Gingko biloba accumulates high levels of secondary metabolites of pharmaceutical value.Ginkgo calli develop a typical browning that reduces its regenerative capacity and thus its usefulness.To elucidate the browning m...Gingko biloba accumulates high levels of secondary metabolites of pharmaceutical value.Ginkgo calli develop a typical browning that reduces its regenerative capacity and thus its usefulness.To elucidate the browning mechanism,histological,transcriptomic,and metabolic alterations were compared between green and browning calli derived from immature ginkgo embryos.Histological observations revealed that browning calli had a more loosely arranged cell structure and accumulated more tannins than in green calli.Integrated metabolic and transcriptomic analyses showed that phenylpropanoid metabolism was specifi-cally activated in the browning calli,and 428 diff erentially expressed genes and 63 diff erentially abundant metabolites,including 12 fl avonoid compounds,were identifi ed in the browning calli compared to the green calli.Moreover,the expression of fl avonol synthase(FLS)and UDP-glucuronosyl-transferase(UGT)genes involved in the fl avonoid pathway was more than tenfold higher in browning calli than in green calli,thus promoting biosynthesis of fl avonol,which serves as a substrate to form glycosylated fl avonoids.Flavonoid glycosides constituted the major coloring component of the browning calli and may act in response to multiple stress conditions to delay cell death caused by browning.Our results revealed the cellular and biochemical changes in browning callus cells that accompanied changes in expression of browning-related genes,providing a scientifi c basis for improving ginkgo tissue culturability.展开更多
Hypertrophic differentiation is not only the terminal process of endochondral ossification in the growth plate but is also an important pathological change in osteoarthritic cartilage.Collagen type II(COL2A1)was previ...Hypertrophic differentiation is not only the terminal process of endochondral ossification in the growth plate but is also an important pathological change in osteoarthritic cartilage.Collagen type II(COL2A1)was previously considered to be only a structural component of the cartilage matrix,but recently,it has been revealed to be an extracellular signaling molecule that can significantly suppress chondrocyte hypertrophy.However,the mechanisms by which COL2A1 regulates hypertrophic differentiation remain unclear.In our study,a Col2a1 p.Gly1170Ser mutant mouse model was constructed,and Col2a1 loss was demonstrated in homozygotes.Loss of Col2a1 was found to accelerate chondrocyte hypertrophy through the bone morphogenetic protein(BMP)-SMAD1 pathway.Upon interacting with COL2A1,integrinβ1(ITGB1),the major receptor for COL2A1,competed with BMP receptors for binding to SMAD1 and then inhibited SMAD1 activation and nuclear import.COL2A1 could also activate ITGB1-induced ERK1/2 phosphorylation and,through ERK1/2-SMAD1 interaction,it further repressed SMAD1 activation,thus inhibiting BMP-SMAD1-mediated chondrocyte hypertrophy.Moreover,COL2A1 expression was downregulated,while chondrocyte hypertrophic markers and BMP-SMAD1 signaling activity were upregulated in degenerative human articular cartilage.Our study reveals novel mechanisms for the inhibition of chondrocyte hypertrophy by COL2A1 and suggests that the degradation and decrease in COL2A1 might initiate and promote osteoarthritis progression.展开更多
Naturally,resistant crop germplasms are important resources for managing the issues of agricultural product safety and environment deterioration.We found a spontaneous mutant of‘Newhall’navel orange(Citrus sinensis ...Naturally,resistant crop germplasms are important resources for managing the issues of agricultural product safety and environment deterioration.We found a spontaneous mutant of‘Newhall’navel orange(Citrus sinensis Osbeck)(MT)with broad-spectrum protections against fungal pathogens in the orchard,postharvest-storage,and artificial inoculation conditions.To understand the defense mechanism of MT fruit,we constructed a genome-scale metabolic network that integrated metabolome and transcriptome datasets.The coordinated transcriptomic and metabolic data were enriched in two sub-networks,showing the decrease in very long chain fatty acid(by 41.53%)and cuticular wax synthesis(by 81.34%),and increase in the synthesis of jasmonic acid(JA)(by 95.23%)and JA-induced metabolites such as 5-dimethylnobietin(by 28.37%)in MT.Furthermore,cytological and biochemical analyses confirmed that the response to fungal infection in MT was independent of wax deficiency and was correlated with the levels of jasmonates,and the expression of plant defensin gene PDF1.2.Results of exogenous application of MeJA and JA inhibitors such as propyl gallate proved that JA-mediated defense contributes to the strong tolerance against pathogens in MT.Our results indicated that jasmonate biosynthesis and signaling are stimulated by the fatty acid redirection of MT,and participate in the tolerance of pathogenic fungi.展开更多
