Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the ...Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.展开更多
Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types ...Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types involved in this process,the underlying molecular and cellular mechanisms remain largely unexplored.In this study,we used single-cell RNA sequencing to profile distinct cell populations at different stages of spinal cord injury in zebrafish.Our analysis revealed that multiple subpopulations of neurons showed persistent activation of genes associated with axonal regeneration post injury,while molecular signals promoting growth cone collapse were inhibited.Radial glial cells exhibited significant proliferation and differentiation potential post injury,indicating their intrinsic roles in promoting neurogenesis and axonal regeneration,respectively.Additionally,we found that inflammatory factors rapidly decreased in the early stages following spinal cord injury,creating a microenvironment permissive for tissue repair and regeneration.Furthermore,oligodendrocytes lost maturity markers while exhibiting increased proliferation following injury.These findings demonstrated that the rapid and orderly regulation of inflammation,as well as the efficient proliferation and redifferentiation of new neurons and glial cells,enabled zebrafish to reconstruct the spinal cord.This research provides new insights into the cellular transitions and molecular programs that drive spinal cord regeneration,offering promising avenues for future research and therapeutic strategies.展开更多
The effects of continuously regenerating diesel particulate filter （CRDPF） systems on regulated gaseous emissions, and number-size distribution and mass of particles emanated from a diesel engine have been investiga...The effects of continuously regenerating diesel particulate filter （CRDPF） systems on regulated gaseous emissions, and number-size distribution and mass of particles emanated from a diesel engine have been investigated in this study. Two CRDPF units （CRDPF-1 and CRDPF-2） with different specifications were separately retrofitted to the engine running with European steady-state cycle （ESC）. An electrical low pressure impactor （ELPI） was used for particle number-size distribution measurement and mass estimation. The conversion/reduction rate （RcR） of hydrocarbons （HC） and carbon monoxide （CO） across CRDPF-1 was 83% and 96.3%, respectively. Similarly, the RCR of HC and CO and across CRDPF-2 was 91.8% and 99.1%, respectively. The number concentration of particles and their concentration peaks; nuclei mode, accumulation mode and total particles; and particle mass were highly reduced with the CRDPF units. The nuclei mode particles at downstream of CRDPF-1 and CRDPF-2 decreased by 99.9% to 100% and 97.8% to 99.8% respectively; and the particle mass reduced by 73% to 92.2% and 35.3% to 72.4%, respectively, depending on the engine conditions. In addition, nuclei mode particles increased with the increasing of engine speed due to the heterogeneous nucleation initiated by the higher exhaust temperature, while accumulation mode particles were higher at higher loads due to the decrease in the air-to-fuel ratio （A/F） at higher loads.展开更多
Two continuously regenerating diesel particulate filter （CRDPF） with different configurations and one particles oxidation catalyst （POC） were employed to perform experiments in a controlled laboratory setting to e...Two continuously regenerating diesel particulate filter （CRDPF） with different configurations and one particles oxidation catalyst （POC） were employed to perform experiments in a controlled laboratory setting to evaluate their effects on NO2, smoke and particle number emissions. The results showed that the application of the after-treatments increased the emission ratios of NO2/NOx significantly. The results of smoke emissions and particle number （PN） emissions indicated that both CRDPFs had sufficient capacity to remove more than 90% of total particulate matter （PM） and more than 97% of solid particles. However, the POC was able to remove the organic components of total PM, and only partially to remove the carbonaceous particles with size less than 30 nm. The negligible effects of POC on larger particles were observed due to its honeycomb structure leads to an inadequate residence time to oxidize the solid particles or trap them. The particles removal efficiencies of CRDPFs had high degree of correlations with the emission ratio of NO2/NOx. The PN emission results from two CRDPFs indicated that more NO2 generating in diesel oxidation catalyst section could obtain the higher removal efficiency of solid particles. However this also increased the risk of NO2 exposure in atmosphere.展开更多
AIM： To investigate the prognostic significance of phosphatase regenerating liver 3 （PRL-3） protein expression in gastric cancer.METHODS： PRL-3 expression in paraffin-embedded tumor specimens from 293 patients wit...AIM： To investigate the prognostic significance of phosphatase regenerating liver 3 （PRL-3） protein expression in gastric cancer.METHODS： PRL-3 expression in paraffin-embedded tumor specimens from 293 patients with gastric cancer was studied retrospectively by immunohistochemistry. Nonoclonal antibody specifically against PRL-3, 3B6, was obtained with hybridoma technique.RESULTS： Positive PRL-3 expression was detected in 43.3% （227 of 293） of gastric cancer cases. High expression of PRL-3 was positively correlated with tumor size, depth of invasion, vascular/lymphatic invasion, lymph node metastasis, high TNM stage and tumor recurrence. Patients with positive PRL-3 expression had a significantly lower 5-year survival rate than those with negative expression （28.3% vs 52.9%, P 〈 0.0001）. Patients who received curative surgery, and with positive PRL-3 expression had a significant shorter overall survival and disease-free disadvantage over patients with negative expression （hazard ratio of 16.7 and 16.6, respectively; P 〈 0.0001 for both）. Multivariate analysis revealed that PRL-3 expression was an independent prognostic indicator for overall and disease-free survival of gastric cancer patients, particularly for survival in TNM stage Ⅲ patients. CONCLUSION： PRL-3 expression is a new independent prognostic indicator to predict the potential of recurrence and survival in patients with gastric cancer at the time of tumor resection,展开更多
BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous stud...BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism.AIM To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance.METHODS We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC.The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells.We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells.Finally,we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells.RESULTS Compared to normal mucosa,REG4 mRNA expression was high in CRC(P<0.05)but protein expression was low.An inverse correlation existed between lymph node and distant metastases,tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression(P<0.05),but vice versa for REG4 protein expression.REG4-related genes included:Chemokine activity;taste receptors;protein-DNA and DNA packing complexes;nucleosomes and chromatin;generation of second messenger molecules;programmed cell death signals;epigenetic regulation and DNA methylation;transcription repression and activation by DNA binding;insulin signaling pathway;sugar metabolism and transfer;and neurotransmitter receptors(P<0.05).REG4 exposure or overexpression promoted proliferation,antiapoptosis,migration,and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide 3-kinase-Akt-nuclear factor-κB pathway.REG4 was involved in chemoresistance not through de novo lipogenesis,but lipid droplet assembly.REG4 inhibited the transcription of acetyl-CoA carboxylase 1(ACC1)and ATP-citrate lyase(ACLY)by disassociating the complex formation of anti-acetyl(AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY.CONCLUSION REG4 may be involved in chemoresistance through lipid droplet assembly.REG4 reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.展开更多
The regenerating islet-derived members （Reg）, a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers...The regenerating islet-derived members （Reg）, a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers, functioning as trophic or antiapoptotic factors. Regenerat- ing islet-derived type Ⅳ （RegⅣ）, a member of the Reg gene family, has been reported to be overexpressed in gastroenterological cancers. RegIV overexpression in tumor cells has been associated with carcinogen- esis, cell growth, survival and resistance to apoptosis. Cancer tissue expressing RegIV is generally associated with more malignant characteristics than that with- out such expression, and RegⅣ is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers. We previously investigated the expression levels of RegⅣ mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegⅣ gene expression was a significant independent predictor of colorec- tal cancer. The biologic functions of RegⅣ protein in cancer tissue, associated with carcinogenesis, anti- apoptosis and invasiveness, are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegIV, and the feasibility of antibody therapy targeting RegIV is being assessed. These studies may lead to novel therapeutic strate- gies for gastroenterological cancers expressing RegⅣ. This review article summarizes the current information related to biological functions as well as clinical impor- tance of RegⅣ gene to clarify the significance of Reg~ expression in gastroenterological cancers.展开更多
The primary purpose of this study was to investigate the effect of a catalyzed continuously regenerating trap(CCRT)system composed of a diesel oxidation catalyst(DOC)and a catalyzed diesel particulate filter(CDPF)on t...The primary purpose of this study was to investigate the effect of a catalyzed continuously regenerating trap(CCRT)system composed of a diesel oxidation catalyst(DOC)and a catalyzed diesel particulate filter(CDPF)on the main gaseous and particulate emissions from an urban diesel bus,as well as the durability performance of the CCRT system.Experiments were conducted based on a heavy chassis dynamometer,and a laboratory activity test as well as X-ray photoelectron spectroscopy(XPS)test were applied to evaluate the changes of the aged CCRT catalyst.Results showed that the CCRT could reduce the CO by 71.5%and the total hydrocarbons(THC)by 88.9%,and meanwhile promote the oxidation of NO.However,the conversion rates for CO and THC dropped to 25.1%and 55.1%,respectively,after the CCRT was used for one year(~60,000 km),and the NO oxidation was also weakened.For particulate emissions,the CCRT could reduce 97.4%of the particle mass(PM)and almost 100%of the particle number(PN).The aging of the CCRT resulted in a reduced PM trapping efficiency but had no observable effect on the PN;however,it increased the proportion of nucleation mode particles.The activity test results indicated that the deterioration of the CCRT was directly relevant to the increase in the light-off temperatures of the catalyst for CO,C3H8 and NO2.In addition,the decreased concentrations of the active components Pt2+ and Pt4+ in the catalyst are also important factors in the CCRT deterioration.展开更多
In distributed cloud storage systems, inevitably there exist multiple node failures at the same time. The existing methods of regenerating codes, including minimum storage regenerating(MSR) codes and minimum bandwidth...In distributed cloud storage systems, inevitably there exist multiple node failures at the same time. The existing methods of regenerating codes, including minimum storage regenerating(MSR) codes and minimum bandwidth regenerating(MBR) codes, are mainly to repair one single or several failed nodes, unable to meet the repair need of distributed cloud storage systems. In this paper, we present locally minimum storage regenerating(LMSR) codes to recover multiple failed nodes at the same time. Specifically, the nodes in distributed cloud storage systems are divided into multiple local groups, and in each local group(4, 2) or(5, 3) MSR codes are constructed. Moreover, the grouping method of storage nodes and the repairing process of failed nodes in local groups are studied. Theoretical analysis shows that LMSR codes can achieve the same storage overhead as MSR codes. Furthermore, we verify by means of simulation that, compared with MSR codes, LMSR codes can reduce the repair bandwidth and disk I/O overhead effectively.展开更多
