This study investigates the heat dissipation mechanism of the insulation layer and other plane insulation layers in the polar drilling rig system.Combining the basic theory of heat transfer with the environmental requ...This study investigates the heat dissipation mechanism of the insulation layer and other plane insulation layers in the polar drilling rig system.Combining the basic theory of heat transfer with the environmental requirements of polar drilling operations and the characteristics of polar drilling processes,we analyze the factors that affect the insulation effect of the drilling rig system.These factors include the thermal conductivity of the insulation material,the thickness of the insulation layer,ambient temperature,and wind speed.We optimize the thermal insulation material of the polar drilling rig system using a steady-state method to measure solid thermal conductivity.By analyzing the distribution of temperature in space after heating,we optimize the distribution and air outlet angle of the heater using Fluent hydrodynamics software.The results demonstrate that under polar conditions,polyisocyanurate with stable thermodynamic properties is selected as the thermal insulation material.The selection of thermal insulation material and thickness significantly affects the thermal insulation effect of the system but has little effect on its heating effect.Moreover,when the air outlet angle of the heater is set to 32.5°,the heating efficiency of the system can be effectively improved.According to heat transfer equations and heat balance theory,we determine that the heating power required for the system to reach 5°C is close to numerical simulation.展开更多
BACKGROUND Venous thrombosis(VT) is one of the minor complications of pacemaker lead extraction. It is often found due to the swelling of the limbs after the extraction. It is easy to be neglected or even misdiagnosed...BACKGROUND Venous thrombosis(VT) is one of the minor complications of pacemaker lead extraction. It is often found due to the swelling of the limbs after the extraction. It is easy to be neglected or even misdiagnosed in the absence of typical clinical symptoms. The incidence, risk factors, and long-term impact of this complication are still unclear. Herein, we report a case of deep VT caused by transvenous lead extraction, which is easily misdiagnosed.CASE SUMMARY A 66-year-old woman underwent a pacemaker lead extraction at our hospital because of a pacemaker pocket infection. After the extraction, she began to experience intermittent fever accompanied by sweating. The highest body temperature recorded was 37.9℃. Additionally, she reported migratory pain that made her uncomfortable. The pain was mistakenly thought to be caused by operation trauma. At first, the pain radiated from the left chest to the mandible.Then, the pain in the left chest was alleviated, but pain in the left neck and throat appeared. Finally, the pain was confined to the mandible and a submandibular mass was palpated with no other abnormalities upon physical examination.Computed tomography venography and angiography finally indicated that the fever and pain were the symptoms of thrombophlebitis caused by lead extraction.The patient was then treated with rivaroxaban for more than three months and has shown no symptoms since she left the hospital.CONCLUSION The possibility of thrombosis should be considered when pain and recurrent fever occur after pacemaker lead extraction.展开更多
The post-infarcted related ventricular tachycardia (VT) is considered associated with increase in mortality or sudden cardiac death (SCD). Implantable cardioverter defibrillation (ICD) has been the standard therapy fo...The post-infarcted related ventricular tachycardia (VT) is considered associated with increase in mortality or sudden cardiac death (SCD). Implantable cardioverter defibrillation (ICD) has been the standard therapy for the first or second prevention of SCD after myocardial infarction (MI). Incessant VT, which has poor response to anti-arrhythmic drugs and can cause repetitive ICD shock, is usually a tough problem in clinical practice. According to the guideline, incessant infracted related VT could be treated with catheter ablation.[1] Herein we reported a case of refractory scar-induced VT accompanied with thrombus in the left chamber, which was full with ups and downs during the therapy.展开更多
Objective The aim of this study was to construct a prognostic model of esophageal adenocarcinoma(EAC)based on immune-related long noncoding RNAs(immune-related lncRNAs)and identify prognostic biomarkers using the Canc...Objective The aim of this study was to construct a prognostic model of esophageal adenocarcinoma(EAC)based on immune-related long noncoding RNAs(immune-related lncRNAs)and identify prognostic biomarkers using the Cancer Genome Atlas(TCGA)database.Methods Whole genomic mRNA expression and clinical data of esophageal adenocarcinoma were obtained from the TCGA database.The software Strawberry Perl,R and R packets were used to identify the immune-related genes and lncRNAs of esophageal adenocarcinoma,and for data processing and analysis.The differentially expressed lncRNAs were detected while comparing esophageal adenocarcinoma and normal tissue samples.The key immune-related lncRNAs were screened using lasso regression analysis and univariate cox regression analysis,and used to construct the prognostic model using multivariate cox