Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
The Rock-soil interface is a common geological interface.Due to mechanical differences between soil and rock,the stress waves generated by underground blasting undergo intense polarization when crossing the rock-soil ...The Rock-soil interface is a common geological interface.Due to mechanical differences between soil and rock,the stress waves generated by underground blasting undergo intense polarization when crossing the rock-soil interface,making propagation laws difficult to predict.Currently,the characteristics of the impact of the rock-soil interface on blasting stress waves remain unclear.Therefore,the vibration field caused by cylindrical charge blasting in elastic rock and partial-saturation poro-viscoelastic soil was solved.A forward algorithm for the underground blasting vibration field in rock-soil sites was proposed,considering medium damping and geometric diffusion effects of stress waves.Further investigation into the influence of rock and soil parameters and blasting source parameters revealed the following conclusions:stress waves in soil exhibit dispersion,causing peak particle velocity(PPV)to display a discrete distribution.Soil parameters affect PPV attenuation only within the soil,while blasting source parameters affect PPV attenuation throughout the entire site.Multi-wave coupling effects induced by the rocksoil interface result in zones of enhanced and attenuated PPV within the site.The size of the enhancement zone is inversely correlated with the distance from the blasting source and positively correlated with the blasting source attenuation rate and burial depth,providing guidance for selecting explosives and blasting positions.Additionally,PPV attenuation rate increases with distance from the rock-soil interface,but an amplification effect occurs near the interface,most noticeable at 0.1 m.Thus,a sufficient safety distance from the rock-soil interface is necessary during underground blasting.展开更多
Seed storability (SS), also called seed longevity, is a valuable trait for seed banks and providing reliable crop seeds to farmers, which is usually negatively correlated to lipoxygenase (LOX) activity. In this study,...Seed storability (SS), also called seed longevity, is a valuable trait for seed banks and providing reliable crop seeds to farmers, which is usually negatively correlated to lipoxygenase (LOX) activity. In this study, the seed storability of 60 accessions of CIMMYT core wheat germplasm panel (CIMCOG) was investigated through artificial aging (AA) test, including three parameters relative germination potential (RGP), relative germination rate (RGR) and relative seedling vigor index (RVI). Significant positive relationships were observed among RGP, RGR and RVI. And the genotypes at three LOX activity related QTLs/genes <em>QLpx.caas</em>-4<em>B</em>, <em>QLpx.caas</em>-1<em>AL</em> and <em>TaLOX</em>-<em>B</em>1 were also identified with published trait-associated molecular markers. For <em>QLpx.caas</em>-4<em>B</em>, a total of five alleles were detected at the locus of <em>Xgwm</em>251, and one marker-trait association was identified for RVI. Four and two alleles were detected at the loci of <em>QLpx.caas</em>-1<em>AL</em> and <em>TaLoxB</em>1 that were significantly associated with RGP, RGR and RVI, respectively. A total of 9 haplotypes were detected at three lipoxygenase activity related gene loci, and the haplotype of three lipoxygenase loci showed a significant association with RGP, RGR and RVI. The haplotype of <em>Xgwm</em>251<sub>-125<em>bp</em> </sub>+ <em>Xwmc</em>312<sub>-247<em>bp</em></sub> + <em>TaLox</em>-<em>B</em>1<em>b</em> produced seeds with the best storability in the CIMCOG, which could benefit the breeding for wheat with good seed storability.展开更多
This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. ...This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelia cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema.展开更多
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 processe...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.展开更多
The Zhujiang River Estuary is becoming eutrophic due to the impact of anthropogenic activities in the past decades.To understand nutrient dynamics and fluxes to the Lingdingyang water via four outlets(Humen,Jiaomen,Ho...The Zhujiang River Estuary is becoming eutrophic due to the impact of anthropogenic activities in the past decades.To understand nutrient dynamics and fluxes to the Lingdingyang water via four outlets(Humen,Jiaomen,Hongqimen and Hengmen),we investigated the spatial distribution and seasonal variation of dissolved nutrients in the Zhujiang River Estuary,based on fourteen cruises conducted from March 2015 to October 2017,covering both wet(April to September)and dry(October to March next year)seasons.Our results showed that riverine fluxes of dissolved inorganic nitrogen(DIN)and dissolved silicate(DSi)into the Lingdingyang water through four outlets varied seasonally due to the influence of river discharge,with the highest in spring and the lowest in winter.However,riverine flux of phosphate exhibited little significant seasonal variability.Riverine nutrients into the Lingdingyang water most resulted through Humen Outlet.The estuarine export fluxes of DIN out of the Zhujiang River Estuary derived from a box model were higher than fluxes of riverine nutrients in May,likely due to the influence of local sewage,while lower than riverine flux in August.The export fluxes of phosphate were higher than the fluxes of riverine phosphate in May and August.In contrast,large amounts of DSi were buried in the estuary in May and August.Although excess DIN was delivered into the Zhujiang River Estuary,eutrophication effect was not as severe as expected in the Zhujiang River Estuary,since the light limitation restricted the utilization of nutrients by phytoplankton.展开更多
