The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent year...The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.展开更多
Background:Ischemic stroke(IS)is a global health issue and the current treatment options for IS are inadequate.Buyang Huanwu decoction(BHD)has demonstrated effectiveness in treating IS.However,the mechanisms by which ...Background:Ischemic stroke(IS)is a global health issue and the current treatment options for IS are inadequate.Buyang Huanwu decoction(BHD)has demonstrated effectiveness in treating IS.However,the mechanisms by which BHD treats IS remain unclear,and no studies have been conducted to analyze these mechanisms from the perspective of Cuproptosis.In order to investigate the potential of BHD to intervene in IS through Cuproptosis,this study employed a systematic pharmacological approach and molecular docking verification.Methods:To investigate the mechanism of BHD in treating IS through Cuproptosis,relevant information on the structure,targets,and major biological functions and pathways of compounds related to BHD was collected from databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were then visualized using Cytoscape3.6.1,Ledock,and pymol software.Results:BHD is composed of 7 Chinese medicines,which contain 82 compounds,including 10 core compounds.These compounds are associated with 241 genes,of which 97 are common to BHD,IS,and Cuproptosis.The 97 common genes,including 10 core genes,are involved in biological processes such as proteolysis,regulation of apoptosis and cholesterol storage,as well as cellular components and molecular functions.The common genes among BHD,IS,and Cuproptosis,including 10 core genes,participate mainly in Kyoto Encyclopedia of Genes and Genomes pathways such as pathways in cancer,PI3K-Akt signaling pathway,and Estrogen signaling pathway.According to molecular docking results,linolenic acid showed good docking scores with 9 out of 10 core genes,except for SRC.13-hydroxy-9,11-octadecadienoic acid also demonstrated good docking scores with EGFR,MAPK14,and F2.Similarly,senkyunone also had good docking scores with EGFR,MAPK14,and F2,all of which had docking energy greater than−5 kcal.Conclusion:In this study,the potential of BHD for treating IS through Cuproptosis and its underlying mechanisms were explored and partially validated through molecular docking.However,due to the limitations of the systems pharmacology research method,further validation through cell experiments,animal experiments,and clinical trials may be necessary to confirm these findings.展开更多
Background:Prior research has established a strong link between cerebral aneurysm(CA)occurrence and inflammation.Tea intake(TI)has been found to have anti-inflammatory properties through multiple mechanisms,potentiall...Background:Prior research has established a strong link between cerebral aneurysm(CA)occurrence and inflammation.Tea intake(TI)has been found to have anti-inflammatory properties through multiple mechanisms,potentially lowering CA incidence.This study aims to employ Mendelian Randomization(MR)methodology to explore the genetic causality between TI and CA.Methods:We collected Genome-wide association study(GWAS)data for CA,TI,Green tea intake(GTI),Herbal tea intake(HTI),and Rooibos tea intake(RTI).The MR analysis employed the TwoSampleMR package and utilized the inverse variance-weighted(IVW)method.Results:The findings suggest no genetic causal relationship between TI and CA(IVW:OR=1.10,95%CI:0.59–2.05,P=0.772).Similarly,there is no genetic causal association between GTI and CA(IVW:OR=1.07,95%CI:0.91–1.26,P=0.388),HTI and CA(IVW:OR=1.00,95%CI:0.89–1.13,P=0.943),or RTI and CA(IVW:OR=1.02,95%CI:0.96–1.09,P=0.472).Conclusion:There is no genetic causal relationship between TI and CA,and the different types of tea do not change this result.Further MR analysis is needed to investigate whether there is a potential genetic causal association between the quantity of TI and CA.展开更多
Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is ...Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment.This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment,with preliminary validation conducted through molecular docking.Methods:Information on the structure,targets,main biological functions,and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were visualized using software such as Cytoscape 3.6.1,Ledock,and pymol.Results:We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases,and GeneCards database was used to search 3350 IS-related gene targets,including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS.Enrichment analysis of these 78 targets using gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed the involvement of 48 GO terms in the treatment of IS,mainly in biological processes such as metabolism,biological regulation,and stress response.The composition of biological devices such as supercavitary membrane,cell fluid,and extracellular space was also involved.The biological functions mainly included protein binding,ion binding,hydrolytic enzyme activity,and others.The identified pathways were estrogen signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-AKT signaling pathway,RAP1 signaling pathway,P53 signaling pathway,PPAR signaling pathway,FOXO signaling pathway,RAS signaling pathway,prolactin signaling pathway,HIF-1 signaling pathway,and TNF signaling pathway.Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets.Conclusion:Through the application of network pharmacology methods,it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways,involving several crucial compounds and genes.Nevertheless,additional in vitro and in vivo studies are needed to verify these findings.展开更多