Hepatocellular carcinoma(HCC) is one of the most deadly and frequent cancers worldwide,although great advancement in the treatment of this malignancy have been made within the past few decades.It continues to be a maj...Hepatocellular carcinoma(HCC) is one of the most deadly and frequent cancers worldwide,although great advancement in the treatment of this malignancy have been made within the past few decades.It continues to be a major health issue due to an increasing incidence and a poor prognosis.The majority of patients have their HCC diagnosed at an intermediate or advanced stage in theUSA or China.Curative therapy such as surgical resection or liver transplantation is not considered anoption of treatment at these stages.Transarterial chemoembolization(TACE),the most widely used locoregional therapeutic approach,used to be the mainstay of treatment for cases with unresectable cancer entities.However,for those patients with hypovascular tumors or impaired liver function reserve,TACE is a suboptimal treatment option.For example,embolization does not result in complete coverage of a hypovascular tumor,and may rather promotes postoperative tumor recurrence,or leave residual tumor,in these TACE-resistance patients.In addition,TACE carries a higher risk of hepatic decompensation in patients with poor liver function or reserve.Non-vascular interventional locoregional therapies for HCC include radiofrequency ablation(RFA),microwave ablation(MWA),high-intensity focused ultrasound(HIFU),laser-induced thermotherapy(LITT),cryosurgical ablation(CSA),irreversible Electroporation(IRE),percutaneous ethanol injection(PEI),and brachytherapy.Recent advancements in these techniques have significantly improved the treatment efficacy of HCC and expanded the population of patients who qualify for treatment.This review embraces the current status of imaging-guided locoregional non-intravascular interventional treatments for HCCs,with a primary focus on the clinical evaluation and assessment of the efficacy of combined therapies using these interventional techniques.展开更多
Ginkgo biloba is a famous living“fossil”and has played an important role in the evolution of the Plant Kingdom.Here,the complete chloroplast genome of G.biloba was sequenced and analysed.The chloroplast genome was 1...Ginkgo biloba is a famous living“fossil”and has played an important role in the evolution of the Plant Kingdom.Here,the complete chloroplast genome of G.biloba was sequenced and analysed.The chloroplast genome was 156,990 bp long and predicted to encode 134 genes including 85 protein-coding genes,41 tRNA genes and 8 rRNA genes.The chloroplast genome has a typical quadripartite structure with a pair of inverted repeat regions(IRa and IRb,17,732 bp),a large(LSC,99,259 bp)and small single(SSC,22,267 bp)copy region.After an extensive comparison to previously published gymnosperm plastomes,the gene content and organisation of G.biloba showed high divergence,although part was relatively conserved.The two typical IR regions in the G.biloba chloroplast genome were relatively shorter because it the ycf2 gene.In addition,it was obvious that the IR regions and gene loss were responsible for changes in chloroplast genome size and structure stability,which influenced plastome evolution in different gymnosperms.Phylogenetic analysis revealed that G.biloba is sister to cycads rather than to gnetophytes,cupressophytes,and Pinaceae.Overall,the study showed that the genomic characteristics of G.biloba would be of great help in the further research on the taxonomy,species identification and evolutionary history of gymnosperms,especially for their position in plant systematics and evolution.展开更多
The first balloon angioplasty performed by Dr.Charles T.Dotter in 1964 marked the birth of a new discipline in radiology(1),which was initially named'interventional diagnostic radiology'by Dr.Alexander R.Margu...The first balloon angioplasty performed by Dr.Charles T.Dotter in 1964 marked the birth of a new discipline in radiology(1),which was initially named'interventional diagnostic radiology'by Dr.Alexander R.Margulis in 1967(2),and later defined as'Interventional Radiology(IR)'by Dr.Sidney Wallace in 1976(3).Along with the wide adaptation of Seldinger’s technique for percutaneous vascular access(4),interventional radiology expanded the horizon of traditional radiology.展开更多
