Mechanism of SET8 Activates the Nrf2-KEAP1-ARE Signaling Pathway to Promote the Recovery of Motor Function after Spinal Cord Injury.

Background: Spinal cord injury (SCI) is a common injury of the central nervous system (CNS), and astrocytes are relatively abundant glial cells in the CNS that impairs the recovery of motor function after SCI. It was confirmed that the oxidative stress of mitochondria leads to the accumulation of reactive oxygen species (ROS) in cells, which plays a key role in the motor function of astrocytes. However, the mechanism by which oxidative stress affects astrocyte motility after SCI is still unexplained. Therefore, this study investigated the influence of SET8-regulated oxidative stress on astrocyte autophagy levels after SCI in rats and the potential mechanisms of action. Methods: We used real-time quantitative PCR, western blotting, and immunohistochemical staining to analyze SET8, Keap1, and Nrf2 expression at the cellular level and in SCI tissues. ChIP to detect H4K20me1 enrichment in the Keap1 promoter region under OE-SET8 (overexpression of SET8) conditions. Western blotting was used to assess the expression of signature proteins of astrocytes, proteins associated with autophagy, proteins associated with glial scar formation, reactive oxygen species (ROS) levels in cells using DHE staining, and astrocyte number, morphological alterations, and induction of glial scar formation processes using immunofluorescence. In addition, the survival rate of neurons after SCI in rats was examined by using NiSSl staining. Results: OE-SET8 upregulates the enrichment of H4K20me1 in Keap1, inhibits Keap1 expression, activates the Nrf2-ARE signaling pathway to suppress ROS accumulation, inhibits oxidative stress-induced autophagy and glial scar formation in astrocytes, and leads to reduced neuronal loss, which promoted the recovery and improvement of motor function after SCI in rats. Conclusion: Overexpression of SET8 alleviated oxidative stress by regulating Keap1/Nrf2/ARE, inhibited astrocyte autophagy levels, and reduced glial scar formation as well as neuronal loss, thereby promoting improved recovery of motor function after SCI. Thus, the SET8/H4K20me1 regulatory function may be a promising cellular therapeutic intervention point after SCI.

Budesonide and N-acetylcysteine inhibit activation of the NLRP3 inflammasome by regulating miR-381 to alleviate acute lung injury caused by the pyroptosis-mediated inflammatory response.

Background: The anti-inflammatory effects of budesonide (BUN) and N-acetylcysteine (NAC) attenuate acute lung injury (ALI). The aim of this study was to investigate the effects of combination therapy consisting of BUN and NAC on ALI and the underlying mechanisms. Methods: In vitro and in vivo models of ALI were generated by LPS induction. Western blotting was used to detect the expression levels of pyroptosis-related proteins and inflammation-related factors, and RT-qPCR was used to detect the expression of miR-381. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. ELISA was used to detect the levels of inflammation-related factors. HE staining was used to detect lung injury. Results: The results showed that LPS effectively induced pyroptosis in cells and promoted the expression of pyroptosis-related proteins (Caspase1, Gasdermin D and NLRP3) and inflammatory cytokines (TNF-α, IL-6 and IL-1ß). The combination of BUN and NAC significantly alleviated LPS-induced pyroptosis and inflammation. In addition, the combination of BUN and NAC effectively promoted miR-381 expression. Transfection of miR-381 mimics effectively alleviated LPS-induced pyroptosis and inflammation, while transfection of miR-381 inhibitors had the opposite effect. miR-381 negatively regulates NLRP3 expression. Treatment with a miR-381 inhibitor or pc-NLRP3 reversed the effects of the combination of BUN and NAC. In a mouse model of ALI, the combination of BUN and NAC effectively improved lung injury, while treatment with a miR-381 inhibitor or pc-NLRP3 effectively reversed this effect. Conclusion: Overall, this study revealed that BUN + NAC inhibits the activation of NLRP3 by regulating miR-381, thereby alleviating ALI caused by pyroptosis-mediated inflammation.

Synthesis, characterization, and in vitro pH-controllable drug release from mesoporous silica spheres with switchable gates.

