Background: It is uncertain that whether smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas, so we peformed the case-control study to explore this issue. Material and Methods: Th...Background: It is uncertain that whether smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas, so we peformed the case-control study to explore this issue. Material and Methods: The cases were defined as patients with advanced adenomas and the controls were patients with nonadvanced adenomas. Clinical data were extracted from the hospital information system. Missing data were imputed with the multiple imputation of chained equations method, and the effect of smoking on the risk of advanced adenomas was calculated by binary logistic regression models to obtain odds ratios (ORs) and 95% confidence interval. Results: Current smoking rate in patients with advanced adenomas was significantly higher than that in patients with nonadvanced adenomas (31.6% VS 23.1%), the OR of advanced adenoma for current smoking compared with nonsmoking was 1.54 (1.09, 2.18), P = 0.013, and the weighted ORs ranged from 1.50 (1.01, 2.23) to 1.58 (1.09, 2.30), and the results of sensitivity analyses were still consistent. Conclusion: In adults with Han ethnicity in South China, current smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas.展开更多
The Yangjiang-Yitongdong Fault (YJF) is an important NW-trending regional fault, which divides the Zhujiang (Pearl) River Mouth Basin (ZRMB) into western and eastern segments. In Cenozoic, the northern continental mar...The Yangjiang-Yitongdong Fault (YJF) is an important NW-trending regional fault, which divides the Zhujiang (Pearl) River Mouth Basin (ZRMB) into western and eastern segments. In Cenozoic, the northern continental margin of the South China Sea (SCS) underwent continental rifting, breakup, seafloor spreading and thermal subsidence processes, and the Cenozoic activities of YJF is one part of this series of complex processes. Two long NW-trending multichannel seismic profiles located on both sides of the YJF extending from the continental shelf to Continent-Ocean Boundary (COB) were used to study the tectonic and sedimentary characteristics of western ZRMB. Using the 2D-Move software and back-stripping method, we constructed the balance cross-section model and calculated the fault activity rate. Through the comprehensive consideration of tectonic position, tectonic evolution history, featured structure, and stress analysis, we deduced the activity history of the YJF in Cenozoic. The results showed that the YJF can be divided into two segments by the central uplift belt. From 65 Ma to 32 Ma, the YJF was in sinistral motion as a whole, inherited the preexisting sinistral motion of Mesozoic YJF, in which, the southern part of YJF was mainly in extension activity, controlling the formation and evolution of Yunkai Low Uplift, coupled with slight sinistral motion. From 32 Ma to 23.8 Ma, the sinistral motion in northern part of YJF continued, while the sinistral motion in southern part began to stop or shifted to a slightly dextral motion. After 23.8 Ma, the dextral motion in southern part of YJF continued, while the sinistral motion in northern part of YJF gradually stopped, or shifted to the slightly dextral motion. The shift of the YJF strike-slip direction may be related to the magmatic underplating in continent-ocean transition, southeastern ZRMB. According to the analysis of tectonic activity intensity and rift sedimentary structure, the activities of YJF in Cenozoic played a regulating role in the rift extension process of ZRMB.展开更多
Due to the scarcity of resources of Ziziphi spinosae semen (ZSS), many inferior goods and even adulterants are generally found in medicine markets. To strengthen the quality control, HPLC fingerprint common pattern ...Due to the scarcity of resources of Ziziphi spinosae semen (ZSS), many inferior goods and even adulterants are generally found in medicine markets. To strengthen the quality control, HPLC fingerprint common pattern established in this paper showed three main bioactive compounds in one chromatogram simultaneously. Principal component analysis based on DAD signals could discriminate adulterants and inferiorities. Principal component analysis indicated that all samples could be mainly regrouped into two main clusters according to the first principal component (PC1, redefined as Vicenin II) and the second principal component (PC2, redefined as zizyphusine). PC1 and PC2 could explain 91.42%of the variance. Content of zizyphusine fluctuated more greatly than that of spinosin, and this result was also confirmed by the HPTLC result. Samples with low content of jujubosides and two common adulterants could not be used equivalently with authenticated ones in clinic, while one reference standard extract could substitute the crude drug in pharmaceutical production. Giving special consideration to the well-known bioactive saponins but with low response by end absorption, a fast and cheap HPTLC method for quality control of ZSS was developed and the result obtained was commensurate well with that of HPLC analysis. Samples having similar fingerprints to HPTLC common pattern targeting at saponins could be regarded as authenticated ones. This work provided a faster and cheaper way for quality control of ZSS and laid foundation for establishing a more effective quality control method for ZSS.展开更多
