Accumulation of p25 is thought to be a causative risk factor for Alzheimer's disease (AD). As a cleaved product of p35, p25 binds to cyclin-dependent kinase 5 (Cdk5) and leads to the hyperactivity of ...Cdk5. Then, Cdk5/p25 phosphorylates many pathological substrates related to neurodegenerative diseases. p25 transgenic (Tg) mouse model recaptures some pathological changes of AD, including tau hyperphosphorylation, neurofibrillary tangles, neuroinflammation, and neuronal death, which can be prevented by transgenic expression of Cdk5 inhibitory peptide (CIP) before the insult of p25.
In the present study, we would like to know whether adeno-associated virus serotype-9 (AAV9)-mediated CIP can protect neurons after insult of p25 in p25Tg mice.
Administration of AAV9-CIP or control virus were delivered in the brain of p25Tg mice via intracerebroventricular infusions following the induction of p25. Western blotting, immunohistochemistry and immunofluorescence assessment, and animal behavioral evaluation were performed.
Brain atrophy, neuronal death, tau phosphorylation and inflammation in the hippocampus, and cognitive decline were observed in p25Tg mice. Administration of CIP but not the control virus in p25Tg mice reduced levels of tau phosphorylation and inflammation in the hippocampus, which is correlated with inhibition of brain atrophy and neuronal apoptosis in the hippocampus, and improvement of cognitive decline.
Our results provide further evidence that the neurotoxicity of p25 can be alleviated by CIP.
Traditional Chinese medicine in COVID-19 Lyu, Ming; Fan, Guanwei; Xiao, Guangxu ...
Acta pharmaceutica Sinica. B,
11/2021, Letnik:
11, Številka:
11
Journal Article
Recenzirano
Odprti dostop
COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across the globe, posing an enormous threat to public health and safety. Traditional Chinese ...medicine (TCM), in combination with Western medicine (WM), has made important and lasting contributions in the battle against COVID-19. In this review, updated clinical effects and potential mechanisms of TCM, presented in newly recognized three distinct phases of the disease, are summarized and discussed. By integrating the available clinical and preclinical evidence, the efficacies and underlying mechanisms of TCM on COVID-19, including the highly recommended three Chinese patent medicines and three Chinese medicine formulas, are described in a panorama. We hope that this comprehensive review not only provides a reference for health care professionals and the public to recognize the significant contributions of TCM for COVID-19, but also serves as an evidence-based in-depth summary and analysis to facilitate understanding the true scientific value of TCM.
The potential mechanisms of TCM remedy in three phases of distinct disease stages for COVID-19 are systematically described within a panorama by integrating available clinical and preclinical evidence. Display omitted
Piezoelectric materials that generate electricity when deforming are ideal for many implantable medical sensing devices. In modern piezoelectric materials, inorganic ceramics and polymers are two ...important branches, represented by lead zirconate titanate (PZT) and polyvinylidene difluoride (PVDF). However, PVDF is a nondegradable plastic with poor crystallinity and a large coercive field, and PZT suffers from high sintering temperature and toxic heavy element. Here, we successfully design a metal-free small-molecule ferroelectric, 3,3-difluorocyclobutanammonium hydrochloride ((3,3-DFCBA)Cl), which has high piezoelectric voltage coefficients
g
33
(437.2 × 10
−3
V m N
−1
) and
g
31
(586.2 × 10
−3
V m N
−1
), a large electrostriction coefficient
Q
33
(about 4.29 m
4
C
−2
) and low acoustic impedance
z
0
(2.25 × 10
6
kg s
−1
m
−2
), significantly outperforming PZT (
g
33
= 34 × 10
−3
V m N
−1
and
z
0
= 2.54 × 10
7
kg s
−1
m
−2
) and PVDF (
g
33
= 286.7 × 10
−3
V m N
−1
,
g
31
= 185.9 × 10
−3
V m N
−1
,
Q
33
= 1.3 m
4
C
−2
, and
z
0
= 3.69 × 10
6
kg s
−1
m
−2
). Such a low acoustic impedance matches that of the body (1.38-1.99 × 10
6
kg s
−1
m
−2
) reasonably well, making it attractive as next-generation biocompatible piezoelectric devices for health monitoring and "disposable" invasive medical ultrasound imaging.
