To meet the high demand for reliability based design of slopes, we present in this paper a simplified HLRF(Hasofere Linde Rackwitze Fiessler) iterative algorithm for first-order reliability method(FORM). It is simply ...To meet the high demand for reliability based design of slopes, we present in this paper a simplified HLRF(Hasofere Linde Rackwitze Fiessler) iterative algorithm for first-order reliability method(FORM). It is simply formulated in x-space and requires neither transformation of correlated random variables nor optimization tools. The solution can be easily improved by iteratively adjusting the step length. The algorithm is particularly useful to practicing engineers for geotechnical reliability analysis where standalone(deterministic) numerical packages are used. Based on the proposed algorithm and through direct perturbation analysis of random variables, we conducted a case study of earth slope reliability with complete consideration of soil uncertainty and spatial variability.展开更多
This study proposed a random Smoothed Particle Hydrodynamics method for analyzing the post-failure behavior of landslides,which is based on the Karhunen-Loeve(K-L) expansion,the non-Newtonian fluid model,and the OpenM...This study proposed a random Smoothed Particle Hydrodynamics method for analyzing the post-failure behavior of landslides,which is based on the Karhunen-Loeve(K-L) expansion,the non-Newtonian fluid model,and the OpenMP parallel framework.Then,the applicability of this method was validated by comparing the generated random field with theoretical result and by simulating the post-failure process of an actual landslide.Thereafter,an illustrative landslide example was created and simulated to obtain the spatial variability effect of internal friction angle on the post-failure behavior of landslides under different coefficients of variation(COVs) and correlation lengths(CLs).As a conclusion,the reinforcement with materials of a larger friction angle can reduce the runout distance and impact the force of a landslide.As the increase of COV,the distribution range of influence zones also increases,which indicates that the deviation of influence zones becomes large.In addition,the correlation length in Monte Carlo simulations should not be too small,otherwise the variation range of influence zones will be underestimated.展开更多
A fractional plasticity model for geomaterials is proposed by using the fractional derivative.Due to the integral definition of the fractional derivative,the range of load memory for calculating the flow direction may...A fractional plasticity model for geomaterials is proposed by using the fractional derivative.Due to the integral definition of the fractional derivative,the range of load memory for calculating the flow direction may influence the subsequent model performance.Therefore,an investigation on the memory dependence of the model was conducted.It was found that the load memory affected the stress-dilatancy behavior of the geomaterial.Due to the loss of memory from zero-to confiningstress states,slightly higher strain is reported,whereas an insignificant difference in the predicted deviator stress is observed.Thus,for engineering applications,starting the memory from the zero-stress state,which avoids mathematical complexity,is suggested.展开更多
Background:The conversion of adenosine(A)to inosine(I)through deamination is the prevailing form of RNA editing,impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species.Millions of high...Background:The conversion of adenosine(A)to inosine(I)through deamination is the prevailing form of RNA editing,impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species.Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases,providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets.However,the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods:We downloaded RNA sequencing(RNA-seq)data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database,and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used.We performed sequence alignment,identified RNA editing sites,and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results:We established a new database,"REDH",represents RNA editome in hematopoietic differentiation and malignancy.REDH is a curated database of associations between RNA editome and hematopoiesis.REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts(human).Through the Differentiation,Disease,Enrichment,and knowledge modules,each A-to-I editing site is systematically integrated,including its distribution throughout the genome,its clinical information(human sample),and functional editing sites under physiological and pathological conditions.Furthermore,REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions:REDH is accessible at http://www.redhdatabase.com/.This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies.It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.展开更多
