Low-density Fraction Research Articles

A novel genetic mouse model of osteoporosis with double heterozygosity of Irx3 and Irx5 characterizes sex-dependent phenotypes in bone homeostasis

Iroquois homeobox gene 3 (Irx3) and Irx5 encode transcription factors that play crucial roles in limb development and bone formation. Previous studies using knockout mice have revealed a role of Irx3 and Irx5 in osteogenesis in young adult mice. However, whether these genes are also essential for bone homeostasis in adulthood and contribute to bone diseases remain poorly understood. Osteoporosis is a disease characterized by lower bone mineral density and disrupted bone microarchitecture, typically occurs in postmenopausal women. Here, we demonstrate that Irx3/5dHet mice with a half-reduction of Irx3 and Irx5 dosage serve as a novel model of osteoporosis. By micro-computed tomography, we found that Irx3/5dHet mice exhibited sex-dependent bone loss patterns. While male Irx3/5dHet mice progressively lost trabecular microstructures with aging, female mutants exhibited lower bone mineral density (BMD) and bone volume fraction (BV/TV) at early adulthood (9–15 weeks old) but without further loss later at 1 year of age. Bone marrow adipocytes are known to be elevated at the expenses of lower osteogenesis in osteoporotic bone marrow. Surprisingly, we found sex-dependent changes in adipogenesis at the age of skeletal maturity that bone marrow adipocytes were reduced in female Irx3/5dHet mice along with deteriorated osteogenesis, while male mice exhibited elevated adipogenesis. In summary, we reported a novel genetic model for osteoporosis-like phenotypes, highlighting sex-dependent bone mineral density and bone marrow adipocyte characteristics.

Effect of 67-years of manuring, fertilization and amendments on fractions of soil organic carbon, nutrient dynamics and yield sustainability in an acidic Alfisol

Amending a problem soil in addition to nutrient input is crucial for maintaining a healthy and productive soil in the long run. The study aimed at evaluating the long-term impact of manuring and fertilization with or without liming on different soil attributes and crop yield in an acidic Alfisol. Surface soil samples (0–15 cm) were collected from selected 7 treatments, viz. Control; N; FYM; ½(N+FYM)+PX/2+KY/2; NPK; NPK+L; and P(A-X)K(B-Y)+FYM+L of the Permanent Manurial Trial (PMT) of Birsa Agricultural University, Ranchi, after the harvesting of rainy (kharif) maize (Zea mays L.) at the 67th crop cycle (2023 and 2024) and assessed for various fractions of soil organic carbon (SOC), available nutrients and yield attributes. The experiment was laid out in a randomized block design (RBD) and replicated thrice. The treatments which received manures either alone or in combination with chemical fertilizers recorded significantly higher amount of all the fractions of SOC, available nitrogen and lower bulk density as compare to the unfertilized plot or treatment with inorganic alone. The study also revealed that, addition of lime helped maintaining an optimum pH level, enhanced microbial activities and nutrient availability in the soil leading to a higher crop yield. Therefore, integrated use of manures and fertilizers in addition to lime for a prolonged period would have significant positive impact on soil health and sustaining its productivity.

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We investigate the medium modifications in mass and decay width of ϕ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\phi $$\\end{document} meson in the presence of an external magnetic field. The in-medium mass of ϕ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\phi $$\\end{document} meson has been calculated using the decay process ϕ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\phi $$\\end{document}→\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\rightarrow $$\\end{document}KK¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$K {\\bar{K}}$$\\end{document} at one-loop level. The medium modifications are introduced by using a chiral SU(3) model employing a mean-field effective approach. Due to the introduction of the magnetic field, masses of charged K+\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$K^+$$\\end{document} and K-\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$K^-$$\\end{document} increases with advancing magnetic field values. A negligible change in the value of neutral K0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$K^0$$\\end{document} and K¯0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\bar{K}}^0$$\\end{document} has been observed for varying magnetic fields. Due to electromagnetic interactions with charged K and K¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\bar{K}}$$\\end{document} mesons, there is a gradual augmentation in the effective mass of ϕ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\phi $$\\end{document} meson. The probability of the mentioned decay process ceases to be zero for low density and strangeness fraction values at higher magnetic field values. Investigating the decay width and effective mass of ϕ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\phi $$\\end{document} meson under the influence of an external magnetic field is relevant to understanding the hadronic matter properties under extreme conditions achievable at heavy-ion collision experiments.

