Practice of O2O Education Model

This paper introduces the characteristics of the education mode of O2O, and clarifies the shortcomings of the training of network engineering and information security professionals. Later Anhui Institute of Information Engineering puts forward the theory of O2O education in network engineering and information security professionals, and lastly discusses the detailed plan and implementation of the education model of O2O in detail. This model has achieved good results.

Gedunin Degrades Aggregates of Mutant Huntingtin Protein and Intranuclear Inclusions via the Proteasomal Pathway in Neurons and Fibroblasts from Patients with Huntington’s Disease

Huntington's disease(HD) is a deadly neurodegenerative disease with abnormal expansion of CAG repeats in the huntingtin gene. Mutant Huntingtin protein(m HTT) forms abnormal aggregates and intranuclear inclusions in specific neurons, resulting in cell death. Here,we tested the ability of a natural heat-shock protein 90 inhibitor, Gedunin, to degrade transfected m HTT in Neuro-2 a cells and endogenous m HTT aggregates and intranuclear inclusions in both fibroblasts from HD patients and neurons derived from induced pluripotent stem cells from patients. Our data showed that Gedunin treatment degraded transfected m HTT in Neuro-2 a cells, endogenous m HTT aggregates and intranuclear inclusions in fibroblasts from HD patients, and in neurons derived from induced pluripotent stem cells from patients in a dose-and time-dependent manner, and its activity depended on the proteasomal pathway rather than the autophagy route. These findings also showed that although Gedunin degraded abnormal m HTT aggregates and intranuclear inclusions in cells from HD patient, it did not affect normal cells, thus providing a new perspective for using Gedunin to treat HD.

Tau Accumulation via Reduced Autophagy Mediates GGGGCC Repeat Expansion-Induced Neurodegeneration in Drosophila Model of ALS

Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders,including Huntington disease[caused by expanded CAG repeats(CAGr)in the HTT gene],and amyotrophic lateral sclerosis[ALS,possibly caused by expanded GGGGCC repeats(G4C2r)in the C9ORF72 gene],of which the molecular mechanisms remain unclear.Here,we demonstrated that lowering the Drosophila homologue of tau protein(dtau)significantly rescued in vivo neurodegeneration,motor performance impairments,and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r.Expression of human tau(htau4 R)restored the disease-related phenotypes that had been mitigated by the loss of dtau,suggesting an evolutionarily-conserved role of tau in neurodegeneration.We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome-lysosome fusion,possibly due to lowering the level of BAG3,a regulator of autophagy and tau.Taken together,our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism.Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.