Traumatic brain injury （TBI） is a mechanical injury to brain tissue that leads to an impairment of function and a broad spectrum of symptoms and disabilities; often, it is followed by diffuse axonal injury, which ca...Traumatic brain injury （TBI） is a mechanical injury to brain tissue that leads to an impairment of function and a broad spectrum of symptoms and disabilities; often, it is followed by diffuse axonal injury, which causes denaturation of the white matter and axon retraction, leaving patients with severe brain damage or even in a persistent vegetative state.展开更多
Two after treatment units, selective catalytic reduction （SCR） and continuously regenerating trap （CRT）, were independently retrofitted to a diesel engine, with the objective to investigate their impact on the con...Two after treatment units, selective catalytic reduction （SCR） and continuously regenerating trap （CRT）, were independently retrofitted to a diesel engine, with the objective to investigate their impact on the conversion/reduction （CR） of polycyclic aromatic hydrocarbons （PAHs）. The experiments were conducted under the European steady state cycle （ESC） first without any retrofits to get baseline emissions, and then with SCR and CRT respectively, on the same engine. The particulate matter （PM）-phase PAHs were trapped in fiberglass filters, whereas gas-phase PAHs were collected in cartridges, and then analyzed using a gas chromatograph-mass spectrometer （GC-MS）. Both PM-phase and gas-phase PAHs were greatly reduced with CRT showing respective CR of 90.7% and above 80%, whereas only gas-phase PAHs were abated in the case of SCR, with CR of above 75%. Lower molecular weight （LMW） PAHs were in abundance, while naphthalene exhibited a maximum relative contribution （RC） to LMW-PAHs for all three cases. Further, the CR of naphthalene and anthracene were increased with increasing catalyst temperature of SCR, most likely due to their conversion to solid particles. Moreover, the Benzo[a]Pyrene equivalent （BaPeq） of PAHs was greatly reduced with CRT, owing to substantial reduction of total PAHs.展开更多
We study the construction of minimum bandwidth regenerating code with combinatorial design. At first, a method of constructing minimum storage regenerating （MBR） codes is presented, which can tolerate only one-node ...We study the construction of minimum bandwidth regenerating code with combinatorial design. At first, a method of constructing minimum storage regenerating （MBR） codes is presented, which can tolerate only one-node failure. Then, we give examples to explain the code. Finally, we discuss the case of repairing multiple nodes, and analyze the performance with an example.展开更多
Inflammatory bowel disease(IBD)is an inflammatory disorder of the gastrointestinal tract that affects millions of patients worldwide.It has a complex and multifactorial etiology leading to excessive exposure of intest...Inflammatory bowel disease(IBD)is an inflammatory disorder of the gastrointestinal tract that affects millions of patients worldwide.It has a complex and multifactorial etiology leading to excessive exposure of intestinal epithelium to microbial antigens,inappropriate activation of the immune system and ultimately to the damage of intestinal tissues.Although numerous efforts have been made to improve the disease management,IBD remains persistently recurring and beyond cure.This is due largely to the gaps in our understanding of the pathogenesis of IBD that hamper the development of timely diagnoses and effective treatment.However,some recent discoveries,including the beneficial effects of interleukin-22(IL-22)on the inflamed intestine,have shed light on a self-protective mechanism in IBD.Regenerating islet-derived(REG/Reg)proteins are small secretory proteins which function as IL-22’s downstream effectors.Mounting studies have demonstrated that IBD patients have significantly increased REG expressions in the injured intestine,but with undefined mechanisms and roles.The reported functions of REG/Reg proteins in intestinal homeostasis,such as those of antibacterial,anti-inflammatory and tissue repair,lead us to discuss their potential mechanisms and clinical relevance in IBD in order to advance IBD research and management.展开更多
Erasure code is widely used as the redundancy scheme in distributed storage system. When a storage node fails, the repair process often requires to transfer a large amount of data. Regenerating code and hierarchical c...Erasure code is widely used as the redundancy scheme in distributed storage system. When a storage node fails, the repair process often requires to transfer a large amount of data. Regenerating code and hierarchical code are two classes of codes proposed to reduce the repair bandwidth cost. Regenerating codes reduce the amount of data transferred by each helping node, while hierarchical codes reduce the number of nodes participating in the repair process. In this paper, we propose a "sub-code nesting framework" to combine them together. The resulting regenerating hierarchical code has low repair degree as hierarchical code and lower repair cost than hierarchical code. Our code can achieve exact regeneration of the failed node, and has the additional property of low updating complexity.展开更多
Citation： Utine CA, Engin Durmaz C, Koqak N. Corneal matrix repair therapy with the regenerating agent in neurotrophic persistent epithelial defects, lntJOphthalmo12017;10（12）：1935-1939
Ephrin receptors are the most common tyrosine kinase effectors operating during development. Ephrin receptor genes are reported to be up-regulated in the regenerating tail of the Podarcis muralis lizard. Thus, in the ...Ephrin receptors are the most common tyrosine kinase effectors operating during development. Ephrin receptor genes are reported to be up-regulated in the regenerating tail of the Podarcis muralis lizard. Thus, in the current study, we investigated immunolocalization of ephrin receptors in the Podarcis muralis tail during regeneration. Weak immunolabelled bands for ephrin receptors were detected at 15–17 kDa, with a stronger band also detected at 60–65 kDa. Labelled cells and nuclei were seen in the basal layer of the apical wound epidermis and ependyma, two key tissues stimulating tail regeneration. Strong nuclear and cytoplasmic labelling were present in the segmental muscles of the regenerating tail, sparse blood vessels, and perichondrium of regenerating cartilage. The immunolocalization of ephrin receptors in muscle that gives rise to large portions of new tail tissue was correlated with their segmentation. This study suggests that the high localization of ephrin receptors in differentiating epidermis, ependyma, muscle, and cartilaginous cells is connected to the regulation of cell proliferation through the activation of programs for cell differentiation in the proximal regions of the regenerating tail. The lower immunolabelling of ephrin receptors in the apical blastema, where signaling proteins stimulating cell proliferation are instead present, helps maintain the continuous growth of this region.展开更多
