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
Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors ...Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors have been gradually elucidated,the potential mechanisms of O-GlcNAcylation in bone metabolism,particularly,in the osteogenic differentiation of bone marrow mesenchymal stromal cells(BMSCs)remains unexplored.In this study,the literature related to O-GlcNAcylation and BMSC osteogenic differentiation was reviewed,assuming that it could trigger more scholars to focus on research related to OGlcNAcylation and bone metabolism and provide insights into the development of novel therapeutic targets for bone metabolism disorders such as osteoporosis.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
Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two s...Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes,in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes.Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis.However,the mechanism underlying the adipogenic differentiation of MSCs is not fully understood.Here,the current knowledge of adipogenic differentiation in MSCs is reviewed,focusing on signaling pathways,noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation.Finally,the relationship between maladipogenic differentiation and diseases is briefly discussed.We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.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
Objective:Polyploid giant cancer cells(PGCCs)with daughter cells express epithelial–mesenchymal transition(EMT)-associated proteins.Highly malignant tumor cells with EMT properties can transdifferentiate into mature ...Objective:Polyploid giant cancer cells(PGCCs)with daughter cells express epithelial–mesenchymal transition(EMT)-associated proteins.Highly malignant tumor cells with EMT properties can transdifferentiate into mature tumor cells.In this study,we elucidated the potential for,and underlying mechanism of,adipogenic differentiation of PGCCs with daughter cells(PDCs).Methods:Cobalt chloride was used to induce PGCC formation in HEY(wild-type P53)and MDA-MB-231(mutant P53)cells;these cells were then cultured in adipogenic differentiation medium.Oil red O staining was used to confirm adipogenic differentiation,and the cell cycle was detected with flow cytometry.The expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation.Animal xenograft models were used to confirm the adipogenic differentiation of PDCs.Results:PDCs transdifferentiated into functional adipocytes.Two different cell cycle distributions were observed in PDCs after adipogenic differentiation.The expression levels of PPARγ,Ace-PPARγ,and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic differentiation.Ace-PPARγand FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown.A485 treatment increased Ace-P53,Ace-PPARγ,and FABP4 expression in HEY PDCs by inhibiting SUMOylation of P53.In MDA-MB-231 PDCs,A485 treatment decreased Ace-P53,Ace-PPARγ,and FABP4 expression.Animal experiments also confirmed the adipogenic differentiation of PDCs.Conclusions:Acetylation of P53 and PPARγplays an important role in the adipogenic differentiation of PDCs.展开更多
Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).S...Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).Serum biomarkers,substances that quantitatively change in sera during disease development,are a promising non-invasive tool with high utility for differentiating between these diseases.In this way,the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4(IgG4)antibody are elevated.However,this approach has some drawbacks.Notably,IgG4 antibody concentrations are also elevated in sera from some patients with PDAC.This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC,evaluating the usefulness of immunoglobulins,autoantibodies,chemokines,and cytokines.The proposed serum biomarkers have proven useful,although most studies had a small sample size,did not examine their presence in patients with PDAC,or did not test them in humans.In addition,current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity,either alone or in combination with clinical data and/or radiological images.展开更多
The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory ...The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory molecules,which lead to repair failure.Accordingly,blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination.In the central nervous system,oligodendrocytes form the myelin sheath.We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation.Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function.Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation,as well as PI3K signaling pathways that are needed in the mid-late stages.When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination,it enhanced myelin regeneration and promoted motor function recovery.These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.展开更多
