Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation ene...Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.展开更多
We demonstrate the feasibility of performing a systematic screen for human gene functions in Drosophila by assaying for their ability to induce overexpression phenotypes. Over 1 500 transgenic fly lines corresponding ...We demonstrate the feasibility of performing a systematic screen for human gene functions in Drosophila by assaying for their ability to induce overexpression phenotypes. Over 1 500 transgenic fly lines corresponding to 236 human genes have been established. In all, 51 lines are capable of eliciting a phenotype suggesting that the human genes are functional. These heterologous genes are functionally relevant as we have found a similar mutant phenotype caused either by a dominant negative mutant form of the human ribosomal protein L8 gene or by RNAi downregulation of the Drosophila RPL8. Significantly, the Drosophila RPL8 mutant can be rescued by wild-type human RPL8. We also provide genetic evidence that Drosophila RPL8 is a new member of the insulin signaling pathway. In summary, the functions of many human genes appear to be highly conserved, and the ability to identify them in Drosophila represents a powerful genetic tool for large-scale analysis of human transcripts in vivo.展开更多
Fault prognosis is mainly referred to the estimation of the operating time before a failure occurs,which is vital for ensuring the stability,safety and long lifetime of degrading industrial systems.According to the re...Fault prognosis is mainly referred to the estimation of the operating time before a failure occurs,which is vital for ensuring the stability,safety and long lifetime of degrading industrial systems.According to the results of fault prognosis,the maintenance strategy for underlying industrial systems can realize the conversion from passive maintenance to active maintenance.With the increased complexity and the improved automation level of industrial systems,fault prognosis techniques have become more and more indispensable.Particularly,the datadriven based prognosis approaches,which tend to find the hidden fault factors and determine the specific fault occurrence time of the system by analysing historical or real-time measurement data,gain great attention from different industrial sectors.In this context,the major task of this paper is to present a systematic overview of data-driven fault prognosis for industrial systems.Firstly,the characteristics of different prognosis methods are revealed with the data-based ones being highlighted.Moreover,based on the different data characteristics that exist in industrial systems,the corresponding fault prognosis methodologies are illustrated,with emphasis on analyses and comparisons of different prognosis methods.Finally,we reveal the current research trends and look forward to the future challenges in this field.This review is expected to serve as a tutorial and source of references for fault prognosis researchers.展开更多
AIM: To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer (HNPCC) and hMLH1 gene promoter methylation, and to improve the screening strategy and explore t...AIM: To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer (HNPCC) and hMLH1 gene promoter methylation, and to improve the screening strategy and explore the pertinent test methods. METHODS: A systematic analysis of 30 probands from HNPCC families in the north of China was performed by immunohistochemistry, microsatellite instability (MSI), gene mutation and methylation detection. RESULTS: High frequency microsatellite instability occurred in 25 probands (83.3%) of HNPCC family. Loss of hMLH1 and hMSH2 protein expression accounted for 88% of all microsatellite instability. Pathogenic muta-tion occurred in 14 samples and 3 novel mutational sites were discovered. Deletion of exons 1-6, 1-7 and 8 of hMSH2 was detected in 3 samples and no large fragment deletion was found in hMLH1. Of the 30 probands, hMLH1 gene promoter methylation occurred in 3 probands. The rate of gene micromutation detection combined with large fragment deletion detection was 46.7%-56.7%. The rate of the two methods in combination with methylation detection was 63.3%. CONCLUSION: Scientific and rational detection strategy can improve the detection rate of HNPCC. Based on traditional molecular genetics and combined with epigenetics, multiple detection methods can accurately diagnose HNPCC.展开更多
