Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

Mechanical properties of fine-grained dual phase low-carbon steels based on dynamic transformation

The fine grained dual phase （FG-DP） steel with ferrite grains of 2-4.5 μm and martensite islands smaller than 3 μm was obtained through the mechanism of deformation-enhanced ferrite transformation （DEFT）. Mechanical properties of the steel were tested at room temperature. The results indicated that with a similar volume fraction of martensite （about 20vol%）,FG-DP steel exhibited a superior combination of higher strength and more rapid strain hardening at low strains compared with the coarse-grained dual phase （CG-DP） steel obtained by critical annealing. The combination of higher strength,large elongation,and more rapid strain hardening of FG-DP steel can be attributed to the fine ferrite grain and finely dispersed martensite islands. In addition,the uniformly distributed martensite islands in FG-DP steel have smaller interspacing compared with that of CG-DP steel. So,at the initial plastic deformation stage,the plastic deformation of ferrite was restrained and more pronounced load was transferred from ferrite to martensite. The plastic deformation of martensite in FG-DP steel started earlier.

Synthesis and Bioactivity of Natural Occurring Petasin-Like Derivatives as Antitumor Agents

Petasin is a potential antitumor against human neuroblastoma cell SK-N-SH by inhibiting the ERK1/2 phosphorylation. In view of its great activity and new antiproliferative mechanisms, a series of petasin derivatives were designed and synthesized, which showed great antiproliferative activity. Among them compounds 1h and 1f were more effective against SK-N-SH cells than petasin with the IC50 values of 0.87 and 2.63 μM, respectively.

The effect of clinical-grade retinal pigment epithelium derived from human embryonic stem cells using different transplantation strategies

Dear Editor, Many forms of sight-threatening diseases, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD), are caused by the dysfunction, degeneration and loss of the retinal pigment epithelium (RPE)(Strauss, 2005). RPE cell transplantation may potentially recover or halt disease progression, in which human embryonic stem cells (hESCs) could serve as an unlimited donor source for RPE differentiation, and a few clinical trials have shown the safety and effective of transplantation of hESCs-derived RPE (hESC-RPE) for AMD patients (Schwartz et al., 2012;Schwartz etal., 2015;Song etal., 2015;da Cruz et al., 2018;Kashani et al., 2018;Liu et al., 2018).

A Highly Diastereoselective Three-component Domino Reac- tion in Water Yielding Poly-substituted 4,5-Dihydropyrroles

An efficient methodology for highly diastereoselective synthesis ofpoly-substituted 4,5-dihydropyrrole deriva- tives from readily available common reactants in water has been developed. During domino processes, the forma- tion of pyrrole skeleton and its C2-hydroxylation and C3-arylamination were readily achieved via metal-free [3 ＋2] heterocyclization in a one-pot operation.

Toxicity of silicon dioxide nanoparticles with varying sizes on the cornea and protein corona as a strategy for therapy

The human cornea is exposed directly to particulate matter （PM） in polluted air. This exposure can cause eye discomfort and corneal injury. Ultrafine PM （diameter ~100 nm） is thought to be particularly harmful to health, but there is limited research investigating its toxicity to the eye. In this study, we evaluated toxiciW differences among 30-, 40-, 100- and 150-nm silicon dioxide nanoparticles （Si02 NPs） on the cornea. A 24-hour in vitro exposure of primary human corneal epithelial cells （hCECs） to ultrafine （30 and 40 nm） SiO2 NPs produced toxicity, as evidenced by cell membrane damage, reduced cell viability, increased cell death and mitochondrial dysfunction. In vivo exposure to the same nanoparticles produced observable corneal injury. These effects were more severe with ultrafine than with fine （100 and 150 nm） Si02 NPs. Common antioxidant compounds, e.g., glutathione, did not protect the cornea from SiO2 NP-induced damage. However, foetal bovine serum （FBS） did significantly reduce toxicity, likely by forming a protective protein corona around the nanoparticles. This finding suggests that FBS （or its derivatives） may be a useful clinical therapy for corneal toxicity caused by ultrafine particulates.