Artificial neural networks have shown great proficiency in transforming low-resolution microscopic images into high-resolution images.However,training data remains a challenge,as large-scale open-source databases of m...Artificial neural networks have shown great proficiency in transforming low-resolution microscopic images into high-resolution images.However,training data remains a challenge,as large-scale open-source databases of microscopic images are rare,particularly 3D data.Moreover,the long training times and the need for expensive computational resources have become a burden to the research community.We introduced a deep-learning-based self-supervised volumetric imaging approach,which we termed“Self-Vision.”The self-supervised approach requires no training data,apart from the input image itself.The lightweight network takes just minutes to train and has demonstrated resolution-enhancing power on par with or better than that of a number of recent microscopybased models.Moreover,the high throughput power of the network enables large image inference with less postprocessing,facilitating a large field-of-view(2.45 mm×2.45 mm)using a home-built two-photon microscopy system.Self-Vision can recover images from fourfold undersampled inputs in the lateral and axial dimensions,dramatically reducing the acquisition time.Self-Vision facilitates the use of a deep neural network for 3D microscopy imaging,easing the demanding process of image acquisition and network training for current resolutionenhancing networks.展开更多
Mantle cell lymphoma(MCL)is an aggressive subtype of non-Hodgkin lymphoma(NHL)characterized by the overexpression of cyclin D1 and deregulated cell cycle.1 Ganetespib(STA-9090),a second-generation HSP90 inhibitor,dram...Mantle cell lymphoma(MCL)is an aggressive subtype of non-Hodgkin lymphoma(NHL)characterized by the overexpression of cyclin D1 and deregulated cell cycle.1 Ganetespib(STA-9090),a second-generation HSP90 inhibitor,dramatically disrupted oncogenic cellular processes resulting in the inhibition of client protein-derived tumors in preclinical studies.2 The synthetic lethal strategy using poly(ADP-ribose)polymerase(PARP)inhibitors(PARPis)has been reported as a powerful therapeutic intervention in MCL and their effectiveness can be increased by a deficiency in DNA damage repair(DDR),especially homologous recombination deficiency.3 Since we found earlier that transient ganetespib treatment can induce defects in DDR,we hypothesized that ganetespib treatment can possibly enhance the sensitivity of MCL cells to PARPis and HSP90 and PARP is can be demonstrated as promising combination therapies for MCL.展开更多
In order to accurately identify a bearing fault on a wind turbine, a novel fault diagnosis method based on stochastic subspace identification(SSI) and multi-kernel support vector machine(MSVM) is proposed. Firstly, th...In order to accurately identify a bearing fault on a wind turbine, a novel fault diagnosis method based on stochastic subspace identification(SSI) and multi-kernel support vector machine(MSVM) is proposed. Firstly, the collected vibration signal of the wind turbine bearing is processed by the SSI method to extract fault feature vectors. Then, the MSVM is constructed based on Gauss kernel support vector machine(SVM) and polynomial kernel SVM. Finally, fault feature vectors which indicate the condition of the wind turbine bearing are inputted to the MSVM for fault pattern recognition. The results indicate that the SSI-MSVM method is effective in fault diagnosis for a wind turbine bearing and can successfully identify fault types of bearing and achieve higher diagnostic accuracy than that of K-means clustering, fuzzy means clustering and traditional SVM.展开更多
Cracks at the crest of slopes frequently occur during earthquakes. Such cracks result from limited tension strength of the soil. A tension cut-off in Mohr-Coulomb shear strength can represent this limited strength. Pr...Cracks at the crest of slopes frequently occur during earthquakes. Such cracks result from limited tension strength of the soil. A tension cut-off in Mohr-Coulomb shear strength can represent this limited strength. Presented is an extension of variational analysis of slope stability with a tension crack considering seismicity. Both translational and rotational failure mechanisms are included in a pseudo-static analysis of slope stability. Developed is a closed-form to assess the seismic stability of slopes with zero tensile strength. The results indicate that the presence of the tension crack has significant effects on the seismic stability of slopes, i.e., leading to small value of the yield acceleration. Considering soil tension strength in seismic slope analysis may lead to overestimation on the stability, as much as 50% for vertical slopes. Imposing tension crack results in transit of the critical failure mode to a straight line from a log-spiral, except for flat slopes with small soil cohesion. Under seismic conditions, large cohesion may increase the depth of crack, moving it closer to the slope.展开更多
In this paper,we report the fabrication of cobalt-doped de-NO_(x)catalyst by pyrolyzing an analogous metal-organic framework-74(MOF-74)containing Fe&Mn.The resulted catalyst exhibits distinctive microstructures of...In this paper,we report the fabrication of cobalt-doped de-NO_(x)catalyst by pyrolyzing an analogous metal-organic framework-74(MOF-74)containing Fe&Mn.The resulted catalyst exhibits distinctive microstructures of manganese,cobalt,and iron immobilized on N-doped carbon nanotubes(CNTs).It is found through experiments that the trimetallic catalyst Fe_(2)Mn_(1)Co_(0.5)/CNTs-50 has the best NH_(3)-selective catalytic reduction(SCR)performance.The Fe_(2)Mn_(1)Co_(0.5)/CNTs-50 exhibited excellent water and sulfur resistance and good stability under the harsh gas environment of 250℃ and/or 170℃,NO=NH_(3)=1,000 ppm,8 vol.%O_(2),20 vol.%H2O,1,000 ppm SO_(2),and gas hourly space velocity(GHSV)=75,000 h^(-1).The de-NO_(x)conversion was maintained about 55%and 25%after 192 h.The water and sulfur resistance performance were much higher than commercial vanadium series catalyst.The highly water and sulfur resistance performance may be attributed to the unique core-shell microstructure and the synergistic effect of manganese,cobalt,and iron which helps reduce the formation for byproducts(NH_(4)HSO_(4)).This study may promote to explore the development of a high stability catalyst for low-temperature selective catalytic reduction of NO_(x)with NH_(3).展开更多