The repair of peripheral nerve injuries with autologous nerve remains the gold standard （Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al.,...The repair of peripheral nerve injuries with autologous nerve remains the gold standard （Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al., 2014; Zhu and Lou, 2014）. With advances in tissue engineering and biomaterials, tissue-engineered nerve conduits with various biomaterials and structures, such as collagen and chitosan nerve conduits, have already been used in the clinic as alternatives to autologous nerve in the repair of peripheral nerve injury （Wang et al., 2012; Svizenska et al., 2013; Eppenberger et al., 2014; Gu et al., 2014; Koudehi et al., 2014; MoyaDiaz et al., 2014; Novajra et al., 2014; Okamoto et al., 2014; Shea et al., 2014; Singh et al., 2014; Tamaki et al., 2014; Yu et al., 2014）. Therefore, new simple and effective methods展开更多
The performance of spin–orbit torque(SOT)in heavy metal/ferromagnetic metal periodic multilayers has attracted widespread attention.In this paper,we have successfully fabricated a series of perpendicular magnetized[P...The performance of spin–orbit torque(SOT)in heavy metal/ferromagnetic metal periodic multilayers has attracted widespread attention.In this paper,we have successfully fabricated a series of perpendicular magnetized[Pt(2-t)/Ni(t)]_4 multilayers,and studied the SOT in the multilayers by varying the thickness of Ni layer t.The current induced magnetization switching was achieved with a critical current density of 1×10^(7)A/cm^(2).The damping-like SOT efficiencyξ_(DL)was extracted from an extended harmonic Hall measurement.We demonstrated that theξ_(DL)can be effectively modulated by t_(Pt)/t_(Ni)ratio of Pt and Ni in the multilayers.The SOT investigation about the[Pt/Ni]N multilayers might provide new material candidates for practical perpendicular SOT-MRAM devices.展开更多
The aim of this study was to investigate the changes in the molecular structure and physiological activities of silk fibroin induced by three different sterilization methods (steam, gamma radiation and ethylene oxide)...The aim of this study was to investigate the changes in the molecular structure and physiological activities of silk fibroin induced by three different sterilization methods (steam, gamma radiation and ethylene oxide) with different dose or time period of sterilization by means of Fourier transform infrared (FT-IR) spec-troscopy, X-ray diffraction, mechanical properties and assessment of molecular weight. The results showed that the steam sterilization darkened the color of silk fibroin and obviously affected the mechanical property;gamma irradiation slightly degraded the molecular weight of silk fibroin and the speed of degradation increased with increasing irradiation dose;and ethylene oxide almost had no influence on silk fibroin expect for some slight hydrolysis on mo-lecular weight. Because ethylene oxide sterilization had the smallest influence on the quality of silk fi-broin with compared to other sterilization methods, it could be used as an efficient method to make fibroin more suitable for the development of functional foods and cosmetics.展开更多
High-temperature ionothermal synthesis has been proven effective in preparing environment-friendly carbon nitride(CN)-based photocatalysts in either triazine or heptazine form for CO_(2)reduction reaction(CO_(2)RR).Ho...High-temperature ionothermal synthesis has been proven effective in preparing environment-friendly carbon nitride(CN)-based photocatalysts in either triazine or heptazine form for CO_(2)reduction reaction(CO_(2)RR).However,such a process is usually energy-intensive and suffers from partial carbonization that results in non-porous catalysts and degenerating their activities.Herein,we report the preparation of highly porous CN polymers(porous C_(6)N_(7),C_3N_3,C_(4.5)N_5)through a low-temperature solvothermal polymerization of cyameluric chloride itself or cyanuric chloride itself,or both,respectively.As such,it avoids unfavorable carbonization and allows for fine control of its chemical structure and significantly enlarged surface area(up to 669 m^(2)g^(-1)).The pincer-like 2,2′-bipyridine sites of porous C_(6)N_(7)alter the photocatalytic CO_(2)reduction pathways via stabilizing the^(*)HCO intermediates,which promotes further hydrogenation to produce CH_(4)in a high selectivity.Benefiting from the carbonization-free polymerization,high porosity,and^(*)HCO intermediate activation,porous C_(6)N_(7)gave a superior CO_(2)RR to CH_(4)performance(17.18μmol g^(-1)h^(-1))as well as high stability(5 successive cycles),outperforming the bulk and state-of-the-art counterparts of CN.This opens an avenue for the rational construction of efficient porous CN-based photocatalytic systems,demonstrating their great potential in energy conversion reactions.展开更多
Peripheral nerve injury is a complex and challenging medical condition due to the limited ability of nerves to regenerate, resulting in the loss of both sensory and motor function. Hydrogels have emerged as a promisin...Peripheral nerve injury is a complex and challenging medical condition due to the limited ability of nerves to regenerate, resulting in the loss of both sensory and motor function. Hydrogels have emerged as a promising biomaterial for promoting peripheral nerve regeneration, while conventional hydrogels are generally unable to support endogenous cell infiltration due to limited network dynamics, thereby compromising the therapeutic outcomes. Herein, we present a cell adaptable hydrogel containing a tissue-mimetic silk fibroin network and a dynamically crosslinked bisphosphonated-alginate network. The dynamic network of this hydrogel can respond to cell-generated forces to undergo the cell-mediated reorganization, thereby effectively facilitating the rapid infiltration of Schwann cells and macrophages, as well as the ingrowth of axons. We further show that the magnesium ions released from the hydrogel not only promote neurite outgrowth but also regulate the polarization of macrophages in a sequential manner, contributing to the formation of a regenerative microenvironment. Therefore, this hydrogel effectively prevents muscle atrophy and promotes the regeneration and functional recovery of nerve defects of up to 10 mm within 8 weeks. The findings from this study demonstrate that adaptable hydrogels are promising inductive biomaterials for enhancing the therapeutic outcomes of peripheral nerve injury treatments.展开更多
