Case Report: Taxifolin for neurosurgery-associated early-onset cerebral amyloid angiopathy.

Cases of iatrogenic cerebral amyloid angiopathy (CAA) have been increasingly reported recently, particularly those associated with neurosurgery. Preclinical studies have shown taxifolin to be promising for treating CAA. We describe a young 42-year-old man with a history of childhood traumatic brain injury that required a craniotomy for hematoma evacuation. He later presented with recurrent lobar intracerebral hemorrhage (ICH) decades later, which was histologically confirmed to be CAA. Serial 11C-Pittsburgh compound B positron emission tomography (11C-PiB-PET) imaging showed a 24% decrease in global standardized uptake value ratio (SUVR) at 10 months after taxifolin use. During this period, the patient experienced clinical improvement with improved consciousness and reduced recurrent ICH frequency, which may be partly attributable to the potential amyloid-ß (Aß) clearing the effect of taxifolin. However, this effect seemed to have diminished at 15 months, CAA should be considered in young patients presenting with recurrent lobar ICH with a history of childhood neurosurgery, and serial 11C-PiB-PET scans warrant further validation as a strategy for monitoring treatment response in CAA for candidate Aß-clearing therapeutic agents such as taxifolin.

Plasma-Induced Changes in the Metabolome Following Vistula Tart Cherry Consumption.

Evidence suggests that tart cherry (TC) supplementation has beneficial effects on health indices and recovery following strenuous exercise. However, little is known about the mechanisms and how TC might modulate the human metabolome. The aim of this study was to evaluate the influence of an acute high- and low-dose of Vistula TC supplementation on the metabolomic profile in humans. In a randomised, double-blind, placebo controlled, cross-over design, 12 healthy participants (nine male and three female; mean ± SD age, stature, and mass were 29 ± 7 years old, 1.75 ± 0.1 m, and 77.3 ± 10.5 kg, respectively) visited the laboratory on three separate occasions (high dose; HI, low dose; LO, or placebo), separated by at least seven days. After an overnight fast, a baseline venous blood sample was taken, followed by consumption of a standardised breakfast and dose conditions (HI, LO, or placebo). Subsequent blood draws were taken 1, 2, 3, 5, and 8 h post consumption. Following sample preparation, an untargeted metabolomics approach was adopted, and the extracts analysed by LCMS/MS. When all time points were collated, a principal component analysis showed a significant difference between the conditions (p < 0.05), such that the placebo trial had homogeneity, and HI showed greater heterogeneity. In a sub-group analysis, cyanidine-3-O-glucoside (C3G), cyanidine-3-O-rutinoside (C3R), and vanillic acid (VA) were detected in plasma and showed significant differences (p < 0.05) following acute consumption of Vistula TC, compared to the placebo group. These results provide evidence that phenolics are bioavailable in plasma and induce shifts in the metabolome following acute Vistula TC consumption. These data could be used to inform future intervention studies where changes in physiological outcomes could be influenced by metabolomic shifts following acute supplementation.

Cointegrations in house price dynamics and ageing population risks.

How does the riskiness of an ageing population change with house price dynamics of rural areas? Why do rural house prices increase faster than cities despite their ageing populations? Life cycle theory predicts working age households have higher demand for housing than retirement households. An issue that has seen much less attention in the literature is that rural house prices have been increasing despite their populations age rapidly. To answer these issues, our paper introduces an empirical cointegration-based framework designed to be flexible for empirical settings. Our cointegration framework reveals crucial information about rural housing and ageing which has not been found previously: the short-term deviation of house prices from cointegration restrictions is a strong predictor of future rural house prices and migration rate from 1 to 4 year ahead. This is not the case for urban areas nor where cointegration restrictions are being ignored. Rural house prices, not urban ones, are the key to understand this cointegration restriction. Our framework is pertinent to most ageing societies with available housing and demographic data. When a government formulates macroprudential policies internalizing these cointegration restrictions and supporting rural developments, migration into rural areas and population increases are possible. Our evidence highlights the importance of cointegration-based long-run ageing risks for rural housing markets.

Use of remote sensing to assess vegetative stress as a proxy for soil contamination.