The self-healing microcapsules can be buried in the coating to improve the anticorrosive ability.In this paper,self-healing microcapsules of polyurea(PU)/melamine resin(MF)double shell were prepared by in-situ polymer...The self-healing microcapsules can be buried in the coating to improve the anticorrosive ability.In this paper,self-healing microcapsules of polyurea(PU)/melamine resin(MF)double shell were prepared by in-situ polymerization and interfacial polymerization with isocyanate as the core material.Scanning electron microscope was used to observe the microcapsule morphology.The structures of microcapsules prepared with different chain extenders were characterized by Fourier transform infrared spectroscopy.The micromanipulation system was used to loading–holding,loading–unloading and loading to rupture individual microcapsules,so as to explore the mechanical properties of microcapsules.The Young’s modulus corresponding to microcapsules was calculated by mathematical model fitting.The self-healing properties of microcapsule coating were characterized by optical microscope.The experimental results showed that the microcapsule shell prepared under optimized conditions had a complete morphology and good mechanical properties.The microcapsule was in the elastic deformation stage under small deformation,and the plastic deformation stage under large deformation.The Young’s modulus range of microcapsules was 9.29–14.51 MPa,and the corresponding Young’s modulus could be prepared by adjusting the process.The surface crack of the coating containing microcapsule could heal itself after48 h in a humid environment.展开更多
Objective.To develop an artificial intelligence method predicting lymph node metastasis(LNM)for patients with colorectal cancer(CRC).Impact Statement.A novel interpretable multimodal AI-based method to predict LNM for...Objective.To develop an artificial intelligence method predicting lymph node metastasis(LNM)for patients with colorectal cancer(CRC).Impact Statement.A novel interpretable multimodal AI-based method to predict LNM for CRC patients by integrating information of pathological images and serum tumor-specific biomarkers.Introduction.Preoperative diagnosis of LNM is essential in treatment planning for CRC patients.Existing radiology imaging and genomic tests approaches are either unreliable or too costly.Methods.A total of 1338 patients were recruited,where 1128 patients from one centre were included as the discovery cohort and 210 patients from other two centres were involved as the external validation cohort.We developed a Multimodal Multiple Instance Learning(MMIL)model to learn latent features from pathological images and then jointly integrated the clinical biomarker features for predicting LNM status.The heatmaps of the obtained MMIL model were generated for model interpretation.Results.The MMIL model outperformed preoperative radiology-imaging diagnosis and yielded high area under the curve(AUCs)of 0.926,0.878,0.809,and 0.857 for patients with stage T1,T2,T3,and T4 CRC,on the discovery cohort.On the external cohort,it obtained AUCs of 0.855,0.832,0.691,and 0.792,respectively(T1-T4),which indicates its prediction accuracy and potential adaptability among multiple centres.Conclusion.The MMIL model showed the potential in the early diagnosis of LNM by referring to pathological images and tumor-specific biomarkers,which is easily accessed in different institutes.We revealed the histomorphologic features determining the LNM prediction indicating the model ability to learn informative latent features.展开更多
In image acquisition process, the quality of microscopic images will be degraded by electrical noise, quantizing noise, light illumination etc. Hence, image preprocessing is necessary and important to improve the qual...In image acquisition process, the quality of microscopic images will be degraded by electrical noise, quantizing noise, light illumination etc. Hence, image preprocessing is necessary and important to improve the quality. The background noise and pulse noise are two common types of noise existing in microscopic images. In this paper, a gradient-based anisotropic filtering algorithm was proposed, which can filter out the background noise while preserve object boundary effectively. The filtering performance was evaluated by comparing that with some other filtering algorithms.展开更多
