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Chemical conversion of human and mouse fibroblasts into motor neurons

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Science China(Life Sciences) 2018年第10期61卷 1151-1167页

作者： Hua Qin ANDong Zhao kui ma Xiaobing Fu Graduate School of Tianjin Medical University Tianjin 300070 China Cell Biology and Tissue Repair Laboratory Key Laboratory of Wound Repair and Regeneration of PLA First Affiliated Hospital of PLA General HospitalBeijing 100048 China College of Life Sciences PLA General Hospital PLA Medical College Beijing 100853 China

Transplantation of motor neurons can provide long-term functional benefits in animal models of neurodegenerative motor neuron diseases such as amyotrophic lateral sclerosis and traumatic spinal cord injury. Although embryonic stem cells can differentiate into motor neurons, alternative sources of motor neurons may be controllable for disease modeling and transplantation. Here, we show that human and mouse fibroblasts can be efficiently and directly converted into motor neurons by a cocktail of five small molecules, without the involvement of the neural progenitor stage. The chemically-induced motor neurons display the distinct neuronal morphology and express motor neuron markers. Interestingly, when the same chemical compounds were soaked in beads and implanted in the hypodermis of the back skins of mice, surrounding cells begin to express motor neuron markers,indicating in vivo motor neuron reprogramming. Taken together, we provide an efficient approach for chemically converting human and mouse fibroblasts into motor neurons suitable for cell replacement therapy and neurodegenerative disease modeling.

关键词： fibroblast motor neuron small molecule transdifferentiation reprogramming conversion regeneration neurodegenerative diseases

Constant Barrier Strategies in a Two-state markov-modulated Dual Risk Model

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Acta mathematicae Applicatae Sinica 2011年第4期27卷 679-690页

作者： Xue-min ma kui LUO Guang-ming WANG Yi-jun HU School of mathematics and Statistics Wuhan University Wuhan 430072 China

In this paper, we consider the dividend problem in a two-state markov-modulated dual risk model, in which the gain arrivals, gain sizes and expenses are influenced by a markov process. A system of integro-differential equations for the expected value of the discounted dividends until ruin is derived. In the case of exponential gain sizes, the equations are solved and the best barrier is obtained via numerical example. Finally, using numerical example, we compare the best barrier and the expected discounted dividends in the two-state markov-modulated dual risk model with those in an associated averaged compound Poisson risk model. Numerical results suggest that one could use the results of the associated averaged compound Poisson risk model to approximate those for the two-state markov-modulated dual risk model.

关键词： Dual risk model markov-modulated risk model barrier strategy

Efficient and rapid conversion of human astrocytes and ALS mouse model spinal cord astrocytes into motor neuron-like cells by defined small molecules

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Military Medical Research 2021年第1期8卷 62-78页

作者： An-Dong Zhao Hua Qin Meng-Li Sun kui ma Xiao-Bing Fu Tianjin Medical University Tianjin 300070China Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and 4th Medical Center PLA General Hospital and PLA Medical College28 Fu Xing RoadHaidian DistrictBeijing 100853China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and RegenerationBeijing 100048China Research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical SciencesBeijing 100048China

Background: Motor neuron degeneration or loss in the spinal cord is the characteristic phenotype of motor neuron diseases or spinal cord injuries. Being proliferative and located near neurons, astrocytes are considered ideal cell sources for regenerating ***: We selected and tested different combinations of the small molecules for inducing the conversion of human and mouse astrocytes into neurons. Microscopic imaging and immunocytochemistry analyses were used to characterize the morphology and phenotype of the induced neurons while RT-q PCR was utilized to analyze changes in gene expression. In addition, whole-cell patch-clamp recordings were measured to examine the electrophysiological properties of induced ***: The results showed that human astrocytes could be rapidly and efficiently converted into motor neuronlike cells by treatment with defined small molecules, with a yield of over 85% motor neuron-like cells attained. The induced motor neuron-like cells expressed the pan-neuronal markers TUJ1, maP2, Neu N, and Synapsin 1 and motor neuron markers HB9, ISL1, CHAT, and VACh T. During the conversion process, the cells did not pass through a proliferative neural progenitor cell intermediate. The induced motor neurons were functional, showing the electrophysiological properties of neurons. The same chemical cocktail could induce spinal cord astrocytes from an amyotrophic lateral sclerosis mouse model carrying a SOD1 mutation to become motor neuron-like cells that exhibited a decrease in cell survival and an increase in oxidative stress compared to that observed in wild-type MNs derived from healthy mice. Moreover, the chemical induction reduced oxidative stress in the mutant ***: The results of the present study demonstrated the feasibility of chemically converting human and mouse astrocytes into motor neuron-like cells that are useful for neurodegenerative disease modeling and regenerative medicine.

