Algorithm-assisted discovery of an intrinsic order among mathematical constants.

In recent decades, a growing number of discoveries in mathematics have been assisted by computer algorithms, primarily for exploring large parameter spaces. As computers become more powerful, an intriguing possibility arises-the interplay between human intuition and computer algorithms can lead to discoveries of mathematical structures that would otherwise remain elusive. Here, we demonstrate computer-assisted discovery of a previously unknown mathematical structure, the conservative matrix field. In the spirit of the Ramanujan Machine project, we developed a massively parallel computer algorithm that found a large number of formulas, in the form of continued fractions, for numerous mathematical constants. The patterns arising from those formulas enabled the construction of the first conservative matrix fields and revealed their overarching properties. Conservative matrix fields unveil unexpected relations between different mathematical constants, such as π and ln(2), or e and the Gompertz constant. The importance of these matrix fields is further realized by their ability to connect formulas that do not have any apparent relation, thus unifying hundreds of existing formulas and generating infinitely many new formulas. We exemplify these implications on values of the Riemann zeta function ζ (n), studied for centuries across mathematics and physics. Matrix fields also enable new mathematical proofs of irrationality. For example, we use them to generalize the celebrated proof by Apéry of the irrationality of ζ (3). Utilizing thousands of personal computers worldwide, our research strategy demonstrates the power of large-scale computational approaches to tackle longstanding open problems and discover unexpected connections across diverse fields of science.

Iron supplementation and iron accumulation promote adipocyte thermogenesis through PGC1α-ATGL-mediated lipolysis.

Iron homeostasis is essential for maintaining metabolic health and iron disorder has been linked to chronic metabolic diseases. Increasing thermogenic capacity in adipose tissue has been considered as a potential approach to regulate energy homeostasis. Both mitochondrial biogenesis and mitochondrial function are iron-dependent and essential for adipocyte thermogenic capacity, but the underlying relationships between iron accumulation and adipose thermogenesis is unclear. Firstly, we confirmed that iron homeostasis and the iron regulatory markers (e.g., Tfr1 and Hfe) are involved in cold-induced thermogenesis in subcutaneous adipose tissues using RNA-seq and bioinformatic analysis. Secondly, an Hfe (Hfe-/-)-deficient mouse model, in which tissues become overloaded with iron, was employed. We found iron accumulation caused by Hfe deficiency enhanced mitochondrial respiratory chain expression in subcutaneous white adipose in vivo and resulted in enhanced tissue thermogenesis with upregulation of PGC-1α and adipose triglyceride lipase, mitochondrial biogenesis and lipolysis. To investigate the thermogenic capacity in vitro, stromal vascular fraction from adipose tissues was isolated, followed with adipogenic differentiation. Primary adipocyte from Hfe-/- mice exhibited higher cellular oxygen consumption, associated with enhanced expression of mitochondrial oxidative respiratory chain protein, while primary adipocytes or stromal vascular fractions from WT mice supplemented with iron citrate) exhibited similar effect in thermogenic capacity. Taken together, these findings indicate iron supplementation and iron accumulation (Hfe deficiency) can regulate adipocyte thermogenic capacity, suggesting a potential role for iron homeostasis in adipose tissues.

Sufficient potassium improves inorganic phosphate-limited photosynthesis in Brassica napus by enhancing metabolic phosphorus fractions and Rubisco activity.

Crop photosynthesis (A) and productivity are often limited by a combination of nutrient stresses, such that changes in the availability of one nutrient may affect the availability of another nutrient, in turn influencing A. In this study, we examined the synergistic effects of phosphorus (P) and potassium (K) on leaf A in a nutrient amendment experiment, in which P and K were added individually or in combination to Brassica napus grown under P and K co-limitation. The data revealed that the addition of P gradually removed the dominant limiting factor (i.e. the limited availability of P) and improved leaf A. Strikingly, the addition of K synergistically improved the overall uptake of P, mainly by boosting plant growth, and compensated for the physiological demand for P by prioritizing investment in metabolic pools of P (P-containing metabolites and inorganic phosphate, Pi). The enlarged pool of metabolically active P was partially associated with the upregulation of Pi regeneration through release from triose phosphates rather than replacement of P-containing lipids. This process mitigated P restrictions on A by maintaining the ATP/NADPH and NADPH/NADP+ ratios and increasing the content and activity of Rubisco. Our findings demonstrate that sufficient K increased Pi-limited A by enhancing metabolic P fractions and Rubisco activity. Thus, ionic synergism may be exploited to mitigate nutrient-limiting factors to improve crop productivity.

