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Abstract 63: Age-related Changes In Gray Matter Cerebral Metabolism And Vascular Reactivity In Children

Introduction: Metabolic demand changes throughout childhood as the brain develops, peaking in the 2 nd decade of life. Cerebral blood flow (CBF) is dynamic throughout childhood, likely in response to the increased metabolic demand of brain development. Cerebrovascular reactivity (CVR) reflects the ability to further increase CBF in response to a stimulus, such as carbon dioxide (CO 2 ). We hypothesized that gray matter oxygen metabolism (GM CMRO 2 ) is increased in younger children, corresponding to higher GM CBF and lower GM CVR. Methods: CVR was calculated as the proportional change of a subject’s MRI-measured blood oxygen level dependent signal in response to an increase in end-tidal CO 2 administered by the RespirAct® RA-MR™ device. GM CMRO 2 was calculated voxel-by-voxel as the product of GM CBF (arterial spin labeling), GM oxygen extraction fraction (asymmetric spin echo), and arterial oxygen content (= Hb х (oxygen saturation)х1.34). Univariate relationships were tested using Spearman’s correlation coefficient, and corrected for multiple comparisons. Results: GM CVR, CBF, and CMRO 2 were calculated for 15 healthy participants (ages 8-19, 7 male). GM CMRO 2 was highest in young children and decreased with age (ρ=-0.68, P=0.005), as did CBF (ρ =-0.67, P=0.006). CVR was lower in young children, increasing with age (ρ=0.58, P=0.02). However, while GM CVR correlated with CBF (ρ=-0.64, P=0.01) it did not significantly associate with CMRO 2 (ρ=-0.43, P=0.114). Conclusion: Although GM CMRO 2 and CVR both have age-related changes, CVR does not directly correlate with CMRO 2 . Rather, their relationship may be moderated through other influences on CBF, as further study will investigate. Figure: Linear fits and 95% confidence intervals of subject data, including age, GM CBF, and GM CMRO 2 , versus GM CVR. P-values are from Spearman’s test for monotonic correlation.

The Use of biochar in the Remediation of Pb, Cd, and Cu-Contaminated Soils. The Impact of biochar Feedstock and Preparation Conditions on Its Remediation Capacity

Soil constitutes an important part of terrestrial ecosystems, prone to be adversely impacted by human activities. During the last decades, several methods have been developed aiming at its remediation, including the use of biochar as a soil amendment. In the present work, we have assessed the reduction of Pb, Cd, and Cu soil concentrations as a function of the mixing ratio of biochar added to soil, as well as the source of biochar employed. Furthermore, we have investigated the effects of biochar addition relating to the chemical forms of heavy metals (HMs) related to their bioavailability and mobility. The concentrations of HMs were determined by the BCR (European Community Bureau of Reference) sequential extraction procedure before and after biochar addition to the soils. Five types of biochar were used, obtained as by-products of sugarcane bagasse (Β), bamboo (ΒΒ), rice straw (RSB), garden waste (GB), and paulownia (PB) treatment, respectively. Biochar derived from sugarcane (B) reduced the availability of metals, as it decreased their concentration in the acid extractable fraction, by 40.5, 66.6, and 50% for Pb, Cd, and Cu, respectively. In addition, (B) application increased the residual fraction of Cu and Pb by 9% and 24.8%, respectively. Biochar derived from garden residues (GB) and paulownia plant (PB) dramatically increased the residual fraction of Cd over 97%, minimizing its availability. Sugarcane-derived biochar appeared to significantly increase Cu and Pb residual fraction concentrations and decrease available Cd concentration. Similar changes are caused by the types of biochar in the following order: biochar from sugarcane > paulownia > garden wastes > bamboo > rice straw. The redistribution of HM concentrations causes a significant improvement of environmental quality in polluted soils, as it limits the mobility and availability of toxic metals to the soil ecosystem. The use of biochar is a low-cost and eco-friendly method for the remediation of contaminated with HMs soils in the framework of a circular economy.

Non-contrast estimate of blood-brain barrier permeability in humans using arterial spin labeling and magnetization transfer at 7T.

