The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting ...The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting MET,the only receptor of HGF,have yielded unimpressive results in GBM.3,4 Here we found that HGF induced strong chemotaxis on GBM cells,but MET expression was extremely low.We,therefore,used single-cell RNA sequencing(scRNA-seq)coupled with label-free proteome profiling to identify membrane proteins associated with HGF/MET signaling amplification in GBM and to provide a novel modulator,MPZL1,for HGF/MET-targeted therapy.展开更多
Alzheimer’s disease(AD),the most common neurodegenerative disorder,is characterized by memory loss and cognitive dysfunction.The accumulation of misfolded protein aggregates including amyloid beta(Aβ)peptides and mi...Alzheimer’s disease(AD),the most common neurodegenerative disorder,is characterized by memory loss and cognitive dysfunction.The accumulation of misfolded protein aggregates including amyloid beta(Aβ)peptides and microtubule associated protein tau(MAPT/tau)in neuronal cells are hallmarks of AD.So far,the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited.Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes.Recently,there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis.Interestingly,the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD.Here,we first summarize the recent genetic,pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD.We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins,Aβand MAPT/tau,in AD.Finally,we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials.Overall,this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment.展开更多
The North China Plain(NCP) is one of the water shortage areas of China. Lack of water resources restricted the economic and social development of North China area and resulted in deterioration of ecosystem and natur...The North China Plain(NCP) is one of the water shortage areas of China. Lack of water resources restricted the economic and social development of North China area and resulted in deterioration of ecosystem and natural environment. Influenced by the climate change and human activities, the water circulation of NCP was largely changed and the crisis of water resources was aggravated. Therefore, it is important to study the features of the extreme climate and the response mechanism of groundwater to climate change. We analyzed the trend of climate change and extreme climate features in the past 60 years based on the monitoring data of meteorological stations. And then the response characteristics of groundwater to climate change were discussed. The average temperature of NCP was in an obviously upward trend. The overall precipitation variation was in a downward trend. The climate change in this area showed a warming-drying trend. The intensity of extreme precipitation displayed a trend of declining and then increasing from north to south as well as declining from eastern coastal plain to the piedmont plain. Grey correlation degree analysis indicated that groundwater depth had a close relationship with precipitation and human activities in NCP. The response of groundwater level to precipitation differed from the piedmont alluvial-pluvial plain to the coastal plain. The response was more obvious in the coastal plain than the piedmont alluvial-pluvial plain and the middle plain. The precipitation influenced the groundwater depth both directly and indirectly. Under the condition of extreme precipitation, the impact would aggravate, in the forms of rapid or lag raise of groundwater levels.展开更多
This paper has investigated the concentration and distribution of polycyclic aromatic hydrocarbons in shallow groundwater from an alluvial-diluvial fan of the Hutuo River in North concentration levels of China.Results...This paper has investigated the concentration and distribution of polycyclic aromatic hydrocarbons in shallow groundwater from an alluvial-diluvial fan of the Hutuo River in North concentration levels of China.Results show that the 16 priority polycyclic aromatic hydrocarbons range from 0 to 92.06 ng/L,do not conform to drinking water quality standards in China (GB 5749-2006).However,the concentration figures of priority polycyclic aromatic hydrocarbons are much lower than that of other studies conducted elsewhere in China.In addition,highly-concentrated polycyclic aromatic hydrocarbons (50-92 ng/L)are fragmentarily distributed.The composition of polycyelic aromatic hydrocarbons from this study indicates that low molecular polycyclic aromatic hydrocarbons are predominant in groundwater samples, medium molecular compounds occur at low concentrations,and high molecular hydrocarbons are not detected. The polycyclic aromatic hydrocarbon composition in groundwater samples is basically the same as that of gaseous samples in the atmosphere in this study.Therefore, the atmospheric input is assumed to be an important source of polycyclic aromatic hydrocarbons,no less than wastewater discharge,adhesion on suspended solids,and surface water leakage.Ratios of specific polycyclic aromatic hydrocarbons demonstrate that they mainly originate from wood or coal combustion as well as natural gas and partially from petroleum according to the result of principal component analysis.On the whole,conclusions are drawn that the contamination sources of these polycyclic aromatic hydrocarbons are likely petrogenic and pyrolytic inputs.Future investigations by sampling topsoil,vadose soil,and the atmosphere can further verify aforementioned conclusions.展开更多
基金the Natural Science Foundation of Guangdong Province,China(No.2022A1515012552)Shenzhen Science and Technology Innovation Committee of China(SZSTI+3 种基金No.JCYJ20220818102611025)Research Initiation Project of Shunde Hospital,Southern Medical University(No.CRSP2022002)Research Initiation Project of the First Affiliated Hospital of Gannan Medical University(No.QD202316)Beijing Sisco Clinical Oncology Research Foundation of China(No.Y-2022METAZMS-0118).
