Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer...Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine tumors.However,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains uncertain.Methods:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were examined.Grade of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was evaluated.Results:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS.The GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic factors.The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions:Ki-67 is a valuable prognostic indicator for PDAC.Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.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
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
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
BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,...BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.展开更多
Objective:To reveal the distribution characteristics and demographic factors of traditional Chinese medicine(TCM)constitution among elderly individuals in China.Methods: Elderly individuals from seven regions in China...Objective:To reveal the distribution characteristics and demographic factors of traditional Chinese medicine(TCM)constitution among elderly individuals in China.Methods: Elderly individuals from seven regions in China were selected as samples in this study using a multistage cluster random sampling method.The basic information questionnaire and Constitution in Chinese Medicine Questionnaire(Elderly Edition)were used.Descriptive statistical analysis,chi-squared tests,and binary logistic regression analysis were used.Results: The single balanced constitution(BC)accounted for 23.9%.The results of the major TCM constitution types showed that BC(43.2%)accounted for the largest proportion and unbalanced constitutions ranged from 0.9%to 15.7%.East China region(odds ratio[OR]=2.097;95%confidence interval[CI],1.912 to 2.301),married status(OR=1.341;95%CI,1.235 to 1.457),and managers(OR=1.254;95%CI,1.044 to 1.505)were significantly associated with BC.Age>70 years was associated with qi-deficiency constitution and blood stasis constitution(BSC).Female sex was significantly associated with yang-deficiency constitution(OR=1.646;95%CI,1.52 to 1.782).Southwest region was significantly associated with phlegm-dampness constitution(OR=1.809;95%CI,1.569 to 2.086).North China region was significantly associated with inherited special constitution(OR=2.521;95%CI,1.569 to 4.05).South China region(OR=2.741;95%CI,1.997 to 1.3.763),Central China region(OR=8.889;95%CI,6.676 to 11.835),senior middle school education(OR=2.442;95%CI,1.932 to 3.088),and managers(OR=1.804;95%CI,1.21 to 2.69)were significantly associated with BSC.Conclusions: This study defined the distribution characteristics and demographic factors of TCM constitution in the elderly population.Adjusting and improving unbalanced constitutions,which are correlated with diseases,can help promote healthy aging through the scientific management of these demographic factors.展开更多
Objective To explore the value of contrast-enhanced ultrasound(CEUS)for predicting differentiation degree of hepatocellular carcinoma(HCC).Methods Totally 86 HCC patients confirmed by postoperative pathology were retr...Objective To explore the value of contrast-enhanced ultrasound(CEUS)for predicting differentiation degree of hepatocellular carcinoma(HCC).Methods Totally 86 HCC patients confirmed by postoperative pathology were retrospectively enrolled and divided into poorly differentiated,moderately differentiated and highly differentiated groups according to postoperative Edmondson-Steiner grading.Preoperative CEUS parameters were compared among groups,and binary logistic regression was used to analyze CEUS-related independent predictors of HCC with different differentiation.The receiver operating characteristic curves of parameters being significant different among groups were drawn,the areas under the curve(AUC)were calculated,and the efficacy for predicting HCC with different differentiation degree was evaluated.Results There were 29 cases in poorly differentiated group,37 in moderately differentiated group and 20 cases in highly differentiated group.The arrival time of contrast agent in poorly differentiated group was earlier than that in moderately and high differentiated groups(both P<0.05),while in moderately differentiated group was not significantly different with that in highly differentiated group(P>0.05).The washout grade were significantly different between each 2 groups(all P<0.05).The arrival time of contrast agent and washout grade were independent predictors of highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC,and washout grade also was independent predictor of highly or moderately differentiated HCC(all P<0.05).The AUC of the arrival time of contrast agent for predicting highly or moderately differentiated,highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC was 0.615,0.787,0.690 and 0.724,respectively,while of washout grade was 0.801,0.927,0.795 and 0.841,respectively.Conclusion CEUS could be used to effectively predict differentiation degree of HCC.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