Boiogito (BOT) ameliorates insulin resistance and diabetes in several animal models;however, the underlying mechanisms for these in vivo effects remain unclear. Thiazolidine derivatives, which are peroxisome prolifera...Boiogito (BOT) ameliorates insulin resistance and diabetes in several animal models;however, the underlying mechanisms for these in vivo effects remain unclear. Thiazolidine derivatives, which are peroxisome proliferator-activated receptor γ (PPARγ) agonists for the treatment of type II diabetes, promote adiponectin production by inducing adipocyte differentiation, thereby reducing insulin resistance. This study aimed to evaluate the effect of BOT on adipocyte differentiation using cultured human visceral preadipocytes (HVPAds) compared with the thiazolidine derivative troglitazone (TRG). We investigated the effects of BOT (0.125 - 1 mg/mL) and TRG (10 μM) on the differentiation of adipocytes treated with or without tumor necrosis factor-α (TNF-α: 5 ng/mL). On day 14 of culture, the following adipocyte differentiation marker levels were measured: intracellular lipids, extracellular (i.e., medium) adiponectin, and intracellular differentiation-related genes (PPARγ, CCAAT/enhancer binding protein, adiponectin, differentiation cluster 36, glucose transporter type 4). BOT and TRG increased factors associated with differentiation including lipid, adiponectin, and differentiation-related gene expression levels compared with the controls. The increases in these differentiation markers were inhibited by the PPARγ antagonist GW9662 (20 μM). Furthermore, TNF-α decreased all differentiation marker levels. The decreases in differentiation markers were inhibited by BOT and TRG;however, these inhibitory effects were blocked by GW9662. The results suggest that BOT increases the synthesis and secretion of adiponectin by promoting differentiation similar to TRG. This study is the first to demonstrate that adipocyte differentiation-promoting activity is a mechanism for the beneficial effects of BOT on diabetes and insulin resistance.展开更多
The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and ...The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and osteogenic lineages.In this study,exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its 0.52-fold downregulation in patients with MDS compared with controls(NOR)and was downregulated 0.55-fold in MDS-MSCs compared with NOR-MSCs.Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic differentiation and decreased adipogenic differentiation in vitro,while inhibition of miR-103-3p showed the opposite results in NOR-MSCs.Thus,the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs,significantly impacting MDS-MSCs differentiation.The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while weakening lipid differentiation,thereby providing possible target for the treatment of MDS pathogenesis.展开更多
Tissue curvature has long been recognized as an important anatomical parameter that affects intracellular behaviors,and there is emerging interest in applying cell-scale curvature as a designer property to drive cell ...Tissue curvature has long been recognized as an important anatomical parameter that affects intracellular behaviors,and there is emerging interest in applying cell-scale curvature as a designer property to drive cell fates for tissue engineering purposes.Although neural cells are known to undergo dramatic and terminal morphological changes during development and curvature-limiting behaviors have been demonstrated in neurite outgrowth studies,there are still crucial gaps in understanding neural cell behaviors,particularly in the context of a three-dimensional(3D)curvature landscape similar to an actual tissue engineering scaffold.In this study,we fabricated two substrates of microcurvature(curvature-substrates)that present a smooth and repeating landscape with focuses of either a concave or a convex pattern.Using these curvature-substrates,we studied the properties of morphological differentiation in N2a neuroblastoma cells.In contrast to other studies where two-dimensional(2D)curvature was demonstrated to limit neurite outgrowth,we found that both the concave and convex substrates acted as continuous and uniform mechanical protrusions that significantly enhanced neural polarity and differentiation with few morphological changes in the main cell body.This enhanced differentiation was manifested in various properties,including increased neurite length,increased nuclear displacement,and upregulation of various neural markers.By demonstrating how the micron-scale curvature landscape induces neuronal polarity,we provide further insights into the design of biomaterials utilizing the influence of surface curvature in neural tissue engineering.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
Mesenchymal stem cells(MSCs),distributed in many tissues in the human body,are multipotent cells capable of differentiating in specific directions.It is usually considered that the differentiation process of MSCs depe...Mesenchymal stem cells(MSCs),distributed in many tissues in the human body,are multipotent cells capable of differentiating in specific directions.It is usually considered that the differentiation process of MSCs depends on specialized external stimulating factors,including cell signaling pathways,cytokines,and other physical stimuli.Recent findings have revealed other underrated roles in the differentiation process of MSCs,such as material morphology and exosomes.Although relevant achievements have substantially advanced the applicability of MSCs,some of these regulatory mechanisms still need to be better understood.Moreover,limitations such as long-term survival in vivo hinder the clinical application of MSCs therapy.This review article summarizes current knowledge regarding the differentiation patterns of MSCs under specific stimulating factors.展开更多
