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Objective: The dysregulated host response to infections can lead to sepsis. The disease progression and outcome are determined by a complex balance between mechanisms responsible for controlling the pathogen growth and mechanisms to avoid and repair organ dysfunctions. It is a disease with a spectrum of clinical phenotypes associated with the host immune response and clinical outcomes, making difficult the implementation of specific therapeutic. Despite sepsis phenotypes being well distinguished, the mechanisms underlying the heterogeneous responses are currently limited. The cecal-ligation and puncture (CLP) sepsis model resembles the disease characteristics of the higher inflammation phenotype, which has higher mortality. The CLP induction in the same mice inbred strain and same weight, age, sex, and co-housed evoked a heterogeneous host response, in which approximately half of the mice succumbed. Thus, we take advantage of the CLP-septic survived and non-survived mice immune cell activation profiling, to gain further insights into immunological mechanisms related to the worsening of the hyperinflammatory septic phenotype. Methods: We profiled CLP-septic survived and non-survived mice immune cell activation using single-cell RNA sequencing (scRNA-seq). Results: The initial response is similar between septic mice. However, after 6 hours, mice that did not survive had increased inflammation parameters, organ damage markers, and bacteremia compared with the survived mice. Thus, our data suggest that after the same initial inflammatory response between all mice, the non-surviving mice showed a failure of resistance and tissue damage tolerance mechanisms. Subsequently, we took advantage of the scRNA-seq technology to gain further insight into the cellular diversity and transcriptional landscape of the immunological heterogeneous response at the initial phase of sepsis. Our findings demonstrated an enrichment of the apoptosis pathway in the subsets of T and B cells but not in the CD8+ T ISGs population in the non-survived group. The CD8+ T ISGs population has an immunosuppressive profile, as we observed an enrichment of genes related to the HIF-1alpha and PD-L1 expression. It is interesting that we observed an increased enrichment of IFN-gamma signaling pathways in lymphocytes, neutrophils, and monocytes from non-survived septic mice which is associated with the induction of HIF-1alpha and PD-L1 expression. Neutrophils play both protective and deleterious role in experimental models of sepsis, promoting infection control and increasing organ damage. We observed that non-survived septic mice have an increase of immature CXCR4+ PD-L1+ neutrophils and monocytes frequencies in the bloodstream, followed by an increased accumulation of trafficking-specific neutrophils PD-L1+ CXCR4+ into the lungs. The increased PD-L1 expression on neutrophils is associated with an increase of IFN-gamma signaling pathways, and upon abrogating the IFN-gamma signaling pathway using IFN-gamma deficient mice, we noticed less susceptibility to CLP-sepsis and less induction of PD-L1 expressionon neutrophils. We also demonstrated that the neutrophils PD-L1 were able to do immune sinapsis with linfocytes T CD8+ and T CD4+, which could explain the increase of lymphocyte apoptosis in our results. Conclusions: This study highlights the modulation of IFN-gamma and PD-L1 expression on neutrophils as potential therapeutic targets in the clinical sepsis hyperinflammatory phenotype.

The Sapotaceae family encompasses the genus Pouteria spp., comprising approximately 1,250 species of fruits cherished by consumers for their delightful assortment and flavors. Over the years, extensive research has been devoted to exploring the natural bioactive compounds present in these fruits, with the primary goal of preventing and/or mitigating the risk of degenerative diseases. Despite their widespread popularity in numerous countries, the chemistry, nutritional content, and biological potential of these fruits remain relatively unexplored. This comprehensive review aims to shed light on the principal volatile and non-volatile chemical components found in Pouteria fruits, which present notable antioxidant properties. By doing so, a broad perspective on the current trends in characterizing these compounds and their potential applications were provided, as well as the associated health benefits. Additionally, the prospects and potential applications of Pouteria fruits in the food industry were explored herein., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Preservation of the periareolar dermis, after de-epithelization in reduction mammaplasty, may result in reduced nipple-areola complex (NAC) mobility. Consequently, distortion in shape and difficulty correcting the areola position can occur., Objectives: The aim of this study was to evaluate NAC viability and sensitivity resulting from periareolar dermis section after de-epithelization in patients who underwent reduction mammaplasty surgery., Methods: This study was a randomized, controlled double-blind clinical trial. A total of 41 patients (82 breasts) were randomly allocated into 2 groups and underwent reduction mammaplasty-involving the superior pedicle-with a final inverted T-shaped scar. A sectioning of the periareolar dermis was performed on the breasts in the experimental group. Semmes-Weinstein monofilaments were used to evaluate NAC sensitivity at the preoperative evaluation, and 3, 6, and 52 weeks after surgery., Results: No cases of partial or total NAC necrosis were noted in either group. The comparison between the groups did not show significant differences regarding NAC sensitivity. However, a statistically significant difference was noted when sensitivity levels at the preoperative evaluation and 3 weeks after surgery were compared in the experimental group. A significant difference was noted when the scores of the sensitivity 3 weeks after surgery were compared between the control and the experiment groups. Nevertheless, after 1 year, no statistical differences were observed in the experimental group or between both groups., Conclusions: The sectioning of the periareolar dermis does not affect the viability or the pressure sensitivity of the NAC., (© 2020 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)