncadura* foi utilizada para potencializar a pesquisa. Resultados: identificaram-se 681 artigos, dos quais 239 eram duplicatas. Analisaram-se 442 estudos, excluindo-se 409 por não refletirem o tema. Recuperou-se o texto integral de 33 artigos, sendo que oito foram incluídos na revisão. Os cuidados de enfermagem promotores do conforto integram as dimensões física, psicoespiritual, ambiental e sociocultural. Destacam-se a implementação de medidas farmacológicas, o respeito pelas crenças religiosas e culturais, a facilitação da presença de familiares, a comunicação e a flexibilização das normas. Conclusões: a promoção do conforto para a pessoa em situação paliativa inclui o cuidado direto e o apoio à família. Da individualização dos cuidados e da resposta às necessidades específicas, pode resultar alívio, facilidade e transcendência.

Nonalcoholic fatty liver disease (NAFLD) can be ameliorated by calorie restriction, which leads to the suppressed somatotroph axis. Paradoxically, the suppressed somatotroph axis is associated with patients with NAFLD and is correlated with the severity of fibrosis. How the somatotroph axis becomes dysregulated and whether the repressed somatotroph axis impacts liver damage during the progression of NAFLD are unclear. Here, we identify a regulatory branch of the hepatic integrated stress response (ISR), which represses the somatotroph axis in hepatocytes through ATF3, resulting in enhanced cell survival and reduced cell proliferation. In mouse models of NAFLD, the ISR represses the somatotroph axis, leading to reduced apoptosis and inflammation but decreased hepatocyte proliferation and exacerbated fibrosis in the liver. NAD+ repletion reduces the ISR, rescues the dysregulated somatotroph axis, and alleviates NAFLD. These results establish that the hepatic ISR suppresses the somatotroph axis to control cell fate decisions and liver damage in NAFLD.

We carried out integrated host and pathogen metagenomic RNA and DNA next generation sequencing (mNGS) of whole blood (n = 221) and plasma (n = 138) from critically ill patients following hospital admission. We assigned patients into sepsis groups on the basis of clinical and microbiological criteria. From whole-blood gene expression data, we distinguished patients with sepsis from patients with non-infectious systemic inflammatory conditions using a trained bagged support vector machine (bSVM) classifier (area under the receiver operating characteristic curve (AUC) = 0.81 in the training set; AUC = 0.82 in a held-out validation set). Plasma RNA also yielded a transcriptional signature of sepsis with several genes previously reported as sepsis biomarkers, and a bSVM sepsis diagnostic classifier (AUC = 0.97 training set; AUC = 0.77 validation set). Pathogen detection performance of plasma mNGS varied on the basis of pathogen and site of infection. To improve detection of virus, we developed a secondary transcriptomic classifier (AUC = 0.94 training set; AUC = 0.96 validation set). We combined host and microbial features to develop an integrated sepsis diagnostic model that identified 99% of microbiologically confirmed sepsis cases, and predicted sepsis in 74% of suspected and 89% of indeterminate sepsis cases. In summary, we suggest that integrating host transcriptional profiling and broad-range metagenomic pathogen detection from nucleic acid is a promising tool for sepsis diagnosis.

Single-cell RNA sequencing (scRNA-seq) provides unique insights into the pathology and cellular origin of disease. We introduce single-cell disease relevance score (scDRS), an approach that links scRNA-seq with polygenic disease risk at single-cell resolution, independent of annotated cell types. scDRS identifies cells exhibiting excess expression across disease-associated genes implicated by genome-wide association studies (GWASs). We applied scDRS to 74 diseases/traits and 1.3 million single-cell gene-expression profiles across 31 tissues/organs. Cell-type-level results broadly recapitulated known cell-type-disease associations. Individual-cell-level results identified subpopulations of disease-associated cells not captured by existing cell-type labels, including T cell subpopulations associated with inflammatory bowel disease, partially characterized by their effector-like states; neuron subpopulations associated with schizophrenia, partially characterized by their spatial locations; and hepatocyte subpopulations associated with triglyceride levels, partially characterized by their higher ploidy levels. Genes whose expression was correlated with the scDRS score across cells (reflecting coexpression with GWAS disease-associated genes) were strongly enriched for gold-standard drug target and Mendelian disease genes.