Osteoarthritis(OA)is a common degenerative joint disease that often involves progressive cartilage degeneration and bone destruction of subchondral bone.At present,clinical treatment is mainly for pain relief,and ther...Osteoarthritis(OA)is a common degenerative joint disease that often involves progressive cartilage degeneration and bone destruction of subchondral bone.At present,clinical treatment is mainly for pain relief,and there are no effective methods to delay the progression of the disease.When this disease progresses to the advanced stage,the only treatment option for most patients is total knee replacement surgery,which causes patients great pain and anxiety.As a type of stem cell,mesenchymal stem cells(MSCs)have multidirectional differentiation potential.The osteogenic differentiation and chondrogenic differentiation of MSCs can play vital roles in the treatment of OA,as they can relieve pain in patients and improve joint function.The differentiation direction of MSCs is accurately controlled by a variety of signaling pathways,so there are many factors that can affect the differentiation direction of MSCs by acting on these signaling pathways.When MSCs are applied to OA treatment,the microenvironment of the joints,injected drugs,scaffold materials,source of MSCs and other factors exert specific impacts on the differentiation direction of MSCs.This review aims to summarize the mechanisms by which these factors influence MSC differentiation to produce better curative effects when MSCs are applied clinically in the future.展开更多
Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therap...Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis.Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy.In this work,we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid(ATRA)via biomineralization.This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters,which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration.With the help of CSC differentiation induced by ATRA,IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner.Furthermore,ATRA can boost immunogenic cell death induced by phototherapy,thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells.Taken together,this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation,improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.展开更多
Background:Cardiomyocytes derived from human embryonic stem cells(hESCs)are regulated by complex and stringent gene networks during differentiation.Long non-coding RNAs(lncRNAs)exert critical epigenetic regulatory fun...Background:Cardiomyocytes derived from human embryonic stem cells(hESCs)are regulated by complex and stringent gene networks during differentiation.Long non-coding RNAs(lncRNAs)exert critical epigenetic regulatory functions in multiple differentiation processes.However,the involvement of lncRNAs in the differentiation of hESCs into cardiomyocytes has not yet been fully elucidated.Here,we identified the key roles of ZFAS1(lncRNA zinc finger antisense 1)in the differentiation of cardiomyocytes from hESCs.Methods:A model of cardiomyocyte differentiation from stem cells was established using the monolayer differentiation method,and the number of beating hESCs-derived cardiomyocytes was calculated.Gene expression was analyzed by quantitative real-time PCR(qRTPCR).Immunofluorescence assays were performed to assess the expression of cardiac troponin T(cTnT)andα-actinin protein in cardiomyocytes.Results:qRT-PCR showed that ZFAS1 expression in the mesoderm was significantly higher than that in embryonic stem cells,cardiac progenitor cells,and cardiomyocytes.Knockdown of ZFAS1 inhibited cardiomyocyte differentiation from hESCs,which was characterized by reduced expression of the cardiac-specific markers cTnT,α-actinin,myosin heavy chain 6(MYH6),and myosin heavy chain 7(MYH7).In contrast,ZFAS1 overexpression remarkably increased the percentage of spontaneously beating cardiomyocytes.In terms of the mechanism,we found that ZFAS1 is an antisense lncRNA at the 5′end of the protein-coding gene ZNFX1.Knockdown of ZFAS1 could increase the mRNA expression level of ZNFX1.Furthermore,qRT-PCR demonstrated that the silencing of ZNFX1 led to an increase in cardiac-specific markers that predicted the promotion of cardiomyocyte differentiation.Conclusion:Altogether,these data suggest that lncRNA-ZFAS1 is required for cardiac differentiation by functionally inhibiting the expression of ZNFX1,which may provide a reference for the treatment of heart disease to a certain extent.展开更多
Mesenchymal stem cells(MSCs)can differentiate into various tissue cell types including bone,adipose,cartilage,and muscle.Among those,osteogenic differentiation of MSCs has been widely explored in many bone tissue engi...Mesenchymal stem cells(MSCs)can differentiate into various tissue cell types including bone,adipose,cartilage,and muscle.Among those,osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies.Moreover,the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing.Recently,with the gra-dual recognition of adipokines,the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism,inflammation,immune regulation,energy disorders,and bone homeostasis.At the same time,the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely.Therefore,this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs,emphasizing bone formation and bone regeneration.