The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MA...The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MACF1)is downregulated in association with the decreased osteoblast differentiation and bone formation under simulated microgravity conditions.These findings suggest that MACF1 is sensitive to mechanical condition and may be critical for osteoblast differentiation and bone formation.To verify this hypothesis,current study investigates the role and mechanism of MACF1 in regulatingosteoblast differentiation by adopting MACF1 knockdown(MACF1-KD)osteoblasts.The results showed that MACF1 knockdown suppressed mineralized nodules formation,alkaline phosphatase(ALP)activity,osteogenic gene expression andβ-catenin signaling transduction.Moreover,we used RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)to investigate further mechanism.Interestingly,we found that MACF1 sequesterd repressors of osteoblast differentiation in cytoplasm.In conclusion,MACF1 is sensitive to mechanical condition and plays key role in activatingβ-catenin signaling transduction and sequestering repressors of osteoblast differentiation,which further promotes osteoblast differentiation.展开更多
OBJECTIVE To investigate the effect of Pinctadafucata mantle gene 1(pfmg1)on osteoporotic bone lossand the role in osteoblast differentiation and matrix mineralization,and to explore the molecular mechanismof how PFMG...OBJECTIVE To investigate the effect of Pinctadafucata mantle gene 1(pfmg1)on osteoporotic bone lossand the role in osteoblast differentiation and matrix mineralization,and to explore the molecular mechanismof how PFMG1 functions through both animal and cellular experiments.METHODS For animal experiments,female BALB/c mice were subjected to sham-operation(sham)or ovariectomy(ovx)at 5weeks of age,control and pfmg1 lentiviral particles were packaged and injected through tail vein to ovx mice(2×107TU/mouse),respectively.Bone mineral density(BMD)was detected 2 months after the surgery,and the proximal tibia was scanned in three dimensions byμCT.For cellular experiments,GST-PFMG1 protein was expressed and purified,then added to MC3T3E1 cell culture medium.MTT,ALP activity and the level of matrix mineralization were detected after the treatment.RESULTSEctopic expression of pfmg1 gene enhanced the BMD level of ovx mice.μCT images revealed that PFMG1 improvedthe osteoporotic characteristics caused by ovariectomy,including the decreases in trabecular number(Tb.N),trabecular thickness(Tb.Th),and in trabecular bone volume as a percentage of total bone volume(BV/TV);and the increases in trabecular spacing(Tb.Sp)and trabecular bone pattern factor(TBPf).The alkaline phosphatase(ALP)activity and the level of matrix mineralization increased,while the MTT activity decreased after treated with PFMG1 in the osteoblast cell line MC3T3E1.CONCLUSION PFMG1 from the mental of P.fucatacould promote osteoblast differentiation and matrix mineralization in vitro,and couldprevent bone loss caused by ovariectomy in vivo.These findings showed the potential of PFMG1 from nacre as a therapeutic drug for osteoporosis.展开更多
Aims: Previous studies reported that reduced bone formation was identified in fasting adult female mice compared with the ad libitum control group. An increasing number of studies have shown that miRNAs contribute to ...Aims: Previous studies reported that reduced bone formation was identified in fasting adult female mice compared with the ad libitum control group. An increasing number of studies have shown that miRNAs contribute to bone homeostasis. Unfortunately, there are minor concerns about the underlying mechanisms in osteoblastic differentiation under malnutrition conditions. Methods: We investigated microRNAs (miRNAs) in osteoblastic differentiation under malnutrition conditions using high-throughput bioinformatics approaches. To screen for targeted microRNAs, sequences were quantified by aligning reads to miRbase using miRDeep2 software. Unadjusted p-values were calculated using the Student’s t-test. Genes with a p-value of <0.05 and log 2FC (fold change) ≥ 1 were considered differentially expressed genes (DEGs). DEGs were submitted to Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, respectively. Results: They were mainly enriched in biological process terms type and biological pathways, respectively. Particularly, we evaluated seven microRNAs, mir-494 3p, mir-466, mir-455, mir-708, mir-298, mir-92 and mir-224, which likely play roles in osteoblastogenesis in fasting adult mice. Conclusion: To our knowledge, this is the first study on the expression pattern of miRNA in osteoblasts of malnourished adult mice. These targeting miRNAs may provide a potential therapeutic approach to treat osteoporosis.展开更多
Objective:To study the effects of neurotrophin-3 (NT-3) intervention on bone marrow mesenchymal stem cell osteoblast differentiation as well as cell proliferation and apoptosis. Methods: Bone marrow mesenchymal stem c...Objective:To study the effects of neurotrophin-3 (NT-3) intervention on bone marrow mesenchymal stem cell osteoblast differentiation as well as cell proliferation and apoptosis. Methods: Bone marrow mesenchymal stem cells were cultured and divided into control group, 25 ng/mL NT-3 group, 50 ng/mL NT-3 group and 100 ng/mL NT-3 group, they were treated with different doses of NT-3 for 24 h, and then osteoblast marker gene, cell proliferation gene and apoptosis gene expression were determined.Results: RUNX2, Osterix, ALP, OCN, BMP-2, Bcl-2, Nrf2, ERK1/2 and PCNA mRNA expression in 25 ng/mL NT-3 group, 50 ng/mL NT-3 group and 100 ng/mL NT-3 group were significantly higher than those in control group whereas Bim, Bax, Caspase-3, CHOP and Beclin1 mRNA expression were significantly lower than those in control group, and the larger the dose of NT-3, the higher the RUNX2, Osterix, ALP, OCN, BMP-2, Bcl-2, Nrf2, ERK1/2 and PCNA mRNA expression whereas the lower the Bim, Bax, Caspase-3, CHOP and Beclin1 mRNA expression.Conclusion: NT-3 intervention in bone marrow mesenchymal stem cells can promote osteoblast differentiation and cell proliferation and inhibit apoptosis.展开更多
Objective: To study the effect of low-level laser irradiation (LLLI) combined with ferulic acid on the osteoblast differentiation and maturation as well as osteogenesis signaling pathway expression. Methods: The crani...Objective: To study the effect of low-level laser irradiation (LLLI) combined with ferulic acid on the osteoblast differentiation and maturation as well as osteogenesis signaling pathway expression. Methods: The cranium was collected from the SD rats born within 24 h, osteoblasts were separated, cultured and then divided into control group, ferulic acid group, LLLI group, ferulic acid + LLLI group, and the expression osteoblast differentiation markers, proliferation molecules and signaling pathway molecules were detected after continuous treatment with different conditions for three days. Results: 3 d after treatment, the Bax and Bid mRNA expression in ferulic acid group, LLLI group and ferulic acid + LLLI group of cells were significantly lower than those in control group while Bcl-2, CyclinD1, E2F, Col-I, OC and ALP mRNA expression as well as Wnt, β-catenin, Runx2, cAMP and PKA protein expression were significantly higher than those in control group;Bax and Bid mRNA expression in ferulic acid + LLLI group of cells were significantly lower than those in ferulic acid group and LLLI group while Bcl-2, CyclinD1, E2F, Col-I, OC and ALP mRNA expression as well as Wnt, β-catenin, Runx2, cAMP and PKA protein expression were significantly higher than those in ferulic acid group and LLLI group;Col-I, OC, ALP, Bax, Bid, Bcl-2, CyclinD1 and E2F mRNA expression as well as Wnt, β-catenin, Runx2, cAMP and PKA protein expression were not significantly different between ferulic acid group and LLLI group. Conclusion: Low-level laser irradiation (LLLI) combined with ferulic acid can promote osteoblast differentiation and maturation and activate osteogenesis signaling pathway.展开更多
