A solvent‐free induced self‐assembly technology for the synthesis of nitrogen‐doped ordered mesoporous polymers (N‐OMPs) is developed, which is realized by mixing polymer precursors with block ...copolymer templates, curing at 140–180 °C, and calcination to remove the templates. This synthetic strategy represents a significant advancement in the preparation of functional porous polymers through a fast and scalable yet environmentally friendly route, since no solvents or catalysts are used. The synthesized N‐OMPs and their derived catalysts are found to exhibit competitive CO2 capacities (0.67–0.91 mmol g−1 at 25 °C and 0.15 bar), extraordinary CO2/N2 selectivities (98–205 at 25 °C), and excellent activities for catalyzing conversion of CO2 into cyclic carbonate (conversion >95% at 100 °C and 1.2 MPa for 1.5 h). The solvent‐free technology developed in this work can also be extended to the synthesis of N‐OMP/SiO2 nanocomposites, mesoporous SiO2, crystalline mesoporous TiO2, and TiPO, demonstrating its wide applicability in porous material synthesis.
A novel and green strategy in which no solvents are used, for the fast synthesis of nitrogen‐doped ordered mesoporous polymers (N‐OMPs) is developed. The N‐OMPs display competitive CO2 capacities and extraordinary CO2/N2 selectivities, as well as excellent activity for catalytic conversion of CO2. The methodology can also be extended to the synthesis of N‐OMP/SiO2 nanocomposites, mesoporous SiO2, TiO2, and TiPO.
Serine/threonine kinase 17b (STK17B, also known as DRAK2) is known to be a downstream effector of protein kinase C (PKC) in the immune system, in particular T lymphocytes. PKC activity also plays a ...critical role for dendritic development and synaptic maturation and plasticity in cerebellar Purkinje cells. We present evidence that STK17B is strongly expressed in mouse cerebellar Purkinje cells starting in the early postnatal period and remaining highly expressed throughout adult stages and that STK17B is a target of PKC phosphorylation in the cerebellum. STK17B overexpression potentiates the morphological changes of Purkinje cells seen after PKC activation, suggesting that it is a downstream effector of PKC. A phosphorylation mimetic STK17B variant induced a marked reduction of Purkinje cell dendritic tree size, whereas the inhibition of STK17B with the novel compound 16 (Cpd16) could partially rescue the morphological changes of the Purkinje cell dendritic tree after PKC activation. These findings show that STK17B signalling is an important downstream effector of PKC activation in Purkinje cells. Furthermore, STK17B was identified as a molecule being transcriptionally downregulated in mouse models of SCA1, SCA7, SCA14 and SCA41. The reduced expression of STK17B in these mouse models might protect Purkinje cell dendrites from the negative effects of overactivated PKC signalling. Our findings provide new insights in the role of STK17B for Purkinje cell dendritic development and the pathology of SCAs.
In a mouse model of SCA14 with constitutive activation of PKCγ signalling, we show that serine/threonine kinase 17b (STK17B) is strongly phosphorylated and is involved in the increased downstream signalling of PKCγ. Furthermore, STK17B was identified as a molecule being dysregulated in three more mouse models of diverse types of spinocerebellar ataxias (SCAs).
Protein arginine methyltransferases (PRMTs) are emerging as attractive therapeutic targets. PRMTs regulate transcription, splicing, RNA biology, the DNA damage response and cell metabolism; these ...fundamental processes are altered in many diseases. Mechanistically understanding how these enzymes fuel and sustain cancer cells, especially in specific metabolic contexts or in the presence of certain mutations, has provided the rationale for targeting them in oncology. Ongoing inhibitor development, facilitated by structural biology, has generated tool compounds for the majority of PRMTs and enabled clinical programmes for the most advanced oncology targets, PRMT1 and PRMT5. In-depth mechanistic investigations using genetic and chemical tools continue to delineate the roles of PRMTs in regulating immune cells and cancer cells, and cardiovascular and neuronal function, and determine which pathways involving PRMTs could be synergistically targeted in combination therapies for cancer. This research is enhancing our knowledge of the complex functions of arginine methylation, will guide future clinical development and could identify new clinical indications.
Mixed lineage kinase domain-like protein （Mlkl） was recently found to interact with receptor interacting protein 3 （Rip3） and to be essential for tumor necrosis factor （TNF）-induced programmed ...necrosis （necroptosis） in cultured cell lines. We have generated Mlkl-deficient mice by transcription activator-like effector nucleases （TALENs）-mediated gene disruption and found Mlkl to be dispensable for normal mouse development as well as immune cell develop- ment. Mlkl-deficient mouse embryonic fibroblasts （MEFs） and macrophages both showed resistance to necrotic but not apoptotic stimuli. Mlkl-deficient MEFs and macrophages were indistinguishable from wild-type cells in their abil- ity to activate NF-KB, ERK, JNK, and p38 in response to TNF and lipopolysaccharides （LPS）, respectively. Consis- tently, Mlkl-deficient macrophages and mice exhibited normal interleukin-lp （IL-1β）, IL-6, and TNF production after LPS treatment. Mlkl deficiency protects mice from cerulean-induced acute pancreatitis, a necrosis-related disease, but has no effect on polymicrobial septic shock-induced animal death. Our results provide genetic evidence for the role of Mlkl in necroptosis.
