As the number of patients with Alzheimer’s disease (AD) increases, it brings great suffering to their families and causes a heavy socioeconomic burden to society. A vast amount of funds and a mass of ...research have been devoted to elucidating the pathology of AD. However, the main pathogenesis is still elusive, and its mechanism is not completely clear. Research on the mechanisms of AD mainly focuses on the amyloid cascade, tau protein, neuroinflammation, metal ions, and oxidative stress hypotheses. Oxidative stress is as a bridge that connects the different hypotheses and mechanisms of AD. It is a process that causes neuronal damage and occurs in various pathways. Oxidative stress plays a critical role in AD and can even be considered a crucial central factor in the pathogenesis of AD. Previous reviews have also summarized the role of oxidative stress in AD, but these mainly review a specific signaling pathway. Taking oxidative stress as the central point, this review comprehensively expands on the roles of oxidative stress that are involved in the pathogenesis of AD. The vivid and easy-to-understand figures systematically clarify the connected roles of oxidative stress in AD and allow readers to further understand oxidative stress and AD.
•AD brings great suffering to patients’ families and causes a heavy socioeconomic burden to society.•Oxidative stress is the key "bridge" connecting various AD pathogenesis and pathways.•Oxidative stress is a key process and unavoidable stage of all AD mechanisms.•The "central role" of oxidative stress in AD was comprehensively reviewed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A facile and efficient method is presented for the synthesis of 6‐alkylated phenanthridine, possessing hindered quaternary carbon centers, by Zn‐mediated reductive trapping of tertiary alkyl radicals ...with both electron‐rich and electron‐deficient aryl isocyanides using nickel as a promoter. Bench‐stable and operation‐friendly tertiary alkyl oxalates derived from abundant tertiary alkyl alcohols were first used as radical precursors for the alkylation of isocyanobiphenyl species. This reaction displays excellent functional group tolerance and broad substrate scope, allowing access to desired products in good to excellent yields.
The efficient radical cascade cyclization protocol for the reductive cleavage of C−O bonds followed by phenanthridine formation is reported. The method involves generating tertiary alkyl radical intermediates that are invoked by single‐electron reduction by Zn, wherein MgCl2 serves as the indispensable additive and nickel as the promoter. The reaction displays excellent functional group tolerance and broad substrate scope.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Exploiting radio frequency signals is promising for locating and tracking objects. Prior works focus on per-tag localization, in which each object is attached with one tag. In this paper, we propose ...a comprehensive localization and tracking scheme by attaching two RFID tags to one object. Instead of using per-tag localization pattern, adding one-more RFID tag to the object exhibits several benefits: 1) providing rich freedom in RFID reader's antenna spacing and placement; 2) supporting accurate calibration of the reader's antenna location and spacing, and 3) enabling fine-grained calculation on the orientation of the tags. All of these advantages ultimately improve the localization/tracking accuracy. Our extensive experimental results demonstrate that the average errors of localization and orientation of target tags are 6.415 cm and 1.330°, respectively. Our results also verify that the reader's antenna geometry does have impact on tag positioning performance.