We report, for the first time, a multimodal investigation of current crude oil reprocessing and storage sites to assess their impact on the environment after 50 years of continuous operation. We have adopted a dual approach to investigate potential soil contamination. The first approach uses conventional analytical techniques i.e. energy dispersive X-ray fluorescence (ED-XRF) for metal analysis, and a complementary metabolomic investigation using hydrophilic liquid interaction chromatography hi-resolution mass spectrometry (HILIC-MS) for organic contaminants. Secondly, the deployment of an unmanned aerial vehicle (UAV) with a multispectral image (MSI) camera, for the remote sensing of vegetation stress, as a proxy for sub-surface soil contamination. The results identified high concentrations of barium (mean 21 017 ± 5950 µg g-1, n = 36) as well as metabolites derived from crude oil (polycyclic aromatic hydrocarbons), cleaning processes (surfactants) and other organic pollutants (e.g. pesticides, plasticizers and pharmaceuticals) in the reprocessing site. This data has then been correlated, with post-flight data analysis derived vegetation indices (NDVI, GNDVI, SAVI and Cl green VI), to assess the potential to identify soil contamination because of vegetation stress. It was found that strong correlations exist (an average R2 of >0.68) between the level of soil contamination and the ground cover vegetation. The potential to deploy aerial remote sensing techniques to provide an initial survey, to inform decision-making, on suspected contaminated land sites can have global implications.

Comparative analysis of climate-induced changes in distribution of representative fish species in the Yellow Sea.

Climate changes are posing remarkable impacts on marine fish and fisheries. Although many studies have addressed the distributional effects of climate change on single fish species or taxa in recent years, comparative studies focusing on different types of fish are still lacking. In this study, we applied dynamic bioclimate envelop models (DBEM), based on three earth system models, to predict sea surface and bottom temperature, as well as the spatial and temporal distribution of nine representative fishes in the Yellow Sea, contain two habitats, i.e., continental shelf benthopelagic (CBD) and continental shelf pelagic-neritic (CPN) fishes, and two thermophilies, i.e., warm temperate (WT) and warm water (WW) fishes. Under a low emissions scenario (RCP 2.6) and a high emissions scenario (RCP 8.5) between 1970 and 2060, results reveal that: a) CPN fishes show a distinct tendency to move to higher latitudes than CBD fishes, and WW fishes show a significant tendency to migrate more widely to the north than WT fishes; b) The relative abundance of CPN fishes is expected to be higher than that of CBD fishes, while there is no apparent difference in relative abundance between WW fishes and WT fishes. The main reasons for this difference are presumed to be: variance of temperature rise between the sea surface and bottom layers, divergent adaptations of the species, and disparate degrees of anthropogenic influence.

The core phageome and its interrelationship with preterm human milk lipids.

Phages and lipids in human milk (HM) may benefit preterm infant health by preventing gastrointestinal pathobiont overgrowth and microbiome modulation. Lipid association may promote vertical transmission of phages to the infant. Despite this, interrelationships between lipids and phages are poorly characterized in preterm HM. Shotgun metagenomics and untargeted lipidomics of phage and lipid profiles from 99 preterm HM samples reveals that phages are abundant and prevalent from the first week and throughout the first 100 days of lactation. Phage-host richness of preterm HM increases longitudinally. Core phage communities characterized by Staphylococcus- and Propionibacterium-infecting phages are significantly correlated with long-chain fatty acid abundances over lactational age. We report here a phage-lipid interaction in preterm HM, highlighting the potential importance of phage carriage in preterm HM. These results reveal possible strategies for phage carriage in HM and their importance in early-life microbiota development.

Climate change exacerbates nutrient disparities from seafood.

Seafood is an important source of bioavailable micronutrients supporting human health, yet it is unclear how micronutrient production has changed in the past or how climate change will influence its availability. Here combining reconstructed fisheries databases and predictive models, we assess nutrient availability from fisheries and mariculture in the past and project their futures under climate change. Since the 1990s, availabilities of iron, calcium and omega-3 from seafood for direct human consumption have increased but stagnated for protein. Under climate change, nutrient availability is projected to decrease disproportionately in tropical low-income countries that are already highly dependent on seafood-derived nutrients. At 4 oC of warming, nutrient availability is projected to decline by ~30% by 2100 in low income countries, while at 1.5-2.0 oC warming, decreases are projected to be ~10%. We demonstrate the importance of effective mitigation to support nutritional security of vulnerable nations and global health equity.

