Neural cell differentiation and maturation is a critical step during central nervous system devel-opment. The oligodendrocyte transcription family (Olig family) is known to be an important factor in regulating neura...Neural cell differentiation and maturation is a critical step during central nervous system devel-opment. The oligodendrocyte transcription family (Olig family) is known to be an important factor in regulating neural cell differentiation. Because of this, the Olig family also affects acute and chronic central nervous system diseases, including brain injury, multiple sclerosis, and even gliomas. Improved understanding about the functions of the Olig family in central nervous system development and disease will greatly aid novel breakthroughs in central nervous system diseases. This review investigates the role of the Olig family in central nervous system develop- ment and related diseases.展开更多
The basic helix-loop-helix(bHLH)transcription factor family is the second-largest family in plants,where it plays essential roles in development,and the responses to multiple abiotic and biotic stressors.However,littl...The basic helix-loop-helix(bHLH)transcription factor family is the second-largest family in plants,where it plays essential roles in development,and the responses to multiple abiotic and biotic stressors.However,little information is available about this gene family in Prunus mume,which is widely cultivated in East Asia as an ornamental fruit tree.Here,100 PmbHLH genes were identified,and their evolution and functions were explored in P.mume for the first time.The PmbHLH genes were classified into 21 subfamilies.The chromosomal distribution,physicochemical properties,bHLH domain,conserved motif,and intron/exon compositions were also analyzed.Furthermore,the evolutionary pattern,divergence time of the PmbHLH family,and genetic relationships among P.mume,Arabidopsis thaliana,and Prunus persica and Fragaria vesca of Rosaceae were explored.The functional prediction analysis of these PmbHLHs indicated that their functions varied,and included participating in the formation of organs and tissues,responding to stress,and the biosynthesis and metabolism of hormones and other secondary metabolites.Interestingly,expression analyses of PmbHLHs also revealed diverse expression patterns.Most of the PmbHLH genes were highly expressed in roots and stems,and a few were highly expressed in leaves,buds,and fruits,indicating tissue expression specificity.Eight PmbHLH genes,which were upregulated during low-temperature stress,may have critical roles in the response to cold stress.Ten PmbHLHs were differentially expressed between weeping and upright branches in a P.mume F_(1) population.These results shed light on the structure and evolution of the PmbHLH gene family,and lay a foundation for further functional studies of the bHLH genes.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
Heat shock transcription factors(Hsfs)have important roles during plant growth and development and responses to abiotic stresses.The identification and func-tion of Hsf genes have been thoroughly studied in various he...Heat shock transcription factors(Hsfs)have important roles during plant growth and development and responses to abiotic stresses.The identification and func-tion of Hsf genes have been thoroughly studied in various herbaceous plant species,but not woody species,especially Phoebe bournei,an endangered,unique species in China.In this study,17 members of the Hsf gene family were identi-fied from P.bournei using bioinformatic methods.Phyloge-netic analysis indicated that PbHsf genes were grouped into three subfamilies:A,B,and C.Conserved motifs,three-dimensional structure,and physicochemical properties of the PbHsf proteins were also analyzed.The structure of the PbHsf genes varied in the number of exons and introns.Pre-diction of cis-acting elements in the promoter region indi-cated that PbHsf genes are likely involved in responses to plant hormones and stresses.A collinearity analysis dem-onstrated that expansions of the PbHsf gene family mainly take place via segmental duplication.The expression levels of PbHsf genes varied across different plant tissues.On the basis of the expression profiles of five representative PbHsf genes during heat,cold,salt,and drought stress,PbHsf pro-teins seem to have multiple functions depending on the type of abiotic stress.This systematic,genome-wide investigation of PbHsf genes in P.bournei and their expression patterns provides valuable insights and information for further func-tional dissection of Hsf proteins in this endangered,unique species.展开更多
Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and mortality.The MMP family assumes a crucial role in tumor invasion and metastasis.This study aimed to uncover...Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and mortality.The MMP family assumes a crucial role in tumor invasion and metastasis.This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma(KIRC)through a comprehensive approach encompassing both computational and molecular analyses.STRING,Cytoscape,UALCAN,GEPIA,OncoDB,HPA,cBioPortal,GSEA,TIMER,ENCORI,DrugBank,targeted bisulfite sequencing(bisulfite-seq),conventional PCR,Sanger sequencing,and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC.By performing STRING and Cytohubba analyses of the 24 MMP gene family members,MMP2(matrix metallopeptidase 2),MMP9(matrix metallopeptidase 9),MMP12(matrix metallopeptidase 12),and MMP16(matrix metallopeptidase 16)genes were denoted as hub genes having highest degree scores.After analyzing MMP2,MMP9,MMP12,and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines,interestingly,all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls.The notable effect of the up-regulated MMP2,MMP9,MMP12,and MMP16 was also documented on the overall survival(OS)of the KIRC patients.Moreover,targeted bisulfite-sequencing(bisulfite-seq)analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes(MMP2,MMP9,MMP12,and MMP16).In addition to this,hub genes were involved in various diverse oncogenic pathways.The MMP gene family members(MMP2,MMP9,MMP12,and MMP16)may serve as therapeutic targets and prognostic biomarkers in KIRC.展开更多
