Ethnic Differences in Survival among Brazilian Modern-era Olympic Medalists from 1920 to 1992: A Cohort Study. / Diferenças Étnicas na Sobrevida entre Medalhistas Olímpicos Brasileiros da Era Moderna de 1920 a 1992: Um Estudo de Coorte.

BACKGROUND: Disparities in health outcomes among racial groups warrant investigation, even among elite athletes. Therefore, understanding the impact of race upon post-medal survival in Brazilian Olympians becomes essential. OBJECTIVE: To compare post-medal survival between white and non-white Brazilian Olympic medalists from 1920 to 1992. METHODS: This study used publicly available data for a retrospective cohort study on all Brazilian Olympic medalists from 1920 to 1992 (males only). Athletes were classified into white and non-white groups using structured ethnicity determination. Kaplan-Meier analyses computed the restricted mean survival time (RMST) for each ethnic group. A Cox proportional hazards analysis assessed ethnicity-based survival differences, adjusting for medal-winning age and birth year (p<0.05). RESULTS: Among 123 athletes (73.9% white), the mean age of medal achievement was 25.03±4.8 years. During the study, 18.7% of white and 37.5% of non-white athletes died (p=0.031). White athletes had a mean age at death of 75.10±18.01 years, while non-white athletes had an age of 67.13±14.90 years (p=0.109). The RMST for white athletes was 51.59 (95% CI 49.79-53.39) years, while for non-white athletes, it was 45.026 (95% CI 41.31-48.74) years, resulting in a ΔRMST of 6.56 (95% CI 2.43-10.70; p=0.0018). Multivariate analysis showed that non-white athletes had a higher mortality risk than did white athletes (HR 5.58; 95% CI, 2.18-14.31). CONCLUSION: Following their first medal, white Brazilian Olympians typically enjoy a six-year longer lifespan than their non-white counterparts, illustrating a marked mortality gap and health disparities among healthy individuals in Brazil.

FUNDAMENTO: As disparidades nos resultados de saúde entre grupos raciais merecem investigação, mesmo em atletas de elite. Portanto, compreender o impacto da raça na sobrevida pós-medalha em atletas olímpicos brasileiros torna-se essencial. OBJETIVO: Comparar a sobrevida pós-medalha entre medalhistas olímpicos brasileiros brancos e não brancos de 1920 a 1992. MÉTODOS: Utilizamos dados disponíveis publicamente para um estudo de coorte retrospectivo de todos os medalhistas olímpicos brasileiros de 1920 a 1992 (somente homens). Os atletas foram classificados nos grupos brancos e não brancos usando determinação estruturada de etnia. As análises de Kaplan-Meier calcularam o tempo médio de sobrevida restrito (TMSR) para cada grupo étnico. Uma análise de riscos proporcionais de Cox avaliou as diferenças de sobrevida baseadas na etnia, ajustando para a idade da conquista da medalha e ano de nascimento (p<0,05). RESULTADOS: Entre 123 atletas (73,9% brancos), a idade média da conquista de medalhas foi de 25,03 ± 4,8 anos. Durante o estudo, 18,7% dos atletas brancos e 37,5% dos atletas não brancos morreram (p=0,031). Os atletas brancos tiveram média de idade ao óbito de 75,10 ± 18,01 anos, enquanto os atletas não brancos tiveram idade média de 67,13 ± 14,90 anos (p=0,109). O TMSR para atletas brancos foi de 51,59 (IC 95%, 49,79 - 53,39) anos, e para atletas não brancos foi de 45,026 (IC 95%, 41,31 - 48,74) anos, resultando em um ΔTMSR de 6,56 (IC 95%, 2,43 - 10,70; p=0,0018). A análise multivariada mostrou que atletas não brancos apresentavam maior risco de mortalidade do que atletas brancos (RC 5,58; IC 95%, 2,18 - 14,31). CONCLUSÃO: Após a primeira medalha, os atletas olímpicos brasileiros brancos normalmente desfrutam de uma expectativa de vida seis anos mais longa do que seus colegas não brancos, ilustrando uma acentuada diferença de mortalidade e disparidades de saúde entre indivíduos saudáveis no Brasil.