Abstract Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

Enquadramento: Os estudantes de Enfermagem relatam fatores associados a elevados níveis de stress em ensino clínico (EC) e que são comumente experienciados neste processo de ensino aprendizagem. Objetivo: Mapear a evidência científica sobre os fatores indutores de stress nos estudantes de enfermagem em ensino clínico. Metodologia: Scoping review baseada no método de Joanna Briggs Institute (JBI). Utilizada a mnemónica PCC para dimensionar a população, conceito e contexto. No processo de seleção, extração e análise dos artigos, estiveram envolvidos dois revisores independentes. Resultados: Da pesquisa efetuada foram incluídos 17 estudos. Foram identificados fatores que integram aspetos pessoais e profissionais, fatores relacionados com o ambiente/estrutura do EC e a sua organização, bem como fatores associados aos sistemas de apoio, nomeadamente ao modelo de supervisão que acompanha este processo. Conclusão: Os fatores de stress influenciam o processo de ensino aprendizagem dos estudantes em EC, por isso, devem ser desenvolvidas estratégias de ensino que permitam assegurar a efetividade no desenvolvimento de competências dos estudantes em EC.

Background Colitis caused by checkpoint inhibitors (CPI) is frequent and is treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear.Methods Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations.Results CPI colitis biopsies showed enrichment of CD4+resident memory (RM) T cells in addition to CD8+ RM and cytotoxic CD8+ T cells. Matching T cell receptor (TCR) clonotypes suggested that both RMs are progenitors that yield cytotoxic effectors. Activated, CD38+ HLA-DR+ CD4+ RM and cytotoxic CD8+ T cells were enriched in steroid-experienced and a validation data set of steroid-naïve CPI colitis, underscoring their pathogenic potential across steroid exposure. Distinct from ulcerative colitis, CPI colitis exhibited perturbed stromal metabolism (NAD+, tryptophan) impacting epithelial survival and inflammation. Endothelial cells in CPI colitis after anti-TNF and anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) upregulated the integrin α4β7 ligand molecular vascular addressin cell adhesion molecule 1 (MAdCAM-1), which may preferentially respond to vedolizumab (anti-α4β7).Conclusions These findings nominate CD4+ RM and MAdCAM-1+ endothelial cells for targeting in specific subsets of CPI colitis patients.

Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept to identify cell types of origin using the Tabula Sapiens transcriptomic cell atlas as well as individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset. We define cell type signature scores, which allow the inference of cell types that contribute to cell-free RNA for a variety of diseases.

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.

El objetivo de esta investigación fue caracterizar reológicamente una bebida formulada y elaborada con exudado de cacao (Theobroma cacao L.) CCN51 y suero láctico. La formulación se optimizó mediante la metodología de superficie respuesta para los atributos color, olor, sabor y aceptabilidad; posteriormente se realizó un análisis de superficie múltiple para determinar los parámetros óptimos globales mediante la función deseabilidad. Los resultados aseguran que la proporción exudado y suero láctico debe ser de 40/60 con 10% de sacarosa. La reología de la bebida demuestra que es un fluido no newtoniano del tipo seudoplástico. En general la temperatura y el tiempo de almacenamiento tienen un efecto significativo en el índice de flujo e índice de consistencia. Los análisis químicos proximal y microbiológicos cumplen con las normas y la bebida es apto para el consumo humano. Los resultados reológicos de las bebidas a base exudado de cacao y suero láctico pueden usarse como parámetro de control de calidad y dimensionamiento de máquinas, equipos, tuberías, conexiones, filtros, bombas de impulsión y también la investigación aporta conocimientos para el aprovechamiento del residuo agroindustrial y de la industria láctica.

