Facial Synthesis and Bioevaluation of Well-Defined OEGylated Betulinic Acid-Cyclodextrin Conjugates for Inhibition of Influenza Infection

Betulinic acid (BA) and its derivatives exhibit a variety of biological activities, especially their anti-HIV-1 activity, but generally have only modest inhibitory potency against influenza virus. The entry of influenza virus into host cells can be competitively inhibited by multivalent derivatives targeting hemagglutinin. In this study, a series of hexa-, hepta- and octavalent BA derivatives based on α-, β- and γ-cyclodextrin scaffolds, respectively, with varying lengths of flexible oligo(ethylene glycol) linkers was designed and synthesized using a microwave-assisted copper-catalyzed 1,3-dipolar cycloaddition reaction. The generated BA-cyclodextrin conjugates were tested for their in vitro activity against influenza A/WSN/33 (H1N1) virus and cytotoxicity. Among the tested compounds, 58, 80 and 82 showed slight cytotoxicity to Madin-Darby canine kidney cells with viabilities ranging from 64 to 68% at a high concentration of 100 μM. Four conjugates 51 and 69–71 showed significant inhibitory effects on influenza infection with half maximal inhibitory concentration values of 5.20, 9.82, 7.48 and 7.59 μM, respectively. The structure-activity relationships of multivalent BA-cyclodextrin conjugates were discussed, highlighting that multivalent BA derivatives may be potential antiviral agents against influenza infection.     

Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis

Low back pain (LBP) is a major musculoskeletal disorder and the socioeconomic problem with a high prevalence that mainly involves intervertebral disc (IVD) degeneration, characterized by progressive nucleus pulposus (NP) cell death and the development of an inflammatory microenvironment in NP tissue. Excessively accumulated cytosolic DNA acts as a damage-associated molecular pattern (DAMP) that is monitored by the cGAS-STING axis to trigger the immune response in many degenerative diseases. NLRP3 inflammasome-dependent pyroptosis is a type of inflammatory programmed death that promotes a chronic inflammatory response and tissue degeneration. However, the relationship between the cGAS-STING axis and NLRP3 inflammasome-induced pyroptosis in the pathogenesis of IVD degeneration remains unclear. Here, we used magnetic resonance imaging (MRI) and histopathology to demonstrate that cGAS, STING, and NLRP3 are associated with the degree of IVD degeneration. Oxidative stress induced cGAS-STING axis activation and NLRP3 inflammasome-mediated pyroptosis in a STING-dependent manner in human NP cells. Interestingly, the canonical morphological and functional characteristics of mitochondrial permeability transition pore (mPTP) opening with the cytosolic escape of mitochondrial DNA (mtDNA) were observed in human NP cells under oxidative stress. Furthermore, the administration of a specific pharmacological inhibitor of mPTP and self-mtDNA cytosolic leakage effectively reduced NLRP3 inflammasome-mediated pyroptotic NP cell death and microenvironmental inflammation in vitro and degenerative progression in a rat disc needle puncture model. Collectively, these data highlight the critical roles of the cGAS-STING-NLRP3 axis and pyroptosis in the progression of IVD degeneration and provide promising therapeutic approaches for discogenic LBP.Subject terms: Cell death, Diseases     

Observation of no significant surface enhancement of Raman scattering from benzoic acid molecules on mercury

There is controversy regarding the surface enhancement of Raman scattering due to liquid Hg, and the enhancement of benzoic acid molecules adsorbed on liquid Hg has been determined to be essentially zero. However, if the noise error bar is taken into account, the maximum enhancement is estimated to be less than 30. The same enhancement was observed when the temperature was reduced in solidifying liquid Hg.     

关于一类四阶非线性系统李雅普诺夫函数构造的研究

本文导出了四维线性系统的李雅普诺夫函数公式,研究了一类四阶非线性系统平凡解的稳定性。     

产电对微生物燃料电池参数的影响

测试了pH值和电导率的变化规律,分析了MFC开路电压的变化情况,为改善MFC的性能提供理论依据.采用驯化培养的菌种,MFC启动时间更短;在恒温、高温和高底物浓度条件下,开路电压更高、更稳.产物在阳极液中的积累会降低开路电压.阴极液和阳极液的pH值的差值与电流正相关.阳极液的电导率会减小,而阴极液的电导率会增大;阳极液中...     

