To reduce the dependence on oil and environmental pollution, the development of electric vehicles has been accelerated in many countries. The implementation of EVs, especially battery electric ...vehicles, is considered a solution to the energy crisis and environmental issues. This paper provides a comprehensive review of the technical development of EVs and emerging technologies for their future application. Key technologies regarding batteries, charging technology, electric motors and control, and charging infrastructure of EVs are summarized. This paper also highlights the technical challenges and emerging technologies for the improvement of efficiency, reliability, and safety of EVs in the coming stages as another contribution.
The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation and supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, ...and gene therapy products) have been approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 of these 1050 drugs were identified as cancer therapeutics or cancer-related drugs, and 120 of them were classified as therapeutic drugs for solid tumors according to their initial indications. These drugs have evolved from small molecules with broad-spectrum antitumor properties in the early stage to monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) with a more precise targeting effect during the most recent decade. These drugs have extended indications for other malignancies, constituting a cancer treatment system for monotherapy or combined therapy. However, the available targets are still mainly limited to receptor tyrosine kinases (RTKs), restricting the development of antitumor drugs. In this review, these 120 drugs are summarized and classified according to the initial indications, characteristics, or functions. Additionally, RTK-targeted therapies and immune checkpoint-based immunotherapies are also discussed. Our analysis of existing challenges and potential opportunities in drug development may advance solid tumor treatment in the future. Keywords: The United States Food and Drug Administration, Solid tumors, Receptor tyrosine kinase inhibitors, Immune checkpoint blockades
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•Adsorption and diffusion of Li on heteroatom-doped MoS2 were investigated.•Doping enhance the adsorption of Li on monolayer MoS2.•Heteroatom-doped monolayer MoS2 can be used as anode ...materials of LIBs.
In this work, heteroatom doping in monolayer MoS2 by substitution of S with nonmetal elements (N, P, As, F, Cl, and I) and substitution of Mo with metal elements (Fe, Co, Ni, Cu, and Zn) was investigated using density functional theory. The adsorption and diffusion of Li on the heteroatom-doped MoS2 monolayer were also studied. Results showed that heteroatom doping can be realized by controlling the synthesis condition, and can enhance the adsorption of Li on monolayer MoS2, especially for p-type doped monolayers. The diffusion energy barriers were slightly decreased as Li diffused towards the doping site, whereas they were increased for the diffusion around the doping site. The maximum values of the diffusion energy barriers were 0.82, 0.62, and 0.72 eV for Ni, Cu, and Cu dopants, respectively, with others around 0.25 eV. The diffusion was not affected by the doping for sites far from the doping position. Thus, heteroatom-doped monolayer MoS2 can be used as an anode material for lithium ion batteries.
The exploitation of deep-blue polymeric emitters is of great importance for the application of solution-processed organic light-emitting diodes (OLEDs) in full color display. The highly efficient ...deep-blue thermally activated delayed fluorescence (TADF) polymers are rarely reported up to now. Herein, we developed a series of deep-blue TADF polymers to fabricate highly efficient nondoped solution-processed OLEDs. By incorporating appropriate host with high triplet energy and deep-blue emitter with high fluorescent efficiency, the polymers are endowed with distinct TADF features. Using these deep-blue polymeric emitters, the nondoped single polymer based OLEDs achieve a maximum external quantum efficiency of 5.3% with the Commission Internationale de L’Eclairage (CIE) coordinates of (0.15, 0.09), which represents the state-of-the-art device performance for the TADF-based deep-blue polymer light-emitting diodes (PLEDs).
Matrix metalloproteinase-10 (MMP-10) is a zinc-dependent endopeptidase with the ability to degrade a broad spectrum of extracellular matrices and other protein substrates. The expression of MMP-10 is ...induced in acute kidney injury (AKI) and chronic kidney disease (CKD), as well as in renal cell carcinoma (RCC). During the different stages of kidney injury, MMP-10 may exert distinct functions by cleaving various bioactive substrates including heparin-binding epidermal growth factor (HB-EGF), zonula occludens-1 (ZO-1), and pro-MMP-1, -7, -8, -9, -10, -13. Functionally, MMP-10 is reno-protective in AKI by promoting HB-EGF-mediated tubular repair and regeneration, whereas it aggravates podocyte dysfunction and proteinuria by disrupting glomerular filtration integrity via degrading ZO-1. MMP-10 is also involved in cancerous invasion and emerges as a promising therapeutic target in patients with RCC. As a secreted protein, MMP-10 could be detected in the circulation and presents an inverse correlation with renal function. Due to the structural similarities between MMP-10 and the other MMPs, development of specific inhibitors targeting MMP-10 is challenging. In this review, we summarize our current understanding of the role of MMP-10 in kidney diseases and discuss the potential mechanisms of its actions.