AIM:To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). METHODS:Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univari...AIM:To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). METHODS:Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined asP < 0.05. RESULTS:The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage Ⅲ CRC (P < 0.0001). We divided 341 stage Ⅲ patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups:LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001). CONCLUSION:The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage Ⅲ CRC patients.展开更多
Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled geno...Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled genome is essential for understanding the genetic features and biology of this animal. In this study, we used long-read single-molecule sequencing and high-throughput chromosome conformation capture (Hi-C) technology to obtain a high-qualitychromosome-scale scaffolding of the Chinese tree shrew genome. The new reference genome (KIZ version 2: TS_2.0) resolved problems in presently available tree shrew genomes and enabled accurate identification of large and complex repeat regions, gene structures, and species-specific genomic structural variants. In addition, by sequencing the genomes of six Chinese tree shrew individuals, we produced a comprehensive map of 12.8 M single nucleotide polymorphisms and confirmed that the major histocompatibility complex (MHC) loci and immunoglobulin gene family exhibited high nucleotide diversity in the tree shrew genome. We updated the tree shrew genome database (TreeshrewDB v2.0: http://www.treeshrewdb.org) to include the genome annotation information and genetic variations. The new high-quality reference genome of the Chinese tree shrew and the updated TreeshrewDB will facilitate the use of this animal in many different fields of research.展开更多
Gold films deposited by direct current magnetron sputtering are used for synchrotron radiation optics. In this study, the microstructure and surface roughness of gold films were investigated for the purpose of develop...Gold films deposited by direct current magnetron sputtering are used for synchrotron radiation optics. In this study, the microstructure and surface roughness of gold films were investigated for the purpose of developing high-reflectivity mirrors. The deposition process was first optimized. Films were fabricated at different sputtering powers (15, 40, 80, and 120 W) and characterized using grazing incidence X-ray reflectometry, X-ray diffraction, and atomic force microscopy. The results showed that all the films were highly textured, having a dominant Au (111) orientation, and the film deposited at 80 W had the lowest surface roughness. Subsequently, post-deposition annealing from 100 to 200℃ in a vacuum was performed on the films deposited at 80 W to investigate the effect of annealing on the microstructure and surface roughness of the films. The grain size, surface roughness, and their relationship were investigated as a function of annealing temperature. AFM and XRD results revealed that at annealing temperatures of 175 ℃ and below, microstructural change of the films was mainly manifested by the elimination of voids. At annealing temperatures higher than 175℃, grain coalescence occurred in addition to the void elimination, causing the surface roughness to increase.展开更多
In pig-to-human xenotransplantation,the transmission risk of porcine endogenous retroviruses(PERVs)is of great concern.However,the distribution of PERVs in pig genomes,their genetic variation among Eurasian pigs,and t...In pig-to-human xenotransplantation,the transmission risk of porcine endogenous retroviruses(PERVs)is of great concern.However,the distribution of PERVs in pig genomes,their genetic variation among Eurasian pigs,and their evolutionary history remain unclear.We scanned PERVs in the current pig reference genome(assembly Build 11.1),and identified 36 long complete or near-complete PERVs(lc PERVs)and 23 short incomplete PERVs(si PERVs).Besides three known PERVs(PERV-A,-B,and-C),four novel types(PERV-JX1,-JX2,-JX3,and-JX4)were detected in this study.According to evolutionary analyses,the newly discovered PERVs were more ancient,and PERV-Bs probably experienced a bottleneck~0.5 million years ago(Ma).By analyzing63 high-quality porcine whole-genome resequencing data,we found that the PERV copy numbers in Chinese pigs were lower(32.0±4.0)than in Western pigs(49.1±6.5).Additionally,the PERV sequence diversity was lower in Chinese pigs than in Western pigs.Regarding the lc PERV copy numbers,PERV-A and-JX2 in Western pigs were higher than in Chinese pigs.Notably,Bama Xiang(BMX)pigs had the lowest PERV copy number(27.8±5.1),and a BMX individual had no PERV-C and the lowest PERV copy number(23),suggesting that BMX pigs were more suitable for screening and/or modification as xenograft donors.Furthermore,we identified 451 PERV transposon insertion polymorphisms(TIPs),of which 86 were shared by all 10 Chinese and Western pig breeds.Our findings provide systematic insights into the genomic distribution,variation,evolution,and possible biological function of PERVs.展开更多
