To mitigate the wastage of seed resources and reduce the usage of pesticides and fertilizers, seed coating agentshave gained popularity. This study employs single-factor and multi-index orthogonal experimental design ...To mitigate the wastage of seed resources and reduce the usage of pesticides and fertilizers, seed coating agentshave gained popularity. This study employs single-factor and multi-index orthogonal experimental design methodsto investigate the seed coating formula and physical properties of Tartary buckwheat. The specific effects ofeach component on Tartary buckwheat seed germination are analyzed. The findings reveal that the seed coatingagent formulated with 1.5% polyvinyl alcohol, 0.15% sodium alginate, 0.2% op-10, 0.1% polyacrylamide, 8% colorant,3% ammonium sulfate, 1% potassium dihydrogen phosphate, and 0.15% carbendazim exhibits the mosteffective coating. It demonstrates optimal physical properties and promotes seed germination efficiently. The suspensionrate of this seed coating agent reaches 91.12%, with a mere 2.13% coating shedding rate and 2.5% coatingseed rot rate. Furthermore, it achieves a germination percentage of 99.17%, which is 20.84% higher than the lowestgroup. The germination potential and index are also significantly higher than the lowest group, with anincrease of 20.84% and 26.56%, respectively. Additionally, the vitality index is 553.08, a 15.75% increase comparedto the lowest group. The application of seed coating agents helps reduce seed resource loss, increase plant numbers,and ultimately enhance agricultural yields. This finding holds practical significance in agriculturalproduction.展开更多
According to the signal processing characteristic of MIMO radars,an adaptive dwell scheduling algorithm is proposed.It is based on a novel pulse interleaving technique,which makes full use of transmitting,waiting and ...According to the signal processing characteristic of MIMO radars,an adaptive dwell scheduling algorithm is proposed.It is based on a novel pulse interleaving technique,which makes full use of transmitting,waiting and receiving durations of radar dwells.The utilization of transmitting duration is unique for MIMO radars and is realized through transmitting duration overlapping.Simulation results show that,compared with the conventional scheduling algorithm,the scheduling performance of MIMO radars can be improved effectively by the proposed algorithm,and the scheduling rule can be chosen arbitrarily when using the proposed algorithm.展开更多
Access block,known as exit block or boarding,is defined as a situation in which patients who are admitted or planned for admission remain in the emergency department(ED)as they are unable to be transferred to an inpat...Access block,known as exit block or boarding,is defined as a situation in which patients who are admitted or planned for admission remain in the emergency department(ED)as they are unable to be transferred to an inpatient unit within a reasonable time frame(no longer than 8 hours).[1,2]Access block often occurs due to insufficient hospital capacity and is a major issue in emergency medicine.[3]展开更多
Background:Epidemiological studies have shown a close association between osteoarthritis(OA)and cardiovascular disease(CVD),but reliable evidence needs to be provided.We performed a two-sample Mendelian randomization(...Background:Epidemiological studies have shown a close association between osteoarthritis(OA)and cardiovascular disease(CVD),but reliable evidence needs to be provided.We performed a two-sample Mendelian randomization(MR)study to examine the potential causal effect between OA and CVD.Methods:Exposures were self-reported OA,knee osteoarthritis(KOA),and hip osteoarthritis(HOA).The outcomes were 12 CVDs,including heart failure,atrial fibrillation,coronary artery disease,pulmonary embolism,stroke and its subtypes,myocardial infarction,coronary heart disease,and primary hypertension.All outcomes were obtained from published genomewide association studies.The inverse-variance weighted method was used as the primary MR analysis.Heterogeneity tests and sensitivity analyses were conducted to validate the accuracy of the MR results.Results:Self-reported OA increased the incidence of small vessel stroke(odds ratio[OR]=1.25,95%confidence interval[CI]:1.02–1.52,p=0.03)and primary hypertension(1.01[1.00–1.02],p<0.01).HOA increased the incidence of stroke(1.06[1.01–1.11],p=0.02)and two subtypes(cardioembolic stroke:1.12[1.02–1.23],p=0.02;ischemic stroke:1.06[1.01–1.11],p=0.03).Patients with KOA had an increased risk of heart failure(1.10[1.04–1.16],p<0.01),atrial fibrillation(1.08[1.02–1.13],p<0.01),small vessel stroke(1.21[1.06–1.39],p=0.01),and primary hypertension(1.01[1.01–1.02],p<0.01).Conclusions:Patients with OA have an increased risk of several CVDs.The causality of this relationship may have clinical implications for improving the quality of prevention and treatment.展开更多