关键词： Human astrocyte Motor neuron Reprogramming Transdifferentiation Conversion Regeneration Amyotrophic lateral sclerosis Neurodegenerative

Direct conversion of human fibroblasts into dopaminergic neuron-like cells using small molecules and protein factors

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Military Medical Research 2021年第2期8卷 162-173页

作者： Hua Qin An-Dong Zhao Meng-Li Sun kui ma Xiao-Bing Fu Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Division and 4th Medical Center PLA General Hospital and PLA Medical College28 Fu Xing RoadHaidian DistrictBeijing 100853China Tianjin Medical University Tianjin 300070China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and RegenerationBeijing 100048China Research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048China

Background:Generation of neurons is essential in cell replacement therapy for neurodegenerative disorders like Parkinson’s *** studies have reported the generation of dopaminergic(DA)neurons from mouse and human fibroblasts by ectopic expression of transcription factors,in which genetic manipulation is associated with potential ***:The small molecules and protein factors were selected based on their function to directly induce human fetal lung IMR-90 fibroblasts into DA neuron-like ***,immunocytochemical,and RT-qPCR analyses were used to characterize the morphology,phenotype,and gene expression features of the induced *** wholecell patch-clamp recordings were exploited to measure the electrophysiological ***:Human IMR-90 fibroblasts were rapidly converted into DA neuron-like cells after the chemical induction using small molecules and protein factors,with a yield of approximately 95%positive TUJ1-positive *** induced DA neuron-like cells were immunopositive for pan-neuronal markers maP2,NEUN,and Synapsin 1 and DA markers TH,DDC,DAT,and *** chemical induction process did not involve a neural progenitor/stem cell intermediate *** induced neurons could fire single action potentials,which reflected partially the electrophysiological properties of ***:We developed a chemical cocktail of small molecules and protein factors to convert human fibroblasts into DA neuron-like cells without passing through a neural progenitor/stem cell intermediate *** induced DA neuron-like cells from human fibroblasts might provide a cellular source for cell-based therapy of Parkinson’s disease in the future.

关键词： Human fibroblasts Dopaminergic neurons Parkinson's disease Small molecules Reprogramming Transdifferentiation

Enhanced carbon dioxide adsorption performance and kinetic study of K and Al co-doped Li4SiO4

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Chinese Chemical Letters 2018年第3期29卷 482-484页

作者： Nuonuo Gao kui ma Tong Ding Jinmeng Cai Ye Tian Xingang Li Collaborative Innovation Center for Chemical Sdence & Engineering (Tianjin) Tianjin Key laboratory of Applied Catalysis Science & Engineering School of Chemical Engineering & Technology Tianjin University Tianjin 30072 China

Herein, we report the effects of doped K and Al on the carbon dioxide （CO2） adsorption performance of the Li4SiO4-based adsorbents. The CO2 adsorption capacity of 0.8 wt% K and 1.5 wt% AI doped Li4SiO4 is ～2.2 times and ～1.3 times higher than that of the pristine Li4SiO4 at 500 and 600℃, respectively. The kinetic study further indicated that the reaction rates of the lithium diffusion process is greatly improved by K and AI doping, and the lithium diffusion rate of 0.8 wt% K and 1.5 wt% AI doped Li4SiO4 is ～2 times higher than that of the pristine Li4SiO4 at 575-650 ℃. K and AI doping increases the adsorption capacity of Li4SiO4-based adsorbents, and widens its effective adsorption temperature range

关键词： Li4SiO K and AI doping CO2 adsorption Kinetic study Adsorption stability

Influence of pore structure on thermal stress distribution inside coal particles during primary fragmentation

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Particuology 2024年第2期85卷 49-61页

作者： Kai Qiao Shan Zhong Siyang Tang Ke Yang Hairong Yue kui ma Lei Song Bin Liang School of Chemical Engineering Sichuan UniversityChengdu610065China Institute of New Energy and Low-carbon Technology Chengdu610207China

Thermal stress is an important reason of coal particle primary fragmentation,during which the role of pore structure is *** stress induced fragmentation experiments were conducted with low volatile coal/char particles,and the results show that the fragmentation severity enhances with increasing *** porous thermal stress models were developed with finite element method,and the influences of the pore shape,size,position and porosity on the thermal stress were *** maximum thermal stress inside particle increases with pore curvature,the pore position affects the thermal stress more significantly at the particle center and *** expectation of the maximum tensile thermal stress linearly increases with porosity,making the particles with higher porosity easier to fragment,contrary to the conclusion deduced from the devolatilization *** obtained results are valuable for the analysis of different thermal processes concerning the thermal stresses of the solid feedstocks.

