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ADNP syndrome is a neurodevelopmental disorder characterized by autism, intellectual disability, and other physical and behavioral health manifestations. Mutations in ADNP gene is responsible for ADNP syndrome. A human iPSC line with a de novo heterozygous ADNP mutation (ADNP c. 2059 T>C) was generated from peripheral blood mononuclear cells of a patient with ADNP syndrome. This iPSC line showed typical human embryonic stem cell-like morphology, normal karyotype, pluripotency, and ability to differentiate into three germ layers. This iPSC line provides a useful resource to study the pathogenesis and drug screening of ADNP syndrome.

Human pluripotent stem cell-based (hPSC-based) replacement therapy holds great promise for the treatment of Parkinson's disease (PD). However, the heterogeneity of hPSC-derived donor cells and the low yield of midbrain dopaminergic (mDA) neurons after transplantation hinder its broad clinical application. Here, we have characterized the single-cell molecular landscape during mDA neuron differentiation. We found that this process recapitulated the development of multiple but adjacent fetal brain regions including the ventral midbrain, the isthmus, and the ventral hindbrain, resulting in a heterogenous donor cell population. We reconstructed the differentiation trajectory of the mDA lineage and identified calsyntenin 2 (CLSTN2) and protein tyrosine phosphatase receptor type O (PTPRO) as specific surface markers of mDA progenitors, which were predictive of mDA neuron differentiation and could facilitate high enrichment of mDA neurons (up to 80%) following progenitor cell sorting and transplantation. Marker-sorted progenitors exhibited higher therapeutic potency in correcting motor deficits of PD mice. Different marker-sorted grafts had a strikingly consistent cellular composition, in which mDA neurons were enriched, while off-target neuron types were mostly depleted, suggesting stable graft outcomes. Our study provides a better understanding of cellular heterogeneity during mDA neuron differentiation and establishes a strategy to generate highly purified donor cells to achieve stable and predictable therapeutic outcomes, raising the prospect of hPSC-based PD cell replacement therapies., Introduction Stem cell-based replacement therapy has been one of the most promising strategies for treating Parkinson's disease (PD) (1-4). Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) [...]

This study prepared silicon oxide anode materials with nitrogen-doped carbon matrices (SiOx/C–N) through silicon-containing polyester thermal carbonization. Melamine was introduced as a nitrogen source during the experiment. This nitrogen doping process resulted in a porous structure in the carbon matrices, a fact confirmed by scanning electron microscopy (SEM). Pyridinic and quaternary nitrogen, but mainly tertiary nitrogen, were generated, as shown via X-ray photoelectron spectroscopy (XPS). Electrochemical tests confirmed that, as anode materials for a lithium-ion battery, SiOx/C–N provided better cycle stability, improved rate capability, and lower Li+ diffusion resistance. The best performance showed an activated capacity at 493.5 mAh/g, preserved at 432.8 mAh/g after the 100th cycle, with 87.7% total Columbic efficiency. Those without nitrogen doping gave 1126.7 mAh/g, 249.0 mAh/g, and 22.1%, respectively. The most noteworthy point was that, after 100 cycles, anodes without nitrogen doping were pulverized into fine powders (SEM); meanwhile, in the case of anodes with nitrogen doping, powders of a larger size (0.5–1.0 µm) formed, with the accumulation of surrounding cavities. We suggest that the formation of more prominent powders may have resulted from the more substantial nitrogen-doped carbon matrices, which prevented the anode from further breaking down to a smaller size. The volume expansion stress decreased when the powders decreased to nanosize, which is why the nanosized silicon anode materials showed better cycling stability. When the anodes were cracked into powders with a determined diameter, the stress from volume expansion decreased to a level at which the powders could preserve their shape, and the breakage of the powders was stopped. Hence, the diameters of the final reserved powders are contingent on the strength of the matrix. As reported, nitrogen-doped carbon matrices are more robust than those not doped with nitrogen. Thus, in our research, anodes with nitrogen-doped carbon matrices presented more large-diameter powders, as SEM confirmed. Anodes with nitrogen doping will not be further broken at a larger diameter. At this point, the SEI film will not show continuous breakage and formation compared to the anode without doping. This was validated by the lower deposition content of the SEI-film-related elements (phosphorous and fluorine) in the cycled anodes with nitrogen doping. The anode without nitrogen doping presented higher content, meaning that the SEI films were broken many times during lithiation/delithiation (EDS mapping). [ABSTRACT FROM AUTHOR]

Perinatal hypoxic–ischaemic encephalopathy is the leading cause of neonatal death and permanent neurological deficits, while the basal ganglia is one of the major nuclei that is selectively and greatly affected in the brains of hypoxic–ischaemic encephalopathy patients, especially in severe cases. Human embryonic stem cell-derived neurons have shown great potential in different types of brain disorders in adults. However, it remains unknown whether and how grafted human embryonic stem cell-derived neurons can repair immature brains with hypoxic–ischaemic encephalopathy. Here, by administrating genetically labelled human embryonic stem cell-derived striatal neural progenitors into the ipsilateral striatum of hypoxic–ischaemic encephalopathy-injured mice, we found that the grafted cells gradually matured into GABA spiny projection neurons morphologically and electrophysiologically, and significantly rescued the area loss of hypoxic–ischaemic encephalopathy-injured brains. Intriguingly, using immunohistochemical staining combined with enhanced ascorbate peroxidase-based immunoelectron microscopy and rabies virus-mediated trans-synaptic tracing, we show that the grafts start to extend axonal projections to the endogenous target areas (globus pallidus externa, globus pallidus internus, substantia nigra), form synapses with host striatal, globus pallidus and nigra neurons, and receive extensive and stable synaptic inputs as early as 2 months post-transplantation. Importantly, we further demonstrated functional neural circuits re-established between the grafted neurons and host cortical, striatal and substantial nigra neurons at 3–6 months post-transplantation in the hypoxic–ischaemic encephalopathy-injured brain by optogenetics combined with electrophysiological recording. Finally, the transplanted striatal spiny projection neurons but not spinal GABA neurons restored the motor defects of hypoxic–ischaemic encephalopathy, which were reversed by clozapine- N -oxide-based inhibition of graft function. These findings demonstrate anatomical and functional reconstruction of the basal ganglia neural circuit including multiple loops by striatal spiny projection neurons in hypoxic–ischaemic encephalopathy-injured immature brains, which raises the possibility of such a cell replacement therapeutic strategy for hypoxic–ischaemic encephalopathy in neonates. [ABSTRACT FROM AUTHOR]