Wnt signaling executes an indispensable performance in osteoblast differentiation,bone development,homeostasis,and remodeling.Wnt signals trigger the intracellular Wnt signaling cascade to initiate regulating the impl...Wnt signaling executes an indispensable performance in osteoblast differentiation,bone development,homeostasis,and remodeling.Wnt signals trigger the intracellular Wnt signaling cascade to initiate regulating the implication of b-catenin in the bone environment.Going through the novel discoveries done via high-throughput sequencing technologies on ge-netic mouse models,we highlighted the significant contribution of Wnt ligands,co-receptors,inhibitors,their related skeletal phenotypes in mouse models and the similar bone disorders clinically observed in human beings.Moreover,the crosstalk between Wnt signaling pathway and BMP,TGF-b,FGF,Hippo,Hedgehog,Notch and PDGF signaling pathways is thoroughly demonstrated to be the underlying gene regulatory network that orchestrates osteoblast dif-ferentiation and bone development.We also introspected the significance of Wnt signaling transduction in the reorganization of cellular metabolism by stimulating glycolysis,glutamine catabolism,and fatty acid oxidation in osteoblast-lineage cells that display an important reg-ulatory arbor in the cellular bioenergetics of the bone.Throughout this evaluation,most to date therapeutical approaches towards osteoporosis and other bone maladies found in human beings,are formulated with an aspiration to holistically revamp the present clinical applica-tions involving various monoclonal antibodies therapies that lack specificity,efficacy,and safety into more requisite advanced therapeutics that satisfy these three requirements for further clinical considerations.Conclusively,our review provides comprehensive scientific findings related to the fundamental significance of Wnt signaling cascades in skeletal system and the underlying gene regulatory network with other signaling pathways enlightening re-searchers with the possibility to further integrate the identified target molecules into thera-peutic strategies for skeletal disorders treatment in the clinic.展开更多
Increasing the osteogenic differentiation ability and decreasing the adipogenic differentiation ability of bone marrow mesenchymal stem cells(BMSCs)is a potential strategy for the treatment of osteoporosis(OP).Natural...Increasing the osteogenic differentiation ability and decreasing the adipogenic differentiation ability of bone marrow mesenchymal stem cells(BMSCs)is a potential strategy for the treatment of osteoporosis(OP).Naturally derived oligosaccharides have shown significant anti-osteoporotic effects.Nystose(NST),an oligosaccharide,was isolated from the roots of Morinda officinalis How.(MO).The aim of the present study was to investigate the effects of NST on bone loss in ovariectomized mice,and explore the underlying mechanism of NST in promoting differentiation of BMSCs to osteoblasts.Administration of NST(40,80 and 160 mg/kg)and the positive control of estradiol valerate(0.2 mg/kg)for 8 weeks significantly prevented bone loss induced by ovariectomy(OVX),increased the bone mass density(BMD),improved the bone microarchitecture and reduced urine calcium and deoxypyridinoline(DPD)in ovariectomized mice,while inhibited the increase of body weight without significantly affecting the uterus weight.Furthermore,we found that NST increased osteogenic differentiation,inhibited adipogenic differentiation of BMSCs in vitro,and upregulated the expression of the key proteins of BMP and Wnt/β-catenin pathways.In addition,Noggin and Dickkopf-related protein-1(DKK-1)reversed the effect of NST on osteogenic differentiation and expression of the key proteins in BMP and Wnt/β-catenin pathway.The luciferase activities and the molecular docking analysis further supported the mechanism of NST.In conclusion,these results indicating that NST can be clinically used as a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis.展开更多
Areca nut is used worldwide as a hallucinogenic addicting drug along the tropical belt.Arecoline,a toxic compound,is the most important alkaloid in areca nuts.The adverse effects of oral uptake and chewing of areca nu...Areca nut is used worldwide as a hallucinogenic addicting drug along the tropical belt.Arecoline,a toxic compound,is the most important alkaloid in areca nuts.The adverse effects of oral uptake and chewing of areca nut are well known.For example,the possibility of cancer caused by chewing areca nuts is widely discussed.Chewing areca nut has other adverse effects on other organs,including abnormal cell differentiation,oral cancer,and several other diseases.The use of areca nut is also associated with low birthweight.Skeletal musculature is the largest organ in the body and is attached to the bones.During embryo development,the differentiation of bone and muscle cells is critical.In this article,we reviewed the effects of areca nut and arecoline on embryonic cell differentiation,particularly osteoblasts,myoblasts,and fibroblasts.展开更多
BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by...BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.展开更多
Rural settlement is the basic spatial unit for compact communities in rural area. Scientific exploration of spatial-temporal differentiation and its influencing factors is the premise of spatial layout rationalization...Rural settlement is the basic spatial unit for compact communities in rural area. Scientific exploration of spatial-temporal differentiation and its influencing factors is the premise of spatial layout rationalization. Based on land use data of Liangshan Yi Autonomous Prefecture(hereinafter referred to as Liangshan Prefecture) in Sichuan Province, China from 1980 to 2020, compactness index, fractal dimension, imbalance index, location entropy and the optimal parameters-based geographical detector(OPGD) model are used to analyze the spatial-temporal evolution of the morphological characteristics of rural settlements, and to explore the influence of natural geographical factors, socioeconomic factors, and policy factors on the spatial differentiation of rural settlements. The results show that:(1) From 1980 to 2020, the rural settlements area in Liangshan Prefecture increased by 15.96 km^(2). In space, the rural settlements are generally distributed in a local aggregation, dense in the middle and sparse around the periphery. In 2015, the spatial density and expansion index of rural settlements reached the peak.(2) From 1980 to 2020, the compactness index decreased from 0.7636 to 0.7496, the fractal dimension increased from 1.0283 to 1.0314, and the fragmentation index decreased from 0.1183 to 0.1047. The spatial morphological structure of rural settlements tended to be loose, the shape contour tended to be complex, the degree of fragmentation decreased, and the spatial distribution was significantly imbalanced.(3) The results of OPGD detection in 2015 show that the influence of each factor is slope(0.2371) > traffic accessibility(0.2098) > population(0.1403) > regional GDP(0.1325) > elevation(0.0987) > poverty alleviation(0). The results of OPGD detection in 2020 show that the influence of each factor is slope(0.2339) > traffic accessibility(0.2198) > population(0.1432) > regional GDP(0.1219) > poverty alleviation(0.0992) > elevation(0.093). Natural geographical factors(slope and elevation) are the basic factors affecting the spatial distribution of rural settlements, and rural settlements are widely distributed in the river valley plain and the second half mountain area. Socioeconomic factors(traffic accessibility, population, and regional GDP) have a greater impact on the spatial distribution of rural settlements, which is an important factor affecting the spatial distribution of rural settlements. Policy factors such as poverty alleviation relocation have an indispensable impact on the spatial distribution of rural settlements. The research results can provide decisionmaking basis for the spatial arrangement of rural settlements in Liangshan Prefecture, and optimize the implementation of rural revitalization policies.展开更多
Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune response.These properties and their ability to both maintain self-renewal ...Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune response.These properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative medicine.While many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular aspects.Recent evidence suggests that DSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress conditions.This comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC differentiation.To achieve this goal,we dissect the intricacies of autophagy and its mechanisms.Subsequently,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic trajectories.Furthermore,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic milieu.The implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.展开更多
BACKGROUND The study on predicting the differentiation grade of colorectal cancer(CRC)based on magnetic resonance imaging(MRI)has not been reported yet.Developing a non-invasive model to predict the differentiation gr...BACKGROUND The study on predicting the differentiation grade of colorectal cancer(CRC)based on magnetic resonance imaging(MRI)has not been reported yet.Developing a non-invasive model to predict the differentiation grade of CRC is of great value.AIM To develop and validate machine learning-based models for predicting the differ-entiation grade of CRC based on T2-weighted images(T2WI).METHODS We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023.Patients were randomly assigned to a training cohort(n=220)or a validation cohort(n=95)at a 7:3 ratio.Lesions were delineated layer by layer on high-resolution T2WI.Least absolute shrinkage and selection operator regression was applied to screen for radiomic features.Radiomics and clinical models were constructed using the multilayer perceptron(MLP)algorithm.These radiomic features and clinically relevant variables(selected based on a significance level of P<0.05 in the training set)were used to construct radiomics-clinical models.The performance of the three models(clinical,radiomic,and radiomic-clinical model)were evaluated using the area under the curve(AUC),calibration curve and decision curve analysis(DCA).RESULTS After feature selection,eight radiomic features were retained from the initial 1781 features to construct the radiomic model.Eight different classifiers,including logistic regression,support vector machine,k-nearest neighbours,random forest,extreme trees,extreme gradient boosting,light gradient boosting machine,and MLP,were used to construct the model,with MLP demonstrating the best diagnostic performance.The AUC of the radiomic-clinical model was 0.862(95%CI:0.796-0.927)in the training cohort and 0.761(95%CI:0.635-0.887)in the validation cohort.The AUC for the radiomic model was 0.796(95%CI:0.723-0.869)in the training cohort and 0.735(95%CI:0.604-0.866)in the validation cohort.The clinical model achieved an AUC of 0.751(95%CI:0.661-0.842)in the training cohort and 0.676(95%CI:0.525-0.827)in the validation cohort.All three models demonstrated good accuracy.In the training cohort,the AUC of the radiomic-clinical model was significantly greater than that of the clinical model(P=0.005)and the radiomic model(P=0.016).DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process.CONCLUSION In this study,we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC.This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.展开更多
This paper presents a new method of using a convolutional neural network(CNN)in machine learning to identify brand consistency by product appearance variation.In Experiment 1,we collected fifty mouse devices from the ...This paper presents a new method of using a convolutional neural network(CNN)in machine learning to identify brand consistency by product appearance variation.In Experiment 1,we collected fifty mouse devices from the past thirty-five years from a renowned company to build a dataset consisting of product pictures with pre-defined design features of their appearance and functions.Results show that it is a challenge to distinguish periods for the subtle evolution of themouse devices with such traditionalmethods as time series analysis and principal component analysis(PCA).In Experiment 2,we applied deep learning to predict the extent to which the product appearance variation ofmouse devices of various brands.The investigation collected 6,042 images ofmouse devices and divided theminto the Early Stage and the Late Stage.Results show the highest accuracy of 81.4%with the CNNmodel,and the evaluation score of brand style consistency is 0.36,implying that the brand consistency score converted by the CNN accuracy rate is not always perfect in the real world.The relationship between product appearance variation,brand style consistency,and evaluation score is beneficial for predicting new product styles and future product style roadmaps.In addition,the CNN heat maps highlight the critical areas of design features of different styles,providing alternative clues related to the blurred boundary.The study provides insights into practical problems for designers,manufacturers,and marketers in product design.It not only contributes to the scientific understanding of design development,but also provides industry professionals with practical tools and methods to improve the design process and maintain brand consistency.Designers can use these techniques to find features that influence brand style.Then,capture these features as innovative design elements and maintain core brand values.展开更多
BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development,as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation.AIM To invest...BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development,as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation.AIM To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms.METHODS 20 growing mice were randomly divided into two groups:Con group(control group,n=10)and Ex group(treadmill exercise group,n=10).Hematoxylin-eosin staining,immunohistochemistry,and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur.Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19(lncRNA H19).RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation.RESULTS Compared with the Con group,the expression of bone morphogenetic protein 2 was also significantly increased.The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density,bone volume fraction,and the number of trabeculae,and decreased trabecular segregation in the femur of mice.Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation.In addition,knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers,which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence.CONCLUSION Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice,thus enhancing the peak bone mass of mice.The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.展开更多
BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological char...BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely related to the safety and efficacy of ESD.展开更多
PIP5k1βis crucial to the generation of phosphotidylinosotol(4,5)P2.PIP5k1βparticipates in numerous cellular activities,such as B cell and platelet activation,cell phagocytosis and endocytosis,cell apoptosis,and cyto...PIP5k1βis crucial to the generation of phosphotidylinosotol(4,5)P2.PIP5k1βparticipates in numerous cellular activities,such as B cell and platelet activation,cell phagocytosis and endocytosis,cell apoptosis,and cytoskeletal organization.In the present work,we aimed to examine the function of PIP5k1βin osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment.We discovered that PIP5k1β deletion in mice resulted in obvious bone loss and that PIP5k1β was highly expressed during both osteoclast and osteoblast differentiation.Deletion of the gene was found to enhance the proliferation and migration of bone marrow-derived macrophage-like cells to promote osteoclast differentiation.PIP5k1β-/-osteoclasts exhibited normal cytoskeleton architecture but stronger resorption activity.PIP5kip deficiency also promoted activation of mitogen-activated kinase and Akt signaling,enhanced TRAF6 and c-Fos expression,facilitated the expression and nuclear translocation of NFATC1,and upregulated Grb2 expression,thereby accelerating osteoclast differentiation and function.Finally,PIP5k1β enhanced osteoblast differentiation by upregulating master gene expression through triggering smad1/5/8 signaling.Therefore,PIP5k1βmodulates bone homeostasis and remodeling.展开更多
