Decentralized Adaptive Secure Control of Uncertain Nonlinear Time-Varying Interconnected Systems Against Sensor and Actuator Attacks.

In this article, the decentralized adaptive secure control problem for cyber-physical systems (CPSs) against deception attacks is investigated. The CPSs are formed as a type of nonlinear interconnected strict-feedback systems with uncertain time-varying parameters. The attack affects the information transmission between sensor and actuator in a multiplicative manner. A novel decentralized adaptive backstepping secure control strategy is established by exploiting a particular kind of Nussbaum functions and a flat-zone Lyapunov function analysis approach. It is shown that all of closed-loop signals remain globally bounded, and each output signal eventually converges into a small neighborhood of the origin. Simulation results on an illustrative example are provided to display the effectiveness of the proposed control scheme.

Cav3.1 t-type calcium channel is critical for cell proliferation and survival in newly generated cells of the adult hippocampus.

AIMS: Adult hippocampal neurogenesis plays an important role in neuronal plasticity and maintenance in mammals. Low-threshold voltage-gated T-type calcium channels produce calcium spikes that increase fast action potentials in newborn cells in the hippocampal dentate gyrus (DG); however, their role in adult hippocampal neurogenesis remains unclear. Here, we demonstrate impaired adult hippocampal neurogenesis in Cav3.1T-type calcium channel knockout mice. METHODS AND RESULTS: Cav3.1T-type calcium channel was predominantly localized in neuronal progenitor cells of the mouse hippocampal DG. By counting the number of 5-bromo-2'-deoxyuridine-labeled cells, decreased proliferation and survival of newly generated cells were observed in the adult hippocampal DG in Cav3.1 knockout mice as compared to wild-type (WT) mice. Moreover, the degree of maturation of doublecortin-positive cells in Cav3.1 knockout mice was lower than that in WT mice, suggesting that Cav3.1 deletion may impair neuronal differentiation. Consistent with impaired hippocampal neurogenesis, Cav3.1 knockout mice showed decreased social interaction. Reduced phosphorylation levels of calcium/calmodulin-dependent protein kinase II and protein kinase B were closely associated with impaired hippocampal neurogenesis in Cav3.1 knockout mice. Moreover, the mRNA and protein expression levels of brain-derived neurotrophic factor, important for neurogenesis, were significantly decreased in Cav3.1 knockout mice. Finally, gene ontology analysis revealed alterations in genes related to the promotion of cell death/apoptosis and suppression of cell proliferation/neuronal differentiation pathways, including Bdnf. CONCLUSION: These results suggest that the Cav3.1T-type calcium channel may be a key molecule required for cell proliferation, survival and neuronal differentiation in newly generated cells of the adult mouse hippocampus.

T-type calcium channel enhancer SAK3 produces anti-depressant-like effects by promoting adult hippocampal neurogenesis in olfactory bulbectomized mice.

T-type calcium channels are involved in the pathophysiology of epilepsy, pain, and sleep. Recently, we developed a novel spiroimidazopyridine compound, SAK3 (ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo[1,2-a]pyridine]-2-ene-3-carboxylate), which enhances T-type calcium channel currents and improves memory deficits in olfactory bulbectomized (OBX) mice. Here, we demonstrated the anti-depressant effects of SAK3 in OBX mice. Chronic SAK3 administration (0.5 or 1.0 mg/kg, p.o.) improved depressive-like behaviors in OBX mice. The impaired adult neurogenesis in the hippocampal dentate gyrus (DG) that occurred 4 weeks after OBX administration was significantly restored by chronic SAK3 administration (0.5 or 1.0 mg/kg, p.o.). Additionally, SAK3 (0.5 mg/kg, p.o.) promoted the proliferation and survival of newborn cells in the naïve DG. Moreover, SAK3 administration (0.5 mg/kg, p.o.) antagonized the reduction of calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKIV phosphorylation levels, thereby rescuing the decreased levels of cAMP response element-binding protein (CREB)/brain derived neurotrophic factor (BDNF) signaling in the OBX DG. The effects of SAK3 were completely blocked by the T-type calcium channel selective blocker NNC 55-0396 (12.5 mg/kg, i.p.). Altogether, these results suggest that SAK3 improves depressive-like behaviors by promoting adult neurogenesis via T-type calcium channel stimulation in the hippocampus.

Development of near-infrared ratiometric fluorescent probe based on cationic conjugated polymer and CdTe/CdS QDs for label-free determination of glucose in human body fluids.

Quantum dots (QDs) have attracted extensive attention in biomedical applications， because of their broad excitation spectra, narrow and symmetric emission peaks etc. Furthermore, near-infrared (NIR) QDs have further advantages including low autofluorescence, good tissue penetration and low phototoxicity. In this work, the electrostatic interaction and fluorescence resonance energy transfer (FRET) between NIR CdTe/CdS QDs and cationic conjugated polymer (CCP) was studied for the first time. Based on the newly discovered phenomena and the result that hydrogen peroxide (H2O2) can efficiently quench the fluorescence of NIR CdTe/CdS QDs, a novel NIR ratiometric fluorescent probe for determination of H2O2 and glucose was developed. Under the optimized conditions, the detection limit of H2O2 and glucose assay were 0.1mM and 0.05mM (S/N=3), with a linear range of 0.2-4mM and 0.1-5mM, respectively. Because of the NIR spectrum, this ratiometric probe can be also applied for the determination of glucose in whole blood samples directly, providing a valuable platform for glucose sensing in clinic diagnostic and drug screening.

Near-infrared dual-emission quantum dots-gold nanoclusters nanohybrid via co-template synthesis for ratiometric fluorescent detection and bioimaging of ascorbic acid in vitro and in vivo.

Near-infrared (NIR) quantum dots (QDs) have emerged as an attractive bioimaging toolkit for exploring biological events because they can provide deep imaging penetration and low fluorescence background. However, the quantitation process of such NIR QDs generally relies on single-emission intensity change, which is susceptible to a variety of environmental factors. Herein, for the first time, we proposed a protein-directed co-template strategy to synthesize a NIR-based, dual-emission fluorescent nanohybrid (DEFN) constructed from far-red gold nanoclusters and NIR PbS QDs (AuNCs-PbS-QDs). The convenient protein-directed co-template synthesis avoids the tedious chemical coupling and modification required in conventional preparation approaches of DEFNs. Additionally, the dual-emission signals of AuNCs-PbS-QDs exhibit two well-resolved emission peaks (640 and 813 nm) separated by 173 nm, which can eliminate environmental interferences by the built-in correction of ratiometric signal, resulting in a more favorable system for bioimaging and biosensing. Next, the target-responsive capability of this NIR-based DEFN to ascorbic acid (AA) was discovered, enabling the proposed DEFN to ratiometrically detect AA with a linear range of 3-40 µM and a detection limit of 1.5 µM. This DEFN sensor possesses high selectivity, rapid response, and excellent photostability. Moreover, the feasibility of this NIR nanosensor has been fully proved by the ratiometric detection of AA for fruit internal quality assessment, in vitro cellular imaging, and in vivo imaging in nude mice.