Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic ...Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.展开更多
Purple-leafed plants not only have a higher resistance to biotic and abiotic stresses,but also have higher ornamental value.Anthocyanins are vital for leaf color formation,growth and development of purple leaves.Howev...Purple-leafed plants not only have a higher resistance to biotic and abiotic stresses,but also have higher ornamental value.Anthocyanins are vital for leaf color formation,growth and development of purple leaves.However,the molecular mechanism underlying purple leaf formation in Lagerstroemia indica remains unclear.Metabolomic and transcriptomic analysis of purple-leafed cultivar‘Ebony Embers’and greenleafed cultivar‘Arapahoe’showed that the high expression of anthocyanin structure genes induced hyperaccumulation of cyanidin and pelargonidin derivatives,making the leaves purple.LfiHY5,LfiMYB75 and LfibHLH1 were identified using correlation analysis and weighted gene co-expression network analysis.In‘Arapahoe’‘Ebony Embers’population,LfiHY5 and LfiMYB75 showed significant positive correlation with leaf anthocyanin content.Transient expression of LfiMYB75 and LfiHY5 in tobacco and purple-leafed crape myrtle indicated that the two genes activated anthocyanin synthesis.Yeast two-hybrid analysis showed that LfiMYB75 and LfibHLH1 could form a complex that enhanced anthocyanin synthesis.Yeast monohybrid and dual-luciferase assays confirmed that LfiHY5 activated the expression of LfiMYB75,to activate the transcription of anthocyanin structural genes LfiCHS and LfiANS.Moreover,there were three alleles of LfiHY5 in crape myrtle,and the different sequences had different activation effects on LfiMYB75.In conclusion,the results showed that LfiHY5 led to upregulate the transcription of LfiMYB75,and LfiMYB75 formed a complex with LfibHLH1,which increased the transcription level of LfiCHS and LfiANS to affect anthocyanin synthesis in crape myrtle.展开更多
BACKGROUND Ampullary cancer is a relatively rare malignant tumor in the digestive system.Its incidence has increased in recent years.As for now,its biological characteristics have not been fully clarified.Recent studi...BACKGROUND Ampullary cancer is a relatively rare malignant tumor in the digestive system.Its incidence has increased in recent years.As for now,its biological characteristics have not been fully clarified.Recent studies have primarily focused on the histological classification and genetic changes,but there are fewer investigations into the differences among site-specific subgroups.The clinicopathological charac-teristics of ampullary cancer occurring in different positions have not been elucidated.Furthermore,the role of adjuvant therapy in the treatment of patients with ampullary cancer remains controversial.ampullary cancer and explore the factors affecting prognosis.METHODS A total of 356 patients who met the inclusion and exclusion criteria were enrolled.Patients were divided into ampulla of Vater cancer(AVC)and duodenal papilla cancer(DPC)based on the gross and microscopic findings.Baseline data,admission examination results,and perioperative outcomes were collected and analyzed.The Kaplan-Meier curve was used for survival analysis.Univariate and multivariate analysis was performed to explore the independent risk factors affecting the overall survival(OS)of both groups.RESULTS The preoperative total bilirubin level in patients with AVC was significantly higher than those with DPC(P=0.04).The OS for patients with DPC was 58.90±38.74 months,significantly longer than 44.31±35.90 months for patients with AVC(P<0.01).The independent risk factors affecting the OS of AVC included:Preoperative albumin level(P=0.009),total bilirubin level(P=0.017),and number of positive lymph nodes(P=0.005).For DPC,risk factors included:Age(P=0.004),tumor size(P=0.023),number of positive lymph nodes(P=0.010)and adjuvant treatment(P=0.020).Adjuvant therapy significantly improved the OS rate of patients with DPC,but not for those with AVC.CONCLUSION Patients with AVC had a shorter OS compared to those with DPC.The prognosis factors and the role of adjuvant therapy of two groups were different.展开更多
It is important to understand and manage rockburst challenges in deep mining operations.This paper presents a systematic study of rockburst risk in underground mining,offering a detailed examination of influencing fac...It is important to understand and manage rockburst challenges in deep mining operations.This paper presents a systematic study of rockburst risk in underground mining,offering a detailed examination of influencing factors,risk assessment,and various control and mitigation methods.The complexities of rockburst phenomena are explained by examining factors that lead to the occurrence of rockbursts.A rockburst risk assessment using a bow-tie analysis is conducted,which provides insights into both risk evaluation and proactive control and mitigation systems.The core of the paper presents a comprehensive array of rockburst risk control and mitigation methods,which range from controls to reduce rockburst hazard,and excavation vulnerability,to controls and mitigations to reduce exposure.Strategic engineering control methods,including mine design and mining sequencing,are discussed.Tactical engineering control measures,such as ground pre-conditioning and rock support,are scrutinized,along with administrative controls like evacuation and re-entry protocols and the use of mechanized equipment.A multiple-line defense system is advocated for rockburst risk management to address the uncertainties involved in the process.Finally,emerging technologies and innovations as well as challenges are discussed,providing a roadmap for continued advancements in rockburst risk management in the future.This work serves as a valuable resource for mining professionals,researchers,and policymakers seeking a comprehensive understanding of rockburst risk management in deep mining.展开更多
In this study,we put forward a radiative-convective-transportive energy balance model of a gray atmosphere to examine individual roles of the greenhouse effect of water vapor,vertical convection,and atmospheric polewa...In this study,we put forward a radiative-convective-transportive energy balance model of a gray atmosphere to examine individual roles of the greenhouse effect of water vapor,vertical convection,and atmospheric poleward energy transport as well as their combined effects for a quasi-linear relationship between the outgoing longwave radiation(OLR)and surface temperature(T_(S)).The greenhouse effect of water vapor enhances the meridional gradient of surface temperature,thereby directly contributing to a quasi-linear OLR-T_(S) relationship.The atmospheric poleward energy transport decreases the meridional gradient of surface temperature.As a result of the poleward energy transport,tropical(high-latitude)atmosphere-surface columns emit less(more)OLR than the solar energy input at their respective locations,causing a substantial reduction of the meridional gradient of the OLR.The combined effect of reducing the meridional gradients of both OLR and surface temperature by the poleward energy transport also contributes to the quasi-linear OLR-T_(S) relationship.Vertical convective energy transport reduces the meridional gradient of surface temperature without affecting the meridional gradient of OLR,thereby suppressing part of the reduction to the increasing rate of OLR with surface temperature by the greenhouse effect of water vapor and poleward energy transport.Because of the nature of the energy balance in the climate system,such a quasi-linear relationship is also a good approximation for the relationship between the annual-mean net downward solar energy flux at the top of the atmosphere and surface temperature.展开更多
