Aliphatic carboxylates are the most common class of surface ligands to stabilize colloidal nanocrystals. The widely used approach to identify the coordination modes between surface cationic sites and ...carboxylate ligands is based on the empirical infrared (IR) spectroscopic assignment, which is often ambiguous and thus hampers the practical control of surface structures. In this report, multiple techniques based on nuclear magnetic resonance (NMR) and IR spectra are applied to distinguish the different coordination structures in a series of zinc-blende CdSe nanocrystals with unique facet structures, including nanoplatelets dominated with {100} basal planes, hexahedrons with only three types of low-index facets (i.e., {100}, {110}, and {111}), and spheroidal dots without well-defined facets. Interpretation and assignment of NMR and IR signals were assisted by density functional theory (DFT) calculations. In addition to the identification of facet-sensitive bonding modes, the present methods also allow a nondestructive quantification of mixed ligands.
FADD is a common adaptor shared by several death receptors for signalling apoptosis through recruitment and activation of caspase 8 (refs 1-3). Death receptors are essential for immune homeostasis, ...but dispensable during embryogenesis. Surprisingly, Fadd(-/-) mice die in utero and conditional deletion of FADD leads to impaired lymphocyte proliferation. How FADD regulates embryogenesis and lymphocyte responses has been a long-standing enigma. FADD could directly bind to RIP1 (also known as RIPK1), a serine/threonine kinase that mediates both necrosis and NF-κB activation. Here we show that Fadd(-/-) embryos contain raised levels of RIP1 and exhibit massive necrosis. To investigate a potential in vivo functional interaction between RIP1 and FADD, null alleles of RIP1 were crossed into Fadd(-/-) mice. Notably, RIP1 deficiency allowed normal embryogenesis of Fadd(-/-) mice. Conversely, the developmental defect of Rip1(-/-) lymphocytes was partially corrected by FADD deletion. Furthermore, RIP1 deficiency fully restored normal proliferation in Fadd(-/-) T cells but not in Fadd(-/-) B cells. Fadd(-/-)Rip1(-/-) double-knockout T cells are resistant to death induced by Fas or TNF-α and show reduced NF-κB activity. Therefore, our data demonstrate an unexpected cell-type-specific interplay between FADD and RIP1, which is critical for the regulation of apoptosis and necrosis during embryogenesis and lymphocyte function.
The ubiquitination status of RIPK1 is considered to be critical for cell fate determination. However, the in vivo role for RIPK1 ubiquitination remains undefined. Here we show that mice expressing ...RIPK1
which is defective in RIPK1 ubiquitination die during embryogenesis. This lethality is fully rescued by concomitant deletion of Fadd and Ripk3 or Mlkl. Mechanistically, cells expressing RIPK1
are more susceptible to TNF-α induced apoptosis and necroptosis with more complex II formation and increased RIPK1 activation, which is consistent with the observation that Ripk1
lethality is effectively prevented by treatment of RIPK1 kinase inhibitor and is rescued by deletion of Tnfr1. However, Tnfr1
Ripk1
mice display systemic inflammation and die within 2 weeks. Significantly, this lethal inflammation is rescued by deletion of Ripk3. Taken together, these findings reveal a critical role of Lys376-mediated ubiquitination of RIPK1 in suppressing RIPK1 kinase activity-dependent lethal pathways during embryogenesis and RIPK3-dependent inflammation postnatally.
The cyclical impact signal aroused by mechanical fault contains feature information, such as fault type and fault stage. However, a transient impact component is usually modulated on the fundamental ...frequency and mixed with a large amount of noise. Thus, it is difficult to be extracted effectively. A feature extraction method of faults stage is presented based on morphological filter theory. An antinoise morphological gradient operator is applied to signal filtering. This operator can weaken the noise and clearly highlight the impact characteristics of different fault stages. The kurtosis of the spectrum band, including the passing frequencies of mechanical components, is used to differentiate fault stages. The applications on simulation signals and bearing test data indicate that this method can realize accurate extraction of fault characteristic frequency submerged in noise and effective distinction of different fault stages.
Stiffened plates are widely used in engineering due to their excellent manufacturing and mechanical properties. This paper introduces a novel method for designing stiffener plates that combines the ...H-DGTP formulation, robust topology optimization formulation, and maximum length-scale control. In comparison to existing methods, the proposed approach not only provides a clear layout of stiffeners but also optimizes their height. Sensitivity analysis of all design variables is derived for utilization with gradient-based optimizers. The study demonstrates that the implementation of the robust filter approach enables precise control of both structural features and gap widths, effectively avoiding sharp angles. Moreover, as the maximum length approaches the minimum length, the stiffeners assume uniform thickness, which better meets engineering requirements. Numerical examples are presented to validate the effectiveness of the proposed method.
