Male sterile lines serve as a pivotal tool in plant breeding,offering an effective strategy for developing hybrid cultivars.In cucumber(Cucumis sativus L.),the creation of male sterile lines,most of which exhibit abno...Male sterile lines serve as a pivotal tool in plant breeding,offering an effective strategy for developing hybrid cultivars.In cucumber(Cucumis sativus L.),the creation of male sterile lines,most of which exhibit abnormal pollen development,is essential for harnessing heterosis.Accumulating evidence suggests that male sterility in plants is linked to the overaccumulation of Reactive Oxygen Species(ROS),which causes oxidative damage to biomolecules and cellular structures,ultimately leading to aberrant anther development(Li et al.,2004).展开更多
Oat avenanthramides(AVNs)have been found to exhibit novel lipid-lowering effects.However,the mechanism remains unclear.In this study,the effect of avenanthramide B(AVN B),as one of the major AVNs,on highfat diet(HFD)-...Oat avenanthramides(AVNs)have been found to exhibit novel lipid-lowering effects.However,the mechanism remains unclear.In this study,the effect of avenanthramide B(AVN B),as one of the major AVNs,on highfat diet(HFD)-induced mice was investigated.Results showed that AVN B significantly inhibited weight gain and improved hepatic and serum lipid biochemical indices.Hepatic RNA-sequencing analysis suggested that AVN B significantly modulates fatty acid(FA)metabolism.Hepatic real-time qualitative polymerase chain reaction(RT-q PCR)and Western blot results indicated that AVN B could alleviate FA synthesis by activating the adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)-sterol regulatory element binding protein-1c(SREBP1c)-fatty acid synthase(FAS),and increase FA oxidation by activating the AMPK/carnitine palmitoyltransferase 1A(CPT1A)and peroxisome proliferator-activated receptorα(PPARα).Additionally,AVN B had a regulating effect on ileum lipid metabolism by inhibiting intestinal cell differentiation and downregulating the expression levels of FA absorption-related protein and gene.Moreover,AVN B promoted the growth of beneficial bacteria and fungi such as Coriobacteriaceae_UCG-002,Parvibacter,Enterococcus,and Aspergillus,while decreasing the abundance of Roseburia,unclassified_f_Lachnospiraceae,Cladosporium,Eurotium,unclassified_f_Aspergillaceae and unclassified_f_Ceratocystidaceae.All these results provided new points of the lipid-lowing mechanism of AVNs and oats via the gut-liver axis.展开更多
Whole-grain foods have attracted emerging attention due to their health benefits.Whole grains are rich in bound polyphenols(BPs)linked with dietary fibers,which is largely underestimated compared with free polyphenols...Whole-grain foods have attracted emerging attention due to their health benefits.Whole grains are rich in bound polyphenols(BPs)linked with dietary fibers,which is largely underestimated compared with free polyphenols.In this study,in vitro simulated gastrointestinal digestion and colonic fermentation models were used to study the release profile and metabolism of BPs of oat bran.Significantly higher level of BPs was released during in vitro colon fermentation(3.05 mg GAE/g)than in gastrointestinal digestion(0.54 mg GAE/g).Five polyphenols were detected via LC-MS and their possible conversion pathways were speculated.Released BPs exhibited chemical antioxidant capacity.16S rRNA sequencing further revealed that Clostridium butyricum,Enterococcus faecalis,Bacteroides acidifaciens were the key bacteria involved in the release of BPs,and this was verified by whole-cell transformation.Our results helped to explain the possible mechanism of the health benefits of BPs in whole grains.展开更多
This paper is mainly to deal with the problem of direction of arrival(DOA) estimations of multiple narrow-band sources impinging on a uniform linear array under impulsive noise environments. By modeling the impulsive ...This paper is mainly to deal with the problem of direction of arrival(DOA) estimations of multiple narrow-band sources impinging on a uniform linear array under impulsive noise environments. By modeling the impulsive noise as α-stable distribution, new methods which combine the sparse signal representation technique and fractional lower order statistics theory are proposed. In the new algorithms, the fractional lower order statistics vectors of the array output signal are sparsely represented on an overcomplete basis and the DOAs can be effectively estimated by searching the sparsest coefficients. To enhance the robustness performance of the proposed algorithms,the improved algorithms are advanced by eliminating the fractional lower order statistics of the noise from the fractional lower order statistics vector of the array output through a linear transformation. Simulation results have shown the effectiveness of the proposed methods for a wide range of highly impulsive environments.展开更多
Resilience of air&space defense system of systems(SoSs)is critical to national air defense security.However,the research on it is still scarce.In this study,the resilience of air&space defense SoSs is firstly ...Resilience of air&space defense system of systems(SoSs)is critical to national air defense security.However,the research on it is still scarce.In this study,the resilience of air&space defense SoSs is firstly defined and the kill network theory is established by combining super network and kill chain theory.Two cases of the SoSs are considered:(a)The kill chains are relatively homogenous;(b)The kill chains are relatively heterogenous.Meanwhile,two capability assessment methods,which are based on the number of kill chains and improved self-information quantity,respectively,are proposed.The improved self-information quantity modeled based on nodes and edges can achieve qualitative and quantitative assessment of the combat capability by using linguistic Pythagorean fuzzy sets.Then,a resilient evaluation index consisting of risk response,survivability,and quick recovery is proposed accordingly.Finally,network models for regional air defense and anti-missile SoSs are established respectively,and the resilience measurement results are verified and analyzed under different attack and recovery strategies,and the optimization strategies are also proposed.The proposed theory and method can meet different demands to evaluate combat capability and optimize resilience of various types of air&space defense and similar SoSs.展开更多
AIM: To investigate the association between colorectal cancer(CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population.METHODS: A case-control study was conducted including 360 esophageal...AIM: To investigate the association between colorectal cancer(CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population.METHODS: A case-control study was conducted including 360 esophageal cancer patients and310 healthy controls. Thirty-one single-nucleotide polymorphisms(SNPs) associated with CRC risk from previous genome-wide association studies were analyzed. SNPs were genotyped using Sequenom Mass-ARRAY technology, and genotypic frequencies in controls were tested for departure from HardyWeinberg equilibrium using a Fisher's exact test. The allelic frequencies were compared between cases and controls using a χ 2 test. Associations between the SNPs and the risk of esophageal cancer were tested using various genetic models(codominant, dominant,recessive, overdominant, and additive). ORs and95%CIs were calculated by unconditional logistic regression with adjustments for age and sex.RESULTS: The minor alleles of rs1321311 and rs4444235 were associated with a 1.53-fold(95%CI:1.15-2.06; P = 0.004) and 1.28-fold(95%CI: 1.03-1.60;P = 0.028) increased risk of esophageal cancer in the allelic model analysis, respectively. In the genetic model analysis, the C/C genotype of rs3802842 was associated with a reduced risk of esophageal cancer in the codominant model(OR = 0.52, 95%CI:0.31-0.88; P = 0.033) and recessive model(OR =0.55, 95%CI: 0.34-0.87; P = 0.010). The rs4939827C/T-T/T genotype was associated with a 0.67-fold(95%CI: 0.46-0.98; P = 0.038) decreased esophageal cancer risk under the dominant model. In addition,rs6687758, rs1321311, and rs4444235 were associated with an increased risk. In particular, the T/T genotype of rs1321311 was associated with an 8.06-fold(95%CI: 1.96-33.07; P = 0.004) increased risk in the codominant model.CONCLUSION: These results provide evidence that known genetic variants associated with CRC risk confer risk for esophageal cancer, and may bring risk for other digestive system tumors.展开更多