Blood-brain barrier (BBB) dysfunction is associated with a number of central nervous system diseases. This study demonstrates the application of a novel noninvasive technique to measure the BBB permeability in the human brain at 7T. The technique exploits the fact that, when tissue macromolecules are saturated by off-resonance RF pulse, the intravascular and the extravascular (tissue) water experience different magnetization transfer effects. This principle was combined with arterial spin labeling to distinguish between the intravascular and the tissue water, and was used to calculate perfusion, water extraction fraction (E), and BBB permeability surface area product for water (PS). Simultaneous coregistered magnetization transfer ratio maps were also generated that can provide valuable additional information. Eighteen healthy volunteers (seven females), age = 27 ± 11 years and weight = 65 ± 9kg, participated in the study. Average perfusion was 67 ± 5 and 29 ± 4ml/100 g/min (p< 0.05); and E was 0.921 ± 0.025 and 0.962 ± 0.015 (p < 0.05) in the gray matter (GM) and the white matter (WM), respectively. PS was higher in the GM (171 ± 20 ml/100 g/min) compared with the WM (95 ± 18 ml/100 g/min) (p < 0.05). The parameters exhibited good reliability with test re-test experiments. The sensitivity of this technique was demonstrated by 200 mg caffeine intake, which resulted in a decrease in the resting PS by ~31%.

Aloe barbadensis rinds employ physical and chemical defense mechanisms against insect herbivores with varying success

Plants deter herbivory through a suite of physical and chemical defenses. While most studies have focused on understanding one or the other, efficient plant defense against herbivory is often cumulative. To examine this, we used Aloe barbadensis (Asphodelaceae) as a model, since in natural settings, the species is found to be well-defended against insect herbivores. To start with, we hypothesized that the epicuticular wax potentially plays an important role in herbivore defense as the major physical defense. To test our hypothesis, we conducted bioactivity-guided extraction and polarity-based fractionation of A. barbadensis rinds. We then mixed them into an artificial diet, to determine the effect of these compounds on the growth and development of two species of caterpillars, tobacco hornworm (Manduca sexta; Lepidoptera: Sphingidae) and fall armyworm (Spodoptera frugiperda; Lepidoptera: Noctuidae). Thereafter, we identified and quantified different volatile compounds emitted by the epicuticular waxes to analyze if any herbivore deterrent compounds are emitted and might be responsible for A. barbadensis repelling insect herbivores. Our results show that the surface waxes and volatiles prevented the feeding of the larvae, and the extracts from the rinds differentially affected their growth and development. Our results do not definitively explain the entire defense phenotype; however, they do help to shed light on the combination of physical and chemical mechanisms enacted by the species.

A New ent-kaurene Diterpenoid Isolated from Leaves of Espeletia semiglobulata Cuatrec. and its Potential Antimicrobial Activity

The fraction of the neutral extraction of the leaves of Espeletia semiglobulata Cuatrec. was subjected to chromatographic separation, it yielded four ent-kaurene type diterpenoids: three known [ent-kaur-16-en-19-al (I), ent-kaur-18-nor-16-en-4-ol (III), ent-kaur-16-en-19-ol (IV)] and a new one elucidated as ent-kaur-3-acetoxy-15-ene (II), based on the physicochemical and spectroscopic data of FTIR, GC-MS, and 1D and 2D NMR. These compounds were subjected to antimicrobial bioassay studies. This new ent-kaurene showed a significant inhibition potential against the growth of gram negative bacterial strains [Escherichia coli (ATCC 25922): 8 mm, Klebsiella pneumoniae (ATCC 23357): 10 mm, Pseudomonas aeruginosa (ATCC 27853): 8 mm], it also showed inhibition against the growth of fungal strain (Candida krusei: 8 mm), at a 2 mg/mL concentration. The compounds (I), (III) and (IV) failed to show any significant results in the antimicrobial screening against five bacterial strains [Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Klebsiella pneumoniae (ATCC 23357), Escherichia coli (ATCC 25922) y Pseudomonas aeruginosa (ATCC 27853)] and one fungal strain [Candida krusei (ATCC 6558)]. These results reveal a remarkable natural structure-activity relationship of the ent-kaurene core regarding the C-3 position (A ring of perhydrophenanthrene unit), whose oxygenation or addition of a hydrogen bond acceptor or donor group, improves the antimicrobial activity.