The iso fl avone calycosin-7-O-β-D-glucopyranoside(CG) is a principal constituent of Astragalus membranaceus(AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this...The iso fl avone calycosin-7-O-β-D-glucopyranoside(CG) is a principal constituent of Astragalus membranaceus(AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this study was to investigate the osteogenic effects of CG and its underlying mechanism in ST2 cells. The results show that exposure of cells to CG in osteogenic differentiation medium increases ALP activity, osteocalcin(Ocal) m RNA expression and the osteoblastic mineralization process. Mechanistically, CG treatment increased the expression of bone morphogenetic protein 2(BMP-2), p-Smad 1/5/8, β-catenin and Runx2, all of which are regulators of the BMP- or wingless-type MMTV integration site family(WNT)/β-catenin-signaling pathways. Moreover, the osteogenic effects of CG were inhibited by Noggin and DKK-1 which are classical inhibitors of the BMP and WNT/β-catenin-signaling pathways, respectively. Taken together, the results indicate that CG promotes the osteoblastic differentiation of ST2 cells through regulating the BMP/WNT signaling pathways. On this basis, CG may be a useful lead compound for improving the treatment of bone-decreasing diseases and enhancing bone regeneration.展开更多
Amyloid beta(AB)peptide 40 enhances the activation of receptor for advanced glycation end products(RAGE)in immune-inflammatory diseases.RAGE exhibits several ffects in the setting of numerous cardiovascular events.We ...Amyloid beta(AB)peptide 40 enhances the activation of receptor for advanced glycation end products(RAGE)in immune-inflammatory diseases.RAGE exhibits several ffects in the setting of numerous cardiovascular events.We bypothesized that the Aβ40/RAGE pathway is involved in the osteoblastic differentiation of the valvular interstitial cell(VIC)phenotype,and RAGE knockout intervention could reduce the calcification of aortic valve interstitial cells(AVICs)by inhibiting the extracellular-regulated kinase1/2(ERK 1/2)/nuclear factor kappa-B(NF-kB)signaling pathway.To test this hypothesis,the activation of AB40/RAGE pathway in human calcific AVs was evaluated with immunohistochemical staining.Cultured calcific VIC models were used in vitro.The VICs were stimulated using Aβ40,with or without RAGE small interfering ribonucleic acid(siRNA),and ERK1/2 and NF-κB inhibitors for analysis.Our data revealed that AB40 induced the ERK 1/2/NF-κB signaling pathway and osteoblastic differentiation of AVICs via the RAGE pathway in vitro.展开更多
Bone-resorbing osteoclasts are formed from a monocyte/macrophage lineage under the strict control o bone-forming osteoblasts. So far,macrophage colonystimulating factor(M-CSF),receptor activator o nuclear factor-κB l...Bone-resorbing osteoclasts are formed from a monocyte/macrophage lineage under the strict control o bone-forming osteoblasts. So far,macrophage colonystimulating factor(M-CSF),receptor activator o nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG) produced by osteoblasts play major roles in the regulation of osteoclast differentiation. Recent studies have shown that osteoblasts regulate osteoclastogenesis through several mechanisms independent o M-CSF,RANKL,and OPG production. Identification o osteoclast-committed precursors in vivo demonstrated that osteoblasts are involved in the distribution o osteoclast precursors in bone. Interleukin 34(IL-34)a novel ligand for c-Fms,plays a pivotal role in maintaining the splenic reservoir of osteoclast-committed precursors in M-CSF deficient mice. IL-34 is also able to act as a substitute for osteoblast-producing M-CSF in osteoclastogenesis. Wnt5 a,produced by osteoblasts,enhances osteoclast differentiation by upregulating RANK expression through activation of the noncanonical Wnt pathway. Semaphorin 3A produced by osteoblasts inhibits RANKL-induced osteoclast differentiation through the suppression of immunoreceptortyrosine-based activation motif signals. Thus,recent findings show that osteoclast differentiation is tightly regulated by osteoblasts through several different mechanisms. These newly identified molecules are expected to be promising targets of therapeutic agents in bone-related diseases.展开更多
The effects of cerium ion(Ce3+) on the proliferation,differentiation,adipocytic transdifferentiation and mineralization function of primary mouse osteoblasts(OBs) were investigated.The results indicated that Ce3+ at a...The effects of cerium ion(Ce3+) on the proliferation,differentiation,adipocytic transdifferentiation and mineralization function of primary mouse osteoblasts(OBs) were investigated.The results indicated that Ce3+ at all concentrations(1×10-9,1×10-8,1×10-7,1×10-6,1×10-5,and 1×10-4 mol/L) promoted the proliferation of osteoblasts(OBs).On day 1 and 3,Ce3+ promoted the differentiation of OBs at concentrations of 1×10-9,1×10-7,and 1×10-6 mol/L,but inhibited the differentiation of OBs at higher concentrations.On day 2,Ce3+ inhibited the differentiation of OBs at tested concentrations.On day 9 and 12,Ce3+ inhibited the adipocytic transdifferentiation of OBs at most concentrations.On day 15,Ce3+ promoted the adipocytic transdifferentiation of OBs at concentrations of 1×10-9,1×10-6,1×10-5,and 1×10-4 mol/L,but had no effects at other concentrations.Ce3+ inhibited the formation of mineralized matrix nodules of OBs at concentrations of 1×10-9,1×10-8 and 1×10-7 mol/L,and promoted the formation of mineralized matrix nodules of OBs at other concentrations.These findings suggested that the effects of Ce3+ on the proliferation,differentiation,adipocytic transdifferentiation and mineralization function of primary OBs depended on the concentration and culture time;moreover,they were pivotal factors for switching the biological effects of Ce3+ from toxicity to activity,from damage to protection,or from down-regulation to up-regulation.展开更多
基金supported by the National Natural Science Foundation of China ( 81772017,31570940)Young Talent Fund of University Association for Science and Technology in Shaanxi,China ( 20170401)Supported by Natural Science Basic Research Plan in Shaanxi Province of China ( 2018JM3040)
文摘The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MACF1)is downregulated in association with the decreased osteoblast differentiation and bone formation under simulated microgravity conditions.These findings suggest that MACF1 is sensitive to mechanical condition and may be critical for osteoblast differentiation and bone formation.To verify this hypothesis,current study investigates the role and mechanism of MACF1 in regulatingosteoblast differentiation by adopting MACF1 knockdown(MACF1-KD)osteoblasts.The results showed that MACF1 knockdown suppressed mineralized nodules formation,alkaline phosphatase(ALP)activity,osteogenic gene expression andβ-catenin signaling transduction.Moreover,we used RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)to investigate further mechanism.Interestingly,we found that MACF1 sequesterd repressors of osteoblast differentiation in cytoplasm.In conclusion,MACF1 is sensitive to mechanical condition and plays key role in activatingβ-catenin signaling transduction and sequestering repressors of osteoblast differentiation,which further promotes osteoblast differentiation.