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has very low overall survival.According to global cancer statistics,approximately 905677 new cases were reported in 2020,with at least 830180 of them being fatal.Cluster of diff...BACKGROUND Hepatocellular carcinoma(HCC)has very low overall survival.According to global cancer statistics,approximately 905677 new cases were reported in 2020,with at least 830180 of them being fatal.Cluster of differentiation 147(CD147)is a novel,transmembrane glycoprotein that is expressed in a wide variety of tumor cells and plays an important role in various stages of tumor development.Based on the reports described previously,we theorize that CD147 may be used as a novel biological indicator to predict the prognosis of HCC.To study this possibility,expression profiles of CD147 and corresponding clinical data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were analyzed,and a hazard ratio(HR)was established.AIM To explore the pattern of CD147 expression and its applicability in the prognosis of HCC.To establish HRs and probability points for predicting the prognosis of HCC by correlating CD147 expression with clinical characteristics.To determine if CD147 can be a reliable biomarker in HCC prognosis.METHODS The CD147 expression profile in HCC and corresponding clinical data were obtained from TCGA database.The expression patterns of CD147 were then validated by analyzing data from the GEO database.In addition,CD147 immunohistochemistry in HCC was obtained from the Human Protein Atlas.CD147 expression patterns and clinical characteristics in the prognosis of HCC were analyzed by accessing the UALCAN web resource.Accuracy,sensitivity,and specificity of the CD147 expression profile in predictive prognosis were determined by the time-dependent receiver operating characteristic(ROC)curves.Kaplan-Meier curves were plotted to estimate the HR of survival in HCC.Univariate and multivariate Cox regression proportional hazards analyses of CD147 expression levels and clinical characteristics as prognostic factors of HCC were performed.Nomograms were used to establish probability points and predict prognosis.RESULTS Data from TCGA and GEO databases revealed that CD147 was significantly overexpressed in HCC(P=1.624×10^(-12) and P=1.2×10^(-5),respectively).The expression of CD147 and prognosis of HCC were significantly correlated with the clinical characteristics of HCC as per the data from the UALCAN web resource(P<0.05).Kaplan-Meier analysis of CD147 expression in HCC revealed that the high expression groups showed poor prognosis and an HR of survival>1[log-rank test,P=0.000542,HR(in high expression group):1.856,95%confidence interval(CI):1.308 to 2.636].ROC curves were plotted to analyze the 1-year,3-year,and 5-year survival rates.The area under the ROC curve values were 0.675(95%CI:0.611 to 0.740),0.623(95%CI:0.555 to 0.692),and 0.664(95%CI:0.582 to 9.745),respectively.Univariate Cox analysis of CD147 expression and clinical characteristics of HCC and multivariate Cox analysis of CD147 patterns and pathological tumor-node-metastasis stage showed significant differences(univariate Cox,P=0.00013,HR:1.424,95%CI:1.884 to 1.707 and P=0.00066,HR:1.376,95%CI:1.145 to 1.654,respectively;multivariate Cox,P=0.00578,HR:1.507,95%CI:1.126 to 2.018 and P=0.00336,HR:1.443,95%CI:1.129 to 1.844,respectively).Nomograms were plotted to establish the probability points and predict prognosis.The total points ranged from 0 to 180,and the C-index value was 0.673(95%CI:0.600 to 1.000,P<0.01).CONCLUSION Overexpression of CD147 was correlated with poor prognosis in HCC.The CD147 expression profile combined with clinical characteristics can reliably predict the prognosis of HCC.CD147 can serve as a biomarker to predict the prognosis of HCC.展开更多
Flowering is a prerequisite for apple fruiting,and apple flower buds are mixed buds,that is,the vegetative organs and flower structure exist in the same terminal bud simultaneously,which are formed in the year before ...Flowering is a prerequisite for apple fruiting,and apple flower buds are mixed buds,that is,the vegetative organs and flower structure exist in the same terminal bud simultaneously,which are formed in the year before flowering and fruiting,mainly including spur terminal buds and axillary buds.The infrequent formation of flower buds during its growth and biennial bearing are closely related to flower bud differentiation.Therefore,this paper reviews the research progress of flower bud differentiation of apple from the morphological differentiation,plant hormones and flowering-related genes,in order to provide a theoretical reference for efficient cultivation and stable yield of apple.展开更多
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.
文摘Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors have been gradually elucidated,the potential mechanisms of O-GlcNAcylation in bone metabolism,particularly,in the osteogenic differentiation of bone marrow mesenchymal stromal cells(BMSCs)remains unexplored.In this study,the literature related to O-GlcNAcylation and BMSC osteogenic differentiation was reviewed,assuming that it could trigger more scholars to focus on research related to OGlcNAcylation and bone metabolism and provide insights into the development of novel therapeutic targets for bone metabolism disorders such as osteoporosis.