Alismatis Rhizoma(AR)is widely used in Chinese medicine,and its major bioactive components,triterpenes,reportedly possess various pharmacological activities.Therefore,it is very important to study the metabolism of tr...Alismatis Rhizoma(AR)is widely used in Chinese medicine,and its major bioactive components,triterpenes,reportedly possess various pharmacological activities.Therefore,it is very important to study the metabolism of triterpenes in vivo.However,the metabolism of AR triterpene extract has not been comprehensively elucidated due to its complex chemical components and metabolic pathways.In this study,an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method,which was based on the characteristic ions from an established database of known triterpenes,was used to analyze the major metabolites in rats following the oral administration of Alismatis Rhizoma extracts(ARE).As a result,a total of 233 constituents,with 85 prototype compounds and 148 metabolites,were identified for the first time.Hydrogenation,oxidation,sulfate and glucuronidation conjugation were the major metabolic pathways for triterpenes in AR.In addition,the mutual in vivo transformation of known ARE triterpenes was discovered and confirmed for the first time.Those results provide comprehensive insights into the metabolism of AR in vivo,which will be useful for future studies on its pharmacodynamics and pharmacokinetics.Moreover,this established strategy may be useful in metabolic studies of similar compounds.展开更多
Prunus species include many important perennial fruit crops,such as peach,plum,apricot,and related wild species.Here,we report de novo genome assemblies for five species,including the cultivated species peach(Prunus p...Prunus species include many important perennial fruit crops,such as peach,plum,apricot,and related wild species.Here,we report de novo genome assemblies for five species,including the cultivated species peach(Prunus persica),plum(Prunus salicina),and apricot(Prunus armeniaca),and the wild peach species Tibetan peach(Prunus mira)and Chinese wild peach(Prunus davidiana).The genomes ranged from 240 to 276 Mb in size,with contig N50 values of 2.27−8.30Mb and 25,333−27,826 protein-coding gene models.As the phylogenetic tree shows,plum diverged from its common ancestor with peach,wild peach species,and apricot~7 million years ago(MYA).We analyzed whole-genome resequencing data of 417 peach accessions,called 3,749,618 high-quality SNPs,577,154 small indels,31,800 deletions,duplications,and inversions,and 32,338 insertions,and performed a structural variant-based genome-wide association study(GWAS)of key agricultural traits.From our GWAS data,we identified a locus associated with a fruit shape corresponding to the OVATE transcription factor,where a large inversion event correlates with higher OVATE expression in flat-shaped accessions.Furthermore,a GWAS revealed a NAC transcription factor associated with fruit developmental timing that is linked to a tandem repeat variant and elevated NAC expression in early-ripening accessions.We also identified a locus encoding microRNA172d,where insertion of a transposable element into its promoter was found in double-flower accessions.Thus,our efforts have suggested roles for OVATE,a NAC transcription factor,and microRNA172d in fruit shape,fruit development period,and floral morphology,respectively,that can be connected to traits in other crops,thereby demonstrating the importance of parallel evolution in the diversification of several commercially important domesticated species.In general,these genomic resources will facilitate functional genomics,evolutionary research,and agronomic improvement of these five and other Prunus species.We believe that structural variant-based GWASs can also be used in other plants,animal species,and humans and be combined with deep sequencing GWASs to precisely identify candidate genes and genetic architecture components.展开更多
Fermentation substrates of rice with different milling degrees(MDs) were prepared and fermented with human feces to compare their fermentation properties and effects on gut microbiota.MD 0s,MD 5s and MD 60s represente...Fermentation substrates of rice with different milling degrees(MDs) were prepared and fermented with human feces to compare their fermentation properties and effects on gut microbiota.MD 0s,MD 5s and MD 60s represented brown rice,moderately-milled rice and white rice,respectively.After in vitro fermentation,the MD 5s group showed higher starch utilization,compared with the MD 0s and 60s groups evaluated by Fourier transform infrared spectrometer,and confocal laser scanning microscope.Effects of fermentation substrates of rice with different MDs on gut microbiota were evaluated by 16S rDNA sequencing.All the sample groups reduced the pH and produced short-chain fatty acids(SCFAs) and branched-chain fatty acids.The MD 5s group exhibited higher α-diversity than the MD 0s and 60s groups.Abundances of Phascolarctobacterium,Blautia and norank_f_Ruminococcaceae were higher in the MD 0s and 5s groups,compared with the MD 60s group.These bacteria were also positively correlated with the SCFAs production via Spearman correlation analysis.In vitro culture assay revealed that fermentation substrates of MD 0s and 5s promoted the growth of two probiotics(Akkermansia muciniphila and Bifidobacterium adolescentis).Our results showed that moderate milling might be an appropriate way to produce rice products with richer nutrients and better fermentation properties.展开更多
Three-dimensional reconstruction nerve models are classically obtained from two-dimensional images of ＂visible human＂ frozen sections. However, because of the flexibility of nerve tissues and small color differences...Three-dimensional reconstruction nerve models are classically obtained from two-dimensional images of ＂visible human＂ frozen sections. However, because of the flexibility of nerve tissues and small color differences compared with surrounding tissues, the integrity and validity of nerve tissues can be impaired during milling. Thus, in the present study, we obtained two-dimensional data from a healthy volunteer based on continuous CT angiography and magnetic resonance myelography. Semi-automatic segmentation and reconstruction were then conducted at different thresholds in different tissues using Mimics software. Small anatomical structures such as muscles and cervical nerves were reconstructed using the medical computer aided design module. Three-dimensional digital models of the cervical nerves and their surrounding structures were successfully developed, which allowed visualization of the spatial relation of anatomical structures with a strong three-dimensional effect, distinct appearance, clear distribution, and good continuity, precision, and integrality. These results indicate the validity of a three-dimensional digital visualization model of healthy human cervical nerves, which overcomes the disadvantages of milling, avoids data loss, and exhibits a realistic appearance and three-dimensional image.展开更多
