Objective To examine the expression of cell division cycle associated 2(CDCA 2) in pancreatic ductal adenocarcinoma(PDAC) and investigate its role in prognosis of PDAC patients.Methods This retrospective study include...Objective To examine the expression of cell division cycle associated 2(CDCA 2) in pancreatic ductal adenocarcinoma(PDAC) and investigate its role in prognosis of PDAC patients.Methods This retrospective study included 155 PDAC patients who underwent surgical treatment and complete post-operative follow-up.Clinicopathologic data were collected through clinical database.Tissue microarray was constructed and immunohistochemistry was performed to detect CDCA2 expression in the PDAC tumor tissues and adjacent non-tumor tissues.Clinicopathological characteristics between high and low CDCA2 expression were compared.Correlation of CDCA2 expressions with patients' survival was analyzed using Kaplan-Meier method and Cox regression analysis.Results Expression of CDCA2 in PDAC cells was significantly higher than that in adjacent non-tumor tissues(U=4056.5,P<0.001).Univariate analysis showed that CDCA2 expression [hazard ratio(HR)=1.574,95% confidence interval(CI)=1.014-2.443,P=0.043] and node metastasis(HR=1.704,95%CI=1.183-2.454,P=0.004) were significantly associated with prognosis.Cox regression analysis showed CDCA2 expression was not an independent prognostic risk factor(HR=1.418,95%CI=0.897-2.242,P=0.135) for PDCA patients.Stratification survival analysis demonstrated CDCA2 expression as an independent prognostic risk factor in male patients(HR=2.554,95%CI=1.446-4.511,P=0.003) or in non-perineural invasion patients(HR=2.290,95%CI=1.146-4.577,P=0.012).Conclusions CDCA2 is highly expressed in PDAC tumor tissue.Although CDCA2 is not an independent prognostic risk factor for PDAC patients,it might be used to help predict prognosis of male or non-perineural invasion patients of PDAC.展开更多
To the Editor:Kinase cell division cycle 7(CDC7),a cell division cycle protein,takes a vital role in mediating DNA replication1.CDC7 complexes in the nucleus can phosphorylate the minichromosome maintenance complex(MC...To the Editor:Kinase cell division cycle 7(CDC7),a cell division cycle protein,takes a vital role in mediating DNA replication1.CDC7 complexes in the nucleus can phosphorylate the minichromosome maintenance complex(MCM)family members that bind to chromosomes.In addition,CDC7 kinase,as a molecular switch regulating DNA replication,can mediate DNA damage signaling pathways to stimulate cell cycle termination as well as DNA replication2.Studies have shown that CDC7 is overexpressed in many types of cancer cells,and its overexpression was related to poor patient survival,tumor grade,genetic instability,aneuploidy and so on3.Therefore,CDC7 is a promising target for antitumor therapy.展开更多
Based on a deterministic cell cycle model of fission yeast, the effects of the finite cell size on the cell cycle regulation in wee1- cdc25△ double mutant type are numerically studied by using of the chemical Langevi...Based on a deterministic cell cycle model of fission yeast, the effects of the finite cell size on the cell cycle regulation in wee1- cdc25△ double mutant type are numerically studied by using of the chemical Langevin equations. It is found that at a certain region of cell size, our numerical results from the chemical Langevin equations are in good qualitative agreement with the experimental observations. The two resettings to the G2 phase from early stages of mitosis can be induced under the moderate cell size. The quantized cycle times can be observed during such a cell size region. Therefore, a coarse estimation of cell size is obtained from the mesoscopic stochastic cell cycle model.展开更多
BACKGROUND Pancreatic cancer(PC)is an aggressive malignancy.As a member of the BTN/BTNL family,BTNL9 has been identified as a tumor suppressor in breast cancer,lung adenocarcinoma,and colon cancer;however,its role and...BACKGROUND Pancreatic cancer(PC)is an aggressive malignancy.As a member of the BTN/BTNL family,BTNL9 has been identified as a tumor suppressor in breast cancer,lung adenocarcinoma,and colon cancer;however,its role and underlying mechanisms in PC remain to be elucidated.AIM To investigate the role of BTNL9 in the pathogenesis and development of PC.METHODS The difference of BTNL9 expression in cancer and adjacent normal tissues was analyzed by RNA sequencing data from a public