Huntington's disease (HD) is a neurodegenerative disorder that manifests with movement dysfunction. The expression of mutant Huntingtin (mHTT) disrupts the functions of brain cells. Galectin-3 (Gal3) ...is a lectin that has not been extensively explored in brain diseases. Herein, we showed that the plasma Gal3 levels of HD patients and mice correlated with disease severity. Moreover, brain Gal3 levels were higher in patients and mice with HD than those in controls. The up-regulation of Gal3 in HD mice occurred before motor impairment, and its level remained high in microglia throughout disease progression. The cell-autonomous up-regulated Gal3 formed puncta in damaged lysosomes and contributed to inflammation through NFκB- and NLRP3 inflammasome-dependent pathways. Knockdown of Gal3 suppressed inflammation, reduced mHTT aggregation, restored neuronal DARPP32 levels, ameliorated motor dysfunction, and increased survival in HD mice. Thus, suppression of Gal3 ameliorates microglia-mediated pathogenesis, which suggests that Gal3 is a novel druggable target for HD.
Rechargeable lithium metal batteries are next generation energy storage devices with high energy density, but face challenges in achieving high energy density, high safety, and long cycle life. Here, ...lithium metal batteries in a novel nonflammable ionic‐liquid (IL) electrolyte composed of 1‐ethyl‐3‐methylimidazolium (EMIm) cations and high‐concentration bis(fluorosulfonyl)imide (FSI) anions, with sodium bis(trifluoromethanesulfonyl)imide (NaTFSI) as a key additive are reported. The Na ion participates in the formation of hybrid passivation interphases and contributes to dendrite‐free Li deposition and reversible cathode electrochemistry. The electrolyte of low viscosity allows practically useful cathode mass loading up to ≈16 mg cm−2. Li anodes paired with lithium cobalt oxide (LiCoO2) and lithium nickel cobalt manganese oxide (LiNi0.8Co0.1Mn0.1O2, NCM 811) cathodes exhibit 99.6–99.9% Coulombic efficiencies, high discharge voltages up to 4.4 V, high specific capacity and energy density up to ≈199 mAh g−1 and ≈765 Wh kg−1 respectively, with impressive cycling performances over up to 1200 cycles. Highly stable passivation interphases formed on both electrodes in the novel IL electrolyte are the key to highly reversible lithium metal batteries, especially for Li–NMC 811 full batteries.
A nonflammable ionic‐liquid electrolyte is developed for high‐safety and high‐energy‐density Li metal batteries, allowing practically useful cathode mass loading up to 16 mg cm−2, realizing high specific capacity and energy density (199 mAh g−1 and 765 Wh kg−1) with impressive cycling performances. The robust passivation interphases formed on both electrodes are key to realizing impressive battery performances.
All‐inorganic CsPbX3 (X=I, Br, Cl) perovskite quantum dots (PQDs) have been investigated because of their optical properties, such as tunable wavelength, narrow band, and high quantum efficiency. ...These features have been used in light emitting diode (LED) devices. LED on‐chip fabrication uses mixed green and red quantum dots with silicone gel. However, the ion‐exchange effect widens the narrow emission spectrum. Quantum dots cannot be mixed because of anion exchange. We address this issue with a mesoporous PQD nanocomposite that can prevent ion exchange and increase stability. We mixed green quantum‐dot‐containing mesoporous silica nanocomposites with red PQDs, which can prevent the anion‐exchange effect and increase thermal and photo stability. We applied the new PQD‐based LEDs for backlight displays. We also used PQDs in an on‐chip LED device. Our white LED device for backlight display passed through a color filter with an NTSC value of 113 % and Rec. 2020 of 85 %.
Points of light: Green CsPbBr3 perovskite quantum dots (PQDs), embedded in mesoporous silica (MP), were mixed with red CsPb(Br0.4I0.6)3 quantum dots in a silicone resin and placed on an InGaN blue chip. The green and red QDs were excited by blue light with λ=450 nm. The resulting PQD white light emitting diode (LED) exhibits a wide color gamut because of its narrow emission wavelength.