The Mudui stratigraphic section represents the typical records of sedimentation processes of sand dunes and interdune depressions on the east coast of Hainan Island.Based on high-density sampling and optically stimula...The Mudui stratigraphic section represents the typical records of sedimentation processes of sand dunes and interdune depressions on the east coast of Hainan Island.Based on high-density sampling and optically stimulated luminescence(OSL) dating of the strata of the section,the grain-size composition,grain-size parameters,cumulative distribution probability curve,and grain-size-sensitivity indexes(SC/D) were analyzed.The analyzed results show that the grain-size features of aeolian sand,weakly developed sandy paleosol,two-facies(aeolian and aqueous) deposits,and lagoon deposits are all different.This indicates four evolutionary phases of the sedimentary environment of the east coast of Hainan Island since 38 ka B.P.Phase I:38-22 ka B.P.;phase II:22-17 ka B.P.;phase III:17-10 ka B.P.;phase IV:10 ka B.P.-present.The climate experienced the hot-wet/hot-dry,hot-wet/hot-dry,and warm-wet/hot-wet fluctuations,and the sedimentary environment also underwent lagoon deposition,dune and interdune depression deposition,dune stabilization and soil development,shifting sand deposition,and evolutionary processes.展开更多
Profound understanding on the diversity of local residents’willingness to pay(WTP)for ecosystem services(ESs)may aid evaluation of policy impacts by uncovering trade-offs and synergies for achieving sustainable envir...Profound understanding on the diversity of local residents’willingness to pay(WTP)for ecosystem services(ESs)may aid evaluation of policy impacts by uncovering trade-offs and synergies for achieving sustainable environmental resource management.However,the reasons for the spatial preference heterogeneity of WTP are still unclear.In this study,an extensive survey with 4,580 residents in the Yangtze River Middle Reaches Megalopolis(YRMRM),central China,was carried out to investigate the public’s WTP to maintain and improve ESs.We identified key influencing factors and explored how they shaped the preference heterogeneity in WTP by random forest model and surface fitting method.Our results showed that 81.4% of residents reported WTP for ESs greater than zero.Water supply,waste treatment,food supply and raw material supply were the preferred ESs for residents.Living environment factors(i.e.,extent of farmland,water and forest near the residence)were found as the key drivers of WTP.Proximity to farmland,water and forests resulted in high WTP values for a series of specific ESs.The reasons for the heterogeneity of WTP are(1)the difference in proximity to farmland,water and forest(i.e.,the contributor to ESs),(2)the divergence of local residents’preferences for ESs.This study disclosed the heterogeneity and causes of public preferences in YRMRM,which could help policy and decision makers to develop eco-compensation initiatives towards conservative and sustainable use of the environmental resources.展开更多
Developing an effective approach to rapidly assess the effects of restoration projects on soil erosion intensity and theirextensive spatial and temporal dynamics is important for regional ecosystem management and the ...Developing an effective approach to rapidly assess the effects of restoration projects on soil erosion intensity and theirextensive spatial and temporal dynamics is important for regional ecosystem management and the development of soilconservation strategies in the future. This study applied a model that was developed at the pixel scale using water soilerosion indicators （land use, vegetation coverage and slope） to assess the soil erosion intensity in the Loess Plateau,China. Landsat TM/ETM＋ images in 2000, 2005 and 2010 were used to produce land use maps based on the object-oriented classification method. The MODIS product MOD13Q1 was adopted to derive the vegetation coveragemaps. The slope gradient maps were calculated based on data from the digital elevation model. The area of watersoil-eroded land was classified into six grades by integrating slope gradients, land use and vegetation coverage. Resultsshow that the Grain-To-Green Project in the Loess Plateau worked based on the land use changes from 2000 to 2010and enhanced vegetation restoration and ecological conservation. These projects effectively prevented soil erosion.During this period, lands with moderate, severe, more severe and extremely severe soil erosion intensities significantlydecreased and changed into less severe levels, respectively. Lands with slight and light soil erosion intensities increased.However, the total soil-eroded area in the Loess Plateau was reduced. The contributions of the seven provincesto the total soil-eroded area in the Loess Plateau and the composition of the soil erosion intensity level in eachprovince are different. Lands with severe, more severe and extremely severe soil erosion intensities are mainly distributedin Qinghai, Ningxia, Gansu and Inner Mongolia. These areas, although relatively small, must be prioritised andpreferentially treated.展开更多
Over the last few decades,the ecological quality of the Qinghai-Tibet Plateau(QTP)has significantly changed due to climate warming,humidification,and increasing human activities.Thus,evaluating this region's ecolo...Over the last few decades,the ecological quality of the Qinghai-Tibet Plateau(QTP)has significantly changed due to climate warming,humidification,and increasing human activities.Thus,evaluating this region's ecological quality and dominant factors is crucial for sustainable development.In this study,the changes in the ecological quality on the QTP from 2000 to 2020 were evaluated based on aggregated indices and Sen-MK trend analyses,and the dominant factors affecting the ecological quality of the QTP were quantitatively analyzed using decision tree classification.The results revealed that(1)the ecological quality of the QTP exhibited an overall high trend in the east and a low pattern in the west;(2)the ecological quality of the QTP significantly increased from 2000 to 2020,and human activities were the dominant factors causing this change;and(3)the changes in the ecological quality and dominant factors exhibited obvious spatiotemporal heterogeneity.The area with an improved ecological quality occurred mainly in the northern QTP region.It was governed by human activities and precipitation.In contrast,the area with a deteriorated ecological quality occurred largely in the southern QTP region and was dominated by human activities and temperature.The 2000-2010 period was the most significant period of heterogeneity regarding of ecological quality and its driving factors.(4)The change in the ecological quality was mainly affected by the synergistic relationship between human activities and climate change in this region,which encompassed multiple dominant factors.This study provides important information on the spatiotemporal heterogeneity of ecological quality change and its dominant factors on the QTP and offers systematic guidance for the planning and implementation of ecological protection projects.展开更多
The Asian lotus(Nelumbo nucifera)has a history of cultivation in Asia dating back over 3,000 years where it has been an important food crop producing edible rhizomes and seeds as well as flowers of great aesthetic and...The Asian lotus(Nelumbo nucifera)has a history of cultivation in Asia dating back over 3,000 years where it has been an important food crop producing edible rhizomes and seeds as well as flowers of great aesthetic and cultural value.Here,we de novo assembled the plastomes of 316 lotus accessions including five North American lotus(N.lutea)and 311 Asian lotus(N.nucifera)to construct a pan-plastome genome map,and investigate the phylogeography and genetic diversity among the only two extant species within this living fossil lineage.A total of 113 unique genes were annotated and plastome sizes varied between 163,457 and 163,672 bp with only minor differences in each of the four major genomic units.The most abundant nucleotide differences among plastomes were single nucleotide variants followed by insertions/deletions and block substitutions mainly found in intergenic spacer regions of the large single copy portion of the plastome.Seven well-supported genetic clusters were resolved using multiple different population structure analyses.The different lotus types(flower,seed,rhizome,or wild)were disproportionally assigned to multiple different genetic clusters.This pattern indicates that the domestication of Asian lotus involved multiple genetic origins and possible matrilineal introgression.Geographic mapping of accessions also revealed that genetic diversity is unevenly distributed with eastern China possessing the highest genetic diversity and regions such as Yunnan,Indonesian,and Thailand possessing unique haplotypes.These results provide an important maternal history of Nelumbo and necessary groundwork for future studies on intergenomic gene transfer,cytonuclear incompatibility,and conservation genetics.展开更多