Incidence and associated factors of surgical site infection in patients undergoing foot and ankle surgery: a 7-year cohort study.

Surgical site infections (SSI) constitute 31% of all hospital-acquired conditions, with ankle and foot surgical procedures showing an incidence of SSI ranging from 0.5% to 6.5%. This study aimed to assess the incidence of both superficial and deep surgical site infections in foot and ankle surgery, along with associated factors. Conducted as a retrospective cohort study, it included 2180 patients undergoing foot and ankle surgery in a private hospital between 2014 and 2020, encompassing elective and trauma cases. Outcome variables comprised SSI, while predictor variables encompassed sex, age, diabetes mellitus, systemic arterial hypertension, smoking, American Society of Anesthesiologists (ASA) score, and body mass index. Logistic regression models were employed to identify associations between study variables. The incidence of surgical site infections stood at 4% (83/2180), comprising a rate of 2.8% (57/2180) for superficial infections and 1.2% (26/2180) for deep infections. Smoking (OR 2.9, 95%CI 1.4-5.3) and ASA score >2 (OR 3.4, 95%CI 1.2-8.4) emerged as independent factors associated with surgical site infections. The group with deep infections exhibited higher proportions of smokers (p = 0.002), systemic arterial hypertension (p = 0.018), trauma surgery (p = 0.049), and an ASA score >2 (p = 0.011). Overall infection incidence in this cohort reached 4%, with trauma cases, smoking, hypertension, and an ASA score >2 independently linked to deep infections. Surgeons should be cognizant of these risk factors when managing prophylactic antibiotic regimens for patients.

Evidence of a pan-tissue decline in stemness during human aging.

Despite their biological importance, the role of stem cells in human aging remains to be elucidated. In this work, we applied a machine learning methodology to GTEx transcriptome data and assigned stemness scores to 17,382 healthy samples from 30 human tissues aged between 20 and 79 years. We found that ~60% of the studied tissues exhibit a significant negative correlation between the subject's age and stemness score. The only significant exception was the uterus, where we observed an increased stemness with age. Moreover, we observed that stemness is positively correlated with cell proliferation and negatively correlated with cellular senescence. Finally, we also observed a trend that hematopoietic stem cells derived from older individuals might have higher stemness scores. In conclusion, we assigned stemness scores to human samples and show evidence of a pan-tissue loss of stemness during human aging, which adds weight to the idea that stem cell deterioration may contribute to human aging.

BjussuMP-II, a venom metalloproteinase, induces the release and cleavage of pro-inflammatory cytokines and disrupts human umbilical vein endothelial cells.

Snake venom metalloproteases (SVMPs) are hydrolytic enzymes dependent on metal binding, primarily zinc (Zn2+), at their catalytic site. They are classified into three classes (P-I to P-III). BjussuMP-II, a P-I SVMP isolated from Bothrops jararacussu snake venom, has a molecular mass of 24 kDa. It exhibits inhibitory activity on platelet aggregation and hydrolyzes fibrinogen. TNF-α upregulates the expression of adhesion molecules on endothelial cell surfaces, promoting leukocyte adhesion and migration during inflammation. Literature indicates that SVMPs may cleave the TNF-α precursor, possibly due to significant homology between metalloproteases from mammalian extracellular matrix and SVMPs. This study aimed to investigate BjussuMP-II's effects on human umbilical vein endothelial cells (HUVEC), focusing on viability, detachment, adhesion, release, and cleavage of TNF-α, IL-1ß, IL-6, IL-8, and IL-10. HUVEC were incubated with BjussuMP-II (1.5-50 µg/mL) for 3-24 h. Viability was determined using LDH release, MTT metabolization, and 7AAD for membrane integrity. Adhesion and detachment were assessed by incubating cells with BjussuMP-II and staining with Giemsa. Cytokines were quantified in HUVEC supernatants using EIA. TNF-α cleavage was evaluated using supernatants from PMA-stimulated cells or recombinant TNF-α. Results demonstrated BjussuMP-II's proteolytic activity on casein. It was not toxic to HUVEC at any concentration or duration studied but interfered with adhesion and promoted detachment. PMA induced TNF-α release by HUVEC, but this effect was not observed with BjussuMP-II, which cleaved TNF-α. Additionally, BjussuMP-II cleaved IL-1ß, IL-6, and IL-10. These findings suggest that the zinc metalloprotease BjussuMP-II could be a valuable biotechnological tool for treating inflammatory disorders involving cytokine deregulation.