A discrete element method(DEM) model was used to simulate the development of compaction-induced stress in a granular base course, with and without geogrid reinforcement. The granular base course was modeled as a mixtu...A discrete element method(DEM) model was used to simulate the development of compaction-induced stress in a granular base course, with and without geogrid reinforcement. The granular base course was modeled as a mixture of uniformly sized triangular particles. The geogrid was modeled as a series of equally spaced balls that interact with each other through long-range interaction contacts. The longrange interaction contact was also used to simulate a deformable subgrade. The compactor was modeled as a solid cylinder rolling at a constant speed. The DEM model shows that the geogridreinforced granular base course gains additional compaction-induced stress due to the residual tensile stress developed in the geogrid. The residual tensile stress in the geogrid increases with the number of compaction passes. Parametric analyses were also conducted to assess the effects of geogrid stiffness and subgrade modulus on the compaction-induced stress.展开更多
The technique of ocean bottom cable (OBC) dual-sensor acquisition is an effective method to suppress the ghost wave and the reverberation at the receiver. With the advent of this technique, the processing method has b...The technique of ocean bottom cable (OBC) dual-sensor acquisition is an effective method to suppress the ghost wave and the reverberation at the receiver. With the advent of this technique, the processing method has become the key to the effective use of the OBC dual-sensor data. This paper has developed a new set of processing workflow based on the principle of combining the hydrophone and geophone data. This new process was applied to the OBC data acquired in Bohai area. The actual processing results show that the ghost and the reverberation are attenuated effectively. The frequency energy of the first notch point of the hydrophone data increased from −22 dB to −13 dB, and the frequency energy of the first notch point of the geophone data increased from −18 dB to −10 dB. The spectral characteristics of the dual-sensor data are more reasonable. The frequency spectrum is broadened and richer, and the resolution of the stack profile is improved greatly.展开更多
Ginkgol C17:1 has been shown to inhibit apoptosis and migration of cancer cells,but the underlying mechanisms are not fully elucidated.In this study,we explored whether the inhibitory effects of Ginkgol C17:1 were ass...Ginkgol C17:1 has been shown to inhibit apoptosis and migration of cancer cells,but the underlying mechanisms are not fully elucidated.In this study,we explored whether the inhibitory effects of Ginkgol C17:1 were associated with epidermal growth factor receptor(EGFR) and PI3K/Akt signaling.The results showed that EGF treatment increased the phosphorylation of EGFR,PI3 K,Akt,mTOR and NF-κB,and also enhanced the proliferation,migration and invasion of HepG2 cells.Ginkgol C17:1 dose-dependently inhibited EGF-induced phosphorylation/activation of all the key components including EGFR,PI3 K,Akt,mTOR and NF-kB,leading to a significant reduction either of proliferation or migration and invasion of HepG2 cells.Notably,treatment with Ginkgol C17:1 in mice suppressed the growth of tumor mass in vivo,and expression of EGFR in the tumor tissue.The results suggest that Ginkgol C17:1 is a potent tumor inhibiting compound that acts on EGF-induced signal transduction of the PI3K/Akt signaling pathways,and may represent a clinically interesting candidate for cancer therapy.展开更多
Big data knowledge,such as customer demands and consumer preferences,is among the crucial external knowledge that firms need for new product development in the big data environment.Prior research has focused on the pr...Big data knowledge,such as customer demands and consumer preferences,is among the crucial external knowledge that firms need for new product development in the big data environment.Prior research has focused on the profit of big data knowledge providers rather than the profit and pricing schemes of knowledge recipients.This research addresses this theoretical gap and uses theoretical and numerical analysis to compare the profitability of two pricing schemes commonly used by knowledge recipients:subscription pricing and pay-per-use pricing.We find that:(1)the subscription price of big data knowledge has no effect on the optimal time of knowledge transaction in the same pricing scheme,but the usage ratio of the big data knowledge affects the optimal time of knowledge transaction,and the smaller the usage ratio of big data knowledge the earlier the big data knowledge transaction conducts;(2)big data knowledge with a higher update rate can bring greater profits to the firm both in subscription pricing scheme and pay-per-use pricing scheme;(3)a knowledge recipient will choose the knowledge that can bring a higher market share growth rate regardless of what price scheme it adopts,and firms can choose more efficient knowledge in the pay-per-use pricing scheme by adjusting the usage ratio of knowledge usage according to their economic conditions.The model and findings in this paper can help knowledge recipient firms select optimal pricing method and enhance future new product development performance.展开更多
