DNA translesion synthesis(TLS)is a DNA damage tolerance mechanism that relies on a series of specialized DNA polymerases able to bypass a lesion on a DNA template strand during replication or post-repair synthesis.TLS...DNA translesion synthesis(TLS)is a DNA damage tolerance mechanism that relies on a series of specialized DNA polymerases able to bypass a lesion on a DNA template strand during replication or post-repair synthesis.TLS DNA polymerases pursue replication by inserting a base opposite this lesion,correctly or incorrectly展开更多
Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of...Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of various elements such as antigens, antibodies, linkers, and payloads. While ADCs aim to target tumor cells specifically, several antigens can also be found in regular tissues, potentially compromising the specificity of ADCs in therapeutic applications. The complexity extends to antibody selection, necessitating effective targeting of the desired antigen and ensuring compatibility with linkers for effective payload delivery. Additionally, the linker and payload combination are critical for the ADC’s therapeutic efficiency, balancing stability in circulation and timely payload release upon target binding. ADC doses must be safe for normal tissues while ensuring the released payloads are effective. The success of ADCs is attributed to their unmatched efficacy compared to traditional chemotherapy agents. The current research article aims to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer therapies. A brief discussion on the basics of ADCs, regulatory approach, overview, and technical complexities for quantification is presented. This review also summarizes recently approved ADCs and introduces the concepts of antibodies, linkers, and payloads. The article also outlines cancer-specific ADCs currently in late-stage clinical trials for cancer treatment.展开更多
China＇s reform and opening-up policy has brought the country a great development opportunity. The high-speed growth of the economy not only led China to a period of industrialization, urbanization, informatization an...China＇s reform and opening-up policy has brought the country a great development opportunity. The high-speed growth of the economy not only led China to a period of industrialization, urbanization, informatization and agricultural modernization, but also exacerbated the situation of the urban–rural dual structure. Based on the review of current studies, we first used the analytic hierarchy process（AHP） method to evaluate the urban–rural development and transformation level by population transformation index, land transformation index, industrial transformation index and social transformation index between 1996 and 2012 around the Bohai Rim Region. Then, based on the results of each index, we used the exploratory spatial data analysis（ESDA） method to investigate the spatial autocorrelation of the change in the urban–rural development transformation index during the 16-year period using Global Moran＇s I index and Local Moran＇s I index. Finally, we investigated the mechanism of change of the urban–rural development transformation index at county level, summarizing five main factors：（1） the radiation from the surrounding big cities,（2） the acceleration of the urbanization process,（3） the upgrading of the industrial structure,（4） the publishing and implementation of a macro development strategy and regional policy, and（5） natural factors such as topology.展开更多
文摘DNA translesion synthesis(TLS)is a DNA damage tolerance mechanism that relies on a series of specialized DNA polymerases able to bypass a lesion on a DNA template strand during replication or post-repair synthesis.TLS DNA polymerases pursue replication by inserting a base opposite this lesion,correctly or incorrectly
文摘Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of various elements such as antigens, antibodies, linkers, and payloads. While ADCs aim to target tumor cells specifically, several antigens can also be found in regular tissues, potentially compromising the specificity of ADCs in therapeutic applications. The complexity extends to antibody selection, necessitating effective targeting of the desired antigen and ensuring compatibility with linkers for effective payload delivery. Additionally, the linker and payload combination are critical for the ADC’s therapeutic efficiency, balancing stability in circulation and timely payload release upon target binding. ADC doses must be safe for normal tissues while ensuring the released payloads are effective. The success of ADCs is attributed to their unmatched efficacy compared to traditional chemotherapy agents. The current research article aims to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer therapies. A brief discussion on the basics of ADCs, regulatory approach, overview, and technical complexities for quantification is presented. This review also summarizes recently approved ADCs and introduces the concepts of antibodies, linkers, and payloads. The article also outlines cancer-specific ADCs currently in late-stage clinical trials for cancer treatment.
基金National Natural Science Foundation of China,No.41130748No.41471143
文摘China＇s reform and opening-up policy has brought the country a great development opportunity. The high-speed growth of the economy not only led China to a period of industrialization, urbanization, informatization and agricultural modernization, but also exacerbated the situation of the urban–rural dual structure. Based on the review of current studies, we first used the analytic hierarchy process（AHP） method to evaluate the urban–rural development and transformation level by population transformation index, land transformation index, industrial transformation index and social transformation index between 1996 and 2012 around the Bohai Rim Region. Then, based on the results of each index, we used the exploratory spatial data analysis（ESDA） method to investigate the spatial autocorrelation of the change in the urban–rural development transformation index during the 16-year period using Global Moran＇s I index and Local Moran＇s I index. Finally, we investigated the mechanism of change of the urban–rural development transformation index at county level, summarizing five main factors：（1） the radiation from the surrounding big cities,（2） the acceleration of the urbanization process,（3） the upgrading of the industrial structure,（4） the publishing and implementation of a macro development strategy and regional policy, and（5） natural factors such as topology.