Ear differentiation,grain development and their interaction with factors in the growing environment,such as temperature,solar radiation and precipitation,greatly influence grain number and grain weight,and ultimately ...Ear differentiation,grain development and their interaction with factors in the growing environment,such as temperature,solar radiation and precipitation,greatly influence grain number and grain weight,and ultimately affect summer maize production.In this study,field experiments involving different sowing dates were conducted over three years to evaluate the effects of temperature factors,average solar radiation and total precipitation on the growth process,ear differentiation,fertilization characteristics,grain filling and yield of summer maize varieties with different growth durations.Four hybrids were evaluated in Huang-Huai-Hai Plain(HHHP),China from 2018 to 2020 with five different sowing dates.The results showed that the grain yield formation of summer maize was strongly impacted by the environment from the silking(R1)to milking(R3)stage.Average minimum temperature(AT_(min))was the key environmental factor that determined yield.Reductions in the length of the growing season(r=–0.556,P<0.01)and the total floret number on ear(R^(2)=0.200,P<0.001)were found when AT_(min) was elevated from the emerging(VE)to R1 stage.Both grain-filling rate(R^(2)=0.520,P<0.001)and the floret abortion rate on ear(R^(2)=0.437,P<0.001)showed quadratic relationships with AT_(min) from the R1 to physiological maturity(R6)stage,while the number of days after the R1 stage(r=–0.756,P<0.01)was negatively correlated with AT_(min).An increase in AT_(min) was beneficial for the promotion of yield when it did not exceeded a certain level(above 23°C during the R1–R3 stage and 20–21°C during the R1-R6 stage).Enhanced solar radiation and precipitation during R1–R6 increased the grain-filling rate(R^(2)=0.562,P<0.001 and R^(2)=0.229,P<0.05,respectively).Compared with short-season hybrids,full-season hybrids showed much greater suitability for a critical environment.The coordinated regulation of AT_(min),ear differentiation and grain development at the pre-and post-silking stages improved maize yield by increasing total floret number and grain-filling rate,and by reducing the floret abortion rate on ear.展开更多
The wild Lepista sordida is a kind of precious and rare edible fungus.An excellent strain of it by artificial domestication was obtained,which was high-yield and high in iron content.In this study,high-throughput comp...The wild Lepista sordida is a kind of precious and rare edible fungus.An excellent strain of it by artificial domestication was obtained,which was high-yield and high in iron content.In this study,high-throughput comparative proteomics was used to reveal the regulatory mechanism of its primordium differentiation in the early fruiting body formation.The mycelium before the primordium differentiation mainly expressed high levels of mitochondrial functional proteins and carbon dioxide concentration regulatory proteins.In young mushrooms,the highly expressed proteins were mainly involved in cell component generation,cell proliferation,nitrogen compound metabolism,nucleotide metabolism,glutathione metabolism,and purine metabolism.The differential regulation patterns of pileus and stipe growth to maturity were also revealed.The highly expressed proteins related to transcription,RNA splicing,the production of various organelles,DNA conformational change,nucleosome organization,protein processing,maturation and transport,and cell detoxification regulated the pileus development and maturity.The proteins related to carbohydrate and energy metabolism,large amounts of obsolete cytoplasmic parts,nutrient deprivation,and external stimuli regulated the stipe development and maturity.Multiple CAZymes regulated nutrient absorption,morphogenesis,spore production,stress response,and other life activities at different growth and development stages.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
Objective To construct a precise model for identifying traditional Chinese medicine(TCM)constitutions;thereby offering optimized guidance for clinical diagnosis and treatment plan-ning;and ultimately enhancing medical...Objective To construct a precise model for identifying traditional Chinese medicine(TCM)constitutions;thereby offering optimized guidance for clinical diagnosis and treatment plan-ning;and ultimately enhancing medical efficiency and treatment outcomes.Methods First;TCM full-body inspection data acquisition equipment was employed to col-lect full-body standing images of healthy people;from which the constitutions were labelled and defined in accordance with the Constitution in Chinese Medicine Questionnaire(CCMQ);and a dataset encompassing labelled constitutions was constructed.Second;heat-suppres-sion valve(HSV)color space and improved local binary patterns(LBP)algorithm were lever-aged for the extraction of features such as facial complexion and body shape.In addition;a dual-branch deep network was employed to collect deep features from the full-body standing images.Last;the random forest(RF)algorithm was utilized to learn the extracted multifea-tures;which were subsequently employed to establish a TCM constitution identification mod-el.Accuracy;precision;and F1 score were the three measures selected to assess the