Developmental Temporal Patterns and Molecular Network Features in the Transcriptome of Rat Spinal Cord

The molecular network features of spinal cord development that are integral to tissue engineering remain poorly understood in placental mammals,especially in terms of their relationships with vital biological processes such as regeneration.Here,using a large-scale temporal transcriptomic analysis of rat spinal cord from the embryonic stage to adulthood,we show that fluctuating RNA expression levels reflect highly active transcriptional regulation,which may initiate spinal cord patterning.We also demonstrate that microRNAs(miRNAs)and transcriptional factors exhibit a mosaic profile based on their expression patterns,while differential alternative splicing events reveal that alternative splicing may be a driving force for the development of the node of Ranvier.Our study also supports the existence of a negative correlation between innate immunity and intrinsic growth capacity.Epigenetic modifications appear to perform their respective regulatory functions at different stages of development,while guanine nucleotidebinding protein(G protein)-coupled receptors(including olfactory receptors(ORs))may perform pleiotropic roles in axonal growth.This study provides a valuable resource for investigating spinal cord development and complements the increasing number of single-cell datasets.These findings also provide a genetic basis for the development of novel tissue engineering strategies.

Biodegradable Materials and the Tissue Engineering of Nerves

1.Introduction Over the past 100 years,the development of biodegradable materials has helped to advance innovation in tissue-engineering technology by making such materials more feasible,resulting in technological breakthroughs and new clinical applications[1,2].Classical tissue-engineering theory involves three elements:biological materials,seed cells,and factors.Research progress suggests that biodegradable materials with low immunogenicity,high biodegradability,good biocompatibility,and favorable regeneration microenvironments are of great significance[3].

Knockdown of polypyrimidine tract binding protein facilitates motor function recovery after spinal cord injury

After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.

Current Challenges for the Practical Application of Electroencephalography-Based Brain-Computer Interfaces

It has been almost 50 years since the term“brain–computer interface”(BCI)was first proposed by Jacques J.Vidal in 1973[1].Unlike traditional electronic interfaces that transmit nonliving information between devices,BCIs set up a communication bridge between a living brain and nonliving devices.Technically speaking,a BCI is a system that measures brain activity and converts it into the artificial outputs that replace,restore,enhance,supplement,or improve the natural central nervous system outputs[2].At present,electroencephalography(EEG)is the most commonly used brain signal for BCIs.

Biophysical Regulation of Cell Behavior-Cross Talk between Substrate Stiffness and Nanotopography

细胞外基质(ECM)的刚性和纳米拓扑结构影响生物体发育及生理和病理进程。因此,这些生物物理特征被用于调节细胞黏附、铺展至增殖、分化的各种细胞行为。描述细胞行为的生物物理调节对合理设计新型生物材料、植入物和医疗装置十分关键。已有学者就基质刚性和纳米拓扑结构特征对细胞行为的影响分别进行了综述,然而,刚性和纳米拓扑结构与细胞行为的交织影响尚未有人总结。此次,我们首次综述了基质刚性和纳米拓扑结构对细胞行为的影响,然后聚焦于生物物理信号从整合素到细胞核的细胞内传递,并试图将细胞行为的细胞外调节与基质的生物物理学特征联系在一起。最后,我们讨论了在剖析细胞行为的生物物理调节和将基质的刚性和纳米拓扑结构生物力学特性转化到组织工程和再生医学时存在的挑战。

Genetic dissection of glutathione S-transferase omega-1:identification of novel downstream targets and Alzheimer's disease pathways

Alzheimer's disease(AD)is affected by genetic factors.Polymorphisms in the glutathione S-transfe rase omega-1(Gsto1)gene have been shown by genetic correlation analyses performed in different ethnic populations to be genetic risk factors for AD.Gene expression profile data from BXD recombinant inbred mice were used in combination with genetic and bioinformatic analyses to chara cterize the mechanisms underlying regulation of Gstol variation regulation and to identify network membe rs that may contribute to AD risk or progression.Allele-specific assays confirmed that variation in Gstol expression is controlled by cis-expression quantitative trait loci.We found that Gstol mRNA levels were related to several central nervous system traits,such as glial acidic fibrillary protein levels in the caudate putamen,co rtical gray matter volume,and hippocampus mossy fiber pathway volume.We identified 2168 genes whose expression was highly correlated with that of Gsto1.Some genes were enriched for the most common neurodegenerative diseases.Some Gsto1-related genes identified in this study had previously been identified as susceptibility genes for AD,such as APP,Grin2 b,Ide,and Psenen.To evaluate the relationships between Gstol and candidate network members,we transfected astrocytes with Gstol siRNA and assessed the effect on putative downstream effecto rs.We confirmed that knockdown of Gstol had a significant influence on Pa2g4 expression,suggesting that Pa2g4 may be a downstream effector of Gstol,and that both genes intera ct with other genes in a network during AD pathogenesis.