Nocardia cyriacigeorgica Elicits Gut Disturbances in a Leaky Gut Model of Colitis, but Not the Harmful Cascade Leading to Gut-First Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with an unknown cause. Recent research has highlighted the importance of the gut in neuronal and immune maturation through the exchange of nutrients and cellular signals. This has led to the "gut-first PD" hypothesis, which aims to explain many of the sporadic cases and their prodromal intestinal symptoms, such as constipation and intestinal α-synuclein (aSyn) aggregation. The link between mitochondrial dysfunction and aSyn deposition is central to PD pathophysiology, since they can also trigger pro-inflammatory signals associated with aSyn deposition, potentially contributing to the onset of PD. As mitochondria are derived from ancestral alpha-proteobacteria, other bacteria may specifically target this organelle. We sought to use Nocardia cyriacigeorgica, a bacterium previously associated with parkinsonism, and dextran sulfate sodium (DSS) as pro-inflammatory modulators to gain further insight into the onset of PD. This study indicates that aSyn aggregation plus mitochondrial dysfunction without intestinal barrier leakage are not sufficient to trigger gut-first PD.

Cardiorespiratory fitness and muscular fitness correlates in youth: A hierarchy of behavioral, contextual, and health-related outcomes.

OBJECTIVES: Despite the health importance of identifying correlates of physical fitness in youth, no investigation to date has explored the influence of behavioral, health-related, and contextual correlates simultaneously. We investigated the hierarchical relationship of multiple modifiable correlates favoring or diminishing cardiorespiratory and muscular fitness in youth. DESIGN: Cross-sectional investigation. METHODS: In a sample of 5174 children and adolescents, 31 correlates were hierarchized according to their impact on cardiorespiratory and muscular fitness assessed using the FITESCOLA® fitness battery. A Chi-squared Automatic Interaction Detection approach was employed and measures of correlation and association were used to investigate the relationship between physical fitness and correlates. RESULTS: In children, body mass index was the most relevant factor to discriminate between high and low cardiorespiratory and muscular fitness of the upper, middle, and lower body. While body mass index was more important than any other correlate to differentiate levels of upper and lower body muscular fitness during adolescence, specific characteristics of sports participation emerged as key factors to discriminate between high and low cardiorespiratory fitness and middle body muscular fitness. Other correlates, including the self-report of active recess time, active commuting to school, favorable neighborhood conditions, and limited time on screens and cellphones, were demonstrative of favorable physical fitness levels. CONCLUSIONS: Both body composition and sports-related characteristics emerged as the two most relevant factors of physical fitness in youth. Additional health benefits may be obtained from building supportive environments for sports and healthy exercise habits within the household and at different school education levels.

Somatic mutations in human ageing: New insights from DNA sequencing and inherited mutations.

