Vasoactive intestinal peptide: Mediator of laminin synthesis in cultured Schwann cells

To learn more about neuropeptide-induced glial responses which accompany axon regeneration, we studied effects of VIP on laminin production by cultured Schwann cells. Schwann cells were isolated from sciatic nerves of neonatal mice, purified, and incubated for 5 days in either control medium (DMEM + 15% FCS) or control medium containing 10⁻⁷ -10⁻¹¹ M VIP. At 10⁻⁷ and 10⁻⁸ M VIP, laminin levels measured by enzyme-linked immunosorbent assay were significantly higher (55% and 35%) than those in control cultures. Lower VIP concentrations (10⁻⁹ -10⁻¹¹ M) produced smaller increases which were not significant. Low-affinity VIP receptors which mediated this effect were demonstrated on Schwann cells by radioligand binding studies. The increased Schwann cell synthesis of laminin induced by VIP was blocked when either a VIP antagonist or a VIP receptor antagonist was added to the VIP-containing incubation medium. In contrast to astrocytes, when Schwann cells were loaded with fura-2, VIP did not increase cytosolic Ca²⁺. This indicates that Schwann cells and astrocytes may have different intracellular transduction pathways; their receptor subtypes also may differ. We suggest that the VIP-induced increase in laminin synthesis which we have observed in cultured Schwann cells may also occur in vivo and might be an important component of axon-Schwann cell interactions during nerve regeneration. © 1996 Wiley-Liss, Inc.     

Genetic elevation of monoamine oxidase levels in dopaminergic PC12 cells results in increased free radical damage and sensitivity to MPTP

Production of hydrogen peroxide as a by-product of the breakdown of catecholamines by the enzyme monoamine oxidase (MAO) has been hypothesized to contribute to the increased proclivity of dopaminergic neurons for oxidative injury. We established clonal dopaminergic PC12 cell lines which have elevated MAO activity levels resulting from transgenic expression of the B isoform of the enzyme. Both MAO-A and MAO-B have relatively equivalent affinities for dopamine, and since PC12 primarily express the A and not the B form of the enzyme, this allowed us to distinguish the transgenic MAO activity in these cells from endogenous using the MAO-B specific substrate PEA. Elevation of MAO activity levels in the MAO-B+ cells resulted in higher levels of both free radicals and free radical damage compared with controls. In addition, increased MAO-B levels within PC12 cells caused a dose-dependent increase in sensitivity to the toxin MPTP. Our data suggests that oxidation of catecholamines by MAO can contribute to free radical damage in catecholaminergic neurons and that the low MAO-B activity levels found endogenously in these cells likely accounts for their relative resistance to MPTP toxicity. © 1996 Wiley-Liss, Inc.     

Parental Bonding Reports of Clients with Obsessive–Compulsive Disorder and Agoraphobia

The study was designed to address two broad purposes: (a) to investigate further the reliability and validity of the Parental Bonding Instrument (PBI) and (b) to examine the relationship of parental warmth and overprotection to specific anxiety disorders and their symptoms, anxious personality traits, and social functioning. The PBI was administered, before and after exposure treatment, to an outpatient sample of 52 adults with obsessive–compulsive disorder and 35 with panic disorder with agoraphobia, and to their parents (n=42), if they resided with the patient. PBI scores remained stable despite improvement in symptom severity and mood. Parents' and patients' recollections of the parents' behaviour towards the patient did not agree. According to patients, their parents most often raised them using affectionless control, whereas parents most often rated themselves as having provided optimal parenting. Patients' PBI scores were not related to type or severity of anxiety disorder. However, reports of poorer parenting were associated with worse social adjustment and higher levels of anxious personality disorder characteristics.     

水凝胶负载pVAX1-SpaP/P防龋DNA疫苗以4种途径产生免疫效应

背景:防龋DNA疫苗价格低廉、安全有效,有望成为人类抵抗龋病的重要手段,因而学者在寻找一种能高效诱导抗体产生的免疫途径或保护疫苗效价的缓释系统及佐剂,成为近年研究的热点.目的:观察聚乳酸乙醇酸-聚乙二醇-聚乳酸乙醇酸水凝胶负载pVAX1-SpaP/P防龋基因疫苗的免疫效应.方法:以聚乳酸乙醇酸-聚乙二醇-聚乳酸乙醇酸水...     

Gold nanoclusters as prospective carriers and detectors of pramipexole

Pramipexole (PPX) is known in the treatment of Parkinson''s disease and restless legs syndrome. We carried out a theoretical investigation on pramipexole–Au cluster interactions for the applications of drug delivery and detection. Three Au_N clusters with sizes N = 6, 8 and 20 were used as reactant models to simulate the metallic nanostructured surfaces. Quantum chemical computations were performed in both gas phase and aqueous environments using density functional theory (DFT) with the PBE functional and the cc-pVDZ-PP/cc-pVTZ basis set. The PPX drug is mainly adsorbed on gold clusters via its nitrogen atom of the thiazole ring with binding energies of ca. −22 to −28 kcal mol⁻¹ in vacuum and ca. −18 to −24 kcal mol⁻¹ in aqueous solution. In addition to such Au–N covalent bonding, the metal–drug interactions are further stabilized by electrostatic effects, namely hydrogen-bond NH⋯Au contributions. Surface-enhanced Raman scattering (SERS) of PPX adsorbed on the Au surfaces and its desorption process were also examined. In comparison to Au₈, both Au₆ and Au₂₀ clusters undergo a shorter recovery time and a larger change of energy gap, being possibly conducive to electrical conversion, thus signaling for detection of the drug. A chemical enhancement mechanism for SERS procedure was again established in view of the formation of nonconventional hydrogen interactions Au⋯H–N. The binding of PPX to a gold cluster is expected to be reversible and triggered by the presence of cysteine residues in protein matrices or lower-shifted alteration of environment pH. These findings would encourage either further theoretical probes to reach more accurate views on the efficiency of pramipexole–Au interactions, or experimental attempts to build appropriate gold nanostructures for practical trials, harnessing their potentiality for applications.