This paper presents a new approach to the selection of new product family development. First,the factors are discussed that contribute to the new product family development. Due to the vagueness and uncertain existing...This paper presents a new approach to the selection of new product family development. First,the factors are discussed that contribute to the new product family development. Due to the vagueness and uncertain existing in the factors,the fuzzy continue-semantic scale is introduced. Then,the fuzzy analytic hierarchy process (AHP) has been used in weighting the importance of the factors. Next,the fuzzy clustering method is applied to the selection of new product family developments. Lostly,one case is provided to illustrate the proposed approach.展开更多
Sesame(Sesamum indicum L.)is an ancient oilseed crop of the Pedaliaceae family with high oil content and potential health benefits.SHI RELATED SEQUENCE(SRS)proteins are the transcription factors(TFs)specific to plants...Sesame(Sesamum indicum L.)is an ancient oilseed crop of the Pedaliaceae family with high oil content and potential health benefits.SHI RELATED SEQUENCE(SRS)proteins are the transcription factors(TFs)specific to plants that contain RING-like zinc finger domain and are associated with the regulation of several physiological and biochemical processes.They also play vital roles in plant growth and development such as root formation,leaf development,floral development,hormone biosynthesis,signal transduction,and biotic and abiotic stress responses.Nevertheless,the SRS gene family was not reported in sesame yet.In this study,identification,molecular characterization,phylogenetic relationship,cis-acting regulatory elements,protein-protein interaction,syntenic relationship,duplication events and expression pattern of SRS genes were analyzed in S.indicum.We identified total six SiSRS genes on seven different linkage groups in the S.indicum genome by comparing with the other species,including the model plant Arabidopsis thaliana.The SiSRS genes showed variation in their structure like2–5 exons and 1–4 introns.Like other species,SiSRS proteins also contained‘RING-like zinc finger'and‘LRP1'domains.Then,the SiSRS genes were clustered into subclasses via phylogenetic analysis with proteins of S.indicum,A.thaliana,and some other plant species.The cis-acting regulatory elements analysis revealed that the promoter region of SiSRS4(SIN_1011561)showed the highest 13 and 16 elements for light-and phytohormone-responses whereas,SiSRS1(SIN_1015187)showed the highest 15 elements for stress-response.The ABREs,or ABA-responsive elements,were found in a maximum of 8 copies in the SiSRS3(SIN 1009100).Moreover,the available RNA-seq based expression of SiSRS genes revealed variation in expression patterns between stress-treated and non-treated samples,especially in drought and salinity conditions in.S.indicum.Two SiSRS genes like SiSRS1(SIN_1015187)and SiSRS5(SIN_1021065),also exhibited variable expression patterns between control vs PEG-treated sesame root samples and three SiSRS genes,including SiSRS1(SIN_1015187),SiSRS2(SIN_1003328)and SiSRS5(SIN_1021065)were responsive to salinity treatments.The present outcomes will encourage more research into the gene expression and functionality analysis of SiSRS genes in S.indicum and other related species.展开更多
In plants,the lysine and histidine transporter(LHT)family represent a class of proteins that mediate the uptake,translocation,and utilization of amino acids.The tea plant(Camellia sinensis)is a perennial evergreen wit...In plants,the lysine and histidine transporter(LHT)family represent a class of proteins that mediate the uptake,translocation,and utilization of amino acids.The tea plant(Camellia sinensis)is a perennial evergreen with a relatively high level of amino acids.However,systematic identification and molecular characterization of the LHT gene family has rarely been reported in tea plants.In this study,22 CsLHTs were identified from the‘Shuchazao’genome and classified into two groups.The modeled three-dimensional structure and the conserved domains presented a high similarity among the LHTs proteins.Moreover,it was predicted that a few genes were conserved through the analysis of the physiochemical characters,structures and cis-elements in promoters.The expression patterns in tea plants revealed that CsLHT7 was mainly expressed in the roots,and CsLHT4 and CsLHT11 exhibited relatively high expression in both the roots and leaves.Moreover,the expression of all three genes could be induced by organic nitrogen.Additionally,heterogeneous expression of CsLHT4,CsLHT7 and CsLHT11 in Arabidopsis thaliana decreased the aerial parts biomass compared with that in WT plants while significantly increased the rosette biomass only for CsLHT11transgenic plants versus WT plants.Overall,our results provide fundamental information about CsLHTs and potential genes in N utilization for further analysis in tea plants.展开更多