The skin is a formidable physical and biological barrier which communicates continuously with the outside of the body. And the stratum corneum, the outermost layer of human epidermis, plays a central role in the inter...The skin is a formidable physical and biological barrier which communicates continuously with the outside of the body. And the stratum corneum, the outermost layer of human epidermis, plays a central role in the interaction between the cutaneous tissue and the external environment. The horny layer, and more generally the whole skin layers, avoid the penetration of harmful exogenous agents, produce molecules named anti-microbial peptides which impact the composition of the cutaneous microbiota, regulate the internal corporal temperature, avoid the water loss from the inside of the body and constitute an incredible efficient anti-oxidant network. Nevertheless, nowadays, the skin is more and more solicited by the different elements of the cutaneous exposome, including atmospheric pollution and solar radiations, which can cause a dramatic acceleration of the skin ageing process. As a consequence, due to the multifunctional protective role of the skin, during the recent decade the cosmetic industry invested massively in the development of new raw materials and end-products (dermo-cosmetics) able to preserve an optimal state of the skin regarding the external environment. Based on their physical-chemical properties thermal spring waters, which are extremely rich in inorganics ions, are interesting and powerful candidates to be part, as integral component, of new efficient dermo-cosmetic formulations dedicated to protect the skin from the external stimuli. The aim of the present work was to investigate and characterize the activity of Jonzac thermal spring water on the skin. Using different models, we proved for the first time that Jonzac thermal spring water reinforces the barrier function of the skin by modulating the expression of key markers including filaggrin and human beta defensin 2 on ex vivo human skin. The ex vivo and in vivo hydration activity, by Raman spectroscopy and corneometry respectively, has been also demonstrated. We have also shown that Jonzac thermal spring water ameliorates significantly the cutaneous microrelief in vivo. To conclude, we characterize the soothing effect of Jonzac thermal spring water by the analysis of histamine release in Substance P treated skin explants and by measuring the redness of the skin following UV exposure of the skin in vivo. We observed that both parameters decreased following a preventive treatment of the skin with Jonzac thermal spring water. Taken together our results indicate that Jonzac thermal spring water is a promising and powerful dermo-cosmetic which can be used to preserve an optimal state of the cutaneous tissue.展开更多
In regenerating liver of mice, marked increase of the activity of phosphotyrosyl protein phosphatase (PTPP) in cytosol was observed. The PTPP activity varied with time and reached the highest level between 24 to 48 ho...In regenerating liver of mice, marked increase of the activity of phosphotyrosyl protein phosphatase (PTPP) in cytosol was observed. The PTPP activity varied with time and reached the highest level between 24 to 48 hours after partial hepatectomy. In H22a cells the PTPP activity found in every subcellular fraction was lower than that of the normal liver. The PTPP activity was mostly concentrated in lysosomes of normal liver, but mainly distributed in nucleus, cytosol and microsome of regenerating liver. In H22a cells PTPP activity seemed distribute evenly. Five similar major PTPP peaks (I-V) were obtained on DEAE cellulose chromatography of cytosols from all three of liver cells studied. However, two additional PTPP peaks, a and b, were also obtained from cytosol of liver.展开更多
Scientists conclude that a combination of treatments involving rehabilitation,drug delivery,surgery and cell transplantation are necessary to achieve significant progress in regenerating the injured central nervous sy...Scientists conclude that a combination of treatments involving rehabilitation,drug delivery,surgery and cell transplantation are necessary to achieve significant progress in regenerating the injured central nervous system（CNS）.展开更多
Planarians can be used as invertebrate bioassays to evaluate the role of neurotransmitters on regenerating cells. The influence of the nervous system is crucial to regenerate a normal complete animal. The neurotrophic...Planarians can be used as invertebrate bioassays to evaluate the role of neurotransmitters on regenerating cells. The influence of the nervous system is crucial to regenerate a normal complete animal. The neurotrophic action of the nervous system has been attributed to the major neurohormones present throughout the animal kingdom. The same type of transmitters found in mammals have been extensively found in many invertebrates, including planarians, but their role in regeneration is unclear. Neurotransmitters and drugs which act on neurohumoral transmission have been used to determine the role of each neurohormonc on regenerating planarians. Biochemical and pharmacological mechanisms of neurohormones on regenerative planarians are reviewed, as is their putative role on regeneration. Correlations with the roles of neurotransmitters in the central nervous system of higher organisms are also addressed.展开更多
基金supported by the Lorenz B?hler Fonds,#2/19 (obtained by the Neuroregeneration Group,Ludwig Boltzmann Institute for Traumatology)the City of Vienna project ImmunTissue,MA23#30-11 (obtained by the Department Life Science Engineering,University of Applied Sciences Technikum Wien)。
文摘Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.