database and tissue microarray detection.The relationship between BTNL9 expression and the prognosis of patients was also studied.The effects of BTNL9 on proliferation,metastasis,and cell cycle of PC cells were investigated by phenotypic experiments.The mechanism was investigated by RNA sequencing,western blotting,and immunofluorescence detection.RESULTS The mRNA and protein levels of BTNL9 in PC tissues were downregulated compared with normal tissues.Based on survival data from The Cancer Genome Atlas and tissue microarray,BTNL9 was an independent influencing factor for overall survival,and its low expression predicted a shortened overall survival of patients.In vitro,BTNL9 could inhibit cell proliferation and metastasis in both PANC-1 and MIA PaCa-2 cells and induce cell cycle arrest in G2/M phases.Downregulation of BTNL9 could activate the cell cycle signaling pathway.Furthermore,overexpression of BTNL9 could significantly inhibit the expression of cell division cycle 20(CDC20).Rescue experiments demonstrated that overexpression of CDC20 reversed the effect of BTNL9 on the proliferation,metastasis,and cell cycle of PC cells.CONCLUSION The expression of BTNL9 was downregulated in PC,and it has the prediction ability for prognosis.Functionally,BTNL9 exerted an anti-cancer effect by suppressing downstream CDC20 expression in PC.展开更多
The big data generated by tunnel boring machines(TBMs)are widely used to reveal complex rock-machine interactions by machine learning(ML)algorithms.Data preprocessing plays a crucial role in improving ML accuracy.For ...The big data generated by tunnel boring machines(TBMs)are widely used to reveal complex rock-machine interactions by machine learning(ML)algorithms.Data preprocessing plays a crucial role in improving ML accuracy.For this,a TBM big data preprocessing method in ML was proposed in the present study.It emphasized the accurate division of TBM tunneling cycle and the optimization method of feature extraction.Based on the data collected from a TBM water conveyance tunnel in China,its effectiveness was demonstrated by application in predicting TBM performance.Firstly,the Score-Kneedle(S-K)method was proposed to divide a TBM tunneling cycle into five phases.Conducted on 500 TBM tunneling cycles,the S-K method accurately divided all five phases in 458 cycles(accuracy of 91.6%),which is superior to the conventional duration division method(accuracy of 74.2%).Additionally,the S-K method accurately divided the stable phase in 493 cycles(accuracy of 98.6%),which is superior to two state-of-the-art division methods,namely the histogram discriminant method(accuracy of 94.6%)and the cumulative sum change point detection method(accuracy of 92.8%).Secondly,features were extracted from the divided phases.Specifically,TBM tunneling resistances were extracted from the free rotating phase and free advancing phase.The resistances were subtracted from the total forces to represent the true rock-fragmentation forces.The secant slope and the mean value were extracted as features of the increasing phase and stable phase,respectively.Finally,an ML model integrating a deep neural network and genetic algorithm(GA-DNN)was established to learn the preprocessed data.The GA-DNN used 6 secant slope features extracted from the increasing phase to predict the mean field penetration index(FPI)and torque penetration index(TPI)in the stable phase,guiding TBM drivers to make better decisions in advance.The results indicate that the proposed TBM big data preprocessing method can improve prediction accuracy significantly(improving R2s of TPI and FPI on the test dataset from 0.7716 to 0.9178 and from 0.7479 to 0.8842,respectively).展开更多
Aim To investigate the influences of melatonin (MT) on the growth of HeLa cells in vitro. Methods Theantiprolfferation activities of MT were evaluated in HeLa cells by means of trypan blue dye exclusion and MTT vital ...Aim To investigate the influences of melatonin (MT) on the growth of HeLa cells in vitro. Methods Theantiprolfferation activities of MT were evaluated in HeLa cells by means of trypan blue dye exclusion and MTT vital staining.The morphological changes of HeLa cells induced by MT were observed under transmission electronic microscope. Cell divisioncycle influenced by MT was assessed by a flow cytometry. Results MT produced a certain inhibition of HeLa cells at the con-centration of 2 mmol@ L-1 and prolonged the TD. The fraction of cells inhibited was 61.0%. The IC. so of HeLa cells exposed toMT for 96 h was 2.039 mmol@ L- 1. The flow cytometric analyses showed that exposure to MT for 72 h reduced the number ofHeLa cells in phase S. Under electronic microscope, the HeLa cells exposed to MT for 72 h displayed morphological changesof necrosis, apoptosis, more hetero-chromosome and less somatic chromosome. Conclusion MT showed certain influences onthe growth of HeLa cells. Its mechanism may probably be attributable to reduction of the number of cells in phase S.展开更多