Osteoporosis is a systemic chronic metabolic bone disease,mainly in the elderly and postmenopausal women.At present,most of the clinical treatment is western medicine,but the curative effect is not very significant.In...Osteoporosis is a systemic chronic metabolic bone disease,mainly in the elderly and postmenopausal women.At present,most of the clinical treatment is western medicine,but the curative effect is not very significant.In the treatment of osteoporosis,traditional Chinese medicine(TCM)is mainly based on the overall concept of TCM.This article briefly analyzes osteoporosis from the theory of"liver and kidney homology,"discusses the research on osteoporosis in TCM,and hopes to provide reference for the clinical treatment and research of osteoporosis.展开更多
Postmitotic neurons in the neocortex migrate to appropriate positions and form layered structures of nascent cortex during brain development. The migration of these neurons requires precise control and coordination of...Postmitotic neurons in the neocortex migrate to appropriate positions and form layered structures of nascent cortex during brain development. The migration of these neurons requires precise control and coordination of a large number of molecules such as axon guidance cues. The Eph-ephrin signaling pathway plays important roles in the development of the nervous system in a wide variety of ways, including cell segregation, axon pathfinding, and neuron migration. However, the role of ephrin-B2/ EphA4 signaling in cortical neuron migration remains elusive. Here we demonstrated that ephrin-B2 and its receptor EphA4 were expressed in complementary and overlapping patterns in the developing neocortex. Deletion of the EphA4 gene in the embryonic cerebral cortex resulted in faster migration of cortical neurons, whereas knockdown or overexpression of ephdn-B2 did not alter the normal process of migration. These results suggest that ephrin-B2 forward signaling through EphA4 is required for the precise control of cortical neuron migration.展开更多
Objective:Cholesteryl esters(CEs)are composed of various fatty acyl chains attached to the hydroxyl groups of cholesterol,and abnormalities in their metabolism are related to many diseases.This study aimed to develop ...Objective:Cholesteryl esters(CEs)are composed of various fatty acyl chains attached to the hydroxyl groups of cholesterol,and abnormalities in their metabolism are related to many diseases.This study aimed to develop an ultrahigh-performance liquid chromatography-quadrupole exactive mass spectrometry(UPLC-Q-Exactive MS)method to identify the CEs in plasma.Methods:First,the MS fragmentation patterns were investigated using seven commercial CE standards.Then,the CEs in plasma were characterized through the accurate mass data of precursor ions and characteristic product ions.A strategy of step-by-step m/z scans in a narrow range was proposed to identify more trace CEs by the full-scan data-dependent MS/MS(ddMS2)mode.Results:A total of 50 CE species consisting of 55 regioisomers were identified in human plasma.Among them,two species were reported for the first time.Conclusion:This study is the most comprehensive identification of CE species in human plasma to date.These results will contribute to the in-depth profiling of CEs in human plasma and provide guidance for animal model selection when studying lipid-related diseases.展开更多
Target identification is a critical step following the discovery of small molecules that elicit a biological phenotype. G-protein coupled recaptors (GPCRs) are among the most important drug targets for the pharmaceuti...Target identification is a critical step following the discovery of small molecules that elicit a biological phenotype. G-protein coupled recaptors (GPCRs) are among the most important drug targets for the pharmaceutical industry. The present work seeks to provide an in silico model of known GPCR protein fishing technologies in order to rapidly fish out potential drug targets on the basis of amino acid sequences and seven transmembrane regions (TMs) of GPCRs. Some scoring matrices were trained on 22 groups of GPCRs in the GPCRDB database. These models were employed to predict the GPCR proteins in two groups of test sets. On average, the mean correct rate of each TM of 38 GPCRs from two test sets (ST23 and ST24) was found 62% and 57.5%, respectively, using training set 18 (SLD18);the mean hit rate of each TM of 38 GPCRs from ST23 and ST24 was found 68.1% and 64.7%, respectively. Based on the scoring matrices of PreMod, the mean correct rate of each TM of GPCRs from ST23 and ST24 was found 62% and 62.04%, respectively;the mean hit rate of each TM of GPCRs from ST23 and ST24 was found 67.7% and 68.0%, respecttively. The means of GPCRs in ST23 based on SLD18 is close to those based on PreMod;whereas the means of GPCRs in ST24 based on?SLD18 is less than those based on PreMod. Moreover, the accuracy (“2”) and validity (“2 + 1”) rates of prediction all seven TMs of 38 GPCRs by the scoring matrices of PreMod are more than those by SLD18, SLA14 and SLA3;whereas the hit rates (94.74% and 97.37%) by PreMod are less than those of?SLA3 but bigger than those of?SLD18 and SLA14, respectively. This is the reason that we choose PreMod to predict some potential drug targets. 22 GPCR proteins in the sense chain of chromosome 19 constructing validation set were predicted and validated by PreMod whose hit rate is up to 90.91%. Further evaluation is under investigation.展开更多
Alzheimer disease has been defined as Type 3 Diabetes due to their shared metabolic profiles. Like our previously research, results of Alzheimer’s disease and other neurodegenerative diseases, systematic analysis of ...Alzheimer disease has been defined as Type 3 Diabetes due to their shared metabolic profiles. Like our previously research, results of Alzheimer’s disease and other neurodegenerative diseases, systematic analysis of diabetes- and glucose metabolism-related proteins also provides help in the treatment of Alzheimer’s patients. Some interesting results indicate that diabetes-related proteins (DRPs) are rich in Lys and the content of Trp can distinguish between type 1 and type 2 diabetes mellitus in particular, while glucose metabolism-related proteins (GMRPs) possess Leurich and Trp-poor character. Moreover, the usage biases of codons depend on GC contents to a great extent, in concord with all codons of the highly expressed genes with the terminal of C/G. Especially, the deficit of CpG dinucleotides is largely attributed to the hypermutability of methylated CpGs to UpGs by the mutational pressure. Besides a common node insulin receptor, there are some similar node proteins, such as glucose transporter member, protein tyrosine phosphatase, and adipose metabolism signal protein. The sharing proteins involve glucagon, amylin, insulin, PPARγ, angiopoietin, PC-1/ENPP1, and adiponectin mediated signal pathway. Meanwhile, the gene sequences of node proteins contained the binding sites of 37 transcription factors divide into four kinds of superclasses. Additionally, BAD complex can integrate pathways of glucose metabolism and apoptosis by BH3 domain of BAD directly interacting with GK as well as GK binding with the consensus motif [G]-[1]-[K]-[2]-[S/T] or [L/M]-[R/K]-[2]-[T] of PP1 or WAVE1. This facilitates the therapies for diabetes mellitus as well as Alzheimer’s disease.展开更多
基金supported by the Project of National Key Research and Development Program‘Strategic Science and Technology Innovation Cooperation’Key Special Project(Grant No.2023YFE0206900)the 2115 Talent Development Program of China Agricultural University,the 111 project(B17043)the Project of Yazhouwan Scientific,Technological Administration of Sanya.