基金The project supported by Tsinghua University Initiative Scientific Research Program(2011THZ0)the National Natural Science Foundation of China(81270425)
文摘OBJECTIVE To investigate the effect of Pinctadafucata mantle gene 1(pfmg1)on osteoporotic bone lossand the role in osteoblast differentiation and matrix mineralization,and to explore the molecular mechanismof how PFMG1 functions through both animal and cellular experiments.METHODS For animal experiments,female BALB/c mice were subjected to sham-operation(sham)or ovariectomy(ovx)at 5weeks of age,control and pfmg1 lentiviral particles were packaged and injected through tail vein to ovx mice(2×107TU/mouse),respectively.Bone mineral density(BMD)was detected 2 months after the surgery,and the proximal tibia was scanned in three dimensions byμCT.For cellular experiments,GST-PFMG1 protein was expressed and purified,then added to MC3T3E1 cell culture medium.MTT,ALP activity and the level of matrix mineralization were detected after the treatment.RESULTSEctopic expression of pfmg1 gene enhanced the BMD level of ovx mice.μCT images revealed that PFMG1 improvedthe osteoporotic characteristics caused by ovariectomy,including the decreases in trabecular number(Tb.N),trabecular thickness(Tb.Th),and in trabecular bone volume as a percentage of total bone volume(BV/TV);and the increases in trabecular spacing(Tb.Sp)and trabecular bone pattern factor(TBPf).The alkaline phosphatase(ALP)activity and the level of matrix mineralization increased,while the MTT activity decreased after treated with PFMG1 in the osteoblast cell line MC3T3E1.CONCLUSION PFMG1 from the mental of P.fucatacould promote osteoblast differentiation and matrix mineralization in vitro,and couldprevent bone loss caused by ovariectomy in vivo.These findings showed the potential of PFMG1 from nacre as a therapeutic drug for osteoporosis.
文摘Aims: Previous studies reported that reduced bone formation was identified in fasting adult female mice compared with the ad libitum control group. An increasing number of studies have shown that miRNAs contribute to bone homeostasis. Unfortunately, there are minor concerns about the underlying mechanisms in osteoblastic differentiation under malnutrition conditions. Methods: We investigated microRNAs (miRNAs) in osteoblastic differentiation under malnutrition conditions using high-throughput bioinformatics approaches. To screen for targeted microRNAs, sequences were quantified by aligning reads to miRbase using miRDeep2 software. Unadjusted p-values were calculated using the Student’s t-test. Genes with a p-value of <0.05 and log 2FC (fold change) ≥ 1 were considered differentially expressed genes (DEGs). DEGs were submitted to Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, respectively. Results: They were mainly enriched in biological process terms type and biological pathways, respectively. Particularly, we evaluated seven microRNAs, mir-494 3p, mir-466, mir-455, mir-708, mir-298, mir-92 and mir-224, which likely play roles in osteoblastogenesis in fasting adult mice. Conclusion: To our knowledge, this is the first study on the expression pattern of miRNA in osteoblasts of malnourished adult mice. These targeting miRNAs may provide a potential therapeutic approach to treat osteoporosis.
文摘Objective:To study the effects of neurotrophin-3 (NT-3) intervention on bone marrow mesenchymal stem cell osteoblast differentiation as well as cell proliferation and apoptosis. Methods: Bone marrow mesenchymal stem cells were cultured and divided into control group, 25 ng/mL NT-3 group, 50 ng/mL NT-3 group and 100 ng/mL NT-3 group, they were treated with different doses of NT-3 for 24 h, and then osteoblast marker gene, cell proliferation gene and apoptosis gene expression were determined.Results: RUNX2, Osterix, ALP, OCN, BMP-2, Bcl-2, Nrf2, ERK1/2 and PCNA mRNA expression in 25 ng/mL NT-3 group, 50 ng/mL NT-3 group and 100 ng/mL NT-3 group were significantly higher than those in control group whereas Bim, Bax, Caspase-3, CHOP and Beclin1 mRNA expression were significantly lower than those in control group, and the larger the dose of NT-3, the higher the RUNX2, Osterix, ALP, OCN, BMP-2, Bcl-2, Nrf2, ERK1/2 and PCNA mRNA expression whereas the lower the Bim, Bax, Caspase-3, CHOP and Beclin1 mRNA expression.Conclusion: NT-3 intervention in bone marrow mesenchymal stem cells can promote osteoblast differentiation and cell proliferation and inhibit apoptosis.
文摘Objective: To study the effect of low-level laser irradiation (LLLI) combined with ferulic acid on the osteoblast differentiation and maturation as well as osteogenesis signaling pathway expression. Methods: The cranium was collected from the SD rats born within 24 h, osteoblasts were separated, cultured and then divided into control group, ferulic acid group, LLLI group, ferulic acid + LLLI group, and the expression osteoblast differentiation markers, proliferation molecules and signaling pathway molecules were detected after continuous treatment with different conditions for three days. Results: 3 d after treatment, the Bax and Bid mRNA expression in ferulic acid group, LLLI group and ferulic acid + LLLI group of cells were significantly lower than those in control group while Bcl-2, CyclinD1, E2F, Col-I, OC and ALP mRNA expression as well as Wnt, β-catenin, Runx2, cAMP and PKA protein expression were significantly higher than those in control group;Bax and Bid mRNA expression in ferulic acid + LLLI group of cells were significantly lower than those in ferulic acid group and LLLI group while Bcl-2, CyclinD1, E2F, Col-I, OC and ALP mRNA expression as well as Wnt, β-catenin, Runx2, cAMP and PKA protein expression were significantly higher than those in ferulic acid group and LLLI group;Col-I, OC, ALP, Bax, Bid, Bcl-2, CyclinD1 and E2F mRNA expression as well as Wnt, β-catenin, Runx2, cAMP and PKA protein expression were not significantly different between ferulic acid group and LLLI group. Conclusion: Low-level laser irradiation (LLLI) combined with ferulic acid can promote osteoblast differentiation and maturation and activate osteogenesis signaling pathway.
