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Emerging epidemiological evidence indicates nature exposure could be associated with greater health benefits among groups in lower versus higher socioeconomic positions. One possible mechanism underpinning this evidence is described by our framework: (susceptibility) adults in low socioeconomic positions face higher exposure to persistent psychosocial stressors in early life, inducing a pro-inflammatory phenotype as a lifelong susceptibility to stress; (differential susceptibility) susceptible adults are more sensitive to the health risks of adverse (stress-promoting) environments, but also to the health benefits of protective (stress-buffering) environments. Experimental investigation of a pro-inflammatory phenotype as a mechanism facilitating greater stress recovery from nature exposure. We determined differences in stress recovery (via heart rate variability) caused by exposure to a nature or office virtual reality environment (10 min) after an acute stressor among 64 healthy college-age males with varying levels of susceptibility (socioeconomic status, early life stress, and a pro-inflammatory state [inflammatory reactivity and glucocorticoid resistance to an in vitro bacterial challenge]). Findings for inflammatory reactivity and glucocorticoid resistance were modest but consistently trended towards better recovery in the nature condition. Differences in recovery were not observed for socioeconomic status or early life stress. Among healthy college-age males, we observed expected trends according to their differential susceptibility when assessed as inflammatory reactivity and glucocorticoid resistance, suggesting these biological correlates of susceptibility could be more proximal indicators than self-reported assessments of socioeconomic status and early life stress. If future research in more diverse populations aligns with these trends, this could support an alternative conceptualization of susceptibility as increased environmental sensitivity, reflecting heightened responses to adverse, but also protective environments. With this knowledge, future investigators could examine how individual differences in environmental sensitivity could provide an opportunity for those who are the most susceptible to experience the greatest health benefits from nature exposure.

Strains belonging to R. opacus , R. jostii , R. fascians , R. erythropolis and R. equi exhibited differential ability to grow and produce lipids from fruit residues (grape marc and apple pomace), as well as single carbohydrates, such as glucose, gluconate, fructose and sucrose. The oleaginous species, R. opacus (strains PD630 and MR22) and R. jostii RHA1, produced higher yields of biomass (5.1–5.6 g L −1 ) and lipids (38–44% of CDW) from apple juice wastes, in comparison to R. erythropolis DSM43060, R. fascians F7 and R. equi ATCC6939 (4.1–4.3 g L −1 and less than 10% CDW of lipids). The production of cellular biomass and lipids were also higher in R. opacus and R. jostii (6.8–7.2 g L −1 and 33.9–36.5% of CDW of lipids) compared to R. erythropolis , R. fascians , and R. equi (3.0–3.6 g L −1 and less than 10% CDW of lipids), during cultivation of cells on wine grape waste. A genome-wide bioinformatic analysis of rhodococci indicated that oleaginous species possess a complete set of genes/proteins necessary for the efficient utilization of carbohydrates, whereas genomes from non-oleaginous rhodococcal strains lack relevant genes coding for transporters and/or enzymes for the uptake, catabolism and assimilation of carbohydrates, such as gntP , glcP , edd , eda , among others. Results of this study highlight the potential use of the oleaginous rhodococcal species to convert sugar-rich agro-industrial wastes, such as apple pomace and grape marc, into single-cell oils.

Emerging epidemiological evidence indicates that groups in low socioeconomic positions exhibit more pronounced health benefits from nature exposure compared to more privileged groups. We have previously posited one possible mechanism underlying this phenomenon through our framework: (susceptibility to stress) groups in low socioeconomic positions are often exposed to more early-life stressors, which can induce a lifelong susceptibility to stress through various neurobiological pathways; (environmental sensitivity) susceptibility to stress, traditionally understood as heightened reactivity to stressors, could also encompass enhanced responsivity to health-protective exposures, inducing greater risks in adverse environments, but also greater benefits in protective environments. Examine the moderation effect of early life stress on the association between residential nature exposure and fasting glucose. We assessed the impact of residential nature exposure (Normalized Difference Vegetation Index) on glucose dysregulation (elevated levels of fasting blood glucose) with a specific focus on the moderation effect of early life stress (Stress and Adversity Inventory for Adults) using baseline data from a cohort of 340 nursing students. An initial analysis did not support our linear dose-response hypothesis. However, a theory-guided exploration revealed a significant curvilinear trend wherein participants with higher but also lower exposure to early-life stressors both exhibited lower levels of fasting glucose when living in greener neighborhoods. By contrast, for participants with relatively moderate early-life stressor exposure, there was no association between neighborhood greenness and fasting glucose. Our findings contribute to growing evidence and further support the idea that increasing access to nature within disadvantaged neighborhoods could be an effective strategy to mitigate metabolic risks and attenuate health disparities among vulnerable populations. As the evidence for this framework expands, it could inform more targeted interventions that leverage individual differences in environmental sensitivity to promote health equity, ultimately providing more nuanced and socioeconomically attuned approaches to public health.