Mapping the lipidome in mitochondria-associated membranes (MAMs) in an in vitro model of Alzheimer's disease.

The disruption of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) plays a relevant role in Alzheimer's disease (AD). MAMs have been implicated in neuronal dysfunction and death since it is associated with impairment of functions regulated in this subcellular domain, including lipid synthesis and trafficking, mitochondria dysfunction, ER stress-induced unfolded protein response (UPR), apoptosis, and inflammation. Since MAMs play an important role in lipid metabolism, in this study we characterized and investigated the lipidome alterations at MAMs in comparison with other subcellular fractions, namely microsomes and mitochondria, using an in vitro model of AD, namely the mouse neuroblastoma cell line (N2A) over-expressing the APP familial Swedish mutation (APPswe) and the respective control (WT) cells. Phospholipids (PLs) and fatty acids (FAs) were isolated from the different subcellular fractions and analyzed by HILIC-LC-MS/MS and GC-MS, respectively. In this in vitro AD model, we observed a down-regulation in relative abundance of some phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE) species with PUFA and few PC with saturated and long-chain FA. We also found an up-regulation of CL, and antioxidant alkyl acyl PL. Moreover, multivariate analysis indicated that each organelle has a specific lipid profile adaptation in N2A APPswe cells. In the FAs profile, we found an up-regulation of C16:0 in all subcellular fractions, a decrease of C18:0 levels in total fraction (TF) and microsomes fraction, and a down-regulation of 9-C18:1 was also found in mitochondria fraction in the AD model. Together, these results suggest that the over-expression of the familial APP Swedish mutation affects lipid homeostasis in MAMs and other subcellular fractions and supports the important role of lipids in AD physiopathology.

Investigating foliar application of bulk and nanoparticles titanium dioxide on fennel productivity to mitigate the negative effects of saline irrigation water.

BACKGROUND: Fennel essential oils are fragrance compounds used in food and pharmaceutical sectors. One of the major impediments to expansion of fennel farming in Egypt's reclamation areas is saline water. Titanium dioxide (TiO2) or TiO2 nano particles (TiO2NP) can be utilized to boost the yield of aromatic plants cultivated under saline irrigation water. Saline water, particularly which contains sodium chloride can harm fennel plant; consequently, it was predicted that fennel production would fail in Egypt's reclaimed area, where the primary source of irrigation is groundwater consisting sodium chloride. This study sought to help fennel respond to sodium chloride by applying Ti forms to their leaves in order to reduce the detrimental effects of sodium chloride on them for expanding their production in the newly reclamation areas as a natural source of essential oil. Ti forms were applied as foliar application at 0, 0.1, 0.2 TiO2, 0.1 TiO2NP, and 0.2 TiO2NP, mM under irrigation with fresh water (0.4 dS m-1), or saline water (51.3 mM or 4.7 dS m-1). RESULTS: Plants exposed to 0.1 mM TiO2NP under fresh water resulted in the maximum values of morphological characters, estragole, oxygenated monoterpenes and photosynthetic pigments; while those subjected to 0.1 mM TiO2NP under saline water gave the greatest values of essential oil, proline, antioxidant enzymes and phenols. The greatest amounts of soluble sugars were recorded with 0.2 mM TiO2NP irrigated with saline water. Plants subjected to 0 mM TiO2 under saline water produced the greatest values of flavonoids, hydrogen peroxide and malondialdehyde. CONCLUSION: To mitigate the negative effects of salty irrigation water on fennel plant production, TiO2NP application is suggested as a potential strategy.

Temporal trends in population attributable fractions of modifiable risk factors for dementia: a time-series study of the English Longitudinal Study of Ageing (2004-2019).