Background:N4-acetylcytidine(ac4C)represents a novel messenger RNA(mRNA)modification,and its associated acetyltransferaseN-acetyltransferase 10(NAT10)plays a crucial role in the initiation and progression of tumors by...Background:N4-acetylcytidine(ac4C)represents a novel messenger RNA(mRNA)modification,and its associated acetyltransferaseN-acetyltransferase 10(NAT10)plays a crucial role in the initiation and progression of tumors by regulating mRNA functionality.However,its role in hepatocellular carcinoma(HCC)development and prognosis is largely unknown.This study aimed to elucidate the role of NAT10-mediated ac4C in HCC progression and provide a promising therapeutic approach.Methods:The ac4C levels were evaluated by dot blot and ultra-performance liquid chromatography-tandem mass spectrometry with harvested HCC tissues.The expression of NAT10 was investigated using quantitative real-time polymerase chain reaction,western blotting,and immunohistochemical staining across 91 cohorts of HCC patients.To explore the underlying mechanisms of NAT10-ac4C in HCC,we employed a comprehensive approach integrating acetylated RNA immunoprecipitation and sequencing,RNA sequencing and ribosome profiling analyses,along with RNA immunoprecipitation,RNA pulldown,mass spectrometry,and site-specific mutation analyses.The drug affinity responsive targets stability,cellular thermal shift assay,and surface plasmon resonance assays were performed to assess the specific binding of NAT10 and Panobinostat.Furthermore,the efficacy of targeting NAT10-ac4C for HCC treatment was elucidated through in vitro experiments using HCC cells and in vivo HCCmouse models.Results:Our investigation revealed a significant increase in both the ac4C RNA level and NAT10 expression in HCC.Notably,elevated NAT10 expression was associated with poor outcomes in HCC patients.Functionally,silencing NAT10 suppressed HCC proliferation and metastasis in vitro and in vivo.Mechanistically,NAT10 stimulates the ac4C modification within the coding sequence(CDS)of high mobility group protein B2(HMGB2),which subsequently enhances HMGB2 translation by facilitating eukaryotic elongation factor 2(eEF2)binding to the ac4C sites on HMGB2 mRNA’s CDS.Additionally,high-throughput compound library screening revealed Panobinostat as a potent inhibitor of NAT10-mediated ac4C modification.This inhibition significantly attenuated HCC growth and metastasis in both in vitro experiments using HCC cells and in vivo HCC mouse models.Conclusions:Our study identified a novel oncogenic epi-transcriptome axis involving NAT10-ac4C/eEF2-HMGB2,which plays a pivotal role in regulating HCC growth and metastasis.The drug Panobinostat validates the therapeutic potential of targeting this axis for HCC treatment.展开更多
In this study, we examine how the quantum circuit of the Advanced Encryption Standard(AES) can be optimized from two aspects, i.e., number of qubits and T-depth. To reduce the number of qubits, we present three kinds ...In this study, we examine how the quantum circuit of the Advanced Encryption Standard(AES) can be optimized from two aspects, i.e., number of qubits and T-depth. To reduce the number of qubits, we present three kinds of improved quantum circuits of S-box for different phases in the AES. We found that the number of qubits in the round function can be decreased by introducing the circuit sending |a> to |S(a)>. As a result, compared with the previous quantum circuits where 400/640/768 qubits are required,our circuits of AES-128/-192/-256 only require 270/334/398 qubits. To reduce the T-depth, we propose a new circuit of AES's S-box with a T-depth of 4. Accordingly, the T-depth of our AES-128/-192/-256 quantum circuits become 80/80/84 instead of120/120/126 in a previous study.展开更多
Nanoparticles are widely observed in the natural shear zone and experimental slip faults, which can lubricate the fault and significantly reduce the friction coefficient during seismic slip. But it is still not clear ...Nanoparticles are widely observed in the natural shear zone and experimental slip faults, which can lubricate the fault and significantly reduce the friction coefficient during seismic slip. But it is still not clear how the nanoparticles develop during the process of sliding. Clarifying the development stage of nanoparticles in a fault zone is critical to understanding the formation mechanisms of nanoparticles and the mechanism of fault weakening from a nanoperspective. In this study, four types of nanoparticles were found in the Indosinian Xiaomei shear zone, including spherical nanoparticles, rod-like nanograins and their aggregations. Ultramicroscopic analyses indicate that polished patches are highly smooth and composed of tightly packed spherical nanoparticles and well orientated rod-like nanograins during slip at high velocities. Meanwhile, the dome nanoparticles were formed by the calcite thermal decomposition due to frictional heat during highspeed sliding. The polygonal grooves are possibly related to high temperature(>900℃) grain boundary sliding deformation mechanisms. However, the porous and rough surfaces are accompanied by a series of holes and parallel "scratches" during a subsequent low-velocity stage. To ascertain the chemical composition of these nanoparticles, the energy dispersive spectrometer(EDS) test were conducted. The results suggest that materials rich in Fe, MgO and wollastonite are likely to form the rod-like nanograins, while materials rich in SiO2 are likely to form the spherical nanoparticles.展开更多