regression analysis.To evaluate the accuracy of the risk prognostic model,all esophageal adenocarcinomas were divided into high-risk and low-risk groups according to the median risk score,after which Kaplan-Meier(K-M)survival curves,operating characteristic(ROC)curve and independent prognostic analysis of clinical traits were created.In addition,statistically significant immune-related lncRNAs and potential prognostic biomarkers were identified using the prognostic model and multifactor cox regression analysis for k-m survival analysis.Results A total of 1322 differentially expressed immune-related lncRNAs were identified,28 of which were associated with prognosis via univariate cox regression analysis.In addition,K-M survival analysis showed that the total survival time of the higher risk group was significantly shorter than that of the lower risk group(P=1.063e-10).The area under the ROC curve of 5-year total survival rate was 0.90.The risk score showed independent prognostic risk for esophageal adenocarcinoma via single factor and multifactorial independent prognostic analyses.In addition,the HR and 95%CI of each key immune-related lncRNA were calculated using multivariate Cox regression.Using k-m survival analysis,we found that 5 out of 12 key significant immune-related lncRNAs had independent prognostic value[AL136115.1(P=0.006),AC079684.1(P=0.008),AC07916394.1(P=0.0386),AC087620.1(P=0.041)and MIRLET7BHG(P=0.044)].Conclusion The present study successfully constructed a prognostic model of esophageal adenocarcinoma based on the TCGA database,with moderate predictive accuracy.The model consisted of the expression level of 12 immune-related lncRNAs.Furthermore,the study identified one favorable prognostic biomarker,MIRLET7BHG,and four poor prognostic biomarkers(AL136115.1,AC079684.1,AC016394.1,and AC087620.1).展开更多
The comparative study of submerged arc welding(SAW)and laser hybrid welding(LHW)was carried out for a 690 MPa high strength steel with thickness of 20 mm.Microstructure and ductile–brittle transition temperature(DBTT...The comparative study of submerged arc welding(SAW)and laser hybrid welding(LHW)was carried out for a 690 MPa high strength steel with thickness of 20 mm.Microstructure and ductile–brittle transition temperature(DBTT)evolution in welded zone were elucidated from the aspect of crystallographic structure,particularly,digitization and visualization of 24 variants.The impact toughness of each micro zone in LHW joint is better than that of SAW,in which the DBTT of equivalent fusion line and heat-affected zone(HAZ)can reach−70 and−80℃,while that of SAW is only−50℃.LHW technology induces narrowing of the HAZ and refining of the microstructure obtained in weld metal and HAZ.Meanwhile,the austenite grain size and transformation driving force in the coarse grained heat-affected zone(CGHAZ)are reduced and increased,respectively.It makes variant selection mechanism occurring in CGHAZ of LHW dominate by close-packed plane grouping,which promotes lath bainite formation with high density of high angle grain boundary,especially block boundary dominated by V1/V2 pair.While for SAW,the lower transformation driving force inferred from the large amount of retained austenite in CGHAZ induces Bain grouping of variants,and thus triggers the brittle crack propagating straightly in granular bainite,resulting in lower impact toughness and higher DBTT.展开更多
Endophytic fungi are promising producers of bioactive small molecules.Bioinformatic analysis of the genome of an endophytic fungus Penicillium dangeardii revealed 43 biosynthetic gene clusters,exhibited its strong abi...Endophytic fungi are promising producers of bioactive small molecules.Bioinformatic analysis of the genome of an endophytic fungus Penicillium dangeardii revealed 43 biosynthetic gene clusters,exhibited its strong ability to produce numbers of secondary metabolites.However,this strain mainly produce rubratoxins alone with high yield in varied culture conditions,suggested most gene clusters are silent.Efforts for mining the cryptic gene clusters in P.dangeardii,including epigenetic regulation and one-strain-many-compounds(OSMAC)approach were failed probably due to the high yield of rubratoxins.A metabolic shunting strategy by deleting the key gene for rubratoxins biosynthesis combining with optimization of culture condition successfully activated multiple silent genes encoding for other polyketide synthases(PKSs),and led to the trace compounds detectable.As a result,a total of 23 new compounds including azaphilone monomers,dimers,turimers with unprecedented polycyclic bridged heterocycle and spiral structures,as well as siderophores were identified.Some compounds showed significant cytotoxicities,anti-inflammatory or antioxidant activities.The attractive dual PKS s gene clusters for azaphilones biosynthesis were mined by bioinformatic analysis and overexpression of a pathway specific transcription factor.Our work therefor provides an efficient approach to mine the chemical diversity of endophytic fungi.展开更多
Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in Calcarisporiu...Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in Calcarisporium arbuscula had led to pleiotropic activation and overexpression of more than 75% of the biosynthetic genes and isolation of ten compounds. Further investigation of the crude extract of C. arbuscula Δhda A strain resulted in the isolation of twelve new diterpenoids including three cassanes(1-3), one cleistanthane(4), six pimaranes(5-10), and two isopimaranes(11 and 12) along with two know cleistanthane analogues. Their structures were elucidated by extensive NMR spectroscopic data analysis. Compounds 2 and 4 showed potent inhibitory effects on the expression of MMP1 and MMP2(matrix metalloproteinases family) in human breast cancer(MCF-7) cells.展开更多