BACKGROUND: Interest in modifiable risk factors (MRFs) for dementia is high, given the personal, social, and economic impact of the disorder, especially in ageing societies such as the United Kingdom. Exploring the population attributable fraction (PAF) of dementia attributable to MRFs and how this may have changed over time remains unclear. Unravelling the temporal dynamics of MRFs is crucial for informing the development of evidence-based and effective public health policies. This investigation examined the temporal trajectories of MRFs for dementia in England. METHODS: We used data from the English Longitudinal Study of Ageing, a panel study over eight waves collected between 2004 and 2019 (76,904 interviews in total). We calculated the PAFs for twelve MRFs (including six early- to mid-life factors and six late-life factors), as recommended by the Lancet Commission, and the individual weighted PAFs (IW-PAFs) for each risk factor. Temporal trends were analysed to understand the changes in the overall PAF and IW-PAF over the study period. Subgroup analyses were conducted by sex and socioeconomic status (SES). RESULTS: The overall PAF for dementia MRFs changed from 46.73% in 2004/2005 to 36.79% in 2018/2019, though this trend was not statistically significant. During 2004-2019, hypertension, with an average IW-PAF of 8.21%, was the primary modifiable determinant of dementia, followed by obesity (6.16%), social isolation (5.61%), hearing loss (4.81%), depression (4.72%), low education (4.63%), physical inactivity (3.26%), diabetes mellitus (2.49%), smoking (2.0%), excessive alcohol consumption (1.16%), air pollution (0.42%), and traumatic brain injury (TBI) (0.26%). During 2004-2019, only IW-PAFs of low education, social isolation, and smoking showed significant decreasing trends, while IW-PAFs of other factors either did not change significantly or increased (including TBI, diabetes mellitus, and air pollution). Upon sex-specific disaggregation, a higher overall PAF for MRFs was found among women, predominantly associated with later-life risk factors, most notably social isolation, depression, and physical inactivity. Additionally, hearing loss, classified as an early- to mid-life factor, played a supplementary role in the identified sex disparity. A comparable discrepancy was evident upon PAF evaluation by SES, with lower income groups experiencing a higher dementia risk, largely tied to later-life factors such as social isolation, physical inactivity, depression, and smoking. Early- to mid-life factors, in particular, low education and obesity, were also observed to contribute to the SES-associated divergence in dementia risk. Temporal PAF and IW-PAF trends, stratified by sex and SES, revealed that MRF PAF gaps across sex or SES categories have persisted or increased. CONCLUSIONS: In England, there was little change over time in the proportion of dementia attributable to known modifiable risk factors. The observed trends underscore the continuing relevance of these risk factors and the need for targeted public health strategies to address them.

Effects of calcium phosphate and phosphorus-dissolving bacteria on microbial structure and function during Torreya Grandis branch waste composting.

BACKGROUND BURKHOLDERIA: is a phosphorus solubilizing microorganism discovered in recent years, which can dissolve insoluble phosphorus compounds into soluble phosphorus. To investigate the effects of Burkholderia and calcium phosphate on the composting of Torreya grandis branches and leaves, as well as to explain the nutritional and metabolic markers related to the composting process. METHODS: In this study, we employed amplicon sequencing and untargeted metabolomics analysis to examine the interplay among phosphorus (P) components, microbial communities, and metabolites during T. grandis branch and leaf waste composting that underwent treatment with calcium phosphate and phosphate-solubilizing bacteria (Burkholderia). There were four composting treatments, 10% calcium phosphate (CaP) or 5 ml/kg (1 × 108/ml Burkholderia) microbial inoculum (WJP) or both (CaP + WJP), and the control group (CK). RESULTS: The results indicated that Burkholderia inoculation and calcium phosphate treatment affected the phosphorus composition, pH, EC, and nitrogen content. Furthermore, these treatments significantly affected the diversity and structure of bacterial and fungal communities, altering microbial and metabolite interactions. The differential metabolites associated with lipids and organic acids and derivatives treated with calcium phosphate treatment are twice as high as those treated with Burkholderia in both 21d and 42d. The results suggest that calcium phosphate treatment alters the formation of some biological macromolecules. CONCLUSION: Both Burkholderia inoculation and calcium phosphate treatment affected the phosphorus composition, nitrogen content and metabolites of T. grandis branch and leaf waste compost.These results extend our comprehension of the coupling of matter transformation and community succession in composting with the addition of calcium phosphate and phosphate-solubilizing bacteria.

Life at the conservative end of the leaf economics spectrum: intergeneric variation in the allocation of phosphorus to biochemical fractions in species of Banksia (Proteaceae) and Hakea (Proteaceae).