BRAF is a serine/threonine kinase that harbors activating mutations in^7%of human malignancies and^60%of melanomas.Despite initial clinical responses to BRAF inhibitors,patients frequently develop drug resistance.To i...BRAF is a serine/threonine kinase that harbors activating mutations in^7%of human malignancies and^60%of melanomas.Despite initial clinical responses to BRAF inhibitors,patients frequently develop drug resistance.To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma,we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors.To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas,we integrate expression,ATAC-seq,and CRISPR screen data.We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6,which together enable resistance to BRAF inhibitors in melanoma cells.Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720,providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.展开更多
Dear Editor,The pandemic of COVID-19,a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2;previously known as 2019-n Co V),has placed an enormous burden on health authorities in 213 countrie...Dear Editor,The pandemic of COVID-19,a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2;previously known as 2019-n Co V),has placed an enormous burden on health authorities in 213 countries and territories.At the time of writing,over 26 million cases have been recorded across the world,with more than 870 k associated deaths(www.worldometers.info/coronavirus/).World Bank warns COVID-19 pandemic risks dramatic rise in poverty,with the majority of economies expecting to suffer from falling levels of GDP in 2020.展开更多
文摘Background: It is uncertain that whether smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas, so we peformed the case-control study to explore this issue. Material and Methods: The cases were defined as patients with advanced adenomas and the controls were patients with nonadvanced adenomas. Clinical data were extracted from the hospital information system. Missing data were imputed with the multiple imputation of chained equations method, and the effect of smoking on the risk of advanced adenomas was calculated by binary logistic regression models to obtain odds ratios (ORs) and 95% confidence interval. Results: Current smoking rate in patients with advanced adenomas was significantly higher than that in patients with nonadvanced adenomas (31.6% VS 23.1%), the OR of advanced adenoma for current smoking compared with nonsmoking was 1.54 (1.09, 2.18), P = 0.013, and the weighted ORs ranged from 1.50 (1.01, 2.23) to 1.58 (1.09, 2.30), and the results of sensitivity analyses were still consistent. Conclusion: In adults with Han ethnicity in South China, current smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas.
基金The National Natural Science Foundation of China under contract Nos 41776072,41476039,41674092 and 41676045the Geotectonic Evolution of China and Compilation of International Asian Geotectonic Map under contract No.DD20190364the Marine Basic Geological Survey Project under contract No.DD20190627
文摘The Yangjiang-Yitongdong Fault (YJF) is an important NW-trending regional fault, which divides the Zhujiang (Pearl) River Mouth Basin (ZRMB) into western and eastern segments. In Cenozoic, the northern continental margin of the South China Sea (SCS) underwent continental rifting, breakup, seafloor spreading and thermal subsidence processes, and the Cenozoic activities of YJF is one part of this series of complex processes. Two long NW-trending multichannel seismic profiles located on both sides of the YJF extending from the continental shelf to Continent-Ocean Boundary (COB) were used to study the tectonic and sedimentary characteristics of western ZRMB. Using the 2D-Move software and back-stripping method, we constructed the balance cross-section model and calculated the fault activity rate. Through the comprehensive consideration of tectonic position, tectonic evolution history, featured structure, and stress analysis, we deduced the activity history of the YJF in Cenozoic. The results showed that the YJF can be divided into two segments by the central uplift belt. From 65 Ma to 32 Ma, the YJF was in sinistral motion as a whole, inherited the preexisting sinistral motion of Mesozoic YJF, in which, the southern part of YJF was mainly in extension activity, controlling the formation and evolution of Yunkai Low Uplift, coupled with slight sinistral motion. From 32 Ma to 23.8 Ma, the sinistral motion in northern part of YJF continued, while the sinistral motion in southern part began to stop or shifted to a slightly dextral motion. After 23.8 Ma, the dextral motion in southern part of YJF continued, while the sinistral motion in northern part of YJF gradually stopped, or shifted to the slightly dextral motion. The shift of the YJF strike-slip direction may be related to the magmatic underplating in continent-ocean transition, southeastern ZRMB. According to the analysis of tectonic activity intensity and rift sedimentary structure, the activities of YJF in Cenozoic played a regulating role in the rift extension process of ZRMB.