This paper describes a novel,semiautomated design methodology based on a genetic algorithm(GA)using freeform geometries for microelectromechanical systems(MEMS)devices.The proposed method can design MEMS devices compr...This paper describes a novel,semiautomated design methodology based on a genetic algorithm(GA)using freeform geometries for microelectromechanical systems(MEMS)devices.The proposed method can design MEMS devices comprising freeform geometries and optimize such MEMS devices to provide high sensitivity,large bandwidth,and large fabrication tolerances.The proposed method does not require much computation time or memory.The use of freeform geometries allows more degrees of freedom in the design process,improving the diversity and performance of MEMS devices.A MEMS accelerometer comprising a mechanical motion amplifier is presented to demonstrate the effectiveness of the design approach.Experimental results show an improvement in the product of sensitivity and bandwidth by 100%and a sensitivity improvement by 141%compared to the case of a device designed with conventional orthogonal shapes.Furthermore,excellent immunities to fabrication tolerance and parameter mismatch are achieved.展开更多
Investigation on how nature produces natural compounds with chemical and biological diversity at the genetic level offers inspiration for the discovery of new natural products and even their biological targets.The pol...Investigation on how nature produces natural compounds with chemical and biological diversity at the genetic level offers inspiration for the discovery of new natural products and even their biological targets.The polyketide rumbrin(1)is a lipid peroxide production and calcium accumulation inhibitor,which contains a chlorinated pyrrole moiety that is a rare chemical feature in fungal natural products.Here,we identify the biosynthetic gene cluster(BGC)rum of 1 and its isomer 12E-rumbrin(2)from Auxarthron umbrinum DSM3193,and elucidate their biosynthetic pathway based on heterolo-gous expression,chemical complementation,and isotopic labeling.We show that rumbrins are assembled by a highly reducing polyketide synthase(HRPKS)that uniquely incorporates a proline-derived pyrrolyl-CoA starer unit,and followed by methylation and chlorination.Sequent precursor directed biosynthesis was able to yield a group of rumbrin analogues.Remarkably,inspired by the presence of a human immunodeficiency virus(HIV)-Nef associated gene in the rum cluster,we predicted and pharmacologically demonstrated rumbrins as potent inhibitors of HIV at the nanomolar level.This work enriches the recognition of unconventional starter units of fungal PKSs and provides a new strategy for genome mining-guided drug discovery.展开更多
This paper describes a novel electrostatically actuated microgripper with freeform geometries designed by a genetic algorithm.This new semiautomated design methodology is capable of designing near-optimal MEMS devices...This paper describes a novel electrostatically actuated microgripper with freeform geometries designed by a genetic algorithm.This new semiautomated design methodology is capable of designing near-optimal MEMS devices that are robust to fabrication tolerances.The use of freeform geometries designed by a genetic algorithm significantly improves the performance of the microgripper.An experiment shows that the designed microgripper has a large displacement(91.5μm)with a low actuation voltage(47.5 V),which agrees well with the theory.The microgripper has a large actuation displacement and can handle micro-objects with a size from 10 to 100μm.A grasping experiment on human hair with a diameter of 77μm was performed to prove the functionality of the gripper.The result confirmed the superior performance of the new design methodology enabling freeform geometries.This design method can also be extended to the design of many other MEMS devices.展开更多
Fungal genomes carry many gene clusters seemingly capable of natural products biosynthesis,yet most clusters remain cryptic or down-regulated. Genome mining revealed an unconventional paraherquonin-like meroterpenoid ...Fungal genomes carry many gene clusters seemingly capable of natural products biosynthesis,yet most clusters remain cryptic or down-regulated. Genome mining revealed an unconventional paraherquonin-like meroterpenoid biosynthetic gene cluster in the chromosome of Neosartorya glabra.The cryptic or down-regulated pathway was activated by constitutive expression of pathway-specific regulator gene ber A encoded within ber biosynthetic gene cluster. Chemical analysis of mutant Ng-OE:ber A extracts enabled the isolation of four berkeleyacetal congeners, in which two of them are new. On the basis of careful bioinformatic analysis of the coding enzymes in the ber gene cluster, the biosynthetic pathway of berkeleyacetals was proposed. These results indicate that this approach would be valuable for discovery of novel natural products and will accelerate the exploitation of prodigious natural products in filamentous fungi.展开更多