Improving nutrient digestibility and health in rabbits: effect of fermented rapeseed meal supplementation on haematological and lipid parameters of blood

BackgroundMany studies conducted on livestock point to fermented rapeseed meal (FRSM) as a component that provides adequate quality and quantity of protein. Additionally, it is a very good source of probiotics, prebiotics, enzymes, and antioxidants. A study was undertaken to assess the impact of a feed supplemented with FRSM fermented with Bacillus subtilis strain 87Y on production parameters, nutrient digestibility, and haematological and lipid indicators of the blood in growing rabbits. Forty New Zealand White rabbits (body weight 816,25 ± 24,98 g) aged 35 days were used in this study. The animals were divided into four groups, a control group (C) was fed a standard diet, while in the diet of three experimental groups, soybean meal (SBM) was replaced with FRSM at 4% (FR4 group), 8% (FR8 group), or 12% (FR12 group).ResultsDetailed analysis revealed that the contribution of FRSM in the rabbit feed, regardless of the amount, had a significant effect on body weight gain (BWG), as well as average daily gain (ADG), compared to the control group (C), (P = 0.017). All groups receiving FRSM had a significantly lower (P = 0.05) feed conversion ratio (FCR) compared to the control group. In rabbits fed a diet containing 8% FRSM, the blood haematological parameters, such as red blood cells (RBC), haematocrit (HCT), haemoglobin (HGB), and mean corpuscular volume (MCV), were significantly higher compared to the control group (P = 0.037). In addition, a significant reduction in the plasma levels of the low-density lipoprotein fraction (LDL-chol), the ratio of total cholesterol to high-density lipoprotein (CHOL/HDL), (P = 0.001), and triacylglycerols (TG), (P = 0.004) were observed in the experimental groups compared to the control group.ConclusionsBased on the encouraging outcomes, it is possible to recommend domestically produced FRSM as a viable substitute for genetically-modified (GM) SBM in rabbit feed.

FeSiBCCr bulk metallic glasses with excellent soft magnetic properties prepared using spark plasma sintering technology

Fe-based amorphous alloys have received much attention in the fields of electronics and electrical due to their excellent soft magnetic properties at high frequency. However, the controllable preparation of large-sized Fe-based bulk metallic glasses (BMGs) still faces numerous challenges. In this study, FeSiBCCr amorphous powders prepared by gas-water combined atomization were used as raw materials, and FeSiBCCr BMGs were prepared through spark plasma sintering (SPS) at different pressures. The microstructure, phase and magnetic properties of the compacts were systematically characterized using SEM, XRD, TEM, DSC, and VSM. The results showed that when the sintering pressure was 50 MPa, the slow densification process dominated by particle rearrangement at the initial densification process made the internal contact resistance of the compacts larger. This led to macroscopic inhomogeneous physical fields and severe local overheating during the later stages of sintering, causing the precipitation of α-(Fe, Si) and Fe3B phases. Although the material exhibited a relatively high saturation magnetization (Bs) of 1.08 ± 0.01 T, the low density and amorphous fraction resulted in a high coercivity (Hc) of 1060.8 ± 37.8 A·m-1. When the sintering pressure was increased to 250 MPa, the degree of particle densification significantly improved, and the temperature inhomogeneity was markedly suppressed due to reduced internal resistance. Thus, the prepared FeSiBCCr BMGs exhibited an extremely high density of 6.66 ± 0.06 g·cm-3 and excellent soft magnetic properties with Bs of 1.23 ± 0.01 T and Hc of 18.8 ± 1.8 A·m-1. This indicated that the FeSiBCCr BMGs prepared in this study exhibited broad application prospects in efficient electromagnetic conversion and advanced electronic devices.

Role of Piezo1 in Terminal Density Reversal of Red Blood Cells.