Ionic Liquid-Assisted Selective Extraction and Partitioning of Biomolecules from Macroalgae.

Macroalgae are a promising feedstock for several industries due to their large content of proteins and carbohydrates and the high biomass productivities. A novel extraction and fractionation concept based on ionic liquids (ILs) using Ulva lactuca as model organism is presented. Biomolecules are first extracted by means of IL-assisted mechanical shear, followed by two-phase partitioning or ultrafiltration in order to fractionate proteins and carbohydrates and to recover the IL. Ethyl methyl imidazolium dibutyl phosphate ([Emim][DBP]) is strongly selective to proteins, leading to extraction yields up to 80.4% for proteins and 30.7% for carbohydrates. The complete process, including extraction and ultrafiltration, allowed protein recovery of up to 64.6 and 15.4% of the carbohydrates in the retentate phase, while a maximum of 85.7% of the IL was recovered in the permeate phase. The native structure of the extracted proteins was preserved during extraction and fractionation as shown by gel electrophoresis. Selective extraction of proteins from macroalgae under non-denaturing conditions using ILs followed by the recovery of IL using ultrafiltration is for the first time reported. The proposed extraction-fractionation approach is simple and can be potentially applied for the biorefinery of macroalgae at the commercial scale.

Long-term manure application improves soil health and stabilizes carbon in continuous maize production system

Soil health lies at the core of a sustainable food production system. A comprehensive evaluation of different agronomic practices and their effect on soil health is essential to determine the best practices that support soil ecosystem services. However, it may take years or decades to observe measurable changes in soil health under varying management practices. The objective of this experiment was to evaluate the effects of long-term (>77 years) manure and inorganic nitrogen (N) fertilizer on soil health and determine the interrelationship among the measured soil bio-physicochemical indicators. The study also aims to understand the sustainability of the monocropping maize production system under long-term manure and inorganic N fertilizer management. The experiment site is the historic Knorr–Holden Plot, established in 1910 and continued till today. Over the years, the treatments were constant, with manure as the main factor and N rates as the sub-plot factor. Aligning with advancements in agronomic management, the rates of fertilizer and manure have been revised from time to time. Analysis of soil health indicators showed a significant effect of manure on different labile carbon (C) & N fractions, soil enzymes, and soil organic matter (SOM). Manure treatment improved C stabilization and reached a C equilibrium for management. Water holding capacity was significantly improved at wilting point and field capacity for manure treatment. Nitrogen treatments only affected soil pH, cationic exchange capacity (CEC), and phosphorus. Analysis of the interrelationship among soil health indicators showed SOM was determinative for C & N fractions and CEC. Soil organic carbon can be used as a proxy for soil total N (R2 = 0.98). Water extractable fractions of C and N were interrelated and can be used as determinative factors for each other. The results inform that a sustainable monocropping system can be maintained using long-term manure application, where soil health and organic carbon improve over time. The results also indicate that soil health measurement can be minimized to a few key indicators based on the functional interrelationship, which can broaden the adoption of soil health monitoring and measurement.

Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins

Blood-brain barrier (BBB) plays a critical role in protecting the brain from toxins and pathogens. However, in vivo tools to assess BBB permeability are scarce and often require the use of exogenous contrast agents. In this study, we aimed to develop a non-contrast arterial-spin-labeling (ASL) based MRI technique to estimate BBB permeability to water in mice. By determining the relative fraction of labeled water spins that were exchanged into the brain tissue as opposed to those that remained in the cerebral veins, we estimated indices of global BBB permeability to water including water extraction fraction (E) and permeability surface-area product (PS). First, using multiple post-labeling delay ASL experiments, we estimated the bolus arrival time (BAT) of the labeled spins to reach the great vein of Galen (VG) to be 691.2 ± 14.5 ms (N = 5). Next, we investigated the dependence of the VG ASL signal on labeling duration and identified an optimal imaging protocol with a labeling duration of 1200 ms and a PLD of 100 ms. Quantitative E and PS values in wild-type mice were found to be 59.9 ± 3.2% and 260.9 ± 18.9 ml/100 g/min, respectively. In contrast, mice with Huntington's disease (HD) revealed a significantly higher E (69.7 ± 2.4%, P = 0.026) and PS (318.1 ± 17.1 ml/100 g/min, P = 0.040), suggesting BBB breakdown in this mouse model. Reproducibility studies revealed a coefficient-of-variation (CoV) of 4.9 ± 1.7% and 6.1 ± 1.2% for E and PS, respectively. The proposed method may open new avenues for preclinical research on pathophysiological mechanisms of brain diseases and therapeutic trials in animal models.