Abstracts
AF6, a known polarity protein, contributes to the maintenance of homeostasis while ensuring tissue architecture, repair, and integrity. Mice that lack AF6 display embryonic lethality owing ...to cell–cell junction disruption. However, we show AF6 promotes necroptosis via regulating the ubiquitination of RIPK1 by directly interact with the intermediate domain of RIPK1, which was mediated by the deubiquitylase enzyme USP21. Consistently, while injection of mice with an adenovirus providing AF6 overexpression resulted in accelerated TNFα-induced necroptosis-mediated mortality in vivo, we observed that mice with hepatocyte-specific deletion of AF6 prevented hepatocytes from necroptosis and the subsequent inflammatory response in various liver diseases model, including non-alcoholic steatohepatitis (NASH) and the systemic inflammatory response syndrome (SIRS).Together, these data suggest that AF6 represents a novel regulator of RIPK1-RIPK3 dependent necroptotic pathway. Thus, the AF6-RIPK1-USP21 axis are potential therapeutic targets for treatment of various liver injuries and metabolic diseases.
Hydrogen embrittlement, as one of the major concerns for austenitic stainless steel, is closely linked to the diffusion of hydrogen through the grain boundary of materials. The phenomenon is still ...not well understood yet, especially the full interaction between hydrogen diffusion and the misorientation of the grains. This work aimed at the development of a robust numerical strategy to model the full coupling of the hydrogen diffusion and the anisotropic behavior of crystals in 316 stainless steel. A constitutive model, which allows easy incorporation of crystal orientation, various loading conditions, and arbitrary model geometries, was established by using the finite element package ABAQUS. The study focuses on three different bicrystal models composed of misoriented crystals, and the results indicate that the redistribution of hydrogen is significant closely to the grain boundary, and the redistribution is driven by the hydrostatic pressure caused by the misorientation of two neighboring grains. A higher elastic modulus ratio along the tensile direction will lead to a higher hydrogen concentration difference in the two grains equidistant from the grain boundary. The hydrogen concentration shows a high value in the crystal along the direction with stiff elastic modulus. Moreover, there exists a large hydrogen concentration gradient in a narrow region very close to the grain boundary to balance the concentration difference of the neighboring grains.
Conductive hydrogels feature the flexibility of soft materials plus conductive properties providing functionality for effectively sticking to the epidermis and detecting human activity signals. Their ...stable electrical conductivity also effectively avoids the problem of uneven distribution of solid conductive fillers inside traditional conductive hydrogels. However, the simultaneous integration of high mechanical strength, stretchability, and transparency through a simple and green fabrication method remains a great challenge. Herein, a polymerizable deep eutectic solvent (PDES) composed of choline chloride and acrylic acid was added to a biocompatible PVA matrix. The double-network hydrogels were then simply prepared by thermal polymerization and one freeze-thaw method. The introduction of the PDES significantly improved the tensile properties (1.1 MPa), ionic conductivity (2.1 S/m), and optical transparency (90%) of the PVA hydrogels. When the gel sensor was fixed to human skin, real-time monitoring of a variety of human activities could be implemented with accuracy and durability. Such a simple preparation method performed by combining a deep eutectic solvent with traditional hydrogels offers a new avenue to construct multifunctional conductive hydrogel sensors with excellent performance.
Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemia. ChemR23 signaling is involved in the pathophysiology of various inflammatory diseases. ...Nevertheless, the role of ChemR23 signaling in ischemic stroke remains largely unknown.
Permanent ischemic stroke mouse model was accomplished by middle cerebral artery occlusion (MCAO). Resolvin E1 (RvE1) or chemerin-9 (C-9), the agonists of ChemR23, were administered by intracerebroventricular (i.c.v) injection before MCAO induction. Then, analysis of neurobehavioral deficits and brain sampling were done at Day 1 after MCAO. The brain samples were further analyzed by histological staining, immunofluorescence, RNA sequencing, ELISA, transmission electron microscope, and western blots. Furthermore, oxygen-glucose deprivation (OGD) was employed in SH-SY5Y to mimic MCAO in vitro, and ChemR23 signaling pathway was further studied by overexpression of ChemR23 or administration of related agonists or antagonists. Analysis of cell death and related pathway markers were performed.
ChemR23 expression was upregulated following MCAO. Under in vitro and in vivo ischemic conditions, ChemR23 deficiency or inhibition contributed to excessive NLRP3-mediated maturation and release of IL-1β and IL-18, as well as enhanced cleavage of GSDMD-N and neuronal pyroptosis. These influences ultimately aggravated brain injury and neuronal damage. On the other hand, ChemR23 activation by RvE1 or C-9 mitigated the above pathophysiological abnormalities in vivo and in vitro, and overexpression of ChemR23 in SH-SY5Y cells also rescued OGD-induced neuronal pyroptosis. Blockade of NLRP3 mimics the protective effects of ChemR23 activation in vitro.
Our data indicated that ChemR23 modulates NLRP3 inflammasome-mediated neuronal pyroptosis in ischemic stroke. Activation of ChemR23 may serve as a promising potential target for neuroprotection in cerebral ischemia.
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