This paper addresses some key issues in supporting product family design in a 3 D CAD/ PDM integrated system and introduces the techniques developed or adopted in building the integrated system. The general architectu...This paper addresses some key issues in supporting product family design in a 3 D CAD/ PDM integrated system and introduces the techniques developed or adopted in building the integrated system. The general architecture of a 3D CAD/PDM integrated system is organized as five tiers. Multi-agent technology is applied with a collaborative design environment. The rule-based product family architecture ( PFA ) and tabular layouts of article characteristics (TLAC) technique are applied to represent the knowledge for product families. They make the knowledge understandable, simplified and can be exchanged among heterogeneous information systems. A transparently concentric integrated mode is put forward to enable the heterogeneous processes to interact and communicate regardless of the language used to construct each process. With the mode, function calling and information exchanging among different processes are carried out via message translation/parse approach. Currently, the integrated system is implemented in the platform of Windows NT and 2000.展开更多
Grapes,one of the oldest tree species globally,are rich in vitamins.However,environmental conditions such as low temperature and soil salinization significantly affect grape yield and quality.The glutamate receptor(GLR...Grapes,one of the oldest tree species globally,are rich in vitamins.However,environmental conditions such as low temperature and soil salinization significantly affect grape yield and quality.The glutamate receptor(GLR)family,comprising highly conserved ligand-gated ion channels,regulates plant growth and development in response to stress.In this study,11 members of the VvGLR gene family in grapes were identified using whole-genome sequence analysis.Bioinformatic methods were employed to analyze the basic physical and chemical properties,phylogenetic trees,conserved domains,motifs,expression patterns,and evolutionary relationships.Phylogenetic and collinear analyses revealed that the VvGLRs were divided into three subgroups,showing the high conservation of the grape GLR family.These members exhibited 2 glutamate receptor binding regions(GABAb and GluR)and 3-4 transmembrane regions(M1,M2,M3,and M4).Real-time quantitative PCR analysis demonstrated the sensitivity of all VvGLRs to low temperature and salt stress.Subsequent localization studies in Nicotiana tabacum verified that VvGLR3.1 and VvGLR3.2 proteins were located on the cell membrane and cell nucleus.Additionally,yeast transformation experiments confirmed the functionality of VvGLR3.1 and VvGLR3.2 in response to low temperature and salt stress.Thesefindings highlight the significant role of the GLR family,a highly conserved group of ion channels,in enhancing grape stress resistance.This study offers new insights into the grape GLR gene family,providing fundamental knowledge for further functional analysis and breeding of stress-resistant grapevines.展开更多
BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC...BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.展开更多
Lorenz systems family unifying Lorenz system, Chen system and Lü system is a typical chaotic family. In this paper, we consider impulsive control Lorenz chaotic systems family with time-varying impulse intervals....Lorenz systems family unifying Lorenz system, Chen system and Lü system is a typical chaotic family. In this paper, we consider impulsive control Lorenz chaotic systems family with time-varying impulse intervals. By establishing an effective tool of a set of inequalities, we analyze the asymptotic stability of impulsive control Lorenz systems family and obtain some new less conservative conditions. Based on the stability analysis, we design a novel impulsive controller with time-varying impulse intervals. Illustrative examples are provided to show the feasibility and effectiveness of our method. The obtained results not only can be used to design impulsive control for Lorenz systems family, but also can be extended to other chaotic systems.展开更多
Reform of the corn stockpiling policy is a key initiative for advancing China's market-based grain stockpiling reform. It is a critical component of China's exploration of a price formation mechanism for agric...Reform of the corn stockpiling policy is a key initiative for advancing China's market-based grain stockpiling reform. It is a critical component of China's exploration of a price formation mechanism for agricultural products. Evaluating the effectiveness of such reform is therefore of great relevance. Based on nationwide farm monitoring data of 2014, 2015 and 2016, this paper examines the effects of the corn stockpiling reform on the decision of family farms to join cooperatives. Our finding suggests that after other factors that influence the decision of family farms to join cooperatives are controlled for, the probability of corn farms to join cooperatives in the Northeast and Inner Mongolia, where the corn stockpiling reform was carried out in 2016, is significantly higher compared with the probability of corn farms in non-reform areas that did so. The reason is that after the reform, corn producers must sell their corn to the market instead of to the State, bringing them sales problems, which could be mitigated to some extent by joining cooperatives.Thus, the corn stockpiling reform incentivized the market-based behavior of agricultural producers, giving play to the role of market mechanisms in regulating production and demand.展开更多
Overall socio-economic development of urban and rural areas and laying solid foundation for agricultural and rural development are closely connected with sustainable development of family enterprises of feed and veter...Overall socio-economic development of urban and rural areas and laying solid foundation for agricultural and rural development are closely connected with sustainable development of family enterprises of feed and veterinary drugs.This paper analyzed evolution stages and three-ring administration mode of family enterprises of feed and veterinary drugs and discussed the inevitable requirement for introducing perfect professional manager system.展开更多