Density reversal of senescent red blood cells has been known for a long time, yet the identity of the candidate ion transporter(s) causing the senescent cells to swell is still elusive. While performing fractionation of RBCs from healthy individuals in Percoll density gradient and characterization of the separated fractions, we identified a subpopulation of cells in low-density fraction (1.02% ± 0.47) showing signs of senescence such as loss of membrane surface area associated with a reduction in band 3 protein abundance, and Phosphatidylserine (PS) exposure to the outer membrane. In addition, we found that these cells are overloaded with Na+ and Ca2+. Using a combination of blockers and activators of ion pumps and channels, we revealed reduced activity of Plasma membrane Ca2+ ATPase and an increase in Ca2+ and Na+ leaks through ion channels in senescent-like cells. Our data revealed that Ca2+ overload in these cells is a result of reduced PMCA activity and facilitated Ca2+ uptake via a hyperactive Piezo1 channel. However, we could not exclude the contribution of other Ca2+-permeable ion channels in this scenario. In addition, we found, as a universal mechanism, that an increase in intracellular Ca2+ reduced the initially high selectivity of Piezo1 channel for Ca2+ and allowed higher Na+ uptake, Na+ accumulation, and swelling.

Tumour necrosis factor-alpha serum level is an independent predictor of medium-term all-cause mortality after transcatheter aortic valve replacement

Background Transcatheter aortic valve implantation (TAVI) is a suitable treatment for patients with severe aortic stenosis and severely increased operative risk. There is need for a better preoperative risk assessment for TAVI candidates. Aim To determine whether Tumour necrosis factor-alfa (TNFα) is an independent predictor of survival 500 days after TAVI. Methods Sixty patients undergoing TAVI were enrolled in the study. TNFα was determined. The CT measured low-density muscle fraction (LDM%) of the psoas muscle was determined. Operative risk assessment by Logistic EuroSCORE, EuroSCORE II, and STS score was performed. Frailty scores (FRAIL scale and Barthel index) were determined. Results Mean age was 81.01 ± 7.54 years. Twenty-six (43.3%) of the patients were males. In the univariable analyses, FRAIL scale and Barthel index were no predictors of survival after TAVI. In the multivariable analysis, including EuroSCORE II, LDM% and TNFα serum concentration, TNFα serum level was an independent predictor of survival 500 days after TAVI (HR: 3.167; 95%: 1.279–7.842; p = 0.013). The multivariable analysis, including TNFα as a categorical variable, showed that compared to patients in the conjugated first and second TNFα serum level tertile, patients in the third tertile had a hazard ratio (HR) of 10.606 (95%CI: 1.203 − 93.467) (p = 0.033). Conclusion TNFα is an incremental independent predictor of long-term survival after TAVI.

Functional organic matter components in mangrove soils revealed by density fractionation

ABSTRACT The mechanisms underlying stabilization of soil organic matter (SOM) in vegetated coastal ecosystems, including mangrove forests, are poorly understood, limiting our ability to predict the consequences of disturbances. Here, we introduce density fractionation to mangrove soils to identify the distribution and properties of the functional components of SOM regarding degradation state, stability, and origin, namely, the free low-density fraction (f-LF), mineral-associated LF (m-LF), and high-density fraction (HF). Three soil cores (1 m) were collected in a mangrove forest on Ishigaki Island, Japan, and cut into 10 cm intervals and analyzed. Although HF was the most abundant, the massive production of mangrove fine roots resulted in a high abundance of LFs throughout the cores, which markedly differed from terrestrial soils. Relative abundance of LFs together accounted for 38–66% of total soil C. The m-LF was as abundant as f-LF and 1.6 times higher in relative abundance than the global average of terrestrial soils. The C/N ratios and δ13C values clearly increased with depth in all fractions, which was attributed to the increased contribution from roots. We found a consistent pattern in Δ14C values of density fractions. HF was the oldest with Δ14C between −149‰ and −97‰ followed by m-LF (between −130‰ and −87‰) and then f-LF (between −89‰ and 78‰), suggesting that mineral association may be pivotal in long-term carbon storage in the mangrove mineral soil. Our analysis successfully identified meaningful functional components of mangrove SOM, yet several questions remained unanswered, including a large variability in Δ14C in different cores. Future studies would benefit from a coupled analysis of the quantity and quality of density fractions and geochemical factors in mangrove soils.