As a novel supersonic jet technology,preheating shrouded supersonic jet was developed to deliver oxygen into molten bath efficiently and affordably.However,there has been limited research on the jet behavior and impin...As a novel supersonic jet technology,preheating shrouded supersonic jet was developed to deliver oxygen into molten bath efficiently and affordably.However,there has been limited research on the jet behavior and impingement characteristics of preheating shrouded supersonic jets.Computational fluid dynamics（CFD）models were established to investigate the effects of main and shrouding gas temperatures on the characteristics of flow field and impingement of shrouded supersonic jet.The preheating shrouded supersonic jet behavior was simulated and measured by numerical simulation and jet measurement experiment respectively.The influence of preheating shrouded supersonic jet on gas jet penetration and fluid flow in liquid bath was calculated by the CFD model which was validated against water model experiments.The results show that the uptrend of the potential core length of shrouded supersonic jet would be accelerated with increasing the main and shrouding gas temperatures.Also,preheating supersonic jets demonstrated significant advantages in penetrating and stirring the liquid bath.展开更多
During a study on the diversity of ciliated protists in Lake Weishan Wetland,the largest wetland in northern China,four epibiotic sessilid peritrichs were isolated from aquatic host animals.Two of them,i.e.,Epistylis ...During a study on the diversity of ciliated protists in Lake Weishan Wetland,the largest wetland in northern China,four epibiotic sessilid peritrichs were isolated from aquatic host animals.Two of them,i.e.,Epistylis cambari Kellicott,1885 and Epistylis lwof Fauré-Fremiet,1943,were known species whereas the other two,i.e.,Parapiosoma typicum gen.nov.,sp.nov.and Orborhabdostyla gracilis sp.nov.,are new to science.The new genus Parapiosoma gen.nov.is characterized by its branched non-contractile stalk,everted peristomial lip,obconical macronucleus and transverse silverlines.Two species are assigned to the new genus,namely Parapiosoma typicum sp.nov.and Parapiosoma gasterostei(Fauré-Fremiet,1905)comb.nov.Morphologically,P.typicum sp.nov.is recognized by its goblet-shaped zooids,single-layered peristomial lip,dichotomously branched stalk,and infundibular polykinety 3(P3)containing three equal-length rows.Orborhabdostyla gracilis sp.nov.is characterized by its slender zooid,curved macronucleus,and three equal-length rows in infundibular P3.Improved diagnoses and redescriptions of E.cambari and E.lwof are provided including,for the frst time,data on the ciliature of E.cambari.Phylogenetic analyses based on SSU rDNA,ITS1-5.8S rDNA-ITS2,and LSU rDNA sequence data strongly support the assertion that the family Epistylididae comprises morphospecies with diferent evolutionary lineages and indicate that Parapiosoma gen.nov.may represent a new taxon at family level.展开更多
The study of prehistoric hunter-gatherer subsistence strategies on the Tibetan Plateau is important for understanding the mechanisms and processes of human adaption to high altitude environments.But to date,only a few...The study of prehistoric hunter-gatherer subsistence strategies on the Tibetan Plateau is important for understanding the mechanisms and processes of human adaption to high altitude environments.But to date,only a few Paleolithic sites have been found on the Tibetan Plateau with clear stratigraphy and reliable dating.These sites are mainly distributed in the Qinghai Lake Basin on the northeastern part of the plateau,and the sporadic fauna and flora remains excavated provide limited information about the subsistence strategies of hunter-gatherers.In 2014,relatively abundant animal remains were unearthed in the Lower Cultural Layer (LCL,15400-13100 cal