This paper presents details of the early to mid-stage deterioration in the form of notch growth of two 3 m diameter bored raises that were excavated and slashed to 7.8 m to serve as an internal shaft(winze).In additio...This paper presents details of the early to mid-stage deterioration in the form of notch growth of two 3 m diameter bored raises that were excavated and slashed to 7.8 m to serve as an internal shaft(winze).In addition,the long-term deterioration of a series of ore/waste passes that were excavated with the bottom-up Alimak methodology is investigated.These excavations were completed at depths between 1200 and 1915 m below the surface in a hard rock mine in Sudbury,Ontario,Canada.The ability to see a cross-section of fracturing around the bored raises while slashing into them and observing the progressive growth of fractures was critical for understanding the factors leading to deterioration.The Alimak-driven ore/waste passes were in an advanced state of deterioration,which provided a late-stage notch growth profile that could be compared with the notch growth observed in the bored raises.The methods used to support and stabilize these excavations are detailed;in addition,methodologies to prevent some of the deterioration from occurring are also presented.The findings of this work are useful for understanding the mechanisms driving brittle rock failure in deep mining and subsequently for minimizing or preventing the deterioration from occurring.展开更多
The China-Kazakhstan Horgos Frontier International Cooperation Center has been established for nearly 20 years,and its targeted policies have gone through the stages of initiative,negotiation and modification,official...The China-Kazakhstan Horgos Frontier International Cooperation Center has been established for nearly 20 years,and its targeted policies have gone through the stages of initiative,negotiation and modification,official operation,and optimization and enhancement.This paper explores the problems,policy,and political sources of policy changes since the establishment of the Horgos International Border Cooperation Center by applying the multi-source flow theory to find the opening of the problematic and political windows.It also constructs a model of policy change dynamics to provide suggestions on how the government should better promote the good development of China’s first transnational cooperation center.展开更多
The presence of geological structures such as faults, joints, and dykes has been observed near excavation boundaries in many rockburst case histories. In this paper, the role of discontinuities around tunnels in rockb...The presence of geological structures such as faults, joints, and dykes has been observed near excavation boundaries in many rockburst case histories. In this paper, the role of discontinuities around tunnels in rockburst occurrence was studied. For this purpose, the Abaqus explicit code was used to simulate dynamic rock failure in deep tunnels. Material heterogeneity was considered using Python scripting in Abaqus. Rockbursts near fault regions in deep tunnels under static and dynamic loads were studied.Several tunnel models with and without faults were built and static and dynamic loads were used to simulate rock failure. The velocity and the released kinetic energy of failed rocks, the failure zone around the tunnel, and the deformed mesh were studied to identify stable and unstable rock failures. Compared with models without discontinuities, the results showed that the velocity and the released kinetic energy of failed rocks were higher, the failure zone around the tunnel was larger, and the mesh was more deformed in the models with discontinuities, indicating that rock failure in the models with discontinuities was more violent. The modeling results confirm that the presence of geological structures in the vicinity of deep excavations could be one of the major influence factors for the occurrence of rockburst. It can explain localized rockburst occurrence in civil tunnels and mining drifts. The presented methodology in this paper for rockburst analysis can be useful for rockburst anticipation and control during mining and tunneling in highly stressed ground.展开更多
Structure stability analysis of rock masses is essential for forecasting catastrophic structure failure in coal seam mining. Steeply dipping thick coal seams （SDTCS） are common in the Urumqi coalfield, and some dyna...Structure stability analysis of rock masses is essential for forecasting catastrophic structure failure in coal seam mining. Steeply dipping thick coal seams （SDTCS） are common in the Urumqi coalfield, and some dynamical hazards such as roof collapse and mining-induced seismicity occur frequently in the coal mines. The cause of these events is mainly structure instability in giant rock pillars sand- wiched between SDTCS. Developing methods to predict these events is important for safe mining in such a complex environment. This study focuses on understanding the structural mechanics model of a giant rock pillar and presents a viewpoint of the stability of a trend sphenoid fractured beam （TSFB）. Some stability index parameters such as failure surface dips were measured, and most dips were observed to be between 46° and 51°. We used a digital panoramic borehole monitoring system to measure the TSFB＇s height （△H）, which varied from 56.37 to 60.50 m. Next, FLAC^3D was used to model the distribution and evolution of vertical displacement in the giant rock pillars; the results confirmed the existence of a TSFB structure. Finally, we investigated the acoustic emission （AE） energy accumulation rate and observed that the rate commonly ranged from 20 to 40 kJ/min. The AE energy accumulation rate could be used to anticipate impeding seismic events related to structure failure. The results presented provide a useful approach for forecasting catastrophic events related to structure instability and for developing hazard prevention technology for mining in SDTCS.展开更多
The stratospheric polar vortex oscillation （PVO） in the Northern Hemisphere is examined in a semiLagrangian θ-PVLAT coordinate constructed by using daily isentropic potential vorticity maps derived from NCEP/NCAR r...The stratospheric polar vortex oscillation （PVO） in the Northern Hemisphere is examined in a semiLagrangian θ-PVLAT coordinate constructed by using daily isentropic potential vorticity maps derived from NCEP/NCAR reanalysis Ⅱdataset covering the period from 1979 to 2003. In the semi-Lagrangian θ-PVLAT coordinate, the variability of the polar vortex is solely attributed to its intensity change because the changes in its location and shape would be naturally absent by following potential vorticity contours on isentropic surfaces. The EOF and regression analyses indicate that the PVO can be described by a pair of poleward and downward propagating modes. These two modes together account for about 82% variance of the daily potential vorticity anomalies over the entire Northern Hemisphere. The power spectral analysis reveals a dominant time scale of about 107 days in the time series of these two modes, representing a complete PVO cycle accompanied with poleward propagating heating anomalies of both positive and negative signs from the equator to the pole. The strong polar vortex corresponds to the arrival of cold anomalies over the polar circle and vice versa. Accompanied with the poleward propagation is a simultaneous downward propagation. The downward propagation time scale is about 20 days in high and low latitudes and about 30 days in mid-latitudes. The zonal wind anomalies lag the poleward and downward propagating temperature anomalies of the opposite sign by 10 days in low and high latitudes and by 20 days in mid-latitudes. The time series of the leading EOF modes also exhibit dominant time scales of 8.7, 16.9, and 33.8 months. They approximately follow a double-periodicity sequence and correspond to the 3-peak extratropical Quasi-Biennial Oscillation （QBO） signal.展开更多
Objective To investigate the effects of small interfering RNA （siRNA） recombinant expression vector targeting survivin gene on chemotherapy sensitivity of human colon cancer cells to 5-fluorouracil. Methods siRNA re...Objective To investigate the effects of small interfering RNA （siRNA） recombinant expression vector targeting survivin gene on chemotherapy sensitivity of human colon cancer cells to 5-fluorouracil. Methods siRNA recombinant expression vector targeting survivin gene was constructed and transfected into human colon cancer cell lines LOVO. After 48 hours of transfection, cells were harvested for analysis of survivin mRNA and protein expressions using RT-PCR and Western blot. In addition, after human colon cancer cell lines were treated with Survivin siRNA and/or 5-fluorouracil, MTT assay and flow cytometry were used to analyze cell proliferation and apoptosis. Results Restriction endonuclease analysis confirmed that siRNA recombinant expression vector targeting survivin gene was successfully constructed. Inhibitory ratios of survivin mRNA and protein expressions by Survivin siRNA were 36.33% and 44.65%, respectively. Survivin siRNA combined with 5-fluorouracil significantly increased the cell proliferation inhibitory ratio and apoptosis ratio compared with 5-fluorouracil treatin~ alone （P〈0.05）. Conclusion The siRNA recombinant expression vector targeting survivin gene can inhibit the expression of survivin gene, and enhance chemotherapy sensitivity of human colon cancer cells to 5- fluorouracil.展开更多