In recent years, with the rapid development of the tourist industry, world heritage sites become more and more popular among tourists from home and abroad. Therefore, heritage tourism has become a new hotspot. However...In recent years, with the rapid development of the tourist industry, world heritage sites become more and more popular among tourists from home and abroad. Therefore, heritage tourism has become a new hotspot. However, while world heri- tage sites are making obvious economic benefit from tourism, they also bring various problems and contradictions, of which the most troublesome one is the contradiction between heritage con- servation and tourism development. To discuss and analyze the root and the essence of the above contradiction and find a way to bring about harmony between them is an important program faced by our national heritage management practice and academic re- search. Based on the case of cleaning the Temple and Cemetery of Confucius and the Kong Family Mansion in Qufu, this paper ana- lyzes the reasons why our national world cultural heritage sites bring about the above contradiction in the process of tourism development and points out that the improper system and stake- holders’ benefit imbroglio are respectively the root and the es- sence of the contraction. Then, it also puts forward corresponding solutions.展开更多
BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has sho...BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.展开更多
Traditional surname syster and the idea regarding men as superior to women have ruled Chinese society for thousands of years and caused the occurrence of many tragic events in Chinese history and even now.These ideas ...Traditional surname syster and the idea regarding men as superior to women have ruled Chinese society for thousands of years and caused the occurrence of many tragic events in Chinese history and even now.These ideas sti1l shack1e some people's minds.展开更多
Objective: To inquire into the effect of systematic family nursing guidance on improving the Quality of Life for elderly patients with implanted cardiac pacemaker. Methods: 41 elderly patients in accordance with the c...Objective: To inquire into the effect of systematic family nursing guidance on improving the Quality of Life for elderly patients with implanted cardiac pacemaker. Methods: 41 elderly patients in accordance with the corresponding requirements were studied after offering systematic family nursing guidance and surveyed through the questionnaires about the QOL (quality of life) respectively 1 month, 3 months and 6 months after leaving hospital. Results: Compared with that of 1 month and 3 months after the operation, the questionnaire scores for 6 months after the operation were found to have significant improvement, and the differences were statistically significant. Conclusion: Systematic family nursing guidance can effectively improve the QOL for elderly patients with implanted cardiac pacemaker, which makes them spend their old age in comfort and happiness.展开更多
The highest morbidity and mortality in the world are attributed to digestive system tumors,such as stomach cancer,liver cancer,and pancreatic cancer.Exploring potential biomarkers is a crucial direction of tumor resea...The highest morbidity and mortality in the world are attributed to digestive system tumors,such as stomach cancer,liver cancer,and pancreatic cancer.Exploring potential biomarkers is a crucial direction of tumor research.We use bioinformatics methods to explore potential biomarkers of the digestive system.Mining and analyzing data from Gene Expression Profiling Interactive Analysis(GEPIA),Kaplan-Meier,cBioPortal,and Metabolic gEne RApid Visualizer(MERAV)to explore the correlation between IGF2BP(insulin-like growth factor-2 mRNA-binding protein)family expression and immune infiltration in digestive system tumors,and further probe the prognostic value of IGF2BP family in digestive system tumors.Esophageal cancer tissues showed a significantly higher expression of IGF2BP2 than normal tissues,while IGF2BP3 was notably more expressed in esophageal cancer,pancreatic cancer,and stomach cancer.In the prognosis evaluation,the IGF2BP1 gene in patients with liver cancer and the IGF2BP2 and IGF2BP3 genes in patients with stomach cancer and liver cancer of the low gene expression level groups were better.Multivariate COX regression analysis further suggested that tumor stage,CD8 positive T cells,macrophages,dendritic cell infiltration,and IGF2BP3 expression were independent risk factors affecting the prognosis of patients with stem cell liver cancer.The IGF2BP family may be a potential marker for immunotherapy and the prognosis of digestive system tumors.展开更多
基金the National Natural Science Foundation of China,No.81171859the Natural Science Foundation of Chongqing,No.cstc2012jjA10058the Chongqing Health Bureau Project,No.2011-2-172
文摘Neural cell differentiation and maturation is a critical step during central nervous system devel-opment. The oligodendrocyte transcription family (Olig family) is known to be an important factor in regulating neural cell differentiation. Because of this, the Olig family also affects acute and chronic central nervous system diseases, including brain injury, multiple sclerosis, and even gliomas. Improved understanding about the functions of the Olig family in central nervous system development and disease will greatly aid novel breakthroughs in central nervous system diseases. This review investigates the role of the Olig family in central nervous system develop- ment and related diseases.