Chronic supplementation of a multi-ingredient herbal supplement increases speed of cognitive task performance alongside changes in the urinary metabolism of dopamine and the gut microbiome in cognitively intact older adults experiencing subjective memory decline: a randomized, placebo controlled, parallel groups investigation.

Background: The effects of herbs on brain function are often investigated in isolation, yet herbal preparations are often complex combinations of phytochemicals, designed to target widespread mechanisms. Objective: To assess the effects of chronic, 12 weeks, supplementation of a multi-ingredient herbal supplement (containing Bacopa monnieri, Gotu kola leaf, Turmeric whole powder, Reishi full spectrum, Rosemary, Cardamom, Holy Basil, Turmeric Wholistic™ extract, Green Tea & Seagreens) on cognitive function in older adults with subjective memory decline. Secondly, to investigate whether effects are underpinned by shifts in microbial composition and/or metabolism of the herbs. Methods: Male and female participants (N = 128) aged between 55-75 years completed lab-based cognitive assessments, and provided stool and urine samples, at baseline and then following 90 days of multi-ingredient herb, or placebo, supplementation. Results: Deficits in memory were observed in response to 90 days of multi-ingredient herbal supplement supplementation but the positive effects were all focused on speed of cognitive task performance, with an additional improvement in the false alarm rate on the rapid visual information processing task. These improvements coincided with an increased presence of tyrosine in the urinary metabolome and this may implicate the role of dopamine in these processing and/or motor speed increases. Finally, multi-ingredient herbal supplementation significantly reduced levels of 3 bacterial species in the gut microbiome and one of these, Sutterella, coincides with lower levels of constipation reported in the multi-ingredient herbal supplement condition. Conclusion: A multi-ingredient herbal supplement increases speed of cognitive task performance and increased metabolism of tyrosine suggests that this is modulated by increased dopaminergic activity. Reduced levels of Sutterella in the gut is associated with improved bowel movements of participants. Interpretation of the negative effects on memory are, however, stymied by an unequal randomization of participants into treatment groups pre- and post-COVID 19.Clinical trial registration: identifier NCT05504668.

Extreme and compound ocean events are key drivers of projected low pelagic fish biomass.

Ocean extreme events, such as marine heatwaves, can have harmful impacts on marine ecosystems. Understanding the risks posed by such extreme events is key to develop strategies to predict and mitigate their effects. However, the underlying ocean conditions driving severe impacts on marine ecosystems are complex and often unknown as risks to marine ecosystems arise not only from hazards but also from the interactions between hazards, exposure and vulnerability. Marine ecosystems may not be impacted by extreme events in single drivers but rather by the compounding effects of moderate ocean anomalies. Here, we employ an ensemble climate-impact modeling approach that combines a global marine fish model with output from a large ensemble simulation of an Earth system model, to identify the key ocean ecosystem drivers associated with the most severe impacts on the total biomass of 326 pelagic fish species. We show that low net primary productivity is the most influential driver of extremely low fish biomass over 68% of the ocean area considered by the model, especially in the subtropics and the mid-latitudes, followed by high temperature and low oxygen in the eastern equatorial Pacific and the high latitudes. Severe biomass loss is generally driven by extreme anomalies in at least one ocean ecosystem driver, except in the tropics, where a combination of moderate ocean anomalies is sufficient to drive extreme impacts. Single moderate anomalies never drive extremely low fish biomass. Compound events with either moderate or extreme ocean conditions are a necessary condition for extremely low fish biomass over 78% of the global ocean, and compound events with at least one extreme variable are a necessary condition over 61% of the global ocean. Overall, our model results highlight the crucial role of extreme and compound events in driving severe impacts on pelagic marine ecosystems.

In Search of Complementary Extraction Methods for Comprehensive Coverage of the Escherichia coli Metabolome.