基金supported by grants by Zhejiang Qianjiang Talent Program(No.21040040-E)the Department of Sci-Tech of Zhejiang Province(No.LGF19H140002)+4 种基金a startup grant from Zhejiang Sci-Tech University(No.18042290-Y,2021Q031)funds from National Natural Science Foundation of China(No.81900806,81400489)the basic Public Welfare Planning Project of Zhejiang Province(No.LGD20C040001)Jiaxing Science Technology Foundation(No.2020AY10001)Jiaxing Key Laboratory of Animal Model Generation and Precise Synthesis of New Drug Leads。
文摘Wnt signaling executes an indispensable performance in osteoblast differentiation,bone development,homeostasis,and remodeling.Wnt signals trigger the intracellular Wnt signaling cascade to initiate regulating the implication of b-catenin in the bone environment.Going through the novel discoveries done via high-throughput sequencing technologies on ge-netic mouse models,we highlighted the significant contribution of Wnt ligands,co-receptors,inhibitors,their related skeletal phenotypes in mouse models and the similar bone disorders clinically observed in human beings.Moreover,the crosstalk between Wnt signaling pathway and BMP,TGF-b,FGF,Hippo,Hedgehog,Notch and PDGF signaling pathways is thoroughly demonstrated to be the underlying gene regulatory network that orchestrates osteoblast dif-ferentiation and bone development.We also introspected the significance of Wnt signaling transduction in the reorganization of cellular metabolism by stimulating glycolysis,glutamine catabolism,and fatty acid oxidation in osteoblast-lineage cells that display an important reg-ulatory arbor in the cellular bioenergetics of the bone.Throughout this evaluation,most to date therapeutical approaches towards osteoporosis and other bone maladies found in human beings,are formulated with an aspiration to holistically revamp the present clinical applica-tions involving various monoclonal antibodies therapies that lack specificity,efficacy,and safety into more requisite advanced therapeutics that satisfy these three requirements for further clinical considerations.Conclusively,our review provides comprehensive scientific findings related to the fundamental significance of Wnt signaling cascades in skeletal system and the underlying gene regulatory network with other signaling pathways enlightening re-searchers with the possibility to further integrate the identified target molecules into thera-peutic strategies for skeletal disorders treatment in the clinic.
基金support from the Public Platform of Medical Research Center,Academy of Chinese Medical Science,Zhejiang Chinese Medical Universitysponsored by the National Natural Science Foundation of China(81973534,U1505226)。
文摘Increasing the osteogenic differentiation ability and decreasing the adipogenic differentiation ability of bone marrow mesenchymal stem cells(BMSCs)is a potential strategy for the treatment of osteoporosis(OP).Naturally derived oligosaccharides have shown significant anti-osteoporotic effects.Nystose(NST),an oligosaccharide,was isolated from the roots of Morinda officinalis How.(MO).The aim of the present study was to investigate the effects of NST on bone loss in ovariectomized mice,and explore the underlying mechanism of NST in promoting differentiation of BMSCs to osteoblasts.Administration of NST(40,80 and 160 mg/kg)and the positive control of estradiol valerate(0.2 mg/kg)for 8 weeks significantly prevented bone loss induced by ovariectomy(OVX),increased the bone mass density(BMD),improved the bone microarchitecture and reduced urine calcium and deoxypyridinoline(DPD)in ovariectomized mice,while inhibited the increase of body weight without significantly affecting the uterus weight.Furthermore,we found that NST increased osteogenic differentiation,inhibited adipogenic differentiation of BMSCs in vitro,and upregulated the expression of the key proteins of BMP and Wnt/β-catenin pathways.In addition,Noggin and Dickkopf-related protein-1(DKK-1)reversed the effect of NST on osteogenic differentiation and expression of the key proteins in BMP and Wnt/β-catenin pathway.The luciferase activities and the molecular docking analysis further supported the mechanism of NST.In conclusion,these results indicating that NST can be clinically used as a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis.
基金the funding provided by the Ministry of Science and Technology,Taiwan(108-2314-B-037-075)the Kaohsiung Medical University Research Foundation(KMU-M103001,KMU-M104003,KMU-TP104PR16).
文摘Areca nut is used worldwide as a hallucinogenic addicting drug along the tropical belt.Arecoline,a toxic compound,is the most important alkaloid in areca nuts.The adverse effects of oral uptake and chewing of areca nut are well known.For example,the possibility of cancer caused by chewing areca nuts is widely discussed.Chewing areca nut has other adverse effects on other organs,including abnormal cell differentiation,oral cancer,and several other diseases.The use of areca nut is also associated with low birthweight.Skeletal musculature is the largest organ in the body and is attached to the bones.During embryo development,the differentiation of bone and muscle cells is critical.In this article,we reviewed the effects of areca nut and arecoline on embryonic cell differentiation,particularly osteoblasts,myoblasts,and fibroblasts.
基金Supported by the National Natural Science Foundation of China,No.81471094 and No.82202743.
文摘BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.
基金funded by the National Natural Science Foundation of China (Grant Nos. 41971015)Doctoral research program of China West Normal University (Grant Nos.19E067)。
文摘Rural settlement is the basic spatial unit for compact communities in rural area. Scientific exploration of spatial-temporal differentiation and its influencing factors is the premise of spatial layout rationalization. Based on land use data of Liangshan Yi Autonomous Prefecture(hereinafter referred to as Liangshan Prefecture) in Sichuan Province, China from 1980 to 2020, compactness index, fractal dimension, imbalance index, location entropy and the optimal parameters-based geographical detector(OPGD) model are used to analyze the spatial-temporal evolution of the morphological characteristics of rural settlements, and to explore the influence of natural geographical factors, socioeconomic factors, and policy factors on the spatial differentiation of rural settlements. The results show that:(1) From 1980 to 2020, the rural settlements area in Liangshan Prefecture increased by 15.96 km^(2). In space, the rural settlements are generally distributed in a local aggregation, dense in the middle and sparse around the periphery. In 2015, the spatial density and expansion index of rural settlements reached the peak.(2) From 1980 to 2020, the compactness index decreased from 0.7636 to 0.7496, the fractal dimension increased from 1.0283 to 1.0314, and the fragmentation index decreased from 0.1183 to 0.1047. The spatial morphological structure of rural settlements tended to be loose, the shape contour tended to be complex, the degree of fragmentation decreased, and the spatial distribution was significantly imbalanced.(3) The results of OPGD detection in 2015 show that the influence of each factor is slope(0.2371) > traffic accessibility(0.2098) > population(0.1403) > regional GDP(0.1325) > elevation(0.0987) > poverty alleviation(0). The results of OPGD detection in 2020 show that the influence of each factor is slope(0.2339) > traffic accessibility(0.2198) > population(0.1432) > regional GDP(0.1219) > poverty alleviation(0.0992) > elevation(0.093). Natural geographical factors(slope and elevation) are the basic factors affecting the spatial distribution of rural settlements, and rural settlements are widely distributed in the river valley plain and the second half mountain area. Socioeconomic factors(traffic accessibility, population, and regional GDP) have a greater impact on the spatial distribution of rural settlements, which is an important factor affecting the spatial distribution of rural settlements. Policy factors such as poverty alleviation relocation have an indispensable impact on the spatial distribution of rural settlements. The research results can provide decisionmaking basis for the spatial arrangement of rural settlements in Liangshan Prefecture, and optimize the implementation of rural revitalization policies.