Vascular smooth muscle cell （VSMC） differentiation and proliferation are two important physiological proc- esses during vascular development. The phenotypic alteration from differentiated to proliferative VSMC contr...Vascular smooth muscle cell （VSMC） differentiation and proliferation are two important physiological proc- esses during vascular development. The phenotypic alteration from differentiated to proliferative VSMC contrib- utes to the development of several major cardiovascular diseases including atherosclerosis, hypertension, resteno- sis after angioplasty or bypass, diabetic vascular complications, and transplantation arteriopathy. Since the VSMC phenotype in these pathological conditions resembles that of developing VSMC during embryonic development, understanding of the molecular mechanisms that control VSMC differentiation will provide fundamental insights into the pathological processes of these cardiovascular diseases. Although VSMC differentiation is usually ac- companied by an irreversible cell cycle exit, VSMC proliferation and differentiation occur concurrently during embryonic development. The molecular mechanisms simultaneously regulating these two processes, however, remain largely unknown. Our recent study demonstrates that cell division cycle 7, a key regulator of cell cycle, promotes both VSMC differentiation and proliferation through different mechanisms during the initial phase of VSMC differentiation. Conversely, Kriappel-like factor 4 appears to be a repressor for both VSMC differentia- tion and proliferation. This review attempts to highlight the novel role of cell division cycle 7 in TGF-β-induced VSMC differentiation and proliferation. The role of K141ppel-like factor 4 in suppressing these two processes will also be discussed.展开更多
Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell ...Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods： The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues （P〈0.05）. Fttrthermore, the tissues of stage Ⅱ-Ⅳ carcinoma patients showed higher CDC42 expression levels compared to stage I patients （P=0.05）. In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis （P〉0.05）. Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions： CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.展开更多
The transition from the vegetative phase to the reproductive phase is a major developmental process in flowering plants.The underlying mechanism controlling this cellular process remains a research focus in the field ...The transition from the vegetative phase to the reproductive phase is a major developmental process in flowering plants.The underlying mechanism controlling this cellular process remains a research focus in the field of plant molecular biology.In the present work,we identified a gene encoding the C3H2C3-type RING finger protein Nt RCP1 from tobacco BY-2 cells.Enzymatic analysis demonstrated that Nt RCP1 is a functional E3 ubiquitin ligase.In tobacco plants,expression level of Nt RCP1 was higher in the reproductive shoot apices than in the vegetative ones.Nt RCP1-overexpressing plants underwent a more rapid transition from the vegetative to the reproductive phase and flowered markedly earlier than the wild-type control.Histological analysis revealed that the shoot apical meristem of Nt RCP1-overexpressing plants initiated inflorescence primordia precociously compared to the wild-type plant due to accelerated cell division.Overexpression of Nt RCP1 in BY-2 suspension cells promoted cell division,which was a consequence of the shortened G2 phase in the cell cycle.Together,our data suggest that Nt RCP1 may act as a regulator of the phase transition,possibly through its role in cell cycle regulation,during vegetative/reproductive development in tobacco plant.展开更多
