Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

Strain-dependent alpha-synuclein spreading in Parkinson's disease and multiple system atrophy

Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) aggregates.These a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble aggregates.Oligomeric forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.

Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.

Elucidation of potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa

Dry-cured meat products are considerably popular around the world due to unique flavor.Proteolysis is one of the enzymatic reactions from which flavor substances are derived,which is affected by endogenous proteases.The purpose aimed to reveal the potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa in this paper.The dynamic changes of endogenous proteases activity,free amino acids,and volatiles during dry-cured pork coppa processing were characterized.The results showed that 5 kinds of free amino acids,Glu,Lys,Val,Ala,and Leu,were identified as significant contributors to taste.Meanwhile,key volatiles,such as hexanal,nonanal,octanal,benzaldehyde,3-methyl butanoic acid,2-methyl propanoic acid,and ethyl octanoate,greatly contributed to the flavor characteristics of dry-cured pork coppa.Further partial correlation analysis was performed to better elucidate the relationship among parameters.The results revealed that close relationship between endogenous proteases and key substances.RAP not only significantly affected the accumulation of key active-amino acids,but also affected the accumulation of ethyl octanoate,2,3-pentanedione,and 2,3-octanedione by regulating the accumulation of octanoic acid and Leu.In addition,cathepsin B and D,DPP II,DPP IV and RAP notably affected accumulation of hexanal.

A core scientific problem in the treatment of central nervous system diseases:newborn neurons

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.

Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice

Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in neoplasia.However,the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma(HCC)remain dismal.AIM To establish a cyclin dependent kinase inhibitor 2A(CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC.METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database.Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples.The targeted microRNAs were predicted by lncBasev3.0,and the targeted mRNAs were predicted by miRDB,and Targetscan database.The univariate and multivariate analysis were utilized to identify independent prognostic indicators.RESULTS CDKN2A was frequently mutated and deleted in HCC.The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways.The CDKN2A-related ceRNA network-growth arrest specific 5(GAS5)/miR-25-3p/SRY-box transcription factor 11(SOX11)was successfully established.GAS5 was recognized as an independent prognostic biomarker,whose overexpression was correlated with a poor prognosis in HCC patients.The association between GAS5 expression and methylation,immune infilt-ration was explored.Besides,traditional Chinese medicine effective components targeting GAS5 were obtained.CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression.Moreover,GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p

BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.

Research on the Design of Rural Cultural Tourism Space under the Background of Rural Revitalization: A Case Study of Dujiazhuang Village, Mentougou, Beijing

From the perspective of endogenous development concept,Dujiazhuang Village,Mentougou was taken as an example to explore the development of rural cultural tourism space.The rural tourism resources in the west of Beijing are rich in type and numerous,but the development of cultural tourism is unbalanced and inadequate.Guided by the endogenousconcept and driven by the design of cultural tourism space,rural public space should be as the entry point to integrate the elements of rural resources and create a design that stimulates the endogenous ability of villagers.Culture can promote tourism,and industry can drive the economy to increase income and enhance the villagers'cultural identity.

Cytoplasmic DNA: sources, sensing, and role in aging and disease

Endogenous cytoplasmic DNA(cytoDNA)species are emerging as key mediators of inflammation in diverse physiological and pathological contexts.Although the role of endogenous cytoDNA in innate immune activation is well established,the cytoDNA species themselves are often poorly characterized and difficult to distinguish,and their mechanisms of formation,scope of function and contribution to disease are incompletely understood.

Cytoplasmic DNA:sources,sensing,and role in aging and disease

Endogenous cytoplasmic DNA(cytoDNA)species are emerging as key mediators of inflammation in diverse physiological and pathological contexts.Although the role of endogenous cytoDNA in innate immune activation is well established,the cytoDNA species themselves are often poorly characterized and difficult to distinguish,and their mechanisms of formation,scope of function and contribution to disease are incompletely understood.Here,we summarize current knowledge in this rapidly progressing field with emphases on similarities and differences between distinct cytoDNAs,their underlying molecular mechanisms of formation and function,interactions between cytoDNA pathways,and therapeutic opportunities in the treatment of age-associated diseases.