perfor-mance of the model.Results It was found that the accuracy;precision;and F1 score of the proposed model based on multifeatures for identifying TCM constitutions were 0.842;0.868;and 0.790;respectively.In comparison with the identification models that encompass a single feature;either a single facial complexion feature;a body shape feature;or deep features;the accuracy of the model that incorporating all the aforementioned features was elevated by 0.105;0.105;and 0.079;the precision increased by 0.164;0.164;and 0.211;and the F1 score rose by 0.071;0.071;and 0.084;respectively.Conclusion The research findings affirmed the viability of the proposed model;which incor-porated multifeatures;including the facial complexion feature;the body shape feature;and the deep feature.In addition;by employing the proposed model;the objectification and intel-ligence of identifying constitutions in TCM practices could be optimized.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
On March 14,2004,the Second Session of the 10th National People’s Congress of China adopted the fourth amendment to the Chinese Constitution,the most noticeable highlight of which is the addition of the paragraph“th...On March 14,2004,the Second Session of the 10th National People’s Congress of China adopted the fourth amendment to the Chinese Constitution,the most noticeable highlight of which is the addition of the paragraph“the state respects and protects human rights”as the third clause in Article 33 of Chapter II“Basic Rights and Obligations of Citizens”in the Constitution.The inclusion of the clause of human rights in the Constitution is considered an important milestone in the history of human rights development in the People’s Republic of China.The implementation of the human rights clause not only showcases the values of the Party and the state in respecting and protecting human rights,but also promotes the development of human rights,shapes the culture of human rights,and endows the rule of law with a rich humanistic spirit.Over the past 20 years,the publicity,research and practice of the human rights clause have made the Chi-nese people realize that human rights are not only a“great term”,but also a common value shared by mankind.Amid the once-in-a-century changes of the world,although the development of human rights is facing various challenges,the humanistic spirit contained in the hu-man rights clause has become the internal driving force for building consensus in the whole of society.Reinterpreting the significance and value of the human rights clause can help us conscientiously draw on the experience in the implementation of the clause over the past 20 years and contribute Chinese wisdom and experience to global human rights governance with a more open mind and inclusive attitude.展开更多
AIM:To develop a classifier for traditional Chinese medicine(TCM)syndrome differentiation of diabetic retinopathy(DR),using optimized machine learning algorithms,which can provide the basis for TCM objective and intel...AIM:To develop a classifier for traditional Chinese medicine(TCM)syndrome differentiation of diabetic retinopathy(DR),using optimized machine learning algorithms,which can provide the basis for TCM objective and intelligent syndrome differentiation.METHODS:Collated data on real-world DR cases were collected.A variety of machine learning methods were used to construct TCM syndrome classification model,and the best performance was selected as the basic model.Genetic Algorithm(GA)was used for feature selection to obtain the optimal feature combination.Harris Hawk Optimization(HHO)was used for parameter optimization,and a classification model based on feature selection and parameter optimization was constructed.The performance of the model was compared with other optimization algorithms.The models were evaluated with accuracy,precision,recall,and F1 score as indicators.RESULTS:Data on 970 cases that met screening requirements were collected.Support Vector Machine(SVM)was the best basic classification model.The accuracy rate of the model was 82.05%,the precision rate was 82.34%,the recall rate was 81.81%,and the F1 value was 81.76%.After GA screening,the optimal feature combination contained 37 feature values,which was consistent with TCM clinical practice.The model based on optimal combination and SVM(GA_SVM)had an accuracy improvement of 1.92%compared to the basic classifier.SVM model based on HHO and GA optimization(HHO_GA_SVM)had the best performance and convergence speed compared with other optimization algorithms.Compared with the basic classification model,the accuracy was improved by 3.51%.CONCLUSION:HHO and GA optimization can improve the model performance of SVM in TCM syndrome differentiation of DR.It provides a new method and research idea for TCM intelligent assisted syndrome differentiation.展开更多