yr BP) of the"151 site"located in the Qinghai Lake Basin,providing important information about human subsistence strategies on the Tibetan Plateau during the Last Deglaciation.Zooarchaeological analysis of these faunal remains indicates that hunter-gatherers at the"151 site"mainly targeted large ungulates of Bos and wild horse/ass,and only brought back the most nutritious parts of animal carcasses including upper and intermediate limb bones,heads,and trunks (ribs and vertebrae).People then processed and consumed the carcasses around single hearths.Our comprehensive analyses of contemporaneous sites in the Qinghai Lake Basin show that a subsistence strategy involving opportunistic hunting of ungulates,high mobility,and short occupation of campsites was used by terminal Pleistocene huntergatherers to adapt to the high-altitude environment on the Tibetan Plateau.This subsistence strategy may have been a first step of gradual hunter-gatherer adaptation to the extreme conditions on the Tibetan Plateau after the Last Glacial Maximum,and laid the foundation for the widespread distribution of hunter-gatherers on the plateau during the Holocene.展开更多
Ubiquitin specific peptidase 28(USP28) is closely associated to the occurrence and development of various malignancies, and thus has been validated as a promising therapeutic target for cancer therapy. To date,only fe...Ubiquitin specific peptidase 28(USP28) is closely associated to the occurrence and development of various malignancies, and thus has been validated as a promising therapeutic target for cancer therapy. To date,only few USP28 inhibitors with moderate inhibitory activity have been reported, highly potent and selective USP28 inhibitors with new chemotypes remain to be discovered for pathologically investigating the roles of deubiquitinase. In this current study, we reported the synthesis and biological evaluation of new [1,2,3]triazolo[4,5-d]pyrimidine derivatives as potent USP28 inhibitors. Especially, compound 19 potently inhibited USP28(IC50=1.10 ± 0.02 μmol/L, Kd=40 nmol/L), showing selectivity over USP7 and LSD1(IC50> 100 μmol/L). Compound 19 was cellularly engaged to USP28 in gastric cancer cells. Compound 19 reversibly bound to USP28 and directly affected its protein levels, thus inhibiting the proliferation, cell cycle at S phase, and epithelial-mesenchymal transition(EMT) progression in gastric cancer cell lines. Docking studies were performed to rationalize the potency of compound 19. Collectively, compound 19 could serve as a new tool compound for the development of new USP28 inhibitors for exploring the roles of deubiquitinase in cancers.展开更多
The ciliate Tetrahymena thermophila has been a powerful model system for molecular and cellular biology.However,some investigations have been limited due to the incomplete closure and sequencing of the macronuclear ge...The ciliate Tetrahymena thermophila has been a powerful model system for molecular and cellular biology.However,some investigations have been limited due to the incomplete closure and sequencing of the macronuclear genome assembly,which for many years has been stalled at 1,158 scaffolds,with large sections of unknown sequences(available in Tetrahymena Genome Database,TGD,http://ciliate.org/).Here we completed the first chromosome-level Tetrahymena macronuclear genome assembly,with approximately 300×long Single Molecule,Real-Time reads of the wild-type SB210 cells—the reference strain for the initial macronuclear genome sequencing project.All 181 chromosomes were capped with two telomeres and gaps were entirely closed.The completed genome shows significant improvements over the current assembly(TGD 2014)in both chromosome structure and sequence integrity.The majority of previously identified gene models shown in TGD were retained,with the addition of 36 new genes and 883 genes with modified gene models.The new genome and annotation were incorporated into TGD.This new genome allows for pursuit in some underexplored areas that were far more challenging previously;two of them,genome scrambling and chromosomal copy number,were investigated in this study.We expect that the completed macronuclear genome will facilitate many studies in Tetrahymena biology,as well as multiple lines of research in other eukaryotes.展开更多