A small-molecule organic ferroelectric (3,3-DFCBA)Cl has high piezoelectric voltage coefficients
g
33
(437.2 × 10
−3
V m N
−1
), a large electrostriction coefficient
Q
33
, and low acoustic impedance
z
0
, far beyond that of PZT and PVDF.
Ferroelectric materials, whose electrical polarization can be switched under external stimuli, have been widely used in sensors, data storage, and energy conversion. Molecular orbital breaking can ...result in switchable structural and physical bistability in ferroelectric materials as traditional spatial symmetry breaking does. Differently, molecular orbital breaking interprets the phase transition mechanism from the perspective of electronics and sheds new light on manipulating the physical properties of ferroelectrics. Here, we synthesize a pair of organosilicon Schiff base ferroelectric crystals, (R)- and (S)-N-(3,5-di-tert-butylbenzylidene)-1-((triphenylsilyl)oxy)ethanamine, which show optically controlled phase transition accompanying the molecular orbital breaking. The molecular orbital breaking is manifested as the breaking and reformation of covalent bonds during the phase transition process, that is, the conversion between C = N and C-O in the enol form and C-N and C = O in the keto form. This process brings about photo-mediated bistability with multiple physical channels such as dielectric, second-harmonic generation, and ferroelectric polarization. This work further explores this newly developed mechanism of ferroelectric phase transition and highlights the significance of photo-mediated ferroelectric materials for photo-controlled smart devices and bio-sensors.
The synthetic progress of bioactive 2,7′-cyclolignans is reviewed. After a short introduction to biosynthesis and chemoenzymatic synthesis, the chemical synthesis of various aryltetralin, ...dihydronaphthalene and 7′-arylnaphthalene-types of these lignans is demonstrated. Notably, newly developed methods, such as Pd-catalyzed C-H arylation, organocatalysis and photocatalysis under visible-light, are discussed during the construction of their skeleton. These efforts will stimulate further development of novel synthetic strategies for this kind of natural product with important biological activities.
Diverse strategies for the chemical synthesis and biosynthesis of 2,7′-cyclolignan natural products are reviewed.
We report efficient high-average-power, high-energy passively Q-switched operation of an Er3+-doped fluoride fiber laser at room temperature with wavelength-tunable resonator configuration utilizing ...a plane ruled grating for wavelength selection. The fiber laser produced stable Q-switched pulses with a maximum average output power of 5.16 W at 2811.7 nm and a maximum pulse energy of 27.7 μJ at 2834.6 nm for 30.5-W launched pump power and could be tuned over a wavelength range of 90 nm from 2762.5 to 2852.5 nm, with > 4-W average power over the range of 76.1 nm. Our results present fivefold increase in output power over previously published values directly attained from ~3-μm passively Q-switched fiber lasers and firmly establish a fiber laser as a compact, wavelength-tunable, multiwatt, tens of microjoules mid-infrared pulse source with large scope of both industrial and scientific applications.