A central question in neural tissue engineering is how the tissue-engineered nerve(TEN)translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes.Her...A central question in neural tissue engineering is how the tissue-engineered nerve(TEN)translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes.Here,we report a skin-derived precursor-induced Schwann cell(SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft(SKP-SCs-TEN)that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral,histological,and electrophysiological evidence.For achieving better effect of neuroregeneration,this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix(ECM).To overcome the limitation of traditional tissue-engineered nerve grafts,jointly utilizing SKP-SCs and their ECM components were motivated by the thought of prolongating the effect of support cells and their bioactive cues that promote peripheral nerve regeneration.To further explore the regulatory model of gene expression and the related molecular mechanisms involved in tissue engineering-aided peripheral nerve regeneration,we performed a cDNA microarray analysis of gene expression profiling,a comprehensive bioinformatics analysis and a validation study on the grafted segments and dorsal root ganglia tissues.A wealth of transcriptomic and bioinformatics data has revealed complex molecular networks and orchestrated functional regulation that may be responsible for the effects of SKP-SCs-TEN on promoting peripheral nerve regeneration.Our work provides new insights into transcriptomic features and patterns of molecular regulation in nerve functional recovery aided by SKP-SCs-TEN that sheds light on the broader possibilities for novel repair strategies of peripheral nerve injury.展开更多
Background:Knee osteoarthritis(KOA)is a chronic degenerative joint dis-ease that frequently occurs in middle-aged and older individuals.Although celecoxib is a commonly used drug for the treatment of KOA,its efficacy ...Background:Knee osteoarthritis(KOA)is a chronic degenerative joint dis-ease that frequently occurs in middle-aged and older individuals.Although celecoxib is a commonly used drug for the treatment of KOA,its efficacy and safety have limitations.Zushima,a traditional Chinese medicine,is commonly used for treating joint pain and has anti-inflammatory and analgesic proper-ties.This study aims to explore the effect of the Zushima patch combined with celecoxib on pain and inflammatory factor expression in knee osteoarthritis(KOA)patients with cold-dampness obstruction.Methods:A total of 100 patients with KOA of cold-dampness obstruction were randomly divided into a treatment group(n=50)and a control group(n=50).Patients in the control group received oral administration of cele-coxib capsules,whereas the treatment group received the Zushima patch combined with oral administration of celecoxib capsules.Then,the efficacy and safety were compared,together with the traditional Chinese medicine(TCM)syndrome score,pain,and knee joint function.We also determined the concentrations of osteoprotegerin(OPG),insulin-like growth factor(IGF-1),osteocalcin(OC),and inflammatory factors such as interleukin-1β(IL-1β),interleukin-6(IL-6),and C-reactive protein(CRP).Finally,the safety between the two groups was compared.Results:The total effective rate in the treatment group was significantly higher than that in the control group.After treatment,the levels of the TCM syndrome score,pain score,IL-1,IL-6,and CRP in the treatment group showed significant decreases compared with those in the control group,while the scores of OPG,IGF-1,OC,and knee joint function in the treatment group showed significant increases compared with those in the control group.There was no significant difference in adverse events between the two groups.Conclusions:The Zushima patch combined with celecoxib could relieve the pain of KOA with cold-dampness obstruction and improve knee joint function.These effects may be the result of the downregulation of inflammatory factors and the regulation of joint fluid-related indices.展开更多
环保型CuInSe_(2)量子点具有高消光系数和宽光谱吸收范围,在光电化学催化应用中展现了良好的发展前景.然而,CuInSe_(2)量子点较低的载流子分离能力和严重的界面电荷复合降低了其光电化学性能,制约了其应用.因此,我们设计并合成了具有Ⅱ...环保型CuInSe_(2)量子点具有高消光系数和宽光谱吸收范围,在光电化学催化应用中展现了良好的发展前景.然而,CuInSe_(2)量子点较低的载流子分离能力和严重的界面电荷复合降低了其光电化学性能,制约了其应用.因此,我们设计并合成了具有Ⅱ型能带排列的CuInSe_(2)/CuInS_(2)核/壳结构量子点,以促进载流子分离、减少界面缺陷;进一步通过调节In/Cu前驱体的摩尔比,产生铜空位.光物理性质研究表明,导带电子-铜空位捕获的空穴之间的辐射复合成为主要的复合方式,有效延长了载流子寿命,促进了载流子分离.因此,基于富铜空位的CuInSe_(2)/CuInS_(2)核壳量子点的光阳极获得了~8.0 mA cm^(-2)的最大饱和光电流密度,该性能是当前报道的CISe基量子点光电化学电池中的最高值之一.本工作提供了一种通过表面或内在缺陷的调控来促进光电化学应用中的电荷载流子分离和传输的有效方法.展开更多
Peripheral nerve injury(PNI)seriously affects the health and life of patients,and is an urgent clinical problem that needs to be resolved.Nerve implants prepared from various biomaterials have played a positive role i...Peripheral nerve injury(PNI)seriously affects the health and life of patients,and is an urgent clinical problem that needs to be resolved.Nerve implants prepared from various biomaterials have played a positive role in PNI,but the effect should be further improved and thus new biomaterials is urgently needed.Ovalbumin(OVA)contains a variety of bioactive components,low immunogenicity,tolerance,antimicrobial activity,non-toxicity and biodegradability,and has the ability to promote wound healing,cell growth and antimicrobial properties.However,there are few studies on the application of OVA in neural tissue engineering.In this study,OVA implants with different spatial structures(membrane,fiber,and lyophilized scaffolds)were constructed by casting,electrospinning,and freeze-drying methods,respectively.The results showed that the OVA implants had excellent physicochemical properties and were biocompatible without significant toxicity,and can promote vascularization,show good histocompatibility,without excessive inflammatory response and immunogenicity.The in vitro results showed that OVA implants could promote the proliferation and migration of Schwann cells,while the in vivo results confirmed that OVA implants(the E5/70%and 20 kV 20μL/min groups)could effectively regulate the growth of blood vessels,reduce the inflammatory response and promote the repair of subcutaneous nerve injury.Further on,the high-throughput sequencing results showed that the OVA implants up-regulated differential expression of genes related to biological processes such as tumor necrosis factor-α(TNF-α),phosphatidylinositide 3-kinases/protein kinase B(PI3K-Akt)signaling pathway,axon guidance,cellular adhesion junctions,and nerve regeneration in Schwann cells.The present study is expected to provide new design concepts and theoretical accumulation for the development of a new generation of nerve regeneration implantable biomaterials.展开更多