The goal of village governance is to improve the well-being of farmers,so this study aims to measure the impact the quality of village governance on the well-being of farmers.It also examines the heterogeneity of this...The goal of village governance is to improve the well-being of farmers,so this study aims to measure the impact the quality of village governance on the well-being of farmers.It also examines the heterogeneity of this impact across different farmer groups from the perspectives of income levels and occupational differentiation.To this end,this study developed an indicator system based on survey data collected from 1,442 farmers in the Sichuan,Shaanxi,and Gansu provinces,as well as the Ningxia Hui autonomous region.Multiple linear regression models were then used to analyze this data,and the findings revealed that improvements in the quality of village governance significantly increased the well-being of farmers.Specifically,primary-level empowerment and capacity building were shown to contribute the most to the enhancement of the farmers’well-being,followed by social inclusion,and social cohesion was found to have only a minimal effect.In terms of income levels,improving the quality of village governance benefited middle-income farmers the most,followed by low-income farmers,and it had the least effect on high-income farmers.In terms of occupations,full-time farmers gained the most from improvements in the quality of village governance,followed by off-farm farmers,with part-time farmers benefiting the least.Based on these findings,this study suggests that policymakers should improve the quality of village governance to enhance the well-being of farmers,focusing on the impact that level of income and occupational differentiation have on village governance.展开更多
Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infr...Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of injury.In this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries.We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2.As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects.Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group.Interestingly,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal markers.Through biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor.Overall,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.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 Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying ...BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.展开更多
BACKGROUND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage embryos.ESCs exhibit a unique combination of self-renewal potency,...BACKGROUND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage embryos.ESCs exhibit a unique combination of self-renewal potency,unlimited proliferation,and pluripotency.The latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ layers.Multiple regulatory networks guide ESCs,directing their self-renewal and lineage-specific differentiation.Apoptosis,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic development.How-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly understood.AIM To investigate the regulatory impact of apoptosis on the early differentiation of ESCs into cardiac cells,using mouse ESC(mESC)models-mESC-B-cell lym-phoma 2(BCL-2),mESC-PIM-2,and mESC-metallothionein-1(MET-1)-which overexpress the anti-apoptotic genes Bcl-2,Pim-2,and Met-1,respectively.METHODS mESC-T2(wild-type),mESC-BCL-2,mESC-PIM-2,and mESC-MET-1 have been used to assess the effect of potentiated apoptotic signals on cardiac differentiation.The hanging drop method was adopted to generate embryoid bodies(EBs)and induce terminal differentiation of mESCs.The size of the generated EBs was measured in each condition compared to the wild type.At the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the control.At the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:Troponin T,GATA4,and NKX2.5.Additionally,troponin T protein expression was evaluated through immunofluorescence and western blot assays.RESULTS Our findings showed that the upregulation of Bcl-2,Pim-2,and Met-1 genes led to a reduction in the size of the EBs derived from the manipulated mESCs,in comparison with their wild-type counterpart.Additionally,a decrease in the count of beating cardiomyocytes among differentiated cells was observed.Furthermore,the mRNA expression of three cardiac markers-troponin T,GATA4,and NKX2.5-was diminished in mESCs overexpressing the three anti-apoptotic genes compared to the control cell line.Moreover,the overexpression of the anti-apoptotic genes resulted in a reduction in troponin T protein expression.CONCLUSION Our findings revealed that the upregulation of Bcl-2,Pim-2,and Met-1 genes altered cardiac differentiation,providing insight into the intricate interplay between apoptosis and ESC fate determination.展开更多
文摘Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine tumors.However,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains uncertain.Methods:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were examined.Grade of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was evaluated.Results:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS.The GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic factors.The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions:Ki-67 is a valuable prognostic indicator for PDAC.Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.
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 São Paulo Research Foundation(FAPESP),No.2010/08918-9 and 2020/11564-6the KBSP Young Investigator Fellowship,No.2011/00204-0+2 种基金the DBF Fellowship,No.2019/27492-7the LMG Fellowship,No.2014/01395-1the CFB Fellowship,No.2014/14278-3.