Frugivorous birds vary in seed dispersal effectiveness (SDE) depending on their body mass. It has been suggested that large birds are more effective dispersers than small ones because they consume a large number of fruits, disperse seeds of distinct sizes, and transport seeds over long distances. Yet, few studies have evaluated the impact of body mass on SDE of birds. In this study, we compiled one database for the quantity (i.e., frequency of visits to plants and number of seeds removed per visit) and quality (i.e., germination of seeds after gut passage and gut retention time of seeds) of seed dispersal by frugivorous birds to evaluate the impact of body mass on SDE. In addition, we compiled data on plant characteristics such as life‐form, fruit type, number of seeds per fruit, and size of seed to evaluate their influence on the quantity and quality of seed dispersal. Data were analyzed with linear mixed effects models and quantile regressions to evaluate the relationship between body mass of birds and quantity, quality, and SDE, in addition to the influence of plant characteristics on SDE. The body mass of birds was negatively related to the frequency of visits to plants. Furthermore, it was positively related to the number of seeds removed per visit, although negatively related to seed size. The life‐form of plants was the only factor explaining the germination of seeds after gut passage. Yet, the body mass of birds was positively related to the gut retention time of seeds. Small and medium birds have a relatively higher SDE than large birds. These results differ from the assertion that large birds are more effective dispersers of plants. Small and medium birds are also effective dispersers of plants that should be preserved and protected from the impact of human activities. This manuscript evaluates the effect of body mass on the seed dispersal effectiveness of birds.

Transcatheter aortic valve implantation (TAVI) was established as a standard treatment for high-operative risk patients with severe aortic stenosis (AS). Although coronary artery disease (CAD) often coexists with AS, clinical and angiographic evaluations of stenosis severity are unreliable in this specific setting. To provide precise risk stratification of coronary lesions, combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) was developed to integrate morphological and molecular information on plaque composition. However, there is a lack of evidence on the association between NIRS-IVUS derived findings such as maximum 4mm lipid core burden index (maxLCBI4mm) and clinical outcomes in AS patients undergoing TAVI. This registry aims to assess feasibility and safety of NIRS-IVUS imaging in the setting of routine pre-TAVI coronary angiography to improve assessment of CAD severity. The registry is designed as a non-randomized, prospective, observational, multicenter cohort registry. Patients referred for TAVI with angiographic evidence of CAD receive NIRS-IVUS imaging and are followed up to 24 months. Enrolled patients are classified as NIRS-IVUS positive and NIRS-IVUS negative, respectively, based on their maxLCBI4mm to compare their clinical outcomes. The primary endpoint of the registry is major adverse cardiovascular events over a 24-month follow-up period. Identification of patients likely or unlikely to benefit from revascularization prior to TAVI represents an important unmet clinical need. This registry is designed to investigate whether NIRS-IVUS-derived atherosclerotic plaque characteristics can identify patients and lesions at risk for future adverse cardiovascular events after TAVI, in order to refine interventional decision-making in this challenging patient population.

Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases. Our findings reveal that: (a) nearly all PDAC samples harbor potentially targetable neoantigens; (b) T cells are present but generally show a reduced activation signature; and (c) markers of efficient antigen presentation are associated with a reduced signature of markers characterizing cytotoxic T cells. These findings suggest that despite the presence of tumor specific neoepitopes, T cell activation is actively suppressed in PDAC. Further, we identify iNOS as a potential mediator of immune suppression that might be actionable using pharmacological avenues.

