Mechanisms of rotenone-induced neurotoxicity in PC 12 cells

BACKGROUND： Rotenone-induced neurotoxicity in PC 12 cells has been widely used to study the pathogenesis of Parkinson＇s disease. However, the precise mechanisms underlying rotenone-induced dopaminergic neuronal degeneration in Parkinson＇s disease remains unclear. OBJECTIVE： To establish rotenone-induced neurotoxicity in PC 12 cells, and to investigate the possible action pathways to rotenone-induced neural cell injury at the protein level. DESIGN, TIME AND SETTING： A controlled proteomics study was performed at the Department of Neurology, First Hospital, Jilin University between March 2006 and March 2007. MATERIALS： PC 12 cells were obtained from Shanghai Cell Bank of Chinese Academy of Sciences, China. Rotenone was provided by Sigma, USA. METHODS： PC 12 cells in logarithmic growth phase were treated under experimental and control conditions, respectively. A total of 0.5 μmol/L rotenone, or the same amount of Dulbecco＇s modified eagle＇s medium （DMEM）, was added in the experimental and control conditions, respectively. MAIN OUTCOME MEASURES： Following 72 hours of rotenone treatment, cellular survival rate was determined by methyl thiazolyl tetrazolium assay, and apoptotic changes were detected by Hoechst 33342 staining. Total cellular protein was extracted to acquire differential protein expression data utilizing two-dimensional differential in-gel electrophoresis. To identify differential protein spots, matrix-assisted laser desorption/ionization-time of flight mass spectrometry （MALDI-TOF-MS） was used. RESULTS： In the MTT assay, the experimental condition induced significantly less cell survival compared to the control condition （P 〈 0.01）. Hoechst 33342 staining revealed a larger number of apoptotic cells under the experimental condition compared to the control condition （P 〈 0.01）, as determined by the presence of nuclear condensation, pyknosis, and nuclear fragmentation. Two-dimensional electrophoresis results showed that the differential expression of protein spots 1069 and 1538 was increased by 144% and 124%, respectively, while that of protein spot 1094 was decreased by 123% in the experimental condition compared to the control condition （P 〈 0.01）. By MALDI-TOF-MS analysis and database retrieval, γ-enolase, triosephosphate isomerase 1, and eukaryotic translation initiation factor 4A were confirmed to be involved in rotenone-induced neural cell injury. CONCLUSION： γ-enolase, triosephosphate isomerase 1, and eukaryotic translation initiation factor 4A might participate in rotenone-induced neurotoxicity in PC 12 cells.

Fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage

Unrestrained inflammation is harmful to tissue repair and regeneration.Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation.Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function,but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions.In this study,we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation(early pulpitis as the model)with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo.Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide(E.coli LPS)with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways.Moreover,nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects,attenuating inflammatory conditions in the early stage.Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage,which widens the potential cell types for inflammation regulation.

Inflammatory risk stratification individualizes anti-inflammatory pharmacotherapy for acute type A aortic dissection

The systemic benefits of anti-inflammatory pharmacotherapy vary across cardiovascular diseases in clinical practice.We aimed to evaluate the application of artificial intelligence to acute type A aortic dissection(ATAAD)patients to determine the optimal target population who would benefit from urinary trypsin inhibitor use(ulinastatin).Patient characteristics at admission in the Chinese multicenter 5A study database(2016-2022)were used to develop an inflammatory risk model to predict multiple organ dysfunction syndrome(MODS).

In-plane ferroelectric tunnel junctions based on 2D α-In_(2)Se_(3)/ semiconductor heterostructures

Ferroelectric tunnel junctions(FTJs)have great potential for application in high-density non-volatile memories.Recently,α-In_(2)Se_(3) was found to exhibit robust in-plane and out-of-plane ferroelectric polarizations at a monolayer thickness,which is ideal to serve as a ferroelectric component in miniaturized electronic devices.In this work,we design two-dimensional van der Waals heterostructures composed of anα-In_(2)Se_(3) ferroelectric and a hexagonal IV–VI semiconductor and propose an in-plane FTJ based on these heterostructures.Our first-principles calculations show that the electronic band structure of the designed heterostructures can be switched between insulating and metallic states by ferroelectric polarization.We demonstrate that the in-plane FTJ exhibits two distinct transport regimes,tunneling and metallic,for OFF and ON states,respectively,leading to a giant tunneling electroresistance effect with the OFF/ON resistance ratio exceeding 1×104.Our results provide a promising approach for the high-density ferroelectric memory based on the 2D ferroelectric/semiconductor heterostructures.

Enhanced 1-5 μm near-and mid-infrared emission in Ho/Ybcodoped TeO-ZnF oxyfluorotellurite glasses

Intense 1-5 μm infrared emission from near-to mid-infrared was obtained from Ho3+/Yb3+codoped TeO2-ZnF2 oxyfluorotellurite glasses which were prepared by melt-quenching method under the 980 nm LD excitation,and the emission intensity can be enhanced with the increase of ZnF2 content.Judd-Ofelt analysis was used to evaluate the radiative transition parameters of the excited levels according to the absorption spectra.The stimulated emission cross section of 5 I6→5 I8(1.2 μm),5 I7→5 I8(2.0μm),5 I6→5 I7(2.85 μm) and 5 I5→5 I6(4.0 μm) transitions were calculated to reach 0.639 × 10-20,0.760 ×10-20,0.985×10 20 and 0.484 × 10-20 cm2,respectively.The energy transfer coefficients(CDA) are enhanced with the increase of ZnF2 content and phonon contribution ratios of phonon assisted energy transfer process between Ho3+ and Yb3+were figured out.Our results demonstrate that these TeO2-ZnF2 glasses,which possess good thermal stability and transparency,low phonon energy(about 600 cm-1),excellent near-and mid-infrared emission in the range of 1-5 μm wavelength,would be promising material for infrared optical fibers and infrared lasers.