文摘Male sterile lines serve as a pivotal tool in plant breeding,offering an effective strategy for developing hybrid cultivars.In cucumber(Cucumis sativus L.),the creation of male sterile lines,most of which exhibit abnormal pollen development,is essential for harnessing heterosis.Accumulating evidence suggests that male sterility in plants is linked to the overaccumulation of Reactive Oxygen Species(ROS),which causes oxidative damage to biomolecules and cellular structures,ultimately leading to aberrant anther development(Li et al.,2004).
基金financially supported by the Major Project of Inner Mongolia Science and Technology Department,China(2021ZD0002)National Natural Science Foundation of China,China(32202054)Project Supported by the Shanghai Committee of Science and Technology,China(20DZ2202700)。
文摘Oat avenanthramides(AVNs)have been found to exhibit novel lipid-lowering effects.However,the mechanism remains unclear.In this study,the effect of avenanthramide B(AVN B),as one of the major AVNs,on highfat diet(HFD)-induced mice was investigated.Results showed that AVN B significantly inhibited weight gain and improved hepatic and serum lipid biochemical indices.Hepatic RNA-sequencing analysis suggested that AVN B significantly modulates fatty acid(FA)metabolism.Hepatic real-time qualitative polymerase chain reaction(RT-q PCR)and Western blot results indicated that AVN B could alleviate FA synthesis by activating the adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)-sterol regulatory element binding protein-1c(SREBP1c)-fatty acid synthase(FAS),and increase FA oxidation by activating the AMPK/carnitine palmitoyltransferase 1A(CPT1A)and peroxisome proliferator-activated receptorα(PPARα).Additionally,AVN B had a regulating effect on ileum lipid metabolism by inhibiting intestinal cell differentiation and downregulating the expression levels of FA absorption-related protein and gene.Moreover,AVN B promoted the growth of beneficial bacteria and fungi such as Coriobacteriaceae_UCG-002,Parvibacter,Enterococcus,and Aspergillus,while decreasing the abundance of Roseburia,unclassified_f_Lachnospiraceae,Cladosporium,Eurotium,unclassified_f_Aspergillaceae and unclassified_f_Ceratocystidaceae.All these results provided new points of the lipid-lowing mechanism of AVNs and oats via the gut-liver axis.
基金the support from the research grants by National Natural Science Foundation of China(32202051)National Key R&D Program of China(2022YFF1100104)the Major Project of Inner Mongolia Science and Technology Department,China(2021ZD0002)。
文摘Whole-grain foods have attracted emerging attention due to their health benefits.Whole grains are rich in bound polyphenols(BPs)linked with dietary fibers,which is largely underestimated compared with free polyphenols.In this study,in vitro simulated gastrointestinal digestion and colonic fermentation models were used to study the release profile and metabolism of BPs of oat bran.Significantly higher level of BPs was released during in vitro colon fermentation(3.05 mg GAE/g)than in gastrointestinal digestion(0.54 mg GAE/g).Five polyphenols were detected via LC-MS and their possible conversion pathways were speculated.Released BPs exhibited chemical antioxidant capacity.16S rRNA sequencing further revealed that Clostridium butyricum,Enterococcus faecalis,Bacteroides acidifaciens were the key bacteria involved in the release of BPs,and this was verified by whole-cell transformation.Our results helped to explain the possible mechanism of the health benefits of BPs in whole grains.
基金supported in part by the National Natural Science Foundation of China(61301228,61371091)the Fundamental Research Funds for the Central Universities(3132014212)
文摘This paper is mainly to deal with the problem of direction of arrival(DOA) estimations of multiple narrow-band sources impinging on a uniform linear array under impulsive noise environments. By modeling the impulsive noise as α-stable distribution, new methods which combine the sparse signal representation technique and fractional lower order statistics theory are proposed. In the new algorithms, the fractional lower order statistics vectors of the array output signal are sparsely represented on an overcomplete basis and the DOAs can be effectively estimated by searching the sparsest coefficients. To enhance the robustness performance of the proposed algorithms,the improved algorithms are advanced by eliminating the fractional lower order statistics of the noise from the fractional lower order statistics vector of the array output through a linear transformation. Simulation results have shown the effectiveness of the proposed methods for a wide range of highly impulsive environments.
基金supported by National Natural Science Foundation of China,grant numbers 72001214National Social Science Foundation of China,Young Talent Fund of University Association for Science and Technology in Shaanxi,China,No.20190108Natural Science Foundation of Shaanxi Province,grant number 2020JQ-484.
文摘Resilience of air&space defense system of systems(SoSs)is critical to national air defense security.However,the research on it is still scarce.In this study,the resilience of air&space defense SoSs is firstly defined and the kill network theory is established by combining super network and kill chain theory.Two cases of the SoSs are considered:(a)The kill chains are relatively homogenous;(b)The kill chains are relatively heterogenous.Meanwhile,two capability assessment methods,which are based on the number of kill chains and improved self-information quantity,respectively,are proposed.The improved self-information quantity modeled based on nodes and edges can achieve qualitative and quantitative assessment of the combat capability by using linguistic Pythagorean fuzzy sets.Then,a resilient evaluation index consisting of risk response,survivability,and quick recovery is proposed accordingly.Finally,network models for regional air defense and anti-missile SoSs are established respectively,and the resilience measurement results are verified and analyzed under different attack and recovery strategies,and the optimization strategies are also proposed.The proposed theory and method can meet different demands to evaluate combat capability and optimize resilience of various types of air&space defense and similar SoSs.
基金Supported by National 863 High-Technology Research and Development Program,No.2012AA02A519
文摘AIM: To investigate the association between colorectal cancer(CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population.METHODS: A case-control study was conducted including 360 esophageal cancer patients and310 healthy controls. Thirty-one single-nucleotide polymorphisms(SNPs) associated with CRC risk from previous genome-wide association studies were analyzed. SNPs were genotyped using Sequenom Mass-ARRAY technology, and genotypic frequencies in controls were tested for departure from HardyWeinberg equilibrium using a Fisher's exact test. The allelic frequencies were compared between cases and controls using a χ 2 test. Associations between the SNPs and the risk of esophageal cancer were tested using various genetic models(codominant, dominant,recessive, overdominant, and additive). ORs and95%CIs were calculated by unconditional logistic regression with adjustments for age and sex.RESULTS: The minor alleles of rs1321311 and rs4444235 were associated with a 1.53-fold(95%CI:1.15-2.06; P = 0.004) and 1.28-fold(95%CI: 1.03-1.60;P = 0.028) increased risk of esophageal cancer in the allelic model analysis, respectively. In the genetic model analysis, the C/C genotype of rs3802842 was associated with a reduced risk of esophageal cancer in the codominant model(OR = 0.52, 95%CI:0.31-0.88; P = 0.033) and recessive model(OR =0.55, 95%CI: 0.34-0.87; P = 0.010). The rs4939827C/T-T/T genotype was associated with a 0.67-fold(95%CI: 0.46-0.98; P = 0.038) decreased esophageal cancer risk under the dominant model. In addition,rs6687758, rs1321311, and rs4444235 were associated with an increased risk. In particular, the T/T genotype of rs1321311 was associated with an 8.06-fold(95%CI: 1.96-33.07; P = 0.004) increased risk in the codominant model.CONCLUSION: These results provide evidence that known genetic variants associated with CRC risk confer risk for esophageal cancer, and may bring risk for other digestive system tumors.
