3D Fast Sodium Transport Network of MoS2 Endowed by Coupling of Sulfur Vacancies and Sn Doping for Outstanding Sodium Storage.

A sulfur vacancy-rich, Sn-doped as well as carbon-coated MoS2 composite (Vs-SMS@C) is rationally synthesized via a simple hydrothermal method combined with ball-milling reduction, which enhances the sodium storage performance. Benefiting from the 3D fast Na+ transport network composed of the defective carbon coating, Mo─S─C bonds, enlarged interlayer spacing, S-vacancies, and lattice distortion in the composite, the Na+ storage kinetics is significantly accelerated. As expected, Vs-SMS@C releases an ultrahigh reversible capacity of 1089 mAh g-1 at 0.1 A g-1, higher than the theoretical capacity. It delivers a satisfactory capacity of 463 mAh g-1 at a high current density of 10 A g-1, which is the state-of-the-art rate capability compared to other MoS2 based sodium ion battery anodes to the knowledge. Moreover, a super long-term cycle stability is achieved by Vs-SMS@C, which keeps 91.6% of the initial capacity after 3000 cycles under the current density of 5 A g-1 in the voltage of 0.3-3.0 V. The sodium storage mechanism of Vs-SMS@C is investigated by employing electrochemical methods and ex situ techniques. The synergistic effect between S-vacancies and doped-Sn is evidenced by DFT calculations. This work opens new ideas for seeking excellent metal sulfide anodes.

Single-cell analysis reveals dynamic changes of neural cells in developing human spinal cord.

During central nervous system development, neurogenesis and gliogenesis occur in an orderly manner to create precise neural circuitry. However, no systematic dataset of neural lineage development that covers both neurogenesis and gliogenesis for the human spinal cord is available. We here perform single-cell RNA sequencing of human spinal cord cells during embryonic and fetal stages that cover neuron generation as well as astrocytes and oligodendrocyte differentiation. We also map the timeline of sensory neurogenesis and gliogenesis in the spinal cord. We further identify a group of EGFR-expressing transitional glial cells with radial morphology at the onset of gliogenesis, which progressively acquires differentiated glial cell characteristics. These EGFR-expressing transitional glial cells exhibited a unique position-specific feature during spinal cord development. Cell crosstalk analysis using CellPhoneDB indicated that EGFR glial cells can persistently interact with other neural cells during development through Delta-Notch and EGFR signaling. Together, our results reveal stage-specific profiles and dynamics of neural cells during human spinal cord development.

Purinergic receptors mediate endothelial dysfunction and participate in atherosclerosis.

Atherosclerosis is the main pathological basis of cardiovascular disease and involves damage to vascular endothelial cells (ECs) that results in endothelial dysfunction (ED). The vascular endothelium is the key to maintaining blood vessel health and homeostasis. ED is a complex pathological process involving inflammation, shear stress, vascular tone, adhesion of leukocytes to ECs, and platelet aggregation. The activation of P2X4, P2X7, and P2Y2 receptors regulates vascular tone in response to shear stress, while activation of the A2A, P2X4, P2X7, P2Y1, P2Y2, P2Y6, and P2Y12 receptors promotes the secretion of inflammatory cytokines. Finally, P2X1, P2Y1, and P2Y12 receptor activation regulates platelet activity. These purinergic receptors mediate ED and participate in atherosclerosis. In short, P2X4, P2X7, P2Y1, and P2Y12 receptors are potential therapeutic targets for atherosclerosis.

Epidermal growth factor receptor-extracellular-regulated kinase blockade upregulates TRIM32 signaling cascade and promotes neurogenesis after spinal cord injury.