基金financially supported by National Key R&D Program of China (Grant No. 2019YFD1001500)National Natural Science Foundation of China (Grant No. 31700619)+1 种基金Nature Science Foundation of Hubei Province (Grant No. 2019CFB504)the Fundamental Research Funds for the Central Universities (Grant No. 2662020YLPY006)
文摘The basic helix-loop-helix(bHLH)transcription factor family is the second-largest family in plants,where it plays essential roles in development,and the responses to multiple abiotic and biotic stressors.However,little information is available about this gene family in Prunus mume,which is widely cultivated in East Asia as an ornamental fruit tree.Here,100 PmbHLH genes were identified,and their evolution and functions were explored in P.mume for the first time.The PmbHLH genes were classified into 21 subfamilies.The chromosomal distribution,physicochemical properties,bHLH domain,conserved motif,and intron/exon compositions were also analyzed.Furthermore,the evolutionary pattern,divergence time of the PmbHLH family,and genetic relationships among P.mume,Arabidopsis thaliana,and Prunus persica and Fragaria vesca of Rosaceae were explored.The functional prediction analysis of these PmbHLHs indicated that their functions varied,and included participating in the formation of organs and tissues,responding to stress,and the biosynthesis and metabolism of hormones and other secondary metabolites.Interestingly,expression analyses of PmbHLHs also revealed diverse expression patterns.Most of the PmbHLH genes were highly expressed in roots and stems,and a few were highly expressed in leaves,buds,and fruits,indicating tissue expression specificity.Eight PmbHLH genes,which were upregulated during low-temperature stress,may have critical roles in the response to cold stress.Ten PmbHLHs were differentially expressed between weeping and upright branches in a P.mume F_(1) population.These results shed light on the structure and evolution of the PmbHLH gene family,and lay a foundation for further functional studies of the bHLH genes.
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
基金supported by the Fujian Province Seed Industry Innovation and Industrialization Project“Innovation and Industrialization Development of Precious Tree Seed Industries(Phoebe bornei)”(ZYCX-LY-202102)the Sub-project of National Key R&D Program“Phoebe bornei Efficient Cultivation Technology”(2016YFD0600603-2).
文摘Heat shock transcription factors(Hsfs)have important roles during plant growth and development and responses to abiotic stresses.The identification and func-tion of Hsf genes have been thoroughly studied in various herbaceous plant species,but not woody species,especially Phoebe bournei,an endangered,unique species in China.In this study,17 members of the Hsf gene family were identi-fied from P.bournei using bioinformatic methods.Phyloge-netic analysis indicated that PbHsf genes were grouped into three subfamilies:A,B,and C.Conserved motifs,three-dimensional structure,and physicochemical properties of the PbHsf proteins were also analyzed.The structure of the PbHsf genes varied in the number of exons and introns.Pre-diction of cis-acting elements in the promoter region indi-cated that PbHsf genes are likely involved in responses to plant hormones and stresses.A collinearity analysis dem-onstrated that expansions of the PbHsf gene family mainly take place via segmental duplication.The expression levels of PbHsf genes varied across different plant tissues.On the basis of the expression profiles of five representative PbHsf genes during heat,cold,salt,and drought stress,PbHsf pro-teins seem to have multiple functions depending on the type of abiotic stress.This systematic,genome-wide investigation of PbHsf genes in P.bournei and their expression patterns provides valuable insights and information for further func-tional dissection of Hsf proteins in this endangered,unique species.
基金The authors would like to extend their sincere appreciation to the Researchers Supporting Project Number(RSP2023R457),King Saud University,Riyadh,Saudi Arabia.