基金supported by the Jiangsu Province Traditional Chinese Medicine Technology Development Plan Project,Nos.MS2023113(to JC),MS2022090Young and Middle-aged Academic Leaders of Jiangsu Qing-Lan Project(to GL).
文摘Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types involved in this process,the underlying molecular and cellular mechanisms remain largely unexplored.In this study,we used single-cell RNA sequencing to profile distinct cell populations at different stages of spinal cord injury in zebrafish.Our analysis revealed that multiple subpopulations of neurons showed persistent activation of genes associated with axonal regeneration post injury,while molecular signals promoting growth cone collapse were inhibited.Radial glial cells exhibited significant proliferation and differentiation potential post injury,indicating their intrinsic roles in promoting neurogenesis and axonal regeneration,respectively.Additionally,we found that inflammatory factors rapidly decreased in the early stages following spinal cord injury,creating a microenvironment permissive for tissue repair and regeneration.Furthermore,oligodendrocytes lost maturity markers while exhibiting increased proliferation following injury.These findings demonstrated that the rapid and orderly regulation of inflammation,as well as the efficient proliferation and redifferentiation of new neurons and glial cells,enabled zebrafish to reconstruct the spinal cord.This research provides new insights into the cellular transitions and molecular programs that drive spinal cord regeneration,offering promising avenues for future research and therapeutic strategies.
基金supported by the National Natural Science Foundation of China (No. 40805053)
文摘The effects of continuously regenerating diesel particulate filter （CRDPF） systems on regulated gaseous emissions, and number-size distribution and mass of particles emanated from a diesel engine have been investigated in this study. Two CRDPF units （CRDPF-1 and CRDPF-2） with different specifications were separately retrofitted to the engine running with European steady-state cycle （ESC）. An electrical low pressure impactor （ELPI） was used for particle number-size distribution measurement and mass estimation. The conversion/reduction rate （RcR） of hydrocarbons （HC） and carbon monoxide （CO） across CRDPF-1 was 83% and 96.3%, respectively. Similarly, the RCR of HC and CO and across CRDPF-2 was 91.8% and 99.1%, respectively. The number concentration of particles and their concentration peaks; nuclei mode, accumulation mode and total particles; and particle mass were highly reduced with the CRDPF units. The nuclei mode particles at downstream of CRDPF-1 and CRDPF-2 decreased by 99.9% to 100% and 97.8% to 99.8% respectively; and the particle mass reduced by 73% to 92.2% and 35.3% to 72.4%, respectively, depending on the engine conditions. In addition, nuclei mode particles increased with the increasing of engine speed due to the heterogeneous nucleation initiated by the higher exhaust temperature, while accumulation mode particles were higher at higher loads due to the decrease in the air-to-fuel ratio （A/F） at higher loads.
基金supported by the National Natural Science Foundation of China (No. 50876013)
文摘Two continuously regenerating diesel particulate filter （CRDPF） with different configurations and one particles oxidation catalyst （POC） were employed to perform experiments in a controlled laboratory setting to evaluate their effects on NO2, smoke and particle number emissions. The results showed that the application of the after-treatments increased the emission ratios of NO2/NOx significantly. The results of smoke emissions and particle number （PN） emissions indicated that both CRDPFs had sufficient capacity to remove more than 90% of total particulate matter （PM） and more than 97% of solid particles. However, the POC was able to remove the organic components of total PM, and only partially to remove the carbonaceous particles with size less than 30 nm. The negligible effects of POC on larger particles were observed due to its honeycomb structure leads to an inadequate residence time to oxidize the solid particles or trap them. The particles removal efficiencies of CRDPFs had high degree of correlations with the emission ratio of NO2/NOx. The PN emission results from two CRDPFs indicated that more NO2 generating in diesel oxidation catalyst section could obtain the higher removal efficiency of solid particles. However this also increased the risk of NO2 exposure in atmosphere.