Background:To investigate the underlying molecular mechanisms of radiofrequency hyperthermia(RFH)-enhanced direct chemotherapy of pancreatic cancers.Method:Rat ductal PaCa cell line DSL-6A/C1 and orthotopic pancreatic...Background:To investigate the underlying molecular mechanisms of radiofrequency hyperthermia(RFH)-enhanced direct chemotherapy of pancreatic cancers.Method:Rat ductal PaCa cell line DSL-6A/C1 and orthotopic pancreatic cancers of Lewis rats were divided into four study groups with various treatments:i)phosphate-buffered saline(PBS)as a control;ii)RFH alone;iii)intratumoral chemotherapy alone(gemcitabine);and(iv)combination therapy of gemcitabine plus intratumoral RFH at 42°C for30 min.In the in-vitro confirmation experiments,the viability and apoptosis of DSL-6A/C1 cells in each treatment group were evaluated using cell live/dead staining,flow cytometry,and Western blot.In the in vivo validation experiments,related proteins were evaluated by immunohistochemistry(IHC)staining of tumors.Results:Of the in-vitro experiments,the lowest cell viability and more apoptotic cells were shown in the group with combination therapy compared to other treatments.Western blot data showed elevated Bax/Bcl-2,Caspase-3,and HSP70 expressions in DSL cells with combination therapy,compared to other treatments.Of the in vivo experiments,IHC staining detected the significantly increased expressions of HSP70,IL-1β,TNF-ɑ,Bax,and Caspase-3 in pancreatic cancer tissues of the animal group treated by combination therapy of gemcitabine with RFH.Conclusion:Molecular imaging-guided interventional RFH can significantly enhance the chemotherapeutic effect on pancreatic cancers via potential molecular mechanisms of up-regulating Bax/caspase-3-dependent apoptosis pathways.展开更多
Purpose To evaluate the performance of diffusion-weighted imaging(DWI) and variable flip angle(VFA) T1 mapping as a supplement to image-guided biopsy in follow-up analysis of liver fibrosis. Materials and Methods This...Purpose To evaluate the performance of diffusion-weighted imaging(DWI) and variable flip angle(VFA) T1 mapping as a supplement to image-guided biopsy in follow-up analysis of liver fibrosis. Materials and Methods This prospective study was approved by the institution's committee on human research, and written informed consent was provided from the enrolled patients. We investigated five MRI parameters of DWI and VFA T1 mapping, collected from 11 patients who underwent serial ultrasound image-guided biopsy with follow-up MRI within 1.5 years after treatment for liver fibrosis/cirrhosis. For each patient, four consecutive MRI examinations were conducted, including baseline MRI before treatment and three follow-up MRI examinations after treatment at each 0.5-year interval. ADC values at four b values and T1 relaxation times were correlated to pathology-confirmed liver fibrosis stages, which were subsequently divided into two groups, stages F2–3 and F4. The receiver operating characteristic(ROC) analysis and repeated measurement analysis of variance were used for statistical analysis. Results Among these ADC parameters, ADC value(b = 500 s/mm^2) was the most consistent in differentiating between stage F2–3 and F4 liver fibrosis. Repeated measurement analysis showed that the intra-group and inter-group differences were 0.447 and 0.024, respectively. T1 relaxation time could not consistently differentiate between the F2–3 and F4 groups; however, it was repeatable, and the intra-group and inter-group differences were 0.410 and 0.042, respectively. Conclusion MRI-ADC value at a b value of 500 s/mm^2 can be a promising biomarker for differentiating stages F2–3 and F4 liver fibrosis. A combination of this biomarker with repeatable T1 relaxation time may function as a non-invasive tool for follow-up liver fibrosis in patients who reject repeated image-guided biopsy.展开更多
In order to suppress the surface wave in three-component seismic exploration, according to the polarization characteristics of body wave and surface wave, a time-frequency domain polarization filtering method based on...In order to suppress the surface wave in three-component seismic exploration, according to the polarization characteristics of body wave and surface wave, a time-frequency domain polarization filtering method based on wavelet transform was studied. A covariance matrix was constructed in the time-frequency domain for the three-component seismic data, measured the polarization parameters of seismic waves. Combining the corresponding eigenvalues and eigenvectors of the matrix, the elliptic rate and elevation angle were used as constraints, and the polarization filter function was built to separate the surface waves. The separated surface waves were inversely transformed and then were adaptively subtracted from the original records. After the polarization filtering suppressed the surface wave, the signal-to-noise ratio of the converted wave was effectively improved. It laid a good foundation for the next seismic data processing and seismic exploration development. The actual data processing results show that the method can effectively extract surface waves from three-component seismic records and avoid the interference of surface waves on seismic signals.展开更多
