Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity

Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored with insulin in pancreatic cells and also co-secreted to the circulation, is associated with beta-cell death in type-2 diabetes (T2D). In T2D patients IAPP is found aggregating in the extracellular space of the islets of Langerhans. Although the physiological environments of these intra- and extra-cellular compartments and vascular systems significantly differ, the presence of proteins is ubiquitous but the effects of protein binding on IAPP aggregation are largely unknown. Here we examined the binding of freshly-dissolved IAPP as well as pre-formed fibrils with two homologous proteins, namely cationic lysozyme (Lys) and anionic alpha-lactalbumin (aLac), both of which can be found in the circulation. Biophysical characterizations and a cell viability assay revealed distinct effects of Lys and aLac on IAPP amyloid aggregation, fibril remodelling and cytotoxicity, pointing to the role of protein “corona” in conferring the biological impact of amyloidogenic peptides. Systematic molecular dynamics simulations further provided molecular and structural details for the observed differential effects of proteins on IAPP amyloidosis. This study facilitates our understanding of the fate and transformation of IAPP in vivo, which are expected to have consequential bearings on IAPP glycemic control and T2D pathology

Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity

Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored with insulin in pancreatic cells and also co-secreted to the circulation, is associated with beta-cell death in type-2 diabetes (T2D). In T2D patients IAPP is found aggregating in the extracellular space of the islets of Langerhans. Although the physiological environments of these intra- and extra-cellular compartments and vascular systems significantly differ, the presence of proteins is ubiquitous but the effects of protein binding on IAPP aggregation are largely unknown. Here we examined the binding of freshly-dissolved IAPP as well as pre-formed fibrils with two homologous proteins, namely cationic lysozyme (Lys) and anionic alpha-lactalbumin (aLac), both of which can be found in the circulation. Biophysical characterizations and a cell viability assay revealed distinct effects of Lys and aLac on IAPP amyloid aggregation, fibril remodelling and cytotoxicity, pointing to the role of protein “corona” in conferring the biological impact of amyloidogenic peptides. Systematic molecular dynamics simulations further provided molecular and structural details for the observed differential effects of proteins on IAPP amyloidosis. This study facilitates our understanding of the fate and transformation of IAPP in vivo, which are expected to have consequential bearings on IAPP glycemic control and T2D pathology

Research on correlation between dynamic resilient modulus and CBR of coarse-grained chlorine saline soil

Abstract A large area of coarse-grained saline soil is distributed in saline soil areas, and chlorine saline soil with a high salt content is a typical representative. The dynamic resilient modulus was accurately predicted using the California-bearing ratio (CBR) value to determine the relationship between the dynamic resilient modulus of coarse-grained chloride saline soil and its CBR value. Indoor dynamic triaxial tests and CBR tests were conducted to investigate the evolution of the dynamic resilient modulus (M R) and CBR of coarse-grained chlorine saline soil under the influence of the stress level, water content, and salt content. The test results showed that the dynamic resilient modulus increased with an increase in the confining pressure and bulk stress and decreased as the deviator stress increased; however, the CBR increased with an increase in the corresponding unit pressure. The higher the salt and water contents, the more obvious the influence of stress on the dynamic resilient modulus and CBR value. Under the same stress level, the decrease in the dynamic resilient modulus and CBR gradually increased with increasing salt and moisture content, and the effect of salt tended to be more significant than that of water. Based on the correlation between the dynamic resilient modulus and CBR revealed by the experiment, a more widely applicable model was selected from the existing theoretical models related to CBR for the regression analysis of the test data, and a prediction model of the dynamic resilient modulus based on the CBR value was proposed (M R = 21.06CBR 0.52). This prediction model had a high correlation coefficient (R 2 = 0.893) and could effectively predict the dynamic resilient modulus of coarse-grained chlorine saline soil using CBR values. The results provide a simple and reliable method for determining the design parameters of a coarse-grained saline soil subgrade

Experimental Study on the Strength and Hydration Products of Cement Mortar with Hybrid Recycled Powders Based Industrial-Construction Residue Cement Stabilization of Crushed Aggregate