In severely phosphorus (P)-impoverished environments, plants have evolved to use P very efficiently. Yet, it is unclear how P allocation in leaves contributes to their photosynthetic P-use efficiency (PPUE) and position along the leaf economics spectrum (LES). We address this question in 10 species of Banksia and Hakea, two highly P-efficient Proteaceae genera. We characterised traits in leaves of Banksia and Hakea associated with the LES: leaf mass per area, light-saturated photosynthetic rates, P and nitrogen concentrations, and PPUE. We also determined leaf P partitioning to five biochemical fractions (lipid, nucleic acid, metabolite, inorganic and residual P) and their possible association with the LES. For both genera, PPUE was negatively correlated with fractional allocation of P to lipids, but positively correlated with that to metabolites. For Banksia only, PPUE was negatively correlated with residual P, highlighting a strategy contrasting to that of Hakea. Phosphorus-allocation patterns significantly explained PPUE but were not linked to the resource acquisition vs resource conservation gradient defined by the LES. We conclude that distinct P-allocation patterns enable species from different genera to achieve high PPUE and discuss the implications of different P investments. We surmise that different LES axes representing different ecological strategies coexist in extremely P-impoverished environments.

Growing in phosphorus-impoverished habitats in south-western Australia: How general are phosphorus-acquisition and -allocation strategies among Proteaceae, Fabaceae and Myrtaceae species?

Numerous phosphorus (P)-acquisition and -utilisation strategies have evolved in plants growing in severely P-impoverished environments. Although these strategies have been well characterised for certain taxa, like Proteaceae, P-poor habitats are characterised by a high biodiversity, and we know little about how species in other families cope with P scarcity. We compared the P-acquisition and leaf P-allocation strategies of Fabaceae and Myrtaceae with those of Proteaceae growing in the same severely P-impoverished habitat. Myrtaceae and Fabaceae exhibited multiple P-acquisition strategies: P-mining by carboxylates or phosphatases, P uptake facilitated by carboxylate-releasing neighbours, and dependence on the elevated soil P availability after fire. Surprisingly, not all species showed high photosynthetic P-use efficiency (PPUE). Highly P-efficient species showed positive correlations between PPUE and the proportion of metabolite P (enzyme substrates), and negative correlations between PPUE and phospholipids (cellular membranes) and nucleic acid P (mostly ribosomal RNA), while we found no correlations in less P-efficient species. Overall, we found that Myrtaceae and Fabaceae used a wider range of strategies than Proteaceae to cope with P scarcity, at both the rhizosphere and leaf level. This knowledge is pivotal to better understand the mechanisms underlying plant survival in severely nutrient-impoverished biodiverse ecosystems.

Association of Sacubitril/Valsartan vs Valsartan With Blood Pressure Changes and Symptomatic Hypotension: the PARAGLIDE-HF Trial.

BACKGROUND: In PARAGLIDE-HF, in patients with ejection fraction (EF) > 40%, stabilized after worsening heart failure (WHF), sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared to valsartan alone, despite more symptomatic hypotension (SH). Concern about SH may be limiting the use of sacubitril/valsartan in appropriate patients. METHODS: We characterized patients by the occurrence of SH (investigator-reported) after randomization to either sacubitril/valsartan or valsartan. A key trial inclusion criterion was systolic blood pressure (SBP) ≥ 100 mmHg for the preceding 6 hours and no SH. We also compared outcomes based on baseline SBP stratified by the median blood pressure. The primary endpoint was time-averaged proportional change in NT-proBNP levels from baseline through weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: (1) cardiovascular death; (2) hospitalizations due to HF; (3) urgent HF visits; and (4) change in NT-proBNP levels. RESULTS: Among 466 randomized patients, 92 (19.7%) experienced SH (sacubitril/valsartan, n = 56 [24.0%]; valsartan, n = 36 [15.5%]; P = 0.020). The median time to the first SH event was similar between treatment arms (18 days vs 15 days, respectively; P = 0.42) as was the proportion of first SH events classified as serious by investigators. Patients who experienced SH with sacubitril/valsartan were more likely to be white (OR 1.87 [95% CI: 0.31, 11.15]), to have a lower baseline SBP (per 10 mmHg increase, OR 0.68 [95% CI: 0.55, 0.85]), or to have a left ventricular ejection fraction (LVEF) of > 60% (OR 2.21 [95% CI: 1.05, 4.65]). Time-averaged change in NT-proBNP levels did not differ between patients with baseline SBP ≥ 128 mmHg vs SBP < 128 mmHg (interaction, P = 0.43). The composite hierarchical outcome for sacubitril/valsartan in patients with baseline SBP ≥ 128 mmHg had a win ratio of 1.34 ([95% CI: 0.91, 1.99]; P = 0.096) vs SBP < 128 mmHg with a win ratio of 1.09 ([95%CI: 0.73, 1.66]; P = 0 .62; interaction P value = 0.42). CONCLUSION: Among patients with LVEF > 40% stabilized after WHF, incident SH was more common with sacubitril/valsartan compared with valsartan. SH was associated with lower baseline SBP, being white, and having higher LVEF. Treatment benefits with sacubitril/valsartan may be more pronounced in patients with higher baseline SBP and lower LVEF (≤ 60%). (Funded by Novartis Pharmaceutical Corporation; ClinicalTrials.gov number, NCT03988634.).