The fluid identification of carbonate reservoir is a key factor to hydrocarbon exploration and reservoir development. In order to simulate the seismic response characteristics of the cave in the carbonate reservoir, t...The fluid identification of carbonate reservoir is a key factor to hydrocarbon exploration and reservoir development. In order to simulate the seismic response characteristics of the cave in the carbonate reservoir, three sets of models were designed, including the caves varied in width, the caves filled with different solids, and the oil-gas-water model. The numerical simulation technique was used to carry out the forward modeling and the AVO (Amplitude varies with offset) response characteristics of the three groups of models were analyzed. The results show that the AVO characteristics can be observed when the cave reaches a certain extent in the horizontal direction. When the surrounding rock is constant, the absolute value of the intercept of the AVO curve increases with the Vp/Vs decrease. The AVO technology can effectively identify the gas cave. The effect is not obvious to water or oil cave.展开更多
Mutation of the MAPK7 gene was related to human scoliosis.Mapk7 regulated the development of limb bones and skulls in mice.However,the role of MAPK7 in vertebral development is still unclear.In this study,we construct...Mutation of the MAPK7 gene was related to human scoliosis.Mapk7 regulated the development of limb bones and skulls in mice.However,the role of MAPK7 in vertebral development is still unclear.In this study,we constructed Col2a1-cre;Mapk7 f/f transgenic mouse model to delete Mapk7 in cartilage,which displayed kyphosis and osteopenia.Mechanistically,Mapk7 loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes,which impaired chondrocyte hypertrophy and attenuated vertebral ossification.In vivo,systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by Mapk7 deficiency.Our study firstly clarified the mechanism by which MAPK7 was involved in vertebral development,which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.展开更多
Long-wavelength fluorescence carbon dots (CDs) show great importance in multiple fields,especially for the biochemical sensing.Here,we proposed one type of CDs doped with nitrogen and sulfur through the hydrothermal m...Long-wavelength fluorescence carbon dots (CDs) show great importance in multiple fields,especially for the biochemical sensing.Here,we proposed one type of CDs doped with nitrogen and sulfur through the hydrothermal method,which exhibited obvious yellow-fluorescence in aqueous solution.Importantly,the fluorescence intensity of CDs decreased with pH decreasing in the acidic range,thus a linear relationship between pH and fluorescence intensity was established,exhibiting the potential of pH sensing.Additionally,introducing tigecycline into CDs resulted in their decreased fluorescence,thus,we further established a strategy of detecting tigecycline with the concentration range of 200 μM to 7 nM.Meanwhile,we elucidated the static quenching as the major mechanism for CDs responding tigecycline,which was induced by the formed new complex between CDs and tigecycline.Furthermore,the practicality of the method was verified by examining the recovery of tigecycline in the actual lake-water samples.展开更多
Redwood trees(Sequoioideae),including Metasequoia glyptostroboides(dawn redwood),Sequoiadendron giganteum(giant sequoia),and Sequoia sempervirens(coast redwood),are threatened and widely recognized iconic tree species...Redwood trees(Sequoioideae),including Metasequoia glyptostroboides(dawn redwood),Sequoiadendron giganteum(giant sequoia),and Sequoia sempervirens(coast redwood),are threatened and widely recognized iconic tree species.Genomic resources for redwood trees could provide clues to their evolutionary relationships.Here,we report the 8-Gb reference genome of M.glyptostroboides and a comparative analysis with two related species.More than 62%of the M.glyptostroboides genome is composed of repetitive sequences.Clade-specific bursts of long terminal repeat retrotransposons may have contributed to genomic differentiation in the three species.The chromosomal synteny between M.glyptostroboides and S.giganteum is extremely high,whereas there has been significant chromosome reorganization in S.sempervirens.Phylogenetic analysis of marker genes indicates that S.sempervirens is an autopolyploid,and more than 48%of the gene trees are incongruent with the species tree.Results of multiple analyses suggest that incomplete lineage sorting(ILS)rather than hybridization explains the inconsistent phylogeny,indicating that genetic variation among redwoods may be due to random retention of polymorphisms in ancestral populations.Functional analysis of ortholog groups indicates that gene families of ion channels,tannin biosynthesis enzymes,and transcription factors for meristem maintenance have expanded in S.giganteum and S.sempervirens,which is consistent with their extreme height.As a wetland-tolerant species,M.glyptostroboides shows a transcriptional response to flooding stress that is conserved with that of analyzed angiosperm species.Our study offers insights into redwood evolution and adaptation and provides genomic resources to aid in their conservation and management.展开更多