To accomplish pH-controllable drug release on mesoporous carrier, one of the best ways is to graft stimuli-responsive organic molecules around mesopore outlets. In this work, the pH-responsive propyldiethylenetriamine groups (abbreviative phrase: multiamine chains) were grafted around mesopore outlets of mesoporous silica spheres (MSS) and expected to act as pH-responsive gates. To this end, three multiamine-grafted MSS (i.e., NM1, NM2, and NM3) were synthesized under different reaction temperatures and reaction times. The reaction temperature and time for multiamine grafting were 25 °C and 12 h for NM1, 100 °C and 1 h for NM2, and 100 °C and 12 h for NM3, respectively. Through systematic investigations of TEM, SEM, N(2) adsorption/desorption, TG, and (29)Si MAS NMR, it was found that NM3 had the highest grafting amount of multiamine chains. It was further confirmed that the multiamine chains around the pore outlets of NM3 played the role of "molecular switch" that could well control the transport of guest drug molecules. In contrast, the multiamine chains around the pore outlets of NM2 and NM3 did not show gate effect. The difference should be decided by the fact whether the grafting amount of multiamine chains around mesopore outlets were sufficient under determined reaction temperature and time. In the tests of in vitro drug release, multiamine-gated MSS (i.e., NM3) showed highly sensitive response to the solution pH. At high pH (pH 7.5), ibuprofen (IBU) in this carrier released rapidly and completely within 2 h; at low pH (pH 4.0 or 5.0), only a small part of the IBU (13 wt %) was slowly released from this carrier and the most of IBU was effectively confined in mesopores.

Extra-framework aluminium species in hydrated faujasite zeolite as investigated by two-dimensional solid-state NMR spectroscopy and theoretical calculations.

Extra-framework aluminium (EFAL) species in hydrated dealuminated HY zeolite were thoroughly investigated by various two-dimensional solid-state NMR techniques as well as density functional theoretical calculations. (27)Al MQ MAS NMR experiments demonstrated that five-coordinated and four-coordinated extra-framework aluminium subsequently disappeared with the increase of water loading, and the quadrupole interaction of each aluminium species decreased gradually during the hydration process. (1)H double quantum MAS NMR revealed that the EFAL species in the hydrated zeolite consisted of three components: a hydroxyl AlOH group, and two types of water molecule (rigid and mobile water). (1)H-(27)Al LG-CP HETCOR experiments indicated that both the extra-framework and the framework Al atoms were in close proximity to the rigid water in the fully rehydrated zeolite. The experimental results were further confirmed by DFT theoretical calculations. Moreover, theoretical calculation results further demonstrated that the EFAL species in the hydrated zeolite consisted of the three components and the calculated (1)H NMR chemical shift for each component agreed well with our NMR observations. It is the rigid water that connects the extra-framework aluminium with the four-coordinated framework aluminium through strong hydrogen bonds.

Influence of implant collar design on stress and strain distribution in the crestal compact bone: a three-dimensional finite element analysis.

PURPOSE: To evaluate the influence of implant collar geometry on the distribution of stress and strain in the crestal compact bone contiguous to an implant collar for four types of bone under axial and oblique loads. MATERIALS AND METHODS: Finite element models of threaded implants with three kinds of implant collar designs (divergent, straight, and convergent) with their corresponding suprastructures embedded in the posterior mandible were created with ANSYS software. Eight different test conditions incorporating four types of bone (orthotropic and effectively isotropic in part 1 and high and low densities in part 2) under separate 100-N axial and 35.6-degree oblique forces were created to investigate the stress and strain distributions in the crestal compact bone around the implant collars. RESULTS: In all eight conditions, the divergent collar demonstrated the lowest maximum von Mises and principal stresses and strains in the crestal compact bone contiguous to the implant collar, followed by the straight and convergent collars. The oblique load induced higher peak values than the axial load. The orthotropic design amplified and increased the pathologic microstrains and tensile stresses in the crestal compact bone compared to the effectively isotropic design, especially in models with a convergent collar design. In part 2 of the study, the maximum von Mises stresses and strains increased with a decrease in the cancellous bone density. Under oblique loading, the convergent and straight collars showed pathologic microstrain values as well as excessive ultimate tensile stresses in the orthotropic bone model with low-density cancellous bone. CONCLUSIONS: Within the limitations, it was concluded that stress and strain distributions in the adjacent compact bone are influenced by the implant collar design. The divergent implant collar design was associated with the lowest stress and strain concentrations in the crestal compact bone.

