Human hepatocellular carcinoma(HCC)occurs almost exclusively in cirrhotic livers.Here,we report that hepatic loss of protein arginine methyltransferase 5(PRMT5)in mice is sufficient to cause cirrhosis and HCC in a cli...Human hepatocellular carcinoma(HCC)occurs almost exclusively in cirrhotic livers.Here,we report that hepatic loss of protein arginine methyltransferase 5(PRMT5)in mice is sufficient to cause cirrhosis and HCC in a clinically relevant way.Furthermore,pathological polyploidization induced by hepatic loss of PRMT5 promotes liver cirrhosis and hepatic tumorigenesis in aged liver.The loss of PRMT5 leads to hyperaccumulation of P21 and endoreplication-dependent formation of pathological mono-nuclear polyploid hepatocytes.PRMT5 and symmetric dimethylation at histone H4 arginine 3(H4R3me2s)directly associate with chromatin of P21 to suppress its transcription.More importantly,loss of P21 rescues the pathological mono-nuclear polyploidy and prevents PRMT5-deficiency-induced liver cirrhosis and HCC.Thus,our results indicate that PRMT5-mediated symmetric dimethylation at histone H4 arginine 3(H4R3me2s)is crucial for preventing pathological polyploidization,liver cirrhosis and tumorigenesis in mouse liver.展开更多
In this study, recombinant baculovirus carrying the microdystrophin and β-catenin genes was used to infect adipose-derived stem cells from a dystrophin-utrophin double knock-out mouse. Results showed that, after bacu...In this study, recombinant baculovirus carrying the microdystrophin and β-catenin genes was used to infect adipose-derived stem cells from a dystrophin-utrophin double knock-out mouse. Results showed that, after baculovirus transgene infection, microdystrophin and β-catenin genes were effectively expressed in adipose-derived stem cells from the dystrophin-utrophin double knock-out mouse. Furthermore, this transgenic expression promoted adipose-derived stem cell differentiation into muscle cells, but inhibited adipogenic differentiation. In addition, protein expression related to the microdystrophin and Wnt/β-catenin signaling pathway was upregulated. Our experimental findings indicate that baculovirus can successfully deliver the microdystrophin and β-catenin genes into adipose-derived stem cells, and the microdystrophin and Wnt/β-catenin signaling pathway plays an important role in myogenesis of adipose-derived stem cells in the dystrophin-utrophin double knock-out mouse.展开更多
Plant root stem cells and their surrounding microenvironment,namely the stem cell niche,are hypersensitive to DNA damage.However,the molecular mechanisms that help maintain the genome stability of root stem cells rema...Plant root stem cells and their surrounding microenvironment,namely the stem cell niche,are hypersensitive to DNA damage.However,the molecular mechanisms that help maintain the genome stability of root stem cells remain elusive.Here we show that the root stem cells in the skbl（Shk1 kinase binding protein 1） mutant undergoes DNA damage-induced cell death,which is enhanced when combined with a lesion of the Ataxia-telangiectasia mutated（ATM） or the ATM/RAD3-related（ATR） genes,suggesting that the SKBI plays a synergistically effect with ATM and ATR in DNA damage pathway.We also provide evidence that SKBI is required for the maintenance of quiescent center（QC）,a root stem cell niche,under DNA damage treatments.Furthermore,we report decreased and ectopic expression of SHORTROOT（SHR） in response to DNA damage in the skbl root tips,while the expression of SCARECROW（SCR） remains unaffected.Our results uncover a new mechanism of plant root stem cell maintenance under DNA damage conditions that requires SKB1.展开更多
With the increasing aging population and personalized health management needs,this paper proposes an IoT-based home heart rate monitoring system.The system uses the STM32 microcontroller as the core,integrating a PPG ...With the increasing aging population and personalized health management needs,this paper proposes an IoT-based home heart rate monitoring system.The system uses the STM32 microcontroller as the core,integrating a PPG sensor and a body temperature sensor to collect physiological data such as heart rate,blood oxygen saturation,and body temperature.The data is transmitted in real-time to the server and mobile application via the ESP8266 module.Users can view historical data,set alarm thresholds,and re ceive alerts through sound alarms and push notifications when abnormalities are detected.The test results show that the heart rate measurement error is less than 5%,verifying the practicality and reliability of the system in home healt h monitoring and ch ronic disease prevention.This research provides a cost-effective solution for home users who require convenient and continuous health monitoring,especially for the elderly and patients with chronic diseases.展开更多
Pulmonary surfactant is a lipid-protein complex secreted by alveolar typeⅡepithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across ...Pulmonary surfactant is a lipid-protein complex secreted by alveolar typeⅡepithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across the air-liquid barrier.The Golgi apparatus plays an important role in pulmonary surfactant modification and secretory trafficking.However,the physiological function of the Golgi apparatus in the transport of pulmonary surfactants is unclear.In the present study,deletion of GM130,which encodes for a matrix protein of the cis-Golgi cisternae,was shown to induce the disruption of the Golgi structure leading to impaired secretion of lung surfactant proteins and lipids.Specifically,the results of in vitro and in vivo analysis indicated that the loss of GM130 resulted in trapping of Sftpa in the endoplasmic reticulum,Sftpb and Sftpc accumulation in the Golgi apparatus,and an increase in the compensatory secretion of Sftpd.Moreover,global and epithelial-specific GM130 knockout in mice resulted in an enlargement of alveolar airspace and an increase in alveolar epithelial autophagy;however,surfactant repletion partially rescued the enlarged airspace defects in GM130-deficient mice.Therefore,our results demonstrate that GM130 and the mammalian Golgi apparatus play a critical role in the control of surfactant protein secretion in pulmonary epithelial cells.展开更多
基金financially supported by grants from the National Key R&D Program of China(2022YFC3600202,2018YFA0800902)the National Natural Science Foundation of China(31730051,32170834).