The accumulation of somatic mutations is a driver of cancer and has long been associated with ageing. Due to limitations in quantifying mutation burden with age in non-cancerous tissues, the impact of somatic mutations in other ageing phenotypes is unclear. Recent advances in DNA sequencing technologies have allowed the large-scale quantification of somatic mutations in ageing tissues. These studies have revealed a gradual accumulation of mutations in normal tissues with age as well as a substantial clonal expansion driven mostly by cancer-related mutations. Nevertheless, it is difficult to envision how the burden and stochastic nature of age-related somatic mutations identified so far can explain most ageing phenotypes that develop gradually. Studies across species have also found that longer-lived species have lower somatic mutation rates, though these could be due to selective pressures acting on other phenotypes such as perhaps cancer. Recent studies in patients with higher somatic mutation burden and no signs of accelerated ageing further question the role of somatic mutations in ageing. Overall, with a few exceptions like cancer, recent DNA sequencing studies and inherited mutations do not support the idea that somatic mutations accumulating with age drive ageing phenotypes, and the phenotypic role, if any, of somatic mutations in ageing remains unclear.

How to design and establish a national school-based physical fitness monitoring and surveillance system for children and adolescents: A 10-step approach recommended by the FitBack network.

BACKGROUND: Providing individual- and population-level data on children's physical fitness (PF) is a crucial public health and education priority. However, few national fitness monitoring or surveillance systems are currently in practice internationally. We aim to summarize the current European PF monitoring and surveillance systems for school-aged children and to provide experience-based guidelines on how to design such systems. METHODS: The FitBack network consists of experts from diverse backgrounds with the common interest to improve the accessibility of PF monitoring for young people globally. Through FitBack network, we identified and compared the national or regional PF monitoring and surveillance systems currently in operation across Europe. We formulated a 10-step approach for designing and establishing one's own system, based on analysis of experienced strengths, weaknesses, opportunities, and threats to monitoring childhood fitness. RESULTS: We identified a total of eight PF monitoring systems in Finland, France, Galicia of Spain, Hungary, Lithuania, Portugal, Serbia, and Slovenia. The FitBack network recommends the following steps for designing and establishing one's own system: (1) set up mission statements and aims, (2) involve stakeholders, (3) utilize scientific background, (4) governance structure, (5) ensure sufficient funding, (6) data management planning, (7) provide meaningful feedback, (8) conduct pilot testing, (9) plan implementation process, and (10) invest in communication with stakeholders. CONCLUSIONS: This study provides an updated overview of the best practices for school-aged children's fitness monitoring and surveillance in Europe. Additionally, it offers a 10-step approach to assist in the creation of similar systems in Europe or globally.

Distinguishing between driver and passenger mechanisms of aging.

Understanding why we age is a long-standing question, and many mechanistic theories of aging have been proposed. Owing to limitations in studying the aging process, including a lack of adequate quantitative measurements, its mechanistic basis remains a subject of debate. Here, I explore theories of aging from the perspective of causal relationships. Many aging-related changes have been observed and touted as drivers of aging, including molecular changes in the genome, telomeres, mitochondria, epigenome and proteins and cellular changes affecting stem cells, the immune system and senescent cell buildup. Determining which changes are drivers and not passengers of aging remains a challenge, however, and I discuss how animal models and human genetic studies have been used empirically to infer causality. Overall, our understanding of the drivers of human aging is still inadequate; yet with a global aging population, elucidating the causes of aging has the potential to revolutionize biomedical research.

Minimally Invasive Peroneal Tenodesis Assisted by Peroneal Tendoscopy: Technique and Preliminary Results.