The coronavirus disease‐19 (COVID‐19) pandemic has become a global threat since its first outbreak at the end of 2019. Several review articles have been published recently, focusing on the aspects of ...target biology, drug repurposing, and mechanisms of action (MOAs) for potential treatment. This review gathers all small molecules currently in active clinical trials, categorizes them into six sub‐classes, and summarizes their clinical progress. The aim is to provide the researchers from both pharmaceutical industries and academic institutes with the handful information and dataset to accelerate their research programs in searching effective small molecule therapy for treatment of COVID‐19.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Genetics, age, environmental factors, and oxidative stress have all been implicated in the development of Parkinson's disease (PD); however, a complete understanding of its pathology remains elusive. ...At present, there is no cure for PD, and currently available therapeutics are insufficient to meet patient needs. Ferroptosis, a distinctive iron‐dependent cell death mode characterized by lipid peroxidation and oxidative stress, has pathophysiological features similar to those of PD, including iron accumulation, reactive oxygen species‐induced oxidative damage, and mitochondrial dysfunction. Ferroptosis has been identified as a specific pathway of neuronal death and is closely related to the pathogenesis of PD. Despite the similarities in the biological targets involved in PD pathogenesis and ferroptosis, the relationship between novel targets in PD and ferroptosis has been neglected in the literature. In this review, the mechanism of ferroptosis is discussed, and the potential therapeutic targets implicated in both PD and ferroptosis are compared. Furthermore, the anti‐PD effects of several ferroptosis inhibitors, as well as clinical studies thereof, and the identification of novel lead compounds for the treatment of PD and the inhibition of ferroptosis are reviewed. It is hoped that this review can promote research to further elucidate the relationship between ferroptosis and PD and provide new strategies for the development of novel ferroptosis‐targeting PD therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Pancreatic cancer (PC) is a great health burden to patients owing to its poor overall survival rate. Long noncoding RNAs (lncRNAs) interact with microRNAs (miRs) to participate in tumorigenesis. ...Therefore, we aim to uncover the role and related mechanism of LINC00473 in PC through the modulation of miR‐195‐5p and programmed death‐ligand 1 (PD‐L1). Increased LINC00473 and PD‐L1 but declined miR‐195‐5p were determined in PC tissues and cell lines, and it was found that LINC00473 mainly situated in the cytoplasm. Also, miR‐195‐5p was verified to bind with both LINC00473 and PD‐L1. Next, with the aim to examine the ability of LINC00473, miR‐195‐5p, and PD‐L1 on the PC progression, the expression of LINC00473, miR‐195‐5p and PD‐L1 were altered with mimics, inhibitors, overexpression vectors or siRNAs in PC cells and cocultured CD8+ T cells. It was demonstrated that LINC00473 sponged miR‐195‐5p to upregulate PD‐L1 expression. More important, the obtained results revealed that LINC00473 silencing or miR‐195‐5p upregulation elevated the expression of Bcl‐2 associated X protein (Bax), interferon (IFN)‐γ, and interleukin (IL)‐4 but reduced the expression of B‐cell lymphoma‐2 (Bcl‐2), matrix metalloproteinase (MMP)‐2, MMP‐9, and IL‐10, thus inducing the enhancement of the apoptosis as along with the inhibition of proliferation, invasion, and migration of the PC cells. LINC00473 silencing or miR‐195‐5p elevation activated the CD8+ T cells. Taken together, LINC00473 silencing blocked the PC progression through enhancing miR‐195‐5p‐targeted downregulation of PD‐L1. This finding offers new therapeutic options for treating this devastating disease.
Taken together, LINC00473 silencing blocked the pancreatic cancer progression through enhancing miR‐195‐5p‐targeted downregulation of PD‐L1. This finding offers new therapeutic options for treating this devastating disease.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Herein, we present a facile and efficient allylation method
via
Ni-catalyzed cross-electrophile coupling of readily available allylic acetates with a variety of substituted alkenyl bromides using ...zinc as the terminal reductant. This Ni-catalyzed modular approach displays excellent functional group tolerance and a broad substrate scope, which the creation of a series of 1,4-dienes including several structurally complex natural products and pharmaceutical motifs. Moreover, the coupling strategy has the potential to realize enantiomeric control. The practicality of this transformation is demonstrated through the potent modification of the naturally antitumor active molecule β-elemene.
Herein, we present a facile and efficient allylation method
via
Ni-catalyzed cross-electrophile coupling of readily available allylic acetates with a variety of substituted alkenyl bromides using zinc as the terminal reductant.
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IJS, KILJ, NUK, UL, UM, UPUK
The Co2P nanoparticles strongly coupled with P-modified NiMoO4 nanorods are designed by a novel carbon encapsulated strategy, representing the highly-active pH-universal electrodes for HER. The ...superior catalytic performance of C-Co2P@P-NiMoO4/NF electrode is mainly deriving from the synergistic coupled effects of multiple metal centers, oxygen vacancies, carbon encapsulated and heterostructure.
