Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson's disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a ...traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined.
Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP
)-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers.
We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP
-induced premature senescence, evidenced by decreased senescence-associated β-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence.
Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.
Hypervirulent
(hvKP) has spread globally since first described in the Asian Pacific Rim. It is an invasive variant that differs from the classical
(cKP), with hypermucoviscosity and hypervirulence, ...causing community-acquired infections, including pyogenic liver abscess, pneumonia, meningitis, and endophthalmitis. It utilizes a battery of virulence factors for survival and pathogenesis, such as capsule, siderophores, lipopolysaccharide, fimbriae, outer membrane proteins, and type 6 secretion system, of which the former two are dominant. This review summarizes these hvKP-associated virulence factors in order to understand its molecular pathogenesis and shed light on new strategies to improve the prevention, diagnosis, and treatment of hvKP-causing infection.
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•PtCuFe nanochains (NCs) are synthesized by a convenient solvothermal method.•Cu2+ plays an important role in the formation of 1D NCs.•The composition-performance relationship of ...PtCuxFey NCs is revealed.•The PtCuFe NCs show excellent activity and durability toward MOR and HER.
The controllable synthesis of 1-dimensional (1D) multi-metal Pt-based alloys, with enhanced electro-chemical properties remains a challenge, despite the wide application of Pt-based catalysts in fuel cells and in the hydrogen evolution reaction (HER). Herein, we fabricate PtCuFe alloy nanochains (NCs) that have a tunable composition by flexibly adjusting the molar ratios of the metal precursors. It was found that Cu2+ is key in the formation of 1D NCs, as confirmed by transmission electron microscopy characterizations. In addition, the alloyed Fe can further increase the content of the metallic state of Cu in the PtCuFe NCs. The as-prepared PtCuFe NCs exhibited higher catalytic activity and stability than those of the Pt nanoparticles (NPs), PtFe NPs, and PtCu NCs, for the methanol oxidation reaction (MOR) and HER. Additionally, the composition-performance relationship of PtCuxFey NCs toward the MOR and HER were investigated. The hybrid density functional theory calculation and analysis showed that the 1D PtCuFe NCs have a lower lowest unoccupied molecular orbital (LUMO) than those of the 2- and 3-dimensional PtCuFe, verifying that the 1D PtCuFe NCs exhibit the highest activity for the MOR. This work has established a new method for the controllable synthesis of multi-metal Pt-based NCs/alloy catalysts and their subsequent applications in other electro-catalytic reactions.
α-Synuclein (α-Syn), a pathological hallmark of Parkinson's disease (PD), has been recognized to induce the production of interleukin-1β in a process that depends, at least in vitro, on nod-like ...receptor protein 3 (NLRP3) inflammasome in monocytes. However, the role of NLRP3 inflammasome activation in the onset of PD has not yet been fully established.
In this study, we showed that NLRP3 inflammasomes were activated in the serum of PD patients and the midbrain of PD model mice. We further clarified that α-syn activated the NLRP3 inflammasome through microglial endocytosis and subsequent lysosomal cathepsin B release. Deficiency of caspase-1, an important component of NLRP3 inflammasome, significantly inhibited α-syn-induced microglia activation and interleukin-1β production, which in turn alleviated the reduction of mesencephalic dopaminergic neurons treated by microglia medium. Specifically, we demonstrated for the first time that Nlrp3 is a target gene of microRNA-7 (miR-7). Transfection of miR-7 inhibited microglial NLRP3 inflammasome activation whereas anti-miR-7 aggravated inflammasome activation in vitro. Notably, stereotactical injection of miR-7 mimics into mouse striatum attenuated dopaminergic neuron degeneration accompanied by the amelioration of microglial activation in MPTP-induced PD model mice.
Our study provides a direct link between miR-7 and NLRP3 inflammasome-mediated neuroinflammation in the pathogenesis of PD. These findings will give us an insight into the potential of miR-7 and NLRP3 inflammasome in terms of opening up novel therapeutic avenues for PD.
•Component-structure-defined carbon nanocages embedded Co/CoxP (Co/CoxP/HNC) are synthesized•The performance-dependence on shell-thickness and doped-P-content are revealed.•Co/CoxP/HNC-5 exhibits ...outstanding electrocatalytic activity for ORR and OER.•Zn-air battery based on Co/CoxP/HNC-5 shows excellent charge/discharge stability.
The design and synthesis of composite-structure-defined bifunctional oxygen reduction and evolution reactions electrocatalysts for rechargeable Zn-air batteries are highly important. Herein, a facile surface functionalization-carbonization-phosphidation strategy is proposed to construct a novel composition-structure-controllable nanomaterial from a zeolite imidazole ester framework (ZIF67), which has been applied in oxygen evolution reaction (OER), oxygen reduction reaction (ORR), and Zn-air batteries. In the typical nanomaterial, Co and CoxP (a mixture of Co2P and CoP) were embedded in hollow N-doped carbon shell (Co/CoxP/HNC-5). The relationship between the activity and shell thicknesses of the carbonization products of ZIF67 coated with different mass ratios of polydopamine has been studied. In addition, the doped P-content showed a significant impact on the bifunctional oxygen activity, especially for Co/CoxP/HNC-5. Benefiting from the unique structure, multiple compositions, and synergistic effects, the superior bifunctional oxygen electrocatalytic activity (ΔE = 0.667 V) were obtained on Co/CoxP/HNC-5. Furthermore, Co/CoxP/HNC-5 served as an air-cathode catalyst and exhibited remarkable peak power density, specific capacity and durability in a practical Zn-air battery. This work provides a strategy for the construction of efficient bifunctional electrocatalysts with special structure and adjustable compositions.