Liver cell death has an essential role in nonalcoholic steatohepatitis (NASH). The activity of the energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK) is repressed in NASH. ...Liver-specific AMPK knockout aggravated liver damage in mouse NASH models. AMPK phosphorylated proapoptotic caspase-6 protein to inhibit its activation, keeping hepatocyte apoptosis in check. Suppression of AMPK activity relieved this inhibition, rendering caspase-6 activated in human and mouse NASH. AMPK activation or caspase-6 inhibition, even after the onset of NASH, improved liver damage and fibrosis. Once phosphorylation was decreased, caspase-6 was activated by caspase-3 or -7. Active caspase-6 cleaved Bid to induce cytochrome c release, generating a feedforward loop that leads to hepatocyte death. Thus, the AMPK-caspase-6 axis regulates liver damage in NASH, implicating AMPK and caspase-6 as therapeutic targets.
The Industry 4.0 concept proposes that new cutting-edge technologies, such as the Internet of Things (IoT), will grow. The acceptance of IoT in the circular economy (CE) is still in its infancy, ...despite its enormous potential. In the face of growing environmental affairs, IoT based Industry 4.0 technologies are altering CE practices and existing business models, according to the World Economic Forum. This research investigates the function of IoT-based Industry 4.0 in circular CE practices, as well as their impact on economic and environmental performance, which in turn influences overall organizational performance. China-based enterprises provide information for the study, which includes data from 300 companies. Utilizing a structural equation modeling framework known as partial least squares structural equation modeling (PLS-SEM). The major findings are presented in the study: (I) the IoT significantly improves the activities of the CE; (II) the IoT significantly improves the practices of the CE; and (III) the IoT meaningfully advances the practices of CE (green manufacturing, circular design, remanufacturing, and recycling). Moreover, the findings shows that environmentally friendly business practices help enhance environmental performance of firm, while also stimulating their economic performance; and improved environmental performance has a significant positive influence on firm performance. This research lays the groundwork for contributing nations/companies to attain economic and long-term sustainability goals at the same time by incorporating IoT-based Industry 4.0 technology into CE practices.
This paper presents a novel approach to substantially improve the detection accuracy of structural damage via a one-dimensional convolutional neural network (1-D CNN) and a decision-level fusion ...strategy. As structural damage usually induces changes in the dynamic responses of a structure, a CNN can effectively extract structural damage information from the vibration signals and classify them into the corresponding damage categories. However, it is difficult to build a large-scale sensor system in practical engineering; the collected vibration signals are usually non-synchronous and contain incomplete structure information, resulting in some evident errors in the decision stage of the CNN. In this study, the acceleration signals of multiple acquisition points were obtained, and the signals of each acquisition point were used to train a 1-D CNN, and their performances were evaluated by using the corresponding testing samples. Subsequently, the prediction results of all CNNs were fused (decision-level fusion) to obtain the integrated detection results. This method was validated using both numerical and experimental models and compared with a control experiment (data-level fusion) in which all the acceleration signals were used to train a CNN. The results confirmed that: by fusing the prediction results of multiple CNN models, the detection accuracy was significantly improved; for the numerical and experimental models, the detection accuracy was 10% and 16–30%, respectively, higher than that of the control experiment. It was demonstrated that: training a CNN using the acceleration signals of each acquisition point and making its own decision (the CNN output) and then fusing these decisions could effectively improve the accuracy of damage detection of the CNN.
In polymer processing operations, the molten polymer chains are frequently subjected to shear or/and elongation flow fields, which will produce molecular chain orientation of the melt. This leads to ...the orientation-induced crystallization has been an important subject in the field of polymer physics. Systematic studies indicated that the chain orientation influences the crystallization kinetics, the final morphology as well as the polymorphic behavior of the polymers. In this article, the effects of preorientation on the crystallization of isotactic polypropylene (iPP) concerning the above mentioned aspects have been reviewed. In particular, the formation mechanism of orientation-induced β-iPP crystallization has been discussed according to the recent experimental results. It is suggested that the local order of the macromolecular chain segments in the melt is most important for β-nucleation of iPP. The formation of β-iPP nuclei may be restricted in a certain chain orientation window of the iPP melts. Chain orientation outside of this window results in the formation of α-iPP.
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Accumulation of mutant proteins is a major cause of many diseases (collectively called proteopathies), and lowering the level of these proteins can be useful for treatment of these diseases. We ...hypothesized that compounds that interact with both the autophagosome protein microtubule-associated protein 1A/1B light chain 3 (LC3)
and the disease-causing protein may target the latter for autophagic clearance. Mutant huntingtin protein (mHTT) contains an expanded polyglutamine (polyQ) tract and causes Huntington's disease, an incurable neurodegenerative disorder
. Here, using small-molecule-microarray-based screening, we identified four compounds that interact with both LC3 and mHTT, but not with the wild-type HTT protein. Some of these compounds targeted mHTT to autophagosomes, reduced mHTT levels in an allele-selective manner, and rescued disease-relevant phenotypes in cells and in vivo in fly and mouse models of Huntington's disease. We further show that these compounds interact with the expanded polyQ stretch and could lower the level of mutant ataxin-3 (ATXN3), another disease-causing protein with an expanded polyQ tract
. This study presents candidate compounds for lowering mHTT and potentially other disease-causing proteins with polyQ expansions, demonstrating the concept of lowering levels of disease-causing proteins using autophagosome-tethering compounds.
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