In order to amplify the complete genome of enJSRV from the strain of Inner Mongolia (enJSRV-NM), we used enJSRV-specific and JSRV-specific DNA probes in dot blot hybridization. Seven pairs of primers were designed bas...In order to amplify the complete genome of enJSRV from the strain of Inner Mongolia (enJSRV-NM), we used enJSRV-specific and JSRV-specific DNA probes in dot blot hybridization. Seven pairs of primers were designed based on Genbank sequences. Seven fragments were obtained by PCR and were cloned into the PMD19-T vectors. The recombinant plasmids were sequenced and analyzed. The results showed that the genome was 7 942 bp in length and contained four overlapping open reading frames corresponding to the gag, pro, pol and env genes as well as an additional open reading frame (orf-x) that overlaps the 3' end of the pol gene. The nucleotide acid sequences of the enJSRV-NM loci were compared with the sequences of South Africa enJS56A1 strain (Accession No. AF153615) and USA JSRV21 strain (Accession No. AF105220). The nucleotide acid identities were 99.2% and 92.3% respectively. Two zinc fingers were found in the NC region in the predicted amino acid sequence. However, the YXXM motif, which is a reliable molecular marker for the infectious exogenous virus, was not found in the TM region. It was found that the enJSRV-NM region was 90%-98% identical at the amino acid level to its exogenous infectious counterparts in most of the retroviral genome. This is the first nucleotide sequence of enJSRV reported in P.R China. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the clinical diagnosis of OPA.展开更多
目的:探讨乳腺原发性腺样囊性癌(adenoid cystic carcinoma,ACC)的影像学表现特征,提高对该病的认识和诊断准确性。方法:回顾性分析2012年1月至2018年9月天津医科大学肿瘤医院31例经病理证实的乳腺原发性ACC患者的临床资料,根据乳腺影...目的:探讨乳腺原发性腺样囊性癌(adenoid cystic carcinoma,ACC)的影像学表现特征,提高对该病的认识和诊断准确性。方法:回顾性分析2012年1月至2018年9月天津医科大学肿瘤医院31例经病理证实的乳腺原发性ACC患者的临床资料,根据乳腺影像报告与数据系统(breast imaging reporting and data system,BI-RADS)标准分析其X线和超声表现,并与病理进行对照。结果:31例乳腺原发性ACC患者的乳腺X线表现为肿物25例和局限不对称致密6例,所有病变均无钙化。25例患者中高或稍高密度肿物16例、等密度肿物7例和混杂密度肿物2例。31例患者的乳腺超声检查表现为肿物25例和非肿块样病变6例。25例患者中22例为低回声肿物和3例为混合回声肿物;6例非肿块样病变患者包括低回声区和偏高回声为主的混合回声区各3例,均无沿导管走行方向分布的趋势。结论:乳腺原发性ACC的影像学表现无特异性,但乳腺X线表现形态不规则且边缘模糊的高密度肿物内含稍低密度或脂肪样密度区域,乳腺超声表现偏高回声为主且不沿导管走行方向分布的非肿块样病变等征象具有一定提示意义,最终确诊依靠病理。展开更多
基金supported by the National Natural Science Foundation of China(No.82172186)the Zhejiang Provincial Natural Science Foundation of China(No.LY21H160030)+1 种基金the National Natural Science Foundation of China(No.82373206,No.82073332)the National Key Research and Development Program of China(No.2022YFE0107800).
文摘Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.
基金We are grateful to Xizhi Ma, Junnian Zhou, Tianhong Xu, Xu Liu, Xu Ding, Yang Liu, Ying Peng, Congwu Chi, Yiying Shang, Mingyao Ying, Sheng Ding, Lei Sun, Lei Tian, Huanhu Zhu, Hua Huang, Hongmei Li, and Xiaomo Wu for cDNA constructs and partial transgenic work, and Lihui Zhou (East China University of Science and Technology, China) for scanning electron microscopy. We thank Duc Nguyen (Yale University, USA) for critical reading and editing of this manuscript. This work is supported by grants from the National Natural Science Foundation of China (Grant Nos. 30030080, 39970408 and 30470840), National Basic Research Program of China (973) (Grant No. 2006CB806700).
文摘We demonstrate the feasibility of performing a systematic screen for human gene functions in Drosophila by assaying for their ability to induce overexpression phenotypes. Over 1 500 transgenic fly lines corresponding to 236 human genes have been established. In all, 51 lines are capable of eliciting a phenotype suggesting that the human genes are functional. These heterologous genes are functionally relevant as we have found a similar mutant phenotype caused either by a dominant negative mutant form of the human ribosomal protein L8 gene or by RNAi downregulation of the Drosophila RPL8. Significantly, the Drosophila RPL8 mutant can be rescued by wild-type human RPL8. We also provide genetic evidence that Drosophila RPL8 is a new member of the insulin signaling pathway. In summary, the functions of many human genes appear to be highly conserved, and the ability to identify them in Drosophila represents a powerful genetic tool for large-scale analysis of human transcripts in vivo.