Distinct, direct and climate-mediated environmental controls on global particulate and mineral-associated organic carbon storage.

Identifying controls on soil organic carbon (SOC) storage, and where SOC is most vulnerable to loss, are essential to managing soils for both climate change mitigation and global food security. However, we currently lack a comprehensive understanding of the global drivers of SOC storage, especially with regards to particulate (POC) and mineral-associated organic carbon (MAOC). To better understand hierarchical controls on POC and MAOC, we applied path analyses to SOC fractions, climate (i.e., mean annual temperature [MAT] and mean annual precipitation minus potential evapotranspiration [MAP-PET]), carbon (C) input (i.e., net primary production [NPP]), and soil property data synthesized from 72 published studies, along with data we generated from the National Ecological Observatory Network soil pits (n = 901 total observations). To assess the utility of investigating POC and MAOC separately in understanding SOC storage controls, we then compared these results with another path analysis predicting bulk SOC storage. We found that POC storage is negatively related to MAT and soil pH, while MAOC storage is positively related to NPP and MAP-PET, but negatively related to soil % sand. Our path analysis predicting bulk SOC revealed similar trends but explained less variation in C storage than our POC and MAOC analyses. Given that temperature and pH impose constraints on microbial decomposition, this indicates that POC is primarily controlled by SOC loss processes. In contrast, strong relationships with variables related to plant productivity constraints, moisture, and mineral surface availability for sorption indicate that MAOC is primarily controlled by climate-driven variations in C inputs to the soil, as well as C stabilization mechanisms. Altogether, these results demonstrate that global POC and MAOC storage are controlled by separate environmental variables, further justifying the need to quantify and model these C fractions separately to assess and forecast the responses of SOC storage to global change.

Exploring the synergy of enhanced weathering and Bacillus subtilis: A promising strategy for sustainable agriculture.

Climate change is one of the most urgent environmental challenges that humanity faces. In addition to the reduction of greenhouse gas emissions, safe and robust carbon dioxide removal (CDR) technologies that capture atmospheric CO2 and ensure long-term sequestration are required. Among CDR technologies, enhanced silicate weathering (ESW) has been suggested as a promising option. While ESW has been demonstrated to depend strongly on pH, water, and temperature, recent studies suggest that biota may accelerate mineral weathering rates. Bacillus subtilis is a plant growth-promoting rhizobacterium that can facilitate weathering to obtain mineral nutrients. It is a promising agricultural biofertilizer, as it helps plants acquire nutrients and protects them from environmental stresses. Given that croplands are optimal implementation fields for ESW, any synergy between ESW and B. subtilis can hold great potential for further practice. B. subtilis was reported to enhance weathering under laboratory conditions, but there is a lack of data for soil applications. In a soil-mesocosm experiment, we examined the effect of B. subtilis on basalt weathering. B. subtilis-basalt interaction stimulated basalt weathering and increased soil extractable Fe. The combined application displayed higher CDR potential compared to basalt-only application (3.7 vs. 2.3 tons CO2 ha-1) taking solid and liquid cation pools into account. However, the cumulative CO2 efflux decreased by approximately 2 tons CO2 ha-1 with basalt-only treatment, while the combined application did not affect the CO2 efflux. We found limited mobilization of cations to the liquid phase as most were retained in the soil. Additionally, we found substantial mobilization of basalt-originated Mg, Fe, and Al to oxide- and organic-bound soil fractions. We, therefore, conclude that basalt addition showed relatively low inorganic CDR potential but a high capacity for SOM stabilization. The outcomes indicated the importance of weathering rate-GHG emission integration and the high potential of SOM stabilization in ESW studies.