The existing research on SiC_(p)/Al composite machining mainly focuses on the machining parameters or surface morphology.However,the surface quality of SiC_(p)/Al composites with a high volume fraction has not been ex...The existing research on SiC_(p)/Al composite machining mainly focuses on the machining parameters or surface morphology.However,the surface quality of SiC_(p)/Al composites with a high volume fraction has not been extensively studied.In this study,32 SiC_(p)/Al specimens with a high volume fraction were prepared and their machining parameters measured.The surface quality of the specimens was then tested and the effect of the grinding parameters on the surface quality was analyzed.The grinding quality of the composite specimens was comprehensively analyzed taking the grinding force,friction coefficient,and roughness parameters as the evaluation standards.The best grinding parameters were obtained by analyzing the surface morphology.The results show that,a higher spindle speed should be chosen to obtain a better surface quality.The final surface quality is related to the friction coefficient,surface roughness,and fragmentation degree as well as the quantity and distribution of the defects.Lower feeding amount,lower grinding depth and appropriately higher spindle speed should be chosen to obtain better surface quality.Lower feeding amount,higher grinding depth and spindle speed should be chosen to balance grind efficiently and surface quality.This study proposes a systematic evaluation method,which can be used to guide the machining of SiC_(p)/Al composites with a high volume fraction.展开更多
This study uses the coupled atmosphere–surface climate feedback–response analysis method（CFRAM） to analyze the surface temperature biases in the Flexible Global Ocean–Atmosphere–Land System model, spectral versi...This study uses the coupled atmosphere–surface climate feedback–response analysis method（CFRAM） to analyze the surface temperature biases in the Flexible Global Ocean–Atmosphere–Land System model, spectral version 2（FGOALS-s2）in January and July. The process-based decomposition of the surface temperature biases, defined as the difference between the model and ERA-Interim during 1979–2005, enables us to attribute the model surface temperature biases to individual radiative processes including ozone, water vapor, cloud, and surface albedo; and non-radiative processes including surface sensible and latent heat fluxes, and dynamic processes at the surface and in the atmosphere. The results show that significant model surface temperature biases are almost globally present, are generally larger over land than over oceans, and are relatively larger in summer than in winter. Relative to the model biases in non-radiative processes, which tend to dominate the surface temperature biases in most parts of the world, biases in radiative processes are much smaller, except in the sub-polar Antarctic region where the cold biases from the much overestimated surface albedo are compensated for by the warm biases from nonradiative processes. The larger biases in non-radiative processes mainly lie in surface heat fluxes and in surface dynamics,which are twice as large in the Southern Hemisphere as in the Northern Hemisphere and always tend to compensate for each other. In particular, the upward/downward heat fluxes are systematically underestimated/overestimated in most parts of the world, and are mainly compensated for by surface dynamic processes including the increased heat storage in deep oceans across the globe.展开更多
BACKGROUND Methods for predicting the prognosis of patients undergoing surgery for recurrent hepatolithiasis after biliary surgery are currently lacking.AIM To establish a nomogram to predict the prognosis of patients...BACKGROUND Methods for predicting the prognosis of patients undergoing surgery for recurrent hepatolithiasis after biliary surgery are currently lacking.AIM To establish a nomogram to predict the prognosis of patients with recurrent hepatolithiasis after biliary surgery.METHODS In this multicenter,retrospective study,data of consecutive patients in four large medical centers who underwent surgery for recurrent hepatolithiasis after biliary surgery were retrospectively analyzed.We constructed a nomogram to predict the prognosis of recurrent hepatolithiasis in a training cohort of 299 patients,following which we independently tested the nomogram in an external validation cohort of 142 patients.Finally,we used the concordance index(C-index),calibration,area under curve,decision curve analysis,clinical impact curves,and visual fit indices to evaluate the accuracy of the nomogram.RESULTS Multiple previous surgeries[2 surgeries:Odds ratio(95%confidence interval),1.451(0.719-2.932);3 surgeries:4.573(2.015-10.378);≥4 surgeries:5.741(1.347-24.470)],bilateral hepatolithiasis[1.965(1.039-3.717)],absence of immediate clearance[2.398(1.304-4.409)],neutrophil-to-lymphocyte ratio≥2.462[1.915(1.099-3.337)],and albumin-to-globulin ratio≤1.5[1.949(1.056-3.595)]were found to be independent factors influencing the prognosis.The nomogram constructed on the basis of these variables showed good reliability in the training(C-index:0.748)and validation(C-index:0.743)cohorts.Compared with predictions using traditional classification models,those using our nomogram showed better agreement with actual observations in the calibration curve for the probability of endpoints and the receiver operating characteristic curve.Dichloroacetate and clinical impact curves showed a larger net benefit of the nomogram.CONCLUSION The nomogram developed in this study demonstrated superior performance and discriminative power compared to the three traditional classifications.It is easy to use,highly accurate,and shows excellent calibration.展开更多
Three extreme cold events successively occurred across East Asia and North America in the 2020/21 winter.This study investigates the underlying mechanisms of these record-breaking persistent cold events from the isent...Three extreme cold events successively occurred across East Asia and North America in the 2020/21 winter.This study investigates the underlying mechanisms of these record-breaking persistent cold events from the isentropic mass circulation(IMC)perspective.Results show that the midlatitude cold surface temperature anomalies always co-occurred with the high-latitude warm anomalies,and this was closely related to the strengthening of the low-level equatorward cold air branch of the IMC,particularly along the climatological cold air routes over East Asia and North America.Specifically,the two cold surges over East Asia in early winter were results of intensification of cold air transport there,influenced by the Arctic sea ice loss in autumn.The weakened cold air transport over North America associated with warmer northeastern Pacific sea surface temperatures(SSTs)explained the concurrent anomalous warmth there.This enhanced a wavenumber-1 pattern and upward wave propagation,inducing a simultaneous and long-lasting stronger poleward warm air branch(WB)of the IMC in the stratosphere and hence a displacement-type Stratospheric Sudden Warming(SSW)event on 4 January.The WB-induced increase in the air mass transported into the polar stratosphere was followed by intensification of the equatorward cold branch,hence promoting the occurrence of two extreme cold events respectively over East Asia in the beginning of January and over North America in February.Results do not yield a robust direct linkage from La Niña to the SSW event,IMC changes,and cold events,though the extratropical warm SSTs are found to contribute to the February cold surge in North America.展开更多