Introduction: Peroneal disorders are a common cause of ankle pain and lateral instability and have been described in as much as 77% of patients with lateral ankle instability. Clicking, swelling, pain, and tenderness in the peroneal tendons track are frequent symptoms, but they can be confused with other causes of lateral ankle pain. The management of peroneal disorders can be conservative or surgical. When the conservative treatment fails, surgery is indicated, and open or tendoscopic synovectomy, tubularization, tenodesis or tendon transfers can be performed. The authors present a surgical technique of tendoscopy associated to minimally invasive tenodesis for the treatment of peroneal tendon tears, as well as the preliminary results of patients submitted to this procedure. Methods: Four patients with chronic lateral ankle pain who were diagnosed with peroneal brevis pathology were treated between 2020 and 2022 with tendoscopic-assisted minimally invasive synovectomy and tenodesis. Using a 2.7 mm 30° arthroscope and a 3.0 mm shaver blade, the entire length of the peroneus brevis tendon and most parts of the peroneus longus tendon can be assessed within Sammarco's zones 1 and 2. After the inspection and synovectomy, a minimally invasive tenodesis is performed. Results: All patients were evaluated at least six months after surgery. All of them reported improvement in daily activities and in the Foot Function Index (FFI) questionnaire (pre-surgery mean FFI = 23.86%; post-surgery mean FFI = 6.15%), with no soft tissue complications or sural nerve complaints. Conclusion: The tendoscopy of the peroneal tendons allows the surgeon to assess their integrity, confirm the extent of the lesion, perform synovectomy, prepare the tendon for tenodesis, and perform it in a safe and minimally invasive way, reducing the risks inherent to the open procedure.

Human Ageing Genomic Resources: updates on key databases in ageing research.

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).

The longevity bottleneck hypothesis: Could dinosaurs have shaped ageing in present-day mammals?

The evolution and biodiversity of ageing have long fascinated scientists and the public alike. While mammals, including long-lived species such as humans, show a marked ageing process, some species of reptiles and amphibians exhibit very slow and even the absence of ageing phenotypes. How can reptiles and other vertebrates age slower than mammals? Herein, I propose that evolving during the rule of the dinosaurs left a lasting legacy in mammals. For over 100 million years when dinosaurs were the dominant predators, mammals were generally small, nocturnal, and short-lived. My hypothesis is that such a long evolutionary pressure on early mammals for rapid reproduction led to the loss or inactivation of genes and pathways associated with long life. I call this the 'longevity bottleneck hypothesis', which is further supported by the absence in mammals of regenerative traits. Although mammals, such as humans, can evolve long lifespans, they do so under constraints dating to the dinosaur era.

m7GHub V2.0: an updated database for decoding the N7-methylguanosine (m7G) epitranscriptome.

With recent progress in mapping N7-methylguanosine (m7G) RNA methylation sites, tens of thousands of experimentally validated m7G sites have been discovered in various species, shedding light on the significant role of m7G modification in regulating numerous biological processes including disease pathogenesis. An integrated resource that enables the sharing, annotation and customized analysis of m7G data will greatly facilitate m7G studies under various physiological contexts. We previously developed the m7GHub database to host mRNA m7G sites identified in the human transcriptome. Here, we present m7GHub v.2.0, an updated resource for a comprehensive collection of m7G modifications in various types of RNA across multiple species: an m7GDB database containing 430 898 putative m7G sites identified in 23 species, collected from both widely applied next-generation sequencing (NGS) and the emerging Oxford Nanopore direct RNA sequencing (ONT) techniques; an m7GDiseaseDB hosting 156 206 m7G-associated variants (involving addition or removal of an m7G site), including 3238 disease-relevant m7G-SNPs that may function through epitranscriptome disturbance; and two enhanced analysis modules to perform interactive analyses on the collections of m7G sites (m7GFinder) and functional variants (m7GSNPer). We expect that m7Ghub v.2.0 should serve as a valuable centralized resource for studying m7G modification. It is freely accessible at: www.rnamd.org/m7GHub2.

Limb-specific isometric and isokinetic strength in adults: The potential role of regional bioelectrical impedance analysis-derived phase angle.