Losses and destabilization of soil organic carbon stocks in coastal wetlands converted into aquaculture ponds.

Coastal-wetlands play a crucial role as carbon (C) reservoirs on Earth due to their C pool composition and functional sink, making them significant for mitigating global climate change. However, due to the development and utilization of wetland resources, many wetlands have been transformed into other land-use types. The current study focuses on the alterations in soil organic-C (SOC) in coastal-wetlands following reclamation into aquaculture ponds. We conducted sampling at 11 different coastal-wetlands along the tropical to temperate regions of the China coast. Each site included two community types, one with solely native species (Suaeda salsa, Phragmites australis and Mangroves) and the other with an adjacent reclaimed aquaculture pond. Across these 11 locations we compared SOC stock, active OC fractions, and soil physicochemical properties between coastal wetlands and aquaculture ponds. We observed that different soil uses, sampling sites, and their interaction had significant effects on SOC and its stock (p < .05). Reclamation significantly declined SOC concentration at depths of 0-15 cm and 15-30 cm by 35.5% and 30.3%, respectively, and also decreased SOC stock at 0-15 cm and 15-30 cm depths by 29.1% and 37.9%, respectively. Similar trends were evident for SOC stock, labile organic-C, dissolved organic-C and microbial biomass organic-C concentrations (p < .05), indicating soil C-destabilization and losses from soil following conversion. Soils in aquaculture ponds exhibited higher bulk density (BD; 11.3%) and lower levels of salinity (61.0%), soil water content (SWC; 11.7%), total nitrogen (TN) concentration (23.8%) and available-nitrogen concentration (37.7%; p < .05) than coastal-wetlands. Redundancy-analysis revealed that pH, BD and TN concentration were the key variables most linked with temporal variations in SOC fractions and stock between two land use types. This study provides a theoretical basis for the rational utilization and management of wetland resources, the achievement of an environment-friendly society, and the preservation of multiple service functions within wetland ecosystems.

Sustainability in radiation oncology: opportunities for enhancing patient care and reducing CO2 emissions in breast cancer radiotherapy at selected German centers.

BACKGROUND AND OBJECTIVE: Radiotherapy often entails a substantial travel burden for patients accessing radiation oncology centers. The total travel distance for such treatments is primarily influenced by two factors: fractionation schedules and the distances traveled. Specific data on these aspects are not well documented in Germany. This study aims to quantify the travel distances for routine breast cancer patients of five radiation oncology centers located in metropolitan, urban, and rural areas of Germany and to record the CO2 emissions resulting from travel. METHODS: We analyzed the geographic data of breast cancer patients attending their radiotherapy treatments and calculated travelling distances using Google Maps. Carbon dioxide emissions were estimated assuming a standard 40-miles-per-gallon petrol car emitting 0.168 kg of CO2 per kilometer. RESULT: Addresses of 4198 breast cancer patients treated between 2018 and 2022 were analyzed. Our sample traveled an average of 37.2 km (minimum average: 14.2 km, maximum average: 58.3 km) for each radiation fraction. This yielded an estimated total of 6.2 kg of CO2 emissions per visit, resulting in 156.2 kg of CO2 emissions when assuming 25 visits (planning, treatment, and follow-up). CONCLUSION: Our study highlights the environmental consequences associated with patient commutes for external-beam radiotherapy, indicating that reducing the number of treatment fractions can notably decrease CO2 emissions. Despite certain assumptions such as the mode of transport and possible inaccuracies in patient addresses, optimizing fractionation schedules not only reduces travel requirements but also achieves greater CO2 reductions while keeping improved patient outcomes as the main focus.

Characterization of the 263K-derived microsomal fraction: a source of prions for nanofiltration validation studies.

