Molecular knowledge of human gastric corpus epithelium remains incomplete.Here,by integrated analyses using single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and single-cell assay for transposase accessibl...Molecular knowledge of human gastric corpus epithelium remains incomplete.Here,by integrated analyses using single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and single-cell assay for transposase accessible chromatin sequencing(scATAC-seq)techniques,we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.Specifically,we identified a stem/progenitor cell population in the isthmus of human gastric corpus,where EGF and WNT signaling pathways were activated.Meanwhile,LGR4,but not LGR5,was responsible for the activation of WNT signaling pathway.Importantly,FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells.Finally,we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level,and identified several important cell-type-specific transcription factors.In summary,our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.展开更多
Enhanced geothermal systems(EGSs)in this study are classified as fracturing-EGS(F-EGS),pipe-EGS(P-EGS)and excavation-EGS(E-EGS)according to reservoir stimulation strategies.However,the heat extraction performances of ...Enhanced geothermal systems(EGSs)in this study are classified as fracturing-EGS(F-EGS),pipe-EGS(P-EGS)and excavation-EGS(E-EGS)according to reservoir stimulation strategies.However,the heat extraction performances of three EGSs employing different stimulation strategies are not fully understood.Here,we define the region where the pore pressure increment calculated by a hydraulic fracturing process is higher than rock tensile strength as the stimulation region for establishing a more accurate F-EGS model,and then compare three geothermal systems to select a appropriate reservoir stimulation strategy.We find that the F-EGS model assuming an entire stimulated region significantly exaggerates the heat extraction results.The optimal conditions for P-EGS are low injection rates and short operation times,which is suiTablefor seasonal heating or multi-energy co-generation projects including a thermal recovery phase.Theoretically,E-EGS has better geothermal extraction performance than F-EGS based on existing model assumptions,but its construction feasibility and economics need further exploration.H2O is more suiTableas a heat exchange fluid in E-EGS than supercritical CO_(2).This study provides a reference for geothermal mining simulation and reservoir stimulation strategy selection.展开更多
Chromatin conformation,localization,and dynamics are crucial regulators of cellular behaviors. Although fluorescence in situ hybridization-based techniques have been widely utilized for investigating chromatin archite...Chromatin conformation,localization,and dynamics are crucial regulators of cellular behaviors. Although fluorescence in situ hybridization-based techniques have been widely utilized for investigating chromatin architectures in healthy and diseased states,the requirement for cell fix-ation precludes the comprehensive dynamic analysis necessary to fully understand chromatin activ-ities. This has spurred the development and application of a variety of imaging methodologies for visualizing single chromosomal loci in the native cellular context. In this review,we describe currently-available approaches for imaging single genomic loci in cells,with special focus on clus-tered regularly interspaced short palindromic repeats (CRISPR)-based imaging approaches. In addition,we discuss some of the challenges that limit the application of CRISPR-based genomic imaging approaches,and potential solutions to address these challenges. We anticipate that,with continued refinement of CRISPR-based imaging techniques,significant understanding can be gained to help decipher chromatin activities and their relevance to cellular physiology and pathogenesis.展开更多
The recent outbreak of COVID-19 has been rapidly spreading on a global scale.To date,there is no specific vaccine against the causative virus,SARS-CoV-2,nor is there an effective medicine for treating COVID-19,thus ra...The recent outbreak of COVID-19 has been rapidly spreading on a global scale.To date,there is no specific vaccine against the causative virus,SARS-CoV-2,nor is there an effective medicine for treating COVID-19,thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19.By extracting and analyzing all available published clinical data,we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19.Specifically,preexisting chronic conditions such as hypertension,cardiovascular disease,chronic kidney disease,and diabetes are strongly associated with an increased risk of developing severe COVID-19;surprisingly,however,we found no correlation between chronic liver disease and increased disease severity.In addition,we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality.Given the high risk of comorbidity and the high mortality rate associated with tissue damage,organ function should be monitored closely in patients diagnosed with COVID-19,and this approach should be included when establishing new guidelines for managing these high-risk patients.Moreover,additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe,potentially fatal complications,and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease.Taken together,these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.展开更多
With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless,...With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless, detailed information regarding RNA processing, trafficking, and localization in living cells has been lacking due to technical limitations in imaging single RNA transcripts in living cells with high spatial and temporal resolution. In this review, we discuss tech- niques that have shown great promise for single RNA imaging, followed by highlights in our recent work in the development of molecular beacons (MBs), a class of nanoscale oligonucleotide-probes, for detecting individual RNA transcripts in living cells. With further refinement of MB design and development of more sophisticated fluorescence microscopy techniques, we envision that MB-based approaches could promote new discoveries of RNA functions and activities.展开更多
A palladium catalyst supported on 2-amino- pyridine functionalized cellulose was synthesized and fully characterized by inductively coupled plasma atomic emission spectroscopy, transmission electron microscope, Fourie...A palladium catalyst supported on 2-amino- pyridine functionalized cellulose was synthesized and fully characterized by inductively coupled plasma atomic emission spectroscopy, transmission electron microscope, Fourier transform infrared spectroscopy, thermogravi- metric analysis and X-ray photoelectron spectrometry. This catalyst can be applied in the Suzuki cross-coupling reaction of aryl halides with arylboronic acids in 50% ethanol to afford biaryls in good yields, and easily recycled by simple filtration after reaction without the loss of metal Pd.展开更多
基金supported by grants from Beijing Advanced Innovation Center for Genomics(ICG),supported by grants from the National Natural Science Foundation of China(No.81672361)supported by grants from the National Natural Science Foundation of China(No.32100672).