Analysis of the Mouse Hepatic Peroxisome Proteome-Identification of Novel Protein Constituents Using a Semi-Quantitative SWATH-MS Approach.

Ongoing technical and bioinformatics improvements in mass spectrometry (MS) allow for the identifying and quantifying of the enrichment of increasingly less-abundant proteins in individual fractions. Accordingly, this study reassessed the proteome of mouse liver peroxisomes by the parallel isolation of peroxisomes from a mitochondria- and a microsome-enriched prefraction, combining density-gradient centrifugation with a semi-quantitative SWATH-MS proteomics approach to unveil novel peroxisomal or peroxisome-associated proteins. In total, 1071 proteins were identified using MS and assessed in terms of their distribution in either high-density peroxisomal or low-density gradient fractions, containing the bulk of organelle material. Combining the data from both fractionation approaches allowed for the identification of specific protein profiles characteristic of mitochondria, the ER and peroxisomes. Among the proteins significantly enriched in the peroxisomal cluster were several novel peroxisomal candidates. Five of those were validated by colocalization in peroxisomes, using confocal microscopy. The peroxisomal import of HTATIP2 and PAFAH2, which contain a peroxisome-targeting sequence 1 (PTS1), could be confirmed by overexpression in HepG2 cells. The candidates SAR1B and PDCD6, which are known ER-exit-site proteins, did not directly colocalize with peroxisomes, but resided at ER sites, which frequently surrounded peroxisomes. Hence, both proteins might concentrate at presumably co-purified peroxisome-ER membrane contacts. Intriguingly, the fifth candidate, OCIA domain-containing protein 1, was previously described as decreasing mitochondrial network formation. In this work, we confirmed its peroxisomal localization and further observed a reduction in peroxisome numbers in response to OCIAD1 overexpression. Hence, OCIAD1 appears to be a novel protein, which has an impact on both mitochondrial and peroxisomal maintenance.

Characterization of a novel model for atherosclerosis imaging: the apolipoprotein E-deficient rat

BackgroundThe apolipoprotein E-deficient (apoE−/−) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE−/− rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE−/− rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging.ResultsApoE−/− rats showed significantly higher [18F]FDG uptake than controls in the aortic arch (+ 18.5%, p < 0.001) and abdominal aorta (+ 31.0%, p < 0.001) at weeks 12, 26, and 51. ApoE−/− rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE−/− rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE−/− rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE−/− rats.ConclusionThese data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE−/− rats. Therefore, this model shows promise for atherosclerosis imaging studies.

Comparative study of the steady-state subcellular distribution of lysosome-associated membrane glycoprotein-2 (LAMP-2) isoforms with GYXXΦ-type tyrosine-based motifs that interact differently with four adaptor protein (AP) complexes.

Lysosome-associated membrane protein-1 and -2 (LAMP-1 and LAMP-2, respectively) are type I transmembrane proteins. LAMP-2 comprises three splice isoforms (LAMP-2A, -B and-C) with different cytoplasmic tails (CTs). These three CTs possess different tyrosine-based motifs (GYXXΦ, where Φ is a bulky hydrophobic amino acid) at their C-termini. Interactions between tyrosine-based motifs and μ-subunits of four tetrameric adaptor protein (AP) complexes are necessary for their vesicular transport to lysosomes. Little is known about how the interaction strengths of these tyrosine motifs with μ-subunits affect the localization of isoforms to lysosomes. The interactions were first investigated using a yeast two-hybrid system to address this question. LAMP-2A-CT interacted with all four μ-subunits (μ1, μ2, μ3A and μ4 of AP-1, AP-2, AP-3 and AP-4, respectively). The interaction with μ3A was more robust than that with other μ-subunits. LAMP-2B-CT interacted exclusively and moderately with μ3A. LAMP-2C-CT did not detectably interact with any of the four μ-subunits. Immunofluorescence microscopy showed that all isoforms were localized in late endosomes and lysosomes. LAMP-2C was present in the plasma membrane and early endosomes; however, LAMP-2A and -2B were barely detectable in these organelles. In cell fractionation, LAMP-2A was the most abundant in the dense lysosomes, whereas LAMP-2C was significantly present in the low-density fraction containing the plasma membrane and early endosomes, in addition to the dense lysosomes. LAMP-2B considerably existed in the low-density late endosomal fraction. These data strongly suggest that the LAMP-2 isoforms are distributed differently in endocytic organelles depending on their interaction strengths with AP-3.

