aggregation

摘要： Parkinson’s disease(PD)is a heterogeneous multifactorial disorder and,during the last years,new scientific evidence has supported this concept.The principal hallmarks of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta and the aggregation of misfolded alpha-synuclein(α-syn).

摘要： Two-dimensional(2D)metal organic frameworks(MOFs)are emerging as low-cost oxygen evolution reaction(OER)electrocatalysts,however,suffering aggregation and poor operation stability.Herein,ultrafine Fe_(3)O_(4) nanoparticles(diameter:6±2 nm)are homogeneously immobilized on 2D Ni based MOFs(Ni-BDC,thickness:5±1 nm)to improve the OER stability.Electronic structure modulation for enhanced catalytic activity is studied via adjusting the amount of Fe_(3)O_(4) nanoparticles on Ni-BDC.The optimal Fe_(3)O_(4)/Ni-BDC achieves the best OER performance with an overpotential of 295 mV at 10 mA cm^(-2),a Tafel slope of 47.8 mV dec^(-1) and a considerable catalytic durability of more than 40 h(less than 5 h for Ni-BDC alone).DFT calculations confirm that the active sites for Fe_(3)O_(4)/Ni-BDC are mainly contributed by Fe species with a higher oxidation state,and the potential-determining step(PDS)is the formation of the adsorbed O*species,which are facilitated in the composite.

摘要： Inhibition of protein misfolding and aggregation is a great challenge in the field of biochemical and biopharmaceutical engineering.Alzheimer’s disease(AD)is a protein-misfolding disease,and the interactions between 40-amino-acid-residueβ-amyloid peptide(Aβ_(40)) and its N-terminal truncated peptide Aβ_(11-40) demonstrate that Aβ_(11-40) may play an important role in the pathological process of AD.However,the effect of inhibitors on Aβ_(11-40) aggregation and on the cross-amyloid aggregation(coassembly)between Aβ_(40) and Aβ_(11-40) has never been studied.Herein,coaggregation and seeding interactions between Aβ_(40) and Aβ_(11-40) as well as the effect of epigallocatechin gallate(EGCG),a small molecule inhibitor,on the cross-amyloid aggregation have been investigated by extensive analyses.It is found that Aβ_(11-40) participates in the aggregation of Aβ_(40) and leads to the formation of coaggregates that contain lessβ-sheet structures than pure Aβ_(40) aggregates.The aggregation kinetics along with morphologies and secondary structures of the coaggregates are also significantly affected by the Aβ_(40)/Aβ_(11-40) ratio.EGCG accelerates the nucleation of Aβ_(40) but retards that of Aβ_(11-40) by affecting their elongation and secondary nucleation processes in solution and on solid surfaces.Meanwhile,EGCG makes the conformations of the seeding-induced Aβaggregates more compact,especially for the homologous seedings.Isothermal titration calorimetry measurement indicates that hydrophobic interactions mainly contribute to the inhibition of the two Aβisoforms by EGCG.The findings of this research have provided new insights into Aβaggregation and the effect of an important inhibitor and the results would benefit in the development of potent inhibitors against co-assembly of different amyloid proteins.

摘要： In this study, a point source mathematical model is proposed to describe the diffusion of adenosine di-phosphate (ADP) from either damaged red blood cell (RBC) or activated platelet. The convective diffusion equation is reduced to describe the suggested problem. The final differential equation is solved using Laplace transforms and ADP concentration profiles around the source are obtained. Thrombi of 5 to 20 μm3 containing platelets and a range of red blood cells (RBCs) (0%, 25%, 50%, 75%, 100%) concentrations are used to apply the model. Reported ADP concentrations in the literature are used and its dynamic release from the point source is calculated. Results suggest that RBC chemical contribution to platelet aggregation in the bulk is much less than that of platelet (almost) negligible. However, the physical effect of RBCs is dominant in the bulk through augmentation of released ADP and platelets diffusivities. Moreover, the chemical contribution reported in previous studies is suggested to be as a result of interaction of RBC with the surface under the influence of shear stresses in the boundary region.

摘要： Protein aggregation is a hallmark of multiple human pathologies.Autophagy selectively degrades protein aggregates via aggrephagy.How selectivity is achieved has been elusive.Here,we identify the chaperonin subunit CCT2 as an autophagy receptor regulating the clearance of aggregation-prone proteins in the cell and the mouse brain.CCT2 associates with aggregation-prone proteins independent of cargo ubiquitination and interacts with autophagosome marker ATG8s through a non-classical VLIR motif.In addition,CCT2 regulates aggrephagy independently of the ubiquitin-binding receptors(P62,NBR1,and TAX1BP1)or chaperone-mediated autophagy.Unlike P62,NBR1,and TAX1BP1,which facilitate the clearance of protein condensates with liquidity,CCT2 specifically promotes the autophagic degradation of protein aggregates with little liquidity(solid aggregates).Furthermore,aggregation-prone protein accumulation induces the functional switch of CCT2 from a chaperone subunit to an autophagy receptor by promoting CCT2 monomer formation,which exposes the VLIR to ATG8s interaction and,therefore,enables the autophagic function.

