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.

A sensitive and accurate method for quantifying endogenous systemin levels and verifying natural occurrence of Leu-Systemin

Dear Editor,Tomato systemin(TomSys),the first discovered plant peptide hormone,can initiate systemic mobile signals to stimulate an immune response in both wounded and intact leaves(Pearce et al.,1991).For decades,biologists have been striving to uncover the mechanisms of TomSys function,but detailed information on the TomSys-regulated systemic defense process remains limited to date.The specific roles of three potential transmissible signaling components,ProSys mRNA,TomSys,and jasmonic acid(JA),in activation of systemic defense responses still need to be clarified(Zhang et al.,2020).

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.

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.

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.

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.

CRISPR/Cas9-mediated multiple gene editing in Brassica oleracea var.capitata using the endogenous tRNA-processing system

Cabbage(Brassica oleracea var.capitata)is a biennial plant with strong self-incompatibility and an obligate requirement for prolonged vernalization by exposure to low temperatures to induce flowering.These characteristics significantly increase the difficulty of exploiting novel germplasm induced by physical or chemical mutagens.In this study,we report a CRISPR/Cas9 gene-editing system based on endogenous tRNA processing to induce high efficiency and inheritable mutagenesis in cabbage.Using the phytoene desaturase gene BoPDS,the S-receptor kinase gene BoSRK,and the male-sterility-associated gene BoMS1 as the target genes,multisite and multiple gene mutations were achieved using a construct with tandemly arrayed tRNA-sgRNA architecture to express multiple sgRNAs.The BoSRK3 gene mutation suppressed self-incompatibility completely,converting the self-incompatible line into a self-compatible line.In addition,the BoMS1 gene mutation produced a completely male-sterile mutant,which was highly cross compatible with its nonmutant isoline at the flowering stage as a result of a simultaneous BoSRK3 gene mutation,enabling the economic propagation of the male-sterile line through bee-mediated cross-pollination.Interestingly,higher site mutation efficiency was detected when a guide sequence was inserted into a location in the tandemly arrayed tRNA-sgRNA architecture that was distal from the upstream Pol III promoter.In addition,mutation sites were also detected in the paralogous genes of the BoPDS and BoSRK genes that had fully consistent sequences or base mismatches but beyond the“seed”region in the spacer sequence compared with the target sgRNAs.Collectively,our results demonstrate that the CRISPR/Cas9 system,coupled with an endogenous tRNA-processing system,is an efficient tool to improve cabbage traits.

Transcriptome analysis reveals the effects of alkali stress on root system architecture and endogenous hormones in apple rootstocks

Soil alkalinity is a major factor that restricts the growth of apple roots.To analyze the response of apple roots to alkali stress, the root structure and endogenous hormones of two apple rootstocks, Malus prunifolia (alkali-tolerant) and Malus hupehensis (alkali-sensitive), were compared. To understand alkali tolerance of M. prunifolia at the molecular level, transcriptome analysis was performed. When plants were cultured in alkaline conditions for 15 d, the root growth of M. hupehensis with weak alkali tolerance decreased significantly. Analysis of endogenous hormone levels showed that the concentrations of indole-3-acetic acid (IAA) and zeatin riboside (ZR) in M. hupehensis under alkali stress were lower than those in the control. However, the trend for IAA and ZR in M. prunifolia was the opposite. The concentration of abscisic acid (ABA) in the roots of the two apple rootstocks under alkali stress increased, but the concentration of ABA in the roots of M. prunifolia was higher than that in M. hupehensis. The expression of IAA-related genes ARF5, GH3.6, SAUR36, and SAUR32 and the Cytokinin (CTK)-related gene IPT5 in M. prunifolia was higher than those in the control, but the expression of these genes in M. hupehensis was lower than those in the control. The expression of ABA-related genes CIPK1 and AHK1 increased in the two apple rootstocks under alkali stress, but the expression of CIPK1 and AHK1 in M. prunifolia was higher than in M. hupehensis. These results demonstrated that under alkali stress, the increase of IAA, ZR, and ABA in roots and the increase of the expression of related genes promoted the growth of roots and improved the alkali tolerance of apple rootstocks.

