This note constructs a functional observer for second‐order linear time‐varying (SOLTV) systems under framework of second‐order systems. Based on the assumption that the SOLTV system is observable, ...sufficient conditions for the existence of a second‐order functional observer are proposed. Combined with the solution of generalized Sylvester equation (GSE), the completely parameterized expressions of coefficient matrices of functional observer are proposed, which includes the free parameters representing degrees of freedom, and can be utilized to achieve some additional performance. Further, the design procedure is put forward, whose validity is verified through an example.
The rational design of artificial solid‐state nanopores is of great importance in the discovery of intriguing ion transport phenomena. 2D metal–organicframework (2D MOF) nanosheets with single ...crystallinity, aligned nanochannels, ultrathin thickness, and diverse functionalities are highly potential solid‐state nanopores. An electrophoretic method is developed to successfully fabricate MOF nanopores supported by SiNx substrate, which is confirmed by high‐resolution transmission electron microscopy. A giant gap around 4 V together with ionic current rectification is discovered in nonlinear voltage‐activated current‐voltage curves, revealing the synergy of the hydrophobic effect and charge effect in MOF nanopores. The charge effect embodies the different contribution current which results from the enrichment and depletion of ions in MOF nanopores by COMSOL simulation. Moreover, 2D MOF nanosheets with different surface charges, hydrophobicity, and pore sizes demonstrate the universality of nanopore fabrication and further confirm the synergistic mechanism. The nonlinear ion transport in the ultrathin MOF nanosheets will provide an opportunity to explore further applications in solid‐state nanopores.
Nonlinear ion transport through the single crystalline two‐dimensional ultrathin metal–organic framework nanosheets is discovered along with a giant gap of low conductance state as well as the rectification inversion. The synergetic mechanism is revealed by the combination of the regulation of physical and chemical parameters and simulations.
For robot swarm applications, accurate positioning is one of the most important requirements for avoiding collisions and keeping formations and cooperation between individuals. However, in some worst ...cases, the GNSS (Global Navigation Satellite System) signals are weak due to the crowd being in a swarm or blocked by a forest, mountains, and high buildings in the environment. Thus, relative localization is an indispensable way to provide position information for the swarm. In this paper, we review the status and development of relative localization. It is first assessed that relative localization to obtain spatio-temporal relationships between individuals is necessary to achieve the stable operation of the group. After analyzing typical relative localization systems and algorithms from the perspective of functionality and practicality, this paper concludes that the UWB-based (ultra wideband) system is suitable for the relative localization of robots in large-scale applications. Finally, after analyzing the current challenges in the field of fully distributed localization for robotic swarms, a complete mechanism encompassing the relative localization process and the relationship between local and global localization that can be a possible direction for future research is proposed.
The utilization of corrugated steel plates in concrete filled steel tube (CFST) structures has shown advantageous performance and considerable economy due to their high out-of-plane stiffness and ...local buckling resistance. A novel composite shear wall composed of multiple CFST components using double horizontally-corrugated steel plates and connected using pure corrugated steel plates with large wave heights was proposed. Fifteen CFST components with double horizontally-corrugated steel plates were designed and statically tested to evaluate the eccentric compression performance. Parameters including nominal eccentricity ratios, nominal sectional aspect ratios, steel plate thicknesses, and diameters of reinforced longitudinal reinforcements were considered. The bearing capacity, stiffness, and ductility of the CFST component with double horizontally-corrugated steel plates were investigated. In addition, the non-uniformities of confinement along with cross-sectional depth was studied through the analysis of measured strains and finite element simulations. Moreover, two capacity models of the eccentrically loaded components were proposed based on eccentricity reduction coefficient and stress balance of the cross-section, respectively. Both models effectively predicted the experimental and simulated results.
•The eccentrically loaded behavior of a novel component utilizing double horizontally-corrugated steel plates was studied.•The corrugated steel plates effectively mitigated longitudinal buckling and effectively confined the core concrete.•The novel component showed good performance even though its sectional width-thickness ratio exceeding the specified limit.•Two capacity models were proposed to predict the strength of the novel CFST components.
Gastric cancer (GC) is the most prevalent gastrointestinal tumor with an unfavorable clinical prognosis. GC patients are largely threatened owing to metastasis and drug resistance. Tumor angiogenesis ...plays an important role in the development of gastric cancer and is a challenge in the treatment of gastric cancer.