文摘Due to the scarcity of resources of Ziziphi spinosae semen (ZSS), many inferior goods and even adulterants are generally found in medicine markets. To strengthen the quality control, HPLC fingerprint common pattern established in this paper showed three main bioactive compounds in one chromatogram simultaneously. Principal component analysis based on DAD signals could discriminate adulterants and inferiorities. Principal component analysis indicated that all samples could be mainly regrouped into two main clusters according to the first principal component (PC1, redefined as Vicenin II) and the second principal component (PC2, redefined as zizyphusine). PC1 and PC2 could explain 91.42%of the variance. Content of zizyphusine fluctuated more greatly than that of spinosin, and this result was also confirmed by the HPTLC result. Samples with low content of jujubosides and two common adulterants could not be used equivalently with authenticated ones in clinic, while one reference standard extract could substitute the crude drug in pharmaceutical production. Giving special consideration to the well-known bioactive saponins but with low response by end absorption, a fast and cheap HPTLC method for quality control of ZSS was developed and the result obtained was commensurate well with that of HPLC analysis. Samples having similar fingerprints to HPTLC common pattern targeting at saponins could be regarded as authenticated ones. This work provided a faster and cheaper way for quality control of ZSS and laid foundation for establishing a more effective quality control method for ZSS.
基金Supported by State Key Laboratory of Advanced Power Transmission Technology(GEIRI-SKL-2018-005)Guangzhou Major Industrial Technology Research Plan(201802010022)Guangzhou Science and Technology Project(201710010186)。
文摘The self-healing microcapsules can be buried in the coating to improve the anticorrosive ability.In this paper,self-healing microcapsules of polyurea(PU)/melamine resin(MF)double shell were prepared by in-situ polymerization and interfacial polymerization with isocyanate as the core material.Scanning electron microscope was used to observe the microcapsule morphology.The structures of microcapsules prepared with different chain extenders were characterized by Fourier transform infrared spectroscopy.The micromanipulation system was used to loading–holding,loading–unloading and loading to rupture individual microcapsules,so as to explore the mechanical properties of microcapsules.The Young’s modulus corresponding to microcapsules was calculated by mathematical model fitting.The self-healing properties of microcapsule coating were characterized by optical microscope.The experimental results showed that the microcapsule shell prepared under optimized conditions had a complete morphology and good mechanical properties.The microcapsule was in the elastic deformation stage under small deformation,and the plastic deformation stage under large deformation.The Young’s modulus range of microcapsules was 9.29–14.51 MPa,and the corresponding Young’s modulus could be prepared by adjusting the process.The surface crack of the coating containing microcapsule could heal itself after48 h in a humid environment.
基金funded by the Guangdong Science and Technology Project (No.2019B030316003)Natural Science Foundation of Guangdong Province (No.2019A1515010901)+1 种基金the Key Area Research and Development Program of Guangdong Province,China (No.2018B010111001)the Science and Technology Program of Shenzhen,China (No.ZDSYS201802021814180).