Personalized medicine is revolutionizing the diagnosis and treatment of cancer; however, for personalized medicine to be used accurately, patient information is essential to determine the appropriate ...diagnosis, prognosis and treatment. The detection of genomic mutations in liquid biopsy samples is a non-invasive method of characterizing the genotype of a tumor. However, next generation sequencing-based plasma genotyping only has a sensitivity of ~70%. Identifying potential indicators that may reflect the sensitivity of a liquid biopsy analysis could offer important information for its clinical application. In the present study, 47 pairs of patient-matched plasma and tumor tissue samples obtained from patients with advanced lung cancer were sequenced using a panel of 56 cancer-associated genes. The plasma maximum allele frequency (Max AF) was identified as a novel biomarker to indicate the sensitivity of plasma genotyping. Using the identified somatic mutations in patient tissue biopsy samples as a reference, the sensitivity of the corresponding patient plasma test was investigated. The by-variant sensitivity of the plasma test was 68.1%, with 79 matched and 37 missed genetic aberrances. The by-patient sensitivity was calculated as 83%. Patients with a high plasma Max AF value (>2.2%) demonstrated a higher concordance with the range of mutations identified in the patient-matched tissue samples. The Max AF observed in patient plasma samples was positively correlated with liquid biopsy sensitivity and could be used as a potential indicator of liquid biopsy sensitivity. Therefore, patients with a low plasma Max AF (≤2.2%) may need to undergo further tissue biopsy to allow personalized oncology treatment. In summary, the present study may offer a non-invasive testing method for a sub-group of patients with advanced lung cancer.
Starting from the concept of the Cloud Radio Access Network (C-RAN), continuing with the virtual Radio Access Network (vRAN) and most recently with the Open RAN (O-RAN) initiative, Radio Access ...Network (RAN) architectures have significantly evolved in the past decade. In the last few years, the wireless industry has witnessed a strong trend towards disaggregated, virtualized and open RANs, with numerous tests and deployments worldwide. One unique aspect that motivates this paper is the availability of new opportunities that arise from using machine learning, more specifically multi-agent team learning (MATL), to optimize the RAN in a closed-loop where the complexity of disaggregation and virtualization makes well-known Self-Organized Networking (SON) solutions inadequate. In our view, Multi-Agent Systems (MASs) with MATL can play an essential role in the orchestration of O-RAN controllers, i.e., near-real-time and non-real-time RAN Intelligent Controllers (RIC). In this article, we first provide an overview of the landscape in RAN disaggregation, virtualization and O-RAN, then we present the state-of-the-art research in multi-agent systems and team learning as well as their application to O-RAN. We present a case study for team learning where agents are two distinct xApps: power allocation and radio resource allocation. We demonstrate how team learning can enhance network performance when team learning is used instead of individual learning agents. Finally, we identify challenges and open issues to provide a roadmap for researchers in the area of MATL based O-RAN optimization.
Recent studies on medical image fusion based on deep learning have made remarkable progress, but the common and exclusive features of different modalities, especially their subsequent feature ...enhancement, are ignored. Since medical images of different modalities have unique information, special learning of exclusive features should be designed to express the unique information of different modalities so as to obtain a medical fusion image with more information and details. Therefore, we propose an attention mechanism-based disentangled representation network for medical image fusion, which designs coordinate attention and multimodal attention to extract and strengthen common and exclusive features. First, the common and exclusive features of each modality were obtained by the cross mutual information and adversarial objective methods, respectively. Then, coordinate attention is focused on the enhancement of the common and exclusive features of different modalities, and the exclusive features are weighted by multimodal attention. Finally, these two kinds of features are fused. The effectiveness of the three innovation modules is verified by ablation experiments. Furthermore, eight comparison methods are selected for qualitative analysis, and four metrics are used for quantitative comparison. The values of the four metrics demonstrate the effect of the DRCM. Furthermore, the DRCM achieved better results on SCD, Nabf, and MS-SSIM metrics, which indicates that the DRCM achieved the goal of further improving the visual quality of the fused image with more information from source images and less noise. Through the comprehensive comparison and analysis of the experimental results, it was found that the DRCM outperforms the comparison method.
Here, we synthesized a series of cholesteryl-based compounds, whose phases and their transformation can be modulated by temperature and the chain length of the fluoroalkyl moieties. To our knowledge, ...this is the first time that the phase transition could be modulated with perfluoroalkyl tail engineering in organic single-component ferroelectric crystals.
This is the first time that the phase transition could be modulated with perfluoroalkyl tail engineering in organic single-component ferroelectric crystals.
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