Tissue regeneration requires exogenous and endogenous signals,and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cel...Tissue regeneration requires exogenous and endogenous signals,and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells.The short-distance peripheral nerve showed a spontaneous regenerative phenomenon,which was initiated by the guiding role of macrophages.However,it cannot sufficiently restore long-distance nerve injury by itself.Based on this principle,we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves.Furthermore,a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles(EVs).The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner.The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells,neuron growth and motor function recovery.Meanwhile,the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction.Overall,we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve.This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment,favoring long-distance peripheral nerve regeneration.It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration,which facilitating the development of pro-regenerative biomaterials.展开更多
Chitosan and its degradation product,oligosaccharides,have been shown to facilitate peripheral nerve regeneration.However,the underlying mechanisms are not well understood.In this study,we analyzed the protein express...Chitosan and its degradation product,oligosaccharides,have been shown to facilitate peripheral nerve regeneration.However,the underlying mechanisms are not well understood.In this study,we analyzed the protein expression profiles in sciatic nerves after injury using proteomics.A group of proteins related to exosome packaging and transport is up-regulated by chitosan oligosaccharides(COS),implying that exosomes are involved in COS-induced peripheral nerve regeneration.In fact,exosomes derived from fibroblasts(f-EXOs)treated with COS significantly promoted axon extension and regeneration.Exosomal protein identification and functional studies,revealed that TFAP2C is a key factor in neurite outgrowth induced by COS-f-EXOs.Furthermore,we showed that TFAP2C targets the pri-miRNA-132 gene and represses miR-132-5p expression in dorsal root ganglion neurons.Camkk1 is a downstream substrate of miR-132-5p that positively affects axon extension.In rats,miR-132-5p antagomir stimulates CAMKK1 expression and improves axon regeneration and functional recovery in sciatic nerves after injury.Our data reveal the mechanism for COS in axon regeneration,that is COS induce fibroblasts to produce TFAP2C-enriched EXOs,which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1.Moreover,these results show a new facet of fibroblasts in axon regeneration in peripheral nerves.展开更多
In recent years,neurodegenerative diseases,such as Parkinson’s or Alzheimer’s diseases,are rapidly rising in prevalence.The main hallmark of Parkinson’s disease is the falling levels of neurotransmitter dopamine in...In recent years,neurodegenerative diseases,such as Parkinson’s or Alzheimer’s diseases,are rapidly rising in prevalence.The main hallmark of Parkinson’s disease is the falling levels of neurotransmitter dopamine in the mid-brain with dopaminergic neurons losing.Typical therapeutic solutions,including drugs,deep brain stimulation,and cell transplantation,can only alleviate the symptoms of Parkinson’s disease.It is a tremendous challenge to reverse the function degeneration of the crucial dopaminergic neurons.Herein,we develop a core-satellite-like nanoassembly(PDA-AFn(by integrating polydopamine nanoparticles and apoferritin))to raise the expression of tyrosine hydroxylase(TH),a rate-limiting enzyme in the formation of the dopamine.Both components in the nanoassembly could cooperate with each other,not only elaborately regulate the iron homeostasis and redox microenvironment,but also utilize excessive reactive oxygen species(ROS)and iron ions in the damaged neurons to supply extra dopamine and enhance TH activity,and consequently restore the function of the degenerated neurons.Remarkably,the nanoassembly-treatment relieves the dyskinesia and dramatical increases the tyrosine hydroxylase and dopamine level in the midbrain of Parkinson’s disease model mice.It is an explicit yet inspiring advance in treatment of the neurodegeneration.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金supported by the National Natural Science Foundation of China(Grant Nos.41972286 and 42102329).
文摘The Rock-soil interface is a common geological interface.Due to mechanical differences between soil and rock,the stress waves generated by underground blasting undergo intense polarization when crossing the rock-soil interface,making propagation laws difficult to predict.Currently,the characteristics of the impact of the rock-soil interface on blasting stress waves remain unclear.Therefore,the vibration field caused by cylindrical charge blasting in elastic rock and partial-saturation poro-viscoelastic soil was solved.A forward algorithm for the underground blasting vibration field in rock-soil sites was proposed,considering medium damping and geometric diffusion effects of stress waves.Further investigation into the influence of rock and soil parameters and blasting source parameters revealed the following conclusions:stress waves in soil exhibit dispersion,causing peak particle velocity(PPV)to display a discrete distribution.Soil parameters affect PPV attenuation only within the soil,while blasting source parameters affect PPV attenuation throughout the entire site.Multi-wave coupling effects induced by the rocksoil interface result in zones of enhanced and attenuated PPV within the site.The size of the enhancement zone is inversely correlated with the distance from the blasting source and positively correlated with the blasting source attenuation rate and burial depth,providing guidance for selecting explosives and blasting positions.Additionally,PPV attenuation rate increases with distance from the rock-soil interface,but an amplification effect occurs near the interface,most noticeable at 0.1 m.Thus,a sufficient safety distance from the rock-soil interface is necessary during underground blasting.