Quantification of blood-brain barrier water exchange and permeability with multidelay diffusion-weighted pseudo-continuous arterial spin labeling.

To present a pulse sequence and mathematical models for quantification of blood-brain barrier water exchange and permeability. Motion-compensated diffusion-weighted (MCDW) gradient-and-spin echo (GRASE) pseudo-continuous arterial spin labeling (pCASL) sequence was proposed to acquire intravascular/extravascular perfusion signals from five postlabeling delays (PLDs, 1590-2790 ms). Experiments were performed on 11 healthy subjects at 3 T. A comprehensive set of perfusion and permeability parameters including cerebral blood flow (CBF), capillary transit time (τc ), and water exchange rate (kw ) were quantified, and permeability surface area product (PSw ), total extraction fraction (Ew ), and capillary volume (Vc ) were derived simultaneously by a three-compartment single-pass approximation (SPA) model on group-averaged data. With information (i.e., Vc and τc ) obtained from three-compartment SPA modeling, a simplified linear regression of logarithm (LRL) approach was proposed for individual kw quantification, and Ew and PSw can be estimated from long PLD (2490/2790 ms) signals. MCDW-pCASL was compared with a previously developed diffusion-prepared (DP) pCASL sequence, which calculates kw by a two-compartment SPA model from PLD = 1800 ms signals, to evaluate the improvements. Using three-compartment SPA modeling, group-averaged CBF = 51.5/36.8 ml/100 g/min, kw = 126.3/106.7 min-1 , PSw = 151.6/93.8 ml/100 g/min, Ew = 94.7/92.2%, τc = 1409.2/1431.8 ms, and Vc = 1.2/0.9 ml/100 g in gray/white matter, respectively. Temporal SNR of MCDW-pCASL perfusion signals increased 3-fold, and individual kw maps calculated by the LRL method achieved higher spatial resolution (3.5 mm3 isotropic) as compared with DP pCASL (3.5 × 3.5 × 8 mm3 ). MCDW-pCASL allows visualization of intravascular/extravascular ASL signals across multiple PLDs. The three-compartment SPA model provides a comprehensive measurement of blood-brain barrier water dynamics from group-averaged data, and a simplified LRL method was proposed for individual kw quantification.

Weikangling capsules combined with omeprazole ameliorates ethanol-induced chronic gastritis by regulating gut microbiota and EGF-EGFR-ERK pathway

AimsWeikangling capsules (WKLCs) have been widely used in the treatment of chronic gastritis. Whether used alone or combined with omeprazole (OME), it shows a significant effect. However, the mechanisms haven't been established. The study aimed to explore the mechanisms of WKLCs and its combination with OME on chronic gastritis. Main methodsThe components of WKLCs and EA (the ethyl acetate extraction extracted from WKLCs) fraction were analyzed. Then chronic gastritis model rats were induced by 56 % ethanol and treated with OME, low dose of WKLCs (WKL), high dose of WKLCs (WKH), WKLCs combined with OME (WO), and EA fraction (EA) to evaluate the mechanisms of WKLCs, drug combination and EA fraction. Key findingsA total of 22 components of WKLCs were quantified, among them 18 were enriched in EA fraction. WKLCs alleviated the morphology and inflammation of gastric mucosa and downregulated the levels of inflammatory factors (IL-1β, TNF-α, IL-6) and epidermal growth factor (EGF) in serum by inhibiting the EGF-EGFR-ERK pathway, regulating gut microbiota composition and SCFAs contents in feces. WKLCs plus OME was better than OME. EA fraction improved digestive function by increasing pepsin activity and decreasing gastrointestinal hormones (GAS and VIP) compared with WKLCs. SignificanceThis study elucidated that the effect of WKLCs and its combination with OME in the treatment of chronic gastritis was attributed to regulating the composition of the gut microbiota and inhibiting the EGF-EGFR-ERK pathway. The EA fraction is an inseparable effective substance of WKLCs. This study provides scientific evidence for clinical application.

