Inorganic perovskite ferroelectrics are widely used in nonvolatile memory elements, capacitors, and sensors because of their excellent ferroelectric and other properties. Organic ferroelectrics are ...desirable for their mechanical flexibility, low weight, environmentally friendly processing, and low processing temperatures. Although almost a century has passed since the first ferroelectric, Rochelle salt, was discovered, examples of highly desirable organic perovskite ferroelectrics are lacking. We found a family of metal-free organic perovskite ferroelectrics with the characteristic three-dimensional structure, among which MDABCO (
-methyl-
-diazabicyclo2.2.2octonium)-ammonium triiodide has a spontaneous polarization of 22 microcoulombs per square centimeter close to that of barium titanate (BTO), a high phase transition temperature of 448 kelvins (above that of BTO), and eight possible polarization directions. These attributes make it attractive for use in flexible devices, soft robotics, biomedical devices, and other applications.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Molecular recognition, which is the process of biological macromolecules interacting with each other or various small molecules with a high specificity and affinity to form a specific complex, ...constitutes the basis of all processes in living organisms. Proteins, an important class of biological macromolecules, realize their functions through binding to themselves or other molecules. A detailed understanding of the protein-ligand interactions is therefore central to understanding biology at the molecular level. Moreover, knowledge of the mechanisms responsible for the protein-ligand recognition and binding will also facilitate the discovery, design, and development of drugs. In the present review, first, the physicochemical mechanisms underlying protein-ligand binding, including the binding kinetics, thermodynamic concepts and relationships, and binding driving forces, are introduced and rationalized. Next, three currently existing protein-ligand binding models--the "lock-and-key", "induced fit", and "conformational selection"--are described and their underlying thermodynamic mechanisms are discussed. Finally, the methods available for investigating protein-ligand binding affinity, including experimental and theoretical/computational approaches, are introduced, and their advantages, disadvantages, and challenges are discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Organic ferroelectrics are highly desirable for their light weight, mechanical flexibility and biocompatibility. However, the rational design of organic ferroelectrics has always faced great ...challenges. Anilinium bromide (AB) has two structures reported in the Cambridge Crystallographic Data Centre, which might be an mmmF2/m type ferroelastic (AB‐1). When we studied its ferroelasticity, we were surprised to discover that there was another crystal (AB‐2) in H2O besides this one, and they were very difficult to separate. By changing the solvent, we found that AB‐1 crystals could be formed in ethanol, where ferroelastic domains were visualized by polarized light microscopy, and AB‐2 crystals could be obtained from various crystallization solvents of methanol, isopropanol, N‐butanol, acetonitrile, dimethyl sulfoxide, and N,N‐dimethylformamide, which undergo a ferroelectric phase transition with mm2Fm, showing clear ferroelectricity in two phases. To our knowledge, the regulation of ferroelasticity to ferroelectricity by solvent selective effect is unprecedented in the field of ferroelectrics. This work reveals the important role of solvent effect in organic ferroelectrics.
A solvent selective effect for the regulation of ferroelasticity and ferroelectricity of anilinium bromide is described, which is unprecedented in organic molecular ferroelectrics. Two forms of crystal structure were obtained from different crystallization solvents: ferroelastic AB‐1 and ferroelectric AB‐2. Atom key: Br (green), N (blue), H (light blue), C (gray).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background and Purpose
Regulating P2X7 receptor‐mediated activation of NLRP3 inflammasomes could be a therapeutic strategy to treat alcoholic hepatosteatosis. We investigated whether this process was ...modulated by gentiopicroside, the main active secoiridoid glycoside from Gentiana manshurica Kitagawa.
Experimental Approach
In vivo models of acute and chronic alcoholic hepatosteatosis were established by intragastrically administered ethanol or using chronic plus binge ethanol feeding of Lieber‐DeCarli liquid diet to male C57BL/6 mice. In vitro, HepG2 cells were treated with ethanol. RAW 264.7 macrophages and murine bone marrow‐derived macrophages (BMDMs) were stimulated with LPS and ATP.
Key Results
In both the acute and chronic alcohol‐induced mouse hepatosteatosis models, gentiopicroside decreased serum aminotransferases and triglyceride accumulation. Up‐regulated SREBP1, down‐regulated PPARα and phosphorylated acetyl‐CoA carboxylase caused by acute and chronic alcohol feeding were modulated by gentiopicroside, through the elevation of LKB1 and AMPK. Suppression of P2X7 receptor‐NLRP3 activation by gentiopicroside inhibited IL‐1β production. In ethanol‐exposed HepG2 cells, gentiopicroside reduced lipogenesis and promoted lipid oxidation via activation of P2X7 receptor‐NLRP3 inflammasomes. Genetic or pharmacological blockade of P2X7 receptors enhanced AMPK activity and reduced SREBP1 expression in ethanol‐treated HepG2 cells. Gentiopicroside down‐regulated P2X7 receptor‐mediated inflammatory responses in LPS/ATP‐stimulated RAW 264.7 macrophages and BMDMs. IL‐1β from macrophages accelerated lipid accumulation in hepatocytes. Depleting macrophages by clodronate liposomes ameliorated alcoholic hepatosteatosis, and it was further alleviated by gentiopicroside.