文摘Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and mortality.The MMP family assumes a crucial role in tumor invasion and metastasis.This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma(KIRC)through a comprehensive approach encompassing both computational and molecular analyses.STRING,Cytoscape,UALCAN,GEPIA,OncoDB,HPA,cBioPortal,GSEA,TIMER,ENCORI,DrugBank,targeted bisulfite sequencing(bisulfite-seq),conventional PCR,Sanger sequencing,and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC.By performing STRING and Cytohubba analyses of the 24 MMP gene family members,MMP2(matrix metallopeptidase 2),MMP9(matrix metallopeptidase 9),MMP12(matrix metallopeptidase 12),and MMP16(matrix metallopeptidase 16)genes were denoted as hub genes having highest degree scores.After analyzing MMP2,MMP9,MMP12,and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines,interestingly,all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls.The notable effect of the up-regulated MMP2,MMP9,MMP12,and MMP16 was also documented on the overall survival(OS)of the KIRC patients.Moreover,targeted bisulfite-sequencing(bisulfite-seq)analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes(MMP2,MMP9,MMP12,and MMP16).In addition to this,hub genes were involved in various diverse oncogenic pathways.The MMP gene family members(MMP2,MMP9,MMP12,and MMP16)may serve as therapeutic targets and prognostic biomarkers in KIRC.
文摘This paper presents a new approach to the selection of new product family development. First,the factors are discussed that contribute to the new product family development. Due to the vagueness and uncertain existing in the factors,the fuzzy continue-semantic scale is introduced. Then,the fuzzy analytic hierarchy process (AHP) has been used in weighting the importance of the factors. Next,the fuzzy clustering method is applied to the selection of new product family developments. Lostly,one case is provided to illustrate the proposed approach.
文摘Sesame(Sesamum indicum L.)is an ancient oilseed crop of the Pedaliaceae family with high oil content and potential health benefits.SHI RELATED SEQUENCE(SRS)proteins are the transcription factors(TFs)specific to plants that contain RING-like zinc finger domain and are associated with the regulation of several physiological and biochemical processes.They also play vital roles in plant growth and development such as root formation,leaf development,floral development,hormone biosynthesis,signal transduction,and biotic and abiotic stress responses.Nevertheless,the SRS gene family was not reported in sesame yet.In this study,identification,molecular characterization,phylogenetic relationship,cis-acting regulatory elements,protein-protein interaction,syntenic relationship,duplication events and expression pattern of SRS genes were analyzed in S.indicum.We identified total six SiSRS genes on seven different linkage groups in the S.indicum genome by comparing with the other species,including the model plant Arabidopsis thaliana.The SiSRS genes showed variation in their structure like2–5 exons and 1–4 introns.Like other species,SiSRS proteins also contained‘RING-like zinc finger'and‘LRP1'domains.Then,the SiSRS genes were clustered into subclasses via phylogenetic analysis with proteins of S.indicum,A.thaliana,and some other plant species.The cis-acting regulatory elements analysis revealed that the promoter region of SiSRS4(SIN_1011561)showed the highest 13 and 16 elements for light-and phytohormone-responses whereas,SiSRS1(SIN_1015187)showed the highest 15 elements for stress-response.The ABREs,or ABA-responsive elements,were found in a maximum of 8 copies in the SiSRS3(SIN 1009100).Moreover,the available RNA-seq based expression of SiSRS genes revealed variation in expression patterns between stress-treated and non-treated samples,especially in drought and salinity conditions in.S.indicum.Two SiSRS genes like SiSRS1(SIN_1015187)and SiSRS5(SIN_1021065),also exhibited variable expression patterns between control vs PEG-treated sesame root samples and three SiSRS genes,including SiSRS1(SIN_1015187),SiSRS2(SIN_1003328)and SiSRS5(SIN_1021065)were responsive to salinity treatments.The present outcomes will encourage more research into the gene expression and functionality analysis of SiSRS genes in S.indicum and other related species.
基金supported by the National Key Research and Development Program of China(Grant No.2018YFD1000600)the National Natural Science Foundation of China(Grant No.32070376)。
文摘In plants,the lysine and histidine transporter(LHT)family represent a class of proteins that mediate the uptake,translocation,and utilization of amino acids.The tea plant(Camellia sinensis)is a perennial evergreen with a relatively high level of amino acids.However,systematic identification and molecular characterization of the LHT gene family has rarely been reported in tea plants.In this study,22 CsLHTs were identified from the‘Shuchazao’genome and classified into two groups.The modeled three-dimensional structure and the conserved domains presented a high similarity among the LHTs proteins.Moreover,it was predicted that a few genes were conserved through the analysis of the physiochemical characters,structures and cis-elements in promoters.The expression patterns in tea plants revealed that CsLHT7 was mainly expressed in the roots,and CsLHT4 and CsLHT11 exhibited relatively high expression in both the roots and leaves.Moreover,the expression of all three genes could be induced by organic nitrogen.Additionally,heterogeneous expression of CsLHT4,CsLHT7 and CsLHT11 in Arabidopsis thaliana decreased the aerial parts biomass compared with that in WT plants while significantly increased the rosette biomass only for CsLHT11transgenic plants versus WT plants.Overall,our results provide fundamental information about CsLHTs and potential genes in N utilization for further analysis in tea plants.