Coherent jets are widely used in electric are furnace （EAF） steelmaking to increase the oxygen utilization and chemical reaction rates. However, the influence of fuel gas combustion on jet behavior is not fully unde...Coherent jets are widely used in electric are furnace （EAF） steelmaking to increase the oxygen utilization and chemical reaction rates. However, the influence of fuel gas combustion on jet behavior is not fully understood yet. The flow and combustion characteristics of a coherent jet were thus investigated at steelmaking temperature using Fluent software, and a detailed chemical kinetic reaction mecha- nism was used in the combustion reaction model. The axial velocity and total temperature of the supersonic jet were measured via hot state experiments. The simulation results were compared with the experimental data and the empirical jet model proposed by Ito and Muchi and good consistency was obtained. The research results indicated that the potential core length of the coherent jet can be prolonged by optimizing the combustion effect of the fuel gas. Besides, the behavior of the supersonic jet in the subsonic section was also investigated, as it is an important factor for controlling the position of the oxygen lance. The investigation indicated that the attenuation of the coherent jet is more notable than that of the conventional jet in the subsonic section.展开更多
Epigenetic research focuses on heritable changes beyond the DNA sequence, which has led to a revolution in biologicalstudies and benefits in many other fields. The well-known model ciliate, Tetrahymena thermophila off...Epigenetic research focuses on heritable changes beyond the DNA sequence, which has led to a revolution in biologicalstudies and benefits in many other fields. The well-known model ciliate, Tetrahymena thermophila offers a unique system forepigenetic studies due to its nuclear dimorphism and special mode of sexual reproduction (conjugation), as well as abundantgenomic resources and genetic tools. In this paper, we summarize recent progress made by our research team and collaboratorsin understanding epigenetic mechanisms using Tetrahymena. This includes: (1) providing the first genome-wide basepair-resolution map of DNA N6-methyladenine (6mA) and revealed it as an integral part of the chromatin landscape;(2)dissecting the relative contribution of cis・ and trans- elements to nucleosome distribution by exploring the unique nucleardimorphism of Tetrahymena, (3) demonstrating the epigenetic controls of RNAi-dependent Polycomb repression pathwayson transposable elements, and (4) identifying a new histone monomethyltransferase, TXR1 (Tetrahymena Trithorax 1), thatfacilitates replication elongation through 让s substrate histone H3 lysine 27 monomethylation (H3K27mel).展开更多
The morphology and divisional morphogenesis in a Chinese population of Neobakuella aenigmatica Moon et al.,2019 are reinvestigated.The body size,number and arrangement of parabuccal cirri and development of nuclear no...The morphology and divisional morphogenesis in a Chinese population of Neobakuella aenigmatica Moon et al.,2019 are reinvestigated.The body size,number and arrangement of parabuccal cirri and development of nuclear nodules in this population are discussed in comparison with closely related genera.The 18S rRNA gene sequence of the Chinese population is identical to that of a Korean population,supporting a distant relationship between N.aenigmatica and the cluster of N.flava and Apobakuella fuse a.We deduce that this may be caused by the differences in the pattern of the parabuccal cirri and the number of parabuccal rows which are important for the phylogeny of Bakuella-like,species.展开更多
Denisovans,well known for their high-coverage genetic sequences,are considered to be a new human species genetically distinct from Neanderthals and modern humans[1].As a close sister group of Neanderthals,Denisovans n...Denisovans,well known for their high-coverage genetic sequences,are considered to be a new human species genetically distinct from Neanderthals and modern humans[1].As a close sister group of Neanderthals,Denisovans not only interbred w让h Neanderthals[2],but they also contributed genetically to extant humans,including modern populations in parts of Oceania and Asia,aboriginal Americans and high-alt让ude modern Tibetans[3-5].展开更多
基金the Sichuan Science and Technology Program(2023NSFSC0214)China Agriculture Research System(CARS-07-B-1)+1 种基金National Natural Sciences Foundation of China(Nos.3230185031771716).