Conclusions and Implications
Activation of LKB1/AMPK signalling by gentiopicroside was mediated by the P2X7 receptor‐NLRP3 inflammasome, suggesting the therapeutic value of blocking P2X7 receptors in the treatment of alcoholic hepatosteatosis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Owing to high intrinsic figure‐of‐merit implemented by multi‐band valleytronics, GeTe‐based thermoelectric materials are promising for medium‐temperature applications. Transition metals are widely ...used as dopants for developing high‐performance GeTe thermoelectric materials. Herein, relevant work is critically reviewed to establish a correlation among transition metal doping, electronic quality factor, and figure‐of‐merit of GeTe. From first‐principle calculations, it is found that Ta, as an undiscovered dopant in GeTe, can effectively converge energy offset between light and heavy conduction band extrema to enhance effective mass at high temperature. Such manipulation is verified by the increased Seebeck coefficient of synthesized Ge1−x−yTaxSbyTe samples from 160 to 180 µV K−1 at 775 K upon doping Ta, then to 220 µV K−1 with further alloying Sb. Characterization using electron microscopy also reveals the unique herringbone structure associated with multi‐scale lattice defects induced by Ta doping, which greatly hinder phonon propagation to decrease thermal conductivity. As a result, a figure‐of‐merit of ≈2.0 is attained in the Ge0.88Ta0.02Sb0.10Te sample, reflecting a maximum heat‐to‐electricity efficiency up to 17.7% under a temperature gradient of 400 K. The rationalized beneficial effects stemming from Ta doping is an important observation that will stimulate new exploration toward high‐performance GeTe‐based thermoelectric materials.
The nexus between electronic quality factor and thermoelectric figure‐of‐merit in transition‐metal‐doped GeTe, which can serve as a facile yet efficient descriptor for high‐throughput screening of good thermoelectric materials, is explained. To clarify this point, Ta‐doped GeTe is designed with optimized electronic quality factor, rendering a figure‐of‐merit over 2.0 and a conceptional efficiency over 15%.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Well‐organized Si‐Cu nanocables are directly anchored on a current collector to promote the cycling stability and high rate capability of Si as a superior anode in lithium‐ion batteries.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Face recognition has made extraordinary progress owing to the advancement of deep convolutional neural networks (CNNs). The central task of face recognition, including face verification and ...identification, involves face feature discrimination. However, the traditional softmax loss of deep CNNs usually lacks the power of discrimination. To address this problem, recently several loss functions such as center loss, large margin softmax loss, and angular softmax loss have been proposed. All these improved losses share the same idea: maximizing inter-class variance and minimizing intra-class variance. In this paper, we propose a novel loss function, namely large margin cosine loss (LMCL), to realize this idea from a different perspective. More specifically, we reformulate the softmax loss as a cosine loss by L2 normalizing both features and weight vectors to remove radial variations, based on which a cosine margin term is introduced to further maximize the decision margin in the angular space. As a result, minimum intra-class variance and maximum inter-class variance are achieved by virtue of normalization and cosine decision margin maximization. We refer to our model trained with LMCL as CosFace. Extensive experimental evaluations are conducted on the most popular public-domain face recognition datasets such as MegaFace Challenge, Youtube Faces (YTF) and Labeled Face in the Wild (LFW). We achieve the state-of-the-art performance on these benchmarks, which confirms the effectiveness of our proposed approach.
Novel imidazolium-based norbornene polymerized ionic liquids (PILs) with different counterions (CH 3 SO 3 − , CF 3 SO 3 − , CF 3 (CF 2 ) 3 SO 3 − , FSI − , Tf 2 N − ) for self-healing are synthesized ...via ring-opening metathesis polymerization (ROMP) utilizing the Grubbs third generation catalyst (G3). As proved by the changes in the chemical shift of the imidazolium proton in 1 H NMR spectra in CDCl 3 , variation of the counterion brings different interaction intensities between imidazolium and counterions. The glass transition temperature ( T g ) was mainly influenced by the size of the counterion. For large counterions such as FSI − and Tf 2 N − , they not only formed loose ionic aggregates leading to weak physical cross-links, but also acted as plasticizers in the polymer matrix, resulting in a decrease of T g . X-ray scattering tests also proved that small counterions were prone to forming packed ion clusters leading to intensive ion aggregation. The ionic associations in the polymer matrix serve as physical cross-links, restricting the mobility of the surrounding polymer chain and improving the mechanical strength. However, sufficient chain mobility was in favor of the dynamic rearrangement of ion aggregation over the fracture surface that imparted the self-healing behavior. To balance the mechanical properties and healing performance, PIL blends with appropriate T g were prepared by blending a high T g PIL (such as CH 3 SO 3 − , CF 3 SO 3 − or CF 3 (CF 2 ) 3 SO 3 − ) with varying amounts of a low T g PIL ( i.e. Tf 2 N − ). Via this approach, the T g of the resulting blends could be systemically tuned by adjusting the blending ratio and counterion. As expected, both excellent mechanical performance and self-healing capability of the well-designed PILs were achieved simultaneously.