Principles for Designing New Types of Housing for a Strong and Resilient Local Economy in the Republic of Congo

The Congolese population is organised into households, which are thus headed by a chief who ensures the social well-being, development and integration into working life of the individuals in his charge. This study examines the functional principles of new housing design as an instrument for transforming the (current) failing economy into a strong and resilient one. Accordingly, a literature review of the practice of designing and building housing in human settlements in the Congo revealed the state of the art on this subject. An analysis of the existing housing stock from a demographic, social and economic point of view made it possible to identify the most common household sizes and numbers, as well as the lifestyle processes that determine the need for developed space. To this end, the experimental method was used to propose configuration plans for various new types of dwelling. To this end, the study highlighted the link between people’s standard of living and the effectiveness of their involvement in the local economy. To achieve the aims of the National Development Plan (NDP), particular attention must be paid to solving the housing problem. The existing housing stock actively contributes to the problems associated with unemployment and insecurity. Functional principles for the design of new types of housing have been developed. Four model types are proposed in line with the demographic structure of the population, their socio-economic characteristics and their lifestyle.

The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

Advances on genetic and genomic studies of ALV resistance

Avian leukosis(AL)is a general term for a variety of neoplastic diseases in avian caused by avian leukosis virus(ALV).No vaccine or drug is currently available for the disease.Therefore,the disease can result in severe economic losses in poultry flocks.Increasing the resistance of poultry to ALV may be one effective strategy.In this review,we provide an overview of the roles of genes associated with ALV infection in the poultry genome,including endogenous retroviruses,virus receptors,interferon-stimulated genes,and other immune-related genes.Furthermore,some methods and techniques that can improve ALV resistance in poultry are discussed.The objectives are willing to provide some valuable references for disease resistance breeding in poultry.

Comprehensive overview of microRNA function in rheumatoid arthritis

MicroRNAs(miRNAs),a class of endogenous single-stranded short noncoding RNAs,have emerged as vital epigenetic regulators of both pathological and physiological processes in animals.They direct fundamental cellular pathways and processes by fine-tuning the expression of multiple genes at the posttranscriptional level.Growing evidence suggests that mi RNAs are implicated in the onset and development of rheumatoid arthritis(RA).RA is a chronic inflammatory disease that mainly affects synovial joints.This common autoimmune disorder is characterized by a complex and multifaceted pathogenesis,and its morbidity,disability and mortality rates remain consistently high.More in-depth insights into the underlying mechanisms of RA are required to address unmet clinical needs and optimize treatment.Herein,we comprehensively review the deregulated mi RNAs and impaired cellular functions in RA to shed light on several aspects of RA pathogenesis,with a focus on excessive inflammation,synovial hyperplasia and progressive joint damage.This review also provides promising targets for innovative therapies of RA.In addition,we discuss the regulatory roles and clinical potential of extracellular mi RNAs in RA,highlighting their prospective applications as diagnostic and predictive biomarkers.

An ethylene-induced NAC transcription factor acts as a multiple abiotic stress responsor in conifer

The proper response to various abiotic stresses is essential for plants’survival to overcome their sessile nature,especially for perennial trees with very long-life cycles.However,in conifers,the molecular mechanisms that coordinate multiple abiotic stress responses remain elusive.Here,the transcriptome response to various abiotic stresses like salt,cold,drought,heat shock and osmotic were systematically detected in Pinus tabuliformis(P.tabuliformis)seedlings.We found that four transcription factors were commonly induced by all tested stress treatments,while PtNAC3 and PtZFP30 were highly up-regulated and co-expressed.Unexpectedly,the exogenous hormone treatment assays and the content of the endogenous hormone indicates that the upregulation of PtNAC3 and PtZFP30 are mediated by ethylene.Time-course assay showed that the treatment by ethylene immediate precursor,1-aminocyclopropane-1-carboxylic acid(ACC),activated the expression of PtNAC3 and PtZFP30 within 8 hours.We further confirm that the PtNAC3 can directly bind to the PtZFP30 promoter region and form a cascade.Overexpression of PtNAC3 enhanced unified abiotic stress tolerance without growth penalty in transgenic Arabidopsis and promoted reproductive success under abiotic stress by shortening the lifespan,suggesting it has great potential as a biological tool applied to plant breeding for abiotic stress tolerance.This study provides novel insights into the hub nodes of the abiotic stresses response network as well as the environmental adaptation mechanism in conifers,and provides a potential biofortification tool to enhance plant unified abiotic stress tolerance.