Increasing Incidence of Diabetes Mellitus, Systemic Hypertension and Germ Cells with Endogenous Estrogen

Background: Era of contraception, abortions, [20th, 21st centuries] implemented as family welfare schemes, witnessed increased global incidence of Type 2 diabetes mellitus, systemic hypertension. Objectives: Altruistic association of contraception [if any], with increasing diabetes mellitus, systemic hypertension, was sought after. Methods: In 2012, retrospective analysis of, prevalence of diabetes mellitus, systemic hypertension, in 350 patients of 20 - 35 years, 35 - 50 years, >50 years, age groups, data collected by convenient, stratified random sampling, from different geographical locations, between 2003-2012 and its association with presence, absence of contraception, abortion was undertaken;simultaneously, serum estrogen levels obtained from 105 patients, were also analysed. Results: 10 - 45 fold increase in Type 2 diabetes mellitus was seen in contraceptive users of >20 years to >50 years;15 - 50 fold increase in incidence of systemic hypertension was seen in contraceptive users of >20 years to >50 years. Endogenous estrogen was reduced below normal in 75% of contraceptive users, and 25% of contraceptive users had low normal serum estrogen. Cholesterol deprived diet, due to decreased synthesis of endogenous estrogen, androgen also was associated with 50% increase in diabetes mellitus, systemic hypertension. Conclusion: Concept is acquired contraception, abortion status, with smashed fragmentation of germ cells, reduced endogenous estrogen, androgen, results in defaulted genomic repertoire, deranged cell metabolism, increased incidence of diabetes mellitus, systemic hypertension as part of metabolic syndrome. Contraception reversal declined the diseases as a cause and effective phenomenon.

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.

Genetics of adult attachment and the endogenous opioid system

Since the pioneering work by Panksepp et al,the neurobiological bases of attachment behavior have been closely linked with opioid neurotransmission.Candidate gene studies of adult individuals have shown that variation in the muopioid receptor gene(OPRM1)influences attachment behavior.Early maternal care and the A/A genotype of the A118G polymorphism interact in modulating levels of fearful attachment.Compared to their counterparts carrying the A/A genotype,individuals expressing the minor 118G allele show lower levels of avoidant attachment and experience more pleasure in social situations.Brain imaging research has strengthened the biological plausibility of candidate gene studies.The avoidance dimension of attachment correlates negatively with muopioid receptor availability in the thalamus and anterior cingulate cortex,as well as the frontal cortex,amygdala,and insula.Overall,findings from human studies combined with those from animal models suggest that research on the genetic bases of attachment should include the endogenous opioid system among the investigated variables.

Smart stimuli-responsive drug delivery systems in spotlight of COVID-19

The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.

Circular RNA expression and the competitive endogenous RNA network in pathological,age-related macular degeneration events:A cross-platform normalization study

Age-related macular degeneration(AMD)causes irreversible blindness in people aged over 50 worldwide.The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD.In the current study,we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database.We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis.Peroxisome and tumor necrosis factor-α(TNF-α)signaling and nuclear factor kappa B(NF-κB)were among the top 10 pathways,and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs(circRNAs).We then constructed a competing endogenous RNA network,which is related to differentially expressed circRNAs.This network included seven circRNAs,15 microRNAs,and 82 mRNAs.The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxia-inducible factor-1(HIF-1)signaling pathway was a common downstream event.The results of the current study may provide insights into the pathological processes of atrophic AMD.

Reciprocal activation of antigen-presenting cells and CAR T cells triggers a widespread endogenous anti-tumor immune response through sustained high-level IFNγproduction

Adoptive cell transfer(ACT)using chimeric antigen receptor(CAR)modified T cells and T cell receptor(TCR)engineered T cells has shown therapeutic efficacy in cancer treatment1,2.CAR T cells are widely applicable to tumor patients because of their ability to directly identify tumor cells in an MHCindependent manner.

Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells

Adult tendon stem/progenitor cells(TSPCs)are essential for tendon maintenance,regeneration,and repair,yet they become susceptible to senescence with age,impairing the self-healing capacity of tendons.In this study,we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness.The top-ranked candidate,prim-O-glucosylcimifugin(POG),a saposhnikovia root extract,could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans,as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs.In vivo,the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals.Mechanistically,POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy.Thus,the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.

Lipolysis supports bone formation by providing osteoblasts with endogenous fatty acid substrates to maintain bioenergetic status

Bone formation is a highly energy-demanding process that can be impacted by metabolic disorders.Glucose has been considered the principal substrate for osteoblasts,although fatty acids are also important for osteoblast function.Here,we report that osteoblasts can derive energy from endogenous fatty acids stored in lipid droplets via lipolysis and that this process is critical for bone formation.As such,we demonstrate that osteoblasts accumulate lipid droplets that are highly dynamic and provide the molecular mechanism by which they serve as a fuel source for energy generation during osteoblast maturation.Inhibiting cytoplasmic lipolysis leads to both an increase in lipid droplet size in osteoblasts and an impairment in osteoblast function.The fatty acids released by lipolysis from these lipid droplets become critical for cellular energy production as cellular energetics shifts towards oxidative phosphorylation during nutrient-depleted conditions.In vivo,conditional deletion of the ATGL-encoding gene Pnpla2 in osteoblast progenitor cells reduces cortical and trabecular bone parameters and alters skeletal lipid metabolism.Collectively,our data demonstrate that osteoblasts store fatty acids in the form of lipid droplets,which are released via lipolysis to support cellular bioenergetic status when nutrients are limited.Perturbations in this process result in impairment of bone formation,specifically reducing ATP production and overall osteoblast function.

