The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predomi...The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.展开更多
Intracellular pH plays a significant role in various biological processes, including cell proliferation,apoptosis, metabolism, enzyme activity and homeostasis. In this work, a novel design strategy for the preparation...Intracellular pH plays a significant role in various biological processes, including cell proliferation,apoptosis, metabolism, enzyme activity and homeostasis. In this work, a novel design strategy for the preparation of pH responsive carbon dots(CDs-pH) for ratiometric intracellular imaging was reported. By using SciFinder database, fluorescent CDs-pH with the required p Kavalue of 6.84 were rationally designed, which is vital important for precise sensing of intracellular pH. As a result, the synthesized CDspH demonstrated robust ability to test pH fluctuations within the physiological range of 5.4-7.4. The CDspH was further utilized for fluorescent ratiometric imaging of pH in living HeLa cells, effectively avoided the influence of autofluorescence from native cellular species. Moreover, real-time monitoring of intracellular pH fluctuation under heat shock was successfully realized. This SciFinder-guided design strategy is simple and flexible, which has a great potential to be used for the development of other types of CDs for various applications.展开更多
Background MicroRNAs （miRNAs） are small noncoding regulatory RNAs whose aberrant expression may be observed in many malignancies. However, few data are yet available on human primary medulloblastomas. This work aime...Background MicroRNAs （miRNAs） are small noncoding regulatory RNAs whose aberrant expression may be observed in many malignancies. However, few data are yet available on human primary medulloblastomas. This work aimed to identify that whether miRNAs would be aberrantly expressed in tumor tissues compared with non-tumorous cerebellum tissues from same patients, and to explore a possible role during carcinogenesis. Methods A high throughput microRNA microarray was performed in human primary medulloblastoma specimens to investigate differentially expressed miRNAs, and some miRNAs were validated using real-time quantitative RT-PCR method. In addition, the predicted target genes for the most significantly downor up-regulated miRNAs were analyzed by using a newly modified ensemble algorithm. Results Nine miRNA species were differentially expressed in medulloblastoma specimens versus normal non-tumorous cerebellum tissues. Of these, 4 were over expressed and 5 were under expressed. The changes ranged from 0.02-fold to 6.61-fold. These findings were confirmed using real-time quantitative RT-PCR for most significant deregulated miRNAs （miR-17, miR-100, miR-106b, and miR-218） which are novel and have not been previously published. Interestingly, most of the predicted target genes for these miRNAs were involved in medulloblastoma carcinogenesis. Conclusions MJRNAs are differentially expressed between human medulloblastoma and non-tumorous cerebellum tissue. MiRNAs may play a role in the tumorigenesis of medulloblastoma and maybe serve as potential targets for novel therapeutic strategies in future.展开更多
Aristolochic acids(AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I(AAI) reacts with DNA to form covalent aristolactam(AL)-DNA adducts,leading to subsequent A to T t...Aristolochic acids(AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I(AAI) reacts with DNA to form covalent aristolactam(AL)-DNA adducts,leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in China's Mainland. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.展开更多
Precision radiotherapy is a critical and indispensable cancer treatment means in the modern clinical workflow with the goal of achieving“quality-up and cost-down”in patient care.The challenge of this therapy lies in...Precision radiotherapy is a critical and indispensable cancer treatment means in the modern clinical workflow with the goal of achieving“quality-up and cost-down”in patient care.The challenge of this therapy lies in developing computerized clinical-assistant solutions with precision,automation,and reproducibility built-in to deliver it at scale.In this work,we provide a comprehensive yet ongoing,incomplete survey of and discussions on the recent progress of utilizing advanced deep learning,semantic organ parsing,multimodal imaging fusion,neural architecture search and medical image analytical techniques to address four corner-stone problems or sub-problems required by all precision radiotherapy workflows,namely,organs at risk(OARs)segmentation,gross tumor volume(GTV)segmentation,metastasized lymph node(LN)detection,and clinical tumor volume(CTV)segmentation.Without loss of generality,we mainly focus on using esophageal and head-and-neck cancers as examples,but the methods can be extrapolated to other types of cancers.High-precision,automated and highly reproducible OAR/GTV/LN/CTV auto-delineation techniques have demonstrated their effectiveness in reducing the inter-practitioner variabilities and the time cost to permit rapid treatment planning and adaptive replanning for the benefit of patients.Through the presentation of the achievements and limitations of these techniques in this review,we hope to encourage more collective multidisciplinary precision radiotherapy workflows to transpire.展开更多
基金supported by the National Key R&D Program of China(2024YFF1306700)the Key Project of Basic Research of Yunnan Province,China(202301AS070001)the Regional Innovative Development Joint Fund of NSFC(U23A20149).