Gold clusters as prospective carriers and detectors of pramipexole.     

Stable cycling of Prussian blue/Zn battery in a nonflammable aqueous/organic hybrid electrolyte

Although rechargeable aqueous batteries are attracting increasing attention in recent years due to high safety, low cost, high power density and environmental friendliness, the aqueous batteries suffer from limited cycle life due to a narrow electrochemical window of the aqueous electrolytes, severe side reaction and instability of electrode materials in aqueous electrolytes. In this work, we propose a hybrid aqueous electrolyte with a mixed solvent of water and acetonitrile (ACN), which exhibits a wide electrochemical window, high ionic conductivity, and nonflammability. An aqueous battery with an iron hexacyanoferrate (FeHCF) cathode, Zn anode and H₂O/ACN hybrid electrolyte shows a high capacity of 69.1 mA h g⁻¹ at 10C (89.5% relative to that at 1C) and an extremely long cycle life with 51.4% capacity retention after 19 000 cycles at 10C. The excellent cycling performance of the aqueous FeHCF/Zn batteries can be attributed to the reduced water activity and extended electrochemical window because of the strong hydrogen-bonding interaction between ACN and H₂O. Besides, the large particle size and good crystallization of FeHCF can inhibit its dissolution in the aqueous electrolyte which further improves cycling performance. This work will shed light on the design of safe aqueous batteries for applications in large-scale energy storage.

Aqueous FeHCF/Zn battery with a hybrid electrolyte exhibits ultralong cycle life with 51.4% capacity retention after 19 000 cycles.     

First principles study of electronic and optical properties and photocatalytic performance of GaN–SiS van der Waals heterostructure

The vertical stacking of two-dimensional materials via van der Waals (vdW) interaction is a promising technique for tailoring the physical properties and fabricating potential devices to be applied in the emerging fields of materials science and nanotechnology. The structural, electronic and optical properties and photocatalytic performance of a GaN–SiS vdW heterostructure were explored using first principles calculations. The most stable stacking configuration found energetically stable, possesses a direct staggered band gap, which is crucial for separating photogenerated charged carriers in different constituents and is efficacious for solar cells. Further, the charge transfer occurred from the SiS to GaN layer, indicating that SiS exhibits p-type doping in the GaN–SiS heterobilayer. Interestingly, a systematic red-shift was observed in the optical absorption spectra of the understudy heterobilayer system. Moreover, the conduction band edge and valence band edge of the monolayers and corresponding heterostructure were located above and below the standard redox potentials for photocatalytic water splitting, making these systems promising for water dissociation for hydrogen fuel production. The results provide a route to design the GaN–SiS vdW heterostructure for the practical realization of next-generation light detection and energy harvesting devices.

The two dimensional GaN–SiS van der Waals heterostructure is a promising candidate for optoelectronic and photocatalytic water splitting.     

Adjusting the electronic properties and contact types of graphene/F-diamane-like C4F2 van der Waals heterostructure: a first principles study

Motivated by the successful exfoliation of two-dimensional F-diamane-like C₄F₂ monolayer and the superior properties of graphene-based vdW heterostructures, in this work, we perform a first principles study to investigate the atomic structure, electronic properties and contact types of the graphene/F-diamane-like C₄F₂ heterostructure. The graphene/C₄F₂ vdW heterostructure is structurally stable at room temperature. In the ground state, the graphene/C₄F₂ heterostructure forms n-type Schottky contact with a Schottky barrier height of 0.46/1.03 eV given by PBE/HSE06. The formation of the graphene/C₄F₂ heterostructure tends to decrease in the band gap of the semiconducting C₄F₂ layer, suggesting that such a heterostructure may have strong optical absorption. Furthermore, the electronic properties and contact types of the graphene/C₄F₂ heterostructure can be adjusted by applying an external electric field, which leads to the change in the Schottky barrier height and the transformation from Schottky to ohmic contact. Our findings reveal the potential of the graphene/C₄F₂ heterostructure as a tunable hybrid material with strong potential in electronic applications.

We perform a first principles study to investigate the atomic structure, electronic properties and contact types of the graphene/F-diamane-like C₄F₂ heterostructure.     

Gasdermin D inhibition confers antineutrophil-mediated cardioprotection in acute myocardial infarction

Acute myocardial infarction (AMI) induces blood leukocytosis, which correlates inversely with patient survival. The molecular mechanisms leading to leukocytosis in the infarcted heart remain poorly understood. Using an AMI mouse model, we identified gasdermin D (GSDMD) in activated leukocytes early in AMI. We demonstrated that GSDMD is required for enhanced early mobilization of neutrophils to the infarcted heart. Loss of GSDMD resulted in attenuated IL-1β release from neutrophils and subsequent decreased neutrophils and monocytes in the infarcted heart. Knockout of GSDMD in mice significantly reduced infarct size, improved cardiac function, and increased post-AMI survival. Through a series of bone marrow transplantation studies and leukocyte depletion experiments, we further clarified that excessive bone marrow–derived and GSDMD-dependent early neutrophil production and mobilization (24 hours after AMI) contributed to the detrimental immunopathology after AMI. Pharmacological inhibition of GSDMD also conferred cardioprotection after AMI through a reduction in scar size and enhancement of heart function. Our study provides mechanistic insights into molecular regulation of neutrophil generation and mobilization after AMI, and supports GSDMD as a new target for improved ventricular remodeling and reduced heart failure after AMI.