Analysis of cellular behavior is significant for studying cell cycle and detecting anti-cancer drugs. It is a very difficult task for image processing to isolate individual cells in confocal microscopic images of non-...Analysis of cellular behavior is significant for studying cell cycle and detecting anti-cancer drugs. It is a very difficult task for image processing to isolate individual cells in confocal microscopic images of non-stained live cell cultures. Because these images do not have adequate textural variations. Manual cell segmentation requires massive labor and is a time consuming process. This paper describes an automated cell segmentation method for localizing the cells of Chinese hamster ovary cell culture. Several kinds of high-dimensional feature descriptors, K-means clustering method and Chan-Vese model-based level set are used to extract the cellular regions. The region extracted are used to classify phases in cell cycle. The segmentation results were experimentally assessed. As a result, the proposed method proved to be significant for cell isolation. In the evaluation experiments, we constructed a database of Chinese Hamster Ovary Cell’s microscopic images which includes various photographing environments under the guidance of a biologist.展开更多
The widespread clinical application of paclitaxel(PTX)in cancer treatment has been significantly limited by the emergence of drug resistance and the presence of drug-tolerant persister cells.To systematically identify...The widespread clinical application of paclitaxel(PTX)in cancer treatment has been significantly limited by the emergence of drug resistance and the presence of drug-tolerant persister cells.To systematically identify key regulators of this resistance,we conducted a genome-wide CRISPR/Cas9 knockout screen,which revealed that cell division cycle 6(CDC6)is a critical determinant of cell adhesion-mediated PTX resistance.Furthermore,our results illustrate that CDC6,an essential DNA replication licensing factor,functions through a pathway distinct from previously well-characterized resistance mechanisms.Genetic depletion of CDC6 considerably sensitizes cells,markedly increasing PTX-induced cell death.In addition to its established role in chromosome stability,CDC6 physically interacts with tropomodulin-3(Tmod3)in the cytoplasmic compartment.This interaction enhances CDC6 protein stability and drives drug resistance phenotypes through the regulation of actin cytoskeleton remodeling and facilitating focal adhesion assembly.In addition,combination treatment with PTX and actin filament inhibitors synergistically enhanced the antitumor efficacy both in vitro and in vivo.Overall,our studies elucidate the mechanisms through which CDC6 functions as a key regulator of PTX resistance and provide a potential therapeutic strategy to increase PTX efficacy through the modulation of the cytoskeletal-adhesion axis.展开更多
Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely...Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely unexplored.In this study,microarray was leveraged for the first time to investigate the role of lncRNA in PT.We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse prognosis.Furthermore,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in vitro.Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in vivo.Mechanistically,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of TNFRSF19.In conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.展开更多
Aim:Cell division cycle 25B(CDC25B)belongs to the CDC25 family of phosphatases that regulate cell cycle progression.CDC25B also contributes to tumor initiation and progression,but no connection between CDC25B levels a...Aim:Cell division cycle 25B(CDC25B)belongs to the CDC25 family of phosphatases that regulate cell cycle progression.CDC25B also contributes to tumor initiation and progression,but no connection between CDC25B levels and drug sensitivity in pancreatic cancer has been reported.Based on our finding that bromodomain and extraterminal domain(BET)inhibitors decrease levels of CDC25B,we aim to compare the sensitivity of models expressing contrasting levels of CDC25B to the BET inhibitor JQ1,in pancreatic cancer cell lines in vitro and in patient-derived xenograft(PDX)models of pancreatic ductal adenocarcinoma(PDAC)in vivo.Methods:We compared the efficacy of the standard of care agent gemcitabine with the BET inhibitor JQ1,using alamarBlue assays to determine IC50s of three pancreatic cancer cell lines in vitro.We used immunohistochemistry(IHC)and immunoblot(IB)to