Side population （SP） cells are a small subset of cells isolated from a cultured cancer cell line that exhibit characteristics similar to those of cancer stem cells （CSCs）, such as high metastatic and tumorigenic p...Side population （SP） cells are a small subset of cells isolated from a cultured cancer cell line that exhibit characteristics similar to those of cancer stem cells （CSCs）, such as high metastatic and tumorigenic potential. The molecular mechanisms that give rise to the malignant properties of SP cells are not clear. We isolated SP cells from the MCF-7 breast cancer cell line and profiled microRNA （miRNA） expression patterns between SP cell-derived spheroids and non-SP cells. SP spheroids were found to possess 42 up-regulated miRNAs and 27 down-regulated ones （above 5-fold changes）. One of the up-regulated miRNAs, miR-888 computationally predicted to participate in the adherens junction （AJ） pathway, was investigated. Over-expression of miR-888 in MCF-7 cells reduced the mRNA levels of all four AJ pathway genes （E-cadherin, ACTG1, PTPRTand CDC42） that were selected for testing, whereas knocking down miR-888 reversed the trends. Western blot and flow cytometric quantitation of the membrane E-cadherin levels showed the same trend of change under these treatments. Luciferase reporter assay showed E-cadherin is a direct target of miR-888. As a potential role in intercellular adhesiveness and maintenance of malignant tissue architecture, the results indicate that miR-888 is a repressor of the AJ pathway in MCF-7 cells and that up-regulation of miR-888 contributes to aggressiveness in MCF-7 SP cells.展开更多
Discontinuity waviness is one of the most important properties that influence shear strength of jointed rock masses,and it should be incorporated into numerical models for slope stability assessment.However,in most ex...Discontinuity waviness is one of the most important properties that influence shear strength of jointed rock masses,and it should be incorporated into numerical models for slope stability assessment.However,in most existing numerical modeling tools,discontinuities are often simplified into planar surfaces.Discrete fracture network modeling tools such as MoFrac allow the simulation of non-planar discontinuities which can be incorporated into lattice-spring-based geomechanical software such as Slope Model for slope stability assessment.In this study,the slope failure of the south wall at Cadia Hill open pit mine is simulated using the lattice-spring-based synthetic rock mass(LS-SRM)modeling approach.First,the slope model is calibrated using field displacement monitoring data,and then the influence of different discontinuity configurations on the stability of the slope is investigated.The modeling results show that the slope with non-planar discontinuities is comparatively more stable than the ones with planar discontinuities.In addition,the slope becomes increasingly unstable with the increases of discontinuity intensity and size.At greater pit depth with higher in situ stress,both the slope models with planar and non-planar discontinuities experience localized failures due to very high stress concentrations,and the slope model with planar discontinuities is more deformable and less stable than that with non-planar discontinuities.展开更多
Crape myrtle(Lagerstroemia indica)is a globally used ornamental woody plant and is the representative species of Lagerstroemia.However,studies on the evolution and genomic breeding of L.indica have been hindered by th...Crape myrtle(Lagerstroemia indica)is a globally used ornamental woody plant and is the representative species of Lagerstroemia.However,studies on the evolution and genomic breeding of L.indica have been hindered by the lack of a reference genome.Here we assembled the first high-quality genome of L.indica using PacBio combined with Hi-C scaffolding to anchor the 329.14-Mb genome assembly into 24 pseudochromosomes.We detected a previously undescribed independent whole-genome triplication event occurring 35.5 million years ago in L.indica following its divergence from Punica granatum.After resequencing 73 accessions of Lagerstroemia,the main parents of modern crape myrtle cultivars were found to be L.indica and L.fauriei.During the process of domestication,genetic diversity tended to decrease in many plants,but this was not observed in L.indica.We constructed a high-density genetic linkage map with an average map distance of 0.33 cM.Furthermore,we integrated the results of quantitative trait locus(QTL)using genetic mapping and bulk segregant analysis(BSA),revealing that the major-effect interval controlling internode length(IL)is located on chr1,which contains CDL15,CRG98,and GID1b1 associated with the phytohormone pathways.Analysis of gene expression of the red,purple,and white flower-colour flavonoid pathways revealed that differential expression of multiple genes determined the flower colour of L.indica,with white flowers having the lowest gene expression.In addition,BSA of purple-and green-leaved individuals of populations of L.indica was performed,and the leaf colour loci were mapped to chr12 and chr17.Within these intervals,we identified MYB35,NCED,and KAS1.Our genome assembly provided a foundation for investigating the evolution,population structure,and differentiation of Myrtaceae species and accelerating the molecular breeding of L.indica.展开更多
Objective:To evaluate the diagnostic value of fluorescence in situ hybridization(FISH)in bladder cancer.Methods:We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and cond...Objective:To evaluate the diagnostic value of fluorescence in situ hybridization(FISH)in bladder cancer.Methods:We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008.Receiver operating characteristic(ROC)curve analysis was performed and the area under curve(AUC)values were calculated for both the FISH and urine cytology tests.Results:A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population.A total of 4807 patients with hematuria were prospectively,randomly enrolled for the simultaneous analysis of urine cytology,FISH testing,and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen.Overall,the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%,while that of cytology was 33.4%(p<0.001).The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7%and 89.6%,respectively(p=0.004).The sensitivity values of FISH for low and high grade bladder cancer were 82.6%and 90.1%,respectively(p=0.002).Conclusion:FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages.Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.展开更多
1.Introduction Artificial intelligence(AI)is committed to the realization of machine-borne intelligence.The technologies underpinning AI have made huge leaps in the past decade,bringing exciting applications such as l...1.Introduction Artificial intelligence(AI)is committed to the realization of machine-borne intelligence.The technologies underpinning AI have made huge leaps in the past decade,bringing exciting applications such as language understanding,vision recognition,and intelligent digital assistants.However,contemporary AI systems are good at specific predefined tasks and are unable to learn by themselves from data or from experience,intuitive reasoning,and adaptation.展开更多
基金supported by the National Science Fund for Excellent Young Scholars(NSFC-82322058)the Program of National Natural Science Foundation of China(NSFC-82103929,NSFC-82273713)+10 种基金the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the National Science Fund for Distinguished Young Scholars of Hubei Province of China(2023AFA046)the Fundamental Research Funds for the Central Universities(WHU:2042022kf1205)Fundamental Research Funds for the Central Universities(WHU:2042022kf1031)for Ying Zhuthe Fundamental Research Funds for the Central Universities(2042022rc0026,2042023kf1005)for Xiao-Ping Miaothe Knowledge Innovation Program of Wuhan(whkxjsj011,2023020201010073)for Jian-Bo Tianthe Science and Technology Innovation Seed Fund of Zhongnan Hospital of Wuhan University(znpy2019060)for Yong-Chang Weithe Distinguished Young Scholars of China(NSFC-81925032)the Key Program of National Natural Science Foundation of China(NSFC-82130098)the Youth Program of National Natural Science Foundation of China(NSFC-82003547)the Program of Health Commission of Hubei Province(WJ2023M045)。
文摘Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.