文摘BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.
基金supported by the National Key R&D Program of China(2020YFC2003102).
文摘Objective:To reveal the distribution characteristics and demographic factors of traditional Chinese medicine(TCM)constitution among elderly individuals in China.Methods: Elderly individuals from seven regions in China were selected as samples in this study using a multistage cluster random sampling method.The basic information questionnaire and Constitution in Chinese Medicine Questionnaire(Elderly Edition)were used.Descriptive statistical analysis,chi-squared tests,and binary logistic regression analysis were used.Results: The single balanced constitution(BC)accounted for 23.9%.The results of the major TCM constitution types showed that BC(43.2%)accounted for the largest proportion and unbalanced constitutions ranged from 0.9%to 15.7%.East China region(odds ratio[OR]=2.097;95%confidence interval[CI],1.912 to 2.301),married status(OR=1.341;95%CI,1.235 to 1.457),and managers(OR=1.254;95%CI,1.044 to 1.505)were significantly associated with BC.Age>70 years was associated with qi-deficiency constitution and blood stasis constitution(BSC).Female sex was significantly associated with yang-deficiency constitution(OR=1.646;95%CI,1.52 to 1.782).Southwest region was significantly associated with phlegm-dampness constitution(OR=1.809;95%CI,1.569 to 2.086).North China region was significantly associated with inherited special constitution(OR=2.521;95%CI,1.569 to 4.05).South China region(OR=2.741;95%CI,1.997 to 1.3.763),Central China region(OR=8.889;95%CI,6.676 to 11.835),senior middle school education(OR=2.442;95%CI,1.932 to 3.088),and managers(OR=1.804;95%CI,1.21 to 2.69)were significantly associated with BSC.Conclusions: This study defined the distribution characteristics and demographic factors of TCM constitution in the elderly population.Adjusting and improving unbalanced constitutions,which are correlated with diseases,can help promote healthy aging through the scientific management of these demographic factors.
文摘Objective To explore the value of contrast-enhanced ultrasound(CEUS)for predicting differentiation degree of hepatocellular carcinoma(HCC).Methods Totally 86 HCC patients confirmed by postoperative pathology were retrospectively enrolled and divided into poorly differentiated,moderately differentiated and highly differentiated groups according to postoperative Edmondson-Steiner grading.Preoperative CEUS parameters were compared among groups,and binary logistic regression was used to analyze CEUS-related independent predictors of HCC with different differentiation.The receiver operating characteristic curves of parameters being significant different among groups were drawn,the areas under the curve(AUC)were calculated,and the efficacy for predicting HCC with different differentiation degree was evaluated.Results There were 29 cases in poorly differentiated group,37 in moderately differentiated group and 20 cases in highly differentiated group.The arrival time of contrast agent in poorly differentiated group was earlier than that in moderately and high differentiated groups(both P<0.05),while in moderately differentiated group was not significantly different with that in highly differentiated group(P>0.05).The washout grade were significantly different between each 2 groups(all P<0.05).The arrival time of contrast agent and washout grade were independent predictors of highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC,and washout grade also was independent predictor of highly or moderately differentiated HCC(all P<0.05).The AUC of the arrival time of contrast agent for predicting highly or moderately differentiated,highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC was 0.615,0.787,0.690 and 0.724,respectively,while of washout grade was 0.801,0.927,0.795 and 0.841,respectively.Conclusion CEUS could be used to effectively predict differentiation degree of HCC.