Assessing Cerebral Oxygen Metabolism Changes in Patients With Preeclampsia Using Voxel-Based Morphometry of Oxygen Extraction Fraction Maps in Magnetic Resonance Imaging.

The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia. Forty-nine women with preeclampsia (mean age 32.4 years; range, 18-44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23-40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20-42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups. Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (all P-values were less than 0.05, after correcting for multiple comparisons). The average OEF values of the preeclampsia group were higher than those of the PHC and NPHC groups. The bilateral superior frontal gyrus/bilateral medial superior frontal gyrus had the largest size of the aforementioned brain regions, and the OEF values in this area were 24.2 ± 4.6, 21.3 ± 2.4, and 20.6 ± 2.8 in the preeclampsia, PHC, and NPHC groups, respectively. In addition, the OEF values showed no significant differences between NPHC and PHC. Correlation analysis revealed that the OEF values of some brain regions (mainly involving the frontal, occipital, and temporal gyrus) were positively correlated with age, gestational week, body mass index, and mean blood pressure in the preeclampsia group (r = 0.361-0.812). Using whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.

Progress of 18F-flurpiridaz in Clinical Trials.

18F-flurpiridaz is a novel positron emission computed tomography (PET) tracer in ongoing clinical trials in United States and Japan. A phase III prospective, open-label, multi-center study to assess the feasibility of 18F-flurpiridaz was reported by Maddahi et al. in patients with known or suspected coronary artery disease (CAD) in 2020 in United States (1). 18F-flurpiridaz binds to mitochondrial complex 1 and would distribute to the myocardium with its higher extraction fraction than those in single-photon emission computed tomography (SPECT) tracers (2). In that phase III trial, 795 participants with known or suspected CAD showed that sensitivity of 18F-flurpiridaz PET (for detection of ≥50% stenosis by invasive coronary angiography) was 71.9%, significantly (p < 0.001) higher than 99mTc labeled SPECT agent (53.7%), while specificity did not meet the prespecified noninferiority criterion (76.2% vs. 86.6%, p=NS) (1). Therefore, a second phase III Food and Drug Administration trial was planned and completed by GE Healthcare. Late phase II open-label multicenter study of PET scan using 18F-flurpiridaz (named NMB58 in Japan) to assess myocardial blood flow and diagnostic feasibility in patients with known or suspected CAD started in Japan of 2023.

The Utility of Arterial Transit Time Measurement for Evaluating the Hemodynamic Perfusion State of Patients with Chronic Cerebrovascular Stenosis or Occlusive Disease: Correlative Study between MR Imaging and 15O-labeled H2O Positron Emission Tomography.

To verify whether arterial transit time (ATT) mapping can correct arterial spin labeling-cerebral blood flow (ASL-CBF) values and to verify whether ATT is a parameter that correlates with positron emission tomography (PET)-oxygen extraction fraction (OEF) and PET-mean transit time (MTT). Eleven patients with unilateral major cerebral artery stenosis or occlusion underwent MRI and PET in the chronic or asymptomatic phase. ASL-MRI acquisitions were conducted with each of two post-label delay (PLD) settings (0.7s and 2.0s) using a pseudo-continuous ASL pulse sequence and 3D-spin echo spiral readout with vascular crusher gradient. ATT maps were obtained using a low-resolution pre-scan approach with five PLD settings. Using the ASL perfusion images and ATT mapping, ATT-corrected ASL-CBF images were obtained. Four kinds of ASL-CBF methods (PLD 0.7s with or without ATT correction and PLD 2.0s with or without ATT correction) were compared to PET-CBF, using vascular territory ROIs. ATT and OEF were compared for all ROIs, unaffected side ROIs, and affected side ROIs, respectively. ATT and MTT were compared by the ratio of the affected side to the unaffected side. Transit time-based ROIs were used for the comparison with ATT. Comparing ASL-CBF and PET-CBF, the correlation was higher with ATT correction than without correction, and for a PLD of 2.0s compared with 0.7s. The best correlation was for PLD of 2.0s with ATT correction (R2 = 0.547). ROIs on the affected side showed a low but significant correlation between ATT and PET-OEF (R2 = 0.141). There was a low correlation between the ATT ratio and the MTT ratio (R2 = 0.133). Low-resolution ATT correction may increase the accuracy of ASL-CBF measurements in patients with unilateral major cerebral artery stenosis or occlusion. In addition, ATT itself might have a potential role in detecting compromised hemodynamic state.