基金funded by grants from the National Natural Science Foundation of China(Nos.81771095,82071235)Key R&D Program of Shaanxi Province(2017SF-103,2021KWZ-26,2023-JC-ZD-56)State Key Laboratory of Military Stomatology(2020ZA01).
文摘Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune response.These properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative medicine.While many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular aspects.Recent evidence suggests that DSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress conditions.This comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC differentiation.To achieve this goal,we dissect the intricacies of autophagy and its mechanisms.Subsequently,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic trajectories.Furthermore,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic milieu.The implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.
基金the Fujian Province Clinical Key Specialty Construction Project,No.2022884Quanzhou Science and Technology Plan Project,No.2021N034S+1 种基金The Youth Research Project of Fujian Provincial Health Commission,No.2022QNA067Malignant Tumor Clinical Medicine Research Center,No.2020N090s.
文摘BACKGROUND The study on predicting the differentiation grade of colorectal cancer(CRC)based on magnetic resonance imaging(MRI)has not been reported yet.Developing a non-invasive model to predict the differentiation grade of CRC is of great value.AIM To develop and validate machine learning-based models for predicting the differ-entiation grade of CRC based on T2-weighted images(T2WI).METHODS We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023.Patients were randomly assigned to a training cohort(n=220)or a validation cohort(n=95)at a 7:3 ratio.Lesions were delineated layer by layer on high-resolution T2WI.Least absolute shrinkage and selection operator regression was applied to screen for radiomic features.Radiomics and clinical models were constructed using the multilayer perceptron(MLP)algorithm.These radiomic features and clinically relevant variables(selected based on a significance level of P<0.05 in the training set)were used to construct radiomics-clinical models.The performance of the three models(clinical,radiomic,and radiomic-clinical model)were evaluated using the area under the curve(AUC),calibration curve and decision curve analysis(DCA).RESULTS After feature selection,eight radiomic features were retained from the initial 1781 features to construct the radiomic model.Eight different classifiers,including logistic regression,support vector machine,k-nearest neighbours,random forest,extreme trees,extreme gradient boosting,light gradient boosting machine,and MLP,were used to construct the model,with MLP demonstrating the best diagnostic performance.The AUC of the radiomic-clinical model was 0.862(95%CI:0.796-0.927)in the training cohort and 0.761(95%CI:0.635-0.887)in the validation cohort.The AUC for the radiomic model was 0.796(95%CI:0.723-0.869)in the training cohort and 0.735(95%CI:0.604-0.866)in the validation cohort.The clinical model achieved an AUC of 0.751(95%CI:0.661-0.842)in the training cohort and 0.676(95%CI:0.525-0.827)in the validation cohort.All three models demonstrated good accuracy.In the training cohort,the AUC of the radiomic-clinical model was significantly greater than that of the clinical model(P=0.005)and the radiomic model(P=0.016).DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process.CONCLUSION In this study,we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC.This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.
基金supported in part by a grant,PHA1110214,from MOE,Taiwan.
文摘This paper presents a new method of using a convolutional neural network(CNN)in machine learning to identify brand consistency by product appearance variation.In Experiment 1,we collected fifty mouse devices from the past thirty-five years from a renowned company to build a dataset consisting of product pictures with pre-defined design features of their appearance and functions.Results show that it is a challenge to distinguish periods for the subtle evolution of themouse devices with such traditionalmethods as time series analysis and principal component analysis(PCA).In Experiment 2,we applied deep learning to predict the extent to which the product appearance variation ofmouse devices of various brands.The investigation collected 6,042 images ofmouse devices and divided theminto the Early Stage and the Late Stage.Results show the highest accuracy of 81.4%with the CNNmodel,and the evaluation score of brand style consistency is 0.36,implying that the brand consistency score converted by the CNN accuracy rate is not always perfect in the real world.The relationship between product appearance variation,brand style consistency,and evaluation score is beneficial for predicting new product styles and future product style roadmaps.In addition,the CNN heat maps highlight the critical areas of design features of different styles,providing alternative clues related to the blurred boundary.The study provides insights into practical problems for designers,manufacturers,and marketers in product design.It not only contributes to the scientific understanding of design development,but also provides industry professionals with practical tools and methods to improve the design process and maintain brand consistency.Designers can use these techniques to find features that influence brand style.Then,capture these features as innovative design elements and maintain core brand values.
文摘BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development,as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation.AIM To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms.METHODS 20 growing mice were randomly divided into two groups:Con group(control group,n=10)and Ex group(treadmill exercise group,n=10).Hematoxylin-eosin staining,immunohistochemistry,and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur.Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19(lncRNA H19).RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation.RESULTS Compared with the Con group,the expression of bone morphogenetic protein 2 was also significantly increased.The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density,bone volume fraction,and the number of trabeculae,and decreased trabecular segregation in the femur of mice.Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation.In addition,knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers,which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence.CONCLUSION Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice,thus enhancing the peak bone mass of mice.The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.
基金Supported by Development Program of Shaanxi Province,No.2021SF-221.
文摘BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely related to the safety and efficacy of ESD.
基金This work was supported by grants from the National Natural Science Foundation of China(81830078,81772347,and 81572123)Science and Technology Commission of Shanghai Municipality(19XD1434100 and 16430723500)+1 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(2016131A)Shanghai Jiao Tong University-The Chinese University of Hong Kong joint Research Collaboration Fund.