Cyclodextrin-Mediated Cholesterol Depletion Induces Adiponectin Secretion in 3T3-L1 Adipocytes.

Adipocytes store a significant amount of cholesterol and triglycerides. However, whether cholesterol modulates adipocyte function remains largely unknown. We modulated the cholesterol level in adipocytes to examine its effect on the secretion of adiponectin, an important hormone specifically secreted by adipocytes. Treating differentiated 3T3-L1 adipocytes with 4 mM methyl-β-cyclodextrin (MβCD), a molecule with a high affinity for cholesterol, rapidly depleted cholesterol in adipocytes. Interestingly, MβCD treatment increased adiponectin in the medium without affecting its intracellular level, suggesting a modulation of secretion. By contrast, cholesterol addition did not affect adiponectin secretion, suggesting that cholesterol-depletion-induced intracellular cholesterol trafficking, but not reduced cholesterol level, accounted for MβCD-induced adiponectin secretion. MβCD-induced adiponectin secretion was reduced after 10 μg/mL U18666A treatment that suppressed cholesterol transport out of late endosomes/lysosomes. Depleting Niemann-Pick type C1 (NPC1) or NPC2 proteins, which mediate endosomal/lysosomal cholesterol export, consistently reduced MβCD-induced adiponectin secretion. Furthermore, treatment with 1 μM bafilomycin A1, which neutralized acidic endosomes/lysosomes, also attenuated MβCD-induced adiponectin secretion. Finally, MβCD treatment redistributed cellular adiponectin to lower-density fractions in sucrose gradient fractionation. Our results show that MβCD-mediated cholesterol depletion elevates the secretion of adiponectin, highlighting the involvement of endosomes and lysosomes in adiponectin secretion in adipocytes.

Serum proteomic identification and validation of two novel atherosclerotic aortic aneurysm biomarkers, profilin 1 and complement factor D

BackgroundEffective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis.MethodsWe performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated.ResultsProfilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study.ConclusionPFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.

Neutrophil activation status and low-density neutrophil fractions in patients with coronary artery disease

Neutrophil activation status and low-density neutrophil fractions in patients with coronary artery disease

Observation of severe pediatric inflammatory multisystem syndrome associated with COVID-19

One of the rare manifestations of COVID-19 is pediatric inflammatory multisystem syndrome, most often in publications it is found out how pediatric inflammatory multisystem syndrome in children (РIMS). The progression of the inflammatory response in РIMS may be a consequence of the development of secondary hemophagocytic syndrome, a significant part of which is refractory fever, an increase in ferritin, AST and ALT, cytopenia, an increase in interleukin 6, severe hepatic and neurological dysfunction. The case with this group of representatives of other multiple organ failure manifestations in the detection of acute distress syndrome and acute heart failure, in the detection of the development of myocarditis.&#x0D; A feature of the described clinical detection is the dynamic observation of a severe pediatric multisystem inflammatory syndrome associated with COVID-19, complicated by myocarditis with acute heart failure, left ventricular dysfunction and secondary hemophagocytic syndrome, in an 11-year-old girl with underlying obesity. The child is taking triple therapy with glucocorticosteroids in combination with intravenous immunoglobulin and cyclosporine A, with an expected effect on the ongoing treatment. Possible features of observation are noted: 1) a very early start of РIMS during the acute phase of СOVID-19; 2) transient dyslipidemia at the onset of РIMS with an increase in cholesterol, mainly due to the low-density lipoprotein fraction, and spontaneous regression without lipid-lowering drugs; 3) MRI signs of myocarditis in a month after the onset of the disease, despite the normalization of echocardiography and pro-BNP.