Two-photon excitation fluorescence microscopy(TPM),owing to its capacity for subcellular resolution,intrinsic optical sectioning,and superior penetration depth in turbid samples,has revolutionized biomedical research....Two-photon excitation fluorescence microscopy(TPM),owing to its capacity for subcellular resolution,intrinsic optical sectioning,and superior penetration depth in turbid samples,has revolutionized biomedical research.However,its layer-by-layer scanning to form a three-dimensional image inherently limits the volumetric imaging speed and increases phototoxicity significantly.In this study,we develop a gradient excitation technique to accelerate TPM volumetric imaging.The axial positions of the fluorophores can be decoded from the intensity ratio of the paired images obtained by sequentially exciting the specimen with two axially elongated two-photon beams of complementary gradient intensities.We achieved a 0.63μm axial localization precision and demonstrate the flexibility of the gradient TPM on various sparsely labeled samples,including bead phantoms,mouse brain tissues,and live macrophages.Compared with traditional TPM,our technique improves volumetric imaging speed(by at least sixfold),decreases photobleaching(i.e.,less than 2.07±2.89%in 25 min),and minimizes photodamages.展开更多
RNA-binding proteins(RBPs)are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes.The transcriptional regulatory ability of RBPs was indicated by the identificati...RNA-binding proteins(RBPs)are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes.The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs(Che-RBPs).One of these proteins,KH-type splicing regulatory protein(KHSRP),is a multifunctional RBP that has been implicated in mRNA decay,alternative splicing,and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129.In this study,we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing.KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation.Of note,KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1.Taken together,our analyses revealed the dual DNA-and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.展开更多
It is generally accepted that the interface effect and surface electronic structure of catalysts have vital impact on catalytic properties.Understanding and tailoring the atomic arrangement of interface structure are ...It is generally accepted that the interface effect and surface electronic structure of catalysts have vital impact on catalytic properties.Understanding and tailoring the atomic arrangement of interface structure are of great importance for electrocatalysis.Herein,we proposed a simple method to synthesize etching-PtNiCu nanowires(e-PtNiCu NWs)enclosed by both(110)and(100)facets evolving from PtNiCu nanowires(PtNiCu NWs)mainly with(111)facets by selectively etching process.After acetic acid etching treatment,the e-PtNiCu NWs possess high total proportions(88.3%)of(110)and(100)facets,whereas the(111)facet is dominant in PtNiCu NWs(64%)by qualitatively and quantitatively evaluation.Combining the structure characterizations and performance tests of ethanol electrooxidation reaction(EOR),we find that the e-PtNiCu NWs display remarkably performance for EOR,which is nearly 4.5 times and 1.5 times enhancement compared with the state-of-the-art Pt/C catalyst,as well as 2.2 and 1.4 times of PtNiCu NWs,in specific activity and mass activity,respectively.The improved performance of e-PtNiCu NWs is attributed to synergistic catalytic effect between(110)and(100)facets that not only significantly decreases the onset potentials of adsorbed CO(CO_(ads))but also favors the oxidation of CO_(ads)on the surface of catalyst.Furthermore,thermodynamics and kinetic studies indicate that the synergistic effect of both(110)and(100)facets in e-PtNiCu NWs can decrease the activation energy barrier and facilitate the charge transfer during the reaction.This work provides a promising approach to construct catalysts with tunable surface electronic structure towards efficient electrocatalysis.展开更多
Dear Editor,A series of studies had focused on the ecological stability of human microbiome(Lozupone et al.,2012;Faith et al.,2013;Moya and Ferrer,2016).Despite the continuous perturbation and the highly personalized ...Dear Editor,A series of studies had focused on the ecological stability of human microbiome(Lozupone et al.,2012;Faith et al.,2013;Moya and Ferrer,2016).Despite the continuous perturbation and the highly personalized composition within the human microbiome(Human Microbiome Project,2012),healthy adults stably maintain their microbial communities in terms of space and time(Faith et al.,2013;Moya and Ferrer,2016;Oh et al.,2016).This stability is proved to be critical for the well-being of human body(Lozupone et al.,2012).On the contrary,major shifts in microbial community composition are often related to diseases(Lynch and Pedersen,2016).展开更多