Background and Purpose
Regulating macrophage–hepatocyte crosstalk through P2X7 receptors has led to new pharmacological strategies to reverse alcoholic hepatosteatosis. We investigated how ...tetrahydroxystilbene glucoside (2354glu), isolated from Polygonum multiflorum, modulates macrophage–hepatocyte crosstalk during alcoholic hepatosteatosis.
Experimental Approach
A model of alcoholic hepatosteatosis was established by giving ethanol intragastrically to C57BL/6 mice. HepG2 cells were incubated in conditioned medium from LPS+ATP‐activated THP‐1 human macrophages with silenced or overexpressed P2X7 receptors. THP‐1 macrophages or mouse peritoneal macrophages were pretreated with 2354glu for 1 hr prior to LPS+ATP stimulation. Western blots, RT‐PCR and immunohistochemical analysis were used, along with over‐expression and silencing of P2X7 receptors.
Key Results
Knockdown or overexpression of P2X7 receptors in THP‐1 macrophages affected release of mature IL‐1β and, subsequently, modulated lipid metabolism in HepG2 cells via the LKB–AMPK pathway. 2354glu ameliorated alcoholic hepatosteatosis in mice by regulating LKB1–AMPK–SREBP1 pathway and its target genes. Suppression of P2X7 receptor activation by 2354glu inhibited IL‐1β release and reduced macrophage and neutrophil infiltration. In macrophages stimulated with LPS+ATP, expression of P2X7 receptors, caspase‐1 and NF‐κB, release of IL‐1β, calcium influx and PI uptake were reduced by 2354glu. SIRT1–LKB1–AMPK–SREBP1 axis‐mediated lipid accumulation in HepG2 cells was reduced when they were cultured with conditioned media from LPS+ATP‐activated THP‐1 macrophages pretreated with 2354glu.
Conclusion and Implications
Modulation of P2X7 receptors in macrophages regulated lipid accumulation in hepatocytes during alcoholic hepatosteatosis. 2354glu might be a promising candidate that targets P2X7 receptors in macrophages interacting with hepatocytes during alcoholic hepatosteatosis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Purpose
Interleukin‐36 is induced by proinflammatory cytokines and promotes inflammatory responses, creating an IL‐36‐based inflammation loop. Although hepatocytes, produce IL‐36 ...responses to drug‐induced liver injury, little is known about the mechanistic role of IL‐36 signalling during the progression of alcoholic steatohepatitis (ASH). Regarding IL‐36/IL‐36R and P2X7R coregulating the inflammatory response, we elucidated that modulation of IL‐36R‐P2X7R‐TLR axis affected hepatocyte steatosis as well as the IL‐36‐based inflammatory feedback loop that accompanies the onset of ASH.
Experimental Approach
C57BL/6J mice were subjected to either chronic‐plus‐binge ethanol feeding or acute gavage with multiple doses of ethanol to establish ASH, followed by pharmacological inhibition or genetic silencing of IL‐36R and P2X7R. AML12 cells or mouse primary hepatocytes were stimulated with alcohol, LPS plus ATP or Poly(I:C) plus ATP, followed by silencing of IL‐36γ, IL‐36R or P2X7R.
Key Results
P2X7R and IL‐36R deficiency blocked the inflammatory loop, specifically initiated by IL‐36 cytokines, in hepatocytes of mice suffering from ASH. Pharmacological inhibition to P2X7R or IL‐36R alleviated lipid accumulation and inflammatory response in ASH. IL‐36R was indispensable for P2X7R modulated NLRP3 inflammasome activation in ASH, and IL‐36 led to a vicious cycle of P2X7R‐driven inflammation in alcohol‐treated hepatocytes. TLR ligands promoted IL‐36γ production in hepatocytes, based on synergism with P2X7R.
Conclusions and Implications
Blockade of IL‐36 based inflammatory feedback loop, via IL‐36R‐P2X7R‐TLRs‐modulated NLRP3 inflammasome activation, circumvented steatosis and inflammation that accompanies the onset of ASH, suggesting that targeting IL‐36 can serve as a novel therapeutic approach to combat ASH.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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