The selection of oleaginous bacteria, potentially applicable to biotechnological approaches, is usually carried out by different expensive and time-consuming techniques. In this study, we used Oil Red O (ORO) as an useful dye for staining of neutral lipids (triacylglycerols and wax esters) on thin-layer chromatography plates. ORO could detect minimal quantities of both compounds (detection limit, 0.0025 mg of tripalmitin or 0.005 mg of cetylpalmitate). In addition, we developed a specific, rapid, and inexpensive screening methodology to detect triacylglycerol-accumulating microorganisms grown on the agar plate. This staining methodology detected 9/13 strains with a triacylglycerol content higher than 20% by cellular dry weight. ORO did not stain polyhydroxyalkanoates-producing bacteria. The four oleaginous strains not detected by this screening methodology exhibited a mucoid morphology of their colonies. Apparently, an extracellular polymeric substance produced by these strains hampered the entry of the lipophilic dye into cells. The utilization of the developed screening methodology would allow selecting of oleaginous bacteria in a simpler and faster way than techniques usually used nowadays, based on unspecific staining protocols and spectrophotometric or chromatographic methods. Furthermore, the use of ORO as a staining reagent would easily characterize the neutral lipids accumulated by microorganisms as reserve compounds. Key points • Oil Red O staining is specific for triacylglycerols • Oil Red O staining is useful to detect oleaginous bacteria • Fast and inexpensive staining to isolate oleaginous bacteria from the environment

Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions.

The wax ester (WE) and triacylglycerol (TAG) biosynthetic potential of marine microorganisms is poorly understood at the microbial community level. The goal of this work was to uncover the prevalence and diversity of bacteria with the potential to synthesize these neutral lipids in coastal sediments of two high latitude environments, and to characterize the gene clusters related to this process. Homolog sequences of the key enzyme, the wax ester synthase/acyl-CoA:diacylglycerol acyltransferase (WS/DGAT) were retrieved from 13 metagenomes, including subtidal and intertidal sediments of a Subantarctic environment (Ushuaia Bay, Argentina), and subtidal sediments of an Antarctic environment (Potter Cove, Antarctica). The abundance of WS/DGAT homolog sequences in the sediment metagenomes was 1.23 ± 0.42 times the abundance of 12 single-copy genes encoding ribosomal proteins, higher than in seawater (0.13 ± 0.31 times in 338 metagenomes). Homolog sequences were highly diverse, and were assigned to the Pseudomonadota, Actinomycetota, Bacteroidota and Acidobacteriota phyla. The genomic context of WS/DGAT homologs included sequences related to WE and TAG biosynthesis pathways, as well as to other related pathways such as fatty-acid metabolism, suggesting carbon recycling might drive the flux to neutral lipid synthesis. These results indicate the presence of abundant and taxonomically diverse bacterial populations with the potential to synthesize lipid storage compounds in marine sediments, relating this metabolic process to bacterial survival.

Although B cell response is frequently found in cancer, there is little evidence that it alters tumor development or progression. The process through which tumor-associated antigens trigger humoral response is not well delineated. We investigate the repertoire of antigens associated with humoral immune response in pancreatic ductal adenocarcinoma (PDAC) using in-depth proteomic profiling of immunoglobulin-bound proteins from PDAC patient plasmas and identify tumor antigens that induce antibody response together with exosome hallmark proteins. Additional profiling of PDAC cell-derived exosomes reveals significant overlap in their protein content with immunoglobulin-bound proteins in PDAC plasmas, and significant autoantibody reactivity is observed between PDAC cell-derived exosomes and patient plasmas compared to healthy controls. Importantly, PDAC-derived exosomes induce a dose-dependent inhibition of PDAC serum-mediated complement-dependent cytotoxicity towards cancer cells. In summary, we provide evidence that exosomes display a large repertoire of tumor antigens that induce autoantibodies and exert a decoy function against complement-mediated cytotoxicity. The humoral immune response role in cancer is unclear. Here the authors perform an in-depth proteomic profiling of immunoglobulin-bound proteins in plasma from pancreatic ductal adenocarcinoma patients and find cancer-cell specific antibodies neutralized by binding to cancer-cell derived exosomes.