Objective:Emetine,an isoquinoline alkaloid that is enriched at high concentrations in the lung,has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The aim of this stu...Objective:Emetine,an isoquinoline alkaloid that is enriched at high concentrations in the lung,has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019(COVID-19).Methods:In this real-world study,63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province,China from February to March 2020.Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial,and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study.The medication course of emetine was less than 10 days.The main symptoms and adverse reactions of all patients were observed and recorded.The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10.Secondary outcomes included axillary temperature,transcutaneous oxygen saturation,and respiratory frequency recovery.The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20,2019(approval No.PJ2020-03-19)and was registered with the Chinese Clinical Trial Registry on February 20,2019(registration number:ChiCTR2000030022).Results:The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital.The axillary body temperature,respiratory rate,and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures.The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect.The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.Conclusion:Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects,suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.展开更多
Strengthening the oxide-metal interfacial synergistic interaction in nanocatalysts is identified as potential strategy to boost intrinsic activities and the availability of active sites by regulating the surface/inter...Strengthening the oxide-metal interfacial synergistic interaction in nanocatalysts is identified as potential strategy to boost intrinsic activities and the availability of active sites by regulating the surface/interface environment of catalysts.Herein,the SnO_(2)/PtNi concave nanocubes(CNCs)enclosed by high-index facets(HIFs)with tunable SnO_(2)composition are successfully fabricated through combining the hydrothermal and self-assembly method.The interfacial interaction between ultrafine SnO_(2)nanoparticles and PtNi with HIFs surface structure is characterized by analytical techniques.The as-prepared 0.20%SnO_(2)/PtNi catalyst exhibits extraordinarily high catalytic performance for ethylene glycol electrooxidation(EGOR)in acidic conditions with specific activity of 3.06 mA/cm^(2),which represents 6.2-fold enhancement compared with the state-of-the-art Pt/C catalyst.Additionally,the kinetic study demonstrates that the strong interfacial interaction between SnO_(2)and PtNi not only degrades the activation energy barrier during the process of EGOR but also enhances the CO-resistance ability and long-term stability.This study provides a novel perspective to construct highly efficient and stable electrocatalysts for energy conversions.展开更多
Background and Aims:Ras-related nuclear(RAN)protein is a small GTP-binding protein that is indispensable for the translocation of RNA and proteins through the nuclear pore complex.Recent studies have indicated that RA...Background and Aims:Ras-related nuclear(RAN)protein is a small GTP-binding protein that is indispensable for the translocation of RNA and proteins through the nuclear pore complex.Recent studies have indicated that RAN plays an important role in virus infection.However,the role of RAN in hepatitis C virus(HCV)infection is unclear.The objective of this study was to investigate the role and underlying mechanisms of RAN in HCV infection.Methods:Huh7.5.1 cells were infected with the JC1-Luc virus for 24 h and then were incubated with complete medium for an additional 48 h.HCV infection and RAN expression were determined using luciferase assay,quantitative reverse transcription-PCR and western blotting.Small interfering RNA was used to silence RAN.Western blotting and immunofluorescence were used to evaluate the cytoplasmic translocation of polypyrimidine tract-binding(PTB),and coimmunoprecipitation was used to examine the interaction between RAN and PTB.Results:HCV infection significantly induced RAN expression and cytoplasmic redistribution of PTB.Knockdown of RAN dramatically inhibited HCV infection and the cytoplasmic accumulation of PTB.Colocalization of RAN and PTB was determined by immunofluorescence,and a direct interaction of RAN with PTB was demonstrated by coimmunoprecipitation.Conclusions:PTB in the host cytoplasm is directly associated with HCV replication.These findings demonstrate that the involvement of RAN in HCV infection is mediated by influencing the cytoplasmic translocation of PTB.展开更多
基金Financial supports from National Science Foundation of China(Grant Nos.51609072,51879091,51479050 and 41630638)the National Key Basic Research Program of China("973" Program)(Grant No.2015CB057901)the Public Service Sector R&D Project of Ministry of Water Resource of China(Grant No.201501035-03)
文摘To meet the high demand for reliability based design of slopes, we present in this paper a simplified HLRF(Hasofere Linde Rackwitze Fiessler) iterative algorithm for first-order reliability method(FORM). It is simply formulated in x-space and requires neither transformation of correlated random variables nor optimization tools. The solution can be easily improved by iteratively adjusting the step length. The algorithm is particularly useful to practicing engineers for geotechnical reliability analysis where standalone(deterministic) numerical packages are used. Based on the proposed algorithm and through direct perturbation analysis of random variables, we conducted a case study of earth slope reliability with complete consideration of soil uncertainty and spatial variability.