基金the National Key R and D Program of China(Grant Nos.2019YFD1000402,2019YFD1001004)the World-Class Discipline Construction and Characteristic Development Guidance Funds for Beijing Forestry University(Grant No.2019XKJS0323).
文摘Purple-leafed plants not only have a higher resistance to biotic and abiotic stresses,but also have higher ornamental value.Anthocyanins are vital for leaf color formation,growth and development of purple leaves.However,the molecular mechanism underlying purple leaf formation in Lagerstroemia indica remains unclear.Metabolomic and transcriptomic analysis of purple-leafed cultivar‘Ebony Embers’and greenleafed cultivar‘Arapahoe’showed that the high expression of anthocyanin structure genes induced hyperaccumulation of cyanidin and pelargonidin derivatives,making the leaves purple.LfiHY5,LfiMYB75 and LfibHLH1 were identified using correlation analysis and weighted gene co-expression network analysis.In‘Arapahoe’‘Ebony Embers’population,LfiHY5 and LfiMYB75 showed significant positive correlation with leaf anthocyanin content.Transient expression of LfiMYB75 and LfiHY5 in tobacco and purple-leafed crape myrtle indicated that the two genes activated anthocyanin synthesis.Yeast two-hybrid analysis showed that LfiMYB75 and LfibHLH1 could form a complex that enhanced anthocyanin synthesis.Yeast monohybrid and dual-luciferase assays confirmed that LfiHY5 activated the expression of LfiMYB75,to activate the transcription of anthocyanin structural genes LfiCHS and LfiANS.Moreover,there were three alleles of LfiHY5 in crape myrtle,and the different sequences had different activation effects on LfiMYB75.In conclusion,the results showed that LfiHY5 led to upregulate the transcription of LfiMYB75,and LfiMYB75 formed a complex with LfibHLH1,which increased the transcription level of LfiCHS and LfiANS to affect anthocyanin synthesis in crape myrtle.
文摘BACKGROUND Ampullary cancer is a relatively rare malignant tumor in the digestive system.Its incidence has increased in recent years.As for now,its biological characteristics have not been fully clarified.Recent studies have primarily focused on the histological classification and genetic changes,but there are fewer investigations into the differences among site-specific subgroups.The clinicopathological charac-teristics of ampullary cancer occurring in different positions have not been elucidated.Furthermore,the role of adjuvant therapy in the treatment of patients with ampullary cancer remains controversial.ampullary cancer and explore the factors affecting prognosis.METHODS A total of 356 patients who met the inclusion and exclusion criteria were enrolled.Patients were divided into ampulla of Vater cancer(AVC)and duodenal papilla cancer(DPC)based on the gross and microscopic findings.Baseline data,admission examination results,and perioperative outcomes were collected and analyzed.The Kaplan-Meier curve was used for survival analysis.Univariate and multivariate analysis was performed to explore the independent risk factors affecting the overall survival(OS)of both groups.RESULTS The preoperative total bilirubin level in patients with AVC was significantly higher than those with DPC(P=0.04).The OS for patients with DPC was 58.90±38.74 months,significantly longer than 44.31±35.90 months for patients with AVC(P<0.01).The independent risk factors affecting the OS of AVC included:Preoperative albumin level(P=0.009),total bilirubin level(P=0.017),and number of positive lymph nodes(P=0.005).For DPC,risk factors included:Age(P=0.004),tumor size(P=0.023),number of positive lymph nodes(P=0.010)and adjuvant treatment(P=0.020).Adjuvant therapy significantly improved the OS rate of patients with DPC,but not for those with AVC.CONCLUSION Patients with AVC had a shorter OS compared to those with DPC.The prognosis factors and the role of adjuvant therapy of two groups were different.
文摘It is important to understand and manage rockburst challenges in deep mining operations.This paper presents a systematic study of rockburst risk in underground mining,offering a detailed examination of influencing factors,risk assessment,and various control and mitigation methods.The complexities of rockburst phenomena are explained by examining factors that lead to the occurrence of rockbursts.A rockburst risk assessment using a bow-tie analysis is conducted,which provides insights into both risk evaluation and proactive control and mitigation systems.The core of the paper presents a comprehensive array of rockburst risk control and mitigation methods,which range from controls to reduce rockburst hazard,and excavation vulnerability,to controls and mitigations to reduce exposure.Strategic engineering control methods,including mine design and mining sequencing,are discussed.Tactical engineering control measures,such as ground pre-conditioning and rock support,are scrutinized,along with administrative controls like evacuation and re-entry protocols and the use of mechanized equipment.A multiple-line defense system is advocated for rockburst risk management to address the uncertainties involved in the process.Finally,emerging technologies and innovations as well as challenges are discussed,providing a roadmap for continued advancements in rockburst risk management in the future.This work serves as a valuable resource for mining professionals,researchers,and policymakers seeking a comprehensive understanding of rockburst risk management in deep mining.
基金part supported by grants from the National Natural Science Foundation of China(Grant Nos.42222502 and 42075028)grants from the National Science Foundation(AGS-2032542 and AGS-2202875)。
文摘In this study,we put forward a radiative-convective-transportive energy balance model of a gray atmosphere to examine individual roles of the greenhouse effect of water vapor,vertical convection,and atmospheric poleward energy transport as well as their combined effects for a quasi-linear relationship between the outgoing longwave radiation(OLR)and surface temperature(T_(S)).The greenhouse effect of water vapor enhances the meridional gradient of surface temperature,thereby directly contributing to a quasi-linear OLR-T_(S) relationship.The atmospheric poleward energy transport decreases the meridional gradient of surface temperature.As a result of the poleward energy transport,tropical(high-latitude)atmosphere-surface columns emit less(more)OLR than the solar energy input at their respective locations,causing a substantial reduction of the meridional gradient of the OLR.The combined effect of reducing the meridional gradients of both OLR and surface temperature by the poleward energy transport also contributes to the quasi-linear OLR-T_(S) relationship.Vertical convective energy transport reduces the meridional gradient of surface temperature without affecting the meridional gradient of OLR,thereby suppressing part of the reduction to the increasing rate of OLR with surface temperature by the greenhouse effect of water vapor and poleward energy transport.Because of the nature of the energy balance in the climate system,such a quasi-linear relationship is also a good approximation for the relationship between the annual-mean net downward solar energy flux at the top of the atmosphere and surface temperature.