基金Supported by Grant for Key Technology Research and Development Program 2002BA711A06National Basic Research Priorities Program 973 Project 1998051203the Ministry of Science and Technology of China,and grant H020920030390,from the Beijing Science and Technology Commission
文摘AIM： To investigate the prognostic significance of phosphatase regenerating liver 3 （PRL-3） protein expression in gastric cancer.METHODS： PRL-3 expression in paraffin-embedded tumor specimens from 293 patients with gastric cancer was studied retrospectively by immunohistochemistry. Nonoclonal antibody specifically against PRL-3, 3B6, was obtained with hybridoma technique.RESULTS： Positive PRL-3 expression was detected in 43.3% （227 of 293） of gastric cancer cases. High expression of PRL-3 was positively correlated with tumor size, depth of invasion, vascular/lymphatic invasion, lymph node metastasis, high TNM stage and tumor recurrence. Patients with positive PRL-3 expression had a significantly lower 5-year survival rate than those with negative expression （28.3% vs 52.9%, P 〈 0.0001）. Patients who received curative surgery, and with positive PRL-3 expression had a significant shorter overall survival and disease-free disadvantage over patients with negative expression （hazard ratio of 16.7 and 16.6, respectively; P 〈 0.0001 for both）. Multivariate analysis revealed that PRL-3 expression was an independent prognostic indicator for overall and disease-free survival of gastric cancer patients, particularly for survival in TNM stage Ⅲ patients. CONCLUSION： PRL-3 expression is a new independent prognostic indicator to predict the potential of recurrence and survival in patients with gastric cancer at the time of tumor resection,
基金Natural Science Foundation of Hebei Province,No.21377772DNo.H2022406034National Natural Scientific Foundation of China,No.81672700.
文摘BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism.AIM To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance.METHODS We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC.The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells.We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells.Finally,we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells.RESULTS Compared to normal mucosa,REG4 mRNA expression was high in CRC(P<0.05)but protein expression was low.An inverse correlation existed between lymph node and distant metastases,tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression(P<0.05),but vice versa for REG4 protein expression.REG4-related genes included:Chemokine activity;taste receptors;protein-DNA and DNA packing complexes;nucleosomes and chromatin;generation of second messenger molecules;programmed cell death signals;epigenetic regulation and DNA methylation;transcription repression and activation by DNA binding;insulin signaling pathway;sugar metabolism and transfer;and neurotransmitter receptors(P<0.05).REG4 exposure or overexpression promoted proliferation,antiapoptosis,migration,and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide 3-kinase-Akt-nuclear factor-κB pathway.REG4 was involved in chemoresistance not through de novo lipogenesis,but lipid droplet assembly.REG4 inhibited the transcription of acetyl-CoA carboxylase 1(ACC1)and ATP-citrate lyase(ACLY)by disassociating the complex formation of anti-acetyl(AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY.CONCLUSION REG4 may be involved in chemoresistance through lipid droplet assembly.REG4 reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.
文摘The regenerating islet-derived members （Reg）, a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers, functioning as trophic or antiapoptotic factors. Regenerat- ing islet-derived type Ⅳ （RegⅣ）, a member of the Reg gene family, has been reported to be overexpressed in gastroenterological cancers. RegIV overexpression in tumor cells has been associated with carcinogen- esis, cell growth, survival and resistance to apoptosis. Cancer tissue expressing RegIV is generally associated with more malignant characteristics than that with- out such expression, and RegⅣ is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers. We previously investigated the expression levels of RegⅣ mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegⅣ gene expression was a significant independent predictor of colorec- tal cancer. The biologic functions of RegⅣ protein in cancer tissue, associated with carcinogenesis, anti- apoptosis and invasiveness, are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegIV, and the feasibility of antibody therapy targeting RegIV is being assessed. These studies may lead to novel therapeutic strate- gies for gastroenterological cancers expressing RegⅣ. This review article summarizes the current information related to biological functions as well as clinical impor- tance of RegⅣ gene to clarify the significance of Reg~ expression in gastroenterological cancers.
基金supported by the National Key Research and Development Program of China (No. YS2017ZY020019)Research Project of Shanghai Committee of Science and Technology (No. 18DZ1202900)the China Scholarship Council (No. 201806260133)
文摘The primary purpose of this study was to investigate the effect of a catalyzed continuously regenerating trap(CCRT)system composed of a diesel oxidation catalyst(DOC)and a catalyzed diesel particulate filter(CDPF)on the main gaseous and particulate emissions from an urban diesel bus,as well as the durability performance of the CCRT system.Experiments were conducted based on a heavy chassis dynamometer,and a laboratory activity test as well as X-ray photoelectron spectroscopy(XPS)test were applied to evaluate the changes of the aged CCRT catalyst.Results showed that the CCRT could reduce the CO by 71.5%and the total hydrocarbons(THC)by 88.9%,and meanwhile promote the oxidation of NO.However,the conversion rates for CO and THC dropped to 25.1%and 55.1%,respectively,after the CCRT was used for one year(~60,000 km),and the NO oxidation was also weakened.For particulate emissions,the CCRT could reduce 97.4%of the particle mass(PM)and almost 100%of the particle number(PN).The aging of the CCRT resulted in a reduced PM trapping efficiency but had no observable effect on the PN;however,it increased the proportion of nucleation mode particles.The activity test results indicated that the deterioration of the CCRT was directly relevant to the increase in the light-off temperatures of the catalyst for CO,C3H8 and NO2.In addition,the decreased concentrations of the active components Pt2+ and Pt4+ in the catalyst are also important factors in the CCRT deterioration.