Nerve regeneration is blocked after spinal cord injury (SCI) by a complex myelin-associated inhibitory (MAI) microenvironment in the lesion site; however, the underlying mechanisms are not fully understood. During the process of neural stem cell (NSC) differentiation, pathway inhibitors were added to quantitatively assess the effects on neuronal differentiation. Immunoprecipitation and lentivirus-induced overexpression were used to examine effects in vitro. In vivo, animal experiments and lineage tracing methods were used to identify nascent neurogenesis after SCI. In vitro results indicated that myelin inhibited neuronal differentiation by activating the epidermal growth factor receptor (EGFR)-extracellular-regulated kinase (ERK) signaling cascade. Subsequently, we found that tripartite motif (TRIM) 32, a neuronal fate-determining factor, was inhibited. Moreover, inhibition of EGFR-ERK promoted TRIM32 expression and enhanced neuronal differentiation in the presence of myelin. We further demonstrated that ERK interacts with TRIM32 to regulate neuronal differentiation. In vivo results indicated that EGFR-ERK blockade increased TRIM32 expression and promoted neurogenesis in the injured area, thus enhancing functional recovery after SCI. Our results showed that EGFR-ERK blockade antagonized MAI of neuronal differentiation of NSCs through regulation of TRIM32 by ERK. Collectively, these findings may provide potential new targets for SCI repair.

A Hidden Chaotic System with Multiple Attractors.

This paper reports a hidden chaotic system without equilibrium point. The proposed system is studied by the software of MATLAB R2018 through several numerical methods, including Largest Lyapunov exponent, bifurcation diagram, phase diagram, Poincaré map, time-domain waveform, attractive basin and Spectral Entropy. Seven types of attractors are found through altering the system parameters and some interesting characteristics such as coexistence attractors, controllability of chaotic attractor, hyperchaotic behavior and transition behavior are observed. Particularly, the Spectral Entropy algorithm is used to analyze the system and based on the normalized values of Spectral Entropy, the state of the studied system can be identified. Furthermore, the system has been implemented physically to verify the realizability.

NLR-A Simple Indicator of Inflammation for the Diagnosis of Left Ventricular Hypertrophy in Patients with Hypertension.

We aimed to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), brain natriuretic peptide (BNP), and left ventricular hypertrophy (LVH) in hypertension. METHODS: This study included 386 patients with hypertension. Mann-Whitney U test and multivariate binary logistic regression analysis were used to investigate the relationship between NLR, CRP, BNP, and LVH in patients with hypertension, as well as compare the levels of NLR, CRP, and BNP in the four configurations. Receiver operator characteristic (ROC) curve was used to compare the diagnostic efficacy of NLR, CRP, and BNP on LVH. RESULTS: The NLR and CRP and BNP levels of the LVH group were significantly higher than those of the non-LVH group. In the multivariate logistic regression analysis, NLR as well as age, BMI, and SBP were associated with LVH. In addition, in patients with eccentric and concentric hypertrophy, the NLR and CRP and BNP levels were higher than those of the normal left ventricular geometry and concentric remodeling groups. The cutoff values of NLR, CRP, and BNP obtained by ROC curve were 2.185, 2.205, and 283.45, respectively, for the prediction of LVH. CONCLUSIONS: NLR is independently associated with LVH in patients with hypertension, and this is consistent with the diagnostic efficacy of CRP and BNP, which may be a simple and convenient indicator for judging LVH.

Anthropometric Indices Predict the Development of Hypertension in Normotensive and Pre-Hypertensive Middle-Aged Women in Tianjin, China: A Prospective Cohort Study.

BACKGROUND The aims of this study were to investigate the relationship between optimal anthropometric indices and their cut-off values and the incidence of hypertension in a cohort of middle-aged women in China. MATERIAL AND METHODS A cohort of 812 women, aged between 40-70 years were recruited between May 2011 and June 2013. An ideal baseline blood pressure was defined as <120/80 mmHg; pre-hypertension was 120-139/80-89 mmHg; hypertension was ≥140/≥90 mmHg. Anthropometric measurements included waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), and waist-height ratio (WHtR). The cohort was divided into an ideal blood pressure group (Group 1) and a pre-hypertensive group (Group 2). Two-year follow-up blood pressure measurements were performed. Receiver-operating characteristic (ROC) curve analysis determined the optimal anthropometric indices and cut-off values for developing hypertension. RESULTS At two-year follow-up, hypertension developed in 9.0% (n=31) in Group 1 and 32.3% (n=121) in Group 2. Logistic regression analysis showed that in both groups, women in the highest quartile for WC, BMI, WHR, and WHtR had a significantly increased risk of developing hypertension compared with the lowest quartile (P<0.05). ROC curve area under the curve (AUC) for these anthropometric indices were greater in Group 1, and for WC in Groups 1 and 2, with the optimal cut-off values greater in Group 1. CONCLUSIONS In a cohort of middle-aged women in China, anthropometric indices of obesity were predictive of the development of hypertension during a two-year follow-up period.