detect CDC25B.We also compared the effect of each agent on the progression of PDX models of PDAC in vivo with contrasting levels of CDC25B.Results:Immunohistochemical data demonstrated that levels of CDC25B differed by~2-to 5-fold in cell lines and PDX models used.In vitro data showed that the level of CDC25B paralleled sensitivity to JQ1.Similarly,in vivo data showed that tumors with high-level CDC25B were more sensitive to JQ1 than tumors with lower CDC25B.The combination of JQ1+a pan CDC25 inhibitor was synergistic in gemcitabine-resistant Panc1.gemR cells that had relatively high levels of CDC25B expression compared to parent cells. Conclusion: The data suggest that CDC25B may be an independent indicator of sensitivity to BET inhibitors and that CDC25B may contribute to gemcitabine insensitivity in this tumor type.展开更多
基金Supported by the National High Technology Research and Development Program of China(863 Program)(2012AA02A212)
文摘Objective To examine the expression of cell division cycle associated 2(CDCA 2) in pancreatic ductal adenocarcinoma(PDAC) and investigate its role in prognosis of PDAC patients.Methods This retrospective study included 155 PDAC patients who underwent surgical treatment and complete post-operative follow-up.Clinicopathologic data were collected through clinical database.Tissue microarray was constructed and immunohistochemistry was performed to detect CDCA2 expression in the PDAC tumor tissues and adjacent non-tumor tissues.Clinicopathological characteristics between high and low CDCA2 expression were compared.Correlation of CDCA2 expressions with patients' survival was analyzed using Kaplan-Meier method and Cox regression analysis.Results Expression of CDCA2 in PDAC cells was significantly higher than that in adjacent non-tumor tissues(U=4056.5,P<0.001).Univariate analysis showed that CDCA2 expression [hazard ratio(HR)=1.574,95% confidence interval(CI)=1.014-2.443,P=0.043] and node metastasis(HR=1.704,95%CI=1.183-2.454,P=0.004) were significantly associated with prognosis.Cox regression analysis showed CDCA2 expression was not an independent prognostic risk factor(HR=1.418,95%CI=0.897-2.242,P=0.135) for PDCA patients.Stratification survival analysis demonstrated CDCA2 expression as an independent prognostic risk factor in male patients(HR=2.554,95%CI=1.446-4.511,P=0.003) or in non-perineural invasion patients(HR=2.290,95%CI=1.146-4.577,P=0.012).Conclusions CDCA2 is highly expressed in PDAC tumor tissue.Although CDCA2 is not an independent prognostic risk factor for PDAC patients,it might be used to help predict prognosis of male or non-perineural invasion patients of PDAC.
基金Zenji Research Laboratories for financial aid to this work
文摘To the Editor:Kinase cell division cycle 7(CDC7),a cell division cycle protein,takes a vital role in mediating DNA replication1.CDC7 complexes in the nucleus can phosphorylate the minichromosome maintenance complex(MCM)family members that bind to chromosomes.In addition,CDC7 kinase,as a molecular switch regulating DNA replication,can mediate DNA damage signaling pathways to stimulate cell cycle termination as well as DNA replication2.Studies have shown that CDC7 is overexpressed in many types of cancer cells,and its overexpression was related to poor patient survival,tumor grade,genetic instability,aneuploidy and so on3.Therefore,CDC7 is a promising target for antitumor therapy.
基金Supported by the National Natural Science Foundation of China under Grant No 10575041.
文摘Based on a deterministic cell cycle model of fission yeast, the effects of the finite cell size on the cell cycle regulation in wee1- cdc25△ double mutant type are numerically studied by using of the chemical Langevin equations. It is found that at a certain region of cell size, our numerical results from the chemical Langevin equations are in good qualitative agreement with the experimental observations. The two resettings to the G2 phase from early stages of mitosis can be induced under the moderate cell size. The quantized cycle times can be observed during such a cell size region. Therefore, a coarse estimation of cell size is obtained from the mesoscopic stochastic cell cycle model.
基金Supported by Sichuan Medical Association Research Project,No.Q2024049Clinical Science Research Fund of Chengdu Medical College,No.24 LHLNYX1-03+1 种基金Chengdu Medical College Elite Peak Program,No.2024qnGzn04Key Clinical Specialty of Sichuan Province,No.YS00109.