•We propose an integrated framework to process aspect-level data and visualize data in TripAdvisor.•Our proposed aspect-level approach outperforms baseline algorithms and well-known sentiment ...classification methods.•Our visual analytics provides multiple perspectives by using the timeline and location-based analyses.•Visual analytics results reveal that business travelers tend to rate lower, while couples tend to rate higher.
Analyzing and extracting insights from user-generated data has become a topic of interest among businesses and research groups because such data contains valuable information, e.g., consumers’ opinions, ratings, and recommendations of products and services. However, the true value of social media data is rarely discovered due to overloaded information. Existing literature in analyzing online hotel reviews mainly focuses on a single data resource, lexicon, and analysis method and rarely provides marketing insights and decision-making information to improve business’ service and quality of products. We propose an integrated framework which includes a data crawler, data preprocessing, sentiment-sensitive tree construction, convolution tree kernel classification, aspect extraction and category detection, and visual analytics to gain insights into hotel ratings and reviews. The empirical findings show that our proposed approach outperforms baseline algorithms as well as well-known sentiment classification methods, and achieves high precision (0.95) and recall (0.96). The visual analytics results reveal that Business travelers tend to give lower ratings, while Couples tend to give higher ratings. In general, users tend to rate lowest in July and highest in December. The Business travelers more frequently use negative keywords, such as “rude,” “terrible,” “horrible,” “broken,” and “dirty,” to express their dissatisfied emotions toward their hotel stays in July.
The antagonism between strength and resistance to hydrogen embrittlement in metallic materials is an intrinsic obstacle to the design of lightweight yet reliable structural components operated in ...hydrogen-containing environments. Economical and scalable microstructural solutions to this challenge must be found. Here, we introduce a counterintuitive strategy to exploit the typically undesired chemical heterogeneity within the material's microstructure that enables local enhancement of crack resistance and local hydrogen trapping. We use this approach in a manganese-containing high-strength steel and produce a high dispersion of manganese-rich zones within the microstructure. These solute-rich buffer regions allow for local micro-tuning of the phase stability, arresting hydrogen-induced microcracks and thus interrupting the percolation of hydrogen-assisted damage. This results in a superior hydrogen embrittlement resistance (better by a factor of two) without sacrificing the material's strength and ductility. The strategy of exploiting chemical heterogeneities, rather than avoiding them, broadens the horizon for microstructure engineering via advanced thermomechanical processing.
This book addresses the pertinent efficiency issue via smart allocation of computing resource in the simulation experiments for optimization, and aims to provide academic researchers and industrial ...practitioners with a comprehensive coverage of OCBA approach for stochastic simulation optimization. Starting with an intuitive explanation of computing budget allocation and a discussion of its impact on optimization performance, a series of OCBA approaches developed for various problems are then presented, from the selection of the best design to optimization with multiple objectives. Finally, this book discusses the potential extension of OCBA notion to different applications such as data envelopment analysis, experiments of design and rare-event simulation.
Nickel cobaltite (NiCo2O4) aerogels, synthesized with a chloride‐based epoxide‐driven sol–gel process, exhibit ultrahigh specific capacitances (1400 F g−1; see figure), excellent reversibility, and ...outstanding cycle stability, at a relatively high mass loading of 0.4 mg cm−2.
Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) ...were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut-brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.
Bisphenol A (BPA) is an estrogen-like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA ...residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE-19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE-19 cells. After BPA treatment, the expression of Bcl-XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase-9 to promote downstream caspase-3 leading to cytotoxicity. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) pathway play a major role in age-related macular degeneration. Our results showed that expression of HO-1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP-activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA-induced ROS generation and cytotoxicity were reduced by N-acetyl-l-cysteine. Taken together, these results suggest that BPA induced ARPE-19 cells via oxidative stress, which was associated with down regulated Nrf2/HO-1 pathway, and the mitochondria dependent apoptotic signaling pathway.
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