Association of microalbuminuria with diabetes is stronger in people with prehypertension compared to those with ideal blood pressure.

AIM: Microalbuminuria (MA) has been demonstrated as a biomarker for microvascular dysfunction. This study is aimed to evaluate the association of glycaemic status with MA in prehypertensive and ideal BP subjects and to evaluate the interaction between glycaemic and blood pressure status as risk factors for MA prevalence. METHODS: 1059 subjects aged 40-70 with non-hypertension who were recruited from six districts of Tianjin were divided into a prehypertensive group (622 cases) and an ideal blood BP group (437 cases). Subjects of the prehypertensive group and the ideal BP group were divided respectively into three subgroups: normoglycaemia subgroup, prediabetes subgroup and diabetes subgroup. The prevalence of MA in the above three subgroups of subjects with prehypertension and ideal BP were assessed. We performed a statistical analysis for interaction test between glycaemia and BP status on microalbuminuria in the overall study sample by a multivariate logistic regression model. The association of glycaemic status (defined as normoglycaemia, prediabetes, and diabetes) with MA was evaluated separately in prehypertensive and ideal BP subjects. RESULTS: Results showed that the prevalence of MA in both prehypertensive and ideal BP groups rose with the increasing of classification of glycaemic level of subgroups (32.6%, 18.3%, 14.8% vs. 23.1%, 16.2%, 13.4%), the differences in prehypertensive group were statistically significant (Pearson χ2 = 15.24, P < 0.001). The ORs (95% CI) of MA were 1.25 (0.86-1.83) for prediabetes and 2.56 (1.62-4.03) for diabetes in the fully adjusted model. There was no interaction between prediabetes and BP status regarding MA (P = 0.237) but we found a significant interaction between diabetes and BP status (P < 0.001). In the prehypertensive group, multivariate logistic regression models showed that the diabetes subgroup had a significant association with MA, and the adjusted odds ratio of the diabetes subgroup to the normoglycaemia subgroup was 2.68 (95%CI 1.54-4.67) (P < 0.001). However, there was no significant association of glycaemic status with MA in the ideal BP group. Stratified analysis by a multivariate logistic regression model in the whole study population showed that people with both prehypertension and diabetes had the highest risk of MA (adjusted OR = 2.50, 95%CI 1.16-5.36; P = 0.019), compared with those with ideal BP and normoglycaemia (reference group). CONCLUSIONS: Our findings suggest that there was a statistically significant association between diabetes and microalbuminuria only in prehypertensive subjects. In addition, our study highlights the interaction between prehypertension and diabetes as a risk factor for MA.

Determinants of the Usage of Splice-Associated cis-Motifs Predict the Distribution of Human Pathogenic SNPs.

Where in genes do pathogenic mutations tend to occur and does this provide clues as to the possible underlying mechanisms by which single nucleotide polymorphisms (SNPs) cause disease? As splice-disrupting mutations tend to occur predominantly at exon ends, known also to be hot spots of cis-exonic splice control elements, we examine the relationship between the relative density of such exonic cis-motifs and pathogenic SNPs. In particular, we focus on the intragene distribution of exonic splicing enhancers (ESE) and the covariance between them and disease-associated SNPs. In addition to showing that disease-causing genes tend to be genes with a high intron density, consistent with missplicing, five factors established as trends in ESE usage, are considered: relative position in exons, relative position in genes, flanking intron size, splice sites usage, and phase. We find that more than 76% of pathogenic SNPs are within 3-69 bp of exon ends where ESEs generally reside, this being 13% more than expected. Overall from enrichment of pathogenic SNPs at exon ends, we estimate that approximately 20-45% of SNPs affect splicing. Importantly, we find that within genes pathogenic SNPs tend to occur in splicing-relevant regions with low ESE density: they are found to occur preferentially in the terminal half of genes, in exons flanked by short introns and at the ends of phase (0,0) exons with 3' non-"AGgt" splice site. We suggest the concept of the "fragile" exon, one home to pathogenic SNPs owing to its vulnerability to splice disruption owing to low ESE density.