文摘To mitigate the wastage of seed resources and reduce the usage of pesticides and fertilizers, seed coating agentshave gained popularity. This study employs single-factor and multi-index orthogonal experimental design methodsto investigate the seed coating formula and physical properties of Tartary buckwheat. The specific effects ofeach component on Tartary buckwheat seed germination are analyzed. The findings reveal that the seed coatingagent formulated with 1.5% polyvinyl alcohol, 0.15% sodium alginate, 0.2% op-10, 0.1% polyacrylamide, 8% colorant,3% ammonium sulfate, 1% potassium dihydrogen phosphate, and 0.15% carbendazim exhibits the mosteffective coating. It demonstrates optimal physical properties and promotes seed germination efficiently. The suspensionrate of this seed coating agent reaches 91.12%, with a mere 2.13% coating shedding rate and 2.5% coatingseed rot rate. Furthermore, it achieves a germination percentage of 99.17%, which is 20.84% higher than the lowestgroup. The germination potential and index are also significantly higher than the lowest group, with anincrease of 20.84% and 26.56%, respectively. Additionally, the vitality index is 553.08, a 15.75% increase comparedto the lowest group. The application of seed coating agents helps reduce seed resource loss, increase plant numbers,and ultimately enhance agricultural yields. This finding holds practical significance in agriculturalproduction.
基金supported by the National Natural Science Foundation of China(6110117161032010)
文摘According to the signal processing characteristic of MIMO radars,an adaptive dwell scheduling algorithm is proposed.It is based on a novel pulse interleaving technique,which makes full use of transmitting,waiting and receiving durations of radar dwells.The utilization of transmitting duration is unique for MIMO radars and is realized through transmitting duration overlapping.Simulation results show that,compared with the conventional scheduling algorithm,the scheduling performance of MIMO radars can be improved effectively by the proposed algorithm,and the scheduling rule can be chosen arbitrarily when using the proposed algorithm.
基金supported by the Project of Science and Technology Commission of Jiading,Shanghai(JDKW-2016-W03)the Scientific Research Projects of the Shanghai Municipal Health Commission for Youths(20204Y0016)+1 种基金the National Natural Science Foundation of China(72174041)。
文摘Access block,known as exit block or boarding,is defined as a situation in which patients who are admitted or planned for admission remain in the emergency department(ED)as they are unable to be transferred to an inpatient unit within a reasonable time frame(no longer than 8 hours).[1,2]Access block often occurs due to insufficient hospital capacity and is a major issue in emergency medicine.[3]
基金The National Natural Science Foundation of China,Grant/Award Number:82001740Natural Science Foundation of Shanxi Province,Grant/Award Number:202203021221269。
文摘Background:Epidemiological studies have shown a close association between osteoarthritis(OA)and cardiovascular disease(CVD),but reliable evidence needs to be provided.We performed a two-sample Mendelian randomization(MR)study to examine the potential causal effect between OA and CVD.Methods:Exposures were self-reported OA,knee osteoarthritis(KOA),and hip osteoarthritis(HOA).The outcomes were 12 CVDs,including heart failure,atrial fibrillation,coronary artery disease,pulmonary embolism,stroke and its subtypes,myocardial infarction,coronary heart disease,and primary hypertension.All outcomes were obtained from published genomewide association studies.The inverse-variance weighted method was used as the primary MR analysis.Heterogeneity tests and sensitivity analyses were conducted to validate the accuracy of the MR results.Results:Self-reported OA increased the incidence of small vessel stroke(odds ratio[OR]=1.25,95%confidence interval[CI]:1.02–1.52,p=0.03)and primary hypertension(1.01[1.00–1.02],p<0.01).HOA increased the incidence of stroke(1.06[1.01–1.11],p=0.02)and two subtypes(cardioembolic stroke:1.12[1.02–1.23],p=0.02;ischemic stroke:1.06[1.01–1.11],p=0.03).Patients with KOA had an increased risk of heart failure(1.10[1.04–1.16],p<0.01),atrial fibrillation(1.08[1.02–1.13],p<0.01),small vessel stroke(1.21[1.06–1.39],p=0.01),and primary hypertension(1.01[1.01–1.02],p<0.01).Conclusions:Patients with OA have an increased risk of several CVDs.The causality of this relationship may have clinical implications for improving the quality of prevention and treatment.