文摘Seed storability (SS), also called seed longevity, is a valuable trait for seed banks and providing reliable crop seeds to farmers, which is usually negatively correlated to lipoxygenase (LOX) activity. In this study, the seed storability of 60 accessions of CIMMYT core wheat germplasm panel (CIMCOG) was investigated through artificial aging (AA) test, including three parameters relative germination potential (RGP), relative germination rate (RGR) and relative seedling vigor index (RVI). Significant positive relationships were observed among RGP, RGR and RVI. And the genotypes at three LOX activity related QTLs/genes <em>QLpx.caas</em>-4<em>B</em>, <em>QLpx.caas</em>-1<em>AL</em> and <em>TaLOX</em>-<em>B</em>1 were also identified with published trait-associated molecular markers. For <em>QLpx.caas</em>-4<em>B</em>, a total of five alleles were detected at the locus of <em>Xgwm</em>251, and one marker-trait association was identified for RVI. Four and two alleles were detected at the loci of <em>QLpx.caas</em>-1<em>AL</em> and <em>TaLoxB</em>1 that were significantly associated with RGP, RGR and RVI, respectively. A total of 9 haplotypes were detected at three lipoxygenase activity related gene loci, and the haplotype of three lipoxygenase loci showed a significant association with RGP, RGR and RVI. The haplotype of <em>Xgwm</em>251<sub>-125<em>bp</em> </sub>+ <em>Xwmc</em>312<sub>-247<em>bp</em></sub> + <em>TaLox</em>-<em>B</em>1<em>b</em> produced seeds with the best storability in the CIMCOG, which could benefit the breeding for wheat with good seed storability.
文摘This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelia cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema.
基金This work was supported by the National Natural Science Foundation of China(31730031)the National Key Research and Development Program of China(2017YFA0104700 and 2016YFC1101603)the Jiangsu Provincial Key Medical Center and Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘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.
基金The Special Project for Marine Economic Development(Six Major Marine Industries)of Guangdong Province under contract No.GDNRC[2020]064the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)under contract Nos GML2019ZD0303,GML2019ZD0305 and GML2019ZD0402+2 种基金the Innovation Academy of South China Sea Ecology and Environmental Engineering,Chinese Academy of Sciences under contract Nos ISEE2019ZR02 and ISEE2019ZR03the National Natural Science Foundation of China under contract Nos 41676075 and 41706085the Department of Science and Technology of Guangdong Province under contract No.2018B030320005。
文摘The Zhujiang River Estuary is becoming eutrophic due to the impact of anthropogenic activities in the past decades.To understand nutrient dynamics and fluxes to the Lingdingyang water via four outlets(Humen,Jiaomen,Hongqimen and Hengmen),we investigated the spatial distribution and seasonal variation of dissolved nutrients in the Zhujiang River Estuary,based on fourteen cruises conducted from March 2015 to October 2017,covering both wet(April to September)and dry(October to March next year)seasons.Our results showed that riverine fluxes of dissolved inorganic nitrogen(DIN)and dissolved silicate(DSi)into the Lingdingyang water through four outlets varied seasonally due to the influence of river discharge,with the highest in spring and the lowest in winter.However,riverine flux of phosphate exhibited little significant seasonal variability.Riverine nutrients into the Lingdingyang water most resulted through Humen Outlet.The estuarine export fluxes of DIN out of the Zhujiang River Estuary derived from a box model were higher than fluxes of riverine nutrients in May,likely due to the influence of local sewage,while lower than riverine flux in August.The export fluxes of phosphate were higher than the fluxes of riverine phosphate in May and August.In contrast,large amounts of DSi were buried in the estuary in May and August.Although excess DIN was delivered into the Zhujiang River Estuary,eutrophication effect was not as severe as expected in the Zhujiang River Estuary,since the light limitation restricted the utilization of nutrients by phytoplankton.
基金supported by the National High Technology Research and Development Program of China,No.2012AA020502the National Natural Science Foundation of China,No.81171457 and 81371687the Priority of Academic Program Development of Jiangsu Higher Education Institutions
文摘The repair of peripheral nerve injuries with autologous nerve remains the gold standard （Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al., 2014; Zhu and Lou, 2014）. With advances in tissue engineering and biomaterials, tissue-engineered nerve conduits with various biomaterials and structures, such as collagen and chitosan nerve conduits, have already been used in the clinic as alternatives to autologous nerve in the repair of peripheral nerve injury （Wang et al., 2012; Svizenska et al., 2013; Eppenberger et al., 2014; Gu et al., 2014; Koudehi et al., 2014; MoyaDiaz et al., 2014; Novajra et al., 2014; Okamoto et al., 2014; Shea et al., 2014; Singh et al., 2014; Tamaki et al., 2014; Yu et al., 2014）. Therefore, new simple and effective methods
基金Project supported by the National Key R&D Program of China(Grant No.2021YFB3502400)the National Natural Science Foundation of China(Grant Nos.52061135105,12074025,11834013,and 12274203)+1 种基金the CAS Project for Yong Scientists in Basic Research(Grant No.YSBR-030)the Key Research Project of Frontier Science of Chinese Academy of Sciences(Grant Nos.XDB44000000 and XDB28000000)。
文摘The performance of spin–orbit torque(SOT)in heavy metal/ferromagnetic metal periodic multilayers has attracted widespread attention.In this paper,we have successfully fabricated a series of perpendicular magnetized[Pt(2-t)/Ni(t)]_4 multilayers,and studied the SOT in the multilayers by varying the thickness of Ni layer t.The current induced magnetization switching was achieved with a critical current density of 1×10^(7)A/cm^(2).The damping-like SOT efficiencyξ_(DL)was extracted from an extended harmonic Hall measurement.We demonstrated that theξ_(DL)can be effectively modulated by t_(Pt)/t_(Ni)ratio of Pt and Ni in the multilayers.The SOT investigation about the[Pt/Ni]N multilayers might provide new material candidates for practical perpendicular SOT-MRAM devices.