A metal‐free domino reaction was developed for efficient synthesis of 4,5‐disubstituted 1,2,3‐(NH)‐triazoles by sequentially coupling sulfur salts with aldehydes and sodium azide. In the presence of ...L‐proline, olefinic sulfur salt intermediates rather than epoxides are formed in situ via the coupling of sulfur salts with aldehydes and cyclize with azide ion. This process features mild conditions, high efficiency, commercially available starting materials, and wide substrate scope.
Coexistence of high local charge mobility and an energy gradient can lead to efficient free charge carrier generation from geminate charge transfer states at the donor–acceptor interface in bulk ...heterojunction organic photovoltaics. It is, however, not clear what polymer microstructures can support such coexistence. Using recent methods from density functional theory, we propose that a stack of similarly curved oligothiophene chains can deliver the requirements for efficient charge separation. Curved stacks are stable because of the polymer’s strong π-stacking ability and because backbone torsions are flexible in neutral chains. However, energy of a charge in a polymer chain has remarkably stronger dependence on torsions. The trend of increasing planarity in curved stacks effectively creates an energy gradient that drives charge in one direction. The curvature of these partially ordered stacks is found to beneficially interact with fullerenes for charge separation. The curved stacks, therefore, are identified as possible building blocks for interfacial structures that lead to efficient free carrier generation in high-performing organic photovoltaic systems.
The control problem of active suspension systems (ASSs) with uncertainties is considered in this article by formulating control goals as a series of equality constraint (i.e., soft constraint) and ...inequality constraint (i.e., hard constraint). Uncertainties are (possibly fast) time varying, bounded, and include large mismatched portions. However, bounds are unknown. The objective is to design an adaptive robust control driving the system to converge to soft constraints provided by the sky-hook model, and simultaneously, ensuring the system to meet hard constraints at every instant. The adaptive robust control design is implemented in four steps. First, we investigate a transformation technique for incorporating hard constraints into soft constraints and the model. Second, a nominal control is presented without considering uncertainty. Third, an orthogonal decomposition technique is proposed for dividing uncertainty into matched and mismatched portions, which creatively allocates the mismatched portion for later control design. Fourth, a continuous adaptive law is constructed to emulate a constant design parameter vector associated with uncertainty bounds. It is proved that the proposed control guarantees uniform boundedness and uniform ultimate boundedness of ASSs in the presence of uncertainties and hard constrains. Furthermore, experimental and simulation results on the 2-DOF ASS are presented to validate the effectiveness of the proposed control.
The tumor microenvironment (TME) is an essential intrinsic portion of hepatocellular carcinoma (HCC) for the regulation of its origination, development, invasion, and metastasis. As emerging ...components of the tumor-host interaction, exosomes are increasingly recognized as professional carriers of information in TME and as pivotal molecular entities involved in tumorigenic microenvironment setup. However, much remains unknown about the role of the exosome communication system within TME in the development and progression of HCC. In this review, we focus on the roles and probable mechanisms of TME in HCC and show the exosome-based immune regulation in TME to promote HCC. Multiple processes are involved in HCC, including tumor survival, growth, angiogenesis, invasion, and metastasis. We also discuss the specific roles of exosomes in HCC processes by molding hospitable TME for HCC, such as providing energy, transmitting protumor signals, and evading inhibitory signals. In addition, exosomes induce angiogenesis by changing the biological characteristics of endothelial cells and directly regulating proangiogenic and propermeability factors. Furthermore, exosomes may lead to HCC metastatic invasion by epithelial-mesenchymal transformation, extracellular matrix degradation, and vascular leakage. Finally, we summarize the therapeutic usage of exosomes in the HCC microenvironment and attempt to provide a theoretical reference for modern antitumor agents designed to target these mechanisms.
In this study, we investigate the impact of online review characteristics on consumers’ purchasing decisions in the context of spatial distance. We consider the product experience of online travel ...routes, geographical location characteristics, and price adjustment factors, as well as the dynamics between consumers and businesses during the booking of travel routes. Through empirical research and large-scale data simulation experiments, we have found that the variability in attributes of tourist routes significantly influences the user recommendation rate, while the overall rating has a positive moderating effect. Furthermore, the number of reviews negatively moderates the relationship between them. Additionally, the product information and service quality of tourist routes also significantly affect the recommendation rate. Finally, we propose a management strategy for tourism route managers to enhance user recommendation rates and achieve greater benefits.
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