Alzheimer’s disease (AD) is a complex neurodegenerative disease in the elderly and the most common cause of human dementia. AD is characterized by accumulation of abnormal protein aggregates ...including amyloid plaques (composed of beta-amyloid (Aβ) peptides) and neurofibrillary tangles (formed by hyper-phosphorylated tau protein). Synaptic plasticity, neuroinflammation, calcium signaling etc. also show dysfunction in AD patients. Autophagy is an evolutionarily conserved lysosome-dependent cellular event in eukaryotes. It is closely linked to modulation of protein metabolism, through which damaged organelles and mis-folded proteins are degraded and then recycled to maintain protein homeostasis. Accumulating evidence has shown that impaired autophagy also contributes to AD pathogenesis. In the present review, we highlight the role of autophagy, including bulk and selective autophagy, in regulating metabolic circuits in AD pathogenesis. We also discuss the potential and future perspectives of autophagy-inducing strategies in AD therapeutics.
•The current knowledge about autophagy and the regulation of autophagic pathway.•The role of autophagy in regulating metabolic circuits during AD pathogenesis.•The potential of autophagy-inducing strategy in AD therapeutics.
Various methods have been exploited to replicate nacre features into artificial structural materials with impressive structural and mechanical similarity. However, it is still very challenging to ...produce nacre-mimetics in three-dimensional bulk form, especially for further scale-up. Herein, we demonstrate that large-sized, three-dimensional bulk artificial nacre with comprehensive mimicry of the hierarchical structures and the toughening mechanisms of natural nacre can be facilely fabricated via a bottom-up assembly process based on laminating pre-fabricated two-dimensional nacre-mimetic films. By optimizing the hierarchical architecture from molecular level to macroscopic level, the mechanical performance of the artificial nacre is superior to that of natural nacre and many engineering materials. This bottom-up strategy has no size restriction or fundamental barrier for further scale-up, and can be easily extended to other material systems, opening an avenue for mass production of high-performance bulk nacre-mimetic structural materials in an efficient and cost-effective way for practical applications.Artificial materials that replicate the mechanical properties of nacre represent important structural materials, but are difficult to produce in bulk. Here, the authors exploit the bottom-up assembly of 2D nacre-mimetic films to fabricate 3D bulk artificial nacre with an optimized architecture and excellent mechanical properties.
Cuproptosis is a novel copper ion-dependent cell death type being regulated in cells, and this is quite different from the common cell death patterns such as apoptosis, pyroptosis, necroptosis, and ...ferroptosis. Interestingly, like with death patterns, cuproptosis-related genes have recently been reported to regulate the occurrence and progression of various tumors. However, in bladder cancer, the link between cuproptosis and clinical outcome, tumor microenvironment (TME) modification, and immunotherapy is unknown. To determine the role of cuprotosis in the tumor microenvironment, we systematically examined the characteristic patterns of 10 cuproptosis-related genes in bladder cancer (BLCA). By analyzing principal component data, we established a cuproptosis score to determine the degree of cuproptosis among patients. Finally, we evaluated the potential of these values in predicting BLCA prognosis and treatment responses. A comprehensive study of the mutations of cuproptosis-related genes in BLCA specimens was conducted at the genetic level, and their expression and survival patterns were evaluated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Two cuproptosis patterns were constructed based on the transcription level of 10 cuproptosis-related genes, featuring differences in the prognosis and the infiltrating landscape of immune cells (especially T and dendritic cells) with interactions between cuproptosis and the TME. Our study further demonstrated that cuproptosis score may predict prognosis, immunophenotype sensitivity to chemotherapy, and immunotherapy response among bladder cancer patients. The development and progression of bladder cancer are likely to be influenced by cuproptosis, which may involve a diverse and complex TME. The cuproptosis pattern evaluated in our study may enhance understanding of immune infiltrations and guide more potent immunotherapy interventions.
Abstract
Background
There are no pharmacological interventions currently available to prevent the transmission of SARS-CoV-2 or to treat COVID-19. The development of vaccines against COVID-19 is ...essential to contain the pandemic. we conducted a cross-sectional survey of Shanghai residents to understand residents’ willingness to be vaccinated with any future COVID-19 vaccines and take measures to further improve vaccination coverage.
Methods
We conducted a cross-sectional survey using self-administered anonymous questionnaires from 1 July to 8 September 2020. The main outcome was willingness of participants, and any children or older individuals living with them, to receive future COVID-19 vaccines. Logistic regression analyses were used to explore potential factors associated with vaccination willingness.
Results
A total of 1071 participants were asked about their willingness to receive future COVID-19 vaccines, for themselves and at least 747 children and 375 older individuals (≥60 years old) living with them. The highest proportion of expected willingness to vaccinate was among participants (88.6%), followed by children (85.3%) and older individuals (84.0%). The main reasons for reluctance to vaccinate among 119 participants were doubts regarding vaccine safety (60.0%) and efficacy (28.8%). Participants with a self-reported history of influenza vaccination were more likely to accept COVID-19 vaccines for themselves adjusted odds ratio (
OR
) = 1.83; 95% confidence interval (
CI
): 1.19–2.82, their children (adjusted
OR
= 2.08; 95%
CI
: 1.30–3.33), and older individuals in their household (adjusted
OR
= 2.12; 95%
CI
: 1.14–3.99). Participants with older individuals in their families were less willing to vaccinate themselves (adjusted
OR
= 0.59; 95%
CI
: 0.40–0.87) and their children (adjusted
OR
= 0.58; 95%
CI
: 0.38–0.89).
Conclusions
Participants were more reluctant to accept COVID-19 vaccines for older individuals living with them. The presence of older individuals in the home also affected willingness of participants and their children to be vaccinated.