Mouse xenograft models were used for screening of therapeutic peptides on GC growth and metastasis. Routine laboratory experimental methods including conditional cell culture, tube formation assay, qRT-PCR, Western blotting, immunohistochemistry (IHC), ubiquitination assay, and immunofluorescence (IF) were used in mechanism investigation; protein docking analysis and coimmunoprecipitation (Co-IP) were used for prediction and confirmation of interactions between JP3/SP1 and TRIM25/MEK1/2.
We identified an MMP2-targeted peptide JP3 that plays inhibiting roles in modulating growth and metastasis of GC in vivo and has no observable toxic side effects. JP3 reduced tumor microvessel density (MVD) in vivo and human umbilical vein endothelial cells (HUVECs) tube formation in vitro. Mechanistic studies revealed that JP3 reduces polyubiquitination-mediated degradation of TRIM25 by increasing the stability of TRIM25 through phosphorylating it at Ser12. TRIM25, as an E3 ubiquitin ligase, promoted the ubiquitin of SP1 at K610, further suppressed expression of MMP2 and inhibited angiogenesis in GC. Importantly, the inversely association between TRIM25 and SP1 protein level was further verified in human GC tissues. Decreased TRIM25 expression and increased SP1 expression in tumor tissues were positively correlated with poor prognosis of GC patients.
MMP2-targeted peptide JP3 plays a therapeutic role in GC through anti-angiogenesis by modulating TRIM25/SP1/MMP2.
Vacuolar protein sorting-35 (VPS35) is essential for endosome-to-Golgi retrieval of membrane proteins. Mutations in the VPS35 gene have been identified in patients with autosomal dominant PD. ...However, it remains poorly understood if and how VPS35 deficiency or mutation contributes to PD pathogenesis. Here we provide evidence that links VPS35 deficiency to PD-like neuropathology. VPS35 was expressed in mouse dopamine (DA) neurons in substantia nigra pars compacta (SNpc) and STR (striatum)--regions that are PD vulnerable. VPS35-deficient mice exhibited PD-relevant deficits including accumulation of α-synuclein in SNpc-DA neurons, loss of DA transmitter and DA neurons in SNpc and STR, and impairment of locomotor behavior. Further mechanical studies showed that VPS35-deficient DA neurons or DA neurons expressing PD-linked VPS35 mutant (D620N) had impaired endosome-to-Golgi retrieval of lysosome-associated membrane glycoprotein 2a (Lamp2a) and accelerated Lamp2a degradation. Expression of Lamp2a in VPS35-deficient DA neurons reduced α-synuclein, supporting the view for Lamp2a as a receptor of chaperone-mediated autophagy to be critical for α-synuclein degradation. These results suggest that VPS35 deficiency or mutation promotes PD pathogenesis and reveals a crucial pathway, VPS35-Lamp2a-α-synuclein, to prevent PD pathogenesis. Significance statement: VPS35 is a key component of the retromer complex that is essential for endosome-to-Golgi retrieval of membrane proteins. Mutations in the VPS35 gene have been identified in patients with PD. However, if and how VPS35 deficiency or mutation contributes to PD pathogenesis remains unclear. We demonstrated that VPS35 deficiency or mutation (D620N) in mice leads to α-synuclein accumulation and aggregation in the substantia nigra, accompanied with DA neurodegeneration. VPS35-deficient DA neurons exhibit impaired endosome-to-Golgi retrieval of Lamp2a, which may contribute to the reduced α-synuclein degradation through chaperone-mediated autophagy. These results suggest that VPS35 deficiency or mutation promotes PD pathogenesis, and reveals a crucial pathway, VPS35-Lamp2a-α-synuclein, to prevent PD pathogenesis.
Stocking density is a crucial factor affecting productivity in aquaculture, and high stocking density is a stressor for aquatic animals. In this study, we aimed to investigate the effects of stocking ...densities on oxidative stress and energy metabolism in the gills of
under rice-crayfish farming. The
were reared at low density (LD), medium density (MD), and high density (HD) for 90 days. The results showed that the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) levels were higher in the HD group than those in the LD group. Transcriptomic analysis revealed 1944 upregulated and 1157 downregulated genes in the gills of the HD group compared to the LD group. Gene ontology (GO) enrichment analysis indicated that these differentially expressed genes (DEGs) were significantly associated with ATP metabolism. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis also showed that high stocking density resulted in the dysregulation of oxidative phosphorylation. Furthermore, high stocking density upregulated six lipid metabolism-related pathways. Overall, our findings, despite the limited number of samples, suggested that high stocking density led to oxidative stress and dysregulation of energy metabolism in the gills of
under rice-crayfish co-culture. Alteration in energy metabolism may be an adaptive response to adverse farming conditions.
