Alzheimer disease (AD) accounts for 60-70% of dementia cases. Given the seriousness of the disease and continual increase in patient numbers, developing effective therapies to treat AD has become ...urgent. Presently, the drugs available for AD treatment, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate receptor, can only inhibit dementia symptoms for a limited period of time but cannot stop or reverse disease progression. On the basis of the amyloid hypothesis, many global drug companies have conducted many clinical trials on amyloid clearing therapy but without success. Thus, the amyloid hypothesis may not be completely feasible. The number of anti-amyloid trials decreased in 2019, which might be a turning point. An in-depth and comprehensive understanding of the contribution of amyloid beta and other factors of AD is crucial for developing novel pharmacotherapies.In ongoing clinical trials, researchers have developed and are testing several possible interventions aimed at various targets, including anti-amyloid and anti-tau interventions, neurotransmitter modification, anti-neuroinflammation and neuroprotection interventions, and cognitive enhancement, and interventions to relieve behavioral psychological symptoms. In this article, we present the current state of clinical trials for AD at clinicaltrials.gov. We reviewed the underlying mechanisms of these trials, tried to understand the reason why prior clinical trials failed, and analyzed the future trend of AD clinical trials.
Polymer encapsulated organic nanoparticles have recently attracted increasing attention in the biomedical field because of their unique optical properties, easy fabrication and outstanding ...performance as imaging and therapeutic agents. Of particular importance is the polymer encapsulated nanoparticles containing conjugated polymers (CP) or fluorogens with aggregation induced emission (AIE) characteristics as the core, which have shown significant advantages in terms of tunable brightness, superb photo- and physical stability, good biocompatibility, potential biodegradability and facile surface functionalization. In this review, we summarize the latest advances in the development of polymer encapsulated CP and AIE fluorogen nanoparticles, including preparation methods, material design and matrix selection, nanoparticle fabrication and surface functionalization for fluorescence and photoacoustic imaging. We also discuss their specific applications in cell labeling, targeted in vitro and in vivo imaging, blood vessel imaging, cell tracing, inflammation monitoring and molecular imaging. We specially focus on strategies to fine-tune the nanoparticle property (e.g. size and fluorescence quantum yield) through precise engineering of the organic cores and careful selection of polymer matrices. The review also highlights the merits and limitations of these nanoparticles as well as strategies used to overcome the limitations. The challenges and perspectives for the future development of polymer encapsulated organic nanoparticles are also discussed.
In the era of big data, strategy is an indicator that determines business growth and directly guides the sustainable development of business. This paper aims to study the construction of the SWOT (S ...stands for strength, W stands for weakness, O stands for opportunity, and T stands for threat.) structure analysis model of e‐commerce tourism development strategy based on the experience of big data. Through empirical analysis, it explores the factors that affect the development strategy of e‐commerce business, and proposes practical measures and development directions. Based on big data theory, this paper uses SWOT analysis to analyze the e‐commerce development strategy of China's rural tourism cooperatives in detail, and uses the analytic hierarchy process to analyze the green development direction of e‐commerce tourism enterprises. The experimental results of this paper show that the order of enterprise development strategy selection in the context of big data for tourism electronics is: SO strategy, ST strategy, WO strategy and WT strategy.
Since the emergence of inorganic–organic hybrid perovskites a few years ago, there have been many promising achievements in the field of green and red perovskite light‐emitting diodes (PeLEDs). ...Nevertheless, the performance of blue‐light PeLEDs faces challenges. In this work, the unique synergy obtained by introducing two different ligands to successfully form quasi‐2D perovskite films, which can exhibit stable blue‐light emission, is utilized. The fabricated PeLEDs have a maximum external quantum efficiency of 2.62% and a half lifetime (T50) of 8.8 min. Meanwhile, the electroluminescence spectrum with its peak located at 485 nm, demonstrates improved stability by applying different voltage bias. The finding in this work offers a new way to achieve steady blue PeLEDs with high performance.
Utilizing synergistic effects with two different ligands, a stable blue perovskite emitter is successfully fabricated. The corresponding blue perovskite light‐emitting diode shows excellent device performance with a peak external quantum efficiency of 2.62% and a T50 lifetime of 8.8 min, demonstrating remarkable color stability under operation.