基金supported in part by the National Natural Science Foundation of China (61640006, 61572188)the Natural Science Foundation of Shaanxi Province, China (2015JM6307, 2016JQ6011)the project of science and technology of Xi’an City (2017088CG/RC051(CADX002))
文摘In distributed cloud storage systems, inevitably there exist multiple node failures at the same time. The existing methods of regenerating codes, including minimum storage regenerating(MSR) codes and minimum bandwidth regenerating(MBR) codes, are mainly to repair one single or several failed nodes, unable to meet the repair need of distributed cloud storage systems. In this paper, we present locally minimum storage regenerating(LMSR) codes to recover multiple failed nodes at the same time. Specifically, the nodes in distributed cloud storage systems are divided into multiple local groups, and in each local group(4, 2) or(5, 3) MSR codes are constructed. Moreover, the grouping method of storage nodes and the repairing process of failed nodes in local groups are studied. Theoretical analysis shows that LMSR codes can achieve the same storage overhead as MSR codes. Furthermore, we verify by means of simulation that, compared with MSR codes, LMSR codes can reduce the repair bandwidth and disk I/O overhead effectively.
基金supported by grants from the Spanish Ministry of Economy and Competitivenessthe European Regional Development Fund 2007-2013(BFU2014-56300-P)+4 种基金the Xunta de Galicia(GPC2014/030)supported by a grant from the Xunta de Galicia(2016-PG008)a grant from the crowdfunding platform Precipita(FECYTSpanish Ministry of Economy and Competitivenessgrant number 2017-CP081)
文摘Traumatic brain injury （TBI） is a mechanical injury to brain tissue that leads to an impairment of function and a broad spectrum of symptoms and disabilities; often, it is followed by diffuse axonal injury, which causes denaturation of the white matter and axon retraction, leaving patients with severe brain damage or even in a persistent vegetative state.
基金supported by the National Natural Science Foundation of China (No. 50876013)
文摘Two after treatment units, selective catalytic reduction （SCR） and continuously regenerating trap （CRT）, were independently retrofitted to a diesel engine, with the objective to investigate their impact on the conversion/reduction （CR） of polycyclic aromatic hydrocarbons （PAHs）. The experiments were conducted under the European steady state cycle （ESC） first without any retrofits to get baseline emissions, and then with SCR and CRT respectively, on the same engine. The particulate matter （PM）-phase PAHs were trapped in fiberglass filters, whereas gas-phase PAHs were collected in cartridges, and then analyzed using a gas chromatograph-mass spectrometer （GC-MS）. Both PM-phase and gas-phase PAHs were greatly reduced with CRT showing respective CR of 90.7% and above 80%, whereas only gas-phase PAHs were abated in the case of SCR, with CR of above 75%. Lower molecular weight （LMW） PAHs were in abundance, while naphthalene exhibited a maximum relative contribution （RC） to LMW-PAHs for all three cases. Further, the CR of naphthalene and anthracene were increased with increasing catalyst temperature of SCR, most likely due to their conversion to solid particles. Moreover, the Benzo[a]Pyrene equivalent （BaPeq） of PAHs was greatly reduced with CRT, owing to substantial reduction of total PAHs.
基金Supported by the National Natural Science Foundation of China(61271174,61301178)
文摘We study the construction of minimum bandwidth regenerating code with combinatorial design. At first, a method of constructing minimum storage regenerating （MBR） codes is presented, which can tolerate only one-node failure. Then, we give examples to explain the code. Finally, we discuss the case of repairing multiple nodes, and analyze the performance with an example.
文摘Inflammatory bowel disease(IBD)is an inflammatory disorder of the gastrointestinal tract that affects millions of patients worldwide.It has a complex and multifactorial etiology leading to excessive exposure of intestinal epithelium to microbial antigens,inappropriate activation of the immune system and ultimately to the damage of intestinal tissues.Although numerous efforts have been made to improve the disease management,IBD remains persistently recurring and beyond cure.This is due largely to the gaps in our understanding of the pathogenesis of IBD that hamper the development of timely diagnoses and effective treatment.However,some recent discoveries,including the beneficial effects of interleukin-22(IL-22)on the inflamed intestine,have shed light on a self-protective mechanism in IBD.Regenerating islet-derived(REG/Reg)proteins are small secretory proteins which function as IL-22’s downstream effectors.Mounting studies have demonstrated that IBD patients have significantly increased REG expressions in the injured intestine,but with undefined mechanisms and roles.The reported functions of REG/Reg proteins in intestinal homeostasis,such as those of antibacterial,anti-inflammatory and tissue repair,lead us to discuss their potential mechanisms and clinical relevance in IBD in order to advance IBD research and management.
基金Supported by 973 Project of China (No. 2012CB315803)Research Fund for the Doctoral Program of Higher Education of China (No. 20100002110033)Open research Fund of National Mobile Communications Research Laboratory, Southeast University (No. 2011D11)
文摘Erasure code is widely used as the redundancy scheme in distributed storage system. When a storage node fails, the repair process often requires to transfer a large amount of data. Regenerating code and hierarchical code are two classes of codes proposed to reduce the repair bandwidth cost. Regenerating codes reduce the amount of data transferred by each helping node, while hierarchical codes reduce the number of nodes participating in the repair process. In this paper, we propose a "sub-code nesting framework" to combine them together. The resulting regenerating hierarchical code has low repair degree as hierarchical code and lower repair cost than hierarchical code. Our code can achieve exact regeneration of the failed node, and has the additional property of low updating complexity.