BACKGROUND: The manufacturing processes of plasma products include steps that can remove prions. The efficacy of these steps is measured in validation studies using animal brain-derived prion materials called spikes. Because the nature of the prion agent in blood is not known, the relevance of these spikes, particularly with steps that are based on retention mechanisms such as nanofiltration, is important to investigate. STUDY DESIGN AND METHODS: The aggregation and sizes of PrPres assemblies of microsomal fractions (MFs) extracted from 263K-infected hamster brains were analyzed using velocity gradients. The separated gradient fractions were either inoculated to Tg7 mice expressing hamster-PrPc to measure infectivity or used in Protein Misfolding Cyclic Amplification for measuring seeding activity. The collected data allowed for reanalyzing results from previous nanofiltration validation studies. RESULTS: A significant portion of MFs was found to be composed of small PrPres assemblies, estimated to have a size ≤24 mers (~22-528 kDa), and to contain a minimum of 20% of total prion infectivity. With this data we could calculate reductions of 4.10 log (15 N), 2.53 log (35 N), and 1.77 log (35 N) from validation studies specifically for these small PrPres objects. CONCLUSION: Our gradient data provided evidence that nanofilters can remove the majority of the smallest PrPres entities within microsomes spikes, estimated to be in a size below 24 mers, giving insight about the fact that, in our conditions, size exclusion may not be the only mechanism for retention nanofiltration.

Prospect of Controlled Autoxidation to Produce High-Value Products from the Low-Value Petroleum Fractions.

Substantial amounts of low-value light petroleum fractions and low-value heavy petroleum fractions, such as light naphtha, HVGO, and vacuum residue, are generated during the upgrading and refining of conventional and unconventional petroleum resources. The oil industry emphasizes economic diversification, aiming to produce high-value products from these low petroleum fractions through cost-effective and sustainable methods. Controlled autoxidation (oxidation with air) has the potential to produce industrially important oxygenates, including alcohols, and ketones, from the low-value light petroleum fractions. The produced alcohols can also be converted to olefin through catalytic dehydration. Following controlled autoxidation, the low-value heavy petroleum fractions can be utilized to produce value-added products, including carbon fiber precursors. It would reduce the production cost of a highly demandable product, carbon fiber. This review highlights the prospect of developing an alternative, sustainable, and economic method to produce value-added products from the low-value petroleum fractions following a controlled autoxidation approach.

The potential impact fraction of population weight reduction scenarios on non-communicable diseases in Belgium: application of the g-computation approach.

BACKGROUND: Overweight is a major risk factor for non-communicable diseases (NCDs) in Europe, affecting almost 60% of all adults. Tackling obesity is therefore a key long-term health challenge and is vital to reduce premature mortality from NCDs. Methodological challenges remain however, to provide actionable evidence on the potential health benefits of population weight reduction interventions. This study aims to use a g-computation approach to assess the impact of hypothetical weight reduction scenarios on NCDs in Belgium in a multi-exposure context. METHODS: Belgian health interview survey data (2008/2013/2018, n = 27 536) were linked to environmental data at the residential address. A g-computation approach was used to evaluate the potential impact fraction (PIF) of population weight reduction scenarios on four NCDs: diabetes, hypertension, cardiovascular disease (CVD), and musculoskeletal (MSK) disease. Four scenarios were considered: 1) a distribution shift where, for each individual with overweight, a counterfactual weight was drawn from the distribution of individuals with a "normal" BMI 2) a one-unit reduction of the BMI of individuals with overweight, 3) a modification of the BMI of individuals with overweight based on a weight loss of 10%, 4) a reduction of the waist circumference (WC) to half of the height among all people with a WC:height ratio greater than 0.5. Regression models were adjusted for socio-demographic, lifestyle, and environmental factors. RESULTS: The first scenario resulted in preventing a proportion of cases ranging from 32.3% for diabetes to 6% for MSK diseases. The second scenario prevented a proportion of cases ranging from 4.5% for diabetes to 0.8% for MSK diseases. The third scenario prevented a proportion of cases, ranging from 13.6% for diabetes to 2.4% for MSK diseases and the fourth scenario prevented a proportion of cases ranging from 36.4% for diabetes to 7.1% for MSK diseases. CONCLUSION: Implementing weight reduction scenarios among individuals with excess weight could lead to a substantial and statistically significant decrease in the prevalence of diabetes, hypertension, cardiovascular disease (CVD), and musculoskeletal (MSK) diseases in Belgium. The g-computation approach to assess PIF of interventions represents a straightforward approach for drawing causal inferences from observational data while providing useful information for policy makers.