The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. Here we performed single-cell RNA sequencing on 20 organs to reveal cell-type-specific responses to young and aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, haematopoietic stem cells and hepatocytes are among those cell types that are especially responsive. On the pathway level, young blood invokes new gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.

We identify the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as a druggable target, using genetic and chemical validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 and MMV084978) selects for mutations in PfAcAS. Metabolic profiling of compound-treated parasites reveals changes in acetyl-CoA levels for both compounds. Genome editing confirms that mutations in PfAcAS are sufficient to confer resistance. Knockdown studies demonstrate that PfAcAS is essential for asexual growth, and partial knockdown induces hypersensitivity to both compounds. In vitro biochemical assays using recombinantly expressed PfAcAS validates that MMV019721 and MMV084978 directly inhibit the enzyme by preventing CoA and acetate binding, respectively. Immunolocalization studies reveal that PfAcAS is primarily localized to the nucleus. Functional studies demonstrate inhibition of histone acetylation in compound-treated wild-type, but not in resistant parasites. Our findings identify and validate PfAcAS as an essential, druggable target involved in the epigenetic regulation of gene expression.

Autoimmune hepatitis (AIH) is a poorly understood, chronic disease, for which corticosteroids are still the mainstay of therapy and most patients undergo liver biopsy to obtain a diagnosis. We aimed to determine if there was a transcriptomic signature of AIH in the peripheral blood and investigate underlying biologic pathways revealed by gene expression analysis. Whole blood RNA from 75 AIH patients and 25 healthy volunteers was extracted and sequenced. Differential gene expression analysis revealed 249 genes that were significantly differentially expressed in AIH patients compared to controls. Using a random forest algorithm, we determined that less than 10 genes were sufficient to differentiate the two groups in our cohort. Interferon signaling was more active in AIH samples compared to controls, regardless of treatment status. Pegivirus sequences were detected in five AIH samples and 1 healthy sample. The gene expression data and clinical metadata were used to determine 12 genes that were significantly associated with advanced fibrosis in AIH. AIH patients with a partial response to therapy demonstrated decreased evidence of a CD8+ T cell gene expression signal. These findings represent progress in understanding a disease in need of better tests, therapies, and biomarkers.

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults whereas disease burden in children is lower. To investigate whether differences in the upper airway immune response may contribute to this disparity, we compare nasopharyngeal gene expression in 83 children (40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes is robustly activated in both children and adults with SARS-CoV-2 infection compared to the respective non-viral groups, with only subtle distinctions. Children, however, demonstrate markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including response to TNF and production of IFNγ, IL-2 and IL-4. Cell type deconvolution confirms greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibit a decrease in proportions of ciliated cells, among the primary targets of SARS-CoV-2, upon infection. These findings demonstrate that children elicit a more robust innate and especially adaptive immune response to SARS-CoV-2 in the upper airway that likely contributes to their protection from severe disease in the lower airway.

A growing interest in healthy diets has increased demand for fish and seafood, with aquaculture playing a crucial role in meeting this need. Developing new aquaculture products can enhance their commercial value and address consumer demand, but it is unclear which products will be well-received. This study aimed to generate ideas for new products derived from sea bream and prawns, and to gather consumer opinions on these ideas, segmented by gender and age. Two methodologies were used: focus groups and Check-All-That-Apply (CATA). In the focus groups, with two sessions per species and 10 participants each, ideas for aquaculture products were generated and categorized as fresh, dehydrated, fermented, marinated, and canned. The CATA technique, applied to 387 individuals, assessed the acceptability of fresh species, yielding average scores of 6.6 for sea bream and 6.8 for prawns. Sea bream was associated with products like fillets and long-shelf-life loins, while prawns were linked to snacks and toppings. In conclusion, the use of tools like focus groups has shown promising results for developing new aquaculture products. CATA analysis indicated that sea bream should be minimally processed with a long shelf life, and prawns should be processed into dehydrated products. Women preferred traditional products, while men favoured innovative options.