文摘This paper presents details of the early to mid-stage deterioration in the form of notch growth of two 3 m diameter bored raises that were excavated and slashed to 7.8 m to serve as an internal shaft(winze).In addition,the long-term deterioration of a series of ore/waste passes that were excavated with the bottom-up Alimak methodology is investigated.These excavations were completed at depths between 1200 and 1915 m below the surface in a hard rock mine in Sudbury,Ontario,Canada.The ability to see a cross-section of fracturing around the bored raises while slashing into them and observing the progressive growth of fractures was critical for understanding the factors leading to deterioration.The Alimak-driven ore/waste passes were in an advanced state of deterioration,which provided a late-stage notch growth profile that could be compared with the notch growth observed in the bored raises.The methods used to support and stabilize these excavations are detailed;in addition,methodologies to prevent some of the deterioration from occurring are also presented.The findings of this work are useful for understanding the mechanisms driving brittle rock failure in deep mining and subsequently for minimizing or preventing the deterioration from occurring.
文摘The China-Kazakhstan Horgos Frontier International Cooperation Center has been established for nearly 20 years,and its targeted policies have gone through the stages of initiative,negotiation and modification,official operation,and optimization and enhancement.This paper explores the problems,policy,and political sources of policy changes since the establishment of the Horgos International Border Cooperation Center by applying the multi-source flow theory to find the opening of the problematic and political windows.It also constructs a model of policy change dynamics to provide suggestions on how the government should better promote the good development of China’s first transnational cooperation center.
基金Financial supports from the Natural Sciences and Engineering Research Council(NSERC)of Canada(CRDPJ 418932-11)Vale,LKAB,CEMI,MIRARCO,and the Open Research Fund of the State Key Laboratory of Geomechanics and Geotechnical Engineering,Institute of Rock and Soil Mechanics,Chinese Academy of Sciences(Grant No.Z015001)for this work are gratefully acknowledged
文摘The presence of geological structures such as faults, joints, and dykes has been observed near excavation boundaries in many rockburst case histories. In this paper, the role of discontinuities around tunnels in rockburst occurrence was studied. For this purpose, the Abaqus explicit code was used to simulate dynamic rock failure in deep tunnels. Material heterogeneity was considered using Python scripting in Abaqus. Rockbursts near fault regions in deep tunnels under static and dynamic loads were studied.Several tunnel models with and without faults were built and static and dynamic loads were used to simulate rock failure. The velocity and the released kinetic energy of failed rocks, the failure zone around the tunnel, and the deformed mesh were studied to identify stable and unstable rock failures. Compared with models without discontinuities, the results showed that the velocity and the released kinetic energy of failed rocks were higher, the failure zone around the tunnel was larger, and the mesh was more deformed in the models with discontinuities, indicating that rock failure in the models with discontinuities was more violent. The modeling results confirm that the presence of geological structures in the vicinity of deep excavations could be one of the major influence factors for the occurrence of rockburst. It can explain localized rockburst occurrence in civil tunnels and mining drifts. The presented methodology in this paper for rockburst analysis can be useful for rockburst anticipation and control during mining and tunneling in highly stressed ground.
基金financially supported by the Key National Basic Research Program of China (Nos.2014CB260404 and 2015CB251602)the Key National Natural Science Foundation of China (No.U13612030)+1 种基金Shaanxi Innovation Team Program (No.2013KCT-16)the High Technology Development Program of Xin Jiang Municipality (No.201432102)
文摘Structure stability analysis of rock masses is essential for forecasting catastrophic structure failure in coal seam mining. Steeply dipping thick coal seams （SDTCS） are common in the Urumqi coalfield, and some dynamical hazards such as roof collapse and mining-induced seismicity occur frequently in the coal mines. The cause of these events is mainly structure instability in giant rock pillars sand- wiched between SDTCS. Developing methods to predict these events is important for safe mining in such a complex environment. This study focuses on understanding the structural mechanics model of a giant rock pillar and presents a viewpoint of the stability of a trend sphenoid fractured beam （TSFB）. Some stability index parameters such as failure surface dips were measured, and most dips were observed to be between 46° and 51°. We used a digital panoramic borehole monitoring system to measure the TSFB＇s height （△H）, which varied from 56.37 to 60.50 m. Next, FLAC^3D was used to model the distribution and evolution of vertical displacement in the giant rock pillars; the results confirmed the existence of a TSFB structure. Finally, we investigated the acoustic emission （AE） energy accumulation rate and observed that the rate commonly ranged from 20 to 40 kJ/min. The AE energy accumulation rate could be used to anticipate impeding seismic events related to structure failure. The results presented provide a useful approach for forecasting catastrophic events related to structure instability and for developing hazard prevention technology for mining in SDTCS.
文摘The stratospheric polar vortex oscillation （PVO） in the Northern Hemisphere is examined in a semiLagrangian θ-PVLAT coordinate constructed by using daily isentropic potential vorticity maps derived from NCEP/NCAR reanalysis Ⅱdataset covering the period from 1979 to 2003. In the semi-Lagrangian θ-PVLAT coordinate, the variability of the polar vortex is solely attributed to its intensity change because the changes in its location and shape would be naturally absent by following potential vorticity contours on isentropic surfaces. The EOF and regression analyses indicate that the PVO can be described by a pair of poleward and downward propagating modes. These two modes together account for about 82% variance of the daily potential vorticity anomalies over the entire Northern Hemisphere. The power spectral analysis reveals a dominant time scale of about 107 days in the time series of these two modes, representing a complete PVO cycle accompanied with poleward propagating heating anomalies of both positive and negative signs from the equator to the pole. The strong polar vortex corresponds to the arrival of cold anomalies over the polar circle and vice versa. Accompanied with the poleward propagation is a simultaneous downward propagation. The downward propagation time scale is about 20 days in high and low latitudes and about 30 days in mid-latitudes. The zonal wind anomalies lag the poleward and downward propagating temperature anomalies of the opposite sign by 10 days in low and high latitudes and by 20 days in mid-latitudes. The time series of the leading EOF modes also exhibit dominant time scales of 8.7, 16.9, and 33.8 months. They approximately follow a double-periodicity sequence and correspond to the 3-peak extratropical Quasi-Biennial Oscillation （QBO） signal.