Effects of Root Cutting on Morphological Characteristics and Endogenous Hormone Levels of Quercus variabilis Seedlings

The objective of this study was to investigate the effects of root cutting stress on the dynamic changes of endogenous hormone content and growth characteristics of Quercus variabilis roots,and to explore the physiological role of endogenous hormones in regulating root-crown interactions in the short term.The morphological characteristics and endogenous hormone contents of normal roots(no root cutting,CK)and cut roots(cut by 1/3 of the length of the main root,RP)were determined by liquid chromatography,which was combined with mass spectrometry at different levels of different developmental stages.The results showed that the root growth indexes and root endogenous hormones in the RP group were superior to those in the CK group.Through comprehensive analysis of endogenous hormones,it was found that the crosstalk of IAA,JA,ABA and SA could activate the root growth defense.After the root cutting treatment,the root growth of Quercus variabilis seedlings could compensate for the inhibition of taproot growth by promoting lateral root growth.The growth and development of compensatory lateral roots contribute to the increase the total root length of plants,thus promoting the absorption of water and nutrients.It is speculated that plant hormones may be the key factors affecting their development,but this is not only related to the content of a single hormone,but more importantly,it is the interaction between various hormones.

Identification and characterization of noncoding RNAs-associated competing endogenous RNA networks in major depressive disorder

BACKGROUND Major depressive disorder(MDD)is a common and serious mental illness.Many novel genes in MDD have been characterized by high-throughput methods such as microarrays or sequencing.Recently,noncoding RNAs(ncRNAs)were suggested to be involved in the complicated environmental-genetic regulatory network of MDD occurrence;however,the interplay among RNA species,including protein-coding RNAs and ncRNAs,in MDD remains unclear.AIM To investigate the RNA expression datasets downloaded from a public database and construct a network based on differentially expressed long noncoding RNA(lncRNAs),microRNAs(miRNAs),and mRNAs between MDD and controls.METHODS Gene expression data were searched in NCBI Gene Expression Omnibus using the search term“major depressive disorder.”Six array datasets from humans were related to the search term:GSE19738,GSE32280,GSE38206,GSE52790,GSE76826,and GSE81152.These datasets were processed for initial assessment and subjected to quality control and differential expression analysis.Differentially expressed lncRNAs,miRNAs,and mRNAs were determined,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed,and protein-protein interaction network was generated.The results were analyzed for their association with MDD.RESULTS After analysis,3 miRNAs,12 lncRNAs,and 33 mRNAs were identified in the competing endogenous RNA network.Two of these miRNAs were earlier shown to be involved in psychiatric disorders,and differentially expressed mRNAs were found to be highly enriched in pathways related to neurogenesis and neuroplasticity as per Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The expression of hub gene fatty acid 2-hydroxylase was enriched,and the encoded protein was found to be involved in myelin formation,indicating that neurological development and signal transduction are involved in MDD pathogenesis.CONCLUSION The present study presents candidate nc RNAs involved in the neurogenesis and neuroplasticity pathways related to MDD.

An Endogenous Feedback and Entropy Analysis in Machine Learning Model for Stock’s Return Forecast

Stock markets exhibit Brownian movement with random,non-linear,uncertain,evolutionary,non-parametric,nebulous,chaotic characteristics and dynamism with a high degree of complexity.Developing an algorithm to predict returns for decision-making is a challenging goal.In addition,the choice of vari-ables that will serve as input to the model represents a non-triviality,since it is possible to observe endogeneity problems between the predictor and the predicted variables.Thus,the goal is to analyze the endogenous origin of the stock return prediction model based on technical indicators.For this,we structure a feed-for-ward neural network.We evaluate the endogenous feedback between the pre-dicted returns and technical analysis indicators based on the generated residues.It is possible to predict the return.The high accuracy of the model indicates that,during the test period,there is a hit rate close to 76%.Regarding endogeneity,the term of interest and the return are the variables that influence the largest number of indicators.The results will help investors build investment strategies based on this expert system applied to forecasting.