摘要： Regulating the catalytic activity of nanozymes is significant for their applications in various fields.Here,we demonstrate a new strategy to achieve reversible regulation of the nanozyme’s activity for sensing purpose.This strategy involves the use of zero-dimensional MoS;quantum dots(MQDs)as the building blocks of nanozymes which display very weak peroxidase(POD)-like activity.Interestingly,such POD-like activity of the MQDs largely enhances in the presence of Fe;while diminishes with the addition of captopril thereafter.Further investigations identify the mechanism of Fe;-mediated aggregation-induced enhancement of the POD-like activity and the inhibitory effect of captopril on the enhancement,which is highly dependent on their concentrations.Based on this finding,a colorimetric method for the detection of captopril is developed.This sensing approach exhibits the merits of simplicity,rapidness,reliability,and low cost,which has been successfully applied in quality control of captopril in pharmaceutical products.Moreover,the present sensing platform allows smartphone read-out,which has promising applications in point-of-care testing devices for clinical diagnosis and drug analysis.

摘要： Type 2 diabetes mellitus(T2DM)and other metabolic disorders are often silent and go unnoticed in patients because of the lack of suitable prognostic and diagnostic markers.The current therapeutic regimens available for managing T2DM do not reverse diabetes;instead,they delay the progression of diabetes.Their efficacy(in principle)may be significantly improved if implemented at earlier stages.The misfolding and aggregation of human islet amyloid polypeptide(hIAPP)or amylin has been associated with a gradual decrease in pancreatic b-cell function and mass in patients with T2DM.Hence,hIAPP has been recognized as a therapeutic target for managing T2DM.This review summarizes hIAPP's role in mediating dysfunction and apoptosis in pancreatic b-cells via induction of endoplasmic reticulum stress,oxidative stress,mitochondrial dysfunction,inflammatory cytokine secretion,autophagy blockade,etc.Furthermore,it explores the possibility of using intermediates of the hIAPP aggregation pathway as potential drug targets for T2DM management.Finally,the effects of common antidiabetic molecules and repurposed drugs;other hIAPP mimetics and peptides;small organic molecules and natural compounds;nanoparticles,nanobodies,and quantum dots;metals and metal complexes;and chaperones that have demonstrated potential to inhibit and/or reverse hIAPP aggregation and can,therefore,be further developed for managing T2DM have been discussed.

摘要： CdO(cadmium oxide)nanoparticles show a strong peak of Plasmon absorption in ultraviolet-visible zone.A strong interaction exists between the surface of CdO nanoparticles and aryl mercaptan compounds.Aryl mercaptan compounds cause aggregation of CdO nanoparticles linked to DNA/RNA(eoxyribonucleic acid/ribonucleic acid)and hence,lead to widening of peak Plasmon of CdO nanoparticles surface at 550 nm and emerge a new peak at higher wavelength.In the current project,this optical characteristic of CdO nanoparticles is used to investigate interaction time between different aryl mercaptanes and CdO nanoparticles.The results showed that aryl mercaptan compounds with shorter chain length interact faster with CdO nanoparticles.Therefore,a simple and fast method for identification of aryl mercaptanes with various chain lengths using red shift in surficial Plasmon absorption is presented.

摘要： To investigate the morphological evolution of the whole growth and aggregation processes of hydrate crystals near the gas–liquid interface,we used a high-pressure visual reactor with high-speed camera to capture the micromorphology of hydrate particles in a natural gas+pure water system with pressure from 2.6 to 3.6 MPa and sub-cooling from 4.7 to 6.23C.The results showed that under low sub-cooling conditions,the amount and size of particles increased first and then decreased in the range of 0–330 lm,and the small particles always dominated.These particles can be roughly classified into two categories:planar flake particles and polyhedral solid particles.Then,the concept of maximum growth dominant particle size was proposed to distinguish the morphological boundary of growth and aggregation.In addition,the micro model was established to better reflect the effects of particle formation process and evolution mechanism near the gas–liquid interface under stirring condition.The results of this study can provide a guidance for flow assurance in multiphase pipeline.

摘要： Federated learning aims to collaboratively train a machine learning model with possibly geo-distributed workers,which is inherently communication constrained.To achieve communication efficiency,the conventional federated learning algorithms allow the worker to decrease the communication frequency by training the model locally for multiple times.Conventional federated learning architecture,inherited from the parameter server design,relies on highly centralised topologies and large nodes-to-server bandwidths,and convergence property relies on the stochastic gradient descent training in local,which usually causes the large end-to-end training latency in real-world federated learning scenarios.Thus,in this study,the authors propose the adaptive partial gradient aggregation method,a gradient partial level decentralised federated learning,to tackle this problem.In FedPGA,they propose a partial gradient exchange mechanism that makes full use of node-to-node bandwidth for speeding up the communication time.Besides,an adaptive model updating method further reduces the convergence rate by adaptive increasing the step size of the stable direction of gradient descent.The experimental results on various datasets demonstrate that the training time is reduced up to 14×compared to baselines without accuracy degrade.