Develop blood oxygen level dependent signal by metabolic/hemodynamic model using numerical methods

Background and objectiveThe metabolic/hemodynamic (MH) model describes the blood flow mechanisms as well as the coupling between the hemodynamic responses and the metabolic activities in a blood vessel in the human brain. In the existing MH model, the blood flow out from a blood vessel is formulated as dependent only on the capillary volume. In fact, the blood flow out from a blood vessel depends not only on the capillary volume but also on the blood flow into the capillary bed. For this reason, the blood flow out formula of the existing model has been modified. In addition to implementing existing model modification to obtain better accuracy, we have used new methods to solve the model instead of conventional methods. MethodThe MH model describes physical phenomena of a blood vessel by eight processes equations (PEs). These PEs are often solved by using a local linearization (LL) scheme and the Taylor series method. In addition to the previously used Taylor series method, we have also used the Euler method and the Runge–Kutta (RK) method to solve the model instead of a LL scheme for estimating dynamical variables (DVs). By using these DVs, a Blood Oxygen Level Dependent (BOLD) signal is generated through a well-defined observation equation (OE). There are two OEs, called Obata and Friston. The Friston OE produces a BOLD signal from the cerebral blood volume and deoxy-hemoglobin content with their nonlinear properties; conversely, the Obata OE produces a BOLD signal without considering nonlinear properties. For this reason, we have used the Friston OE instead of the Obata OE to estimate the BOLD signal perfectly. ResultsAt 20% resting oxygen extraction fraction (ROEF), the BOLD signals of the modified and the existing model are identical, but when the ROEF increased up to 50% at its standard value, the modified model accuracy is increased by 16.12%–23.07% more than that of the existing model. The Euler and RK methods generate a BOLD signal 6.95% more accurately than that of Taylor series method from the modified model. ConclusionIn the model inversion process, this research will be helpful to estimate the model parameters and hidden states accurately.

Impaired oxygen extraction and adaptation of intracellular energy metabolism in cerebral small vessel disease.

We aimed to investigate whether combined phosphorous (31P) magnetic resonance spectroscopic imaging (MRSI) and quantitative mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pHi) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD). 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3-dimensional31P MRSI and oxygenation-sensitive quantitative mapping (1/ =1/T2* - 1/T2) at 3 Tesla (T). PHiwas measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative values were averaged across the entire white matter (WM).Furthermore, values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls. Quantitative values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51±16.94vs. 138.19±12.66ms and 147.45±18.14vs. 137.99±12.19ms, p<0.05).WM values correlated significantly with the WMH load (ρ=0.441, p=0.006). Increased was significantly associated with more alkaline pHi(ρ=0.299, p<0.05). Both and pHi were significantly positively correlated with vascular pulsatility in the distal carotid arteries (ρ=0.596, p=0.001 and ρ=0.452, p=0.016). This exploratory study found evidence of impaired cerebral OEF in SVD, which is associated with intracellular alkalosis as an adaptive mechanism. The employed techniques provide new insights into the pathophysiology of SVD with regard to disease-related consequences on the cellular metabolic state.

Native lignin extraction from soft- and hardwood by green and benign sub/supercritical fluid extraction methodologies.