基金This work is supported by the Natural Science Foundation of China(NSFC Grant No.51808192,51879091,41630638)the Natural Science Foundation of Jiangsu Province(Grant No.BK20170887)the China Postdoctoral Science Foundation(Grant Nos.2017M611673 and 2018T110432).We thank Ms.Ruihua Yu for her contribution in compiling some of the figures in this work.
文摘This study proposed a random Smoothed Particle Hydrodynamics method for analyzing the post-failure behavior of landslides,which is based on the Karhunen-Loeve(K-L) expansion,the non-Newtonian fluid model,and the OpenMP parallel framework.Then,the applicability of this method was validated by comparing the generated random field with theoretical result and by simulating the post-failure process of an actual landslide.Thereafter,an illustrative landslide example was created and simulated to obtain the spatial variability effect of internal friction angle on the post-failure behavior of landslides under different coefficients of variation(COVs) and correlation lengths(CLs).As a conclusion,the reinforcement with materials of a larger friction angle can reduce the runout distance and impact the force of a landslide.As the increase of COV,the distribution range of influence zones also increases,which indicates that the deviation of influence zones becomes large.In addition,the correlation length in Monte Carlo simulations should not be too small,otherwise the variation range of influence zones will be underestimated.
基金the National Natural Science Foundation of China(Grant 41630638)the Priority Academic Program Development of Jiangsu Higher Education Institutions,and the Fundamental Research Funds for the Central Universities(Grant 2017B05214)are appreciated.
文摘A fractional plasticity model for geomaterials is proposed by using the fractional derivative.Due to the integral definition of the fractional derivative,the range of load memory for calculating the flow direction may influence the subsequent model performance.Therefore,an investigation on the memory dependence of the model was conducted.It was found that the load memory affected the stress-dilatancy behavior of the geomaterial.Due to the loss of memory from zero-to confiningstress states,slightly higher strain is reported,whereas an insignificant difference in the predicted deviator stress is observed.Thus,for engineering applications,starting the memory from the zero-stress state,which avoids mathematical complexity,is suggested.
基金supported by grants from the National Key Research and Development Program of China(Nos.2022YFA1106300,2019YFA0802603,2019YFA0801800,2019YFA0111700,and 2021YFA0805703)the National Natural Science Foundation of China(Nos.92268205,82122005,81970154,81970101,82270192)+1 种基金CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-019)Haihe Laboratory of Cell Ecosystem Innovation Fund(No.22HHXBSS00027)
文摘Background:The conversion of adenosine(A)to inosine(I)through deamination is the prevailing form of RNA editing,impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species.Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases,providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets.However,the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods:We downloaded RNA sequencing(RNA-seq)data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database,and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used.We performed sequence alignment,identified RNA editing sites,and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results:We established a new database,"REDH",represents RNA editome in hematopoietic differentiation and malignancy.REDH is a curated database of associations between RNA editome and hematopoiesis.REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts(human).Through the Differentiation,Disease,Enrichment,and knowledge modules,each A-to-I editing site is systematically integrated,including its distribution throughout the genome,its clinical information(human sample),and functional editing sites under physiological and pathological conditions.Furthermore,REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions:REDH is accessible at http://www.redhdatabase.com/.This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies.It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.
基金National Natural Science Foundation of China(62105353,81927803,82071972,91959121,92159104)Natural Science Foundation of Guangdong Province(2019A1515011746,2020B121201010,2021A1515012022)+1 种基金Scientific Instrument Innovation Team of Chinese Academy of Sciences(GJJSTD20180002)Shenzhen Basic Research Program(RCJC20200714114433058,RCYX20210609104445093,ZDSY20130401165820357)。
文摘Artificial neural networks have shown great proficiency in transforming low-resolution microscopic images into high-resolution images.However,training data remains a challenge,as large-scale open-source databases of microscopic images are rare,particularly 3D data.Moreover,the long training times and the need for expensive computational resources have become a burden to the research community.We introduced a deep-learning-based self-supervised volumetric imaging approach,which we termed“Self-Vision.”The self-supervised approach requires no training data,apart from the input image itself.The lightweight network takes just minutes to train and has demonstrated resolution-enhancing power on par with or better than that of a number of recent microscopybased models.Moreover,the high throughput power of the network enables large image inference with less postprocessing,facilitating a large field-of-view(2.45 mm×2.45 mm)using a home-built two-photon microscopy system.Self-Vision can recover images from fourfold undersampled inputs in the lateral and axial dimensions,dramatically reducing the acquisition time.Self-Vision facilitates the use of a deep neural network for 3D microscopy imaging,easing the demanding process of image acquisition and network training for current resolutionenhancing networks.