Biomedical consequences of elevated cholesterol-containing lipoproteins and apolipoproteins on cardiovascular and non-cardiovascular outcomes

BackgroundHigher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increase the risk of cardiovascular disease (CVD). The association of LDL-C with non-CVD traits remains unclear, as are the possible independent contributions of other cholesterol-containing lipoproteins and apolipoproteins.MethodsNuclear magnetic resonance spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), as well as low-density lipoprotein fractions, the apolipoproteins Apo-A1 and Apo-B, as well as total triglycerides (TG), remnant-cholesterol (Rem-Chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 outcomes using univariable and multivariable Mendelian randomization (MR).ResultsThe majority of cholesterol containing lipoproteins and apolipoproteins affect coronary heart disease (CHD), carotid intima-media thickness, carotid plaque, C-reactive protein (CRP) and blood pressure. Multivariable MR indicated that many of these effects act independently of HDL-C, LDL-C and TG, the most frequently measured lipid fractions. Higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B increased heart failure (HF) risk; often independently of LDL-C, HDL-C or TG. Finally, a subset of these exposures associated with non-CVD traits such as Alzheimer’s disease (AD: HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (T2DM: VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (IBD: LDL-C, IDL-C).ConclusionsThe cholesterol content of a wide range of lipoprotein and apolipoproteins associate with measures of atherosclerosis, blood pressure, CRP, and CHD, with a subset affecting HF, T2DM, AD and IBD risk. Many of the observed effects appear to act independently of LDL-C, HDL-C, and TG, supporting the targeting of lipid fractions beyond LDL-C for disease prevention.

Protein Biocargo and Anti-Inflammatory Effect of Tomato Fruit-Derived Nanovesicles Separated by Density Gradient Ultracentrifugation and Loaded with Curcumin

Plant-derived nanovesicles (PDNVs) have become attractive alternatives to mammalian cell-derived extracellular vesicles (EVs) both as therapeutic approaches and drug-delivery vehicles. In this study, we isolated tomato fruit-derived NVs and separated them by the iodixanol density gradient ultracentrifugation (DGUC) into twelve fractions. Three visible bands were observed at densities 1.064 ± 0.007 g/mL, 1.103 ± 0.006 g/mL and 1.122 ± 0.012 g/mL. Crude tomato PDNVs and DGUC fractions were characterized by particle size-distribution, concentration, lipid and protein contents as well as protein composition using mass spectrometry-based proteomics. Cytotoxicity and anti-inflammatory activity of the DGUC fractions associated to these bands were assessed in the lipopolysaccharide (LPS)-stimulated human monocytic THP-1 cell culture. The middle and the low-density visible DGUC fractions of tomato PDNVs showed a significant reduction in LPS-induced inflammatory IL-1β cytokine mRNA production. Functional analysis of proteins identified in these fractions reveals the presence of 14-3-3 proteins, endoplasmic reticulum luminal binding proteins and GTP binding proteins associated to gene ontology (GO) term GO:0050794 and the regulation of several cellular processes including inflammation. The most abundant middle-density DGUC fraction was loaded with curcumin using direct loading, sonication and extrusion methods and anti-inflammatory activity was compared. The highest entrapment efficiency and drug loading capacity was obtained by direct loading. Curcumin loaded by sonication increased the basal anti-inflammatory activity of tomato PDNVs.