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 by the National Natural Science Foundation of China,No.82271843 and 31700779the Key Project supported by Medical Science and Technology Development Foundation,Nanjing Department of Health,No.ZKX20019the Natural Science Foundation of Jiangsu Province,No.BK20200137.
文摘Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes,in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes.Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis.However,the mechanism underlying the adipogenic differentiation of MSCs is not fully understood.Here,the current knowledge of adipogenic differentiation in MSCs is reviewed,focusing on signaling pathways,noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation.Finally,the relationship between maladipogenic differentiation and diseases is briefly discussed.We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.
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.
基金supported partly by grants from the National Natural Science Foundation of China(Grant Nos.82173283 and 82103088)the Foundation of the Committee on Science and Technology of Tianjin(Grant No.20JCYBJC01230)。
文摘Objective:Polyploid giant cancer cells(PGCCs)with daughter cells express epithelial–mesenchymal transition(EMT)-associated proteins.Highly malignant tumor cells with EMT properties can transdifferentiate into mature tumor cells.In this study,we elucidated the potential for,and underlying mechanism of,adipogenic differentiation of PGCCs with daughter cells(PDCs).Methods:Cobalt chloride was used to induce PGCC formation in HEY(wild-type P53)and MDA-MB-231(mutant P53)cells;these cells were then cultured in adipogenic differentiation medium.Oil red O staining was used to confirm adipogenic differentiation,and the cell cycle was detected with flow cytometry.The expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation.Animal xenograft models were used to confirm the adipogenic differentiation of PDCs.Results:PDCs transdifferentiated into functional adipocytes.Two different cell cycle distributions were observed in PDCs after adipogenic differentiation.The expression levels of PPARγ,Ace-PPARγ,and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic differentiation.Ace-PPARγand FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown.A485 treatment increased Ace-P53,Ace-PPARγ,and FABP4 expression in HEY PDCs by inhibiting SUMOylation of P53.In MDA-MB-231 PDCs,A485 treatment decreased Ace-P53,Ace-PPARγ,and FABP4 expression.Animal experiments also confirmed the adipogenic differentiation of PDCs.Conclusions:Acetylation of P53 and PPARγplays an important role in the adipogenic differentiation of PDCs.
文摘Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).Serum biomarkers,substances that quantitatively change in sera during disease development,are a promising non-invasive tool with high utility for differentiating between these diseases.In this way,the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4(IgG4)antibody are elevated.However,this approach has some drawbacks.Notably,IgG4 antibody concentrations are also elevated in sera from some patients with PDAC.This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC,evaluating the usefulness of immunoglobulins,autoantibodies,chemokines,and cytokines.The proposed serum biomarkers have proven useful,although most studies had a small sample size,did not examine their presence in patients with PDAC,or did not test them in humans.In addition,current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity,either alone or in combination with clinical data and/or radiological images.
基金supported by the National Nature Science Foundation of China,Nos.81371338(to HF)and 82071369(PPY)。
文摘The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory molecules,which lead to repair failure.Accordingly,blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination.In the central nervous system,oligodendrocytes form the myelin sheath.We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation.Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function.Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation,as well as PI3K signaling pathways that are needed in the mid-late stages.When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination,it enhanced myelin regeneration and promoted motor function recovery.These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.