基金This paper is supported by National High-Tech Research and Development Plan Foundation in China(2005AA4Z3060) and Electronic Development Fund in 2003.
文摘This paper addresses some key issues in supporting product family design in a 3 D CAD/ PDM integrated system and introduces the techniques developed or adopted in building the integrated system. The general architecture of a 3D CAD/PDM integrated system is organized as five tiers. Multi-agent technology is applied with a collaborative design environment. The rule-based product family architecture ( PFA ) and tabular layouts of article characteristics (TLAC) technique are applied to represent the knowledge for product families. They make the knowledge understandable, simplified and can be exchanged among heterogeneous information systems. A transparently concentric integrated mode is put forward to enable the heterogeneous processes to interact and communicate regardless of the language used to construct each process. With the mode, function calling and information exchanging among different processes are carried out via message translation/parse approach. Currently, the integrated system is implemented in the platform of Windows NT and 2000.
基金This research was funded by the Natural Science Foundation of Shandong Province of China(ZR2022MC144).
文摘Grapes,one of the oldest tree species globally,are rich in vitamins.However,environmental conditions such as low temperature and soil salinization significantly affect grape yield and quality.The glutamate receptor(GLR)family,comprising highly conserved ligand-gated ion channels,regulates plant growth and development in response to stress.In this study,11 members of the VvGLR gene family in grapes were identified using whole-genome sequence analysis.Bioinformatic methods were employed to analyze the basic physical and chemical properties,phylogenetic trees,conserved domains,motifs,expression patterns,and evolutionary relationships.Phylogenetic and collinear analyses revealed that the VvGLRs were divided into three subgroups,showing the high conservation of the grape GLR family.These members exhibited 2 glutamate receptor binding regions(GABAb and GluR)and 3-4 transmembrane regions(M1,M2,M3,and M4).Real-time quantitative PCR analysis demonstrated the sensitivity of all VvGLRs to low temperature and salt stress.Subsequent localization studies in Nicotiana tabacum verified that VvGLR3.1 and VvGLR3.2 proteins were located on the cell membrane and cell nucleus.Additionally,yeast transformation experiments confirmed the functionality of VvGLR3.1 and VvGLR3.2 in response to low temperature and salt stress.Thesefindings highlight the significant role of the GLR family,a highly conserved group of ion channels,in enhancing grape stress resistance.This study offers new insights into the grape GLR gene family,providing fundamental knowledge for further functional analysis and breeding of stress-resistant grapevines.
文摘BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.
基金supported by the Key Project of the Ministry of Education under Grant No.107099the Key Youth Science and Technology Foundation of University of Electronic Science and Technology of China under Grant No.L08010201JX0720
文摘Lorenz systems family unifying Lorenz system, Chen system and Lü system is a typical chaotic family. In this paper, we consider impulsive control Lorenz chaotic systems family with time-varying impulse intervals. By establishing an effective tool of a set of inequalities, we analyze the asymptotic stability of impulsive control Lorenz systems family and obtain some new less conservative conditions. Based on the stability analysis, we design a novel impulsive controller with time-varying impulse intervals. Illustrative examples are provided to show the feasibility and effectiveness of our method. The obtained results not only can be used to design impulsive control for Lorenz systems family, but also can be extended to other chaotic systems.
基金a result of the First-Class Discipline Development Project of Guizhou University for Agricultural and Forestry Economic Management in Guizhou Province,2017(Project No.:GNYL[2017]002)the Project of the National Social Science Foundation of China(NSS)"Summary of the Experiences of the Reform of Separate Ownership,Contract and Operation Rights of Agricultural Land in China and Evaluation of Implementation Effects"(Project No.:17BJY010)the key research project of the Ministry of Education "Study on the Separate Ownership,Contract and Operation Rights of Agricultural Land"(Project No.:16JZD024)
文摘Reform of the corn stockpiling policy is a key initiative for advancing China's market-based grain stockpiling reform. It is a critical component of China's exploration of a price formation mechanism for agricultural products. Evaluating the effectiveness of such reform is therefore of great relevance. Based on nationwide farm monitoring data of 2014, 2015 and 2016, this paper examines the effects of the corn stockpiling reform on the decision of family farms to join cooperatives. Our finding suggests that after other factors that influence the decision of family farms to join cooperatives are controlled for, the probability of corn farms to join cooperatives in the Northeast and Inner Mongolia, where the corn stockpiling reform was carried out in 2016, is significantly higher compared with the probability of corn farms in non-reform areas that did so. The reason is that after the reform, corn producers must sell their corn to the market instead of to the State, bringing them sales problems, which could be mitigated to some extent by joining cooperatives.Thus, the corn stockpiling reform incentivized the market-based behavior of agricultural producers, giving play to the role of market mechanisms in regulating production and demand.