基金Item Sponsored by National Natural Science Foundation of China(51474024,51334001)National Key Technology Research and Development Program of the 12th Five-year Plan of China(12FYP 2015BAF03B01)
文摘As a novel supersonic jet technology,preheating shrouded supersonic jet was developed to deliver oxygen into molten bath efficiently and affordably.However,there has been limited research on the jet behavior and impingement characteristics of preheating shrouded supersonic jets.Computational fluid dynamics（CFD）models were established to investigate the effects of main and shrouding gas temperatures on the characteristics of flow field and impingement of shrouded supersonic jet.The preheating shrouded supersonic jet behavior was simulated and measured by numerical simulation and jet measurement experiment respectively.The influence of preheating shrouded supersonic jet on gas jet penetration and fluid flow in liquid bath was calculated by the CFD model which was validated against water model experiments.The results show that the uptrend of the potential core length of shrouded supersonic jet would be accelerated with increasing the main and shrouding gas temperatures.Also,preheating supersonic jets demonstrated significant advantages in penetrating and stirring the liquid bath.
基金This work was supported by the National Natural Science Foundation of China(Project numbers:32030015,32000300)the Natural Science Foundation of Shandong Province(Project number:ZR2021QC104,ZR2022QC096)+1 种基金China Postdoctoral Science Foundation(Project numbers:2021M701993,2022M711922)the King Saud University,Saudi Arabia(Project number RSP2023R10).We sincerely thank the“Weishan Wetland Station”for institutional support.
文摘During a study on the diversity of ciliated protists in Lake Weishan Wetland,the largest wetland in northern China,four epibiotic sessilid peritrichs were isolated from aquatic host animals.Two of them,i.e.,Epistylis cambari Kellicott,1885 and Epistylis lwof Fauré-Fremiet,1943,were known species whereas the other two,i.e.,Parapiosoma typicum gen.nov.,sp.nov.and Orborhabdostyla gracilis sp.nov.,are new to science.The new genus Parapiosoma gen.nov.is characterized by its branched non-contractile stalk,everted peristomial lip,obconical macronucleus and transverse silverlines.Two species are assigned to the new genus,namely Parapiosoma typicum sp.nov.and Parapiosoma gasterostei(Fauré-Fremiet,1905)comb.nov.Morphologically,P.typicum sp.nov.is recognized by its goblet-shaped zooids,single-layered peristomial lip,dichotomously branched stalk,and infundibular polykinety 3(P3)containing three equal-length rows.Orborhabdostyla gracilis sp.nov.is characterized by its slender zooid,curved macronucleus,and three equal-length rows in infundibular P3.Improved diagnoses and redescriptions of E.cambari and E.lwof are provided including,for the frst time,data on the ciliature of E.cambari.Phylogenetic analyses based on SSU rDNA,ITS1-5.8S rDNA-ITS2,and LSU rDNA sequence data strongly support the assertion that the family Epistylididae comprises morphospecies with diferent evolutionary lineages and indicate that Parapiosoma gen.nov.may represent a new taxon at family level.
基金supported by the National Natural Science Foundation of China (Grant Nos. 41771225 & 41620104007)the Primary Supports for Scientific Research of Lanzhou University (Grant Nos. LZUJBKY-2016-254, LZUJBKY-2016-279 & LZUJBKY-2018-144)China Scholarship Council
文摘The study of prehistoric hunter-gatherer subsistence strategies on the Tibetan Plateau is important for understanding the mechanisms and processes of human adaption to high altitude environments.But to date,only a few Paleolithic sites have been found on the Tibetan Plateau with clear stratigraphy and reliable dating.These sites are mainly distributed in the Qinghai Lake Basin on the northeastern part of the plateau,and the sporadic fauna and flora remains excavated provide limited information about the subsistence strategies of hunter-gatherers.In 2014,relatively abundant animal remains were unearthed in the Lower Cultural Layer (LCL,15400-13100 cal yr BP) of the"151 site"located in the Qinghai Lake Basin,providing important information about human subsistence strategies on the Tibetan Plateau during the Last Deglaciation.Zooarchaeological analysis of these faunal remains indicates that hunter-gatherers at the"151 site"mainly targeted large ungulates of Bos and wild horse/ass,and only brought back the most nutritious parts of animal carcasses including upper and intermediate limb bones,heads,and trunks (ribs and vertebrae).People then processed and consumed the carcasses around single hearths.Our comprehensive analyses of contemporaneous sites in the Qinghai Lake Basin show that a subsistence strategy involving opportunistic hunting of ungulates,high mobility,and short occupation of campsites was used by terminal Pleistocene huntergatherers to adapt to the high-altitude environment on the Tibetan Plateau.This subsistence strategy may have been a first step of gradual hunter-gatherer adaptation to the extreme conditions on the Tibetan Plateau after the Last Glacial Maximum,and laid the foundation for the widespread distribution of hunter-gatherers on the plateau during the Holocene.