文摘Molecular knowledge of human gastric corpus epithelium remains incomplete.Here,by integrated analyses using single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and single-cell assay for transposase accessible chromatin sequencing(scATAC-seq)techniques,we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.Specifically,we identified a stem/progenitor cell population in the isthmus of human gastric corpus,where EGF and WNT signaling pathways were activated.Meanwhile,LGR4,but not LGR5,was responsible for the activation of WNT signaling pathway.Importantly,FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells.Finally,we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level,and identified several important cell-type-specific transcription factors.In summary,our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
文摘Enhanced geothermal systems(EGSs)in this study are classified as fracturing-EGS(F-EGS),pipe-EGS(P-EGS)and excavation-EGS(E-EGS)according to reservoir stimulation strategies.However,the heat extraction performances of three EGSs employing different stimulation strategies are not fully understood.Here,we define the region where the pore pressure increment calculated by a hydraulic fracturing process is higher than rock tensile strength as the stimulation region for establishing a more accurate F-EGS model,and then compare three geothermal systems to select a appropriate reservoir stimulation strategy.We find that the F-EGS model assuming an entire stimulated region significantly exaggerates the heat extraction results.The optimal conditions for P-EGS are low injection rates and short operation times,which is suiTablefor seasonal heating or multi-energy co-generation projects including a thermal recovery phase.Theoretically,E-EGS has better geothermal extraction performance than F-EGS based on existing model assumptions,but its construction feasibility and economics need further exploration.H2O is more suiTableas a heat exchange fluid in E-EGS than supercritical CO_(2).This study provides a reference for geothermal mining simulation and reservoir stimulation strategy selection.
基金supported by grants from the National Key R&D Program of China (Grant Nos. 2016YFA0501603 and 2016YFA0100702)National Natural Science Foundation of China (Grant No. 31771583)+1 种基金Beijing Natural Science Foundation (Grant No. 7162114)Beijing Municipal R&D Key Project (Grant No. Z151100003915081), China
文摘Chromatin conformation,localization,and dynamics are crucial regulators of cellular behaviors. Although fluorescence in situ hybridization-based techniques have been widely utilized for investigating chromatin architectures in healthy and diseased states,the requirement for cell fix-ation precludes the comprehensive dynamic analysis necessary to fully understand chromatin activ-ities. This has spurred the development and application of a variety of imaging methodologies for visualizing single chromosomal loci in the native cellular context. In this review,we describe currently-available approaches for imaging single genomic loci in cells,with special focus on clus-tered regularly interspaced short palindromic repeats (CRISPR)-based imaging approaches. In addition,we discuss some of the challenges that limit the application of CRISPR-based genomic imaging approaches,and potential solutions to address these challenges. We anticipate that,with continued refinement of CRISPR-based imaging techniques,significant understanding can be gained to help decipher chromatin activities and their relevance to cellular physiology and pathogenesis.
基金This study was supported by research grants from the National Key Research&Develop-ment Program of China(2018YFA0507800 to FW and JM).
文摘The recent outbreak of COVID-19 has been rapidly spreading on a global scale.To date,there is no specific vaccine against the causative virus,SARS-CoV-2,nor is there an effective medicine for treating COVID-19,thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19.By extracting and analyzing all available published clinical data,we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19.Specifically,preexisting chronic conditions such as hypertension,cardiovascular disease,chronic kidney disease,and diabetes are strongly associated with an increased risk of developing severe COVID-19;surprisingly,however,we found no correlation between chronic liver disease and increased disease severity.In addition,we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality.Given the high risk of comorbidity and the high mortality rate associated with tissue damage,organ function should be monitored closely in patients diagnosed with COVID-19,and this approach should be included when establishing new guidelines for managing these high-risk patients.Moreover,additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe,potentially fatal complications,and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease.Taken together,these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.
基金supported by grants from the National Key R&D Program of China (Grant Nos. 2016YFA0501603 and 2016YFA0100702)the National Natural Science Foundation of China (Grant Nos. 31771583 and 81371613)+1 种基金the Beijing Natural Science Foundation (Grant No. 7162114)the 1000 Young Talent Program of China
文摘With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless, detailed information regarding RNA processing, trafficking, and localization in living cells has been lacking due to technical limitations in imaging single RNA transcripts in living cells with high spatial and temporal resolution. In this review, we discuss tech- niques that have shown great promise for single RNA imaging, followed by highlights in our recent work in the development of molecular beacons (MBs), a class of nanoscale oligonucleotide-probes, for detecting individual RNA transcripts in living cells. With further refinement of MB design and development of more sophisticated fluorescence microscopy techniques, we envision that MB-based approaches could promote new discoveries of RNA functions and activities.
基金Acknowledgements This work was supported by National Natural Science Foundation of China (Grant No. 20972109) and National Youth Science Foundation of China (No. 51403151).
文摘A palladium catalyst supported on 2-amino- pyridine functionalized cellulose was synthesized and fully characterized by inductively coupled plasma atomic emission spectroscopy, transmission electron microscope, Fourier transform infrared spectroscopy, thermogravi- metric analysis and X-ray photoelectron spectrometry. This catalyst can be applied in the Suzuki cross-coupling reaction of aryl halides with arylboronic acids in 50% ethanol to afford biaryls in good yields, and easily recycled by simple filtration after reaction without the loss of metal Pd.