Escherichia coli is an invaluable research tool for many fields of biology, in particular for the production of recombinant enzymes. However, the activity of many such recombinant enzymes cannot be determined using standard biochemical assays, as often, the relevant substrates are not known, or the products produced are not detectable. Today, the biochemical footprints of such unknown enzyme activities can be revealed via the analysis of the metabolomes of the recombinant E. coli clones in which they are expressed, using sensitive technologies such as mass spectrometry. However, before any metabolites can be identified, it is necessary to achieve as high a coverage of the potential metabolites present within E. coli as possible. We have therefore analyzed a wide range of different extraction methods against the cell free extracts of various recombinant E. coli clones. The results were analyzed to determine the minimum number of extractions that achieved high recovery and coverage of metabolites. Two methods were selected for further analysis due to their ability to produce not only high numbers of ions, but also wide mass coverage and a high degree of complementarity. One extraction method uses acetonitrile and water, in a 4:1 ratio, which is then dried down and reconstituted in the chromatography running buffer prior to injection onto the chromatography column, and the other extraction method uses a combination of methanol, water and chloroform, in a 3:1:1 ratio, which is injected directly onto the chromatography column. These two extraction methods were shown to be complementary to each other, as regards the respective metabolites extracted, and to cover a large range of metabolites.

The effects of substituting red and processed meat for mycoprotein on biomarkers of cardiovascular risk in healthy volunteers: an analysis of secondary endpoints from Mycomeat.

PURPOSE: Mycoprotein is a relatively novel food source produced from the biomass of Fusarium venenatum. It has previously been shown to improve CVD risk markers in intervention trials when it is compared against total meat. It has not hitherto been assessed specifically for benefits relative to red and processed meat. METHODS: We leveraged samples from Mycomeat, an investigator-blind randomised crossover controlled trial in metabolically healthy male adults (n = 20), randomised to consume 240 g/day of red and processed meat for 14 days followed by mycoprotein, or vice versa. Blood biochemical indices were a priori defined secondary endpoints. RESULTS: Mycoprotein consumption led to a 6.74% reduction in total cholesterol (P = 0.02) and 12.3% reduction in LDL cholesterol (P = 0.02) from baseline values. Change in fasted triglycerides was not significantly different between diets (+ 0.19 ± 0.11 mmol/l with mycoprotein, P = 0.09). There was a small but significant reduction in waist circumference for mycoprotein relative to meat (- 0.95 ± 0.42 cm, P = 0.04). Following the mycoprotein diet, mean systolic (- 2.41 ± 1.89 mmHg, P = 0.23) and diastolic blood pressure (- 0.80 ± 1.23 mmHg, P = 0.43) were reduced from baseline. There were no statistically significant effects of the intervention on urinary sodium, nitrite or TMAO; while urinary potassium (+ 126.12 ± 50.30 mmol/l, P = 0.02) and nitrate (+ 2.12 ± 0.90 mmol/l, P = 0.04) were both significantly higher with mycoprotein relative to meat. The study population comprised metabolically healthy adults, therefore, changes in plasma lipids had little effect on cardiovascular risk scores (- 0.34% FRS for mycoprotein P = 0.24). CONCLUSIONS: These results confirm potential cardiovascular benefits when displacing red and processed meat with mycoprotein in the diet. Longer trials in higher risk study populations are needed to fully elucidate suggested benefits for blood pressure and body composition. CLINICALTRIALS: gov Identifier: NCT03944421.

Trophic amplification: A model intercomparison of climate driven changes in marine food webs.

Marine animal biomass is expected to decrease in the 21st century due to climate driven changes in ocean environmental conditions. Previous studies suggest that the magnitude of the decline in primary production on apex predators could be amplified through the trophodynamics of marine food webs, leading to larger decreases in the biomass of predators relative to the decrease in primary production, a mechanism called trophic amplification. We compared relative changes in producer and consumer biomass or production in the global ocean to assess the extent of trophic amplification. We used simulations from nine marine ecosystem models (MEMs) from the Fisheries and Marine Ecosystem Models Intercomparison Project forced by two Earth System Models under the high greenhouse gas emissions Shared Socioeconomic Pathways (SSP5-8.5) and a scenario of no fishing. Globally, total consumer biomass is projected to decrease by 16.7 ± 9.5% more than net primary production (NPP) by 2090-2099 relative to 1995-2014, with substantial variations among MEMs and regions. Total consumer biomass is projected to decrease almost everywhere in the ocean (80% of the world's oceans) in the model ensemble. In 40% of the world's oceans, consumer biomass was projected to decrease more than NPP. Additionally, in another 36% of the world's oceans consumer biomass is expected to decrease even as projected NPP increases. By analysing the biomass response within food webs in available MEMs, we found that model parameters and structures contributed to more complex responses than a consistent amplification of climate impacts of higher trophic levels. Our study provides additional insights into the ecological mechanisms that will impact marine ecosystems, thereby informing model and scenario development.