As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveill...As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveillance systems were used to record the behavior and timing of copulations; embryos at different post-copulation stages were collected and cultured in vitro; and the developmental characteristics of both early-stage and in vitro cultured embryos were determined. A total of 163 females were collected following effective copulation, and 150 were used in either unilateral or bilateral oviduct embryo collections, with 307 embryos from 111 females obtained (conception rate=74%). Among them, 237 embryos were collected from 78 females, bilaterally, i.e., the average embryo number per female was 3.04; 172 fertilized eggs collected from 55 females, bilaterally, were cultured for 24-108 h in vitro for developmental observations; finally, 65 embryos from 23 bilateral cases and 70 embryos from 33 unilateral cases were used in embryo transplantation.展开更多
The mitochondrial unfolded protein response(UPRmt)is an evolutionarily conserved adaptive mechanism for improving cell survival under mitochondrial stress.Under physiological and pathological conditions,the UPRmt is t...The mitochondrial unfolded protein response(UPRmt)is an evolutionarily conserved adaptive mechanism for improving cell survival under mitochondrial stress.Under physiological and pathological conditions,the UPRmt is the key to maintaining intracellular homeostasis and proteostasis.Important roles of the UPRmt have been demonstrated in a variety of cell types and in cell development,metabolism,and immune processes.UPRmt dysfunction leads to a variety of pathologies,including cancer,inflammation,neurodegenerative disease,metabolic disease,and immune disease.Stem cells have a special ability to selfrenew and differentiate into a variety of somatic cells and have been shown to exist in a variety of tissues.These cells are involved in development,tissue renewal,and some disease processes.Although the roles and regulatory mechanisms of the UPRmt in somatic cells have been widely reported,the roles of the UPRmt in stem cells are not fully understood.The roles and functions of the UPRmt depend on stem cell type.Therefore,this paper summarizes the potential significance of the UPRmt in embryonic stem cells,tissue stem cells,tumor stem cells,and induced pluripotent stem cells.The purpose of this review is to provide new insights into stem cell differentiation and tumor pathogenesis.展开更多
Objective To study environment-friendly determination of azobenzene in trace amounts using β-cyclodextrin (β-CD)-modified Au electrode. Methods β-CD-modified Au electrode was fabricated with a two-step approach, ...Objective To study environment-friendly determination of azobenzene in trace amounts using β-cyclodextrin (β-CD)-modified Au electrode. Methods β-CD-modified Au electrode was fabricated with a two-step approach, and then a gold electrode modified with β-CD was used to detect azobenzene by employing Osteryoung square wave voltammetry. Results The modified electrode could detect azobenzene, showing a good linearity between the electrochemical current and concentration. Conclusion Although the electrochemical current is related with concentration, the detection limit is around 1 .0 ×10^-10 mol/L. This study may provide a new environment-friendly approach for monitoring water quality.展开更多
Objective:To clarify the material basis of Chinese medicine pair“Radix Paeoniae Rubra-Cortex Moutan”(Chishao-Mudanpi)and explore their mechanism in the treatment of ICH with network pharmacology.Methods:The active i...Objective:To clarify the material basis of Chinese medicine pair“Radix Paeoniae Rubra-Cortex Moutan”(Chishao-Mudanpi)and explore their mechanism in the treatment of ICH with network pharmacology.Methods:The active ingredients contained in Radix Paeoniae Rubra and Cortex Moutan were searched and selected based on the oral bioavailability prediction and drug-likeness prediction from the TCMSP database.Then the targets of cerebral hemorrhage were collected from GeneCards,OMIM,and DrugBank databases.After obtained the intersections of drugs and disease,the active component target disease interactive network diagram was drawn by Cytoscape software.The obtained key targets were uploaded to the STRING database for analysis and construct a PPI network map.GO function enrichment analysis and KEGG analysis were performed on the key target proteins.Results:Collected the active ingredients of Radix Paeoniae 119,Radix Paeoniae 55,including paeoniflorin,baicalin,β-sitosterol,etc.Related drug target protein 1190,ICH disease-related genes 823,"Radix Paeoniae-Radix Paeoniae"and 72 common targets of ICH,mainly acting on Akt1,IL6,VEGFA,CASP3,EGF,involving 133 related signaling pathways such as AGE-RAGE,TNF,IL-17,HIF1,PI3K-Akt.Conclusion:The combination of"Radix Paeoniae Rubra-Cortex Moutan"in the treatment of ICH has the characteristics of multiple pathways and multiple targets,which provides a reference and basis for further molecular biology verification in the future.展开更多