文摘The aim of this study was to investigate the changes in the molecular structure and physiological activities of silk fibroin induced by three different sterilization methods (steam, gamma radiation and ethylene oxide) with different dose or time period of sterilization by means of Fourier transform infrared (FT-IR) spec-troscopy, X-ray diffraction, mechanical properties and assessment of molecular weight. The results showed that the steam sterilization darkened the color of silk fibroin and obviously affected the mechanical property;gamma irradiation slightly degraded the molecular weight of silk fibroin and the speed of degradation increased with increasing irradiation dose;and ethylene oxide almost had no influence on silk fibroin expect for some slight hydrolysis on mo-lecular weight. Because ethylene oxide sterilization had the smallest influence on the quality of silk fi-broin with compared to other sterilization methods, it could be used as an efficient method to make fibroin more suitable for the development of functional foods and cosmetics.
基金supported by the National Natural Science Foundation of China (52173212 and 52103275)Hunan Province Funds for Distinguished Young Scientists (2022JJ10080)+3 种基金financial support from the European Research Council (ERC)Consolidator (PARIS-101043485)the Swedish Research Council (2022-04533)the Wallenberg Academy Fellow Program (KAW 2017.0166)from the Knut&Alice Wallenberg Foundation in Swedenthe Olle Engkvists Foundation (213-0206)in Sweden。
文摘High-temperature ionothermal synthesis has been proven effective in preparing environment-friendly carbon nitride(CN)-based photocatalysts in either triazine or heptazine form for CO_(2)reduction reaction(CO_(2)RR).However,such a process is usually energy-intensive and suffers from partial carbonization that results in non-porous catalysts and degenerating their activities.Herein,we report the preparation of highly porous CN polymers(porous C_(6)N_(7),C_3N_3,C_(4.5)N_5)through a low-temperature solvothermal polymerization of cyameluric chloride itself or cyanuric chloride itself,or both,respectively.As such,it avoids unfavorable carbonization and allows for fine control of its chemical structure and significantly enlarged surface area(up to 669 m^(2)g^(-1)).The pincer-like 2,2′-bipyridine sites of porous C_(6)N_(7)alter the photocatalytic CO_(2)reduction pathways via stabilizing the^(*)HCO intermediates,which promotes further hydrogenation to produce CH_(4)in a high selectivity.Benefiting from the carbonization-free polymerization,high porosity,and^(*)HCO intermediate activation,porous C_(6)N_(7)gave a superior CO_(2)RR to CH_(4)performance(17.18μmol g^(-1)h^(-1))as well as high stability(5 successive cycles),outperforming the bulk and state-of-the-art counterparts of CN.This opens an avenue for the rational construction of efficient porous CN-based photocatalytic systems,demonstrating their great potential in energy conversion reactions.
基金supported by National Natural Science Foundation of China(32230057,32271385,32371400)Natural Science Foundation of Jiangsu Province(BK20231338)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(21KJA 430011).
文摘Peripheral nerve injury is a complex and challenging medical condition due to the limited ability of nerves to regenerate, resulting in the loss of both sensory and motor function. Hydrogels have emerged as a promising biomaterial for promoting peripheral nerve regeneration, while conventional hydrogels are generally unable to support endogenous cell infiltration due to limited network dynamics, thereby compromising the therapeutic outcomes. Herein, we present a cell adaptable hydrogel containing a tissue-mimetic silk fibroin network and a dynamically crosslinked bisphosphonated-alginate network. The dynamic network of this hydrogel can respond to cell-generated forces to undergo the cell-mediated reorganization, thereby effectively facilitating the rapid infiltration of Schwann cells and macrophages, as well as the ingrowth of axons. We further show that the magnesium ions released from the hydrogel not only promote neurite outgrowth but also regulate the polarization of macrophages in a sequential manner, contributing to the formation of a regenerative microenvironment. Therefore, this hydrogel effectively prevents muscle atrophy and promotes the regeneration and functional recovery of nerve defects of up to 10 mm within 8 weeks. The findings from this study demonstrate that adaptable hydrogels are promising inductive biomaterials for enhancing the therapeutic outcomes of peripheral nerve injury treatments.
基金supported by National Natural Science Foundation of China(Grant No.31730031,82172104,81873767)National Key Research and Development Program of China(2017YFA0104703)+3 种基金Jiangsu Provincial Key Medical Center,Jiangsu Provincial Medical Innovation Center(CXZX202212)Jiangsu Provincial Medical Key Discipline(ZDXK202240)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Technology Project of Nantong(MS22022008).