关键词： Coal particle Primary fragmentation Thermal stress Pore structure Porosity

Application of pulsed chemical vapor deposition on the SiO_(2)-coated TiO_(2) production within a rotary reactor at room temperature

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Chinese Journal of Chemical Engineering 2022年第5期35卷 22-31页

作者： Ke Yang Shan Zhong Hairong Yue Siyang Tang kui ma Changjun Liu Kai Qiao Bin Liang School of Chemical Engineering Sichuan UniversityChengdu 610065China Institute of New Energy and Low-carbon Technology Chengdu 610207China

Pulsed chemical vapor deposition(P-CVD)is a promising technology for the surface modification of TiO_(2) *** the scale-up application of P-CVD,a custom-designed rotary reactor and corresponding coating process at room temperature was developed in the present *** obtained SiO_(2)-coated TiO_(2) particles were characterized by various measures including high-resolution transmission electron microscope,Fourier transform infrared spectroscopy,X-ray diffraction,*** results illustrated that the SiO_(2) films with a thickness of(3.7±0.7)nm were successfully deposited onto the surface of TiO_(2) *** to the dye degradation tests and acid solubility measurement,the deposited film can effectively inhibit the photocatalytic activity and enhance the weatherability of the TiO_(2) *** potential measurements showed that the SiO_(2)-coated TiO_(2) is possible to be stably dispersed in the pH range of 6.9–*** coating process made the whiteness of TiO_(2) particles decreased slightly but still sufficient(97.3±0.1)for ***,the properties of the TiO_(2) particles coated by PCVD were compared with the particles coated by traditional wet chemical *** is shown that the P-CVD can produce thinner but denser films with better photoactivity suppression *** developed coating process within the rotary reactor was proved practically feasible and convenient for the scale-up production of SiO_(2)-coated TiO_(2) via P-CVD.

关键词： Film Pulsed-CVD Scale-up Deactivation Pigmentary properties

Depositional System of the Carboniferous Huanglong Formation,Eastern Sichuan Basin:Constraints from Sedimentology and Geochemistry

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Acta Geologica Sinica(English Edition) 2016年第5期90卷 1795-1808页

作者： WANG Kun HU Suyun LI Wei LIU Wei HUANG Qingyu ma kui SHI Shuyuan Research Institute of Petroleum Exploration and Development CNPC

Using analyses of the lithology,sequences,paleoenvironment,and tectonic setting,the depositional system of the Carboniferous Huanglong Formation in the eastern Sichuan Basin was *** lithological characteristics of the Lower Member,Middle Member,and Upper Member were analyzed and *** the use of carbon,oxygen,and strontium isotopes in the analysis,all of the geochemical data were tested for *** the basis of the Z values obtained from carbon and oxygen isotopes,the paleoenvironments of the three members were *** Member was dominantly an enclosed marine environment with intense evaporation and little freshwater input into the *** Member developed in a semi-enclosed to normal marine environment with many *** Member was formed in a normal marine *** east Sichuan Basin was enclosed by paleouplifts before the deposition of the Huanglong Formation,forming a relatively enclosed depositional *** developed in the Silurian strata that underlie the Carboniferous rocks;these paleogullies can be *** the basis of a comprehensive analysis,we propose that the Huanglong Formation developed in a platform *** microfacies were identified：supratidal flat,dolostone flat,grain shoal,and shelf *** high-permeability and high-porosity characteristics of the grain shoal microfacies are favorable for hydrocarbon accumulation,while the supratidal flat and shelf microfacies developed very few high-quality *** paleogullies,in which increased amounts of grain shoal microfacies developed,controlled the distribution of high-quality reservoirs.

关键词： eastern Sichuan Basin Huanglong Formation depositional system paleoenvironment paleogully reservoir quality

Glucose-conjugated chitosan nanoparticles for targeted drug delivery and their specific interaction with tumor cells

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Frontiers of materials Science 2014年第4期8卷 363-372页

作者： Jing LI Fang-kui ma Qi-Feng DANG Xing-Guo LIANG Xi-Guang CHEN College of Food Science and Engineering Ocean University of China Qingdao 266003 China Freshwater Fisheries Research Institute of Shandong Province Jinan 250013 China College of marine Life Science Ocean University of China Qingdao 266003 China

A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles （GCNPs）, was developed for specific recognition and interaction with glucose transporters （Gluts） over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan （CS）, and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of （187.9 ± 3.8） nm and a zeta potential of （-15.43 ± 0.31） mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin （DOX） could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-Ioaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline （pH 7.4）. In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4-5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.

关键词： drug delivery target nanoparticle glucose transporter (Glut) chitosan(CS)