Objective:To investigate the inhibition effect of dexamethasone with different concentration gradients on the expression of MMP-1,-3,and-13 in a bone joint cell model of IL-1β-induced SW1353 cells.Methods:The SW1353 ...Objective:To investigate the inhibition effect of dexamethasone with different concentration gradients on the expression of MMP-1,-3,and-13 in a bone joint cell model of IL-1β-induced SW1353 cells.Methods:The SW1353 cells were placed in a culture medium containing 10^(1)-10^(8) nmol/L dexamethasone,and after 12 hours of culture,the appropriate intervention concentration range of dexamethasone was screened by the MTS for subsequent experiments.After SW1353 cells were induced with 10 ng/mL IL-1β,10^(1)-10^(7) nmol/L dexamethasone was given for intervention,and RT-PCR was used to detect the mRNA expression of MMP-1,-3,and-13.The protein was extracted after the intervention of 104 nmol/L dexamethasone,and western blot was used to detect the protein expression of MMP-1,-3,and-13.Results:MTS proliferation experiment results showed that 10^(1)-10^(7) nmol/L dexamethasone had no significant effect on SW1353 cell viability,while 10^(8) nmol/L dexamethasone had a significant inhibitory effect on SW1353(p<0.05).There was no obvious effect on cell viability after adding 10 ng/mL IL-1β.RT-PCR results indicated that the IL-1βgroup had a significant increase in the mRNA expression of MMP-1,-3,and-13 compared with the blank control group,and the difference was statistically significant(p<0.05).After intervention with 102-10^(7) nmol/L dexamethasone,MMP-1 mRNA expression decreased(p<0.05);after intervention with 103-10^(7) nmol/L dexamethasone,MMP-3 mRNA expression decreased(p<0.05);after intervention with 10-10^(7) nmol/L dexamethasone,the mRNA expression of MMP-13 decreased(p<0.05).The Western blot results showed that compared with the blank control group,the protein levels of MMP-1,-3,and-13 in the IL-1βgroup were significantly increased;the protein levels of MMP-1,-3,and-13 were significantly reduced after the intervention of 104 nmol/L dexamethasone.Conclusion:Dexamethasone can inhibit the expression of MMP1,MMP-3,and MMP-13 in the IL-1β-induced OA cell model at the mRNA and protein levels.展开更多
Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis,and the androgen receptor regulates prostate cancer(PCa)progression.It is unclear whether the androgen receptor regulates the recr...Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis,and the androgen receptor regulates prostate cancer(PCa)progression.It is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment,even bone metastases,through exosomes.Here,we found that exosomes isolated from PCa cells after knocking down androgen receptor(AR)or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts.In addition,AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase(circ-DHPS)in PCa cells,which can be transported to osteoblasts by exosomes.Circ-DHPS acts as a competitive endogenous RNA(ceRNA)against endogenous miR-214-3p to promote C-C chemokine ligand 5(CCL5)levels in osteoblasts.Increasing the level of CCL5 in osteoblasts could recruit more PCa cells into the bone microenvironment.Thus,blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.展开更多
In order to investigate the characteristics of a vertical axial flow pump under various clearances of flare tube, the bell-shaped inlet and box culvert outlet channels with flare tube are studied numerically and exper...In order to investigate the characteristics of a vertical axial flow pump under various clearances of flare tube, the bell-shaped inlet and box culvert outlet channels with flare tube are studied numerically and experimentally. Then, the cases of inlet and outlet channels with the least hydraulic loss are selected to form an integral pump system, for which both numerical simulation and experimental investigation are carried out. The numerical results agree well with the experimental data. It is shown that the clearances of the interfaces between different components of the pump system have a significant impact on the internal flow structure, turbulent entropy and hydraulic performance of the inlet and outlet channels. For the cases of normalized bottom clearance less than 0.5 and normalized top clearance larger than 0.4, the internal flow and hydraulic performance indexes of inlet and outlet channels are relatively poor. There also exists a critical clearance in either inlet or outlet channel at which the hydraulic loss reaches the maximum. The results serve as an important reference for the design as well as safe and efficient operation of the vertical axial flow pump system.展开更多
Plasmonicnanoparticles(PNPs)with stable nanogaps are important to achieve strong,uniform and quantitative gap-enhanced Raman scattering(GERS)signals.Chiral PNPs with plasmonic circular dichroism(PCD)responses have bee...Plasmonicnanoparticles(PNPs)with stable nanogaps are important to achieve strong,uniform and quantitative gap-enhanced Raman scattering(GERS)signals.Chiral PNPs with plasmonic circular dichroism(PCD)responses have been discovered to be suitable for applications in enantiomeric recognition,cancer therapy and activation of immune system.Herein,two-thiolsmodulated growth was demonstrated to result in the acquisition of PNPs with synergistically enhanced GERS and PCD signals.4-Aminothiophenol(4-ATP)and cysteine(Cys)played the role of Raman reporter and chiral stimulus,respectively.At a fixed 4-ATP concentration,the GERS signal of PNPs was significantly enhanced with the increase of the concentration of Cys.Simultaneously,at a fixed concentration of Cys,an increase in PCD response was observed by elevating the concentration of 4-ATP.Both aforementioned molecules acted as morphology controllers,leading to the formation of helical shell.It is suggested that the giant GERS and PCD response were contributed by the‘‘hot spots''within the PNPs and more perfect helical shells.Our research pointed out a novel synthetic guideline to obtain PNPs with multiple functionalities by incorporating multi-ligands into the growth stages.展开更多
基金supported by the STI2030-Major Projects(2021ZD0200900 to Y.G.Y.)"Light of West China" Program of the Chinese Academy of Sciences(xbzg-zdsys-202302 to Y.G.Y.)
文摘The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.