基金financially supported by the National Natural Science Foundation of China(Grant No.81803717 and U1603104).
文摘Alismatis Rhizoma(AR)is widely used in Chinese medicine,and its major bioactive components,triterpenes,reportedly possess various pharmacological activities.Therefore,it is very important to study the metabolism of triterpenes in vivo.However,the metabolism of AR triterpene extract has not been comprehensively elucidated due to its complex chemical components and metabolic pathways.In this study,an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method,which was based on the characteristic ions from an established database of known triterpenes,was used to analyze the major metabolites in rats following the oral administration of Alismatis Rhizoma extracts(ARE).As a result,a total of 233 constituents,with 85 prototype compounds and 148 metabolites,were identified for the first time.Hydrogenation,oxidation,sulfate and glucuronidation conjugation were the major metabolic pathways for triterpenes in AR.In addition,the mutual in vivo transformation of known ARE triterpenes was discovered and confirmed for the first time.Those results provide comprehensive insights into the metabolism of AR in vivo,which will be useful for future studies on its pharmacodynamics and pharmacokinetics.Moreover,this established strategy may be useful in metabolic studies of similar compounds.
基金This work was supported byNational Key Research and Development Plan,grant No.2018YFD1000104National Natural Science Foundation of China,grant No.31872041+2 种基金Provincial Natural Science Foundation of Shandong,grant No.ZR2018MC023Shandong Province Agricultural Good Seed Project grant,No.2020LZGC007 and 2020LZGC00702Funding for major agricultural application technology innovation projects in Shandong Province.
文摘Prunus species include many important perennial fruit crops,such as peach,plum,apricot,and related wild species.Here,we report de novo genome assemblies for five species,including the cultivated species peach(Prunus persica),plum(Prunus salicina),and apricot(Prunus armeniaca),and the wild peach species Tibetan peach(Prunus mira)and Chinese wild peach(Prunus davidiana).The genomes ranged from 240 to 276 Mb in size,with contig N50 values of 2.27−8.30Mb and 25,333−27,826 protein-coding gene models.As the phylogenetic tree shows,plum diverged from its common ancestor with peach,wild peach species,and apricot~7 million years ago(MYA).We analyzed whole-genome resequencing data of 417 peach accessions,called 3,749,618 high-quality SNPs,577,154 small indels,31,800 deletions,duplications,and inversions,and 32,338 insertions,and performed a structural variant-based genome-wide association study(GWAS)of key agricultural traits.From our GWAS data,we identified a locus associated with a fruit shape corresponding to the OVATE transcription factor,where a large inversion event correlates with higher OVATE expression in flat-shaped accessions.Furthermore,a GWAS revealed a NAC transcription factor associated with fruit developmental timing that is linked to a tandem repeat variant and elevated NAC expression in early-ripening accessions.We also identified a locus encoding microRNA172d,where insertion of a transposable element into its promoter was found in double-flower accessions.Thus,our efforts have suggested roles for OVATE,a NAC transcription factor,and microRNA172d in fruit shape,fruit development period,and floral morphology,respectively,that can be connected to traits in other crops,thereby demonstrating the importance of parallel evolution in the diversification of several commercially important domesticated species.In general,these genomic resources will facilitate functional genomics,evolutionary research,and agronomic improvement of these five and other Prunus species.We believe that structural variant-based GWASs can also be used in other plants,animal species,and humans and be combined with deep sequencing GWASs to precisely identify candidate genes and genetic architecture components.
基金supported by the National Natural Science Foundation of China (32202051)the Shanghai Sailing Program (21YF1431800, 20YF1433400)+1 种基金Shanghai Agriculture Applied Technology Development Program, China (2021-02-08-0012-F00780 )the National Key R&D Program of China (2022YFF1100104, 2023YFF1103404)。
文摘Fermentation substrates of rice with different milling degrees(MDs) were prepared and fermented with human feces to compare their fermentation properties and effects on gut microbiota.MD 0s,MD 5s and MD 60s represented brown rice,moderately-milled rice and white rice,respectively.After in vitro fermentation,the MD 5s group showed higher starch utilization,compared with the MD 0s and 60s groups evaluated by Fourier transform infrared spectrometer,and confocal laser scanning microscope.Effects of fermentation substrates of rice with different MDs on gut microbiota were evaluated by 16S rDNA sequencing.All the sample groups reduced the pH and produced short-chain fatty acids(SCFAs) and branched-chain fatty acids.The MD 5s group exhibited higher α-diversity than the MD 0s and 60s groups.Abundances of Phascolarctobacterium,Blautia and norank_f_Ruminococcaceae were higher in the MD 0s and 5s groups,compared with the MD 60s group.These bacteria were also positively correlated with the SCFAs production via Spearman correlation analysis.In vitro culture assay revealed that fermentation substrates of MD 0s and 5s promoted the growth of two probiotics(Akkermansia muciniphila and Bifidobacterium adolescentis).Our results showed that moderate milling might be an appropriate way to produce rice products with richer nutrients and better fermentation properties.
基金funded by the General Project(class A)of Medical Technology Innovation of Nanjing Military Area in 2011,No.11MA007
文摘Three-dimensional reconstruction nerve models are classically obtained from two-dimensional images of ＂visible human＂ frozen sections. However, because of the flexibility of nerve tissues and small color differences compared with surrounding tissues, the integrity and validity of nerve tissues can be impaired during milling. Thus, in the present study, we obtained two-dimensional data from a healthy volunteer based on continuous CT angiography and magnetic resonance myelography. Semi-automatic segmentation and reconstruction were then conducted at different thresholds in different tissues using Mimics software. Small anatomical structures such as muscles and cervical nerves were reconstructed using the medical computer aided design module. Three-dimensional digital models of the cervical nerves and their surrounding structures were successfully developed, which allowed visualization of the spatial relation of anatomical structures with a strong three-dimensional effect, distinct appearance, clear distribution, and good continuity, precision, and integrality. These results indicate the validity of a three-dimensional digital visualization model of healthy human cervical nerves, which overcomes the disadvantages of milling, avoids data loss, and exhibits a realistic appearance and three-dimensional image.