基金supported by the National Natural Science Foundation of China(61773087)the National Key Research and Development Program of China(2018YFB1601500)High-tech Ship Research Project of Ministry of Industry and Information Technology-Research of Intelligent Ship Testing and Verifacation([2018]473)
文摘Fault prognosis is mainly referred to the estimation of the operating time before a failure occurs,which is vital for ensuring the stability,safety and long lifetime of degrading industrial systems.According to the results of fault prognosis,the maintenance strategy for underlying industrial systems can realize the conversion from passive maintenance to active maintenance.With the increased complexity and the improved automation level of industrial systems,fault prognosis techniques have become more and more indispensable.Particularly,the datadriven based prognosis approaches,which tend to find the hidden fault factors and determine the specific fault occurrence time of the system by analysing historical or real-time measurement data,gain great attention from different industrial sectors.In this context,the major task of this paper is to present a systematic overview of data-driven fault prognosis for industrial systems.Firstly,the characteristics of different prognosis methods are revealed with the data-based ones being highlighted.Moreover,based on the different data characteristics that exist in industrial systems,the corresponding fault prognosis methodologies are illustrated,with emphasis on analyses and comparisons of different prognosis methods.Finally,we reveal the current research trends and look forward to the future challenges in this field.This review is expected to serve as a tutorial and source of references for fault prognosis researchers.
基金Supported by Beijing Natural Science Foundation, No. 7062064
文摘AIM: To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer (HNPCC) and hMLH1 gene promoter methylation, and to improve the screening strategy and explore the pertinent test methods. METHODS: A systematic analysis of 30 probands from HNPCC families in the north of China was performed by immunohistochemistry, microsatellite instability (MSI), gene mutation and methylation detection. RESULTS: High frequency microsatellite instability occurred in 25 probands (83.3%) of HNPCC family. Loss of hMLH1 and hMSH2 protein expression accounted for 88% of all microsatellite instability. Pathogenic muta-tion occurred in 14 samples and 3 novel mutational sites were discovered. Deletion of exons 1-6, 1-7 and 8 of hMSH2 was detected in 3 samples and no large fragment deletion was found in hMLH1. Of the 30 probands, hMLH1 gene promoter methylation occurred in 3 probands. The rate of gene micromutation detection combined with large fragment deletion detection was 46.7%-56.7%. The rate of the two methods in combination with methylation detection was 63.3%. CONCLUSION: Scientific and rational detection strategy can improve the detection rate of HNPCC. Based on traditional molecular genetics and combined with epigenetics, multiple detection methods can accurately diagnose HNPCC.
基金National Natural Science Foundation ofChina (Grant No. 30560108)
文摘In order to amplify the complete genome of enJSRV from the strain of Inner Mongolia (enJSRV-NM), we used enJSRV-specific and JSRV-specific DNA probes in dot blot hybridization. Seven pairs of primers were designed based on Genbank sequences. Seven fragments were obtained by PCR and were cloned into the PMD19-T vectors. The recombinant plasmids were sequenced and analyzed. The results showed that the genome was 7 942 bp in length and contained four overlapping open reading frames corresponding to the gag, pro, pol and env genes as well as an additional open reading frame (orf-x) that overlaps the 3' end of the pol gene. The nucleotide acid sequences of the enJSRV-NM loci were compared with the sequences of South Africa enJS56A1 strain (Accession No. AF153615) and USA JSRV21 strain (Accession No. AF105220). The nucleotide acid identities were 99.2% and 92.3% respectively. Two zinc fingers were found in the NC region in the predicted amino acid sequence. However, the YXXM motif, which is a reliable molecular marker for the infectious exogenous virus, was not found in the TM region. It was found that the enJSRV-NM region was 90%-98% identical at the amino acid level to its exogenous infectious counterparts in most of the retroviral genome. This is the first nucleotide sequence of enJSRV reported in P.R China. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the clinical diagnosis of OPA.
文摘目的:探讨乳腺原发性腺样囊性癌(adenoid cystic carcinoma,ACC)的影像学表现特征,提高对该病的认识和诊断准确性。方法:回顾性分析2012年1月至2018年9月天津医科大学肿瘤医院31例经病理证实的乳腺原发性ACC患者的临床资料,根据乳腺影像报告与数据系统(breast imaging reporting and data system,BI-RADS)标准分析其X线和超声表现,并与病理进行对照。结果:31例乳腺原发性ACC患者的乳腺X线表现为肿物25例和局限不对称致密6例,所有病变均无钙化。25例患者中高或稍高密度肿物16例、等密度肿物7例和混杂密度肿物2例。31例患者的乳腺超声检查表现为肿物25例和非肿块样病变6例。25例患者中22例为低回声肿物和3例为混合回声肿物;6例非肿块样病变患者包括低回声区和偏高回声为主的混合回声区各3例,均无沿导管走行方向分布的趋势。结论:乳腺原发性ACC的影像学表现无特异性,但乳腺X线表现形态不规则且边缘模糊的高密度肿物内含稍低密度或脂肪样密度区域,乳腺超声表现偏高回声为主且不沿导管走行方向分布的非肿块样病变等征象具有一定提示意义,最终确诊依靠病理。