Esophageal squamous cell carcinoma （ESCC） has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exon...Esophageal squamous cell carcinoma （ESCC） has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional sam- ples using Sanger sequencing. Whole-genomc SNP arrays were employed to detect copy number alteration （CNA） and loss of heterozygosity （LOH） in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations （NSSMs） in 102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology （GO） analysis. Tumor genomes with TP53 mutations were signifi- cantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B （30.9%）, amplification of 1 1q13.3 covering CCND1 （30.9%）, and TP53 point mutation （50.9%） occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC. Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p 11.2, and 3p 12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes. These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting.展开更多
Dynamic performance has long been critical for micro-electro-mechanical system(MEMS)devices and is significantly affected by damping.Different structural vibration conditions lead to different damping effects,includin...Dynamic performance has long been critical for micro-electro-mechanical system(MEMS)devices and is significantly affected by damping.Different structural vibration conditions lead to different damping effects,including border and amplitude effects,which represent the effect of gas flowing around a complicated boundary of a moving plate and the effect of a large vibration amplitude,respectively.Conventional models still lack a complete understanding of damping and cannot offer a reasonably good estimate of the damping coefficient for a case with both effects.Expensive efforts have been undertaken to consider these two effects,yet a complete model has remained elusive.This paper investigates the dynamic performance of vibrated structures via theoretical and numerical methods simultaneously,establishing a complete model in consideration of both effects in which the analytical expression is given,and demonstrates a deviation of at least threefold lower than current studies by simulation and experimental results.This complete model is proven to successfully characterize the squeeze-film damping and dynamic performance of oscillators under comprehensive conditions.Moreover,a series of simulation models with different dimensions and vibration statuses are introduced to obtain a quick-calculating factor of the damping coefficient,thus offering a previously unattainable damping design guide for MEMS devices.展开更多
To the Editor： Out-of-hospital cardiac arrest （OHCA） of cardiac origin is one of the leading causes of death in the industrialized world. The American Heart Association recommended patients who have been successful...To the Editor： Out-of-hospital cardiac arrest （OHCA） of cardiac origin is one of the leading causes of death in the industrialized world. The American Heart Association recommended patients who have been successfully resuscitated from OHCA and whose initial electrocardiogram （ECG） showing ST-segment elevation myocardial infarction （STEMI） should undergo emergent cardiac catheterization with the intent to identify and revascularize the culprit lesion by percutmleous intervention （PCI） when clinically applicable. However, few recent retrospective studies and prospective registries observed a beneficial effect of emergency coronary angiography and PCI on the outcome of resuscitated patients with OHCA.展开更多
Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using...Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clocklike mutational processes,and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles.Notably,signature C,characterized by C>T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6%of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites;and individuals’genetic background may also influence their postzygotic mutation profiles.展开更多
Objective: Peptidyl alkaloids, a series of important natural products can be assembled by fungal nonribosomal peptide synthetases(NRPSs). However, many of the NRPSs associated gene clusters are silent under laboratory...Objective: Peptidyl alkaloids, a series of important natural products can be assembled by fungal nonribosomal peptide synthetases(NRPSs). However, many of the NRPSs associated gene clusters are silent under laboratory conditions, and the traditional chemical separation yields are low. In this study, we aim to discovery and efficiently prepare fungal peptidyl alkaloids assembled by fungal NRPSs.Methods: Bioinformatics analysis of gene cluster containing NRPSs from the genome of Penicillium thymicola, and heterologous expression of the putative gene cluster in Aspergillus nidulans were performed.Isolation, structural identification, and biological evaluation of the product from heterologous expression were carried out.Results: The putative tri-modular NRPS Anc A was heterologous-expressed in A. nidulans to give anacine(1) with high yield, which showed moderate and selective cytotoxic activity against A549 cell line.Conclusion: Heterologous expression in A. nidulans is an efficient strategy for mining fungal peptidyl alkaloids.展开更多
基金supported by the Key-Area Research and Development Program of Guangdong Province,Research on the Method of Heat Preservation and Heating for the Drilling System of Polar Offshore Drilling Platform (No.2020B1111010001).