文摘The Mudui stratigraphic section represents the typical records of sedimentation processes of sand dunes and interdune depressions on the east coast of Hainan Island.Based on high-density sampling and optically stimulated luminescence(OSL) dating of the strata of the section,the grain-size composition,grain-size parameters,cumulative distribution probability curve,and grain-size-sensitivity indexes(SC/D) were analyzed.The analyzed results show that the grain-size features of aeolian sand,weakly developed sandy paleosol,two-facies(aeolian and aqueous) deposits,and lagoon deposits are all different.This indicates four evolutionary phases of the sedimentary environment of the east coast of Hainan Island since 38 ka B.P.Phase I:38-22 ka B.P.;phase II:22-17 ka B.P.;phase III:17-10 ka B.P.;phase IV:10 ka B.P.-present.The climate experienced the hot-wet/hot-dry,hot-wet/hot-dry,and warm-wet/hot-wet fluctuations,and the sedimentary environment also underwent lagoon deposition,dune and interdune depression deposition,dune stabilization and soil development,shifting sand deposition,and evolutionary processes.
基金financially supported by the National Key Research and Development Plan,Ministry of Science and Technology of the People’s Republic of China(Grant No.2020YFC1908704)the Innovative Foundation of Huazhong University of Science and Technology(Grant No.2018KFYYXJJ133).
文摘Profound understanding on the diversity of local residents’willingness to pay(WTP)for ecosystem services(ESs)may aid evaluation of policy impacts by uncovering trade-offs and synergies for achieving sustainable environmental resource management.However,the reasons for the spatial preference heterogeneity of WTP are still unclear.In this study,an extensive survey with 4,580 residents in the Yangtze River Middle Reaches Megalopolis(YRMRM),central China,was carried out to investigate the public’s WTP to maintain and improve ESs.We identified key influencing factors and explored how they shaped the preference heterogeneity in WTP by random forest model and surface fitting method.Our results showed that 81.4% of residents reported WTP for ESs greater than zero.Water supply,waste treatment,food supply and raw material supply were the preferred ESs for residents.Living environment factors(i.e.,extent of farmland,water and forest near the residence)were found as the key drivers of WTP.Proximity to farmland,water and forests resulted in high WTP values for a series of specific ESs.The reasons for the heterogeneity of WTP are(1)the difference in proximity to farmland,water and forest(i.e.,the contributor to ESs),(2)the divergence of local residents’preferences for ESs.This study disclosed the heterogeneity and causes of public preferences in YRMRM,which could help policy and decision makers to develop eco-compensation initiatives towards conservative and sustainable use of the environmental resources.
基金supported by the Key Program of the Chinese Academy of Sciences (KZZD-EW-04-04)the Chinese Science Academy STS Program: Construction of information platform of field and remote sensing data in northwestern China (KFJ-EW-STS-006)
文摘Developing an effective approach to rapidly assess the effects of restoration projects on soil erosion intensity and theirextensive spatial and temporal dynamics is important for regional ecosystem management and the development of soilconservation strategies in the future. This study applied a model that was developed at the pixel scale using water soilerosion indicators （land use, vegetation coverage and slope） to assess the soil erosion intensity in the Loess Plateau,China. Landsat TM/ETM＋ images in 2000, 2005 and 2010 were used to produce land use maps based on the object-oriented classification method. The MODIS product MOD13Q1 was adopted to derive the vegetation coveragemaps. The slope gradient maps were calculated based on data from the digital elevation model. The area of watersoil-eroded land was classified into six grades by integrating slope gradients, land use and vegetation coverage. Resultsshow that the Grain-To-Green Project in the Loess Plateau worked based on the land use changes from 2000 to 2010and enhanced vegetation restoration and ecological conservation. These projects effectively prevented soil erosion.During this period, lands with moderate, severe, more severe and extremely severe soil erosion intensities significantlydecreased and changed into less severe levels, respectively. Lands with slight and light soil erosion intensities increased.However, the total soil-eroded area in the Loess Plateau was reduced. The contributions of the seven provincesto the total soil-eroded area in the Loess Plateau and the composition of the soil erosion intensity level in eachprovince are different. Lands with severe, more severe and extremely severe soil erosion intensities are mainly distributedin Qinghai, Ningxia, Gansu and Inner Mongolia. These areas, although relatively small, must be prioritised andpreferentially treated.
基金the Qinghai Province Science and Technology Plan Basic Research Program(grant number 2022-ZJ-718)the Second Tibetan Plateau Scientific Expedition and Research Program(grant number 2019QZKK0608)。
文摘Over the last few decades,the ecological quality of the Qinghai-Tibet Plateau(QTP)has significantly changed due to climate warming,humidification,and increasing human activities.Thus,evaluating this region's ecological quality and dominant factors is crucial for sustainable development.In this study,the changes in the ecological quality on the QTP from 2000 to 2020 were evaluated based on aggregated indices and Sen-MK trend analyses,and the dominant factors affecting the ecological quality of the QTP were quantitatively analyzed using decision tree classification.The results revealed that(1)the ecological quality of the QTP exhibited an overall high trend in the east and a low pattern in the west;(2)the ecological quality of the QTP significantly increased from 2000 to 2020,and human activities were the dominant factors causing this change;and(3)the changes in the ecological quality and dominant factors exhibited obvious spatiotemporal heterogeneity.The area with an improved ecological quality occurred mainly in the northern QTP region.It was governed by human activities and precipitation.In contrast,the area with a deteriorated ecological quality occurred largely in the southern QTP region and was dominated by human activities and temperature.The 2000-2010 period was the most significant period of heterogeneity regarding of ecological quality and its driving factors.(4)The change in the ecological quality was mainly affected by the synergistic relationship between human activities and climate change in this region,which encompassed multiple dominant factors.This study provides important information on the spatiotemporal heterogeneity of ecological quality change and its dominant factors on the QTP and offers systematic guidance for the planning and implementation of ecological protection projects.
基金supported by the National Natural Science Foundation of China(Grant No.31970244)also co-funded by the Training of Excellent Science and Technology Innovation talents in Shenzhen-Basic Research on Outstanding Youth(STIC:RCYX20200714114538196)the Zhejiang Provincial Natural Science Foundation of China[LY21C160001].