文摘Boiogito (BOT) ameliorates insulin resistance and diabetes in several animal models;however, the underlying mechanisms for these in vivo effects remain unclear. Thiazolidine derivatives, which are peroxisome proliferator-activated receptor γ (PPARγ) agonists for the treatment of type II diabetes, promote adiponectin production by inducing adipocyte differentiation, thereby reducing insulin resistance. This study aimed to evaluate the effect of BOT on adipocyte differentiation using cultured human visceral preadipocytes (HVPAds) compared with the thiazolidine derivative troglitazone (TRG). We investigated the effects of BOT (0.125 - 1 mg/mL) and TRG (10 μM) on the differentiation of adipocytes treated with or without tumor necrosis factor-α (TNF-α: 5 ng/mL). On day 14 of culture, the following adipocyte differentiation marker levels were measured: intracellular lipids, extracellular (i.e., medium) adiponectin, and intracellular differentiation-related genes (PPARγ, CCAAT/enhancer binding protein, adiponectin, differentiation cluster 36, glucose transporter type 4). BOT and TRG increased factors associated with differentiation including lipid, adiponectin, and differentiation-related gene expression levels compared with the controls. The increases in these differentiation markers were inhibited by the PPARγ antagonist GW9662 (20 μM). Furthermore, TNF-α decreased all differentiation marker levels. The decreases in differentiation markers were inhibited by BOT and TRG;however, these inhibitory effects were blocked by GW9662. The results suggest that BOT increases the synthesis and secretion of adiponectin by promoting differentiation similar to TRG. This study is the first to demonstrate that adipocyte differentiation-promoting activity is a mechanism for the beneficial effects of BOT on diabetes and insulin resistance.
基金This work was supported by The Nature Science Foundation of China(Nos.82070176,82070128,81900132)the Medical Science and Technology Research Fund of Guangdong Province(No.A2020585).
文摘The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and osteogenic lineages.In this study,exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its 0.52-fold downregulation in patients with MDS compared with controls(NOR)and was downregulated 0.55-fold in MDS-MSCs compared with NOR-MSCs.Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic differentiation and decreased adipogenic differentiation in vitro,while inhibition of miR-103-3p showed the opposite results in NOR-MSCs.Thus,the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs,significantly impacting MDS-MSCs differentiation.The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while weakening lipid differentiation,thereby providing possible target for the treatment of MDS pathogenesis.
基金supported by the Inter-Departmental Open Project of State Key Laboratory in Ultra-Precision Machining Technology(SKL-UPMT,No.P0033576).
文摘Tissue curvature has long been recognized as an important anatomical parameter that affects intracellular behaviors,and there is emerging interest in applying cell-scale curvature as a designer property to drive cell fates for tissue engineering purposes.Although neural cells are known to undergo dramatic and terminal morphological changes during development and curvature-limiting behaviors have been demonstrated in neurite outgrowth studies,there are still crucial gaps in understanding neural cell behaviors,particularly in the context of a three-dimensional(3D)curvature landscape similar to an actual tissue engineering scaffold.In this study,we fabricated two substrates of microcurvature(curvature-substrates)that present a smooth and repeating landscape with focuses of either a concave or a convex pattern.Using these curvature-substrates,we studied the properties of morphological differentiation in N2a neuroblastoma cells.In contrast to other studies where two-dimensional(2D)curvature was demonstrated to limit neurite outgrowth,we found that both the concave and convex substrates acted as continuous and uniform mechanical protrusions that significantly enhanced neural polarity and differentiation with few morphological changes in the main cell body.This enhanced differentiation was manifested in various properties,including increased neurite length,increased nuclear displacement,and upregulation of various neural markers.By demonstrating how the micron-scale curvature landscape induces neuronal polarity,we provide further insights into the design of biomaterials utilizing the influence of surface curvature in neural tissue engineering.
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.
文摘Mesenchymal stem cells(MSCs),distributed in many tissues in the human body,are multipotent cells capable of differentiating in specific directions.It is usually considered that the differentiation process of MSCs depends on specialized external stimulating factors,including cell signaling pathways,cytokines,and other physical stimuli.Recent findings have revealed other underrated roles in the differentiation process of MSCs,such as material morphology and exosomes.Although relevant achievements have substantially advanced the applicability of MSCs,some of these regulatory mechanisms still need to be better understood.Moreover,limitations such as long-term survival in vivo hinder the clinical application of MSCs therapy.This review article summarizes current knowledge regarding the differentiation patterns of MSCs under specific stimulating factors.
基金the Nature Science Foundation of China,No.81701756Sichuan Provincial Department of Education,No.18ZB0215+1 种基金City-School Cooperation Project,No.18SXHZ0389 and No.22SXZRKX0005Chengdu Medical Project,No.2022573.