基金This study was funded by the National Natural Science Foundation of China(81874416)Hunan Science and Technology Innovation Team Project(2020RC4050)+1 种基金Hunan Provincial Innovation Foundation for Postgraduate(CX20220788)Foshan Medical Research Fund(20210311).
文摘Background:Ischemic stroke(IS)is a global health issue and the current treatment options for IS are inadequate.Buyang Huanwu decoction(BHD)has demonstrated effectiveness in treating IS.However,the mechanisms by which BHD treats IS remain unclear,and no studies have been conducted to analyze these mechanisms from the perspective of Cuproptosis.In order to investigate the potential of BHD to intervene in IS through Cuproptosis,this study employed a systematic pharmacological approach and molecular docking verification.Methods:To investigate the mechanism of BHD in treating IS through Cuproptosis,relevant information on the structure,targets,and major biological functions and pathways of compounds related to BHD was collected from databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were then visualized using Cytoscape3.6.1,Ledock,and pymol software.Results:BHD is composed of 7 Chinese medicines,which contain 82 compounds,including 10 core compounds.These compounds are associated with 241 genes,of which 97 are common to BHD,IS,and Cuproptosis.The 97 common genes,including 10 core genes,are involved in biological processes such as proteolysis,regulation of apoptosis and cholesterol storage,as well as cellular components and molecular functions.The common genes among BHD,IS,and Cuproptosis,including 10 core genes,participate mainly in Kyoto Encyclopedia of Genes and Genomes pathways such as pathways in cancer,PI3K-Akt signaling pathway,and Estrogen signaling pathway.According to molecular docking results,linolenic acid showed good docking scores with 9 out of 10 core genes,except for SRC.13-hydroxy-9,11-octadecadienoic acid also demonstrated good docking scores with EGFR,MAPK14,and F2.Similarly,senkyunone also had good docking scores with EGFR,MAPK14,and F2,all of which had docking energy greater than−5 kcal.Conclusion:In this study,the potential of BHD for treating IS through Cuproptosis and its underlying mechanisms were explored and partially validated through molecular docking.However,due to the limitations of the systems pharmacology research method,further validation through cell experiments,animal experiments,and clinical trials may be necessary to confirm these findings.
文摘Background:Prior research has established a strong link between cerebral aneurysm(CA)occurrence and inflammation.Tea intake(TI)has been found to have anti-inflammatory properties through multiple mechanisms,potentially lowering CA incidence.This study aims to employ Mendelian Randomization(MR)methodology to explore the genetic causality between TI and CA.Methods:We collected Genome-wide association study(GWAS)data for CA,TI,Green tea intake(GTI),Herbal tea intake(HTI),and Rooibos tea intake(RTI).The MR analysis employed the TwoSampleMR package and utilized the inverse variance-weighted(IVW)method.Results:The findings suggest no genetic causal relationship between TI and CA(IVW:OR=1.10,95%CI:0.59–2.05,P=0.772).Similarly,there is no genetic causal association between GTI and CA(IVW:OR=1.07,95%CI:0.91–1.26,P=0.388),HTI and CA(IVW:OR=1.00,95%CI:0.89–1.13,P=0.943),or RTI and CA(IVW:OR=1.02,95%CI:0.96–1.09,P=0.472).Conclusion:There is no genetic causal relationship between TI and CA,and the different types of tea do not change this result.Further MR analysis is needed to investigate whether there is a potential genetic causal association between the quantity of TI and CA.
基金funded by the Natural Science Foundation of China(No.81874416)Science,Technology Innovation Team Project of Hunan(No.2020RC4050).
文摘Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment.This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment,with preliminary validation conducted through molecular docking.Methods:Information on the structure,targets,main biological functions,and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were visualized using software such as Cytoscape 3.6.1,Ledock,and pymol.Results:We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases,and GeneCards database was used to search 3350 IS-related gene targets,including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS.Enrichment analysis of these 78 targets using gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed the involvement of 48 GO terms in the treatment of IS,mainly in biological processes such as metabolism,biological regulation,and stress response.The composition of biological devices such as supercavitary membrane,cell fluid,and extracellular space was also involved.The biological functions mainly included protein binding,ion binding,hydrolytic enzyme activity,and others.The identified pathways were estrogen signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-AKT signaling pathway,RAP1 signaling pathway,P53 signaling pathway,PPAR signaling pathway,FOXO signaling pathway,RAS signaling pathway,prolactin signaling pathway,HIF-1 signaling pathway,and TNF signaling pathway.Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets.Conclusion:Through the application of network pharmacology methods,it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways,involving several crucial compounds and genes.Nevertheless,additional in vitro and in vivo studies are needed to verify these findings.