文摘The Asian lotus(Nelumbo nucifera)has a history of cultivation in Asia dating back over 3,000 years where it has been an important food crop producing edible rhizomes and seeds as well as flowers of great aesthetic and cultural value.Here,we de novo assembled the plastomes of 316 lotus accessions including five North American lotus(N.lutea)and 311 Asian lotus(N.nucifera)to construct a pan-plastome genome map,and investigate the phylogeography and genetic diversity among the only two extant species within this living fossil lineage.A total of 113 unique genes were annotated and plastome sizes varied between 163,457 and 163,672 bp with only minor differences in each of the four major genomic units.The most abundant nucleotide differences among plastomes were single nucleotide variants followed by insertions/deletions and block substitutions mainly found in intergenic spacer regions of the large single copy portion of the plastome.Seven well-supported genetic clusters were resolved using multiple different population structure analyses.The different lotus types(flower,seed,rhizome,or wild)were disproportionally assigned to multiple different genetic clusters.This pattern indicates that the domestication of Asian lotus involved multiple genetic origins and possible matrilineal introgression.Geographic mapping of accessions also revealed that genetic diversity is unevenly distributed with eastern China possessing the highest genetic diversity and regions such as Yunnan,Indonesian,and Thailand possessing unique haplotypes.These results provide an important maternal history of Nelumbo and necessary groundwork for future studies on intergenomic gene transfer,cytonuclear incompatibility,and conservation genetics.
文摘Osteoporosis is a systemic chronic metabolic bone disease,mainly in the elderly and postmenopausal women.At present,most of the clinical treatment is western medicine,but the curative effect is not very significant.In the treatment of osteoporosis,traditional Chinese medicine(TCM)is mainly based on the overall concept of TCM.This article briefly analyzes osteoporosis from the theory of"liver and kidney homology,"discusses the research on osteoporosis in TCM,and hopes to provide reference for the clinical treatment and research of osteoporosis.
基金supported by grants from the Chinese Academy of Sciencesthe National Basic Research Development Program of China (2011CB504102)the National Natural Science Foundation of China (31123002 and 31321091)
文摘Postmitotic neurons in the neocortex migrate to appropriate positions and form layered structures of nascent cortex during brain development. The migration of these neurons requires precise control and coordination of a large number of molecules such as axon guidance cues. The Eph-ephrin signaling pathway plays important roles in the development of the nervous system in a wide variety of ways, including cell segregation, axon pathfinding, and neuron migration. However, the role of ephrin-B2/ EphA4 signaling in cortical neuron migration remains elusive. Here we demonstrated that ephrin-B2 and its receptor EphA4 were expressed in complementary and overlapping patterns in the developing neocortex. Deletion of the EphA4 gene in the embryonic cerebral cortex resulted in faster migration of cortical neurons, whereas knockdown or overexpression of ephdn-B2 did not alter the normal process of migration. These results suggest that ephrin-B2 forward signaling through EphA4 is required for the precise control of cortical neuron migration.
基金supported by National Natural Science Foundation of China(No.81874309,No.81903901 and No.81803717)the Youth Foundation of the Zhejiang Academy of Medical Sciences(No.2020Y003).
文摘Objective:Cholesteryl esters(CEs)are composed of various fatty acyl chains attached to the hydroxyl groups of cholesterol,and abnormalities in their metabolism are related to many diseases.This study aimed to develop an ultrahigh-performance liquid chromatography-quadrupole exactive mass spectrometry(UPLC-Q-Exactive MS)method to identify the CEs in plasma.Methods:First,the MS fragmentation patterns were investigated using seven commercial CE standards.Then,the CEs in plasma were characterized through the accurate mass data of precursor ions and characteristic product ions.A strategy of step-by-step m/z scans in a narrow range was proposed to identify more trace CEs by the full-scan data-dependent MS/MS(ddMS2)mode.Results:A total of 50 CE species consisting of 55 regioisomers were identified in human plasma.Among them,two species were reported for the first time.Conclusion:This study is the most comprehensive identification of CE species in human plasma to date.These results will contribute to the in-depth profiling of CEs in human plasma and provide guidance for animal model selection when studying lipid-related diseases.
文摘Target identification is a critical step following the discovery of small molecules that elicit a biological phenotype. G-protein coupled recaptors (GPCRs) are among the most important drug targets for the pharmaceutical industry. The present work seeks to provide an in silico model of known GPCR protein fishing technologies in order to rapidly fish out potential drug targets on the basis of amino acid sequences and seven transmembrane regions (TMs) of GPCRs. Some scoring matrices were trained on 22 groups of GPCRs in the GPCRDB database. These models were employed to predict the GPCR proteins in two groups of test sets. On average, the mean correct rate of each TM of 38 GPCRs from two test sets (ST23 and ST24) was found 62% and 57.5%, respectively, using training set 18 (SLD18);the mean hit rate of each TM of 38 GPCRs from ST23 and ST24 was found 68.1% and 64.7%, respectively. Based on the scoring matrices of PreMod, the mean correct rate of each TM of GPCRs from ST23 and ST24 was found 62% and 62.04%, respectively;the mean hit rate of each TM of GPCRs from ST23 and ST24 was found 67.7% and 68.0%, respecttively. The means of GPCRs in ST23 based on SLD18 is close to those based on PreMod;whereas the means of GPCRs in ST24 based on?SLD18 is less than those based on PreMod. Moreover, the accuracy (“2”) and validity (“2 + 1”) rates of prediction all seven TMs of 38 GPCRs by the scoring matrices of PreMod are more than those by SLD18, SLA14 and SLA3;whereas the hit rates (94.74% and 97.37%) by PreMod are less than those of?SLA3 but bigger than those of?SLD18 and SLA14, respectively. This is the reason that we choose PreMod to predict some potential drug targets. 22 GPCR proteins in the sense chain of chromosome 19 constructing validation set were predicted and validated by PreMod whose hit rate is up to 90.91%. Further evaluation is under investigation.
文摘Alzheimer disease has been defined as Type 3 Diabetes due to their shared metabolic profiles. Like our previously research, results of Alzheimer’s disease and other neurodegenerative diseases, systematic analysis of diabetes- and glucose metabolism-related proteins also provides help in the treatment of Alzheimer’s patients. Some interesting results indicate that diabetes-related proteins (DRPs) are rich in Lys and the content of Trp can distinguish between type 1 and type 2 diabetes mellitus in particular, while glucose metabolism-related proteins (GMRPs) possess Leurich and Trp-poor character. Moreover, the usage biases of codons depend on GC contents to a great extent, in concord with all codons of the highly expressed genes with the terminal of C/G. Especially, the deficit of CpG dinucleotides is largely attributed to the hypermutability of methylated CpGs to UpGs by the mutational pressure. Besides a common node insulin receptor, there are some similar node proteins, such as glucose transporter member, protein tyrosine phosphatase, and adipose metabolism signal protein. The sharing proteins involve glucagon, amylin, insulin, PPARγ, angiopoietin, PC-1/ENPP1, and adiponectin mediated signal pathway. Meanwhile, the gene sequences of node proteins contained the binding sites of 37 transcription factors divide into four kinds of superclasses. Additionally, BAD complex can integrate pathways of glucose metabolism and apoptosis by BH3 domain of BAD directly interacting with GK as well as GK binding with the consensus motif [G]-[1]-[K]-[2]-[S/T] or [L/M]-[R/K]-[2]-[T] of PP1 or WAVE1. This facilitates the therapies for diabetes mellitus as well as Alzheimer’s disease.