The epidemic of corona virus disease 2019(COVID-19)caused by severe acute respiratory syndrome Coronavirus 2 and its variants of concern(VOCs)has been ongoing for over 3 years.Antibody therapies encompassing convalesc...The epidemic of corona virus disease 2019(COVID-19)caused by severe acute respiratory syndrome Coronavirus 2 and its variants of concern(VOCs)has been ongoing for over 3 years.Antibody therapies encompassing convalescent plasma,hyperimmunoglobulin,and neutralizing monoclonal antibodies(mAbs)applied in passive immunotherapy have yielded positive outcomes and played a crucial role in the early COVID-19 treatment.In this review,the development path,action mechanism,clinical research results,challenges,and safety profile associated with the use of COVID-19 convalescent plasma,hyperimmunoglobulin,and mAbs were summarized.In addition,the prospects of applying antibody therapy against VOCs was assessed,offering insights into the coping strategies for facing new infectious disease outbreaks.展开更多
The oral hexavalent live human-bovine reassortant rotavirus vaccine(RV6)developed by Wuhan Institute of Biological Products Co.,Ltd(WIBP)has finished a randomized,placebo-controlled phase III clinical trial in four pr...The oral hexavalent live human-bovine reassortant rotavirus vaccine(RV6)developed by Wuhan Institute of Biological Products Co.,Ltd(WIBP)has finished a randomized,placebo-controlled phase III clinical trial in four provinces of China in 2021.The trail demonstrated that RV6 has a high vaccine efficacy against the prevalent strains and is safe for use in infants.During the phase III clinical trial(2019–2021),200 rotavirus-positive fecal samples from children with RV gastroenteritis(RVGE)were further studied.Using reverse transcription-polymerase chain reaction and high-throughput sequencing,VP7 and VP4 sequences were obtained and their genetic characteristics,as well as the differences in antigenic epitopes of VP7,were analyzed in detail.Seven rotavirus genotypes were identified.The predominant rotavirus genotype was G9P[8](77.0%),followed by prevalent strains G8P[8](8.0%),G3P[8](3.5%),G3P[9](1.5%),G1P[8](1.0%),G2P[4](1.0%),and G4P[6](1.0%).The amino acid sequence identities of G1,G2,G3,G4,G8,and G9 genotypes of isolates compared to the vaccine strains were 98.8%,98.2%–99.7%,88.4%–99.4%,98.2%,94.2%–100%,and 93.9%–100%,respectively.Notably,the vaccine strains exhibited high similarity in amino acid sequence,with only minor differences in antigenic epitopes compared to the Chinese endemic strains.This supports the potential application of the vaccine in preventing diseases caused by rotaviruses.展开更多
基金supported by the Natural Science Foundation of Jiangsu Province(BK20210611)the China Postdoctoral Science Foundation(2018M642261)+2 种基金the Postdoctoral Science Foundation of Jiangsu Province(2018K197C)the Jiangsu Science and Technology Plan Project(BE2021367)the National Natural Science Foundation of China(31971689).
文摘Gingko biloba accumulates high levels of secondary metabolites of pharmaceutical value.Ginkgo calli develop a typical browning that reduces its regenerative capacity and thus its usefulness.To elucidate the browning mechanism,histological,transcriptomic,and metabolic alterations were compared between green and browning calli derived from immature ginkgo embryos.Histological observations revealed that browning calli had a more loosely arranged cell structure and accumulated more tannins than in green calli.Integrated metabolic and transcriptomic analyses showed that phenylpropanoid metabolism was specifi-cally activated in the browning calli,and 428 diff erentially expressed genes and 63 diff erentially abundant metabolites,including 12 fl avonoid compounds,were identifi ed in the browning calli compared to the green calli.Moreover,the expression of fl avonol synthase(FLS)and UDP-glucuronosyl-transferase(UGT)genes involved in the fl avonoid pathway was more than tenfold higher in browning calli than in green calli,thus promoting biosynthesis of fl avonol,which serves as a substrate to form glycosylated fl avonoids.Flavonoid glycosides constituted the major coloring component of the browning calli and may act in response to multiple stress conditions to delay cell death caused by browning.Our results revealed the cellular and biochemical changes in browning callus cells that accompanied changes in expression of browning-related genes,providing a scientifi c basis for improving ginkgo tissue culturability.