Lignin constitutes an impressive resource of high-value low molecular weight compounds. However, robust methods for isolation of the extractable fraction from lignocellulose are yet to be established. In this study, supercritical fluid extraction (SFE) and CO2-expanded liquid extraction (CXLE) were employed to extract lignin from softwood and hardwood chips. Ethanol, acetone, and ethyl lactate were investigated as green organic co-solvents in the extractions. Additionally, the effects of temperature, CO2 percentage and the water content of the co-solvent were investigated using a design of experiment approach employing full factorial designs. Ethyl lactate and acetone provided the highest gravimetric yields. The water content in the extraction mixture had the main impact on the amount of extractable lignin monomers (LMs) and lignin oligomers (LOs) while the type of organic solvent was of minor importance. The most effective extraction was achieved by using a combination of liquid CO2/acetone/water (10/72/18, v/v/v) at 60 °C, 350 bar, 30 min and 2 mL min-1 flow rate. The optimized method provided detection of 13 LMs and 6 lignin dimers (LDs) from the hardwood chips. The results demonstrate the potential of supercritical fluids and green solvents in the field of mild and bening lignin extraction from wood.

Ecological Risk Assessment and Source Analysis of Heavy Metals in the Soils of a Lead-Zinc Mining Watershed Area

In this study, concentrations of Cr, Mn, Pb, Cu, Zn, As, Cd, Sb, and Fe were determined in soils of a Pb-Zn mine watershed in northern Guangxi, China, for ecological risk assessment and source analysis. The atomic fluorescence spectrometry and ICP-OES were used to determine concentrations of heavy metals (HMs), and the total amount of Mn, Cu, Zn, As, Cd, and Pb exceeded the limit. Among them, the weak acid extractable fraction (F1) state masses of Pb, Mn, and Zn accounted for a higher ecological risk. The study area was divided into three distinct areas: highest concentrations of HMs were distributed in front of the Sidi River mountain (1# and 2#) and at the subterranean river entrance (5# and 6#), followed by the area along the river and the irrigated area of the river (3# and 4#), and the central highlands and southwestern parts had low concentrations (7# and 8#). The ecological risk assessment results indicate Cd is of extremely high ecological risk, Pb and Mn are of medium minor ecological risk, Zn is of minor ecological risk, and the rest have almost no impact on the eco-environment. The source apportionment results showed that Cu, Zn, Cd, Sb, and Pb were mainly controlled by anthropogenic activities, such as mining; Cr, Fe, and As were mainly influenced by natural processes, such as soil-forming parent rocks; and Mn is jointly controlled by mining and soil-forming parent rocks. This study can provide scientific guidance and technical support for soil risk control or remediation in mining areas.

Red cell exchange transfusions increase cerebral capillary transit times and may alter oxygen extraction in sickle cell disease.

Persons with sickle cell disease (SCD) suffer from chronic hemolytic anemia, reduced blood oxygen content, and lifelong risk of silent and overt stroke. Major conventional stroke risk factors are absent in most individuals with SCD, yet nearly 50% have evidence of brain infarcts by the age of 30 years, indicating alternative etiologies for ischemia. We investigated whether radiological evidence of accelerated blood water transit through capillaries, visible on arterial spin labeling (ASL) magnetic resonance imaging, reduces following transfusion-induced increases in hemoglobin and relates to oxygen extraction fraction (OEF). Neurological evaluation along with anatomical and hemodynamic imaging with cerebral blood flow (CBF)-weighted pseudocontinuous ASL and OEF imaging with T2 -relaxation-under-spin-tagging were applied in sequence before and after blood transfusion therapy (n = 32) and in a comparator cohort of nontransfused SCD participants on hydroxyurea therapy scanned at two time points to assess stability without interim intervention (n = 13). OEF was calculated separately using models derived from human hemoglobin-F, hemoglobin-A, and hemoglobin-S. Gray matter CBF and dural sinus signal, indicative of rapid blood transit, were evaluated at each time point and compared with OEF using paired statistical tests (significance: two-sided p < 0.05). No significant change in sinus signal was observed in nontransfused participants (p = 0.650), but a reduction was observed in transfused participants (p = 0.034), consistent with slower red cell transit following transfusion. The dural sinus signal intensity was inversely associated with OEF pretransfusion (p = 0.011), but not posttransfusion. Study findings suggest that transfusion-induced increases in total hemoglobin may lengthen blood transit times through cerebral capillaries and alter cerebral OEF in SCD.