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The development of hydrogen evolution reaction (HER) technology that operates stably in a wide potential of hydrogen (pH) range of electrolytes is particular important for large-scale hydrogen production. However, the rational design of low-cost and pH-universal electrocatalyst with high catalytic performance remains a huge challenge. Herein, Co2P nanoparticles strongly coupled with P-modified NiMoO4 nanorods are directly grown on nickel foam (NF) substrates through carbon layer encapsulation (denoted as C-Co2P@P-NiMoO4/NF) by hydrothermal, deposition, and phosphating processes. This novel kind of hierarchical heterojunction has abundant heterogeneous interfaces, strong electronic interactions, and optimized reaction kinetics, representing the highly-active pH-universal electrodes for HER. Remarkably, the C-Co2P@P-NiMoO4/NF catalyst shows excellent HER properties in acidic and basic electrolytes, where the overpotentials of 105 mV and 107 mV are applied to drive the current density of 100 mA cm−2. In addition, a low overpotential of 177 mV at 100 mA cm−2 along with high stability is realized in 1 M phosphate buffer solution (PBS), which is close to the state-of-the-art non-precious metal electrocatalysts. Our work not only provides a class of robust pH-universal electrocatalyst but also offers a novel way for the rational design of other heterogeneous materials bythe interface regulation strategy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To obtain supercapacitors for wearable electronic devices, highly conductive stretchable electrode substrates with excellent tensile recovery are required. However, the simultaneous realization of ...the above mentioned characteristics is difficult. In this study, tough stainless‐steel fibers (SSFs) are employed as the substrates for knitting into stainless‐steel meshes (SSMs), for the fabrication of textile electrodes with typical 2D‐interconnected networks. The obtained knitted networks can transform the angular elasticity of SSFs into the stretchability of the textile electrodes. The electrodes based on the SSM substrates can be obtained via the in situ growth of NiCo2S4 nanosheets covered by CoS2 nanowires, which exhibit a high specific capacity, high rate capability, and excellent cycling stability. Moreover, the first stretchable solid‐state hybrid supercapacitors based on SSM display excellent performances with respect to a high energy density (60.2 Wh kg−1 at 800 W kg−1), remarkable tensile recovery (≤40% elongation), and high stability (≈76.4% capacity retention at 30% strain for 1000 stretching cycles). The highly stretchable supercapacitor is sewn on the elbow of a garment to drive a light‐emitting diode, and it maintains a high performance with respect to the repetitive process of bending and straightening, thus demonstrating the high applicability of the designed SSMs to wearable electronics.
Knitted textile electrodes of typical 2D interconnected networks with special patterns from stainless‐steel fibers are applied in stretchable solid‐state hybrid supercapacitors. The supercapacitors retain 76.4% of the initial capacitance at 30% strain after 1000 stretching cycles, and display excellent electrochemical and mechanical stability, demonstrating high applicability in wearable electronics.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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Epigenetic enzymes histone deacetylases (HDACs) are clinically validated anticancer drug targets which have been studied intensively in the past few decades. Although several drugs ...have been approved in this field, they are still limited to a subset of hematological malignancies (in particular T-cell lymphomas), with therapeutic potential not fully realized and the drug-resistance occurred after a certain period of use. To maximize the therapeutic potential of these classes of anticancer drugs, and to extend their application to solid tumors, numerous combination therapies containing an HDACi and an anticancer agent from other mechanisms are currently ongoing in clinical trials. Recently, dual targeting strategy comprising the HDACs component has emerged as an alternative approach for combination therapies. In this perspective, we intend to gather all HDACs-containing dual inhibitors related to cancer therapy published in literature since 2015, classify them into five categories based on targets’ biological functions, and discuss the rationale why dual acting agents should work better than combinatorial therapies using two separate drugs. The article discusses the pharmacological aspects of these dual inhibitors, including in vitro biological activities, pharmacokinetic studies, in vivo efficacy studies, as well as available clinical trials. The review of the current status and advances should provide better analysis for future opportunities and challenges of this field.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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