Why Selection Might Be Stronger When Populations Are Small: Intron Size and Density Predict within and between-Species Usage of Exonic Splice Associated cis-Motifs.

The nearly neutral theory predicts that small effective population size provides the conditions for weakened selection. This is postulated to explain why our genome is more "bloated" than that of, for example, yeast, ours having large introns and large intergene spacer. If a bloated genome is also an error prone genome might it, however, be the case that selection for error-mitigating properties is stronger in our genome? We examine this notion using splicing as an exemplar, not least because large introns can predispose to noisy splicing. We thus ask whether, owing to genomic decay, selection for splice error-control mechanisms is stronger, not weaker, in species with large introns and small populations. In humans much information defining splice sites is in cis-exonic motifs, most notably exonic splice enhancers (ESEs). These act as splice-error control elements. Here then we ask whether within and between-species intron size is a predictor of the commonality of exonic cis-splicing motifs. We show that, as predicted, the proportion of synonymous sites that are ESE-associated and under selection in humans is weakly positively correlated with the size of the flanking intron. In a phylogenetically controlled framework, we observe, also as expected, that mean intron size is both predicted by Ne.µ and is a good predictor of cis-motif usage across species, this usage coevolving with splice site definition. Unexpectedly, however, across taxa intron density is a better predictor of cis-motif usage than intron size. We propose that selection for splice-related motifs is driven by a need to avoid decoy splice sites that will be more common in genes with many and large introns. That intron number and density predict ESE usage within human genes is consistent with this, as is the finding of intragenic heterogeneity in ESE density. As intronic content and splice site usage across species is also well predicted by Ne.µ, the result also suggests an unusual circumstance in which selection (for cis-modifiers of splicing) might be stronger when population sizes are smaller, as here splicing is noisier, resulting in a greater need to control error-prone splicing.

Association of self-reported sleep duration and hypertension: Results of a Chinese prospective cohort study.

OBJECTIVES: To examine the association of self-reported sleep duration and hypertension using the data from Tianjin China. METHODS: Participants aged 40-70 years without hypertension were recruited with a stratified cluster sampling method across six districts of Tianjin, China. Information regarding their sociodemographic and lifestyle-related characteristics was gathered by questionnaires. After 2 years of follow-up, the second physical examination was taken on the same crowd. RESULTS: During the 2-year period, 874 subjects (221 men, 653 women) were successfully contacted. Multivariate logistic regression was used to analyze the relationship between the frequency of incident hypertension after the 2-year follow-up and sleep duration according to age groups. Among the younger age group (40-<55 years), a short sleep duration (≤ear h) was associated with a significantly higher risk of hypertension compared with sleeping for 7-8 h in unadjusted analyses (OR: 3.15 [95% CI: 1.04-9.54]). In a model after adjustment for the impact factors, a significant difference was also found in the frequency of incident hypertension. CONCLUSIONS: In our study, a short sleep duration (≤sho h) is a significant risk factor for hypertension in younger subjects, with no association among older subjects.

Clinical efficacy comparison of HA280 and DNA280 immunoadsorption column in treating systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to compare the efficacy of HA280 and DNA280 immunoadsorption (IA) column in treating systemic lupus erythematosus (SLE), and provide the basis for seeking cost-effective solution for SLE. METHODS: Fifty-seven severe SLE patients receiving IA treatment from January 2007 to December 2013 were selected. They were divided into HA280 group (31 cases) and DNA280 group (26 cases), which used HA280 and DNA280 IA column, respectively. The efficacy, adverse reactions, and hospitalization cost of the two groups were compared. RESULTS: Both two groups could effectively reduce the SLE-associated antibodies, immunoglobulins, complement levels, serum creatinine, blood urea nitrogen, and 24-h urine protein levels (P < 0.05). The efficiency and incidence of adverse reactions of two groups were similar (P > 0.05), while the hospitalization cost of HA280 group was significantly less than that of DNA280 group (P < 0.05). CONCLUSIONS: Application of HA280 IA column in IA treatment is relatively the most cost-effective adjuvant therapy to severe SLE.