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Antiferroelectric‐based dielectric capacitors are receiving tremendous attention for their outstanding energy‐storage performance and extraordinary flexibility in collecting pulsed powers. ...Nevertheless, the in situ atomic‐scale structural‐evolution pathway, inherently coupling to the energy storage process, has not been elucidated for the ultimate mechanistic understanding so far. Here, time‐ and atomic‐resolution structural phase evolution in antiferroelectric PbZrO3 during storage of energy from the electron‐beam illumination is reported. By employing state‐of‐the‐art negative‐spherical‐aberration imaging technique, the quantitative transmission electron microscopy study presented herein clarifies that the hierarchical evolution of polar oxygen octahedra associated with the unit‐cell volume change and polarization rotation accounts for the stepwise antiferroelectric‐to‐ferroelectric phase transition. In particular, an unconventional ferroelectric category—the ferrodistortive phase characteristic of a unique cycloidal polarization order—is established during the dynamic structure investigation. Through clarifying the atomic‐scale phase transformation pathway, findings of this work unveil a new territory to explore novel ferrodistortive phases in energy‐storage materials with the nonpolar‐to‐polar phase transitions.
Antiferroelectrics are an important material system for electrostatic energy storage. However, the associated antiferroelectric–ferroelectric transition has not been clarified in the past decades. Driven by electron‐beam irradiation, time‐ and atomic‐resolution electron microscopy unveils a novel ferrodistortive phase, characteristic of a cycloidal polarization order, during the phase‐transition process. This opens up a field to search for ferroelectrics with noncollinear polarization orders.
A design method of low-dimensional disturbance rejection fuzzy control (DRFC) via multiple observers is proposed for a class of nonlinear parabolic partial differential equation (PDE) systems, where ...the disturbance is modeled by an exosystem of ordinary differential equations (ODEs) and enters into the PDE system through the control channel. In the proposed scheme, the modal decomposition technique is initially applied to the PDE system to derive a slow subsystem of low-dimensional nonlinear ODEs, which accurately captures the dominant dynamics of the PDE system. The resulting nonlinear slow subsystem is subsequently represented by a Takagi-Sugeno (T-S) fuzzy model. From the T-S fuzzy model and the exosystem, a fuzzy slow mode observer and a fuzzy disturbance observer are constructed to estimate the slow mode and the disturbance, respectively. Furthermore, a nonlinear observation spillover observer is proposed to compensate the effect of observation spillover. Then, based on these observers, a low-dimensional DRFC design is developed in terms of linear matrix inequalities to guarantee the exponential stability of the closed-loop PDE system in the presence of the disturbance. Finally, the effectiveness of the proposed design method is demonstrated on the control of one-dimensional Burgers-KPP-Fisher diffusion-reaction system and the temperature profile of a catalytic rod.
It is highly challenging to activate the basal plane and minimize the π−π stacking of MoS2 sheets, thus enhancing its catalytic performance. Here, we display an approach for making well‐dispersed ...MoS2. By using the N‐doped multi‐walled carbon nanotubes (NMWCNTs) as an isolation unit, the aggregation of MoS2 sheets was effectively reduced, favoring the dispersion of Pt nanoparticles (noted as Pt/NMWCNTs‐isolated‐MoS2). Excellent bifunctional catalytic performance for methanol oxidation and oxygen reduction reaction (MOR/ORR) were demonstrated by the produced Pt/NMWCNTs‐isolated‐MoS2. In comparison to Pt nanoparticles supported on MoS2 (Pt/MoS2), the MOR activity (2314.14 mA mgpt−1) and stability (317.69 mA mgpt−1 after 2 h of operation) on Pt/NMWCNTs‐isolatedMoS2 were 24 and 232 times higher, respectively. As for ORR, Pt/NMWCNTs‐isolated‐MoS2 holds large half‐wave potential (0.88 V) and high stability (92.71 % after 22 h of operation). This work presents a tactic for activating the basal planes and reducing the π−π stacking of 2D materials to satisfy their applications in electrocatalysis. In addition, the proposed sheet‐isolation method can be used for fabricating other 2D materials to promote the dispersion of nanoparticles, which assist its application in other fields of energy as well as the environment.
The isolation of NMWCNTs weakens the π−π stacking, improves the conductivity, and activates basal planes of the MoS2 sheets. Consequently, the prepared Pt/NWMCNTs‐solated‐MoS2 realizes excellent bifunctional catalytic performance for MOR and ORR.
Carbapenem-resistant Enterobacteriaceae (CRE) have spread rapidly around the world in the past few years, posing great challenges to human health. The plasmid-mediated horizontal transmission of ...carbapenem-resistance genes is the main cause of the surge in the prevalence of CRE. Therefore, the timely and accurate detection of CRE, especially carbapenemase-producing Enterobacteriaceae, is very important for the clinical prevention and treatment of these infections. A variety of methods for the rapid detection of CRE phenotypes and genotypes have been developed for use in clinical microbiology laboratories. To overcome the lack of efficient antibiotics, CRE infections are often treated with combination therapies. Moreover, novel drugs and emerging strategies appeared successively and in various stages of development. In this article, we summarized the global distribution of various carbapenemases. And we focused on summarizing and comparing the advantages and limitations of the detection methods and the therapeutic strategies of CRE primarily.
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