文摘This study investigates the heat dissipation mechanism of the insulation layer and other plane insulation layers in the polar drilling rig system.Combining the basic theory of heat transfer with the environmental requirements of polar drilling operations and the characteristics of polar drilling processes,we analyze the factors that affect the insulation effect of the drilling rig system.These factors include the thermal conductivity of the insulation material,the thickness of the insulation layer,ambient temperature,and wind speed.We optimize the thermal insulation material of the polar drilling rig system using a steady-state method to measure solid thermal conductivity.By analyzing the distribution of temperature in space after heating,we optimize the distribution and air outlet angle of the heater using Fluent hydrodynamics software.The results demonstrate that under polar conditions,polyisocyanurate with stable thermodynamic properties is selected as the thermal insulation material.The selection of thermal insulation material and thickness significantly affects the thermal insulation effect of the system but has little effect on its heating effect.Moreover,when the air outlet angle of the heater is set to 32.5°,the heating efficiency of the system can be effectively improved.According to heat transfer equations and heat balance theory,we determine that the heating power required for the system to reach 5°C is close to numerical simulation.
基金Supported by Nanjing Foundation for Development of Science and Technology,No.ZKX14018
文摘BACKGROUND Venous thrombosis(VT) is one of the minor complications of pacemaker lead extraction. It is often found due to the swelling of the limbs after the extraction. It is easy to be neglected or even misdiagnosed in the absence of typical clinical symptoms. The incidence, risk factors, and long-term impact of this complication are still unclear. Herein, we report a case of deep VT caused by transvenous lead extraction, which is easily misdiagnosed.CASE SUMMARY A 66-year-old woman underwent a pacemaker lead extraction at our hospital because of a pacemaker pocket infection. After the extraction, she began to experience intermittent fever accompanied by sweating. The highest body temperature recorded was 37.9℃. Additionally, she reported migratory pain that made her uncomfortable. The pain was mistakenly thought to be caused by operation trauma. At first, the pain radiated from the left chest to the mandible.Then, the pain in the left chest was alleviated, but pain in the left neck and throat appeared. Finally, the pain was confined to the mandible and a submandibular mass was palpated with no other abnormalities upon physical examination.Computed tomography venography and angiography finally indicated that the fever and pain were the symptoms of thrombophlebitis caused by lead extraction.The patient was then treated with rivaroxaban for more than three months and has shown no symptoms since she left the hospital.CONCLUSION The possibility of thrombosis should be considered when pain and recurrent fever occur after pacemaker lead extraction.
基金supported by grants from Municipal Medical Science Technology Development Foundation of Nanjing (No. YKK17085)
文摘The post-infarcted related ventricular tachycardia (VT) is considered associated with increase in mortality or sudden cardiac death (SCD). Implantable cardioverter defibrillation (ICD) has been the standard therapy for the first or second prevention of SCD after myocardial infarction (MI). Incessant VT, which has poor response to anti-arrhythmic drugs and can cause repetitive ICD shock, is usually a tough problem in clinical practice. According to the guideline, incessant infracted related VT could be treated with catheter ablation.[1] Herein we reported a case of refractory scar-induced VT accompanied with thrombus in the left chamber, which was full with ups and downs during the therapy.
基金a grant from the Health Commission of Hubei Province Scientific Research Project(No.WJ2019M118).
文摘Objective The aim of this study was to construct a prognostic model of esophageal adenocarcinoma(EAC)based on immune-related long noncoding RNAs(immune-related lncRNAs)and identify prognostic biomarkers using the Cancer Genome Atlas(TCGA)database.Methods Whole genomic mRNA expression and clinical data of esophageal adenocarcinoma were obtained from the TCGA database.The software Strawberry Perl,R and R packets were used to identify the immune-related genes and lncRNAs of esophageal adenocarcinoma,and for data processing and analysis.The differentially expressed lncRNAs were detected while comparing esophageal adenocarcinoma and normal tissue samples.The key immune-related lncRNAs were screened using lasso regression analysis and univariate cox regression analysis,and used to construct the prognostic model using multivariate cox regression analysis.To evaluate the accuracy of the risk prognostic model,all esophageal adenocarcinomas were divided into high-risk and low-risk groups according to the median risk score,after which Kaplan-Meier(K-M)survival curves,operating characteristic(ROC)curve and independent prognostic analysis of clinical traits were created.In addition,statistically significant immune-related lncRNAs and potential prognostic biomarkers were identified using the prognostic model and multifactor cox regression analysis for k-m survival analysis.Results A total of 1322 differentially expressed immune-related lncRNAs were identified,28 of which were associated with prognosis via univariate cox regression analysis.In addition,K-M survival analysis showed that the total survival time of the higher risk group was significantly shorter than that of the lower risk group(P=1.063e-10).The area under the ROC curve of 5-year total survival rate was 0.90.The risk score showed independent prognostic risk for esophageal adenocarcinoma via single factor and multifactorial independent prognostic analyses.In addition,the HR and 95%CI of each key immune-related lncRNA were calculated using multivariate Cox regression.Using k-m survival analysis,we found that 5 out of 12 key significant immune-related lncRNAs had independent prognostic value[AL136115.1(P=0.006),AC079684.1(P=0.008),AC07916394.1(P=0.0386),AC087620.1(P=0.041)and MIRLET7BHG(P=0.044)].Conclusion The present study successfully constructed a prognostic model of esophageal adenocarcinoma based on the TCGA database,with moderate predictive accuracy.The model consisted of the expression level of 12 immune-related lncRNAs.Furthermore,the study identified one favorable prognostic biomarker,MIRLET7BHG,and four poor prognostic biomarkers(AL136115.1,AC079684.1,AC016394.1,and AC087620.1).