The strength-formation mechanism for industrial-construction residue cement stabilization of crushed aggregate (IRCSCA) is not clear. To expand the application range for recycled micro-powders in road engineering, the dosages of eco-friendly hybrid recycled powders (HRPs) with different proportions of RBP and RCP affecting the strengths of cement-fly ash mortar at different ages, and the strength-formation mechanism, were studied with X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results showed that the early strength of the mortar was 2.62 times higher than that of the reference specimen when a 3/2 mass ratio of brick powder and concrete powder was mixed to form the HRP and replace some of the cement. With increasing HRP content substituted for fly ash, the strength of the cement mortar first increased and then decreased. When the HRP content was 35%, the compressive strength of the mortar was 1.56 times higher than that of the reference specimen, and the flexural strength was 1.51 times higher; XRD and SEM studies of the hydrated cement mixed with HRP showed that the amount of CH in the cement paste was reduced by the pozzolanic reaction of HRP at later hydration ages, and it was very useful in improving the compactness of the mortar. The XRD spectrum of the cement paste made with HRP indicated that the CH crystal plane orientation index R, with a diffraction angle peak of approximately 34.0, was consistent with the cement slurry strength evolution law, and this research provides a reference for the application of HRP to produce IRCSCA

Lysophosphatidylcholine modulates the aggregation of human islet amyloid polypeptide

Amyloid aggregation of human islet amyloid polypeptide (IAPP) is a hallmark of type 2 diabetes (T2D), a metabolic disease and a global epidemic. Although IAPP is synthesized in pancreatic β-cells, its fibrils and plaques are found in the extracellular space indicating a causative transmembrane process. Numerous biophysical studies have revealed that cell membranes as well as model lipid vesicles promote the aggregation of amyloid-β (associated with Alzheimer's), α-synuclein (associated with Parkinson's) and IAPP, through electrostatic and hydrophobic interactions between the proteins/peptides and lipid membranes. Using a thioflavin T kinetic assay, transmission electron microscopy, circular dichroism spectroscopy, discrete molecular dynamics simulations as well as free energy calculations here we show that micellar lysophosphatidylcholine (LPC), the most abundant lysophospholipid in the blood, inhibited the amyloid aggregation of IAPP through nonspecific interactions while elevating the α-helical peptide secondary structure. This surprising finding suggests a native protective mechanism against IAPP aggregation in vivo

Differential effects of silver and iron oxide nanoparticles on IAPP amyloid aggregation

Recent studies have shown promise on the use of small molecules and nanoparticles (NPs) for the inhibition of protein aggregation, a hallmark of neurodegenerative diseases and type 2 diabetes (T2D). Towards this end here we show the differential effects of silver and iron oxide nanoparticles (AgNPs and IONPs) on the mesoscopic properties of human islet amyloid polypeptide (IAPP) aggregation associated with T2D. Both citrate-and branched polyethyleneimine-coated AgNPs (c-AgNPs, bPEI-AgNPs) inhibited IAPP aggregation at 500 mu g mL(-1), likely through electrostatic attraction and sequestering of IAPP monomers from fibrillation. In comparison, bare, brushed polyethylene glycol-and phosphorylcholine-grafted IONPs (bPEG-IONPs, bPC-IONPs) at 500 mu g mL(-1) elicited no major effect on IAPP fibril contour length, while bPC-IONPs induced significant fibril softening and looping likely mediated by dipolar interactions. While monovalent Ag+ up to 50 mu g mL(-1) showed no effect on the contour length or stiffness of IAPP fibrils, multivalent Fe3+ at 5 mu g mL(-1) halted IAPP fibrillation likely through ion-peptide crosslinking. Except bPEI-AgNPs, all three types of IONPs and c-AgNPs at 100 mu g mL(-1) alleviated IAPP toxicity in HEK293 cells indicating no clear correlation between protein aggregation and their induced cytotoxicity. This study demonstrates the complexity of protein aggregation intervened by NPs of different physicochemical properties and - together with existing literature - facilitates nanotechnological applications for mitigating amyloid-mediated pathologies

Isolation and characterization of bacterial cellulose produced from soybean whey and soybean hydrolyzate

Abstract Soybean whey and soybean hydrolyzate can be used for the biotechnological production of high-value products. Herein, we isolate soybean whey (SW)-and soybean hydrolyzate (SH)-derived bacterial cellulose (BC, produced by kombucha) and characterize it by a range of instrumental techniques to reveal differences in micromorphology, crystallinity, and themal behavior. Studies have shown that the amounts of wet state BC produced from HS, SW and SH was 181 g/L, 47 g/L and 83 g/L, respectively. The instrumental analysis of BC, included SEM, AFM, FT-IR, XRD and TGA. It is shown that the FT-IR spectra of BC have a similar character, but we found differences in the micromorphology,crystallinity and thermal temperature of BC. The minimum average widths of the fibers produced from SH medium was 100 ± 29 nm. The CrI values of BC produced from SH medium was 61.8%. The maximum thermal degradation rate temperature of BC produced from SW medium was 355.73 °C. The combined results demonstrate that soybean industrial waste can be used as a cost-effective raw material for BC production