Unbound Fractions of PFAS in Human and Rodent Tissues: Rat Liver a Suitable Proxy for Evaluating Emerging PFAS?

Adverse health effects associated with exposures to perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a concern for public health and are driven by their elimination half-lives and accumulation in specific tissues. However, data on PFAS binding in human tissues are limited. Accumulation of PFAS in human tissues has been linked to interactions with specific proteins and lipids in target organs. Additional data on PFAS binding and unbound fractions (funbound) in whole human tissues are urgently needed. Here, we address this gap by using rapid equilibrium dialysis to measure the binding and funbound of 16 PFAS with 3 to 13 perfluorinated carbon atoms (ηpfc = 3-13) and several functional headgroups in human liver, lung, kidney, heart, and brain tissue. We compare results to mouse (C57BL/6 and CD-1) and rat tissues. Results show that funbound decreases with increasing fluorinated carbon chain length and hydrophobicity. Among human tissues, PFAS binding was generally greatest in brain > liver ≈ kidneys ≈ heart > lungs. A correlation analysis among human and rodent tissues identified rat liver as a suitable surrogate for predicting funbound for PFAS in human tissues (R2 ≥ 0.98). The funbound data resulting from this work and the rat liver prediction method offer input parameters and tools for toxicokinetic models for legacy and emerging PFAS.

Land Use Change from Natural Tropical Forests to Managed Ecosystems Reduces Gross Nitrogen Production Rates and Increases the Soil Microbial Nitrogen Limitation.

Understanding the underlying mechanisms of soil microbial nitrogen (N) utilization under land use change is critical to evaluating soil N availability or limitation and its environmental consequences. A combination of soil gross N production and ecoenzymatic stoichiometry provides a promising avenue for nutrient limitation assessment in soil microbial metabolism. Gross N production via 15N tracing and ecoenzymatic stoichiometry through the vector and threshold element ratio (Vector-TER) model were quantified to evaluate the soil microbial N limitation in response to land use changes. We used tropical soil samples from a natural forest ecosystem and three managed ecosystems (paddy, rubber, and eucalyptus sites). Soil extracellular enzyme activities were significantly lower in managed ecosystems than in a natural forest. The Vector-TER model results indicated microbial carbon (C) and N limitations in the natural forest soil, and land use change from the natural forest to managed ecosystems increased the soil microbial N limitation. The soil microbial N limitation was positively related to gross N mineralization (GNM) and nitrification (GN) rates. The decrease in microbial biomass C and N as well as hydrolyzable ammonium N in managed ecosystems led to the decrease in N-acquiring enzymes, inhibiting GNM and GN rates and ultimately increasing the microbial N limitation. Soil GNM was also positively correlated with leucine aminopeptidase and ß-N-acetylglucosaminidase. The results highlight that converting tropical natural forests to managed ecosystems can increase the soil microbial N limitation through reducing the soil microbial biomass and gross N production.

High-Resolution Spatiotemporal Modeling for PM2.5 Major Components in the Pearl River Delta and Its Implications for Epidemiological Studies.

Distinguishing the effects of different fine particulate matter components (PMCs) is crucial for mitigating their effects on human health. However, the sparse distribution of locations where PM is collected for component analysis makes it challenging to investigate the relevant health effects. This study aimed to investigate the agreement between data-fusion-enhanced exposure assessment and site monitoring data in estimating the effects of PMCs on gestational diabetes mellitus (GDM). We first improved the spatial resolution and accuracy of exposure assessment for five major PMCs (EC, OM, NO3-, NH4+, and SO42-) in the Pearl River Delta region by a data fusion model that combined inputs from multiple sources using a random forest model (10-fold cross-validation R2: 0.52 to 0.61; root mean square error: 0.55 to 2.26 µg/m3). Next, we compared the associations between exposures to PMCs during pregnancy and GDM in a hospital-based cohort of 1148 pregnant women in Heshan, China, using both site monitoring data and data-fusion model estimates. The comparative analysis showed that the data-fusion-based exposure generated stronger estimates of identifying statistical disparities. This study suggests that data-fusion-enhanced estimates can improve exposure assessment and potentially mitigate the misclassification of population exposure arising from the utilization of site monitoring data.