基金supported by the National Natural Science Foundation of China(No.81672582 to HL,31771521 to ZT,and 82200083 to CS),Top Talent of Innovative Research Team of Jiangsu Province,China(to HL and ZT)the Natural Science Foundation of Jiangsu Province,China(No.BK20200891 to CS)the Senior Talent Start-up Funds of Jiangsu University(China)(No.14JDG050 and 14JDG011 to HL and ZT).
文摘Mantle cell lymphoma(MCL)is an aggressive subtype of non-Hodgkin lymphoma(NHL)characterized by the overexpression of cyclin D1 and deregulated cell cycle.1 Ganetespib(STA-9090),a second-generation HSP90 inhibitor,dramatically disrupted oncogenic cellular processes resulting in the inhibition of client protein-derived tumors in preclinical studies.2 The synthetic lethal strategy using poly(ADP-ribose)polymerase(PARP)inhibitors(PARPis)has been reported as a powerful therapeutic intervention in MCL and their effectiveness can be increased by a deficiency in DNA damage repair(DDR),especially homologous recombination deficiency.3 Since we found earlier that transient ganetespib treatment can induce defects in DDR,we hypothesized that ganetespib treatment can possibly enhance the sensitivity of MCL cells to PARPis and HSP90 and PARP is can be demonstrated as promising combination therapies for MCL.
基金supported by National Key Technology Research and Development Program (No. 2015BAA06B03)
文摘In order to accurately identify a bearing fault on a wind turbine, a novel fault diagnosis method based on stochastic subspace identification(SSI) and multi-kernel support vector machine(MSVM) is proposed. Firstly, the collected vibration signal of the wind turbine bearing is processed by the SSI method to extract fault feature vectors. Then, the MSVM is constructed based on Gauss kernel support vector machine(SVM) and polynomial kernel SVM. Finally, fault feature vectors which indicate the condition of the wind turbine bearing are inputted to the MSVM for fault pattern recognition. The results indicate that the SSI-MSVM method is effective in fault diagnosis for a wind turbine bearing and can successfully identify fault types of bearing and achieve higher diagnostic accuracy than that of K-means clustering, fuzzy means clustering and traditional SVM.
基金This study was sponsored by the National Natural Science Foundation of China(Grant Nos.4163063&5187824&and 51578213)the Fundamental Research Funds for the Central Universities(No.2017B00814)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Cracks at the crest of slopes frequently occur during earthquakes. Such cracks result from limited tension strength of the soil. A tension cut-off in Mohr-Coulomb shear strength can represent this limited strength. Presented is an extension of variational analysis of slope stability with a tension crack considering seismicity. Both translational and rotational failure mechanisms are included in a pseudo-static analysis of slope stability. Developed is a closed-form to assess the seismic stability of slopes with zero tensile strength. The results indicate that the presence of the tension crack has significant effects on the seismic stability of slopes, i.e., leading to small value of the yield acceleration. Considering soil tension strength in seismic slope analysis may lead to overestimation on the stability, as much as 50% for vertical slopes. Imposing tension crack results in transit of the critical failure mode to a straight line from a log-spiral, except for flat slopes with small soil cohesion. Under seismic conditions, large cohesion may increase the depth of crack, moving it closer to the slope.
基金The authors acknowledge financial support from the National Natural Science Foundation of China(No.21573286)the Key scientific and technological innovation projects in Shandong Province(No.2019JZZY010343).