文摘PIP5k1βis crucial to the generation of phosphotidylinosotol(4,5)P2.PIP5k1βparticipates in numerous cellular activities,such as B cell and platelet activation,cell phagocytosis and endocytosis,cell apoptosis,and cytoskeletal organization.In the present work,we aimed to examine the function of PIP5k1βin osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment.We discovered that PIP5k1β deletion in mice resulted in obvious bone loss and that PIP5k1β was highly expressed during both osteoclast and osteoblast differentiation.Deletion of the gene was found to enhance the proliferation and migration of bone marrow-derived macrophage-like cells to promote osteoclast differentiation.PIP5k1β-/-osteoclasts exhibited normal cytoskeleton architecture but stronger resorption activity.PIP5kip deficiency also promoted activation of mitogen-activated kinase and Akt signaling,enhanced TRAF6 and c-Fos expression,facilitated the expression and nuclear translocation of NFATC1,and upregulated Grb2 expression,thereby accelerating osteoclast differentiation and function.Finally,PIP5k1β enhanced osteoblast differentiation by upregulating master gene expression through triggering smad1/5/8 signaling.Therefore,PIP5k1βmodulates bone homeostasis and remodeling.
基金supported by the National Natural Science Foundation of China, China (No. 31400304)the Natural Science Foundation of Hubei Province, China (No. 2012FFB00303)+1 种基金the Youth & Middle-aged Talent Project of Hubei Province (No. Q20111005)the Science and Technology Program of Shandong Province (No. J12LL07)
文摘The iso fl avone calycosin-7-O-β-D-glucopyranoside(CG) is a principal constituent of Astragalus membranaceus(AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this study was to investigate the osteogenic effects of CG and its underlying mechanism in ST2 cells. The results show that exposure of cells to CG in osteogenic differentiation medium increases ALP activity, osteocalcin(Ocal) m RNA expression and the osteoblastic mineralization process. Mechanistically, CG treatment increased the expression of bone morphogenetic protein 2(BMP-2), p-Smad 1/5/8, β-catenin and Runx2, all of which are regulators of the BMP- or wingless-type MMTV integration site family(WNT)/β-catenin-signaling pathways. Moreover, the osteogenic effects of CG were inhibited by Noggin and DKK-1 which are classical inhibitors of the BMP and WNT/β-catenin-signaling pathways, respectively. Taken together, the results indicate that CG promotes the osteoblastic differentiation of ST2 cells through regulating the BMP/WNT signaling pathways. On this basis, CG may be a useful lead compound for improving the treatment of bone-decreasing diseases and enhancing bone regeneration.
基金This study was supported by the National Natural Science Foundation of China(No.81800343).
文摘Amyloid beta(AB)peptide 40 enhances the activation of receptor for advanced glycation end products(RAGE)in immune-inflammatory diseases.RAGE exhibits several ffects in the setting of numerous cardiovascular events.We bypothesized that the Aβ40/RAGE pathway is involved in the osteoblastic differentiation of the valvular interstitial cell(VIC)phenotype,and RAGE knockout intervention could reduce the calcification of aortic valve interstitial cells(AVICs)by inhibiting the extracellular-regulated kinase1/2(ERK 1/2)/nuclear factor kappa-B(NF-kB)signaling pathway.To test this hypothesis,the activation of AB40/RAGE pathway in human calcific AVs was evaluated with immunohistochemical staining.Cultured calcific VIC models were used in vitro.The VICs were stimulated using Aβ40,with or without RAGE small interfering ribonucleic acid(siRNA),and ERK1/2 and NF-κB inhibitors for analysis.Our data revealed that AB40 induced the ERK 1/2/NF-κB signaling pathway and osteoblastic differentiation of AVICs via the RAGE pathway in vitro.
文摘Bone-resorbing osteoclasts are formed from a monocyte/macrophage lineage under the strict control o bone-forming osteoblasts. So far,macrophage colonystimulating factor(M-CSF),receptor activator o nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG) produced by osteoblasts play major roles in the regulation of osteoclast differentiation. Recent studies have shown that osteoblasts regulate osteoclastogenesis through several mechanisms independent o M-CSF,RANKL,and OPG production. Identification o osteoclast-committed precursors in vivo demonstrated that osteoblasts are involved in the distribution o osteoclast precursors in bone. Interleukin 34(IL-34)a novel ligand for c-Fms,plays a pivotal role in maintaining the splenic reservoir of osteoclast-committed precursors in M-CSF deficient mice. IL-34 is also able to act as a substitute for osteoblast-producing M-CSF in osteoclastogenesis. Wnt5 a,produced by osteoblasts,enhances osteoclast differentiation by upregulating RANK expression through activation of the noncanonical Wnt pathway. Semaphorin 3A produced by osteoblasts inhibits RANKL-induced osteoclast differentiation through the suppression of immunoreceptortyrosine-based activation motif signals. Thus,recent findings show that osteoclast differentiation is tightly regulated by osteoblasts through several different mechanisms. These newly identified molecules are expected to be promising targets of therapeutic agents in bone-related diseases.
基金supported by the Natural Science Foundation of China (20971034)Foundation for Key Program of Ministry of Education of China (208018)+2 种基金Returned Scholars of Hebei Province (207041)Natural Science Foundation of Hebei Province (B2009000161)Natural Science Foundation of Hebei University
文摘The effects of cerium ion(Ce3+) on the proliferation,differentiation,adipocytic transdifferentiation and mineralization function of primary mouse osteoblasts(OBs) were investigated.The results indicated that Ce3+ at all concentrations(1×10-9,1×10-8,1×10-7,1×10-6,1×10-5,and 1×10-4 mol/L) promoted the proliferation of osteoblasts(OBs).On day 1 and 3,Ce3+ promoted the differentiation of OBs at concentrations of 1×10-9,1×10-7,and 1×10-6 mol/L,but inhibited the differentiation of OBs at higher concentrations.On day 2,Ce3+ inhibited the differentiation of OBs at tested concentrations.On day 9 and 12,Ce3+ inhibited the adipocytic transdifferentiation of OBs at most concentrations.On day 15,Ce3+ promoted the adipocytic transdifferentiation of OBs at concentrations of 1×10-9,1×10-6,1×10-5,and 1×10-4 mol/L,but had no effects at other concentrations.Ce3+ inhibited the formation of mineralized matrix nodules of OBs at concentrations of 1×10-9,1×10-8 and 1×10-7 mol/L,and promoted the formation of mineralized matrix nodules of OBs at other concentrations.These findings suggested that the effects of Ce3+ on the proliferation,differentiation,adipocytic transdifferentiation and mineralization function of primary OBs depended on the concentration and culture time;moreover,they were pivotal factors for switching the biological effects of Ce3+ from toxicity to activity,from damage to protection,or from down-regulation to up-regulation.