Effects of Dietary Halloysite Supplementation on Broiler Chicken’s Blood Parameters, Carcass and Meat Quality, and Bone Characteristics: A Preliminary Study

Abstract The aim of this study was to determine the effect of halloysite supplementation to the complete diets for broiler chickens on selected blood parameters, carcass and organ characteristics, as well as bone and meat traits. The trial was conducted under experimental conditions in a large-scale poultry farm on 18,000 broiler chickens. The one-day broiler Ross 308 chicks were randomly divided into two groups: control (C) and experimental (E) in an amount of 9,000 birds per group. In each group, chicks were separated into five pens (100 m2) with 1800 chicks per pen. The birds were fed granulated complete mixtures without (C group) or with halloysite (E group) distributed in an amount of 1% (based on fresh matter) from the 11 d of life. Analysis revealed that halloysite supplementation to the broiler diet at the level of 1% showed a trend (P = 0.056) towards higher final body weight, significantly improved carcass yield (P = 0.048), and reduced the relative weights of the liver and gizzard (P&lt;0.05). No differences (P&gt;0.05) were observed either in terms of the physicochemical parameters of the broiler chickens’ breast muscles, except a significantly lower b* value of the colour parameter (P = 0.048). In turn, in the blood serum, the addition of 1% halloysite significantly decreased (P&lt;0.05) the content of triglycerides and the total cholesterol and low-density lipoprotein fraction, but did not affect (P&gt;0.05) the high-density lipoprotein fraction, calcium, phosphorus or alkaline phosphate content. Tibia and femur characteristics (weight, length, relative bone weight, bone mineral density, bone mineral content, and breaking strength) were not affected (P&gt;0.05) by the usage of halloysite. In conclusion, supplementation of broiler diet with halloysite in the amount of 1% had beneficial effects on the carcass yield and health status of the animals, without any adverse effect on the bone parameters or meat quality of the broiler chickens.

Valorization of South African Coal Wastes through Dense Medium Separation

Sustainable management of coal waste is one of the major environmental concerns for coal mining, whether active or legacy, worldwide. Coal dump deposits demand a large physical area or footprint for disposal of solid waste, change the topography, and generate both pyritic dust and acid rock drainage (ARD) where pyritic coal waste is deposited. The beneficiation of dump deposits or, preferably, of coal waste prior to its dumping can reduce or even eliminate the liabilities related to coal waste management. In this work, dense medium separation studies of coal discards, using heavy liquids, resulted in three pooled fractions from typical South African coal waste discards from the Mpumalanga region for future use: (a) a fraction of low density with increased calorific value; (b) a fraction of intermediate density, rich in ash and acid neutralizing minerals and lower in sulfur; and (c) a fraction of high density, rich in sulfidic minerals including pyrite. The fractions were characterized using particle size analysis, sink-float studies, static tests to predict ARD potential, proximateand ultimate analysis, and gross calorific value. The results showed that approximately 70% of this discard coal is composed of a material of sufficient quality for energy generation in conventional power stations. A pyrite-rich concentrate made up 2% of the total discard mass; comprising more than 45% of the sulfidic mineral present in the feed and displaying no acid neutralizing capacity (ANC). The remaining discard fraction, with intermediate density, presented potential to be used for several ends including soil fabrication, co-disposal or as aggregate material in civil engineering; additional testing to ensure applicability for the selected re-purposing option should be chosen based on proposed use.

The Effect of Physical Separation and Calcination on Enrichment and Recovery of Critical Elements from Coal Gangue

Critical metallic elements in coal gangue have great utilization potential, especially due to the current shortage of these metals. This paper focused on examining the feasibility of physical separation (screening and float-sink tests) and calcination treatment for the enrichment of critical elements (Li, Ga, and rare earth elements plus yttrium (REY)) from coal gangue. The impacts of these enrichment methods on the acid leaching recovery of these elements were then studied. Screening tests indicated that Li and Ga were enriched in &gt;0.125 mm size fraction and the content of REY was highest in &lt;75 μm size fraction. Float-sink tests showed that high-density fractions were enriched in Li and Ga, and low-density fractions were enriched in REY. Physical separation cannot significantly improve the leaching rate of Li, Ga, and REY. Notably, Li, Ga, and REY were enriched significantly, and their acid leaching recoveries were increased by 54~68% after calcination under 400 °C. Sequential chemical extraction tests showed that the majority of insoluble Li, Ga, and REY was converted into soluble forms at the above temperature, which is attributed to the formation of amorphous metakaolinite and the decomposition of organic matter. Based on the results, a conceptually combined flowsheet was proposed for the extraction of Li and Ga from coal gangue.