基金financially supported by the National Natural Science Foundation of China(No.52001023)the Special Fund for Science and Technology Project of Guangdong Province(No.SDZX2020008)the Key Research and Development Program of Shandong Province,China(No.2019JZZY020238).
文摘The comparative study of submerged arc welding(SAW)and laser hybrid welding(LHW)was carried out for a 690 MPa high strength steel with thickness of 20 mm.Microstructure and ductile–brittle transition temperature(DBTT)evolution in welded zone were elucidated from the aspect of crystallographic structure,particularly,digitization and visualization of 24 variants.The impact toughness of each micro zone in LHW joint is better than that of SAW,in which the DBTT of equivalent fusion line and heat-affected zone(HAZ)can reach−70 and−80℃,while that of SAW is only−50℃.LHW technology induces narrowing of the HAZ and refining of the microstructure obtained in weld metal and HAZ.Meanwhile,the austenite grain size and transformation driving force in the coarse grained heat-affected zone(CGHAZ)are reduced and increased,respectively.It makes variant selection mechanism occurring in CGHAZ of LHW dominate by close-packed plane grouping,which promotes lath bainite formation with high density of high angle grain boundary,especially block boundary dominated by V1/V2 pair.While for SAW,the lower transformation driving force inferred from the large amount of retained austenite in CGHAZ induces Bain grouping of variants,and thus triggers the brittle crack propagating straightly in granular bainite,resulting in lower impact toughness and higher DBTT.
基金supported financially by the National Key Research and Development Program of China(2018YFA0901900)the CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-1-010,2017-I2M-4-004)+1 种基金Fundamental Research Funds for the Central Universities(2017PT35001)supported by the Drug Innovation Major Project(2018ZX09711001-008-001)
文摘Endophytic fungi are promising producers of bioactive small molecules.Bioinformatic analysis of the genome of an endophytic fungus Penicillium dangeardii revealed 43 biosynthetic gene clusters,exhibited its strong ability to produce numbers of secondary metabolites.However,this strain mainly produce rubratoxins alone with high yield in varied culture conditions,suggested most gene clusters are silent.Efforts for mining the cryptic gene clusters in P.dangeardii,including epigenetic regulation and one-strain-many-compounds(OSMAC)approach were failed probably due to the high yield of rubratoxins.A metabolic shunting strategy by deleting the key gene for rubratoxins biosynthesis combining with optimization of culture condition successfully activated multiple silent genes encoding for other polyketide synthases(PKSs),and led to the trace compounds detectable.As a result,a total of 23 new compounds including azaphilone monomers,dimers,turimers with unprecedented polycyclic bridged heterocycle and spiral structures,as well as siderophores were identified.Some compounds showed significant cytotoxicities,anti-inflammatory or antioxidant activities.The attractive dual PKS s gene clusters for azaphilones biosynthesis were mined by bioinformatic analysis and overexpression of a pathway specific transcription factor.Our work therefor provides an efficient approach to mine the chemical diversity of endophytic fungi.
基金supported financially by National Natural Science Foundation of China (Nos. 21502233 and 81522043)CAMS Initiative for Innovative Medicine (CAMS-I2M-1-010)+1 种基金the PUMC Youth Fund (33320140175)the State Key Laboratory Fund for Excellent Young Scientists to Youcai Hu (GTZB201401)
文摘Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in Calcarisporium arbuscula had led to pleiotropic activation and overexpression of more than 75% of the biosynthetic genes and isolation of ten compounds. Further investigation of the crude extract of C. arbuscula Δhda A strain resulted in the isolation of twelve new diterpenoids including three cassanes(1-3), one cleistanthane(4), six pimaranes(5-10), and two isopimaranes(11 and 12) along with two know cleistanthane analogues. Their structures were elucidated by extensive NMR spectroscopic data analysis. Compounds 2 and 4 showed potent inhibitory effects on the expression of MMP1 and MMP2(matrix metalloproteinases family) in human breast cancer(MCF-7) cells.