基金supported by the National Key Research Program of Proteins(No.2016YFA0501800 for Hongmin Liu,China)National Natural Science Foundation of China(Nos.81430085 and 81773562 for Hongmin Liu and Nos.81703326 and 81973177 for Bin Yu)+2 种基金Scientific Program of Henan Province(No.19A350012 for Xiaojing Shi,China)China Postdoctoral Science Foundation(No.2018M630840 and 2019T120641 for Bin Yu)the Henan Scientific Innovation Talent Team,Department for Education(No.19ITSTHN001 for Wen Zhao,China)
文摘Ubiquitin specific peptidase 28(USP28) is closely associated to the occurrence and development of various malignancies, and thus has been validated as a promising therapeutic target for cancer therapy. To date,only few USP28 inhibitors with moderate inhibitory activity have been reported, highly potent and selective USP28 inhibitors with new chemotypes remain to be discovered for pathologically investigating the roles of deubiquitinase. In this current study, we reported the synthesis and biological evaluation of new [1,2,3]triazolo[4,5-d]pyrimidine derivatives as potent USP28 inhibitors. Especially, compound 19 potently inhibited USP28(IC50=1.10 ± 0.02 μmol/L, Kd=40 nmol/L), showing selectivity over USP7 and LSD1(IC50> 100 μmol/L). Compound 19 was cellularly engaged to USP28 in gastric cancer cells. Compound 19 reversibly bound to USP28 and directly affected its protein levels, thus inhibiting the proliferation, cell cycle at S phase, and epithelial-mesenchymal transition(EMT) progression in gastric cancer cell lines. Docking studies were performed to rationalize the potency of compound 19. Collectively, compound 19 could serve as a new tool compound for the development of new USP28 inhibitors for exploring the roles of deubiquitinase in cancers.
基金Supported by the Natural Science Foundation of Shandong Province (JQ201706)The Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology (Qingdao) (2018SDKJ0406-2)+2 种基金Fundamental Research Funds for the Central Universities (201841005)the Blue Life Breakthrough Program of LMBB of Qingdao National Laboratory for Marine Science and Technology (MS2018NO04)and National Institutes of Health (2P40OD010964).
文摘The ciliate Tetrahymena thermophila has been a powerful model system for molecular and cellular biology.However,some investigations have been limited due to the incomplete closure and sequencing of the macronuclear genome assembly,which for many years has been stalled at 1,158 scaffolds,with large sections of unknown sequences(available in Tetrahymena Genome Database,TGD,http://ciliate.org/).Here we completed the first chromosome-level Tetrahymena macronuclear genome assembly,with approximately 300×long Single Molecule,Real-Time reads of the wild-type SB210 cells—the reference strain for the initial macronuclear genome sequencing project.All 181 chromosomes were capped with two telomeres and gaps were entirely closed.The completed genome shows significant improvements over the current assembly(TGD 2014)in both chromosome structure and sequence integrity.The majority of previously identified gene models shown in TGD were retained,with the addition of 36 new genes and 883 genes with modified gene models.The new genome and annotation were incorporated into TGD.This new genome allows for pursuit in some underexplored areas that were far more challenging previously;two of them,genome scrambling and chromosomal copy number,were investigated in this study.We expect that the completed macronuclear genome will facilitate many studies in Tetrahymena biology,as well as multiple lines of research in other eukaryotes.