Cortical disinhibition is a common feature of several neuropsychiatric diseases such as schizophrenia, autism and intellectual disabilities. However, the underlying mechanisms are not fully ...understood. To mimic increased expression of Nrg1, a schizophrenia susceptibility gene in GABAergic interneurons from patients with schizophrenia, we generated gtoNrg1 mice with overexpression of Nrg1 in GABAergic interneurons. gtoNrg1 mice showed cortical disinhibition at the cellular, synaptic, neural network and behavioral levels. We revealed that the intracellular domain of NRG1 interacts with the cytoplasmic loop 1 of Na
1.1, a sodium channel critical for the excitability of GABAergic interneurons, and inhibits Na
currents. Intriguingly, activation of GABAergic interneurons or restoring NRG1 expression in adulthood could rescue the hyperactivity and impaired social novelty in gtoNrg1 mice. These results identify mechanisms underlying cortical disinhibition related to schizophrenia and raise the possibility that restoration of NRG1 signaling and GABAergic function is beneficial in certain neuropsychiatric disorders.
Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, the clinical intervention effect is not ...ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, three characteristics of ferroptosis, are potential therapeutic intervention targets. Here, we confirmed in vitro and in vivo that at least autophagy, apoptosis, and ferroptosis are involved in Dox cardiotoxicity-induced damage. When the neonatal rat cardiomyocytes and H9C2 cells or C57BL/6 mice were subjected to Dox-induced cardiotoxicity, epigallocatechin-3-gallate pretreatment could effectively decrease iron accumulation, inhibit oxidative stress and abnormal lipid metabolism, and thereby alleviate Dox cardiotoxicity-induced ferroptosis and protect the myocardium according to multiple functional, enzymatic, and morphological indices. The underlying mechanism was verified to involve the upregulation and activation of AMP-activated protein kinase α2, which promoted adaptive autophagy, increased energy supply, and maintained mitochondrial function. We believe that epigallocatechin-3-gallate is a candidate phytochemical against Dox-induced cardiotoxicity.
Five heterometallic 3d–4f Co(II)–Ln(III) complexes, CoLLa(Py)(NO3)3(CH3OH) (1), Co2L2La2(4,4′-bipy)(NO3)6(CH3OH)2 (2) and CoLLn(OAc)(NO3)2(CH3OH) (Ln=Gd (3), Tb (4), Dy (5)), derived from a ...hexadentate bisoxime. Moreover, magnetic measurements were performed on the complexes 3, 4 and 5. Display omitted
Five heterometallic Co(II)–Ln(III) complexes, a discrete heterodinuclear complex CoLLa(Py)(NO3)3(CH3OH) (1) (Py=pyridine), a heterotetranuclear dimer Co2L2La2(4,4′-bipy)(NO3)6(CH3OH)2 (2) (4,4′-bipy=4,4′-bipyridine) and three discrete heterodinuclear complexes CoLLn(OAc)(NO3)2(CH3OH) (Ln=Gd (3), Tb (4), Dy (5)), were synthesized with a hexadentate bisoxime ligand 1,2-bis(3-methoxysalicylideneaminooxy)ethane (H2L), and characterized by single crystal X-ray diffraction. The complexes 1, 3, 4 and 5 are discrete heterodinuclear structures, but the assembly of two dinuclear units CoLLa(NO3)3(CH3OH) and one 4,4′-bipyridine results in a discrete heterotetranuclear dimer 2. The Co(II) and La(III) atoms in the complexes 1 and 2 are penta- and decacoordinated, while the Co(II) and Ln(III) (Ln=Gd, Tb and Dy) atoms in the complexes 3, 4 and 5 are hexa- and nonacoordinated, respectively. Magnetic measurements were performed on the complexes 3, 4 and 5, where an intramolecular ferromagnetic interaction is found in the complex 3.
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