基金Supported by National High Technology Research and Development Program of China (2001AA218051)Educational Commission of Hubei Province of China (2005A304B09)
文摘Objective To investigate the effects of small interfering RNA （siRNA） recombinant expression vector targeting survivin gene on chemotherapy sensitivity of human colon cancer cells to 5-fluorouracil. Methods siRNA recombinant expression vector targeting survivin gene was constructed and transfected into human colon cancer cell lines LOVO. After 48 hours of transfection, cells were harvested for analysis of survivin mRNA and protein expressions using RT-PCR and Western blot. In addition, after human colon cancer cell lines were treated with Survivin siRNA and/or 5-fluorouracil, MTT assay and flow cytometry were used to analyze cell proliferation and apoptosis. Results Restriction endonuclease analysis confirmed that siRNA recombinant expression vector targeting survivin gene was successfully constructed. Inhibitory ratios of survivin mRNA and protein expressions by Survivin siRNA were 36.33% and 44.65%, respectively. Survivin siRNA combined with 5-fluorouracil significantly increased the cell proliferation inhibitory ratio and apoptosis ratio compared with 5-fluorouracil treatin~ alone （P〈0.05）. Conclusion The siRNA recombinant expression vector targeting survivin gene can inhibit the expression of survivin gene, and enhance chemotherapy sensitivity of human colon cancer cells to 5- fluorouracil.
基金Supported by University of Science and Technology Liaoning Talent Project Grants(Grant No.601011507-19)National Natural Science Foundation of China(Grant No.51775100).
文摘The existing research on SiC_(p)/Al composite machining mainly focuses on the machining parameters or surface morphology.However,the surface quality of SiC_(p)/Al composites with a high volume fraction has not been extensively studied.In this study,32 SiC_(p)/Al specimens with a high volume fraction were prepared and their machining parameters measured.The surface quality of the specimens was then tested and the effect of the grinding parameters on the surface quality was analyzed.The grinding quality of the composite specimens was comprehensively analyzed taking the grinding force,friction coefficient,and roughness parameters as the evaluation standards.The best grinding parameters were obtained by analyzing the surface morphology.The results show that,a higher spindle speed should be chosen to obtain a better surface quality.The final surface quality is related to the friction coefficient,surface roughness,and fragmentation degree as well as the quantity and distribution of the defects.Lower feeding amount,lower grinding depth and appropriately higher spindle speed should be chosen to obtain better surface quality.Lower feeding amount,higher grinding depth and spindle speed should be chosen to balance grind efficiently and surface quality.This study proposes a systematic evaluation method,which can be used to guide the machining of SiC_(p)/Al composites with a high volume fraction.
基金jointly supported by projects XDA11010402 GYHY201406001the National Basic Key Project (973) 2010CB428603 and 2010CB950400
文摘This study uses the coupled atmosphere–surface climate feedback–response analysis method（CFRAM） to analyze the surface temperature biases in the Flexible Global Ocean–Atmosphere–Land System model, spectral version 2（FGOALS-s2）in January and July. The process-based decomposition of the surface temperature biases, defined as the difference between the model and ERA-Interim during 1979–2005, enables us to attribute the model surface temperature biases to individual radiative processes including ozone, water vapor, cloud, and surface albedo; and non-radiative processes including surface sensible and latent heat fluxes, and dynamic processes at the surface and in the atmosphere. The results show that significant model surface temperature biases are almost globally present, are generally larger over land than over oceans, and are relatively larger in summer than in winter. Relative to the model biases in non-radiative processes, which tend to dominate the surface temperature biases in most parts of the world, biases in radiative processes are much smaller, except in the sub-polar Antarctic region where the cold biases from the much overestimated surface albedo are compensated for by the warm biases from nonradiative processes. The larger biases in non-radiative processes mainly lie in surface heat fluxes and in surface dynamics,which are twice as large in the Southern Hemisphere as in the Northern Hemisphere and always tend to compensate for each other. In particular, the upward/downward heat fluxes are systematically underestimated/overestimated in most parts of the world, and are mainly compensated for by surface dynamic processes including the increased heat storage in deep oceans across the globe.
基金Supported by the Key Research and Development Plan of Anhui Province,No.1804h08020239。
文摘BACKGROUND Methods for predicting the prognosis of patients undergoing surgery for recurrent hepatolithiasis after biliary surgery are currently lacking.AIM To establish a nomogram to predict the prognosis of patients with recurrent hepatolithiasis after biliary surgery.METHODS In this multicenter,retrospective study,data of consecutive patients in four large medical centers who underwent surgery for recurrent hepatolithiasis after biliary surgery were retrospectively analyzed.We constructed a nomogram to predict the prognosis of recurrent hepatolithiasis in a training cohort of 299 patients,following which we independently tested the nomogram in an external validation cohort of 142 patients.Finally,we used the concordance index(C-index),calibration,area under curve,decision curve analysis,clinical impact curves,and visual fit indices to evaluate the accuracy of the nomogram.RESULTS Multiple previous surgeries[2 surgeries:Odds ratio(95%confidence interval),1.451(0.719-2.932);3 surgeries:4.573(2.015-10.378);≥4 surgeries:5.741(1.347-24.470)],bilateral hepatolithiasis[1.965(1.039-3.717)],absence of immediate clearance[2.398(1.304-4.409)],neutrophil-to-lymphocyte ratio≥2.462[1.915(1.099-3.337)],and albumin-to-globulin ratio≤1.5[1.949(1.056-3.595)]were found to be independent factors influencing the prognosis.The nomogram constructed on the basis of these variables showed good reliability in the training(C-index:0.748)and validation(C-index:0.743)cohorts.Compared with predictions using traditional classification models,those using our nomogram showed better agreement with actual observations in the calibration curve for the probability of endpoints and the receiver operating characteristic curve.Dichloroacetate and clinical impact curves showed a larger net benefit of the nomogram.CONCLUSION The nomogram developed in this study demonstrated superior performance and discriminative power compared to the three traditional classifications.It is easy to use,highly accurate,and shows excellent calibration.
基金supported by grants from the National Key R&D Program of China(Grant No.2019YFC1510201)National Natural Science Foundation of China(Grant Nos.42075052 and 42088101)the Natural Science Foundation of Jiangsu Province(Grants No.BK20211288).