基金Supported by Project of Business Management Cultivation Discipline in Department of Business and Trade,Southwest University Rongchang Campus(RCQG207001)
文摘Overall socio-economic development of urban and rural areas and laying solid foundation for agricultural and rural development are closely connected with sustainable development of family enterprises of feed and veterinary drugs.This paper analyzed evolution stages and three-ring administration mode of family enterprises of feed and veterinary drugs and discussed the inevitable requirement for introducing perfect professional manager system.
文摘In recent years, with the rapid development of the tourist industry, world heritage sites become more and more popular among tourists from home and abroad. Therefore, heritage tourism has become a new hotspot. However, while world heri- tage sites are making obvious economic benefit from tourism, they also bring various problems and contradictions, of which the most troublesome one is the contradiction between heritage con- servation and tourism development. To discuss and analyze the root and the essence of the above contradiction and find a way to bring about harmony between them is an important program faced by our national heritage management practice and academic re- search. Based on the case of cleaning the Temple and Cemetery of Confucius and the Kong Family Mansion in Qufu, this paper ana- lyzes the reasons why our national world cultural heritage sites bring about the above contradiction in the process of tourism development and points out that the improper system and stake- holders’ benefit imbroglio are respectively the root and the es- sence of the contraction. Then, it also puts forward corresponding solutions.
基金Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects,No.Z202000962023 Guangxi University Young and Middle-Aged Teachers’Basic Research Ability Improvement Project,No.2023KY0091+1 种基金National Natural Science Foundation of China,No.82260241the Natural Science Foundation of Guangxi Province,No.2015GXNSFAA139171 and No.2020GXNSFAA259053.
文摘BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.
文摘Traditional surname syster and the idea regarding men as superior to women have ruled Chinese society for thousands of years and caused the occurrence of many tragic events in Chinese history and even now.These ideas sti1l shack1e some people's minds.
文摘Objective: To inquire into the effect of systematic family nursing guidance on improving the Quality of Life for elderly patients with implanted cardiac pacemaker. Methods: 41 elderly patients in accordance with the corresponding requirements were studied after offering systematic family nursing guidance and surveyed through the questionnaires about the QOL (quality of life) respectively 1 month, 3 months and 6 months after leaving hospital. Results: Compared with that of 1 month and 3 months after the operation, the questionnaire scores for 6 months after the operation were found to have significant improvement, and the differences were statistically significant. Conclusion: Systematic family nursing guidance can effectively improve the QOL for elderly patients with implanted cardiac pacemaker, which makes them spend their old age in comfort and happiness.
基金from any funding agency in the public,commercial,or not-for-profit sectors.
文摘The highest morbidity and mortality in the world are attributed to digestive system tumors,such as stomach cancer,liver cancer,and pancreatic cancer.Exploring potential biomarkers is a crucial direction of tumor research.We use bioinformatics methods to explore potential biomarkers of the digestive system.Mining and analyzing data from Gene Expression Profiling Interactive Analysis(GEPIA),Kaplan-Meier,cBioPortal,and Metabolic gEne RApid Visualizer(MERAV)to explore the correlation between IGF2BP(insulin-like growth factor-2 mRNA-binding protein)family expression and immune infiltration in digestive system tumors,and further probe the prognostic value of IGF2BP family in digestive system tumors.Esophageal cancer tissues showed a significantly higher expression of IGF2BP2 than normal tissues,while IGF2BP3 was notably more expressed in esophageal cancer,pancreatic cancer,and stomach cancer.In the prognosis evaluation,the IGF2BP1 gene in patients with liver cancer and the IGF2BP2 and IGF2BP3 genes in patients with stomach cancer and liver cancer of the low gene expression level groups were better.Multivariate COX regression analysis further suggested that tumor stage,CD8 positive T cells,macrophages,dendritic cell infiltration,and IGF2BP3 expression were independent risk factors affecting the prognosis of patients with stem cell liver cancer.The IGF2BP family may be a potential marker for immunotherapy and the prognosis of digestive system tumors.