Investigation of crystallographic sites of Eu in La2BaZnO5 by site-selective laser-excitation spectroscopy

La₂BaZnO₅:Eu³⁺ (0.05 mol%) was prepared by a solid-state reaction at high temperature. X-ray powder diffraction analysis confirmed the formation of single phase La₂BaZnO₅. Luminescence properties of La₂BaZnO₅:Eu³⁺ are investigated by site-selective laser-excitation and emission spectroscopy at 18 K. Two different crystallographic sites for Eu³⁺ corresponding to the La³⁺ and Ba²⁺ sites are identified from the ⁷F₀→⁵D₀ excitation spectra obtained by monitoring the ⁵D₀→⁷F_J (J=1, 2, …, 6) emissions. It is found that Eu³⁺ substituted for the Ba²⁺ ion experiences stronger crystal-field strength than Eu³⁺ substituted for the La³⁺ ion. Energy transfer between the two crystallographic Eu³⁺ centers is investigated by luminescence decay curves at 18 K.     

Morphology and elemental behaviour in the alteration layer of borosilicate glass in simulated groundwater

To understand the behaviour of nuclear waste glass in groundwater, borosilicate glasses were placed in simulated groundwater for more than 200 days. The composition of the simulated groundwater was similar to that of the groundwater in Beishan (a potential nuclear waste site). The pH value of groundwater was adjusted to 7.5, and the ratio of the surface area of glass to the volume of the solution (SA/V) was set to 10?m^?1. Solutions and bulk glasses were characterised to obtain the elemental behaviour and surface morphology of the glass/solution interface, which was named the alteration layer. The mean thicknesses of the alteration layer were 5.16?±?0.11?µm and 11.67?±?0.28?µm at 70°C and 90°C, respectively. A thicker alteration layer was attributed to the lower surface activation energy of the glass and a high ion exchange between K⁺ and Na⁺ in the interface between the glass surface and the solution. For the elemental behaviour, mobile species B and Na were depleted, while K and Ca from the solution were enriched in the alteration layer due to ion exchange. Network species Si decreased in the layer, leading to the corrosion of the backbone of the glass; however, species Al increased, which implied that some [SiO₄] units were partially replaced by [AlO₄] units. In this work, glass in groundwater suffered much more intense corrosion than that in de-ionised water.     

Improvement of intelligibility of ideal binary-masked noisy speech by adding background noise

When a target-speech/masker mixture is processed with the signal-separation technique, ideal binary mask (IBM), intelligibility of target speech is remarkably improved in both normal-hearing listeners and hearing-impaired listeners. Intelligibility of speech can also be improved by filling in speech gaps with un-modulated broadband noise. This study investigated whether intelligibility of target speech in the IBM-treated target-speech/masker mixture can be further improved by adding a broadband-noise background. The results of this study show that following the IBM manipulation, which remarkably released target speech from speech-spectrum noise, foreign-speech, or native-speech masking (experiment 1), adding a broadband-noise background with the signal-to-noise ratio no less than 4 dB significantly improved intelligibility of target speech when the masker was either noise (experiment 2) or speech (experiment 3). The results suggest that since adding the noise background shallows the areas of silence in the time-frequency domain of the IBM-treated target-speech/masker mixture, the abruption of transient changes in the mixture is smoothed and the perceived continuity of target-speech components becomes enhanced, leading to improved target-speech intelligibility. The findings are useful for advancing computational auditory scene analysis, hearing-aid/cochlear-implant designs, and understanding of speech perception under "cocktail-party" conditions.     

Calculations of Rydberg energy levels for Ni ⅩⅧ using the weakest bound electron potential model theory

Martin expression about the quantum defect of single-valence atoms is extended to many-valence atoms by identifying the weakest bound electron (WBE) under the weakest bound electron potential model(WBEPM) theory. Six Rydberg series energy levels of 2p6np2P°1/2 (n ≥ 3), 2p6np2P°3/2 (n ≥ 3), 2p6nd2D3/2(n ≥ 3), 2p6nd2D5/2 (n ≥ 3), 2p6nf2F°5/2 (n≥4), and 2p6nf2F°7/2 (n ≥ 4) for Ni ⅩⅧ are calculated by this method. The calculated results are in good agreement with the experimental results.     

STABILITY OF BRIGHT SCREENING-PHOTOVOLTAIC SPATIAL SOLITONS

We present a theoretical analysis of the stability of screening-photovoltaic (SP) spatial solitons in biased photovoltaic-photorefractive materials in the case of neglecting the loss of the material and the effect of diffusion. When an incident optical beam is a SP soliton, this beam propagates along a linear path with its shape kept unchanged. When the maximum amplitude, width and functional form of an incident optical beam are slightly different from those of a SP soliton, the beam reshapes itself and tries to evolve into a solitary wave after a short distance. That is, these SP solitons are stable against small perturbations. However, optical beams that significantly differ from SP soliton solutions tend to experience larger cycles of compression and expansion, and their maximum amplitudes oscillate with propagation distances. The larger the perturbations, the stronger the oscillation.