文摘Three extreme cold events successively occurred across East Asia and North America in the 2020/21 winter.This study investigates the underlying mechanisms of these record-breaking persistent cold events from the isentropic mass circulation(IMC)perspective.Results show that the midlatitude cold surface temperature anomalies always co-occurred with the high-latitude warm anomalies,and this was closely related to the strengthening of the low-level equatorward cold air branch of the IMC,particularly along the climatological cold air routes over East Asia and North America.Specifically,the two cold surges over East Asia in early winter were results of intensification of cold air transport there,influenced by the Arctic sea ice loss in autumn.The weakened cold air transport over North America associated with warmer northeastern Pacific sea surface temperatures(SSTs)explained the concurrent anomalous warmth there.This enhanced a wavenumber-1 pattern and upward wave propagation,inducing a simultaneous and long-lasting stronger poleward warm air branch(WB)of the IMC in the stratosphere and hence a displacement-type Stratospheric Sudden Warming(SSW)event on 4 January.The WB-induced increase in the air mass transported into the polar stratosphere was followed by intensification of the equatorward cold branch,hence promoting the occurrence of two extreme cold events respectively over East Asia in the beginning of January and over North America in February.Results do not yield a robust direct linkage from La Niña to the SSW event,IMC changes,and cold events,though the extratropical warm SSTs are found to contribute to the February cold surge in North America.
基金supported by the grant from the Natural Science Foundation of China (No. 30971625) to Dr. Liangbiao Chen
文摘Side population （SP） cells are a small subset of cells isolated from a cultured cancer cell line that exhibit characteristics similar to those of cancer stem cells （CSCs）, such as high metastatic and tumorigenic potential. The molecular mechanisms that give rise to the malignant properties of SP cells are not clear. We isolated SP cells from the MCF-7 breast cancer cell line and profiled microRNA （miRNA） expression patterns between SP cell-derived spheroids and non-SP cells. SP spheroids were found to possess 42 up-regulated miRNAs and 27 down-regulated ones （above 5-fold changes）. One of the up-regulated miRNAs, miR-888 computationally predicted to participate in the adherens junction （AJ） pathway, was investigated. Over-expression of miR-888 in MCF-7 cells reduced the mRNA levels of all four AJ pathway genes （E-cadherin, ACTG1, PTPRTand CDC42） that were selected for testing, whereas knocking down miR-888 reversed the trends. Western blot and flow cytometric quantitation of the membrane E-cadherin levels showed the same trend of change under these treatments. Luciferase reporter assay showed E-cadherin is a direct target of miR-888. As a potential role in intercellular adhesiveness and maintenance of malignant tissue architecture, the results indicate that miR-888 is a repressor of the AJ pathway in MCF-7 cells and that up-regulation of miR-888 contributes to aggressiveness in MCF-7 SP cells.
基金Ontario Trillium Scholarship for supporting the doctorate program at Laurentian UniversityFinancial supports from the Natural Sciences and Engineering Research Council of Canada(NSERC CRD 470490-14)of Canada+1 种基金Nuclear Waste Management Organization(NWMO)Rio Tinto。
文摘Discontinuity waviness is one of the most important properties that influence shear strength of jointed rock masses,and it should be incorporated into numerical models for slope stability assessment.However,in most existing numerical modeling tools,discontinuities are often simplified into planar surfaces.Discrete fracture network modeling tools such as MoFrac allow the simulation of non-planar discontinuities which can be incorporated into lattice-spring-based geomechanical software such as Slope Model for slope stability assessment.In this study,the slope failure of the south wall at Cadia Hill open pit mine is simulated using the lattice-spring-based synthetic rock mass(LS-SRM)modeling approach.First,the slope model is calibrated using field displacement monitoring data,and then the influence of different discontinuity configurations on the stability of the slope is investigated.The modeling results show that the slope with non-planar discontinuities is comparatively more stable than the ones with planar discontinuities.In addition,the slope becomes increasingly unstable with the increases of discontinuity intensity and size.At greater pit depth with higher in situ stress,both the slope models with planar and non-planar discontinuities experience localized failures due to very high stress concentrations,and the slope model with planar discontinuities is more deformable and less stable than that with non-planar discontinuities.
基金supported by National Key R&D Program of China(2019YFD1001004,2019YFD1000402)the program for Science and Technology of Beijing(Z181100002418006)the Special Fund for Beijing Common Construction Project.
文摘Crape myrtle(Lagerstroemia indica)is a globally used ornamental woody plant and is the representative species of Lagerstroemia.However,studies on the evolution and genomic breeding of L.indica have been hindered by the lack of a reference genome.Here we assembled the first high-quality genome of L.indica using PacBio combined with Hi-C scaffolding to anchor the 329.14-Mb genome assembly into 24 pseudochromosomes.We detected a previously undescribed independent whole-genome triplication event occurring 35.5 million years ago in L.indica following its divergence from Punica granatum.After resequencing 73 accessions of Lagerstroemia,the main parents of modern crape myrtle cultivars were found to be L.indica and L.fauriei.During the process of domestication,genetic diversity tended to decrease in many plants,but this was not observed in L.indica.We constructed a high-density genetic linkage map with an average map distance of 0.33 cM.Furthermore,we integrated the results of quantitative trait locus(QTL)using genetic mapping and bulk segregant analysis(BSA),revealing that the major-effect interval controlling internode length(IL)is located on chr1,which contains CDL15,CRG98,and GID1b1 associated with the phytohormone pathways.Analysis of gene expression of the red,purple,and white flower-colour flavonoid pathways revealed that differential expression of multiple genes determined the flower colour of L.indica,with white flowers having the lowest gene expression.In addition,BSA of purple-and green-leaved individuals of populations of L.indica was performed,and the leaf colour loci were mapped to chr12 and chr17.Within these intervals,we identified MYB35,NCED,and KAS1.Our genome assembly provided a foundation for investigating the evolution,population structure,and differentiation of Myrtaceae species and accelerating the molecular breeding of L.indica.
基金This clinical research was funded by the Ministry of Health People’s Republic of China(No.WKJ2007-3-001).
文摘Objective:To evaluate the diagnostic value of fluorescence in situ hybridization(FISH)in bladder cancer.Methods:We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008.Receiver operating characteristic(ROC)curve analysis was performed and the area under curve(AUC)values were calculated for both the FISH and urine cytology tests.Results:A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population.A total of 4807 patients with hematuria were prospectively,randomly enrolled for the simultaneous analysis of urine cytology,FISH testing,and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen.Overall,the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%,while that of cytology was 33.4%(p<0.001).The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7%and 89.6%,respectively(p=0.004).The sensitivity values of FISH for low and high grade bladder cancer were 82.6%and 90.1%,respectively(p=0.002).Conclusion:FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages.Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.
文摘1.Introduction Artificial intelligence(AI)is committed to the realization of machine-borne intelligence.The technologies underpinning AI have made huge leaps in the past decade,bringing exciting applications such as language understanding,vision recognition,and intelligent digital assistants.However,contemporary AI systems are good at specific predefined tasks and are unable to learn by themselves from data or from experience,intuitive reasoning,and adaptation.
