Hippocampal Synaptic and Neural Network Deficits in Young Mice Carrying the Human APOE4 Gene

Introduction: Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset sporadic Alzheimer disease. Emerging evidence demonstrates a hippocampus-associated learning and memory deficit in aged APOE4 human carriers and also in aged mice carrying human APOE4 gene. This suggests that either exogenous APOE4 or endogenous APOE4 alters the cognitive profile and hippocampal structure and function. However, little is known regarding how Apoe4 modulates hippocampal dendritic morphology, synaptic function, and neural network activity in young mice. Aim: In this study, we compared hippocampal dendritic and spine morphology and synaptic function of young (4 months) mice with transgenic expression of the human APOE4 and APOE3 genes. Methods: Hippocampal dendritic and spine morphology and synaptic function were assessed by neuronal imaging and electrophysiological approaches. Results: Morphology results showed that shortened dendritic length and reduced spine density occurred at hippocampal CA1 neurons in Apoe4 mice compared to Apoe3 mice. Electrophysiological results demonstrated that in the hippocampal CA3-CA1 synapses of young Apoe4 mice, basic synaptic transmission, and paired-pulse facilitation were enhanced but long-term potentiation and carbachol-induced hippocampal theta oscillations were impaired compared to young Apoe3 mice. However, both Apoe genotypes responded similarly to persistent stimulations (4, 10, and 40 Hz for 4 seconds). Conclusion: Our results suggest significant alterations in hippocampal dendritic structure and synaptic function in Apoe4 mice, even at an early age

Persistent Tissue Kinetics and Redistribution of Nanoparticles, Quantum Dot 705, in Mice: ICP-MS Quantitative Assessment

Background: Quantum dots (QDs) are autofluorescent semiconductor nanocrystals that can be used for in vivo biomedical imaging. However, we know little about their in vivo disposition and health consequences. Objectives: We assessed the tissue disposition and pharmacokinetics of QD705 in mice. Methods: We determined quantitatively the blood and tissue kinetics of QD705 in mice after single intravenous (iv) injection at the dose of 40 pmol for up to 28 days. Inductively coupled plasma–mass spectrometry (ICP-MS) measurement of cadmium was the primary method of quantification of QD705. Fluorescence light microscopy revealed the localization of QD705 in tissues. Results: Plasma half-life of QD705 in mice was short (18.5 hr), but ICP-MS analyses revealed QD705 persisted and even continued to increase in the spleen, liver, and kidney 28 days after an iv dose. Considerable time-dependent redistribution from body mass to liver and kidney was apparent between 1 and 28 days postdosing. The recoveries at both time points were near 100%; all QD705s reside in the body. Neither fecal nor urinary excretion of QD705 was detected appreciably in 28 days postdosing. Fluorescence microscopy demonstrated deposition of QD705 in the liver, spleen, and kidneys. Conclusion: Judging from the continued increase in the liver (29–42% of the administered dose), kidney (1.5–9.2%), and spleen (4.8–5.2%) between 1 and 28 days without any appreciable excretion, QD705 has a very long half-life, potentially weeks or even months, in the body and its health consequences deserve serious consideration

Sub-rapid solidification microstructure characteristics and control mechanisms of twin-roll cast aluminum alloys: A review

Rapid growth in industrial sectors such as automotive and shipbuilding has highlighted the significance of strip casting technology to produce lightweight alloys, particularly aluminum alloys widely used in both industrial production and daily life. Twin-roll casting (TRC), as an economically and environmentally friendly method for slab/strip production and processing, has attracted significant interest from researchers. However, the development of TRC aluminum alloys faces many challenges due to limited understanding of microstructural characteristics and control mechanisms. To further enhance comprehension of TRC aluminum alloys, this article reviews the influencing parameters, control methods, and existing issues related to TRC sub-rapid solidification (SRS) microstructure. It firstly summarizes TRC equipment types and their solidification characteristics, followed by a detailed analysis on key parameters affecting the evolution of TRC microstructure including rolling speed, roll separation force (RSF), and heat transfer coefficient (HTC). Finally, solutions to TRC defects are summarized and evaluated alongside their underlying mechanisms. This article provides a comprehensive review of the characteristics and control mechanisms of TRC microstructure while offering valuable insights for the future production of high-quality TRC aluminum strips

Inelastic J/ψJ/\psi production in polarized photon-hadron collisions

Presented here is a calculation of inelastic $J/\psi$ production in polarized photon-hadron collisions under the framework of NRQCD factorization formalism. We consider the photoproduction of \jpsi in the energy range relevant to HERA. The Weizs\"acker-Williams approximation is adopted in the evaluation of the cross sections for $ep$ collisions. We found that this process can give another independent test for the color-octet mechanism, and the different features for the two color-octet processes may provide further informations on the mechanism for inelastic \jpsi photoproduction. And the discrepancy on the production asymmetry $A$ between various sets of polarized gluon distribution functions is also found to be distinctive.Comment: 14pages, 6 PS figure

Toward Stretchable Self-Powered Sensors Based on the Thermoelectric Response of PEDOT:PSS/Polyurethane Blends