文摘A central question in neural tissue engineering is how the tissue-engineered nerve(TEN)translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes.Here,we report a skin-derived precursor-induced Schwann cell(SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft(SKP-SCs-TEN)that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral,histological,and electrophysiological evidence.For achieving better effect of neuroregeneration,this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix(ECM).To overcome the limitation of traditional tissue-engineered nerve grafts,jointly utilizing SKP-SCs and their ECM components were motivated by the thought of prolongating the effect of support cells and their bioactive cues that promote peripheral nerve regeneration.To further explore the regulatory model of gene expression and the related molecular mechanisms involved in tissue engineering-aided peripheral nerve regeneration,we performed a cDNA microarray analysis of gene expression profiling,a comprehensive bioinformatics analysis and a validation study on the grafted segments and dorsal root ganglia tissues.A wealth of transcriptomic and bioinformatics data has revealed complex molecular networks and orchestrated functional regulation that may be responsible for the effects of SKP-SCs-TEN on promoting peripheral nerve regeneration.Our work provides new insights into transcriptomic features and patterns of molecular regulation in nerve functional recovery aided by SKP-SCs-TEN that sheds light on the broader possibilities for novel repair strategies of peripheral nerve injury.
基金New Medical Emergency Requirement Demonstration,Grant/Award Number:LB2023B010100。
文摘Background:Knee osteoarthritis(KOA)is a chronic degenerative joint dis-ease that frequently occurs in middle-aged and older individuals.Although celecoxib is a commonly used drug for the treatment of KOA,its efficacy and safety have limitations.Zushima,a traditional Chinese medicine,is commonly used for treating joint pain and has anti-inflammatory and analgesic proper-ties.This study aims to explore the effect of the Zushima patch combined with celecoxib on pain and inflammatory factor expression in knee osteoarthritis(KOA)patients with cold-dampness obstruction.Methods:A total of 100 patients with KOA of cold-dampness obstruction were randomly divided into a treatment group(n=50)and a control group(n=50).Patients in the control group received oral administration of cele-coxib capsules,whereas the treatment group received the Zushima patch combined with oral administration of celecoxib capsules.Then,the efficacy and safety were compared,together with the traditional Chinese medicine(TCM)syndrome score,pain,and knee joint function.We also determined the concentrations of osteoprotegerin(OPG),insulin-like growth factor(IGF-1),osteocalcin(OC),and inflammatory factors such as interleukin-1β(IL-1β),interleukin-6(IL-6),and C-reactive protein(CRP).Finally,the safety between the two groups was compared.Results:The total effective rate in the treatment group was significantly higher than that in the control group.After treatment,the levels of the TCM syndrome score,pain score,IL-1,IL-6,and CRP in the treatment group showed significant decreases compared with those in the control group,while the scores of OPG,IGF-1,OC,and knee joint function in the treatment group showed significant increases compared with those in the control group.There was no significant difference in adverse events between the two groups.Conclusions:The Zushima patch combined with celecoxib could relieve the pain of KOA with cold-dampness obstruction and improve knee joint function.These effects may be the result of the downregulation of inflammatory factors and the regulation of joint fluid-related indices.
基金supported by the National Natural Science Foundation of China (52011530123,52272134,and 51902019)Beijing Natural Science Foundation (2222061 and 2232082)+4 种基金the IndustryUniversity-Research Cooperative Education of Ministry of Education (2205064205258 and 220606429170400)Shandong Weiqiao Pioneering Group Company Limited (BINTECH-KJZX-20220831-09 and BINTECHKJZX-20220831-29)the support from Swedish Research Council (2021-05319)Danish Villum Foundation Experiment Grant (50350)Swedish Foundation for International Cooperation in Research and Higher Education (F2020/1618)。
文摘环保型CuInSe_(2)量子点具有高消光系数和宽光谱吸收范围,在光电化学催化应用中展现了良好的发展前景.然而,CuInSe_(2)量子点较低的载流子分离能力和严重的界面电荷复合降低了其光电化学性能,制约了其应用.因此,我们设计并合成了具有Ⅱ型能带排列的CuInSe_(2)/CuInS_(2)核/壳结构量子点,以促进载流子分离、减少界面缺陷;进一步通过调节In/Cu前驱体的摩尔比,产生铜空位.光物理性质研究表明,导带电子-铜空位捕获的空穴之间的辐射复合成为主要的复合方式,有效延长了载流子寿命,促进了载流子分离.因此,基于富铜空位的CuInSe_(2)/CuInS_(2)核壳量子点的光阳极获得了~8.0 mA cm^(-2)的最大饱和光电流密度,该性能是当前报道的CISe基量子点光电化学电池中的最高值之一.本工作提供了一种通过表面或内在缺陷的调控来促进光电化学应用中的电荷载流子分离和传输的有效方法.
基金the financial support of the National Natural Science Foundation of China(32171352)Special Funds for Provincial Science and Technology Programs(Key R&D Program for Social Development)of Jiangsu Province(BE2023743)+3 种基金Open Research Fund of State Key Laboratory of Advance Technology for Materials Synthesis and Processing(Wuhan University of Technology,2023-KF-18)Open Research Fund of State Key Laboratory of Bioelectronics,Southeast University(2023-K05)Opening Project of State Key Laboratory of Polymer Materials Engineering(Sichuan University,Sklpme2022-4-01)226 High-level Talent Training Project(2nd level,2022 II-276).