文摘Human hepatocellular carcinoma(HCC)occurs almost exclusively in cirrhotic livers.Here,we report that hepatic loss of protein arginine methyltransferase 5(PRMT5)in mice is sufficient to cause cirrhosis and HCC in a clinically relevant way.Furthermore,pathological polyploidization induced by hepatic loss of PRMT5 promotes liver cirrhosis and hepatic tumorigenesis in aged liver.The loss of PRMT5 leads to hyperaccumulation of P21 and endoreplication-dependent formation of pathological mono-nuclear polyploid hepatocytes.PRMT5 and symmetric dimethylation at histone H4 arginine 3(H4R3me2s)directly associate with chromatin of P21 to suppress its transcription.More importantly,loss of P21 rescues the pathological mono-nuclear polyploidy and prevents PRMT5-deficiency-induced liver cirrhosis and HCC.Thus,our results indicate that PRMT5-mediated symmetric dimethylation at histone H4 arginine 3(H4R3me2s)is crucial for preventing pathological polyploidization,liver cirrhosis and tumorigenesis in mouse liver.
基金supported by the National Natural Science Foundation of China,No.30370510,30170337,30400322,30870851CMB Fund,No.4209347+2 种基金Key Project of the State Ministry of Public Health,No.2001321Fok Ying Tung Education Foundation,No.91029Key Projects in the National Science and Technology Pillar Program During the Eleventh Five-Year Plan Period,No.2006BAI05A07
文摘In this study, recombinant baculovirus carrying the microdystrophin and β-catenin genes was used to infect adipose-derived stem cells from a dystrophin-utrophin double knock-out mouse. Results showed that, after baculovirus transgene infection, microdystrophin and β-catenin genes were effectively expressed in adipose-derived stem cells from the dystrophin-utrophin double knock-out mouse. Furthermore, this transgenic expression promoted adipose-derived stem cell differentiation into muscle cells, but inhibited adipogenic differentiation. In addition, protein expression related to the microdystrophin and Wnt/β-catenin signaling pathway was upregulated. Our experimental findings indicate that baculovirus can successfully deliver the microdystrophin and β-catenin genes into adipose-derived stem cells, and the microdystrophin and Wnt/β-catenin signaling pathway plays an important role in myogenesis of adipose-derived stem cells in the dystrophin-utrophin double knock-out mouse.
文摘Plant root stem cells and their surrounding microenvironment,namely the stem cell niche,are hypersensitive to DNA damage.However,the molecular mechanisms that help maintain the genome stability of root stem cells remain elusive.Here we show that the root stem cells in the skbl（Shk1 kinase binding protein 1） mutant undergoes DNA damage-induced cell death,which is enhanced when combined with a lesion of the Ataxia-telangiectasia mutated（ATM） or the ATM/RAD3-related（ATR） genes,suggesting that the SKBI plays a synergistically effect with ATM and ATR in DNA damage pathway.We also provide evidence that SKBI is required for the maintenance of quiescent center（QC）,a root stem cell niche,under DNA damage treatments.Furthermore,we report decreased and ectopic expression of SHORTROOT（SHR） in response to DNA damage in the skbl root tips,while the expression of SCARECROW（SCR） remains unaffected.Our results uncover a new mechanism of plant root stem cell maintenance under DNA damage conditions that requires SKB1.
文摘With the increasing aging population and personalized health management needs,this paper proposes an IoT-based home heart rate monitoring system.The system uses the STM32 microcontroller as the core,integrating a PPG sensor and a body temperature sensor to collect physiological data such as heart rate,blood oxygen saturation,and body temperature.The data is transmitted in real-time to the server and mobile application via the ESP8266 module.Users can view historical data,set alarm thresholds,and re ceive alerts through sound alarms and push notifications when abnormalities are detected.The test results show that the heart rate measurement error is less than 5%,verifying the practicality and reliability of the system in home healt h monitoring and ch ronic disease prevention.This research provides a cost-effective solution for home users who require convenient and continuous health monitoring,especially for the elderly and patients with chronic diseases.
基金supported by the National Natural Sciences Foundation of China(31730051 and 31601164)the National Key Research and Development Program of China(2018YFA0800900)+1 种基金Natural Science Foundation of Shandong Province,China(ZR2019PH076)the Open Project of Forensic Medicine Key Laboratory of Shanxi Province,China(SFM2019001)。
文摘Pulmonary surfactant is a lipid-protein complex secreted by alveolar typeⅡepithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across the air-liquid barrier.The Golgi apparatus plays an important role in pulmonary surfactant modification and secretory trafficking.However,the physiological function of the Golgi apparatus in the transport of pulmonary surfactants is unclear.In the present study,deletion of GM130,which encodes for a matrix protein of the cis-Golgi cisternae,was shown to induce the disruption of the Golgi structure leading to impaired secretion of lung surfactant proteins and lipids.Specifically,the results of in vitro and in vivo analysis indicated that the loss of GM130 resulted in trapping of Sftpa in the endoplasmic reticulum,Sftpb and Sftpc accumulation in the Golgi apparatus,and an increase in the compensatory secretion of Sftpd.Moreover,global and epithelial-specific GM130 knockout in mice resulted in an enlargement of alveolar airspace and an increase in alveolar epithelial autophagy;however,surfactant repletion partially rescued the enlarged airspace defects in GM130-deficient mice.Therefore,our results demonstrate that GM130 and the mammalian Golgi apparatus play a critical role in the control of surfactant protein secretion in pulmonary epithelial cells.