文摘Objective.To develop an artificial intelligence method predicting lymph node metastasis(LNM)for patients with colorectal cancer(CRC).Impact Statement.A novel interpretable multimodal AI-based method to predict LNM for CRC patients by integrating information of pathological images and serum tumor-specific biomarkers.Introduction.Preoperative diagnosis of LNM is essential in treatment planning for CRC patients.Existing radiology imaging and genomic tests approaches are either unreliable or too costly.Methods.A total of 1338 patients were recruited,where 1128 patients from one centre were included as the discovery cohort and 210 patients from other two centres were involved as the external validation cohort.We developed a Multimodal Multiple Instance Learning(MMIL)model to learn latent features from pathological images and then jointly integrated the clinical biomarker features for predicting LNM status.The heatmaps of the obtained MMIL model were generated for model interpretation.Results.The MMIL model outperformed preoperative radiology-imaging diagnosis and yielded high area under the curve(AUCs)of 0.926,0.878,0.809,and 0.857 for patients with stage T1,T2,T3,and T4 CRC,on the discovery cohort.On the external cohort,it obtained AUCs of 0.855,0.832,0.691,and 0.792,respectively(T1-T4),which indicates its prediction accuracy and potential adaptability among multiple centres.Conclusion.The MMIL model showed the potential in the early diagnosis of LNM by referring to pathological images and tumor-specific biomarkers,which is easily accessed in different institutes.We revealed the histomorphologic features determining the LNM prediction indicating the model ability to learn informative latent features.
文摘In image acquisition process, the quality of microscopic images will be degraded by electrical noise, quantizing noise, light illumination etc. Hence, image preprocessing is necessary and important to improve the quality. The background noise and pulse noise are two common types of noise existing in microscopic images. In this paper, a gradient-based anisotropic filtering algorithm was proposed, which can filter out the background noise while preserve object boundary effectively. The filtering performance was evaluated by comparing that with some other filtering algorithms.
基金State Key Project on Infection Disease of China,Grant/Award Number:2018ZX10723204-003-003Tongji Hospital(HUST)Foundation for Excellent Young Scientist,Grant/Award Number:2020YQ05+3 种基金National Basic Research Program of China,Grant/Award Number:2020YFA0710700Knowledge Innovation Program ofWuhan-Shuguang Project,Grant/Award Number:2022020801020456the first level of the public health youth top talent project of Hubei province,Grant/Award Number:2022SCZ051National Natural Science Foundation of China,Grant/Award Numbers:81874065,81874189,82203823,82273441。
文摘Background:N4-acetylcytidine(ac4C)represents a novel messenger RNA(mRNA)modification,and its associated acetyltransferaseN-acetyltransferase 10(NAT10)plays a crucial role in the initiation and progression of tumors by regulating mRNA functionality.However,its role in hepatocellular carcinoma(HCC)development and prognosis is largely unknown.This study aimed to elucidate the role of NAT10-mediated ac4C in HCC progression and provide a promising therapeutic approach.Methods:The ac4C levels were evaluated by dot blot and ultra-performance liquid chromatography-tandem mass spectrometry with harvested HCC tissues.The expression of NAT10 was investigated using quantitative real-time polymerase chain reaction,western blotting,and immunohistochemical staining across 91 cohorts of HCC patients.To explore the underlying mechanisms of NAT10-ac4C in HCC,we employed a comprehensive approach integrating acetylated RNA immunoprecipitation and sequencing,RNA sequencing and ribosome profiling analyses,along with RNA immunoprecipitation,RNA pulldown,mass spectrometry,and site-specific mutation analyses.The drug affinity responsive targets stability,cellular thermal shift assay,and surface plasmon resonance assays were performed to assess the specific binding of NAT10 and Panobinostat.Furthermore,the efficacy of targeting NAT10-ac4C for HCC treatment was elucidated through in vitro experiments using HCC cells and in vivo HCCmouse models.Results:Our investigation revealed a significant increase in both the ac4C RNA level and NAT10 expression in HCC.Notably,elevated NAT10 expression was associated with poor outcomes in HCC patients.Functionally,silencing NAT10 suppressed HCC proliferation and metastasis in vitro and in vivo.Mechanistically,NAT10 stimulates the ac4C modification within the coding sequence(CDS)of high mobility group protein B2(HMGB2),which subsequently enhances HMGB2 translation by facilitating eukaryotic elongation factor 2(eEF2)binding to the ac4C sites on HMGB2 mRNA’s CDS.Additionally,high-throughput compound library screening revealed Panobinostat as a potent inhibitor of NAT10-mediated ac4C modification.This inhibition significantly attenuated HCC growth and metastasis in both in vitro experiments using HCC cells and in vivo HCC mouse models.Conclusions:Our study identified a novel oncogenic epi-transcriptome axis involving NAT10-ac4C/eEF2-HMGB2,which plays a pivotal role in regulating HCC growth and metastasis.The drug Panobinostat validates the therapeutic potential of targeting this axis for HCC treatment.