Marine heatwaves are not a dominant driver of change in demersal fishes.

Marine heatwaves have been linked to negative ecological effects in recent decades1,2. If marine heatwaves regularly induce community reorganization and biomass collapses in fishes, the consequences could be catastrophic for ecosystems, fisheries and human communities3,4. However, the extent to which marine heatwaves have negative impacts on fish biomass or community composition, or even whether their effects can be distinguished from natural and sampling variability, remains unclear. We investigated the effects of 248 sea-bottom heatwaves from 1993 to 2019 on marine fishes by analysing 82,322 hauls (samples) from long-term scientific surveys of continental shelf ecosystems in North America and Europe spanning the subtropics to the Arctic. Here we show that the effects of marine heatwaves on fish biomass were often minimal and could not be distinguished from natural and sampling variability. Furthermore, marine heatwaves were not consistently associated with tropicalization (gain of warm-affiliated species) or deborealization (loss of cold-affiliated species) in these ecosystems. Although steep declines in biomass occasionally occurred after marine heatwaves, these were the exception, not the rule. Against the highly variable backdrop of ocean ecosystems, marine heatwaves have not driven biomass change or community turnover in fish communities that support many of the world's largest and most productive fisheries.

Novel Iron Chelator SK4 Drives Cytotoxicity through Inhibiting Mitochondrial Metabolism in Ovarian and Triple Negative Breast Cancer Cell Lines.

Anti-cancer therapy by iron chelation has been shown to inhibit many cellular processes including DNA replication, mitochondrial metabolism and oncogenic signalling pathways (e.g., EGFR). Iron chelator SK4 represents a double pronged approach towards treating cancer. SK4 enters through LAT1, a commonly overexpressed amino acid transporter in tumours, thus targeting iron addiction and LAT1 overexpression. The aim of this study was to characterise the mode of action of SK4 through proteomics, metabolomics, lipidomics and seahorse real-time analysis in ovarian cell line SKOV3 and triple negative breast cancer cell line MDA MB 231. Pathway enrichment of proteomics data showed an overrepresentation of metabolism related pathways. Metabolic change after SK4 exposure have been confirmed in investigations of changes in basal and maximal mitochondrial respiration using seahorse real-time analysis of mitochondrial metabolism. Metabolomics also showed an increase in AMP and glucose-1-phosphate. Interestingly, our lipidomics data show a decrease in phospholipid synthesis in the SKOV3 cells which is in contrast with previous data which showed an upregulation of ceramide driven apoptosis. In summary, our data highlight impairment of energy metabolism as a mechanism of action underlying SK4 apoptosis, but also suggest a potential role of ceramide induction in the phenotypic outcome of the cell model.

Spousal concordance in adverse childhood experiences and the association with depressive symptoms in middle-aged and older adults: findings across China, the US, and Europe.

Background: Adverse childhood experiences (ACEs) are associated with higher depressive risks in adulthood. Whether respondents' ACEs are associated with their own depressive symptoms in adulthood and whether this association extends to their spouses' depressive symptoms remain unexplored. Methods: Data were from China Health and Retirement Longitudinal Study (CHARLS), the Health and Retirement Study (HRS), and the Survey of Health, Ageing and Retirement in Europe (SHARE). ACEs were categorized into overall, intra-familial, and extra-familial ACEs. Correlations of couples' ACEs were calculated using Cramer's V and partial Spearman's correlation. Associations of respondents' ACEs with spousal depressive symptoms were assessed using logistic regression, and mediation analyses were conducted to explore the mediating role of respondents' depressive symptoms. Results: Significant associations between husbands' ACEs and wives' depressive symptoms, with odds ratios (ORs) and 95% confidence intervals (CIs) of 2.09 (1.36-3.22) for 4 or more ACEs in CHARLS, and 1.25 (1.06-1.48) and 1.38 (1.06-1.79) for 2 or more ACEs in HRS and SHARE. However, wives' ACEs were associated with husbands' depressive symptoms only in CHARLS and SHARE. Findings in intra-familial and extra-familial ACEs were consistent with our main results. Additionally, respondents' depressive symptoms mediated more than 20% of the effect of respondents' ACEs on spousal depressive symptoms. Conclusion: We found that ACEs were significantly correlated between couples. Respondents' ACEs were associated with spousal depressive symptoms, with respondents' depressive symptoms mediating the association. The bidirectional implications of ACEs on depressive symptoms should be considered within household and effective interventions are warranted.