文摘BACKGROUND Pancreatic cancer(PC)is an aggressive malignancy.As a member of the BTN/BTNL family,BTNL9 has been identified as a tumor suppressor in breast cancer,lung adenocarcinoma,and colon cancer;however,its role and underlying mechanisms in PC remain to be elucidated.AIM To investigate the role of BTNL9 in the pathogenesis and development of PC.METHODS The difference of BTNL9 expression in cancer and adjacent normal tissues was analyzed by RNA sequencing data from a public database and tissue microarray detection.The relationship between BTNL9 expression and the prognosis of patients was also studied.The effects of BTNL9 on proliferation,metastasis,and cell cycle of PC cells were investigated by phenotypic experiments.The mechanism was investigated by RNA sequencing,western blotting,and immunofluorescence detection.RESULTS The mRNA and protein levels of BTNL9 in PC tissues were downregulated compared with normal tissues.Based on survival data from The Cancer Genome Atlas and tissue microarray,BTNL9 was an independent influencing factor for overall survival,and its low expression predicted a shortened overall survival of patients.In vitro,BTNL9 could inhibit cell proliferation and metastasis in both PANC-1 and MIA PaCa-2 cells and induce cell cycle arrest in G2/M phases.Downregulation of BTNL9 could activate the cell cycle signaling pathway.Furthermore,overexpression of BTNL9 could significantly inhibit the expression of cell division cycle 20(CDC20).Rescue experiments demonstrated that overexpression of CDC20 reversed the effect of BTNL9 on the proliferation,metastasis,and cell cycle of PC cells.CONCLUSION The expression of BTNL9 was downregulated in PC,and it has the prediction ability for prognosis.Functionally,BTNL9 exerted an anti-cancer effect by suppressing downstream CDC20 expression in PC.
基金The support provided by the Natural Science Foundation of Hubei Province(Grant No.2021CFA081)the National Natural Science Foundation of China(Grant No.42277160)the fellowship of China Postdoctoral Science Foundation(Grant No.2022TQ0241)is gratefully acknowledged.
文摘The big data generated by tunnel boring machines(TBMs)are widely used to reveal complex rock-machine interactions by machine learning(ML)algorithms.Data preprocessing plays a crucial role in improving ML accuracy.For this,a TBM big data preprocessing method in ML was proposed in the present study.It emphasized the accurate division of TBM tunneling cycle and the optimization method of feature extraction.Based on the data collected from a TBM water conveyance tunnel in China,its effectiveness was demonstrated by application in predicting TBM performance.Firstly,the Score-Kneedle(S-K)method was proposed to divide a TBM tunneling cycle into five phases.Conducted on 500 TBM tunneling cycles,the S-K method accurately divided all five phases in 458 cycles(accuracy of 91.6%),which is superior to the conventional duration division method(accuracy of 74.2%).Additionally,the S-K method accurately divided the stable phase in 493 cycles(accuracy of 98.6%),which is superior to two state-of-the-art division methods,namely the histogram discriminant method(accuracy of 94.6%)and the cumulative sum change point detection method(accuracy of 92.8%).Secondly,features were extracted from the divided phases.Specifically,TBM tunneling resistances were extracted from the free rotating phase and free advancing phase.The resistances were subtracted from the total forces to represent the true rock-fragmentation forces.The secant slope and the mean value were extracted as features of the increasing phase and stable phase,respectively.Finally,an ML model integrating a deep neural network and genetic algorithm(GA-DNN)was established to learn the preprocessed data.The GA-DNN used 6 secant slope features extracted from the increasing phase to predict the mean field penetration index(FPI)and torque penetration index(TPI)in the stable phase,guiding TBM drivers to make better decisions in advance.The results indicate that the proposed TBM big data preprocessing method can improve prediction accuracy significantly(improving R2s of TPI and FPI on the test dataset from 0.7716 to 0.9178 and from 0.7479 to 0.8842,respectively).
