Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome

The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology affects the metabolome is still not understood nor is it known how disturbances change as the disease progresses. For the first time, we have profiled longitudinally (6, 8, 10, 12, and 18 months) both the brain and plasma metabolome of APPswe/PS1deltaE9 double transgenic and wild-type mice. A total of 187 metabolites were quantified using a targeted metabolomic methodology. Multivariate statistical analysis produced models that distinguished APPswe/PS1deltaE9 from wild-type mice at 8, 10, and 12 months. Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids, branched-chain amino acids, and also in the neurotransmitter serotonin. Pronounced imbalances in phospholipid and acylcarnitine homeostasis were evident in 2 age groups. AD-like pathology, therefore, affects greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood

Anti-leukaemia and anti-bacterial activity

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An investigation of the blood metabolome of healthy elderly subjects reveals significant age-dependent alterations.

A zirconia-yttria gel, made by coprecipitation, was treated in six different ways to obtain a nanocrystalline Y-TZP powder: one large gel batch was split into six parts of which one was crystallized in air and the others crystallized either in water with a high pH or in methanol. The batches were subjected to several post treatments. Powder properties and densification characteristics of the six powder batches obtained in this way are described. The aircalcined powder can be sintered to a relative density of about 93% at 1070 °C/10 h, but reproducibility of the sintering characteristics is poor. Optimal hydrothermal treatment of the powder yields a reproducible sintering process, resulting in a relative density of 96% at 1070 °C/10 h and an average grain size between 120 and 130 nm

Evidence That Parietal Lobe Fatty Acids May Be More Profoundly Affected in Moderate Alzheimer’s Disease (AD) Pathology Than in Severe AD Pathology

Brain is a lipid-rich tissue, and fatty acids (FAs) play a crucial role in brain function, including neuronal cell growth and development. This study used GC-MS to survey all detectable FAs in the human parietal cortex (Brodmann area 7). These FAs were accurately quantified in 27 cognitively normal age-matched controls, 16 cases of moderate Alzheimer’s disease (AD), 30 severe AD, and 14 dementia with Lewy bodies (DLB). A total of 24 FA species were identified. Multiple comparison procedures, using stepdown permutation tests, noted higher levels of 13 FAs but the majority of changes were in moderate AD and DLB, rather than severe AD. Subjects with moderate AD and DLB pathology exhibited significantly higher levels of a number of FAs (13 FAs and 12 FAs, respectively). These included nervonic, lignoceric, cis-13,16-docosadienoic, arachidonic, cis-11,14,17-eicosatrienoic, erucic, behenic, α-linolenic, stearic, oleic, cis-10-heptanoic, and palmitic acids. The similarities between moderate AD and DLB were quite striking—arachidic acid was the only FA which was higher in moderate AD than control, and was not similarly affected in DLB. Furthermore, there were no significant differences between moderate AD and DLB. The associations between each FA and a number of variables, including diagnosis, age, gender, Aβ plaque load, tau load, and frontal tissue pH, were also investigated. To conclude, the development of AD or DLB pathology affects brain FA composition but, intriguingly, moderate AD neuropathology impacts this to a much greater extent. Post-mortem delay is a potential confounding factor, but the findings here suggest that there could be a more dynamic metabolic response in the earlier stages of the disease pathology

First case report of PLA2R-related monotypic (IgG-κ positive) membranous nephropathy concurrent with leukocyte chemotactic factor 2 amyloidosis

Abstract Background Membranous nephropathy (MN) is a major pattern of nephrotic syndrome (NS) in adults. Some MN have secondary causes and some may be accompanied with other glomerular diseases. MN patients coexisting with amyloidosis are very rare, and mostly was polytypic MN. Herein, we describe the first report which identifying monotype PLA2R-MN (κ light chain) concurrent with leukocyte chemotactic factor 2 amyloidosis (ALECT2). This rare case highlights the importance of renal pathology for diagnosis. Case presentation We describe a case of a 60-year-old male patient with persistent proteinuria and low serum albumin for nine months. No monoclonal component was revealed by serum and urine immunofixation electrophoresis but serum PLA2R antibody was positive. The patient was empirically treated with Leflunomide and Losartan, but edema was not improved. The diagnosis of renal pathology is PLA2R-related monotypic (IgG-κ positive) MN concurrent with ALECT2. Methylprednisolone, cyclosporine A and anticoagulant (rivaroxaban) were prescribed resulting in a complete remission of NS. Conclusions MN patients concurrent with ALECT2 presented massive proteinuria or NS. When nephrotic range proteinuria is present in ALECT2, it is important to consider that it may be due to a concomitant underlying nephropathy especially MN and treated according to MN will get good therapeutic effect

Thermodynamic Design and Performance Calculation of the Thermochemical Reformers

Thermodynamic design methods and performance calculation models for chemical reformers that can be used to recuperate exhaust heat and to improve combustion quality are investigated in this paper. The basic structure of the chemical reformer is defined as series-wound reforming units that consist of heat exchangers and cracking reactors. The CH4-steam reforming reaction is used in the chemical reformers and a universal model of this reaction is built based on the minimization of Gibbs free energy method. Comparative analyzes between the results of the calculation and a plasma-catalyzed CH4-steam reforming reaction experiment verify that this universal model is applicable and has high precision. Algorithms for simulation of series-wound reforming units are constructed and the complexity of the chemical reformers is studied. A design principle that shows the influence of structural complexity on the quantity of recovered heat and the composites of the reformed fuel can be followed for different application scenarios of chemical reformers

Sliding window soft-SCL decoders for asynchronous polar-coded modulation

Asynchronous polar-coded modulation (A-PCM) outperforms multilevel polar-coded modulation by taking advantage of spatial coupling among several coded blocks. To further improve the performance of A-PCM, a cyclic-redundancy-check (CRC) aided sliding window soft successive cancellation list (CA-SWSCL) decoder is proposed to exploit the benefits of spatial coupling and CRC-aided iterative message passing. This approach includes both soft-output and hard-output iteration processes, where the CRC results are not only used for early termination but also served as an execution flag of the hard-output iteration process. In the case of rate half polar-coded modulation with frame length 128, A-PCM with the proposed CA-SWSCL achieves the best block-error-rate (BLER) performance among the state-of-art polar-coded modulation schemes.This work was partially supported by National Key Research and Development Project (2020YFB1806805)