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supported by Key Technology Research and Development Program of Shandong Province,China(2021LZGC014-2)the National Natural Science Foundation of China(32172115)the National Modern Agriculture Industry Technology System,China(CARS02-21)。
文摘Ear differentiation,grain development and their interaction with factors in the growing environment,such as temperature,solar radiation and precipitation,greatly influence grain number and grain weight,and ultimately affect summer maize production.In this study,field experiments involving different sowing dates were conducted over three years to evaluate the effects of temperature factors,average solar radiation and total precipitation on the growth process,ear differentiation,fertilization characteristics,grain filling and yield of summer maize varieties with different growth durations.Four hybrids were evaluated in Huang-Huai-Hai Plain(HHHP),China from 2018 to 2020 with five different sowing dates.The results showed that the grain yield formation of summer maize was strongly impacted by the environment from the silking(R1)to milking(R3)stage.Average minimum temperature(AT_(min))was the key environmental factor that determined yield.Reductions in the length of the growing season(r=–0.556,P<0.01)and the total floret number on ear(R^(2)=0.200,P<0.001)were found when AT_(min) was elevated from the emerging(VE)to R1 stage.Both grain-filling rate(R^(2)=0.520,P<0.001)and the floret abortion rate on ear(R^(2)=0.437,P<0.001)showed quadratic relationships with AT_(min) from the R1 to physiological maturity(R6)stage,while the number of days after the R1 stage(r=–0.756,P<0.01)was negatively correlated with AT_(min).An increase in AT_(min) was beneficial for the promotion of yield when it did not exceeded a certain level(above 23°C during the R1–R3 stage and 20–21°C during the R1-R6 stage).Enhanced solar radiation and precipitation during R1–R6 increased the grain-filling rate(R^(2)=0.562,P<0.001 and R^(2)=0.229,P<0.05,respectively).Compared with short-season hybrids,full-season hybrids showed much greater suitability for a critical environment.The coordinated regulation of AT_(min),ear differentiation and grain development at the pre-and post-silking stages improved maize yield by increasing total floret number and grain-filling rate,and by reducing the floret abortion rate on ear.
基金funded by the Shandong Edible Fungus Agricultural Technology System(SDAIT-07-02)the National Natural Science Foundation of China(Grant No.32000041 and 32272789)+2 种基金the Shandong Provincial Natural Science Foundation,China(ZR2020QC005)the Qingdao Agricultural University Scientific Research Foundation(6631120076)horizontal project:Breeding and property protection of new varieties of factory produced Hypsizygus marmoreus(20183702012614).
文摘The wild Lepista sordida is a kind of precious and rare edible fungus.An excellent strain of it by artificial domestication was obtained,which was high-yield and high in iron content.In this study,high-throughput comparative proteomics was used to reveal the regulatory mechanism of its primordium differentiation in the early fruiting body formation.The mycelium before the primordium differentiation mainly expressed high levels of mitochondrial functional proteins and carbon dioxide concentration regulatory proteins.In young mushrooms,the highly expressed proteins were mainly involved in cell component generation,cell proliferation,nitrogen compound metabolism,nucleotide metabolism,glutathione metabolism,and purine metabolism.The differential regulation patterns of pileus and stipe growth to maturity were also revealed.The highly expressed proteins related to transcription,RNA splicing,the production of various organelles,DNA conformational change,nucleosome organization,protein processing,maturation and transport,and cell detoxification regulated the pileus development and maturity.The proteins related to carbohydrate and energy metabolism,large amounts of obsolete cytoplasmic parts,nutrient deprivation,and external stimuli regulated the stipe development and maturity.Multiple CAZymes regulated nutrient absorption,morphogenesis,spore production,stress response,and other life activities at different growth and development stages.
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National Key Research and Development Program of China(2022YFC3502302)National Natural Science Foundation of China(82074580)Graduate Research Innovation Program of Jiangsu Province(KYCX23_2078).