High-frequency-link (HFL) power conversion systems (PCSs) are attracting more and more attentions in academia and industry for high power density, reduced weight, and low noise without compromising ...efficiency, cost, and reliability. In HFL PCSs, dual-active-bridge (DAB) isolated bidirectional dc-dc converter (IBDC) serves as the core circuit. This paper gives an overview of DAB-IBDC for HFL PCSs. First, the research necessity and development history are introduced. Second, the research subjects about basic characterization, control strategy, soft-switching solution and variant, as well as hardware design and optimization are reviewed and analyzed. On this basis, several typical application schemes of DAB-IBDC for HPL PCSs are presented in a worldwide scope. Finally, design recommendations and future trends are presented. As the core circuit of HFL PCSs, DAB-IBDC has wide prospects. The large-scale practical application of DAB-IBDC for HFL PCSs is expected with the recent advances in solid-state semiconductors, magnetic and capacitive materials, and microelectronic technologies.
Recently, several tools have been designed for human leukocyte antigen (HLA) typing using single nucleotide polymorphism (SNP) array and next-generation sequencing (NGS) data. These tools provide ...high-throughput and cost-effective approaches for identifying HLA types. Therefore, tools for downstream association analysis are highly desirable. Although several tools have been designed for multi-allelic marker association analysis, they were designed only for microsatellite markers and do not scale well with increasing data volumes, or they were designed for large-scale data but provided a limited number of tests.
We have developed a Python package called PyHLA, which implements several methods for HLA association analysis, to fill the gap. PyHLA is a tailor-made, easy to use, and flexible tool designed specifically for the association analysis of the HLA types imputed from genome-wide genotyping and NGS data. PyHLA provides functions for association analysis, zygosity tests, and interaction tests between HLA alleles and diseases. Monte Carlo permutation and several methods for multiple testing corrections have also been implemented.
PyHLA provides a convenient and powerful tool for HLA analysis. Existing methods have been integrated and desired methods have been added in PyHLA. Furthermore, PyHLA is applicable to small and large sample sizes and can finish the analysis in a timely manner on a personal computer with different platforms. PyHLA is implemented in Python. PyHLA is a free, open source software distributed under the GPLv2 license. The source code, tutorial, and examples are available at https://github.com/felixfan/PyHLA.
By establishing the mathematical model of the current stress of the isolated bidirectional dc-dc converter (IBDC), this paper comparatively analyzes the performances of IBDC under traditional ...single-phase-shift control and dual-phase-shift (DPS) control. On this basis, this paper proposes a current-stress-optimized switching strategy for IBDC with DPS control, and the corresponding control scheme is designed and implemented. The current-stress-optimized switching strategy can minimize the current stress, improve the system efficiency, and increase system power capability, and these performances are particularly effective for operation conditions with high voltage conversion ratio and light load. At last, experimental results verify the excellent performance of the current-stress-optimized switching strategy and correctness of the theoretical analysis.
This paper is concerned with the finite-time synchronization (FTS) issue of switched coupled neural networks with discontinuous or continuous activations. Based on the framework of nonsmooth ...analysis, some discontinuous or continuous controllers are designed to force the coupled networks to synchronize to an isolated neural network. Some sufficient conditions are derived to ensure the FTS by utilizing the well-known finite-time stability theorem for nonlinear systems. Compared with the previous literatures, such synchronization objective will be realized when the activations and the controllers are both discontinuous. The obtained results in this paper include and extend the earlier works on the synchronization issue of coupled networks with Lipschitz continuous conditions. Moreover, an upper bound of the settling time for synchronization is estimated. Finally, numerical simulations are given to demonstrate the effectiveness of the theoretical results.
High‐mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma (HCC) cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism ...through which HMGA2 is transcriptionally regulated in HCC cells remains largely unclear. Here, we showed that the expression HMGA2 was upregulated in HCC, and that elevated HMGA2 could promote tumor metastasis. Incubation of HCC cells with epidermal growth factor (EGF) could promote the expression of HMGA2 mRNA and protein. Mechanistic studies suggested that EGF can phosphorylate p300 at Ser1834 residue through the PI3K/Akt signaling pathway in HCC cells. Knockdown of p300 can reverse EGF‐induced HMGA2 expression and histone H3‐K9 acetylation, whereas a phosphorylation‐mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3‐K9 acetylation in HCC cells. Furthermore, we identified that p300‐mediated H3‐K9 acetylation participates in EGF‐induced HMGA2 expression in HCC. In addition, the levels of H3‐K9 acetylation positively correlated with the expression levels of HMGA2 in a chemically induced HCC model in rats and human HCC specimens.
We first showed that EGF can induce p300 phosphorylation at the Ser1834 site through activation of the PI3K/AKT signaling pathway in hepatocellular carcinoma; p300 subsequently catalyzes histone H3 acetylation at K9 residues, leading to HMGA2 transcription in HCC
Without assuming that the interaction diagraph is strongly connected or contains a directed spanning tree, this paper studies the second-order leader-following consensus problem of nonlinear ...multi-agent systems with general network topologies. Based on graph theory, matrix theory, and LaSalle’s invariance principle, a pinning control algorithm is proposed to achieve leader-following consensus in a network of agents with nonlinear second-order dynamics. Furthermore, a pinning consensus protocol is developed for coupled double-integrators with a constant reference velocity. In particular, this paper addresses what kind of agents and how many agents should be pinned, and establishes some sufficient conditions to guarantee that all agents asymptotically follow the virtual leader. Numerical simulations are given to verify the theoretical analysis.
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