Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focus...Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.展开更多
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
This review summarizes recent multidisciplinary research on South Korea’s significant paleoenvironmental and paleoclimatic events.It is composed of review articles divided into Quaternary geological studies,proxy-bas...This review summarizes recent multidisciplinary research on South Korea’s significant paleoenvironmental and paleoclimatic events.It is composed of review articles divided into Quaternary geological studies,proxy-based Quaternary studies,and applied Quaternary studies.Quaternary geological studies include geomorphological,stratigraphical,and chronological studies.Proxy-based Quaternary studies include environmental magnetism,stable isotope-based,and pollen-and diatom-based studies.Applied Quaternary studies include Quaternary aggregate resources and geoarchaeology.Finally,we ended with suggestions about the future direction of Quaternary research to better understand the Quaternary evolution in the Korean Peninsula.展开更多
For the Anthropocene to get recognized as a real geological era,first and foremost its strata must be identified.Several geological formations such as bogs,lakebeds,reefs,ice sheets,speleothems,river estuary deposits,...For the Anthropocene to get recognized as a real geological era,first and foremost its strata must be identified.Several geological formations such as bogs,lakebeds,reefs,ice sheets,speleothems,river estuary deposits,and sea floors have been considered as potential candidates for the Anthropocene strata.This consideration arises from the emergence of novel materials associated with the Anthropocene,including radioactive isotopes,plastics,and aluminum,started to be discovered in their sediments and dramatically increased since the mid-20th century.Yet,these deposits are no longer considered‘natural’because human activities are largely controlling the transport and depositional processes from source to sink.The Municipal Solid Waste(MSW)in landfills has been also‘unnaturally’transported and deposited(landfilled)by humans.Since the 1950s,the controlled landfills have been made worldwide,and thus the opening time of the landfills is clear.The MSW layers of landfills,which appeared globally,contemporaneously,and with distinct characteristics,are indeed the‘artificial(anthropogenic)’strata showing a new and clear aspect of human influence,unprecedented in geological time.The MSW layers can be considered valuable indicators of the Anthropocene era because they not only preserve the history of human life but also sensitively demonstrate the scale of human activities like mass production,consumption,and disposal.The MSW layers can be expected to serve as a unique window into the Anthropocene.展开更多
Objective:To investigate the relationship between growth patterns and mandibular posterior tooth-alveolar bone complex morphology in a Chinese population with normal occlusion.Methods:Forty-five patients with normal o...Objective:To investigate the relationship between growth patterns and mandibular posterior tooth-alveolar bone complex morphology in a Chinese population with normal occlusion.Methods:Forty-five patients with normal occlusion(23 males,22 females) were included in this study.Among these patients,20 displayed the vertical growth pattern,and 20 had the horizontal growth pattern,while the remaining patients displayed the average growth pattern.All of the patients underwent dental cone beam computed tomography(CBCT),which included the region of the mandibular posterior teeth and the alveolar.A linear regression analysis and a correlation analysis between the facial height index(FHI) and the alveolar bone morphology were performed.Results:The inclination of the molars,the thickness of the cortical bone,and the height of the mandibular bone differed significantly between patients with the horizontal growth pattern and those with the vertical growth pattern(P<0.05).Significant positive correlations were found between:the FHI and the inclination of the molars;the FHI and the thickness of the cortical bone;and the FHI and the height of the mandibular bone.Conclusions:The mandibular posterior tooth-alveolar bone complex morphology may be affected by growth patterns.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
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LY24H300001)the Medical and Health Research Project of Zhejiang Province(KY202302130009)National Health Service Research Project(WKZX2024CX501205).
文摘Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.
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supported by the project“Geological survey in the Korean Peninsula and publication of the geological maps(GP2020-026)”of the Korea Institute of Geoscience and Mineral Resources(KIGAM)funded by the Ministry of Science and ICT,Korea.We sincerely thank the anonymous reviewers for their constructive comments,which allowed us to improve our manuscript.
文摘This review summarizes recent multidisciplinary research on South Korea’s significant paleoenvironmental and paleoclimatic events.It is composed of review articles divided into Quaternary geological studies,proxy-based Quaternary studies,and applied Quaternary studies.Quaternary geological studies include geomorphological,stratigraphical,and chronological studies.Proxy-based Quaternary studies include environmental magnetism,stable isotope-based,and pollen-and diatom-based studies.Applied Quaternary studies include Quaternary aggregate resources and geoarchaeology.Finally,we ended with suggestions about the future direction of Quaternary research to better understand the Quaternary evolution in the Korean Peninsula.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(NRF-2018R1A5A7025409,NP2018-026)the Energy&Mineral Resources Development Association of Korea(EMRD)grant funded by the Korea government(MOTIE)(2021060001).
文摘For the Anthropocene to get recognized as a real geological era,first and foremost its strata must be identified.Several geological formations such as bogs,lakebeds,reefs,ice sheets,speleothems,river estuary deposits,and sea floors have been considered as potential candidates for the Anthropocene strata.This consideration arises from the emergence of novel materials associated with the Anthropocene,including radioactive isotopes,plastics,and aluminum,started to be discovered in their sediments and dramatically increased since the mid-20th century.Yet,these deposits are no longer considered‘natural’because human activities are largely controlling the transport and depositional processes from source to sink.The Municipal Solid Waste(MSW)in landfills has been also‘unnaturally’transported and deposited(landfilled)by humans.Since the 1950s,the controlled landfills have been made worldwide,and thus the opening time of the landfills is clear.The MSW layers of landfills,which appeared globally,contemporaneously,and with distinct characteristics,are indeed the‘artificial(anthropogenic)’strata showing a new and clear aspect of human influence,unprecedented in geological time.The MSW layers can be considered valuable indicators of the Anthropocene era because they not only preserve the history of human life but also sensitively demonstrate the scale of human activities like mass production,consumption,and disposal.The MSW layers can be expected to serve as a unique window into the Anthropocene.
基金Project supported by the Shandong Science and Technology Planning Project (Nos.2010G0020232,2010HM053,and 2010GSF10269)the Shandong Provincial Natural Science Foundation (No.ZR2012HM087)+1 种基金the Jinan Science and Technology Planning Project(No.JN201202042)the Shandong University Project(Nos.2011JC009 and 2012JC031),China
文摘Objective:To investigate the relationship between growth patterns and mandibular posterior tooth-alveolar bone complex morphology in a Chinese population with normal occlusion.Methods:Forty-five patients with normal occlusion(23 males,22 females) were included in this study.Among these patients,20 displayed the vertical growth pattern,and 20 had the horizontal growth pattern,while the remaining patients displayed the average growth pattern.All of the patients underwent dental cone beam computed tomography(CBCT),which included the region of the mandibular posterior teeth and the alveolar.A linear regression analysis and a correlation analysis between the facial height index(FHI) and the alveolar bone morphology were performed.Results:The inclination of the molars,the thickness of the cortical bone,and the height of the mandibular bone differed significantly between patients with the horizontal growth pattern and those with the vertical growth pattern(P<0.05).Significant positive correlations were found between:the FHI and the inclination of the molars;the FHI and the thickness of the cortical bone;and the FHI and the height of the mandibular bone.Conclusions:The mandibular posterior tooth-alveolar bone complex morphology may be affected by growth patterns.
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.