基金supported by the National Natural Science Foundation of China (No.81371907,No.81572134,and No.81802217)the China Postdoctoral Science Foundation (No.2017M622873)+2 种基金the Natural Science Foundation of Guangdong Province,China (No.2018A0303130260,No.2016A030313284,and No.2017A030311008)the Guangzhou Science and Technology Plan (No.201804010057)the Fundamental Research Funds for the Central Universities (No.17ykpy06)
文摘Hypertrophic differentiation is not only the terminal process of endochondral ossification in the growth plate but is also an important pathological change in osteoarthritic cartilage.Collagen type II(COL2A1)was previously considered to be only a structural component of the cartilage matrix,but recently,it has been revealed to be an extracellular signaling molecule that can significantly suppress chondrocyte hypertrophy.However,the mechanisms by which COL2A1 regulates hypertrophic differentiation remain unclear.In our study,a Col2a1 p.Gly1170Ser mutant mouse model was constructed,and Col2a1 loss was demonstrated in homozygotes.Loss of Col2a1 was found to accelerate chondrocyte hypertrophy through the bone morphogenetic protein(BMP)-SMAD1 pathway.Upon interacting with COL2A1,integrinβ1(ITGB1),the major receptor for COL2A1,competed with BMP receptors for binding to SMAD1 and then inhibited SMAD1 activation and nuclear import.COL2A1 could also activate ITGB1-induced ERK1/2 phosphorylation and,through ERK1/2-SMAD1 interaction,it further repressed SMAD1 activation,thus inhibiting BMP-SMAD1-mediated chondrocyte hypertrophy.Moreover,COL2A1 expression was downregulated,while chondrocyte hypertrophic markers and BMP-SMAD1 signaling activity were upregulated in degenerative human articular cartilage.Our study reveals novel mechanisms for the inhibition of chondrocyte hypertrophy by COL2A1 and suggests that the degradation and decrease in COL2A1 might initiate and promote osteoarthritis progression.
基金This work was supported by the National Natural Science Foundation of China(No.31772368,31572176,and 31521092)the National Modern Agriculture(Citrus)Technology Systems of China(No.CARS-27)the National Science&Technology Pillar Program of China(2015BAD16B06).
文摘Naturally,resistant crop germplasms are important resources for managing the issues of agricultural product safety and environment deterioration.We found a spontaneous mutant of‘Newhall’navel orange(Citrus sinensis Osbeck)(MT)with broad-spectrum protections against fungal pathogens in the orchard,postharvest-storage,and artificial inoculation conditions.To understand the defense mechanism of MT fruit,we constructed a genome-scale metabolic network that integrated metabolome and transcriptome datasets.The coordinated transcriptomic and metabolic data were enriched in two sub-networks,showing the decrease in very long chain fatty acid(by 41.53%)and cuticular wax synthesis(by 81.34%),and increase in the synthesis of jasmonic acid(JA)(by 95.23%)and JA-induced metabolites such as 5-dimethylnobietin(by 28.37%)in MT.Furthermore,cytological and biochemical analyses confirmed that the response to fungal infection in MT was independent of wax deficiency and was correlated with the levels of jasmonates,and the expression of plant defensin gene PDF1.2.Results of exogenous application of MeJA and JA inhibitors such as propyl gallate proved that JA-mediated defense contributes to the strong tolerance against pathogens in MT.Our results indicated that jasmonate biosynthesis and signaling are stimulated by the fatty acid redirection of MT,and participate in the tolerance of pathogenic fungi.