文摘Aim To investigate the influences of melatonin (MT) on the growth of HeLa cells in vitro. Methods Theantiprolfferation activities of MT were evaluated in HeLa cells by means of trypan blue dye exclusion and MTT vital staining.The morphological changes of HeLa cells induced by MT were observed under transmission electronic microscope. Cell divisioncycle influenced by MT was assessed by a flow cytometry. Results MT produced a certain inhibition of HeLa cells at the con-centration of 2 mmol@ L-1 and prolonged the TD. The fraction of cells inhibited was 61.0%. The IC. so of HeLa cells exposed toMT for 96 h was 2.039 mmol@ L- 1. The flow cytometric analyses showed that exposure to MT for 72 h reduced the number ofHeLa cells in phase S. Under electronic microscope, the HeLa cells exposed to MT for 72 h displayed morphological changesof necrosis, apoptosis, more hetero-chromosome and less somatic chromosome. Conclusion MT showed certain influences onthe growth of HeLa cells. Its mechanism may probably be attributable to reduction of the number of cells in phase S.
基金supported by grants from National Institutes of Health (HL093429 and HL107526 to S.-Y.C.)
文摘Vascular smooth muscle cell （VSMC） differentiation and proliferation are two important physiological proc- esses during vascular development. The phenotypic alteration from differentiated to proliferative VSMC contrib- utes to the development of several major cardiovascular diseases including atherosclerosis, hypertension, resteno- sis after angioplasty or bypass, diabetic vascular complications, and transplantation arteriopathy. Since the VSMC phenotype in these pathological conditions resembles that of developing VSMC during embryonic development, understanding of the molecular mechanisms that control VSMC differentiation will provide fundamental insights into the pathological processes of these cardiovascular diseases. Although VSMC differentiation is usually ac- companied by an irreversible cell cycle exit, VSMC proliferation and differentiation occur concurrently during embryonic development. The molecular mechanisms simultaneously regulating these two processes, however, remain largely unknown. Our recent study demonstrates that cell division cycle 7, a key regulator of cell cycle, promotes both VSMC differentiation and proliferation through different mechanisms during the initial phase of VSMC differentiation. Conversely, Kriappel-like factor 4 appears to be a repressor for both VSMC differentia- tion and proliferation. This review attempts to highlight the novel role of cell division cycle 7 in TGF-β-induced VSMC differentiation and proliferation. The role of K141ppel-like factor 4 in suppressing these two processes will also be discussed.
基金supported by the National Natural Science Foundation of China(No.11072006,No.10772007 and No.81070078)National Basic Research Program of China(973 Program,2013CB933702)
文摘Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods： The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues （P〈0.05）. Fttrthermore, the tissues of stage Ⅱ-Ⅳ carcinoma patients showed higher CDC42 expression levels compared to stage I patients （P=0.05）. In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis （P〉0.05）. Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions： CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.
基金supported by the Natural Science Foundation of China(Grant Nos.31100870 and30800556)
文摘The transition from the vegetative phase to the reproductive phase is a major developmental process in flowering plants.The underlying mechanism controlling this cellular process remains a research focus in the field of plant molecular biology.In the present work,we identified a gene encoding the C3H2C3-type RING finger protein Nt RCP1 from tobacco BY-2 cells.Enzymatic analysis demonstrated that Nt RCP1 is a functional E3 ubiquitin ligase.In tobacco plants,expression level of Nt RCP1 was higher in the reproductive shoot apices than in the vegetative ones.Nt RCP1-overexpressing plants underwent a more rapid transition from the vegetative to the reproductive phase and flowered markedly earlier than the wild-type control.Histological analysis revealed that the shoot apical meristem of Nt RCP1-overexpressing plants initiated inflorescence primordia precociously compared to the wild-type plant due to accelerated cell division.Overexpression of Nt RCP1 in BY-2 suspension cells promoted cell division,which was a consequence of the shortened G2 phase in the cell cycle.Together,our data suggest that Nt RCP1 may act as a regulator of the phase transition,possibly through its role in cell cycle regulation,during vegetative/reproductive development in tobacco plant.