The few lateral flow assays (LFAs) established for detecting the endocrine disrupting chemical bisphenol A (BPA) have employed citrate‐stabilized gold nanoparticles (GNPs), which have inevitable ...limitations and instability issues. To address these limitations, a more stable and more sensitive biosensor is developed by designing strategies for modifying the surfaces of GNPs with polyethylene glycol and then testing their effectiveness and sensitivity toward BPA in an LFA. Without the application of any enhancement strategy, this modified BPA LFA can achieve a naked‐eye limit of detection (LOD) of 0.8 ng mL−1, which is 12.5 times better than the LOD of regular BPA LFAs, and a quantitative LOD of 0.472 ng mL−1. This modified LFA has the potential to be applied to the detection of various antigens.
A more stable and more sensitive biosensor is developed by designing strategies for modifying the surfaces of gold nanoparticles (GNPs) and then testing their effectiveness and sensitivity toward bisphenol A in a lateral flow assay. The modified GNPs were prevented from aggregation during the strip fabrication and testing processes, and the amount of waste arising from failed experiments is significantly reduced.
·Random distribution of the inclusions in a composite material is simulated by a finite element model.·Effective thermal conductivity is calculated through finite element method.·Proposed numerical ...procedure is validated by experimental results and compared to empirical model results.
Many materials (e.g. soil) are multi-phase composites in engineering, and the thermal conductivity of mixtures is a critical parameter for analyzing the temperature field. Owing to its heterogeneity, the effective thermal conductivity of multi-phase materials is also not deterministic. The prediction of the thermal properties of a multi-phase material remains a challenging task. In this study, soil is considered to be a typical multi-phase material. A numerical simulation model is established by the finite element method to predict the meso-scale effective thermal conductivity of soil. Monte Carlo simulation is employed to account for the random distribution of voids. Comparisons among numerical, experimental and empirical results suggest that the proposed model can predict reasonably accurate results. In addition, the effective thermal conductivity of unfrozen soil, partially frozen soil and fully frozen soil is calculated. The effects of soil type, porosity and saturation degree on effective thermal conductivity are considered via parametric studies. The proposed numerical method can be used as an effective supplement to empirical model and experimental tests for evaluating the thermal conductivity of multi-phase materials.
Ganoderma sinense is a Chinese unique medicinal fungus that has been used in folk medicine for thousands of years. Polysaccharides are considered to be biologically active ingredients due to their ...immune-modulating functions. Previously we found that GSP-2, a new polysaccharide isolated from Ganoderma sinense, exerts an immunomodulatory effect in human peripheral blood mononuclear cells but the underlying mechanism is unclear. The present study aimed to investigate how GSP-2 triggers immunologic responses and the implicated signaling pathways. GSP-2 effects were investigated both in a macrophagic cell line, RAW264.7, and in primary macrophages. Moreover, the molecular basis of GSP-2 recognition by immune cells, and the consequent activation of signaling cascades, were explored by employing recombinant human HEK293-TLR-Blue clones, individually overexpressing various Toll-like receptors. GSP-2 dose-dependently induced the overexpression of Toll-like receptor 4 (TLR4) but did not affect the expression of other TLRs. Moreover, GSP-2 induced TNFα secretion in primary macrophages from wild-type, but not TLR4-knockout mice. In addition, GSP-2 upregulated TLR4 protein expression and activated the MAPK pathway in RAW246.7 macrophages. Finally, GSP-2 induced the production of the cytokines TNFα, IL1β, and IL6. Our data demonstrated that GSP-2 was specifically recognized by TLR4, promoting cytokine secretion and immune modulation in macrophages.
•Studies have been focused on mulberry fruits and their bioactive substances.•Mulberry’s polyphenols profile has been fractionalized, conversely with their bioaccessibility.•Mulberry’s health ...benefits have been well acknowledged especially antioxidant activity.•The processing steps should be optimized to keep the stability of mulberry’s polyphenols.
Mulberry (Morus sp.) fruits provide high levels of anthocyanins, quercetin glycoside, and chlorogenic acid. Recently, mulberry’s polyphenols and their functionalities are spotlighted in different ex vivo and in vivo studies. Meanwhile, the deficiency of systematic knowledge on the health effects and polyphenols composition greatly hinders the development of mulberry as a sustainable fruit. This review briefly summarises the polyphenol compositions, metabolism, health benefits, and their stability in different mulberry production steps. These claimed health effects include anti-oxidative, anti-cancer, anti-diabetes, anti-obesity, and other related effects. However, although the current evidence is promising, further clinical studies are needed to evaluate the role of mulberries' polyphenols to support human health. Besides, the mechanisms by which they confer the health benefits, the bioavailability studies on mulberry’s polyphenols are also scarce. We compile the research findings from the available literatures within the last two decades, and we also suggest some future perspectives in this review.
There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from
, which is widely used in traditional Chinese medicine, has ...been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.
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