基金support by the National Natural Science Foundation of China(NSFC 51474024and 51334001)National Key Technology Research and Development Program of the 12th Five-year Plan of China(12FYP 2015BAF03B01)
文摘Coherent jets are widely used in electric are furnace （EAF） steelmaking to increase the oxygen utilization and chemical reaction rates. However, the influence of fuel gas combustion on jet behavior is not fully understood yet. The flow and combustion characteristics of a coherent jet were thus investigated at steelmaking temperature using Fluent software, and a detailed chemical kinetic reaction mecha- nism was used in the combustion reaction model. The axial velocity and total temperature of the supersonic jet were measured via hot state experiments. The simulation results were compared with the experimental data and the empirical jet model proposed by Ito and Muchi and good consistency was obtained. The research results indicated that the potential core length of the coherent jet can be prolonged by optimizing the combustion effect of the fuel gas. Besides, the behavior of the supersonic jet in the subsonic section was also investigated, as it is an important factor for controlling the position of the oxygen lance. The investigation indicated that the attenuation of the coherent jet is more notable than that of the conventional jet in the subsonic section.
基金supported by Natural Science Foundation ofShandong Province (JQ201706)The Marine S&T Fund of ShandongProvince for Pilot National Laboratory for Marine Science and Technology(Qingdao) (2018SDKJ0406-2)+1 种基金Fundamental Research Fundsfor the Central Universities (201841005)the Blue Life BreakthroughProgram of LMBB of Qingdao National Laboratory for MarineScience and Technology (MS2018N004).
文摘Epigenetic research focuses on heritable changes beyond the DNA sequence, which has led to a revolution in biologicalstudies and benefits in many other fields. The well-known model ciliate, Tetrahymena thermophila offers a unique system forepigenetic studies due to its nuclear dimorphism and special mode of sexual reproduction (conjugation), as well as abundantgenomic resources and genetic tools. In this paper, we summarize recent progress made by our research team and collaboratorsin understanding epigenetic mechanisms using Tetrahymena. This includes: (1) providing the first genome-wide basepair-resolution map of DNA N6-methyladenine (6mA) and revealed it as an integral part of the chromatin landscape;(2)dissecting the relative contribution of cis・ and trans- elements to nucleosome distribution by exploring the unique nucleardimorphism of Tetrahymena, (3) demonstrating the epigenetic controls of RNAi-dependent Polycomb repression pathwayson transposable elements, and (4) identifying a new histone monomethyltransferase, TXR1 (Tetrahymena Trithorax 1), thatfacilitates replication elongation through 让s substrate histone H3 lysine 27 monomethylation (H3K27mel).
基金supported by the Natural Science Foundation of China(No.31872190)。
文摘The morphology and divisional morphogenesis in a Chinese population of Neobakuella aenigmatica Moon et al.,2019 are reinvestigated.The body size,number and arrangement of parabuccal cirri and development of nuclear nodules in this population are discussed in comparison with closely related genera.The 18S rRNA gene sequence of the Chinese population is identical to that of a Korean population,supporting a distant relationship between N.aenigmatica and the cluster of N.flava and Apobakuella fuse a.We deduce that this may be caused by the differences in the pattern of the parabuccal cirri and the number of parabuccal rows which are important for the phylogeny of Bakuella-like,species.
基金supported by the National Key Research & Development Program of China (2018YFA0606400)the National Natural Science Foundation of China (41771225 and 41620104007)the Fundamental Research Funds for the Central Universities (lzujbky2016-279)
文摘Denisovans,well known for their high-coverage genetic sequences,are considered to be a new human species genetically distinct from Neanderthals and modern humans[1].As a close sister group of Neanderthals,Denisovans not only interbred w让h Neanderthals[2],but they also contributed genetically to extant humans,including modern populations in parts of Oceania and Asia,aboriginal Americans and high-alt让ude modern Tibetans[3-5].
