Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in rats

Neural progenitor cells(NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox(VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR(0.5 mM valproic acid, 3 μM CHIR99021, and 1 μM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition(5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6(Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs(ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson’s disease.

Effect of recombinant human endostatin onradiotherapy for esophagus cancer

Objective:To investigate the effect of radiotherapy plus recombinant human endostatin（RHendostatin） on esophageal cancer and its mechanism.Methods:A total of SO nudemice were equally randomized into control group,radiotherapy group,and combined therapy group Ⅰ,Ⅱ,and Ⅲ after inoculating with Ecal09 cell suspension（1×107 cells/mL）.On the day of grouping,control group and radiotherapy group were injected normal saline,while radiotherapy group and 3 combined therapy groups received radiotherapy;besides,combined therapy group Ⅰ,Ⅱ,and Ⅲ was injected RH-endostatin of 2.5,5,10 mg/kg respectively.After 3-week therapy,the tumors of each group were collected and microvessel density and VEGF expression in tumors were determined.In vitro,Eca109 cells were divided into control group,radiotherapy group,and combined therapy group.Forty-eight hours after treatment cell cycle distribution and apoptosis rate were detected,and the activity of VEGF signal paths was semiquantitatively analyzed.Results:Since the 6th day of treatment,the relative tumor proliferation rate of combined therapy group Ⅱ was lower than radiotherapy group（P<0.05） and 40%since the 15 th day.Average microvessel density and EGFR expression in combined therapy group Ⅱ were lower than radiotherapy group（P<0.05）.In vitro,the cell percentage in S and G2/M phase of combined therapy group cells was lower than that in radiotherapy group cells,while the apoptosis rate and the expression of VEGF,AKT,p-AKT,ERK1/2 and p-ERKl/2 in combined group were higher than that in radiotherapy group（P<0.05）.Conclusions:RH-endostatin promotes the efficacy of radiotherapy on esophageal cancer,which may be partly realized by inhibiting the activity of VEGF related signal paths.

A chromosome-level reference genome of nonheading Chinese cabbage[Brassica campestris(syn.Brassica rapa)ssp.chinensis]

Non-heading Chinese cabbage(NHCC)is an important leafy vegetable cultivated worldwide.Here,we report the first high-quality,chromosome-level genome of NHCC001 based on PacBio,Hi-C,and Illumina sequencing data.The assembled NHCC001 genome is 405.33 Mb in size with a contig N50 of 2.83 Mb and a scaffold N50 of 38.13 Mb.Approximately 53%of the assembled genome is composed of repetitive sequences,among which long terminal repeats(LTRs,20.42%of the genome)are the most abundant.Using Hi-C data,97.9%(396.83 Mb)of the sequences were assigned to 10 pseudochromosomes.Genome assessment showed that this B.rapa NHCC001 genome assembly is of better quality than other currently available B.rapa assemblies and that it contains 48,158 protein-coding genes,99.56%of which are annotated in at least one functional database.Comparative genomic analysis confirmed that B.rapa NHCC001 underwent a whole-genome triplication(WGT)event shared with other Brassica species that occurred after the WGD events shared with Arabidopsis.Genes related to ascorbic acid metabolism showed little variation among the three B.rapa subspecies.The numbers of genes involved in glucosinolate biosynthesis and catabolism were higher in NHCC001 than in Chiifu and Z1,due primarily to tandem duplication.The newly assembled genome will provide an important resource for research on B.rapa,especially B.rapa ssp.chinensis.

Deformation behavior and microstructural evolution during hot compression of an a+b Ti-6.5Al-3.5Mo-1.5Zr-0.3Si alloy

The effect of processing parameters on the flow response and microstructural evolution of the a＋b titanium alloy Ti-6.5Al-3.5Mo-1.5Zr-0.3Si has been studied by conducting isothermal hot compressive tests at a strain rate of 0.01-10 s-1 at 860-1100°C. The true stress-true strain curves of the sample hot-compressed in the a＋b phase region exhibit a peak stress followed by continuous flow softening, whereas in the b region, the flow stress attains a steady-state regime. At a strain rate of 10 s-1, the alloy exhibits plastic flow insta-bilities. According to the kinetic rate equation, the apparent activation energies are estimated to be about 674-705 kJ/mol in the a＋b region and 308-335 kJ/mol in the b region, respectively. When deformed in the a＋b region, the globularization process of the a colony structure occurs, and a dynamic recrystallized microstructures are observed to show bimodal. Dynamic recrystallization can take place in the b region irrespective of starting deformed structures.