基金This work was funded by the Science Challenge Project under Grant TZ2016006-0502-02the Natural Science Foundation of Hubei Province under Grant 2019CFB108.
文摘This paper describes a novel,semiautomated design methodology based on a genetic algorithm(GA)using freeform geometries for microelectromechanical systems(MEMS)devices.The proposed method can design MEMS devices comprising freeform geometries and optimize such MEMS devices to provide high sensitivity,large bandwidth,and large fabrication tolerances.The proposed method does not require much computation time or memory.The use of freeform geometries allows more degrees of freedom in the design process,improving the diversity and performance of MEMS devices.A MEMS accelerometer comprising a mechanical motion amplifier is presented to demonstrate the effectiveness of the design approach.Experimental results show an improvement in the product of sensitivity and bandwidth by 100%and a sensitivity improvement by 141%compared to the case of a device designed with conventional orthogonal shapes.Furthermore,excellent immunities to fabrication tolerance and parameter mismatch are achieved.
基金supported financially by the National Key Research and Development Program of China(2018YFA0901900)the CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2021-I2M-1-029, China)
文摘Investigation on how nature produces natural compounds with chemical and biological diversity at the genetic level offers inspiration for the discovery of new natural products and even their biological targets.The polyketide rumbrin(1)is a lipid peroxide production and calcium accumulation inhibitor,which contains a chlorinated pyrrole moiety that is a rare chemical feature in fungal natural products.Here,we identify the biosynthetic gene cluster(BGC)rum of 1 and its isomer 12E-rumbrin(2)from Auxarthron umbrinum DSM3193,and elucidate their biosynthetic pathway based on heterolo-gous expression,chemical complementation,and isotopic labeling.We show that rumbrins are assembled by a highly reducing polyketide synthase(HRPKS)that uniquely incorporates a proline-derived pyrrolyl-CoA starer unit,and followed by methylation and chlorination.Sequent precursor directed biosynthesis was able to yield a group of rumbrin analogues.Remarkably,inspired by the presence of a human immunodeficiency virus(HIV)-Nef associated gene in the rum cluster,we predicted and pharmacologically demonstrated rumbrins as potent inhibitors of HIV at the nanomolar level.This work enriches the recognition of unconventional starter units of fungal PKSs and provides a new strategy for genome mining-guided drug discovery.
基金This research was funded by the Science Challenge Project,grant no.TZ2016006-0502-02the National Key Research and Development Program of China,grant no.2021YFB3201603。
文摘This paper describes a novel electrostatically actuated microgripper with freeform geometries designed by a genetic algorithm.This new semiautomated design methodology is capable of designing near-optimal MEMS devices that are robust to fabrication tolerances.The use of freeform geometries designed by a genetic algorithm significantly improves the performance of the microgripper.An experiment shows that the designed microgripper has a large displacement(91.5μm)with a low actuation voltage(47.5 V),which agrees well with the theory.The microgripper has a large actuation displacement and can handle micro-objects with a size from 10 to 100μm.A grasping experiment on human hair with a diameter of 77μm was performed to prove the functionality of the gripper.The result confirmed the superior performance of the new design methodology enabling freeform geometries.This design method can also be extended to the design of many other MEMS devices.
基金supported financially by the National Natural Science Foundation of China (No. 81522043)CAMS Initiative for Innovative Medicine (2017-I2M-4-004)the Thousand Young Talents Program of China
文摘Fungal genomes carry many gene clusters seemingly capable of natural products biosynthesis,yet most clusters remain cryptic or down-regulated. Genome mining revealed an unconventional paraherquonin-like meroterpenoid biosynthetic gene cluster in the chromosome of Neosartorya glabra.The cryptic or down-regulated pathway was activated by constitutive expression of pathway-specific regulator gene ber A encoded within ber biosynthetic gene cluster. Chemical analysis of mutant Ng-OE:ber A extracts enabled the isolation of four berkeleyacetal congeners, in which two of them are new. On the basis of careful bioinformatic analysis of the coding enzymes in the ber gene cluster, the biosynthetic pathway of berkeleyacetals was proposed. These results indicate that this approach would be valuable for discovery of novel natural products and will accelerate the exploitation of prodigious natural products in filamentous fungi.