BACKGROUND & AIMS: It is not yet known whether regional bioelectrical impedance (BIA) phase angle (PhA) may be informative of different types of strength performed by the lower and upper limbs, independently of lean soft tissue mass (LSTM). Using a sample of healthy adults, we aimed to examine the association and relevance of regional PhA relative to isometric and isokinetic strength of each limb. METHODS: A total of 57 participants (32.7 ± 12.9 years; 24.7 ± 3.5 kg/m2) were included in the present investigation. Regional raw BIA variables were determined using a phase-sensitive BIA device. Dual-energy X-ray absorptiometry was used to evaluate LSTM. Absolute isometric and isokinetic (i.e., 60°/s and 180°/s) strength of each limb (extension and flexion) was assessed using an isokinetic dynamometer and used to calculate relative strength. RESULTS: In absolute strength, only dominant leg PhA was associated with isometric extension strength (ß = 0.283) and isokinetic 180°/s flexion strength (ß = 0.354), regardless of LSTM (p < 0.05). In relative strength, a significant association of regional PhA was found for dominant arm flexion isometric strength (ß = 0.336), and non-dominant arm and dominant leg extension isometric strength (ß = 0.377, ß = 0.565, respectively; p < 0.05), independently of LSTM. Similarly, for isokinetic 180°/s strength, regional PhA significantly explained the variance in the relative strength of both arms and dominant leg (ß = 0.350 to 0.506), regardless of LSTM (p < 0.05). Relative isokinetic 60°/s strength was not consistently associated with regional PhA (p ≥ 0.05). CONCLUSIONS: Regional PhA significantly explained relative (isometric and 180°/s isokinetic strength of both arms and dominant leg), but not absolute muscle strength, independently of regional LSTM. Thus, after accounting for body size, regional PhA seems to have its own characteristics that explain relative strength independently of LSTM.

European Health Union: An emergent reality.

In this article we argue that the Member States of the European Union (EU) have consistently, since its inception, developed a shared framework to measure, monitor and intervene to improve the health status of its population, while invoking the subsidiarity principle for the health sector. As a result, a European Health Union (EHU) has been emerging insidiously and consistently, following the concept of a system for health. Using the World Health Organisation Building Blocks Framework, we analyse the normative and institutional developments related to EU citizens' health that have created a de facto EHU. Developments towards an EHU remain unequally distributed among the different building blocks analysed. The existing EHU is the result of a fragmented and incremental process, mostly grounded in governance, health intelligence and services' development. Health crisis, the Commission's agenda-setting activities and market pressures have been the most important push factors for these step-by-step processes.

Post-acute exercise cardiovagal modulation in older male adults with and without type 2 diabetes.

PURPOSE: We examined heart rate variability (HRV) and baroreflex sensitivity (BRS) disease- and age-related response at 10-and 60-min after an acute high-intensity interval (HIIE) and moderate continuous exercise (MICE) in older adults with and without type 2 diabetes mellitus (T2DM) and healthy young adults. METHODS: Twelve older male adults with (57-84 years) and without T2DM (57-76 years) and 12 healthy young male adults (20-40 years) completed an isocaloric acute bout of HIIE, MICE, and a non-exercise condition in a randomized order. Time and Wavelets-derived frequency domain indices of HRV and BRS were obtained in a supine position and offline over 2-min time-bins using Matlab. RESULTS: HIIE but not MICE reduced natural logarithm root mean square of successive differences (Ln-RMSSD) (d = - 0.85; 95% CI - 1.15 to - 0.55 ms, p < 0.001), Ln-high-frequency power (d = - 1.60; 95% CI - 2.24 to - 0.97 ms2; p < 0.001), and BRS (d = - 6.32; 95% CI - 9.35 to - 3.29 ms/mmHg, p < 0.001) in adults without T2DM (averaged over young and older adults without T2DM), returning to baseline 60 min into recovery. These indices remained unchanged in older adults with T2DM after HIIE and MICE. Older adults with T2DM had lower resting Ln-RMSSD and BRS than aged-matched controls (Ln-RMSSD, d = - 0.71, 95% CI - 1.16 to - 0.262 ms, p = 0.001; BRS d = - 3.83 ms/mmHg), 95% CI - 6.90 to - 0.76, p = 0.01). CONCLUSIONS: Cardiovagal modulation following acute aerobic exercise is intensity-dependent only in adults without T2DM, and appears age-independent. These findings provide evidence of cardiac autonomic impairments in older adults with T2DM at rest and following aerobic exercise.

