The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 ...asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy
. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.
Purpose
Cancer, a major public health problem, exhibits significant redox alteration. Thioredoxin (Trx) system, including Trx and Trx reductase (TrxR), as well as Trx-interacting protein (TXNIP) play ...important roles in controlling the cellular redox balance in cancer cells. In most cancers, Trx and TrxR are usually overexpressed and TXNIP is underexpressed. In recent years, some agents targeting Trx, TrxR, and TXNIP were used to explore a therapy approach for cancer patients.
Methods
A systematic search of PMC and the PubMed Database was conducted to summarize the potential of Trx system inhibitors for cancer treatment.
Results
In this article, we first summarize the functions of Trx, TrxR, and TXNIP in cancers. We also review some small molecule inhibitors of Trx/TrxR and
d
-allose (TXNIP inducer) and discuss their antitumor mechanisms. We highlight the combined inhibition of Trx system and GSH system in cancer therapy. We expect that a highly specific and selective antitumor agent with no cytotoxicity on human normal cells could be developed in the future.
Conclusion
In conclusion, Trx system may be very promising for clinical therapy of cancer in the future.
Parkinson disease (PD) is the second most common neurodegenerative movement disorder. Pharmacological animal models are invaluable tools to study the pathological mechanisms of PD. Currently, ...invertebrate and vertebrate animal models have been developed by using several main neurotoxins, such as 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, paraquat, and rotenone. These models achieve to some extent to reproduce the key features of PD, including motor defects, progressive loss of dopaminergic neurons in substantia nigra pars compacta, and the formation of Lewy bodies. In this review, we will highlight the pathogenic mechanisms of those neurotoxins and summarize different neurotoxic animal models with the hope to help researchers choose among them accurately and to promote the development of modeling PD.
Nanoparticles (NPs) have been increasingly studied for radiosensitization. The principle of NPs radio-enhancement is to use high-atomic number NPs (e.g. gold, hafnium, bismuth and gadolinium) or ...deliver radiosensitizing substances, such as cisplatin and selenium. Nowadays, cancer immunotherapy is emerged as a promising treatment and immune checkpoint regulation has a potential property to improve clinical outcomes in cancer immunotherapy. Furthermore, NPs have been served as an ideal platform for immunomodulator system delivery. Owing to enhanced permeability and retention (EPR) effect, modified-NPs increase the targeting and retention of antibodies in target cells. The purpose of this review is to highlight the latest progress of nanotechnology in radiotherapy (RT) and immunotherapy, as well as combining these three strategies in cancer treatment. Overall, nanomedicine as an effective strategy for RT can significantly enhance the outcome of immunotherapy response and might be beneficial for clinical transformation.
Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads ...to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.
Multiple sclerosis (MS) lesions that do not resolve in the months after they form harbour ongoing demyelination and axon degeneration, and are identifiable in vivo by their paramagnetic rims on MRI ...scans
. Here, to define mechanisms underlying this disabling, progressive neurodegenerative state
and foster development of new therapeutic agents, we used MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter lesions at various stages of inflammation. We uncovered notable glial and immune cell diversity, especially at the chronically inflamed lesion edge. We define 'microglia inflamed in MS' (MIMS) and 'astrocytes inflamed in MS', glial phenotypes that demonstrate neurodegenerative programming. The MIMS transcriptional profile overlaps with that of microglia in other neurodegenerative diseases, suggesting that primary and secondary neurodegeneration share common mechanisms and could benefit from similar therapeutic approaches. We identify complement component 1q (C1q) as a critical mediator of MIMS activation, validated immunohistochemically in MS tissue, genetically by microglia-specific C1q ablation in mice with experimental autoimmune encephalomyelitis, and therapeutically by treating chronic experimental autoimmune encephalomyelitis with C1q blockade. C1q inhibition is a potential therapeutic avenue to address chronic white matter inflammation, which could be monitored by longitudinal assessment of its dynamic biomarker, paramagnetic rim lesions, using advanced MRI methods.
•Multi-kernel extreme learning machine based method is proposed for EEG classification.•Supplementary information from different kernels are integrated for better accuracy.•Extensive experimental ...comparison confirms superiority of the proposed method.