Recent Advances in Aerobic Oxidative of C-H Bond by Molecular Oxygen Focus on Heterocycles.

Aerobic oxidative cross-coupling represents one of the most straightforward and atom-economic methods for construction of C-C and C-X (X=N, O, S, or P) bonds using air as a sustainable external oxidant. The oxidative coupling of C-H bonds in heterocyclic compounds can effectively increase their molecular complexity by introducing new functional groups through C-H bond activation, or by formation of new heterocyclic structures through cascade construction of two or more sequential chemical bonds. This is very useful as it can increase the potential applications of these structures in natural products, pharmaceuticals, agricultural chemicals, and functional materials. This is a representative overview of recent progress since 2010 on green oxidative coupling reactions of C-H bond using O2 or air as internal oxidant focus on Heterocycles. It aims to provide a platform for expanding the scope and utility of air as green oxidant, together with a brief discussion on research into the mechanisms behind it.

Bringing the Nature Futures Framework to life: creating a set of illustrative narratives of nature futures.

To halt further destruction of the biosphere, most people and societies around the globe need to transform their relationships with nature. The internationally agreed vision under the Convention of Biological Diversity-Living in harmony with nature-is that "By 2050, biodiversity is valued, conserved, restored and wisely used, maintaining ecosystem services, sustaining a healthy planet and delivering benefits essential for all people". In this context, there are a variety of debates between alternative perspectives on how to achieve this vision. Yet, scenarios and models that are able to explore these debates in the context of "living in harmony with nature" have not been widely developed. To address this gap, the Nature Futures Framework has been developed to catalyse the development of new scenarios and models that embrace a plurality of perspectives on desirable futures for nature and people. In this paper, members of the IPBES task force on scenarios and models provide an example of how the Nature Futures Framework can be implemented for the development of illustrative narratives representing a diversity of desirable nature futures: information that can be used to assess and develop scenarios and models whilst acknowledging the underpinning value perspectives on nature. Here, the term illustrative reflects the multiple ways in which desired nature futures can be captured by these narratives. In addition, to explore the interdependence between narratives, and therefore their potential to be translated into scenarios and models, the six narratives developed here were assessed around three areas of the transformative change debate, specifically, (1) land sparing vs. land sharing, (2) Half Earth vs. Whole Earth conservation, and (3) green growth vs. post-growth economic development. The paper concludes with an assessment of how the Nature Futures Framework could be used to assist in developing and articulating transformative pathways towards desirable nature futures. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-023-01316-1.

Fungal ß-glucan-facilitated cross-feeding activities between Bacteroides and Bifidobacterium species.

The human gut microbiota (HGM) is comprised of a very complex network of microorganisms, which interact with the host thereby impacting on host health and well-being. ß-glucan has been established as a dietary polysaccharide supporting growth of particular gut-associated bacteria, including members of the genera Bacteroides and Bifidobacterium, the latter considered to represent beneficial or probiotic bacteria. However, the exact mechanism underpinning ß-glucan metabolism by gut commensals is not fully understood. We show that mycoprotein represents an excellent source for ß-glucan, which is consumed by certain Bacteroides species as primary degraders, such as Bacteroides cellulosilyticus WH2. The latter bacterium employs two extracellular, endo-acting enzymes, belonging to glycoside hydrolase families 30 and 157, to degrade mycoprotein-derived ß-glucan, thereby releasing oligosaccharides into the growth medium. These released oligosaccharides can in turn be utilized by other gut microbes, such as Bifidobacterium and Lactiplantibacillus, which thus act as secondary degraders. We used a cross-feeding approach to track how both species are able to grow in co-culture.