基金Supported by The Grants from National Natural Science Foundation of China,No.81102013,No.81101580Zhejiang Provincial Natural Science Foundation of China,No.R2090353National High Technology Research and Development Program of China,No.2012AA02A506
文摘AIM:To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). METHODS:Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined asP < 0.05. RESULTS:The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage Ⅲ CRC (P < 0.0001). We divided 341 stage Ⅲ patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups:LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001). CONCLUSION:The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage Ⅲ CRC patients.
基金supported by the National Natural Science Foundation of China(U1402224,31601010,81571998,and U1702284)Yunnan Province(2015HA038 and 2018FB054)Chinese Academy of Sciences(CAS zsys-02)
文摘Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled genome is essential for understanding the genetic features and biology of this animal. In this study, we used long-read single-molecule sequencing and high-throughput chromosome conformation capture (Hi-C) technology to obtain a high-qualitychromosome-scale scaffolding of the Chinese tree shrew genome. The new reference genome (KIZ version 2: TS_2.0) resolved problems in presently available tree shrew genomes and enabled accurate identification of large and complex repeat regions, gene structures, and species-specific genomic structural variants. In addition, by sequencing the genomes of six Chinese tree shrew individuals, we produced a comprehensive map of 12.8 M single nucleotide polymorphisms and confirmed that the major histocompatibility complex (MHC) loci and immunoglobulin gene family exhibited high nucleotide diversity in the tree shrew genome. We updated the tree shrew genome database (TreeshrewDB v2.0: http://www.treeshrewdb.org) to include the genome annotation information and genetic variations. The new high-quality reference genome of the Chinese tree shrew and the updated TreeshrewDB will facilitate the use of this animal in many different fields of research.
基金supported by the National Key R&D Program of China(Nos.2016YFA0401304 and 2017YFA0403302)the National Natural Science Foundation of China(NSFC)(Nos.61621001,11505129,and U1732268)
文摘Gold films deposited by direct current magnetron sputtering are used for synchrotron radiation optics. In this study, the microstructure and surface roughness of gold films were investigated for the purpose of developing high-reflectivity mirrors. The deposition process was first optimized. Films were fabricated at different sputtering powers (15, 40, 80, and 120 W) and characterized using grazing incidence X-ray reflectometry, X-ray diffraction, and atomic force microscopy. The results showed that all the films were highly textured, having a dominant Au (111) orientation, and the film deposited at 80 W had the lowest surface roughness. Subsequently, post-deposition annealing from 100 to 200℃ in a vacuum was performed on the films deposited at 80 W to investigate the effect of annealing on the microstructure and surface roughness of the films. The grain size, surface roughness, and their relationship were investigated as a function of annealing temperature. AFM and XRD results revealed that at annealing temperatures of 175 ℃ and below, microstructural change of the films was mainly manifested by the elimination of voids. At annealing temperatures higher than 175℃, grain coalescence occurred in addition to the void elimination, causing the surface roughness to increase.
基金supported by the National Swine Industry and Technology System of China(nycytx-009)National Natural Science Foundation of China(31672383)。
文摘In pig-to-human xenotransplantation,the transmission risk of porcine endogenous retroviruses(PERVs)is of great concern.However,the distribution of PERVs in pig genomes,their genetic variation among Eurasian pigs,and their evolutionary history remain unclear.We scanned PERVs in the current pig reference genome(assembly Build 11.1),and identified 36 long complete or near-complete PERVs(lc PERVs)and 23 short incomplete PERVs(si PERVs).Besides three known PERVs(PERV-A,-B,and-C),four novel types(PERV-JX1,-JX2,-JX3,and-JX4)were detected in this study.According to evolutionary analyses,the newly discovered PERVs were more ancient,and PERV-Bs probably experienced a bottleneck~0.5 million years ago(Ma).By analyzing63 high-quality porcine whole-genome resequencing data,we found that the PERV copy numbers in Chinese pigs were lower(32.0±4.0)than in Western pigs(49.1±6.5).Additionally,the PERV sequence diversity was lower in Chinese pigs than in Western pigs.Regarding the lc PERV copy numbers,PERV-A and-JX2 in Western pigs were higher than in Chinese pigs.Notably,Bama Xiang(BMX)pigs had the lowest PERV copy number(27.8±5.1),and a BMX individual had no PERV-C and the lowest PERV copy number(23),suggesting that BMX pigs were more suitable for screening and/or modification as xenograft donors.Furthermore,we identified 451 PERV transposon insertion polymorphisms(TIPs),of which 86 were shared by all 10 Chinese and Western pig breeds.Our findings provide systematic insights into the genomic distribution,variation,evolution,and possible biological function of PERVs.