文摘In this paper,we report the fabrication of cobalt-doped de-NO_(x)catalyst by pyrolyzing an analogous metal-organic framework-74(MOF-74)containing Fe&Mn.The resulted catalyst exhibits distinctive microstructures of manganese,cobalt,and iron immobilized on N-doped carbon nanotubes(CNTs).It is found through experiments that the trimetallic catalyst Fe_(2)Mn_(1)Co_(0.5)/CNTs-50 has the best NH_(3)-selective catalytic reduction(SCR)performance.The Fe_(2)Mn_(1)Co_(0.5)/CNTs-50 exhibited excellent water and sulfur resistance and good stability under the harsh gas environment of 250℃ and/or 170℃,NO=NH_(3)=1,000 ppm,8 vol.%O_(2),20 vol.%H2O,1,000 ppm SO_(2),and gas hourly space velocity(GHSV)=75,000 h^(-1).The de-NO_(x)conversion was maintained about 55%and 25%after 192 h.The water and sulfur resistance performance were much higher than commercial vanadium series catalyst.The highly water and sulfur resistance performance may be attributed to the unique core-shell microstructure and the synergistic effect of manganese,cobalt,and iron which helps reduce the formation for byproducts(NH_(4)HSO_(4)).This study may promote to explore the development of a high stability catalyst for low-temperature selective catalytic reduction of NO_(x)with NH_(3).
基金National Key Research and Development Program of China(2017YFC0110200)National Natural Science Foundation of China(81822023,81927803,91959121,92159104,82071972)+2 种基金Natural Science Foundation of Guangdong Province(2019A1515011746,2020B121201010)Scientific Instrument Innovation Team of Chinese Academy of Sciences(GJJSTD20180002)Shenzhen Basic Research Program(QCYJ20180507182432303,RCJC20200714114433058,ZDSY20130401165820357).
文摘Two-photon excitation fluorescence microscopy(TPM),owing to its capacity for subcellular resolution,intrinsic optical sectioning,and superior penetration depth in turbid samples,has revolutionized biomedical research.However,its layer-by-layer scanning to form a three-dimensional image inherently limits the volumetric imaging speed and increases phototoxicity significantly.In this study,we develop a gradient excitation technique to accelerate TPM volumetric imaging.The axial positions of the fluorophores can be decoded from the intensity ratio of the paired images obtained by sequentially exciting the specimen with two axially elongated two-photon beams of complementary gradient intensities.We achieved a 0.63μm axial localization precision and demonstrate the flexibility of the gradient TPM on various sparsely labeled samples,including bead phantoms,mouse brain tissues,and live macrophages.Compared with traditional TPM,our technique improves volumetric imaging speed(by at least sixfold),decreases photobleaching(i.e.,less than 2.07±2.89%in 25 min),and minimizes photodamages.
基金This work was supported by the National Key Research and Development Program of China(2019YFA0801800,2021YFA1102400,2019YFA0802600 and 2021YFA0805703)the National Natural Science Foundation of China(81530007,31900072,31725013,82022001,82122005,81970103 and 81970101)CAMS Innovation Fund for Medical Sciences[2021-I2M-1-019 and 2021-I2M-1-040].
文摘RNA-binding proteins(RBPs)are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes.The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs(Che-RBPs).One of these proteins,KH-type splicing regulatory protein(KHSRP),is a multifunctional RBP that has been implicated in mRNA decay,alternative splicing,and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129.In this study,we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing.KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation.Of note,KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1.Taken together,our analyses revealed the dual DNA-and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.
基金The authors acknowledge the financial supports from the National Natural Science Foundation of China(No.21573286)the Key Scientific and Technological Innovation Project in Shandong Province(No.2019JZZY010343).
文摘It is generally accepted that the interface effect and surface electronic structure of catalysts have vital impact on catalytic properties.Understanding and tailoring the atomic arrangement of interface structure are of great importance for electrocatalysis.Herein,we proposed a simple method to synthesize etching-PtNiCu nanowires(e-PtNiCu NWs)enclosed by both(110)and(100)facets evolving from PtNiCu nanowires(PtNiCu NWs)mainly with(111)facets by selectively etching process.After acetic acid etching treatment,the e-PtNiCu NWs possess high total proportions(88.3%)of(110)and(100)facets,whereas the(111)facet is dominant in PtNiCu NWs(64%)by qualitatively and quantitatively evaluation.Combining the structure characterizations and performance tests of ethanol electrooxidation reaction(EOR),we find that the e-PtNiCu NWs display remarkably performance for EOR,which is nearly 4.5 times and 1.5 times enhancement compared with the state-of-the-art Pt/C catalyst,as well as 2.2 and 1.4 times of PtNiCu NWs,in specific activity and mass activity,respectively.The improved performance of e-PtNiCu NWs is attributed to synergistic catalytic effect between(110)and(100)facets that not only significantly decreases the onset potentials of adsorbed CO(CO_(ads))but also favors the oxidation of CO_(ads)on the surface of catalyst.Furthermore,thermodynamics and kinetic studies indicate that the synergistic effect of both(110)and(100)facets in e-PtNiCu NWs can decrease the activation energy barrier and facilitate the charge transfer during the reaction.This work provides a promising approach to construct catalysts with tunable surface electronic structure towards efficient electrocatalysis.