文摘Osteoarthritis(OA)is a common degenerative joint disease that often involves progressive cartilage degeneration and bone destruction of subchondral bone.At present,clinical treatment is mainly for pain relief,and there are no effective methods to delay the progression of the disease.When this disease progresses to the advanced stage,the only treatment option for most patients is total knee replacement surgery,which causes patients great pain and anxiety.As a type of stem cell,mesenchymal stem cells(MSCs)have multidirectional differentiation potential.The osteogenic differentiation and chondrogenic differentiation of MSCs can play vital roles in the treatment of OA,as they can relieve pain in patients and improve joint function.The differentiation direction of MSCs is accurately controlled by a variety of signaling pathways,so there are many factors that can affect the differentiation direction of MSCs by acting on these signaling pathways.When MSCs are applied to OA treatment,the microenvironment of the joints,injected drugs,scaffold materials,source of MSCs and other factors exert specific impacts on the differentiation direction of MSCs.This review aims to summarize the mechanisms by which these factors influence MSC differentiation to produce better curative effects when MSCs are applied clinically in the future.
基金supported by National Science and Technology Major Special Project-Major New Drug Creation(2019ZX09301-112)Shandong Natural Science Foundation(ZR2020QH351)+1 种基金Shandong Provincial Program of Taishan Industrial Experts(2019TSCYCX-31)the Fundamental Research Funds of Shandong University(2020GN091)
文摘Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis.Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy.In this work,we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid(ATRA)via biomineralization.This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters,which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration.With the help of CSC differentiation induced by ATRA,IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner.Furthermore,ATRA can boost immunogenic cell death induced by phototherapy,thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells.Taken together,this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation,improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.
基金the National Natural Science Foundation of China[81573434 to BZC]Heilongjiang Touyan Innovation Team Program[BZC],HMU Marshal Initiative Funding(HMUMIF-21018 to BZC)National Nature Science Youth Foudation of China[82000226 to XFG].
文摘Background:Cardiomyocytes derived from human embryonic stem cells(hESCs)are regulated by complex and stringent gene networks during differentiation.Long non-coding RNAs(lncRNAs)exert critical epigenetic regulatory functions in multiple differentiation processes.However,the involvement of lncRNAs in the differentiation of hESCs into cardiomyocytes has not yet been fully elucidated.Here,we identified the key roles of ZFAS1(lncRNA zinc finger antisense 1)in the differentiation of cardiomyocytes from hESCs.Methods:A model of cardiomyocyte differentiation from stem cells was established using the monolayer differentiation method,and the number of beating hESCs-derived cardiomyocytes was calculated.Gene expression was analyzed by quantitative real-time PCR(qRTPCR).Immunofluorescence assays were performed to assess the expression of cardiac troponin T(cTnT)andα-actinin protein in cardiomyocytes.Results:qRT-PCR showed that ZFAS1 expression in the mesoderm was significantly higher than that in embryonic stem cells,cardiac progenitor cells,and cardiomyocytes.Knockdown of ZFAS1 inhibited cardiomyocyte differentiation from hESCs,which was characterized by reduced expression of the cardiac-specific markers cTnT,α-actinin,myosin heavy chain 6(MYH6),and myosin heavy chain 7(MYH7).In contrast,ZFAS1 overexpression remarkably increased the percentage of spontaneously beating cardiomyocytes.In terms of the mechanism,we found that ZFAS1 is an antisense lncRNA at the 5′end of the protein-coding gene ZNFX1.Knockdown of ZFAS1 could increase the mRNA expression level of ZNFX1.Furthermore,qRT-PCR demonstrated that the silencing of ZNFX1 led to an increase in cardiac-specific markers that predicted the promotion of cardiomyocyte differentiation.Conclusion:Altogether,these data suggest that lncRNA-ZFAS1 is required for cardiac differentiation by functionally inhibiting the expression of ZNFX1,which may provide a reference for the treatment of heart disease to a certain extent.
基金the Changzhou Science&Technology Program,No.CJ20210104,CJ20220120,and CJ20210005Qinghai Province Health System Guidance Plan Project,No.2022-wjzdx-106+1 种基金Young Talent Development Plan of Changzhou Health commission,No.CZQM2020059Top Talent of Changzhou“The 14th Five-Year Plan”High-Level Health Talents Training Project,No.2022CZBJ059 and 2022CZBJ061.
