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The flexible aluminum silicate nanofibers separators are prepared by electrospinning method. The results suggest the presence of amorphous phase in aluminum silicate fibers, and the diameters of fibers are mostly in the range of 100~200 nm. The porosity and BET specific surface area of aluminum silicate nanofibers separator with 150 μm thickness are 56.1% and 113.5 m2/g, greater than that of commercial PP separator. When tested in supercapacitors, their ionic conductivity and ion diffusion resistance are 0.041 S/cm and 1.09 Ω, better than that of the commercial PP separator (0.029 S/cm and 2.74 Ω). The specific capacitance of supercapacitors prepared with aluminum silicate nanofibers of 150-μm thickness as separator is up to 150 F/g, which is higher than that of the commercial PP separator (65 F/g). The cyclic and rate performances of supercapacitors prepared with aluminum silicate nanofibers separator are also improved significantly. Compared with commercial PP separator, the aluminum silicate nanofibers separator shows outstanding thermal stability and flame resistance. Hence, the obtained aluminum silicate nanofibers separator has good practical application prospect in supercapacitor.

Background: Genetic compositions play critical roles in pathogenesis of autism spectrum disorders (ASD). Inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants are difficult to address. Here, we identified a recurrent inherited intronic variant in the CHD7 gene among Chinese ASD cohort, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. Here, we use differentiated human embryonic stem cells to investigate whether the ASD-associated CHD7 intronic variant may affect neural development. Methods: 167 ASD probands and their parents performed whole-exome sequencing and a recurrent inherited intronic variant was selected for functional research. We established human embryonic stem cells carrying this intronic variant using CRISPR/Cas methods and differentiated to neural progenitor cells and neurons for analysis. Results: The level of CHD7 mRNA significantly decreased in cell lines carrying homozygous mutants compared to control. Upon differentiation towards the forebrain neuronal lineage, neural cells carrying the CHD7 intronic variant exhibited developmental delay in neuronal differentiation and maturation. Importantly, TBR1, a gene also implicated in ASD, significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations could be rescued by knocking down TBR1, indicating that TBR1 may be responsible for defects in CHD7-related disorders. Finally, the CHD7 intronic variant generates three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function manners in functional assays. Limitations: The probands with CHD7 intronic variant were heterozygous while both cell lines established were homozygous, so the phenotype of the disease could not be completely simulated. Conclusions: Our study provides the crucial evidences for supporting the notion that intronic variant site of CHD7 is a potentially autism susceptible site, shedding new light on identifying functions of intronic variants in autism genetic studies.

The bionic porous zirconia fiber was prepared by the microemulsion electrospinning method. The phase, morphology and pore structure of the fibers were tested by X-ray diffraction, FTIR, RAMAN, SEM, TEM, and BET. The results show that the fiber was t-ZrO2 phase and its average fiber diameter was about 120 nm. There was obvious multi-cavity hollow structure like the polar bear hair in the zirconia fiber. The BET specific surface area and BJH average pore diameter of the fiber was 23.8 m2/g, and 11 nm, respectively. As a result, the bionic porous zirconia fiber had low thermal conductivity of 0.075 W/m k and low infrared emissivity of 0.598 at 3–5 μm. Therefore, the bionic porous zirconia fiber could be used as infrared stealth material.

Degeneration of dopamine (DA) neurons in the midbrain underlies the pathogenesis of Parkinson's disease (PD). Supplement of DA via L-DOPA alleviates motor symptoms but does not prevent the progressive loss of DA neurons. A large body of experimental studies, including those in nonhuman primates, demonstrates that transplantation of fetal mesencephalic tissues improves motor symptoms in animals, which culminated in open-label and double-blinded clinical trials of fetal tissue transplantation for PD1. Unfortunately, the outcomes are mixed, primarily due to the undefined and unstandardized donor tissues1,2. Generation of induced pluripotent stem cells enables standardized and autologous transplantation therapy for PD. However, its efficacy, especially in primates, remains unclear. Here we show that over a 2-year period without immunosuppression, PD monkeys receiving autologous, but not allogenic, transplantation exhibited recovery from motor and depressive signs. These behavioral improvements were accompanied by robust grafts with extensive DA neuron axon growth as well as strong DA activity in positron emission tomography (PET). Mathematical modeling reveals correlations between the number of surviving DA neurons with PET signal intensity and behavior recovery regardless autologous or allogeneic transplant, suggesting a predictive power of PET and motor behaviors for surviving DA neuron number.