The development of new flexible and stretchable sensors addresses the demands of upcoming application fields like internet‐of‐things, soft robotics, and health/structure monitoring. However, finding a reliable and robust power source to operate these devices, particularly in off‐the‐grid, maintenance‐free applications, still poses a great challenge. The exploitation of ubiquitous temperature gradients, as the source of energy, can become a practical solution, since the recent discovery of the outstanding thermoelectric properties of a conductive polymer, poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS). Unfortunately the use of PEDOT:PSS is currently constrained by its brittleness and limited processability. Herein, PEDOT:PSS is blended with a commercial elastomeric polyurethane (Lycra), to obtain tough and processable self‐standing films. A remarkable strain‐at‐break of ≈700% is achieved for blends with 90 wt% Lycra, after ethylene glycol treatment, without affecting the Seebeck voltage. For the first time the viability of these novel blends as stretchable self‐powered sensors is demonstrated

Solar-thermal conversion and steam generation: a review

Recently, steam generation systems based on solar-thermal conversion have received much interest, and this may be due to the widespread use of solar energy and water sources such as oceans and lakes. The photo-thermal desalination system becomes attractive as it can convert absorbed solar light energy into thermal energy and realise the desalination and water purification of saline water through the evaporation process. In this paper, the research status of solar-thermal conversion materials such as metal-based materials, semiconductor materials, carbon-base materials, organic polymer materials, composite photo-thermal materials and their solar-thermal conversion mechanism in recent years are reviewed. The physical process and evaluation principle of solar-thermal conversion are both carefully introduced. The methods of optimising thermal management and increasing the evaporation rate of a hybrid system are also introduced in detail. Four main applications of solar-thermal conversion technologies (seawater desalination, wastewater purification, sterilisation and power generation) are discussed. Finally, based on the above analysis, the prospects and challenges for future research in the field of desalination are discussed from an engineering and scientific viewpoint to promote the direction of research, in order to stimulate future development and accelerate commercial application

KIF5A upregulation in hepatocellular carcinoma: A novel prognostic biomarker associated with unique tumor microenvironment status

Liver hepatocellular carcinoma (LIHC) is one of the most common liver malignancies with high mortality and morbidity. Thus, it is crucial to identify potential biomarker that is capable of accurately predicting the prognosis and therapeutic response of LIHC. Kinesin family member 5A (KIF5A) is a microtubule-based motor protein involved in the transport of macromolecules such as organelle proteins in cells. Recent studies have illustrated that the high expression of KIF5A was related to poor prognosis of solid tumors, including bladder cancer, prostate cancer, and breast cancer. However, little is currently known concerning the clinical significance of KIF5A expression in LIHC. Herein, by adopting multi-omics bioinformatics analysis, we comprehensively uncovered the potential function and the predictive value of KIF5A in stratifying clinical features among patients with LIHC, for which a high KIF5A level predicted an unfavorable clinical outcome. Results from KIF5A-related network and enrichment analyses illustrated that KIF5A might involve in microtubule-based process, antigen processing and presentation of exogenous peptide antigen via MHC class II. Furthermore, immune infiltration and immune function analyses revealed upregulated KIF5A could predict a unique tumor microenvironment with more CD8+T cells and a higher level of anti-tumor immune response. Evidence provided by immunohistochemistry staining (IHC) further validated our findings at the protein level. Taken together, KIF5A might serve as a novel prognostic biomarker for predicting immunotherapy response and could be a potential target for anti-cancer strategies for LIHC

Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain

Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro

Purification and Characterization of Enterovirus 71 Viral Particles Produced from Vero Cells Grown in a Serum-Free Microcarrier Bioreactor System

[[abstract]]Background: Enterovirus 71 (EV71) infections manifest most commonly as a childhood exanthema known as hand-foot-and-mouth disease (HFMD) and can cause neurological disease during acute infection. Principal Finding: In this study, we describe the production, purification and characterization of EV71 virus produced from Vero cells grown in a five-liter serum-free bioreactor system containing 5 g/L Cytodex 1 microcarrier. The viral titer was >106 TCID50/mL by 6 days post infection when a MOI of 10?5 was used at the initial infection. Two EV71 virus fractions were separated and detected when the harvested EV71 virus concentrate was purified by sucrose gradient zonal ultracentrifugation. The EV71 viral particles detected in the 24–28% sucrose fractions had an icosahedral structure 30–31 nm in diameter and had low viral infectivity and RNA content. Three major viral proteins (VP0, VP1 and VP3) were observed by SDS-PAGE. The EV71 viral particles detected in the fractions containing 35–38% sucrose were 33–35 nm in size, had high viral infectivity and RNA content, and were composed of four viral proteins (VP1, VP2, VP3 and VP4), as shown by SDS-PAGE analyses. The two virus fractions were formalin-inactivated and induced high virus neutralizing antibody responses in mouse immunogenicity studies. Both mouse antisera recognized the immunodominant linear neutralization epitope of VP1 (residues 211–225). Conclusion:These results provide important information for cell-based EV71 vaccine development, particularly for the preparation of working standards for viral antigen quantification