文摘The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.
基金financial support from the National Natural Science Foundation of China (No. 21205108)the Foundation for University Key Teacher by Henan Province (No. 2017GGJS007)+1 种基金China Postdoctoral Science Foundation (Nos. 2017M620302, 2018T110736)the Key Scientific Research Project in Universities of Henan Province (No. 19A150048)
文摘Intracellular pH plays a significant role in various biological processes, including cell proliferation,apoptosis, metabolism, enzyme activity and homeostasis. In this work, a novel design strategy for the preparation of pH responsive carbon dots(CDs-pH) for ratiometric intracellular imaging was reported. By using SciFinder database, fluorescent CDs-pH with the required p Kavalue of 6.84 were rationally designed, which is vital important for precise sensing of intracellular pH. As a result, the synthesized CDspH demonstrated robust ability to test pH fluctuations within the physiological range of 5.4-7.4. The CDspH was further utilized for fluorescent ratiometric imaging of pH in living HeLa cells, effectively avoided the influence of autofluorescence from native cellular species. Moreover, real-time monitoring of intracellular pH fluctuation under heat shock was successfully realized. This SciFinder-guided design strategy is simple and flexible, which has a great potential to be used for the development of other types of CDs for various applications.
文摘Background MicroRNAs （miRNAs） are small noncoding regulatory RNAs whose aberrant expression may be observed in many malignancies. However, few data are yet available on human primary medulloblastomas. This work aimed to identify that whether miRNAs would be aberrantly expressed in tumor tissues compared with non-tumorous cerebellum tissues from same patients, and to explore a possible role during carcinogenesis. Methods A high throughput microRNA microarray was performed in human primary medulloblastoma specimens to investigate differentially expressed miRNAs, and some miRNAs were validated using real-time quantitative RT-PCR method. In addition, the predicted target genes for the most significantly downor up-regulated miRNAs were analyzed by using a newly modified ensemble algorithm. Results Nine miRNA species were differentially expressed in medulloblastoma specimens versus normal non-tumorous cerebellum tissues. Of these, 4 were over expressed and 5 were under expressed. The changes ranged from 0.02-fold to 6.61-fold. These findings were confirmed using real-time quantitative RT-PCR for most significant deregulated miRNAs （miR-17, miR-100, miR-106b, and miR-218） which are novel and have not been previously published. Interestingly, most of the predicted target genes for these miRNAs were involved in medulloblastoma carcinogenesis. Conclusions MJRNAs are differentially expressed between human medulloblastoma and non-tumorous cerebellum tissue. MiRNAs may play a role in the tumorigenesis of medulloblastoma and maybe serve as potential targets for novel therapeutic strategies in future.
基金supported by National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2018ZX09101002,2018ZX09101002-001-001,and 2018ZX09101002-001-002,China)sponsored by National Natural Science Foundation of China (81830054,91859205,81988101,81722034,and 81802878)+1 种基金Shanghai Pujiang Program (2019PJD059,China),Shanghai Sailing Program (18YF1400200,China)Key Discipline Project of Shanghai Municipal Education Commission (201901070007E00065,China)。
文摘Aristolochic acids(AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I(AAI) reacts with DNA to form covalent aristolactam(AL)-DNA adducts,leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in China's Mainland. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.
文摘Precision radiotherapy is a critical and indispensable cancer treatment means in the modern clinical workflow with the goal of achieving“quality-up and cost-down”in patient care.The challenge of this therapy lies in developing computerized clinical-assistant solutions with precision,automation,and reproducibility built-in to deliver it at scale.In this work,we provide a comprehensive yet ongoing,incomplete survey of and discussions on the recent progress of utilizing advanced deep learning,semantic organ parsing,multimodal imaging fusion,neural architecture search and medical image analytical techniques to address four corner-stone problems or sub-problems required by all precision radiotherapy workflows,namely,organs at risk(OARs)segmentation,gross tumor volume(GTV)segmentation,metastasized lymph node(LN)detection,and clinical tumor volume(CTV)segmentation.Without loss of generality,we mainly focus on using esophageal and head-and-neck cancers as examples,but the methods can be extrapolated to other types of cancers.High-precision,automated and highly reproducible OAR/GTV/LN/CTV auto-delineation techniques have demonstrated their effectiveness in reducing the inter-practitioner variabilities and the time cost to permit rapid treatment planning and adaptive replanning for the benefit of patients.Through the presentation of the achievements and limitations of these techniques in this review,we hope to encourage more collective multidisciplinary precision radiotherapy workflows to transpire.