基金supported by the National Basic Research Program of China from the National Ministry of Science and Technology(973 Program)to YK(Grant No.2011CB504300)and to HC(Grant No.2012CB910800)the National Natural Science Foundation of China(Grant No.30930102)to YK+3 种基金the National High-tech R&D Program of China(863 ProgramGrant No.2012AA022502)Key Research Program of the Chinese Academy of Sciences of China(Grant No.KJZD-EW-L06-2)to CZthe Open Fund of MOE Key Laboratory of Carcinogenesis and Translational Research(Grant No.2014KAIFANG-4)to JB
文摘Esophageal squamous cell carcinoma （ESCC） has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional sam- ples using Sanger sequencing. Whole-genomc SNP arrays were employed to detect copy number alteration （CNA） and loss of heterozygosity （LOH） in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations （NSSMs） in 102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology （GO） analysis. Tumor genomes with TP53 mutations were signifi- cantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B （30.9%）, amplification of 1 1q13.3 covering CCND1 （30.9%）, and TP53 point mutation （50.9%） occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC. Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p 11.2, and 3p 12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes. These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting.
基金support from programs supported by the Ningbo Natural Science Foundation(No.202003N4062)the National Natural Science Foundation of China(NSFC,No.62004166)+2 种基金the Fundamental Research Funds for the Central Universities(No.31020190QD027)the Natural Science Basic Research Program of Shaanxi(Program No.2020JQ-199)the China National Postdoctoral Program for Innovative Talents(No.BX20200279).
文摘Dynamic performance has long been critical for micro-electro-mechanical system(MEMS)devices and is significantly affected by damping.Different structural vibration conditions lead to different damping effects,including border and amplitude effects,which represent the effect of gas flowing around a complicated boundary of a moving plate and the effect of a large vibration amplitude,respectively.Conventional models still lack a complete understanding of damping and cannot offer a reasonably good estimate of the damping coefficient for a case with both effects.Expensive efforts have been undertaken to consider these two effects,yet a complete model has remained elusive.This paper investigates the dynamic performance of vibrated structures via theoretical and numerical methods simultaneously,establishing a complete model in consideration of both effects in which the analytical expression is given,and demonstrates a deviation of at least threefold lower than current studies by simulation and experimental results.This complete model is proven to successfully characterize the squeeze-film damping and dynamic performance of oscillators under comprehensive conditions.Moreover,a series of simulation models with different dimensions and vibration statuses are introduced to obtain a quick-calculating factor of the damping coefficient,thus offering a previously unattainable damping design guide for MEMS devices.
文摘To the Editor： Out-of-hospital cardiac arrest （OHCA） of cardiac origin is one of the leading causes of death in the industrialized world. The American Heart Association recommended patients who have been successfully resuscitated from OHCA and whose initial electrocardiogram （ECG） showing ST-segment elevation myocardial infarction （STEMI） should undergo emergent cardiac catheterization with the intent to identify and revascularize the culprit lesion by percutmleous intervention （PCI） when clinically applicable. However, few recent retrospective studies and prospective registries observed a beneficial effect of emergency coronary angiography and PCI on the outcome of resuscitated patients with OHCA.
基金supported by the grants from the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB13020500)the National Natural Science Foundation of China(NSFC)(Grant Nos.91131905,31471199,and 91631304)+3 种基金the Key Research Program of Chinese Academy of Sciences(Grant No.KJZD-EW-L14 to CZ)the NSFC(Grant Nos.31440057 and 31701081 to WC)the 111 Project(Grant No.B13003 to WC and DZ)the Innovation Promotion Association of Chinese Academy of Sciences(Grant Nos.2016098 to DZ and 2019103 to AC)。
文摘Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clocklike mutational processes,and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles.Notably,signature C,characterized by C>T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6%of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites;and individuals’genetic background may also influence their postzygotic mutation profiles.
基金supported financially by the Drug Innovation Major Project (No. 2018ZX09711001-006)the CAMS Initiative for Innovative Medicine (No. 2017-I2M-4-004)。
文摘Objective: Peptidyl alkaloids, a series of important natural products can be assembled by fungal nonribosomal peptide synthetases(NRPSs). However, many of the NRPSs associated gene clusters are silent under laboratory conditions, and the traditional chemical separation yields are low. In this study, we aim to discovery and efficiently prepare fungal peptidyl alkaloids assembled by fungal NRPSs.Methods: Bioinformatics analysis of gene cluster containing NRPSs from the genome of Penicillium thymicola, and heterologous expression of the putative gene cluster in Aspergillus nidulans were performed.Isolation, structural identification, and biological evaluation of the product from heterologous expression were carried out.Results: The putative tri-modular NRPS Anc A was heterologous-expressed in A. nidulans to give anacine(1) with high yield, which showed moderate and selective cytotoxic activity against A549 cell line.Conclusion: Heterologous expression in A. nidulans is an efficient strategy for mining fungal peptidyl alkaloids.