文摘Citation： Utine CA, Engin Durmaz C, Koqak N. Corneal matrix repair therapy with the regenerating agent in neurotrophic persistent epithelial defects, lntJOphthalmo12017;10（12）：1935-1939
基金mainly supported by the Comparative Histolab PadovaUniversity of Bologna
文摘Ephrin receptors are the most common tyrosine kinase effectors operating during development. Ephrin receptor genes are reported to be up-regulated in the regenerating tail of the Podarcis muralis lizard. Thus, in the current study, we investigated immunolocalization of ephrin receptors in the Podarcis muralis tail during regeneration. Weak immunolabelled bands for ephrin receptors were detected at 15–17 kDa, with a stronger band also detected at 60–65 kDa. Labelled cells and nuclei were seen in the basal layer of the apical wound epidermis and ependyma, two key tissues stimulating tail regeneration. Strong nuclear and cytoplasmic labelling were present in the segmental muscles of the regenerating tail, sparse blood vessels, and perichondrium of regenerating cartilage. The immunolocalization of ephrin receptors in muscle that gives rise to large portions of new tail tissue was correlated with their segmentation. This study suggests that the high localization of ephrin receptors in differentiating epidermis, ependyma, muscle, and cartilaginous cells is connected to the regulation of cell proliferation through the activation of programs for cell differentiation in the proximal regions of the regenerating tail. The lower immunolabelling of ephrin receptors in the apical blastema, where signaling proteins stimulating cell proliferation are instead present, helps maintain the continuous growth of this region.
文摘The skin is a formidable physical and biological barrier which communicates continuously with the outside of the body. And the stratum corneum, the outermost layer of human epidermis, plays a central role in the interaction between the cutaneous tissue and the external environment. The horny layer, and more generally the whole skin layers, avoid the penetration of harmful exogenous agents, produce molecules named anti-microbial peptides which impact the composition of the cutaneous microbiota, regulate the internal corporal temperature, avoid the water loss from the inside of the body and constitute an incredible efficient anti-oxidant network. Nevertheless, nowadays, the skin is more and more solicited by the different elements of the cutaneous exposome, including atmospheric pollution and solar radiations, which can cause a dramatic acceleration of the skin ageing process. As a consequence, due to the multifunctional protective role of the skin, during the recent decade the cosmetic industry invested massively in the development of new raw materials and end-products (dermo-cosmetics) able to preserve an optimal state of the skin regarding the external environment. Based on their physical-chemical properties thermal spring waters, which are extremely rich in inorganics ions, are interesting and powerful candidates to be part, as integral component, of new efficient dermo-cosmetic formulations dedicated to protect the skin from the external stimuli. The aim of the present work was to investigate and characterize the activity of Jonzac thermal spring water on the skin. Using different models, we proved for the first time that Jonzac thermal spring water reinforces the barrier function of the skin by modulating the expression of key markers including filaggrin and human beta defensin 2 on ex vivo human skin. The ex vivo and in vivo hydration activity, by Raman spectroscopy and corneometry respectively, has been also demonstrated. We have also shown that Jonzac thermal spring water ameliorates significantly the cutaneous microrelief in vivo. To conclude, we characterize the soothing effect of Jonzac thermal spring water by the analysis of histamine release in Substance P treated skin explants and by measuring the redness of the skin following UV exposure of the skin in vivo. We observed that both parameters decreased following a preventive treatment of the skin with Jonzac thermal spring water. Taken together our results indicate that Jonzac thermal spring water is a promising and powerful dermo-cosmetic which can be used to preserve an optimal state of the cutaneous tissue.
文摘In regenerating liver of mice, marked increase of the activity of phosphotyrosyl protein phosphatase (PTPP) in cytosol was observed. The PTPP activity varied with time and reached the highest level between 24 to 48 hours after partial hepatectomy. In H22a cells the PTPP activity found in every subcellular fraction was lower than that of the normal liver. The PTPP activity was mostly concentrated in lysosomes of normal liver, but mainly distributed in nucleus, cytosol and microsome of regenerating liver. In H22a cells PTPP activity seemed distribute evenly. Five similar major PTPP peaks (I-V) were obtained on DEAE cellulose chromatography of cytosols from all three of liver cells studied. However, two additional PTPP peaks, a and b, were also obtained from cytosol of liver.
文摘Scientists conclude that a combination of treatments involving rehabilitation,drug delivery,surgery and cell transplantation are necessary to achieve significant progress in regenerating the injured central nervous system（CNS）.
文摘Planarians can be used as invertebrate bioassays to evaluate the role of neurotransmitters on regenerating cells. The influence of the nervous system is crucial to regenerate a normal complete animal. The neurotrophic action of the nervous system has been attributed to the major neurohormones present throughout the animal kingdom. The same type of transmitters found in mammals have been extensively found in many invertebrates, including planarians, but their role in regeneration is unclear. Neurotransmitters and drugs which act on neurohumoral transmission have been used to determine the role of each neurohormonc on regenerating planarians. Biochemical and pharmacological mechanisms of neurohormones on regenerative planarians are reviewed, as is their putative role on regeneration. Correlations with the roles of neurotransmitters in the central nervous system of higher organisms are also addressed.