Socio-economic and energy-environmental impacts of technological change on China's agricultural development under the carbon neutrality strategy

Promoting agricultural modernisation through technological change is an important strategy for China.China's carbon neutrality strategy is leading to systemic socio-economic changes that could exacerbate the uncertainty of agricultural development.Therefore,applying a computable general equilibrium(CGE)model,this study characterises the agricultural sector in detail,introducing endogenous technological change proxied by research and development(R&D)to assess the impact of different technological change scenarios on agricultural development under the carbon neutrality target.The results show that allocating carbon revenue for R&D inputs can mitigate the significant negative impact of achieving carbon neutrality on knowledge capital and production in agricultural sectors.Overall,using carbon revenue only for R&D input in crop sectors has the optimal effect on increasing the agricultural sectors'knowledge capital,improving crop production and profit,reducing crop external dependence and promoting the synergistic reduction of carbon and pollutant emissions.However,this scenario has the largest negative impact on macro-economics and household welfare.In contrast,allocating carbon revenue to promote technological change in broader non-energy sectors or both crops and non-energy sectors can effectively mitigate negative socio-economic impacts,but the positive impact on agricultural development is minimal.These findings provide practical insights for the rational use of carbon revenue to expand agricultural R&D investment and ensure balanced agricultural and economic development under the carbon neutrality target.

Endogenous Security-Aware Resource Management for Digital Twin and 6G Edge Intelligence Integrated Smart Park

The integration of digital twin(DT)and 6G edge intelligence provides accurate forecasting for distributed resources control in smart park.However,the adverse impact of model poisoning attacks on DT model training cannot be ignored.To address this issue,we firstly construct the models of DT model training and model poisoning attacks.An optimization problem is formulated to minimize the weighted sum of the DT loss function and DT model training delay.Then,the problem is transformed and solved by the proposed Multi-timescAle endogenouS securiTy-aware DQN-based rEsouRce management algorithm(MASTER)based on DT-assisted state information evaluation and attack detection.MASTER adopts multi-timescale deep Q-learning(DQN)networks to jointly schedule local training epochs and devices.It actively adjusts resource management strategies based on estimated attack probability to achieve endogenous security awareness.Simulation results demonstrate that MASTER has excellent performances in DT model training accuracy and delay.

Potential targets and mechanisms of photobiomodulation for spinal cord injury

As a classic noninvasive physiotherapy,photobiomodulation,also known as low-level laser therapy,is widely used for the treatment of many diseases and has anti-inflammatory and tissue repair effects.Photobiomodulation has been shown to promote spinal cord injury repair.In our previous study,we found that 810 nm low-level laser therapy reduced the M1 polarization of macrophages and promoted motor function recovery.However,the mechanism underlying this inhibitory effect is not clear.In recent years,transcriptome sequencing analysis has played a critical role in elucidating the progression of diseases.Therefore,in this study,we performed M1 polarization on induced mouse bone marrow macrophages and applied low-level laser therapy.Our sequencing results showed the differential gene expression profile of photobiomodulation regulating macrophage polarization.We analyzed these genes using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.Networks of protein-protein interactions and competing RNA endogenous networks were constructed.We found that photobiomodulation inhibited STAT3 expression through increasing the expression of miR-330-5p,and that miR-330-5p binding to STAT3 inhibited STAT3 expression.Inducible nitric oxide synthase showed trends in changes similar to the changes in STAT3 expression.Finally,we treated a mouse model of spinal cord injury using photobiomodulation and confirmed that photobiomodulation reduced inducible nitric oxide synthase and STAT3 expression and promoted motor function recovery in spinal cord injury mice.These findings suggest that STAT3 may be a potential target of photobiomodulation,and the miR-330-5p/STAT3 pathway is a possible mechanism by which photobiomodulation has its biological effects.