文摘Objective To construct a precise model for identifying traditional Chinese medicine(TCM)constitutions;thereby offering optimized guidance for clinical diagnosis and treatment plan-ning;and ultimately enhancing medical efficiency and treatment outcomes.Methods First;TCM full-body inspection data acquisition equipment was employed to col-lect full-body standing images of healthy people;from which the constitutions were labelled and defined in accordance with the Constitution in Chinese Medicine Questionnaire(CCMQ);and a dataset encompassing labelled constitutions was constructed.Second;heat-suppres-sion valve(HSV)color space and improved local binary patterns(LBP)algorithm were lever-aged for the extraction of features such as facial complexion and body shape.In addition;a dual-branch deep network was employed to collect deep features from the full-body standing images.Last;the random forest(RF)algorithm was utilized to learn the extracted multifea-tures;which were subsequently employed to establish a TCM constitution identification mod-el.Accuracy;precision;and F1 score were the three measures selected to assess the perfor-mance of the model.Results It was found that the accuracy;precision;and F1 score of the proposed model based on multifeatures for identifying TCM constitutions were 0.842;0.868;and 0.790;respectively.In comparison with the identification models that encompass a single feature;either a single facial complexion feature;a body shape feature;or deep features;the accuracy of the model that incorporating all the aforementioned features was elevated by 0.105;0.105;and 0.079;the precision increased by 0.164;0.164;and 0.211;and the F1 score rose by 0.071;0.071;and 0.084;respectively.Conclusion The research findings affirmed the viability of the proposed model;which incor-porated multifeatures;including the facial complexion feature;the body shape feature;and the deep feature.In addition;by employing the proposed model;the objectification and intel-ligence of identifying constitutions in TCM practices could be optimized.
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On March 14,2004,the Second Session of the 10th National People’s Congress of China adopted the fourth amendment to the Chinese Constitution,the most noticeable highlight of which is the addition of the paragraph“the state respects and protects human rights”as the third clause in Article 33 of Chapter II“Basic Rights and Obligations of Citizens”in the Constitution.The inclusion of the clause of human rights in the Constitution is considered an important milestone in the history of human rights development in the People’s Republic of China.The implementation of the human rights clause not only showcases the values of the Party and the state in respecting and protecting human rights,but also promotes the development of human rights,shapes the culture of human rights,and endows the rule of law with a rich humanistic spirit.Over the past 20 years,the publicity,research and practice of the human rights clause have made the Chi-nese people realize that human rights are not only a“great term”,but also a common value shared by mankind.Amid the once-in-a-century changes of the world,although the development of human rights is facing various challenges,the humanistic spirit contained in the hu-man rights clause has become the internal driving force for building consensus in the whole of society.Reinterpreting the significance and value of the human rights clause can help us conscientiously draw on the experience in the implementation of the clause over the past 20 years and contribute Chinese wisdom and experience to global human rights governance with a more open mind and inclusive attitude.
基金Supported by Hunan Province Traditional Chinese Medicine Research Project(No.B2023043)Hunan Provincial Department of Education Scientific Research Project(No.22B0386)Hunan University of Traditional Chinese Medicine Campus level Research Fund Project(No.2022XJZKC004).
文摘AIM:To develop a classifier for traditional Chinese medicine(TCM)syndrome differentiation of diabetic retinopathy(DR),using optimized machine learning algorithms,which can provide the basis for TCM objective and intelligent syndrome differentiation.METHODS:Collated data on real-world DR cases were collected.A variety of machine learning methods were used to construct TCM syndrome classification model,and the best performance was selected as the basic model.Genetic Algorithm(GA)was used for feature selection to obtain the optimal feature combination.Harris Hawk Optimization(HHO)was used for parameter optimization,and a classification model based on feature selection and parameter optimization was constructed.The performance of the model was compared with other optimization algorithms.The models were evaluated with accuracy,precision,recall,and F1 score as indicators.RESULTS:Data on 970 cases that met screening requirements were collected.Support Vector Machine(SVM)was the best basic classification model.The accuracy rate of the model was 82.05%,the precision rate was 82.34%,the recall rate was 81.81%,and the F1 value was 81.76%.After GA screening,the optimal feature combination contained 37 feature values,which was consistent with TCM clinical practice.The model based on optimal combination and SVM(GA_SVM)had an accuracy improvement of 1.92%compared to the basic classifier.SVM model based on HHO and GA optimization(HHO_GA_SVM)had the best performance and convergence speed compared with other optimization algorithms.Compared with the basic classification model,the accuracy was improved by 3.51%.CONCLUSION:HHO and GA optimization can improve the model performance of SVM in TCM syndrome differentiation of DR.It provides a new method and research idea for TCM intelligent assisted syndrome differentiation.