文摘The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting MET,the only receptor of HGF,have yielded unimpressive results in GBM.3,4 Here we found that HGF induced strong chemotaxis on GBM cells,but MET expression was extremely low.We,therefore,used single-cell RNA sequencing(scRNA-seq)coupled with label-free proteome profiling to identify membrane proteins associated with HGF/MET signaling amplification in GBM and to provide a novel modulator,MPZL1,for HGF/MET-targeted therapy.
基金funding supports from the National Natural Science Foundation of China(82003721,82071193,32170774 and 32000673)Shenzhen Science and Technology Innovation Commission(JCYJ20210324114014039,China)+1 种基金China Postdoctoral Science Foundation(2020M683182)Guangdong Basic and Applied Basic Research Foundation(2020A1515110549,China)。
文摘Alzheimer’s disease(AD),the most common neurodegenerative disorder,is characterized by memory loss and cognitive dysfunction.The accumulation of misfolded protein aggregates including amyloid beta(Aβ)peptides and microtubule associated protein tau(MAPT/tau)in neuronal cells are hallmarks of AD.So far,the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited.Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes.Recently,there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis.Interestingly,the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD.Here,we first summarize the recent genetic,pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD.We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins,Aβand MAPT/tau,in AD.Finally,we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials.Overall,this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment.
基金supported by the National Basic Research Program (973) of China (No. 2010CB428806-2)Environmental Research Special Funds for Public Welfare Project (No. 201409029)
文摘The North China Plain(NCP) is one of the water shortage areas of China. Lack of water resources restricted the economic and social development of North China area and resulted in deterioration of ecosystem and natural environment. Influenced by the climate change and human activities, the water circulation of NCP was largely changed and the crisis of water resources was aggravated. Therefore, it is important to study the features of the extreme climate and the response mechanism of groundwater to climate change. We analyzed the trend of climate change and extreme climate features in the past 60 years based on the monitoring data of meteorological stations. And then the response characteristics of groundwater to climate change were discussed. The average temperature of NCP was in an obviously upward trend. The overall precipitation variation was in a downward trend. The climate change in this area showed a warming-drying trend. The intensity of extreme precipitation displayed a trend of declining and then increasing from north to south as well as declining from eastern coastal plain to the piedmont plain. Grey correlation degree analysis indicated that groundwater depth had a close relationship with precipitation and human activities in NCP. The response of groundwater level to precipitation differed from the piedmont alluvial-pluvial plain to the coastal plain. The response was more obvious in the coastal plain than the piedmont alluvial-pluvial plain and the middle plain. The precipitation influenced the groundwater depth both directly and indirectly. Under the condition of extreme precipitation, the impact would aggravate, in the forms of rapid or lag raise of groundwater levels.
文摘This paper has investigated the concentration and distribution of polycyclic aromatic hydrocarbons in shallow groundwater from an alluvial-diluvial fan of the Hutuo River in North concentration levels of China.Results show that the 16 priority polycyclic aromatic hydrocarbons range from 0 to 92.06 ng/L,do not conform to drinking water quality standards in China (GB 5749-2006).However,the concentration figures of priority polycyclic aromatic hydrocarbons are much lower than that of other studies conducted elsewhere in China.In addition,highly-concentrated polycyclic aromatic hydrocarbons (50-92 ng/L)are fragmentarily distributed.The composition of polycyelic aromatic hydrocarbons from this study indicates that low molecular polycyclic aromatic hydrocarbons are predominant in groundwater samples, medium molecular compounds occur at low concentrations,and high molecular hydrocarbons are not detected. The polycyclic aromatic hydrocarbon composition in groundwater samples is basically the same as that of gaseous samples in the atmosphere in this study.Therefore, the atmospheric input is assumed to be an important source of polycyclic aromatic hydrocarbons,no less than wastewater discharge,adhesion on suspended solids,and surface water leakage.Ratios of specific polycyclic aromatic hydrocarbons demonstrate that they mainly originate from wood or coal combustion as well as natural gas and partially from petroleum according to the result of principal component analysis.On the whole,conclusions are drawn that the contamination sources of these polycyclic aromatic hydrocarbons are likely petrogenic and pyrolytic inputs.Future investigations by sampling topsoil,vadose soil,and the atmosphere can further verify aforementioned conclusions.