Sex-Dependent Glial Signaling in Pathological Pain:Distinct Roles of Spinal Microglia and Astrocytes

Increasing evidence suggests that spinal micro- glia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain follow- ing intrathecal injection in male and female mice. These modulators were the microglial inhibitors minocycline and ZVEID （a caspase-6 inhibitor） and the astroglial inhibitors L-α-aminoadipate （L-AA, an astroglial toxin） and car- benoxolone （a connexin 43 inhibitor）, as well as U0126 （an ERK kinase inhibitor） and D-JNKI-1 （a c-Jun N-terminal kinase inhibitor）. We found that spinal administration of minocycline or ZVEID, or Caspase6 deletion, reduced formalin-induced inflammatory and nerve injury-induced neuropathic pain primarily in male mice. In contrast, intrathecal L-AA reduced neuropathic pain but not inflam- matory pain in both sexes. Intrathecal U0126 and D-JNKI- 1 reduced neuropathic pain in both sexes. Nerve injury caused spinal upregulation of the astroglial markers GFAP and Connexin 43 in both sexes. Collectively, our data confirmed male-dominant microglial signaling but also revealed sex-independent astroglial signaling in the spinal cord in inflammatory and neuropathic pain.

miR-20a Promotes the Axon Regeneration of DRG Neurons by Targeting Nr4a3

Dear Editor,The peripheral nervous system(PNS)regenerates more easily after injury than the central nervous system(CNS)[1].Sensory neurons in the L4–L6 dorsal root ganglia(DRGs)extend axons to form the sciatic nerve along with motor axons.The DRG neuron is one of the exceptional mature neurons whose axons can regenerate after injury.

Dopaminergic signaling is critical for myelin genesis and pathogenesis

Myelin sheets surrounding axons are critical for electrical signal transmission in the central nervous system(CNS).Diseases with myelin defects such as multiple sclerosis(MS)are devastating neurological conditions for which no effective treatment is available.Dysfunction of the dopaminergic system has been observed in multiple neurological disorders.Its role in myelin pathogenesis,however,is unclear.

Tissue Engineering Is Under Way

组织工程包含生物材料、干细胞、组织工程的构建技术和转化应用。世界同行们做出了很大的努力和贡献,推进组织工程转化与应用的巨大突破。近年来,我国学者在组织工程这一领域开展了卓有成效的工作,如治疗烧伤的人工皮肤(Xiaobing Fu et al.:In vitro constitutionand in vivo implantation of engineered skin constructs with sweat glands,Biomaterials)。

Recent Progress in Biomaterials-Tissue Engineering

In recent years,biomaterials-tis-sue engineering research and techno-logical innovation have developed rapidly,especially in the areas of biomimetic tissue engineering,microenvironment regeneration,nanotechnology,and molecular drug delivery.For this issue,we have invited national and international experts to submit their articles on this topic.

Trafficking pathway between plasma membrane and mitochondria via clathrin-mediated endocytosis

Endocytosis is a basic cellular process that describes a form of active transport across the plasma membrane into the cell.The endocytic pathway consists of distinct membrane compartments;internalized molecules are delivered to early endosomes,and some of them are recycled back to the surface,whereas other molecules are sent to late endosomes and lysosomes for degradation.However,little is known about how mitochondria are involved in the endocytic pathway.Here,we report that FM dyes, membrane-impermeant fluorescent lipid probes,can traffic to mitochondria directly from the plasma membrane by clathrinmediated endocytosis.FM dye entry into mitochondria uses microtubule-dependent active transport,but the mechanism is different from the classical endocytic pathway.Hence,this study reveals a previously unrealized lipid trafficking pathway from the plasma membrane to mitochondria.

SOCS3 Attenuates GM-CSF/IFN-γ-Mediated Inflammation During Spontaneous Spinal Cord Regeneration

SOCS3,a feedback inhibitor of the JAK/STAT signal pathway,negatively regulates axonal regrowth and inflammation in the central nervous system(CNS).Here,we demonstrated a distinct role of SOCS3 in the injured spinal cord of the gecko following tail amputation.Severing the gecko spinal cord did not evoke an inflammatory cascade except for an injury-stimulated elevation of the granulocyte/macrophage colony-stimulating factor(GM-CSF) and interferon gamma(IFN-γ) cytokines.Simultaneously,the expression of SOCS3 was upregulated in microglia,and unexpectedly not in neurons.Enforced expression of SOCS3 was sufficient to suppress the GMCSF/IFN-γ-driven inflammatory responses through its KIR domain by attenuating the activities of JAK1 and JAK2.SOCS3 was also linked to GM-CSF/IFN-y-induced crosstolerance.Transfection of adenovirus overexpressing SOCS3 in the injured cord resulted in a significant decrease of inflammatory cytokines.These results reveal a distinct role of SOCS3 in the regenerating spinal cord,and provide new hints for CNS repair in mammals.