文摘Mesenchymal stem cells(MSCs)can differentiate into various tissue cell types including bone,adipose,cartilage,and muscle.Among those,osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies.Moreover,the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing.Recently,with the gra-dual recognition of adipokines,the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism,inflammation,immune regulation,energy disorders,and bone homeostasis.At the same time,the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely.Therefore,this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs,emphasizing bone formation and bone regeneration.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has very low overall survival.According to global cancer statistics,approximately 905677 new cases were reported in 2020,with at least 830180 of them being fatal.Cluster of differentiation 147(CD147)is a novel,transmembrane glycoprotein that is expressed in a wide variety of tumor cells and plays an important role in various stages of tumor development.Based on the reports described previously,we theorize that CD147 may be used as a novel biological indicator to predict the prognosis of HCC.To study this possibility,expression profiles of CD147 and corresponding clinical data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were analyzed,and a hazard ratio(HR)was established.AIM To explore the pattern of CD147 expression and its applicability in the prognosis of HCC.To establish HRs and probability points for predicting the prognosis of HCC by correlating CD147 expression with clinical characteristics.To determine if CD147 can be a reliable biomarker in HCC prognosis.METHODS The CD147 expression profile in HCC and corresponding clinical data were obtained from TCGA database.The expression patterns of CD147 were then validated by analyzing data from the GEO database.In addition,CD147 immunohistochemistry in HCC was obtained from the Human Protein Atlas.CD147 expression patterns and clinical characteristics in the prognosis of HCC were analyzed by accessing the UALCAN web resource.Accuracy,sensitivity,and specificity of the CD147 expression profile in predictive prognosis were determined by the time-dependent receiver operating characteristic(ROC)curves.Kaplan-Meier curves were plotted to estimate the HR of survival in HCC.Univariate and multivariate Cox regression proportional hazards analyses of CD147 expression levels and clinical characteristics as prognostic factors of HCC were performed.Nomograms were used to establish probability points and predict prognosis.RESULTS Data from TCGA and GEO databases revealed that CD147 was significantly overexpressed in HCC(P=1.624×10^(-12) and P=1.2×10^(-5),respectively).The expression of CD147 and prognosis of HCC were significantly correlated with the clinical characteristics of HCC as per the data from the UALCAN web resource(P<0.05).Kaplan-Meier analysis of CD147 expression in HCC revealed that the high expression groups showed poor prognosis and an HR of survival>1[log-rank test,P=0.000542,HR(in high expression group):1.856,95%confidence interval(CI):1.308 to 2.636].ROC curves were plotted to analyze the 1-year,3-year,and 5-year survival rates.The area under the ROC curve values were 0.675(95%CI:0.611 to 0.740),0.623(95%CI:0.555 to 0.692),and 0.664(95%CI:0.582 to 9.745),respectively.Univariate Cox analysis of CD147 expression and clinical characteristics of HCC and multivariate Cox analysis of CD147 patterns and pathological tumor-node-metastasis stage showed significant differences(univariate Cox,P=0.00013,HR:1.424,95%CI:1.884 to 1.707 and P=0.00066,HR:1.376,95%CI:1.145 to 1.654,respectively;multivariate Cox,P=0.00578,HR:1.507,95%CI:1.126 to 2.018 and P=0.00336,HR:1.443,95%CI:1.129 to 1.844,respectively).Nomograms were plotted to establish the probability points and predict prognosis.The total points ranged from 0 to 180,and the C-index value was 0.673(95%CI:0.600 to 1.000,P<0.01).CONCLUSION Overexpression of CD147 was correlated with poor prognosis in HCC.The CD147 expression profile combined with clinical characteristics can reliably predict the prognosis of HCC.CD147 can serve as a biomarker to predict the prognosis of HCC.
基金Supported by Talents Construction Project of Science and Technology Innovation,Hebei Academy of Agriculture and Forestry Sciences(C22R0701)Key Research and Development Program of Hebei(21326308D-2-1)China Agriculture Research System-Apple(CARS-27)。
文摘Flowering is a prerequisite for apple fruiting,and apple flower buds are mixed buds,that is,the vegetative organs and flower structure exist in the same terminal bud simultaneously,which are formed in the year before flowering and fruiting,mainly including spur terminal buds and axillary buds.The infrequent formation of flower buds during its growth and biennial bearing are closely related to flower bud differentiation.Therefore,this paper reviews the research progress of flower bud differentiation of apple from the morphological differentiation,plant hormones and flowering-related genes,in order to provide a theoretical reference for efficient cultivation and stable yield of apple.