文摘Dear Editor,A series of studies had focused on the ecological stability of human microbiome(Lozupone et al.,2012;Faith et al.,2013;Moya and Ferrer,2016).Despite the continuous perturbation and the highly personalized composition within the human microbiome(Human Microbiome Project,2012),healthy adults stably maintain their microbial communities in terms of space and time(Faith et al.,2013;Moya and Ferrer,2016;Oh et al.,2016).This stability is proved to be critical for the well-being of human body(Lozupone et al.,2012).On the contrary,major shifts in microbial community composition are often related to diseases(Lynch and Pedersen,2016).
基金the grant from the Natural Science Foundation of Anhui Province,China(No.202004a07020007).
文摘Objective:Emetine,an isoquinoline alkaloid that is enriched at high concentrations in the lung,has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019(COVID-19).Methods:In this real-world study,63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province,China from February to March 2020.Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial,and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study.The medication course of emetine was less than 10 days.The main symptoms and adverse reactions of all patients were observed and recorded.The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10.Secondary outcomes included axillary temperature,transcutaneous oxygen saturation,and respiratory frequency recovery.The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20,2019(approval No.PJ2020-03-19)and was registered with the Chinese Clinical Trial Registry on February 20,2019(registration number:ChiCTR2000030022).Results:The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital.The axillary body temperature,respiratory rate,and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures.The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect.The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.Conclusion:Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects,suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.
基金the National Natural Science Foundation of China(No.21573286)the Key Scientific and Technological Innovation Project in Shandong Province(No.2019JZZY010343).
文摘Strengthening the oxide-metal interfacial synergistic interaction in nanocatalysts is identified as potential strategy to boost intrinsic activities and the availability of active sites by regulating the surface/interface environment of catalysts.Herein,the SnO_(2)/PtNi concave nanocubes(CNCs)enclosed by high-index facets(HIFs)with tunable SnO_(2)composition are successfully fabricated through combining the hydrothermal and self-assembly method.The interfacial interaction between ultrafine SnO_(2)nanoparticles and PtNi with HIFs surface structure is characterized by analytical techniques.The as-prepared 0.20%SnO_(2)/PtNi catalyst exhibits extraordinarily high catalytic performance for ethylene glycol electrooxidation(EGOR)in acidic conditions with specific activity of 3.06 mA/cm^(2),which represents 6.2-fold enhancement compared with the state-of-the-art Pt/C catalyst.Additionally,the kinetic study demonstrates that the strong interfacial interaction between SnO_(2)and PtNi not only degrades the activation energy barrier during the process of EGOR but also enhances the CO-resistance ability and long-term stability.This study provides a novel perspective to construct highly efficient and stable electrocatalysts for energy conversions.
基金The work was supported by the Anhui Provincial Natural Science Foundation(1608085QH172)States S&T Projects of 13th Five Year(2018ZX10302206),Chinese Founda-tion for Hepatitis Prevention and Control(TQGB20200151,TQGB20180367)Anhui Key Program of Medical Scien-tific Research of China(#2010A010).
文摘Background and Aims:Ras-related nuclear(RAN)protein is a small GTP-binding protein that is indispensable for the translocation of RNA and proteins through the nuclear pore complex.Recent studies have indicated that RAN plays an important role in virus infection.However,the role of RAN in hepatitis C virus(HCV)infection is unclear.The objective of this study was to investigate the role and underlying mechanisms of RAN in HCV infection.Methods:Huh7.5.1 cells were infected with the JC1-Luc virus for 24 h and then were incubated with complete medium for an additional 48 h.HCV infection and RAN expression were determined using luciferase assay,quantitative reverse transcription-PCR and western blotting.Small interfering RNA was used to silence RAN.Western blotting and immunofluorescence were used to evaluate the cytoplasmic translocation of polypyrimidine tract-binding(PTB),and coimmunoprecipitation was used to examine the interaction between RAN and PTB.Results:HCV infection significantly induced RAN expression and cytoplasmic redistribution of PTB.Knockdown of RAN dramatically inhibited HCV infection and the cytoplasmic accumulation of PTB.Colocalization of RAN and PTB was determined by immunofluorescence,and a direct interaction of RAN with PTB was demonstrated by coimmunoprecipitation.Conclusions:PTB in the host cytoplasm is directly associated with HCV replication.These findings demonstrate that the involvement of RAN in HCV infection is mediated by influencing the cytoplasmic translocation of PTB.