MRI assessment of cerebral oxygen extraction fraction in the medial temporal lobe

The medial temporal lobe (MTL) is a key area implicated in many brain diseases, such as Alzheimer's disease. As a functional biomarker, the oxygen extraction fraction (OEF) of MTL may be more sensitive than structural atrophy of MTL, especially at the early stages of diseases. However, there is a lack of non-invasive techniques to measure MTL-OEF in humans. The goal of this work is to develop an MRI technique to assess MTL-OEF in a clinically practical time without using contrast agents. The proposed method measures venous oxygenation (Yv) in the basal veins of Rosenthal (BVs), which are the major draining veins of the MTL. MTL-OEF can then be estimated as the arterio-venous difference in oxygenation. We developed an MRI sequence, dubbed arterial-suppressed accelerated T2-relaxation-under-phase-contrast (AS-aTRUPC), to quantify the blood T2 of the BVs, which was then converted to Yv through a well-established calibration model. MTL-OEF was calculated as (Ya−Yv)/Ya × 100%, where Ya was the arterial oxygenation. The feasibility of AS-aTRUPC to quantify MTL-OEF was evaluated in 16 healthy adults. The sensitivity of AS-aTRUPC in detecting OEF changes was assessed by a caffeine ingestion (200 mg) challenge. For comparison, T2-relaxation-under-spin-tagging (TRUST) MRI, which is a widely used global OEF technique, was also acquired. The dependence of MTL-OEF on age was examined by including another seven healthy elderly subjects. The results showed that in healthy adults, MTL-OEF of the left and right hemispheres were correlated (P=0.005). MTL-OEF was measured to be 23.9±3.6% (mean±standard deviation) and was significantly lower (P<0.0001) than the OEF of 33.3±2.9% measured in superior sagittal sinus (SSS). After caffeine ingestion, there was an absolute percentage increase of 9.1±4.0% in MTL-OEF. Additionally, OEF in SSS measured with AS-aTRUPC showed a strong correlation with TRUST OEF (intra-class correlation coefficient=0.94 with 95% confidence interval [0.91, 0.96]), with no significant bias (P=0.12). MTL-OEF was found to increase with age (MTL-OEF=20.997+0.100 × age; P=0.02). In conclusion, AS-aTRUPC MRI provides non-invasive assessments of MTL-OEF and may facilitate future clinical applications of MTL-OEF as a disease biomarker.

Improving the Measurement of Iron(III) Bioavailability in Freshwater Samples: Methods and Performance.

The toxicity of iron(III) in fresh waters has been detected at concentrations above the iron solubility limit, indicating a contribution of colloidal and particulate forms of iron(III) to the toxicity response. Current water quality guideline values for iron in fresh water are based on analytical determinations of filterable or total iron. Filtration, however, can underestimate bioavailable iron by retaining some of the colloidal fraction, and total determinations overestimate bioavailable iron measurements by recovering fractions of low bioavailability from suspended solids (e.g., iron oxides and oxyhydroxides) naturally abundant in many surface waters. Consequently, there is a need for an analytical method that permits the determination of a bioavailable iron fraction, while avoiding false-negative and false-positive results. Ideally, a measurement technique is required that can be readily applied by commercial laboratories and field sampling personnel, and integrated into established regulatory schemes. The present study investigated the performance of pH 2 and pH 4 extractions to estimate a bioavailable iron(III) fraction in synthetic water samples containing iron phases of different reactivities. The effects of aging on fresh precipitates were also studied. The total recoverable, 0.45-µm filtered, and pH 4 extractable fractions did not discriminate iron phases and age groups satisfactorily. Contrastingly, the pH 2 extraction showed specificity toward iron phases and aging (0.5-2-h interval). Extraction times above 4 h and up to 16 h equally recovered >90% of the spiked iron regardless of its age. Furthermore, <1% of the well-mineralized iron was targeted. The present study shows that a pH 2 dilute-acid extraction is a suitable candidate method to operationally define iron fractions of higher bioavailability avoiding false-negative and false-positive results. Environ Toxicol Chem 2023;42:303-316. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.