Theoretical studies on carbon dioxide adsorption in cation-exchanged molecular sieves.

The capture and storage of the greenhouse gas, CO2, has attracted much interest from scientists in recent years. In this work, density functional theory (DFT) was used to study the adsorption of CO2 in different cation-exchanged molecular sieves. The results show that for the monovalent metal (Li, Na, K, Cu) ion-exchanged molecular sieves (zeolite Y, ZSM-5, CHA and A), the adsorption capacities for CO2 decrease in the order of Li+ > Na+ > K+ > Cu+. Cu+-exchanged zeolites are not suitable as adsorbents for CO2. For the CO2 adsorption capacities in different zeolites with the same exchanged cation, the adsorption energy decreases in the order of Y > A > ZSM-5 ≈ CHA for Li-exchanged zeolites, and ZSM-5 still has the lowest CO2 adsorption energy for both Na- and K-exchanged zeolites. In the cation-exchanged Y zeolites with divalent metals (Be, Mg, Ca and Zn), the CO2 adsorption performance increases in the order of Zn2+ < Be2+ < Ca2+ < Mg2+. Thus, Zn2+-exchanged zeolites are not suitable as adsorbents for CO2.

Amino acid adsorption on mesoporous materials: influence of types of amino acids, modification of mesoporous materials, and solution conditions.

In order to disclose the dominant interfacial interaction between amino acids and ordered mesoporous materials, the adsorption behaviors of five amino acids on four mesoporous materials were investigated in aqueous solutions with adjustable amino acid concentration, ion strength, and pH. The selected amino acids were acidic amino acid glutamic acid (Glu), basic amino acid arginine (Arg), and neutral amino acids phenylalanine (Phe), leucine (Leu), and alanine (Ala), and the selected mesoporous materials were SBA-15, Al-SBA-15, CH3(10%)-SBA-15, and CH3(20%)-SBA-15. The adsorption capacities of Glu and Arg were strongly dependent on pH and surface charge of the mesoporous adsorbent. The adsorption of Phe showed pH insensitivity but depended on the surface organic functionalization of mesoporous adsorbent. On the basis of the theoretical analysis about the interaction between amino acid and adsorbent, such a remarkable difference was attributed to the different nature of the interaction between amino acid and adsorbent. Arg could be readily adsorbed on the surface of SBA-15, especially Al-SBA-15, under appropriate pH in which the electrostatic interaction was predominant. The driving force of Phe adsorption on mesoporous adsorbent mainly came from the hydrophobic interaction. Therefore, the adsorption capability of Arg decreased with increasing ion strength of solution, while the adsorption capability of Phe increased with the increasing degree of CH3 functionalization on SBA-15. For neutral amino acid Phe, Ala, and Leu, the adsorption capability increased with the increase of the length of their side chains, which was another evidence of hydrophobic effect. Thus, all the adsorption of amino acids on mesoporous silica materials can be decided by the combined influence of two fundamental interactions: electrostatic attraction and hydrophobic effect.

Reactivity enhancement of 2-propanol photocatalysis on SO4(2-)/TiO2: insights from solid-state NMR spectroscopy.

Solid-state NMR techniques have been employed to investigate the surface acidic properties of TiO2 and sulfated TiO2, as well as their photocatalytic activities toward 2-propanol. The multinuclear MAS NMR experiments clearly revealed that three different types of Brønsted acid sites with much stronger acid strength were generated after the sulfation of TiO2. Due to the enhanced Brønsted acidity, the protonation of 2-propanol can occur more easily, preferentially leading to the formation of Ti-bound 2-propoxy species on the SO42-/TiO2 catalyst The 2-propoxy species can be directly converted to CO2 and thus the photocatalytic activity of sulfated TiO2 catalyst is remarkably enhanced. For comparison, both hydrogen-bonded 2-propanol and Ti-bound 2-propoxy species are present on the TiO2 catalyst with the former being predominant The hydrogen-bonded 2-propanol species are oxidated into acetone molecules that are difficult to further convert into CO2, and the conversion of 2-propoxy species to 2-propanol hampers the direct mineralization of 2-propoxy species on the TiO2 catalyst.