Increasing evidence suggests that microRNAs’ (miRNAs) abnormal expression is one of the main factors of chemotherapy resistance in various cancers. However, the role of miRNAs in lung adenocarcinoma (LUAD) resistance to cisplatin is still unclear. In this study, we analyzed a microarray dataset to investigate miRNAs related to cisplatin resistance in LUAD. The expression of miRNAs in LUAD tissues and cell lines was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Special AT-Rich Sequence-Binding Protein 2 (SATB2) in LUAD cell lines was detected using RT-qPCR and Western blot. Cell proliferation was measured by CCK8 and colony formation assays, while cell cycle and apoptosis were measured by flow cytometry. A dual-luciferase reporter assay was performed to confirm that SATB2 is a target gene of microRNA-660 (miR-660). We showed that the expression of miR-660 was not only decreased in LUAD cells and tissues but also further decreased in the cisplatin-resistant A549 cell line. The overexpression of miR-660 increased cisplatin sensitivity in LUAD cells. In addition, we identified SATB2 as a direct target gene of miR-660. We also revealed that miR-660 increased cisplatin sensitivity in LUAD cells via targeting SATB2. In conclusion, miR-660/SATB2 axis is a key regulator of cisplatin resistance in LUAD.

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.

Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.5 mm in length to basal brain regions within 1 month. The transplanted cerebral organoids generated human glutamatergic neurons that acquired electrophysiological maturity in the mouse brain. Importantly, the grafted human cerebral organoids functionally integrated into pre-existing neural circuits by forming bidirectional synaptic connections with the mouse host neurons. Furthermore, compared to control mice, the mice transplanted with cerebral organoids showed an increase in freezing time in response to auditory conditioned stimuli, suggesting the potentiation of the startle fear response. Our study showed that subcortical projections can be established by microtransplantation and may provide crucial insights into the therapeutic potential of human cerebral organoids for neurological diseases.

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.

Oligodendrocyte spheroids (OL-spheroids) containing oligodendrocytes and neurons provide an accessible system to dissect demyelinating diseases and test therapeutic treatment. However, generation of human OL-spheroids is still technically challenging and time-consuming until now. Here, we presented evidence that overexpression of SOX10 and OLIG2 (SO) in human embryonic stem cells (hESCs)-derived ventral forebrain neural progenitors is sufficient to produce forebrain pre-oligodendrocytes (pre-OLs) and mature oligodendrocytes (OLs) within 20-40 days. More importantly, optimizing this procedure by overexpression of SO in ventral forebrain spheroids, we successfully generated OL-spheroids with pre-OLs, mature OLs, and neurons 40 days after OL-induction. We further demonstrated oligodendrocyte-neuron interactions and obvious axon myelination in OL-spheroids. Finally, over 30% cells developed into mature oligodendrocytes with forebrain identity and myelinate axons in mouse brain 3 months after transplantation. This study provides a strategy to generate forebrain OL-spheroids rapidly and efficiently which would facilitate development of new therapeutics for demyelinating disorders.

Deciphering mesoscopic connectivity of the mammalian brain is a pivotal step in neuroscience. Most imaging-based conventional neuroanatomical tracing methods identify area-to-area or sparse single neuronal labeling information. Although recently developed barcode-based connectomics has been able to map a large number of single-neuron projections efficiently, there is a missing link in single-cell connectome and transcriptome. Here, combining single-cell RNA sequencing technology, we established a retro-AAV barcode-based multiplexed tracing method called MEGRE-seq (Multiplexed projEction neuRons retroGrade barcodE), which can resolve projectome and transcriptome of source neurons simultaneously. Using the ventromedial prefrontal cortex (vmPFC) as a proof- of-concept neocortical region, we investigated projection patterns of its excitatory neurons targeting five canonical brain regions, as well as corresponding transcriptional profiles. Dedicated, bifurcated or collateral projection patterns were inferred by digital projectome. In combination with simultaneously recovered transcriptome, we find that certain projection pattern has a preferential layer or neuron subtype bias. Further, we fitted single-neuron two-modal data into a machine learning-based model and delineated gene importance by each projection target. In summary, we anticipate that the new multiplexed digital connectome technique is potential to understand the organizing principle of the neural circuit by linking projectome and transcriptome. Highlights MERGE-seq recovers single-neuron transcriptome and projectome simultaneously MERGE-seq partitions projection pattern into neuronal layer and subtype MERGE-seq bridges projection pattern to differentially expressed genes Machine learning models interpret relationship between digital projectome and gene expression