Does elevated serum uric acid level predict the hypertension incidence? A Chinese prospective cohort study.

BACKGROUND AND AIMS: Hyperuricemia is an independent risk factor for hypertension. This study aims to investigate whether SUA predicts 2-year incidence of hypertension in population with pre-hypertension and ideal blood pressure in Tianjin, China. METHODS AND RESULTS: In this population-based prospective study, we analyzed 608 subjects (455 women) aged 40-70 with non-hypertension (SBP < 140 mmHg and DBP < 90 mmHg) who were recruited with stratified cluster sampling method across six districts of Tianjin in 2011-2012. Participants were divided into pre-hypertensive group (group P) and ideal blood pressure group (group I) according to their first physical examination. After 2 years follow-up, the second physical examination was taken on the same crowd. The 2-year hypertension incidence rate in group P (35.6%) was higher than that of group I (8.3%) (p < 0.05). In group P, the hypertension incidence rate increased with the increase of SUA quartiles. Multivariate logistic regression analysis showed that the odd ratio (OR) between the highest SUA quartile group and the lowest SUA quartile group in group P were 2.02 (1.04-3.92), 3.34 (1.10-10.04) in men and 2.43 (1.08-5.45) in women (p < 0.05). However, there is no significant correlation between SUA and the risk for hypertension incidence in group I. Multiple linear regression showed that the SBP increased 0.017 mmHg with the increasing of 1 µmol/L deviation of SUA in group P. CONCLUSIONS: SUA levels predict SBP elevation and hypertension incidence in population with pre-hypertension, however, do not predict the DBP elevation in pre-hypertensive population as well as change of BP in ideal blood pressure population.

A method suitable for DNA extraction from humus-rich soil.

A rapid and convenient method for extracting DNA from soil is presented. Soil DNA is extracted by direct cell lysis in the presence of EDTA, SDS, phenol, chloroform and isoamyl alcohol (3-methyl-1-butanol) followed by precipitation with 2-propanol. The extracted DNA is purified by modified DNA purification kit and DNA gel extraction kit. With this method, DNA extracted from humus-rich dark brown forest soil was free from humic substances and, therefore, could be used for efficient PCR amplification and restriction digestion. In contrast, DNA sample extracted with the traditional CTAB-based method had lower yield and purity, and no DNA could be extracted from the same soil sample with a commonly-used commercial soil DNA isolation kit. In addition, this method is time-saving and convenient, providing an efficient choice especially for DNA extraction from humus-rich soils.

Combinational effect of mutational bias and translational selection for translation efficiency in tomato (Solanum lycopersicum) cv. Micro-Tom.

We conducted a comprehensive analysis of codon usage bias (CUB) based on the available non-redundant full-length cDNA (nrFLcDNA) and expressed sequence tags (ESTs) data of cultivar Micro-Tom and evaluated the associations of observed CUB and measurements of transcriptional and translational effectiveness. The analysis presented in our study suggests a correlation, which is negative but highly correlated between Axis 1 and GC3s (r=-0.827, P<0.01), indicating that mutational bias has a significant and dominant repressive role to the choices of GC3. We also observed a strong positive correlation between codon adaptation index (CAI) and translational adaptation index (tAIg) (0.407, P<0.01), which demonstrates the facilitation of efficient translation by the optimal codon usage patterns of the highly expressed genes. We believe that the complete set of optimal codon usage patterns detected in this study will serve as a model to enhance the transgenesis in the studied cultivar of Solanum lycopersicum.

Polycarbonyl polymer with zincophilic sites as protective coating for highly reversible zinc metal anodes.