文摘Analysis of cellular behavior is significant for studying cell cycle and detecting anti-cancer drugs. It is a very difficult task for image processing to isolate individual cells in confocal microscopic images of non-stained live cell cultures. Because these images do not have adequate textural variations. Manual cell segmentation requires massive labor and is a time consuming process. This paper describes an automated cell segmentation method for localizing the cells of Chinese hamster ovary cell culture. Several kinds of high-dimensional feature descriptors, K-means clustering method and Chan-Vese model-based level set are used to extract the cellular regions. The region extracted are used to classify phases in cell cycle. The segmentation results were experimentally assessed. As a result, the proposed method proved to be significant for cell isolation. In the evaluation experiments, we constructed a database of Chinese Hamster Ovary Cell’s microscopic images which includes various photographing environments under the guidance of a biologist.
基金supported by the National Natural Science Foundation of China(Nos.82173703,82293682).
文摘The widespread clinical application of paclitaxel(PTX)in cancer treatment has been significantly limited by the emergence of drug resistance and the presence of drug-tolerant persister cells.To systematically identify key regulators of this resistance,we conducted a genome-wide CRISPR/Cas9 knockout screen,which revealed that cell division cycle 6(CDC6)is a critical determinant of cell adhesion-mediated PTX resistance.Furthermore,our results illustrate that CDC6,an essential DNA replication licensing factor,functions through a pathway distinct from previously well-characterized resistance mechanisms.Genetic depletion of CDC6 considerably sensitizes cells,markedly increasing PTX-induced cell death.In addition to its established role in chromosome stability,CDC6 physically interacts with tropomodulin-3(Tmod3)in the cytoplasmic compartment.This interaction enhances CDC6 protein stability and drives drug resistance phenotypes through the regulation of actin cytoskeleton remodeling and facilitating focal adhesion assembly.In addition,combination treatment with PTX and actin filament inhibitors synergistically enhanced the antitumor efficacy both in vitro and in vivo.Overall,our studies elucidate the mechanisms through which CDC6 functions as a key regulator of PTX resistance and provide a potential therapeutic strategy to increase PTX efficacy through the modulation of the cytoskeletal-adhesion axis.
基金supported by the National Natural Science Foundation of China(82173054,82222029,82203085)the Guangdong Basic and Applied Basic Research Foundation(2022B1515020048,2022B1515020101,China)Guangzhou Science,Technology and Innovation Commission(202102010148,China).
文摘Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely unexplored.In this study,microarray was leveraged for the first time to investigate the role of lncRNA in PT.We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse prognosis.Furthermore,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in vitro.Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in vivo.Mechanistically,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of TNFRSF19.In conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.
文摘Aim:Cell division cycle 25B(CDC25B)belongs to the CDC25 family of phosphatases that regulate cell cycle progression.CDC25B also contributes to tumor initiation and progression,but no connection between CDC25B levels and drug sensitivity in pancreatic cancer has been reported.Based on our finding that bromodomain and extraterminal domain(BET)inhibitors decrease levels of CDC25B,we aim to compare the sensitivity of models expressing contrasting levels of CDC25B to the BET inhibitor JQ1,in pancreatic cancer cell lines in vitro and in patient-derived xenograft(PDX)models of pancreatic ductal adenocarcinoma(PDAC)in vivo.Methods:We compared the efficacy of the standard of care agent gemcitabine with the BET inhibitor JQ1,using alamarBlue assays to determine IC50s of three pancreatic cancer cell lines in vitro.We used immunohistochemistry(IHC)and immunoblot(IB)to detect CDC25B.We also compared the effect of each agent on the progression of PDX models of PDAC in vivo with contrasting levels of CDC25B.Results:Immunohistochemical data demonstrated that levels of CDC25B differed by~2-to 5-fold in cell lines and PDX models used.In vitro data showed that the level of CDC25B paralleled sensitivity to JQ1.Similarly,in vivo data showed that tumors with high-level CDC25B were more sensitive to JQ1 than tumors with lower CDC25B.The combination of JQ1+a pan CDC25 inhibitor was synergistic in gemcitabine-resistant Panc1.gemR cells that had relatively high levels of CDC25B expression compared to parent cells. Conclusion: The data suggest that CDC25B may be an independent indicator of sensitivity to BET inhibitors and that CDC25B may contribute to gemcitabine insensitivity in this tumor type.