文摘Peripheral nerve injury(PNI)seriously affects the health and life of patients,and is an urgent clinical problem that needs to be resolved.Nerve implants prepared from various biomaterials have played a positive role in PNI,but the effect should be further improved and thus new biomaterials is urgently needed.Ovalbumin(OVA)contains a variety of bioactive components,low immunogenicity,tolerance,antimicrobial activity,non-toxicity and biodegradability,and has the ability to promote wound healing,cell growth and antimicrobial properties.However,there are few studies on the application of OVA in neural tissue engineering.In this study,OVA implants with different spatial structures(membrane,fiber,and lyophilized scaffolds)were constructed by casting,electrospinning,and freeze-drying methods,respectively.The results showed that the OVA implants had excellent physicochemical properties and were biocompatible without significant toxicity,and can promote vascularization,show good histocompatibility,without excessive inflammatory response and immunogenicity.The in vitro results showed that OVA implants could promote the proliferation and migration of Schwann cells,while the in vivo results confirmed that OVA implants(the E5/70%and 20 kV 20μL/min groups)could effectively regulate the growth of blood vessels,reduce the inflammatory response and promote the repair of subcutaneous nerve injury.Further on,the high-throughput sequencing results showed that the OVA implants up-regulated differential expression of genes related to biological processes such as tumor necrosis factor-α(TNF-α),phosphatidylinositide 3-kinases/protein kinase B(PI3K-Akt)signaling pathway,axon guidance,cellular adhesion junctions,and nerve regeneration in Schwann cells.The present study is expected to provide new design concepts and theoretical accumulation for the development of a new generation of nerve regeneration implantable biomaterials.
基金the National Natural Science Foundation of China(No.32230057,32271389,31900987)Jiangsu Natural Science Foundation(No.BK20200974)+5 种基金Heilongjiang Natural Science Foundation(No.YQ2019H022)Shuangchuang Program of Jiangsu Province(No.JSSCBS20211603)Nantong Municipal Commission of Health and Family Planning(No.MB2021011)Nantong Science and Technology Plan Project(No.MSZ2022196)Nantong Science and Technology Plan Project(No.JC2019146)Nantong University Clinical Medicine Project(No.2019JZ004).
文摘Tissue regeneration requires exogenous and endogenous signals,and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells.The short-distance peripheral nerve showed a spontaneous regenerative phenomenon,which was initiated by the guiding role of macrophages.However,it cannot sufficiently restore long-distance nerve injury by itself.Based on this principle,we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves.Furthermore,a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles(EVs).The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner.The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells,neuron growth and motor function recovery.Meanwhile,the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction.Overall,we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve.This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment,favoring long-distance peripheral nerve regeneration.It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration,which facilitating the development of pro-regenerative biomaterials.
基金supported by the National Natural Science Foundation of China(Nos.32230057,81970747,32271193)the National Key Research and Development Program of China(No.2017YFA0701304)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions.
文摘Chitosan and its degradation product,oligosaccharides,have been shown to facilitate peripheral nerve regeneration.However,the underlying mechanisms are not well understood.In this study,we analyzed the protein expression profiles in sciatic nerves after injury using proteomics.A group of proteins related to exosome packaging and transport is up-regulated by chitosan oligosaccharides(COS),implying that exosomes are involved in COS-induced peripheral nerve regeneration.In fact,exosomes derived from fibroblasts(f-EXOs)treated with COS significantly promoted axon extension and regeneration.Exosomal protein identification and functional studies,revealed that TFAP2C is a key factor in neurite outgrowth induced by COS-f-EXOs.Furthermore,we showed that TFAP2C targets the pri-miRNA-132 gene and represses miR-132-5p expression in dorsal root ganglion neurons.Camkk1 is a downstream substrate of miR-132-5p that positively affects axon extension.In rats,miR-132-5p antagomir stimulates CAMKK1 expression and improves axon regeneration and functional recovery in sciatic nerves after injury.Our data reveal the mechanism for COS in axon regeneration,that is COS induce fibroblasts to produce TFAP2C-enriched EXOs,which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1.Moreover,these results show a new facet of fibroblasts in axon regeneration in peripheral nerves.
基金This work was supported by National Natural Science Foundation of China(Nos.22175085 and 21875101)National Key Research and Development Program of China(No.2017YFA0701301)State Key Laboratory of Analytical Chemistry for Life Science(No.SKLACLS2219).
文摘In recent years,neurodegenerative diseases,such as Parkinson’s or Alzheimer’s diseases,are rapidly rising in prevalence.The main hallmark of Parkinson’s disease is the falling levels of neurotransmitter dopamine in the mid-brain with dopaminergic neurons losing.Typical therapeutic solutions,including drugs,deep brain stimulation,and cell transplantation,can only alleviate the symptoms of Parkinson’s disease.It is a tremendous challenge to reverse the function degeneration of the crucial dopaminergic neurons.Herein,we develop a core-satellite-like nanoassembly(PDA-AFn(by integrating polydopamine nanoparticles and apoferritin))to raise the expression of tyrosine hydroxylase(TH),a rate-limiting enzyme in the formation of the dopamine.Both components in the nanoassembly could cooperate with each other,not only elaborately regulate the iron homeostasis and redox microenvironment,but also utilize excessive reactive oxygen species(ROS)and iron ions in the damaged neurons to supply extra dopamine and enhance TH activity,and consequently restore the function of the degenerated neurons.Remarkably,the nanoassembly-treatment relieves the dyskinesia and dramatical increases the tyrosine hydroxylase and dopamine level in the midbrain of Parkinson’s disease model mice.It is an explicit yet inspiring advance in treatment of the neurodegeneration.