The Zn anode of aqueous zinc ion batteries (AZIBs) have suffered from a series of rampant side reactions such as dendrite growth and corrosion, which seriously affect the reversibility and stability of Zn anodes. Herein, a polycarbonyl polymer poly(1,4,5,8-naphthalene tetracarboxylic anhydride anthraquinone) imine (PNAQI) as the protective coating is synthesized through a simple solvothermal method with the raw materials of the equimolar 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTCDA) and 2, 6-aminoanthraquinone (2,6-DAAQ). A series of characterizations such as contact angle measurement and ex-situ XRD analysis confirm that it can effectively prevent some side reactions. Moreover, CO on PNAQI can regulate the uniform distribution of zinc, thereby preventing the occurrence of zinc dendrites. Finally, the PNAQI@Zn//PNAQI@Zn symmetrical cell demonstrates a long cycle life exceeding 1000 h at current density of 1.0 mA cm-2 and a capacity of 1.0 mAh cm-2. The result significantly outperforms the cycling performance of the cell with bare zinc anode. Especially, the full battery of PNAQI@Zn//NH4V4O10 demonstrates an excellent capacity retention and prolonged cycle life (96.9 mAh/g after 1000 cycles at 1.0 A/g) compared to Zn//NH4V4O10. This work provides an effective, simple and low-cost solution for developing high-performance AZIBs.

Effect of moxibustion on the SIRT1/FOXO3a signaling pathway in ApoE-/- mice with atherosclerosis. / 艾灸对ApoE-/-åŠ¨è„‰ç²¥æ ·ç¡¬åŒ–å°é¼ SIRT1/FOXO3a信号通路的影响.

OBJECTIVES: To observe the effects of moxibustion on blood lipid metabolism, pathological morphology of thoracic aorta, and the expression of silent information regulator 1 (SIRT1) and forkhead box transcription factor O3a (FOXO3a) in ApoE-/- atherosclerosis (AS) mice, so as to explore the potential mechanism of moxibustion in preventing and treating AS. METHODS: Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, simvastatin group, and moxibustion group, with 10 mice in each group. From the first day of modeling, mice in the moxibustion group received mild moxibustion treatment at "Shenque"(CV8), "Yinlingquan"(SP9), bilateral "Neiguan"(PC6) and "Xuehai"(SP10) for 30 min per time；the mice in the simvastatin group were given simvastatin orally (2.5 mg·kg-1·d-1), with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. The body weight and general condition of the mice were observed and recorded during the intervention period. After the intervention, the contents of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemistry analyzer. Hematoxylin eosin (HE) staining was used to observe the pathological morphology of the thoracic aorta. ELISA was used to measure the contents of serum oxidized low-density lipoprotein (ox-LDL) and superoxide dismutase (SOD) activity. Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta. RESULTS: Compared with the control group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of the model group mice were significantly increased(P<0.05, P<0.01), while the HDL-C contents, SOD activity, and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05, P<0.01). HE staining showed thickening of the aortic intima, endothelial cell degeneration, swelling, and shedding. Compared with the model group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01), while the serum SOD activity, expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01). The HDL-C contents were significantly increased in the simvastatin group(P<0.05). The thoracic aortic structure was more intact in both groups, with a more regular lumen and orderly arrangement of the elastic membrane in the media, and a slight amount of endothelial cell degeneration and swelling in the intima. There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups. CONCLUSIONS: Moxibustion can reduce the body weight of AS model mice, regulate lipid levels, repair vascular intima, and alleviate endothelial damage. Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.

Constructing Linear-Oriented Pre-Vascularized Human Spinal Cord Tissues for Spinal Cord Injury Repair.

Repairing spinal cord injury (SCI) is a global medical challenge lacking effective clinical treatment. Developing human-engineered spinal cord tissues that can replenish lost cells and restore a regenerative microenvironment offers promising potential for SCI therapy. However, creating vascularized human spinal cord-like tissues (VSCT) that mimic the diverse cell types and longitudinal parallel structural features of spinal cord tissues remains a significant hurdle. In the present study, VSCTs are engineered using embryonic human spinal cord-derived neural and endothelial cells on linear-ordered collagen scaffolds (LOCS). Studies have shown that astrocytes and endothelial cells align along the scaffolds in VSCT, supporting axon extension from various human neurons myelinated by oligodendrocytes. After transplantation into SCI rats, VSCT survives at the injury sites and promotes endogenous neural regeneration and vascularization, ultimately reducing scarring and enhancing behavioral functional recovery. It suggests that pre-vascularization of engineered spinal cord tissues is beneficial for SCI treatment and highlights the important role of exogenous endothelial cells in tissue engineering.

Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys.

Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.

Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids.

Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.