One of the most important issues for the development of a motor-imagery based brain-computer interface (BCI) is how to design a powerful classifier with strong generalization capability. Extreme learning machine (ELM) has recently proven to be comparable or more efficient than support vector machine for many pattern recognition problems. In this study, we propose a multi-kernel ELM (MKELM)-based method for motor imagery electroencephalogram (EEG) classification. The kernel extension of ELM provides an elegant way to circumvent calculation of the hidden layer outputs and inherently encode it in a kernel matrix. We investigate effects of two different kernel functions (i.e., Gaussian kernel and polynomial kernel) on the performance of kernel ELM. The MKELM method is subsequently developed by integrating these two types of kernels with a multi-kernel learning strategy, which can effectively explore the supplementary information from multiple nonlinear feature spaces for more robust classification of EEG. An extensive experimental comparison with two public EEG datasets indicates that the MKELM method gives higher classification accuracy than those of the other competing algorithms. The experimental results confirm that superiority of the proposed MKELM-based method for accurate classification of EEG associated with motor imagery in BCI applications. Our method also provides a promising and generalized solution to investigate the complex and nonlinear information for various applications in the fields of expert and intelligent systems.
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Introduction
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Neurodegeneration and neurofibrillary degeneration in Alzheimer's disease brains
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Dysfunction of protein synthesis mediated by mTOR‐dependent signalling in Alzheimer's disease ...brains
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Neurodegeneration mediated by mTOR‐dependent signalling
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Tau phosphorylation mediated by mTOR‐dependent signalling
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mTOR‐dependent signalling in lymphocytes of AD: potential biomarkers for AD diagnosis
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mTOR‐dependent signalling and other neurodegenerative diseases
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Perspectives
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Conclusions
Neurodegeneration and neurofibrillary degeneration are the two main pathological mechanisms of cognitive impairments in Alzheimer's disease (AD). It is not clear what factors determine the fates of neurons during the progress of the disease. Emerging evidence has suggested that mTOR‐dependent signalling is involved in the two types of degeneration in AD brains. This review focuses on the roles of mTOR‐dependent signalling in the pathogenesis of AD. It summarizes the recent advancements in the understanding of its roles in neu‐rodegeneration and neurofibrillary degeneration, as well as the evidence achieved when mTOR‐related signalling components were tested as potential biomarkers of cognitive impairments in the clinical diagnosis of AD.
Effective common spatial pattern (CSP) feature extraction for motor imagery (MI) electroencephalogram (EEG) recordings usually depends on the filter band selection to a large extent. Subband ...optimization has been suggested to enhance classification accuracy of MI. Accordingly, this study introduces a new method that implements sparse Bayesian learning of frequency bands (named SBLFB) from EEG for MI classification. CSP features are extracted on a set of signals that are generated by a filter bank with multiple overlapping subbands from raw EEG data. Sparse Bayesian learning is then exploited to implement selection of significant features with a linear discriminant criterion for classification. The effectiveness of SBLFB is demonstrated on the BCI Competition IV IIb dataset, in comparison with several other competing methods. Experimental results indicate that the SBLFB method is promising for development of an effective classifier to improve MI classification.
Endoplasmic reticulum (ER) stress has been implicated in Parkinson disease. We previously reported that thioredoxin 1 (Trx-1) suppressed the ER stress caused by ...1-methy-4-phenyl-1,2,3,6-tetrahydropyridine; however, its molecular mechanism remains largely unknown. In the present study, we showed that 1-methyl-4-phenylpyridinium ion (MPP+) induced ER stress by activating glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1α (IRE1α), tumor necrosis factor receptor-associated factor 2 (TRAF2), c-Jun N-terminal kinase (JNK), caspase-12, and C/EBP homologous protein (CHOP) in PC12 cells. The downregulation of Trx-1 aggravated the ER stress and further increased the expression of the above molecules induced by MPP+. In contrast, overexpression of Trx-1 attenuated the ER stress and repressed the expression of the above molecules induced by MPP+. More importantly, the overexpression of Trx-1 in transgenic mice suppressed ER stress by inhibiting the activation of these molecules. We present, for the first time, the molecular mechanism of Trx-1 suppression of endoplasmic reticulum stress in Parkinson disease in vitro and in vivo. Based on our findings, we conclude that Trx-1 plays a neuroprotective role in Parkinson disease by suppressing ER stress by regulating the activation of GRP78, IRE1α, TRAF2, JNK, caspase-12, and CHOP.
•MPP+/MPTP induces ER stress by activating GRP78, IRE1α, TRAF2, JNK, caspase-12, and CHOP.•Trx-1 knockdown aggravates the MPP+-induced ER stress.•Trx-1 overexpression attenuates the MPP+/MPTP-induced ER stress.•Trx-1 play a neuroprotective role in Parkinson disease.
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