基金supported by the Breakthrough Project of Strategic Priority Program of the Chinese Academy of Sciences(XDB13000000)
文摘As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveillance systems were used to record the behavior and timing of copulations; embryos at different post-copulation stages were collected and cultured in vitro; and the developmental characteristics of both early-stage and in vitro cultured embryos were determined. A total of 163 females were collected following effective copulation, and 150 were used in either unilateral or bilateral oviduct embryo collections, with 307 embryos from 111 females obtained (conception rate=74%). Among them, 237 embryos were collected from 78 females, bilaterally, i.e., the average embryo number per female was 3.04; 172 fertilized eggs collected from 55 females, bilaterally, were cultured for 24-108 h in vitro for developmental observations; finally, 65 embryos from 23 bilateral cases and 70 embryos from 33 unilateral cases were used in embryo transplantation.
基金Supported by the Key Projects of Natural Science Foundation of Ningxia,No.2020AAC02020the Funds of Ningxia Medical University,No.XY201808.
文摘The mitochondrial unfolded protein response(UPRmt)is an evolutionarily conserved adaptive mechanism for improving cell survival under mitochondrial stress.Under physiological and pathological conditions,the UPRmt is the key to maintaining intracellular homeostasis and proteostasis.Important roles of the UPRmt have been demonstrated in a variety of cell types and in cell development,metabolism,and immune processes.UPRmt dysfunction leads to a variety of pathologies,including cancer,inflammation,neurodegenerative disease,metabolic disease,and immune disease.Stem cells have a special ability to selfrenew and differentiate into a variety of somatic cells and have been shown to exist in a variety of tissues.These cells are involved in development,tissue renewal,and some disease processes.Although the roles and regulatory mechanisms of the UPRmt in somatic cells have been widely reported,the roles of the UPRmt in stem cells are not fully understood.The roles and functions of the UPRmt depend on stem cell type.Therefore,this paper summarizes the potential significance of the UPRmt in embryonic stem cells,tissue stem cells,tumor stem cells,and induced pluripotent stem cells.The purpose of this review is to provide new insights into stem cell differentiation and tumor pathogenesis.
基金supported by the National Natural Science Foundation of China (Project No. 60471005) Program for Changjiang Scholars and Innovative Research Team in University.
文摘Objective To study environment-friendly determination of azobenzene in trace amounts using β-cyclodextrin (β-CD)-modified Au electrode. Methods β-CD-modified Au electrode was fabricated with a two-step approach, and then a gold electrode modified with β-CD was used to detect azobenzene by employing Osteryoung square wave voltammetry. Results The modified electrode could detect azobenzene, showing a good linearity between the electrochemical current and concentration. Conclusion Although the electrochemical current is related with concentration, the detection limit is around 1 .0 ×10^-10 mol/L. This study may provide a new environment-friendly approach for monitoring water quality.
基金Special scientific research project of the national traditional Chinese medicine clinical base business construction of state administration of traditional Chinese medicine(No.JDZX2015043)。
文摘Objective:To clarify the material basis of Chinese medicine pair“Radix Paeoniae Rubra-Cortex Moutan”(Chishao-Mudanpi)and explore their mechanism in the treatment of ICH with network pharmacology.Methods:The active ingredients contained in Radix Paeoniae Rubra and Cortex Moutan were searched and selected based on the oral bioavailability prediction and drug-likeness prediction from the TCMSP database.Then the targets of cerebral hemorrhage were collected from GeneCards,OMIM,and DrugBank databases.After obtained the intersections of drugs and disease,the active component target disease interactive network diagram was drawn by Cytoscape software.The obtained key targets were uploaded to the STRING database for analysis and construct a PPI network map.GO function enrichment analysis and KEGG analysis were performed on the key target proteins.Results:Collected the active ingredients of Radix Paeoniae 119,Radix Paeoniae 55,including paeoniflorin,baicalin,β-sitosterol,etc.Related drug target protein 1190,ICH disease-related genes 823,"Radix Paeoniae-Radix Paeoniae"and 72 common targets of ICH,mainly acting on Akt1,IL6,VEGFA,CASP3,EGF,involving 133 related signaling pathways such as AGE-RAGE,TNF,IL-17,HIF1,PI3K-Akt.Conclusion:The combination of"Radix Paeoniae Rubra-Cortex Moutan"in the treatment of ICH has the characteristics of multiple pathways and multiple targets,which provides a reference and basis for further molecular biology verification in the future.