基金funded by the Fundamental Research Funds for the Central Universities“Research on the Impact of Social Quality and Political Trust on Farmers’Well-Being in the Post-Poverty Alleviation Era”(21lzujbkydx012)the Project of Gansu Province for Philosophy and Social Sciences Planning“Research on the Strategies to Improve Farmers’Well-Being in Gansu Province From the Perspective of Social Quality”(2021YB012).
文摘The goal of village governance is to improve the well-being of farmers,so this study aims to measure the impact the quality of village governance on the well-being of farmers.It also examines the heterogeneity of this impact across different farmer groups from the perspectives of income levels and occupational differentiation.To this end,this study developed an indicator system based on survey data collected from 1,442 farmers in the Sichuan,Shaanxi,and Gansu provinces,as well as the Ningxia Hui autonomous region.Multiple linear regression models were then used to analyze this data,and the findings revealed that improvements in the quality of village governance significantly increased the well-being of farmers.Specifically,primary-level empowerment and capacity building were shown to contribute the most to the enhancement of the farmers’well-being,followed by social inclusion,and social cohesion was found to have only a minimal effect.In terms of income levels,improving the quality of village governance benefited middle-income farmers the most,followed by low-income farmers,and it had the least effect on high-income farmers.In terms of occupations,full-time farmers gained the most from improvements in the quality of village governance,followed by off-farm farmers,with part-time farmers benefiting the least.Based on these findings,this study suggests that policymakers should improve the quality of village governance to enhance the well-being of farmers,focusing on the impact that level of income and occupational differentiation have on village governance.
基金supported by the National Research Foundation(NRF)S&F-Scarce Skills Postdoctoral Fellowship,No.120752(to AC)the Global Excellence and Stature,Fourth Industrial Revolution(GES 4.0)Postgraduate Scholarship(to MJR)the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa(SARChI/NRF-DST),No.146290(to DDS and HA).
文摘Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of injury.In this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries.We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2.As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects.Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group.Interestingly,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal markers.Through biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor.Overall,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.
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 the National Natural Science Foundation of China,No.82125007Beijing Natural Science Foundation,No.Z200014.
文摘BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.
基金Supported by the National Council for Scientific Research in Lebanon,CNRS-L.
文摘BACKGROUND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage embryos.ESCs exhibit a unique combination of self-renewal potency,unlimited proliferation,and pluripotency.The latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ layers.Multiple regulatory networks guide ESCs,directing their self-renewal and lineage-specific differentiation.Apoptosis,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic development.How-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly understood.AIM To investigate the regulatory impact of apoptosis on the early differentiation of ESCs into cardiac cells,using mouse ESC(mESC)models-mESC-B-cell lym-phoma 2(BCL-2),mESC-PIM-2,and mESC-metallothionein-1(MET-1)-which overexpress the anti-apoptotic genes Bcl-2,Pim-2,and Met-1,respectively.METHODS mESC-T2(wild-type),mESC-BCL-2,mESC-PIM-2,and mESC-MET-1 have been used to assess the effect of potentiated apoptotic signals on cardiac differentiation.The hanging drop method was adopted to generate embryoid bodies(EBs)and induce terminal differentiation of mESCs.The size of the generated EBs was measured in each condition compared to the wild type.At the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the control.At the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:Troponin T,GATA4,and NKX2.5.Additionally,troponin T protein expression was evaluated through immunofluorescence and western blot assays.RESULTS Our findings showed that the upregulation of Bcl-2,Pim-2,and Met-1 genes led to a reduction in the size of the EBs derived from the manipulated mESCs,in comparison with their wild-type counterpart.Additionally,a decrease in the count of beating cardiomyocytes among differentiated cells was observed.Furthermore,the mRNA expression of three cardiac markers-troponin T,GATA4,and NKX2.5-was diminished in mESCs overexpressing the three anti-apoptotic genes compared to the control cell line.Moreover,the overexpression of the anti-apoptotic genes resulted in a reduction in troponin T protein expression.CONCLUSION Our findings revealed that the upregulation of Bcl-2,Pim-2,and Met-1 genes altered cardiac differentiation,providing insight into the intricate interplay between apoptosis and ESC fate determination.