Identification of a muropeptide precursor transporter from gut microbiota and its role in preventing intestinal inflammation.

The gut microbiota is a considerable source of biologically active compounds that can promote intestinal homeostasis and improve immune responses. Here, we used large expression libraries of cloned metagenomic DNA to identify compounds able to sustain an anti-inflammatory reaction on host cells. Starting with a screen for NF-κB activation, we have identified overlapping clones harbouring a heterodimeric ATP-binding cassette (ABC)-transporter from a Firmicutes. Extensive purification of the clone's supernatant demonstrates that the ABC-transporter allows for the efficient extracellular accumulation of three muropeptide precursor, with anti-inflammatory properties. They induce IL-10 secretion from human monocyte-derived dendritic cells and proved effective in reducing AIEC LF82 epithelial damage and IL-8 secretion in human intestinal resections. In addition, treatment with supernatants containing the muropeptide precursor reduces body weight loss and improves histological parameters in Dextran Sulfate Sodium (DSS)-treated mice. Until now, the source of peptidoglycan fragments was shown to come from the natural turnover of the peptidoglycan layer by endogenous peptidoglycan hydrolases. This is a report showing an ABC-transporter as a natural source of secreted muropeptide precursor and as an indirect player in epithelial barrier strengthening. The mechanism described here might represent an important component of the host immune homeostasis.

scDiffCom: a tool for differential analysis of cell-cell interactions provides a mouse atlas of aging changes in intercellular communication.

Dysregulation of intercellular communication is a hallmark of aging. To better quantify and explore changes in intercellular communication, we present scDiffCom and scAgeCom. scDiffCom is an R package, relying on approximately 5,000 curated ligand-receptor interactions, that performs differential intercellular communication analysis between two conditions from single-cell transcriptomics data. Built upon scDiffCom, scAgeCom is an atlas of age-related cell-cell communication changes covering 23 mouse tissues from 58 single-cell RNA sequencing datasets from Tabula Muris Senis and the Calico murine aging cell atlas. It offers a comprehensive resource of tissue-specific and sex-specific aging dysregulations and highlights age-related intercellular communication changes widespread across the whole body, such as the upregulation of immune system processes and inflammation, the downregulation of developmental processes, angiogenesis and extracellular matrix organization and the deregulation of lipid metabolism. Our analysis emphasizes the relevance of the specific ligands, receptors and cell types regulating these processes. The atlas is available online ( https://scagecom.org ).

Exosome Liberation by Human Neutrophils under L-Amino Acid Oxidase of Calloselasma rhodostoma Venom Action.

L-Amino acid oxidase (LAAO) is an enzyme found in snake venom that has multifaceted effects, including the generation of hydrogen peroxide (H2O2) during oxidative reactions, leading to various biological and pharmacological outcomes such as apoptosis, cytotoxicity, modulation of platelet aggregation, hemorrhage, and neutrophil activation. Human neutrophils respond to LAAO by enhancing chemotaxis, and phagocytosis, and releasing reactive oxygen species (ROS) and pro-inflammatory mediators. Exosomes cellular nanovesicles play vital roles in intercellular communication, including immune responses. This study investigates the impact of Calloselasma rhodostoma snake venom-derived LAAO (Cr-LAAO) on human neutrophil exosome release, including activation patterns, exosome formation, and content. Neutrophils isolated from healthy donors were stimulated with Cr-LAAO (100 µg/mL) for 3 h, followed by exosome isolation and analysis. Results show that Cr-LAAO induces the release of exosomes with distinct protein content compared to the negative control. Proteomic analysis reveals proteins related to the regulation of immune responses and blood coagulation. This study uncovers Cr-LAAO's ability to activate human neutrophils, leading to exosome release and facilitating intercellular communication, offering insights into potential therapeutic approaches for inflammatory and immunological disorders.