基金National natural science foundation of China(No.81673941,81704050,81804042)。
文摘Objective:To investigate the inhibition effect of dexamethasone with different concentration gradients on the expression of MMP-1,-3,and-13 in a bone joint cell model of IL-1β-induced SW1353 cells.Methods:The SW1353 cells were placed in a culture medium containing 10^(1)-10^(8) nmol/L dexamethasone,and after 12 hours of culture,the appropriate intervention concentration range of dexamethasone was screened by the MTS for subsequent experiments.After SW1353 cells were induced with 10 ng/mL IL-1β,10^(1)-10^(7) nmol/L dexamethasone was given for intervention,and RT-PCR was used to detect the mRNA expression of MMP-1,-3,and-13.The protein was extracted after the intervention of 104 nmol/L dexamethasone,and western blot was used to detect the protein expression of MMP-1,-3,and-13.Results:MTS proliferation experiment results showed that 10^(1)-10^(7) nmol/L dexamethasone had no significant effect on SW1353 cell viability,while 10^(8) nmol/L dexamethasone had a significant inhibitory effect on SW1353(p<0.05).There was no obvious effect on cell viability after adding 10 ng/mL IL-1β.RT-PCR results indicated that the IL-1βgroup had a significant increase in the mRNA expression of MMP-1,-3,and-13 compared with the blank control group,and the difference was statistically significant(p<0.05).After intervention with 102-10^(7) nmol/L dexamethasone,MMP-1 mRNA expression decreased(p<0.05);after intervention with 103-10^(7) nmol/L dexamethasone,MMP-3 mRNA expression decreased(p<0.05);after intervention with 10-10^(7) nmol/L dexamethasone,the mRNA expression of MMP-13 decreased(p<0.05).The Western blot results showed that compared with the blank control group,the protein levels of MMP-1,-3,and-13 in the IL-1βgroup were significantly increased;the protein levels of MMP-1,-3,and-13 were significantly reduced after the intervention of 104 nmol/L dexamethasone.Conclusion:Dexamethasone can inhibit the expression of MMP1,MMP-3,and MMP-13 in the IL-1β-induced OA cell model at the mRNA and protein levels.
基金supported by grant from the National Natural Science Foundation of China(No.82002693 and No.81803022)the Natural Science Foundation of Shaanxi Province(No.2022JQ-903 and No.2020JQ-519).
文摘Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis,and the androgen receptor regulates prostate cancer(PCa)progression.It is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment,even bone metastases,through exosomes.Here,we found that exosomes isolated from PCa cells after knocking down androgen receptor(AR)or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts.In addition,AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase(circ-DHPS)in PCa cells,which can be transported to osteoblasts by exosomes.Circ-DHPS acts as a competitive endogenous RNA(ceRNA)against endogenous miR-214-3p to promote C-C chemokine ligand 5(CCL5)levels in osteoblasts.Increasing the level of CCL5 in osteoblasts could recruit more PCa cells into the bone microenvironment.Thus,blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.
基金supported by the National Natural Science Foundation of China(Grant Nos.52079057,52106043)the China Postdoctoral Science Foundation(Grant No.2022M711376).
文摘In order to investigate the characteristics of a vertical axial flow pump under various clearances of flare tube, the bell-shaped inlet and box culvert outlet channels with flare tube are studied numerically and experimentally. Then, the cases of inlet and outlet channels with the least hydraulic loss are selected to form an integral pump system, for which both numerical simulation and experimental investigation are carried out. The numerical results agree well with the experimental data. It is shown that the clearances of the interfaces between different components of the pump system have a significant impact on the internal flow structure, turbulent entropy and hydraulic performance of the inlet and outlet channels. For the cases of normalized bottom clearance less than 0.5 and normalized top clearance larger than 0.4, the internal flow and hydraulic performance indexes of inlet and outlet channels are relatively poor. There also exists a critical clearance in either inlet or outlet channel at which the hydraulic loss reaches the maximum. The results serve as an important reference for the design as well as safe and efficient operation of the vertical axial flow pump system.
基金financially supported by the National Natural Science Foundation of China (Nos.22072032 and21902148)the Key Science and Technology Program of Henan Province (No.192102210004)+2 种基金the Research Initiated Project of Chengdu University (No.2081921109)Chengdu University Graduate Talent Training Quality and Teaching Reform Project (No.cdjgy2022034)Chengdu University Talent Training Quality and Teaching Reform Project (No.cdjgb2022103)。
文摘Plasmonicnanoparticles(PNPs)with stable nanogaps are important to achieve strong,uniform and quantitative gap-enhanced Raman scattering(GERS)signals.Chiral PNPs with plasmonic circular dichroism(PCD)responses have been discovered to be suitable for applications in enantiomeric recognition,cancer therapy and activation of immune system.Herein,two-thiolsmodulated growth was demonstrated to result in the acquisition of PNPs with synergistically enhanced GERS and PCD signals.4-Aminothiophenol(4-ATP)and cysteine(Cys)played the role of Raman reporter and chiral stimulus,respectively.At a fixed 4-ATP concentration,the GERS signal of PNPs was significantly enhanced with the increase of the concentration of Cys.Simultaneously,at a fixed concentration of Cys,an increase in PCD response was observed by elevating the concentration of 4-ATP.Both aforementioned molecules acted as morphology controllers,leading to the formation of helical shell.It is suggested that the giant GERS and PCD response were contributed by the‘‘hot spots''within the PNPs and more perfect helical shells.Our research pointed out a novel synthetic guideline to obtain PNPs with multiple functionalities by incorporating multi-ligands into the growth stages.