Effects of Exogenous Application of Glycine Betaine Treatment on ‘Huangguoggan’ Fruit during Postharvest Storage

Loss of quality in citrus fruit is a common occurrence during postharvest storage due to oxidative stress and energy consumption. In recent years, glycine betaine (GB) has been widely applied to postharvest horticulture fruit. This study aimed to investigate the effect of GB treatment (10 mM and 20 mM) on the quality and antioxidant activity of ‘Huangguogan’ fruit during postharvest storage at room temperature. Our results indicated that both 10 mM and 20 mM treatments effectively reduced weight and firmness losses and maintained total soluble solid (TSS), titratable acidity (TA), and ascorbic acid contents. Additionally, GB treatment significantly increased the activity of antioxidant enzymes, maintained higher levels of total phenols and total flavonoids, and led to slower accumulation of H2O2. A transcriptome analysis conducted at 28 days after treatment (DAT)identified 391 differentially expressed genes (DEGs) between 20 mM GB (GB-2) and the control (CK) group. These DEGs were enriched in various pathways, particularly related to oxygen oxidoreductase, peroxidase activity, and flavonoid biosynthesis. Overall, the application of GB proved beneficial in enhancing the storability and extending the shelf life of ‘Huangguogan’ fruit

Human plasma proteome association and cytotoxicity of nano-graphene oxide grafted with stealth polyethylene glycol and poly(2-ethyl-2-oxazoline)

Polyethylene glycol (PEG) is a gold standard against protein fouling. However, recent studies have revealed surprising adverse effects of PEG, namely its immunogenicity and shortened bio-circulation upon repeated dosing. This highlights a crucial need to further examine ‘stealth’ polymers for controlling the protein ‘corona’, a new challenge in nanomedicine and bionanotechnology. Poly(2-ethyl-2-oxazoline) (PEtOx) is another primary form of stealth polymer that, despite its excellent hydrophilicity and biocompatibility, has found considerably less applications compared with PEG. Herein, we performed label-free proteomics to compare the associations of linear PEG- and PEtOx-grafted nano-graphene oxide (nGO) sheets with human plasma proteins, complemented by cytotoxicity and haemolysis assays to compare the cellular interactions of these polymers. Our data revealed that nGO-PEG enriched apolipoproteins, while nGO-PEtOx displayed a preferred binding with pro-angiogenic and structural proteins, despite high similarities in their respective top-10 enriched proteins. In addition, nGO-PEG and nGO-PEtOx exhibited similar levels of enrichment of complement proteins. Both PEG and PEtOx markedly reduced nGO toxicity to HEK 293 cells while mitigating nGO haemolysis. This study provides the first detailed profile of the human plasma protein corona associated with PEtOx-grafted nanomaterials and, in light of the distinctions of PEtOx in chemical adaptability, in vivo clearance and immunogenicity, validates the use of PEtOx as a viable stealth alternative to PEG for nanomedicines and bionanotechnologies

Low‐voltage DC building distribution and utilization system and its implementation in China southern grid

Abstract The demand‐side DC electricity‐using equipment and newly integrated renewables are driving the transformation of power distribution and utilization mode. The building system based on DC technology is emerging as a promising option. In the low‐voltage DC building distribution and utilization system (LVDCBDUS), global energy optimization management and operational control arrangement are key components. To obtain exemplary achievements of those, two different DC building energy management system (DC BEMS) integration schemes are investigated according to the respective features and application‐required functions of various system networking structures. Centralized and decentralized control strategies are presented and discussed for buildings with AC–DC transformation and newly built LVDCBDUSs. On this basis, the centralized DC BEMS and operational control strategy are applied to the first multi‐scenario low‐carbon city‐based future building project—Shenzhen IBR Future Complex. The operation data are recorded and analysed. Problems encountered during the implementation are summarized, and requirements of converter equipment, new technologies and marketization are further discussed to promote the high‐quality development of the LVDCBDUS