Although crop residue return increases upland soil emissions of nitrous oxide (N

Degeneration of dopamine (DA) neurons in the midbrain underlies the pathogenesis of Parkinson's disease (PD). Supplement of DA via L-DOPA alleviates motor symptoms but does not prevent the progressive loss of DA neurons. A large body of experimental studies, including those in nonhuman primates, demonstrates that transplantation of fetal mesencephalic tissues improves motor symptoms in animals, which culminated in open-label and double-blinded clinical trials of fetal tissue transplantation for PD

Prenatal exposure to environmental insults can increase the risk of developing neurodevelopmental disorders. Administration of the antiepileptic drug valproic acid (VPA) during pregnancy is tightly associated with a high risk of neurological disorders in offspring. However, the lack of an ideal human model hinders our comprehensive understanding of the impact of VPA exposure on fetal brain development, especially in early gestation. Herein, we present the first report indicating the effects of VPA on brain development at early stages using engineered cortical organoids from human induced pluripotent stem cells (hiPSCs). Cortical organoids were generated on micropillar arrays in a controlled manner, recapitulating the critical features of human brain development during early gestation. With VPA exposure, cortical organoids exhibited neurodevelopmental dysfunction characterized by increased neuron progenitors, inhibited neuronal differentiation and altered forebrain regionalization. Transcriptome analysis showed new markedly altered genes (e.g., KLHL1, LHX9, and MGARP) and a large number of differential expression genes (DEGs), some of which are related to autism. In particular, comparison of transcriptome data via GSEA and correlation analysis revealed the high similarity between VPA-exposed organoids with the postmortem ASD brain and autism patient-derived organoids, implying the high risk of autism with prenatal VPA exposure, even in early gestation. These new findings facilitate a better understanding of the cellular and molecular mechanisms underlying postnatal brain disorders (such as autism) with prenatal VPA exposure. This established cortical organoid-on-a-chip platform is valuable for probing neurodevelopmental disorders under environmental exposure and can be extended to applications in the study of diseases and drug testing. Miniaturized 3D models of the developing human brain provide a unique opportunity to assess the effects of a widely-used drug for neurological disorders on early-stage fetuses. Evidence suggests that valproic acid, a common treatment for epilepsy and bipolar disorder, may undermine healthy brain development in the first trimester of pregnancy. These effects have proven difficult to study, but researchers led by Jianhua Qin of the Dalian Institute of Chemical Physics have demonstrated that human cortical ‘organoids’ model offer valuable insights into this question. These stem cell-derived complex structures mirror key features of the fetal brain, by generating arrays of these organoids, the researchers could measure how valproic acid affects gene expression, cell growth, and maturation. They identified early signatures of abnormal development, supporting further use of this model to study the drug’s impact during pregnancy.

The devitrification behavior of glass depends on its network structure. High silica glass particles were prepared using a sol-gel method. The network structure modification was achieved by heat treatment at 1050 °C for 1 h after coating with 3 wt%∼ 5 wt% B2O3. The relationship between structure change and devitrification behavior of high silica glass particles with B2O3 modification was investigated by Raman, IR, 11B MAS NMR,29Si MAS NMR, and X-ray powder diffraction. The results demonstrated that the network structure units of high silica glass were comprised of BO (bridging oxygen), NBO (non-bridging oxygen, Q2 and Q3), [BO4], and [BO3]. It was found that Q2, Q3 and [BO3] could be converted into Q4 and [BO4] under the effect of B2O3modification. As the network structure of high silica glass was repaired by B2O3 modification, the devitrification behavior of high silica glass was prevented.