基金supported by the National Natural Science Foundation of China (Grant Nos. 61972048, and 61976024)Beijing Natural Science Foundation (Grant No. 4222031)。
文摘In this study, we examine how the quantum circuit of the Advanced Encryption Standard(AES) can be optimized from two aspects, i.e., number of qubits and T-depth. To reduce the number of qubits, we present three kinds of improved quantum circuits of S-box for different phases in the AES. We found that the number of qubits in the round function can be decreased by introducing the circuit sending |a> to |S(a)>. As a result, compared with the previous quantum circuits where 400/640/768 qubits are required,our circuits of AES-128/-192/-256 only require 270/334/398 qubits. To reduce the T-depth, we propose a new circuit of AES's S-box with a T-depth of 4. Accordingly, the T-depth of our AES-128/-192/-256 quantum circuits become 80/80/84 instead of120/120/126 in a previous study.
基金the National Natural Science Foundation of China(Nos.41776072,41676048,U1701641,91328205)。
文摘Nanoparticles are widely observed in the natural shear zone and experimental slip faults, which can lubricate the fault and significantly reduce the friction coefficient during seismic slip. But it is still not clear how the nanoparticles develop during the process of sliding. Clarifying the development stage of nanoparticles in a fault zone is critical to understanding the formation mechanisms of nanoparticles and the mechanism of fault weakening from a nanoperspective. In this study, four types of nanoparticles were found in the Indosinian Xiaomei shear zone, including spherical nanoparticles, rod-like nanograins and their aggregations. Ultramicroscopic analyses indicate that polished patches are highly smooth and composed of tightly packed spherical nanoparticles and well orientated rod-like nanograins during slip at high velocities. Meanwhile, the dome nanoparticles were formed by the calcite thermal decomposition due to frictional heat during highspeed sliding. The polygonal grooves are possibly related to high temperature(>900℃) grain boundary sliding deformation mechanisms. However, the porous and rough surfaces are accompanied by a series of holes and parallel "scratches" during a subsequent low-velocity stage. To ascertain the chemical composition of these nanoparticles, the energy dispersive spectrometer(EDS) test were conducted. The results suggest that materials rich in Fe, MgO and wollastonite are likely to form the rod-like nanograins, while materials rich in SiO2 are likely to form the spherical nanoparticles.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81872290)the National Key R&D Program of China(Grant No.2017YFC0908500)
文摘BRAF is a serine/threonine kinase that harbors activating mutations in^7%of human malignancies and^60%of melanomas.Despite initial clinical responses to BRAF inhibitors,patients frequently develop drug resistance.To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma,we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors.To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas,we integrate expression,ATAC-seq,and CRISPR screen data.We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6,which together enable resistance to BRAF inhibitors in melanoma cells.Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720,providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.
基金funded by Medical Research Council(UK)[MR/S025480/1]a Key Project of Science and Technology on COVID-19 of Hubei Province[No.2020FCA002]supported by an Institute for Life Sciences(University of Southampton)PhD Studentship。
文摘Dear Editor,The pandemic of COVID-19,a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2;previously known as 2019-n Co V),has placed an enormous burden on health authorities in 213 countries and territories.At the time of writing,over 26 million cases have been recorded across the world,with more than 870 k associated deaths(www.worldometers.info/coronavirus/).World Bank warns COVID-19 pandemic risks dramatic rise in poverty,with the majority of economies expecting to suffer from falling levels of GDP in 2020.