Summary Long-term potentiation and depression, inferred from analysis on brain slices, are considered the cellular processes underlying learning and memory formation. They have not so far been demonstrated in human stem cell-derived neurons. By expressing channelrhodopsin in hESCs-derived glutamate neurons and co-culturing them with GABA neurons, we found that blue light stimulation increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) and decreased the ratio of paired pulse facilitation (PPF) in non-ChR2-expressing GABA neurons, indicating a facilitating action at the presynaptic terminals. When paired with postsynaptic depolarization, the repetitive stimulation significantly increased the amplitude of light-evoked EPSCs that persisted during the period, indicating long-term potentiation (LTP). In contrast, low-frequency light stimulation induced long-term depression (LTD). These effects were blocked by N-methyl-D-aspartic acid (NMDA) receptor antagonists, suggesting NMDA receptor-mediated synaptic plasticity in human neural networks. Furthermore, induced pluripotent stem cell (iPSC)-derived neurons of patient with Down syndrome showed absence of LTP or LTD. Thus, our platform offers a versatile model for assessing human neural plasticity under physiological and pathological conditions., Graphical Abstract, Highlights • Repetitive stimulation induces LTP in hPSC-derived neural networks • Low-frequency light stimulation induces LTD in hPSCs-derived neural networks • The LTP/LTD in human neural networks are NMDAR dependent • Down syndrome neural networks exhibit defective LTP/LTD, Neuroscience; Cellular Neuroscience; Techniques in Neuroscience

Although cell transplantation can rescue motor defects in Parkinson's disease (PD) models, whether and how grafts functionally repair damaged neural circuitry in the adult brain is not known. We transplanted hESC-derived midbrain dopamine (mDA) or cortical glutamate neurons into the substantia nigra or striatum of a mouse PD model and found extensive graft integration with host circuitry. Axonal pathfinding toward the dorsal striatum was determined by the identity of the grafted neurons, and anatomical presynaptic inputs were largely dependent on graft location, whereas inhibitory versus excitatory input was dictated by the identity of grafted neurons. hESC-derived mDA neurons display A9 characteristics and restore functionality of the reconstructed nigrostriatal circuit to mediate improvements in motor function. These results indicate similarity in cell-type-specific pre- and post-synaptic integration between transplant-reconstructed circuit and endogenous neural networks, highlighting the capacity of hPSC-derived neuron subtypes for specific circuit repair and functional restoration in the adult brain.

In the context of Internet of Things (IoT) environments, obtaining the target's location information by analyzing a large number of video data captured by widely distributed camera nodes shows a good development prospect. As far as video analytics is concerned, for the purpose of reducing high processing costs and transmission time of video data, it is an effective solution to offload computing from the cloud to edge devices. In this paper, we design a four-layer video analytics architecture with the concept of edge computing and adopt the lightweight virtualization provided by the container technology to modularize the video analytics process. Based on the proposed architecture, an video analytics-based intelligent indoor positioning system is implemented. The proposed system can provide centimeter-level positioning accuracy and, at the same time, has a lower response delay than traditional cloud computing model. The experimental results show that, high-precision location information could be obtained with the help of billions of camera nodes, while for the large-scale video analytics, the usage of edge computing has great potentials.

Real-Time video analytics, whose applications range from safety, public security to smart cities, is a typical use case of Internet of Things (IoT). However, uploading the video stream to the cloud for analytics cannot meet the requirements of low latency and efficient bandwidth usage. Edge video analytics, which uploads the stream at the edge node, is a key to solve the abovementioned problem. This paper proposes an intelligent video analytics system on edge computing platform. Combining the edge computing and video analytics, this system can analyze the video stream by face recognition, indoor positioning, and semantic analytics in real time and archive the videos automatically. Specifically, applied in conference room, the video analytics system analyzes the conference room scenario and files the conference videos, which reduces the cost of manual recording and promotes the data sharing. The implementation results prove that our system can operate smoothly on the edge computing platform to provide real-time and efficient video analytics services.