基金supported by grants from the National Natural Sciences Foundation of China (NO. 81701800)the Joint Funds of Union Hospital,Huazhong University of Science and Technology,Republic of China (NO.000003720)+2 种基金the Key Laboratory of Molecular Imaging of Hubei Province,China (NO. 000003962)the key program of national natural science foundation of China (no. 81430040)the National Institutes of Health grant (R01EB012467)。
文摘Hepatocellular carcinoma(HCC) is one of the most deadly and frequent cancers worldwide,although great advancement in the treatment of this malignancy have been made within the past few decades.It continues to be a major health issue due to an increasing incidence and a poor prognosis.The majority of patients have their HCC diagnosed at an intermediate or advanced stage in theUSA or China.Curative therapy such as surgical resection or liver transplantation is not considered anoption of treatment at these stages.Transarterial chemoembolization(TACE),the most widely used locoregional therapeutic approach,used to be the mainstay of treatment for cases with unresectable cancer entities.However,for those patients with hypovascular tumors or impaired liver function reserve,TACE is a suboptimal treatment option.For example,embolization does not result in complete coverage of a hypovascular tumor,and may rather promotes postoperative tumor recurrence,or leave residual tumor,in these TACE-resistance patients.In addition,TACE carries a higher risk of hepatic decompensation in patients with poor liver function or reserve.Non-vascular interventional locoregional therapies for HCC include radiofrequency ablation(RFA),microwave ablation(MWA),high-intensity focused ultrasound(HIFU),laser-induced thermotherapy(LITT),cryosurgical ablation(CSA),irreversible Electroporation(IRE),percutaneous ethanol injection(PEI),and brachytherapy.Recent advancements in these techniques have significantly improved the treatment efficacy of HCC and expanded the population of patients who qualify for treatment.This review embraces the current status of imaging-guided locoregional non-intravascular interventional treatments for HCCs,with a primary focus on the clinical evaluation and assessment of the efficacy of combined therapies using these interventional techniques.
基金supported by the Key Forestry Public Welfare Project of China(201504105)the National Key Research and Development Program of China(2017YFD0600700)the Agricultural Science and Technology Independent Innovation Funds of Jiangsu Province[CX(16)1005].
文摘Ginkgo biloba is a famous living“fossil”and has played an important role in the evolution of the Plant Kingdom.Here,the complete chloroplast genome of G.biloba was sequenced and analysed.The chloroplast genome was 156,990 bp long and predicted to encode 134 genes including 85 protein-coding genes,41 tRNA genes and 8 rRNA genes.The chloroplast genome has a typical quadripartite structure with a pair of inverted repeat regions(IRa and IRb,17,732 bp),a large(LSC,99,259 bp)and small single(SSC,22,267 bp)copy region.After an extensive comparison to previously published gymnosperm plastomes,the gene content and organisation of G.biloba showed high divergence,although part was relatively conserved.The two typical IR regions in the G.biloba chloroplast genome were relatively shorter because it the ycf2 gene.In addition,it was obvious that the IR regions and gene loss were responsible for changes in chloroplast genome size and structure stability,which influenced plastome evolution in different gymnosperms.Phylogenetic analysis revealed that G.biloba is sister to cycads rather than to gnetophytes,cupressophytes,and Pinaceae.Overall,the study showed that the genomic characteristics of G.biloba would be of great help in the further research on the taxonomy,species identification and evolutionary history of gymnosperms,especially for their position in plant systematics and evolution.
文摘The first balloon angioplasty performed by Dr.Charles T.Dotter in 1964 marked the birth of a new discipline in radiology(1),which was initially named'interventional diagnostic radiology'by Dr.Alexander R.Margulis in 1967(2),and later defined as'Interventional Radiology(IR)'by Dr.Sidney Wallace in 1976(3).Along with the wide adaptation of Seldinger’s technique for percutaneous vascular access(4),interventional radiology expanded the horizon of traditional radiology.
基金supported by the Southern Plain Transportation Center(SPTC)under Award No.SPTC 15.1e06
文摘A discrete element method(DEM) model was used to simulate the development of compaction-induced stress in a granular base course, with and without geogrid reinforcement. The granular base course was modeled as a mixture of uniformly sized triangular particles. The geogrid was modeled as a series of equally spaced balls that interact with each other through long-range interaction contacts. The longrange interaction contact was also used to simulate a deformable subgrade. The compactor was modeled as a solid cylinder rolling at a constant speed. The DEM model shows that the geogridreinforced granular base course gains additional compaction-induced stress due to the residual tensile stress developed in the geogrid. The residual tensile stress in the geogrid increases with the number of compaction passes. Parametric analyses were also conducted to assess the effects of geogrid stiffness and subgrade modulus on the compaction-induced stress.
文摘The technique of ocean bottom cable (OBC) dual-sensor acquisition is an effective method to suppress the ghost wave and the reverberation at the receiver. With the advent of this technique, the processing method has become the key to the effective use of the OBC dual-sensor data. This paper has developed a new set of processing workflow based on the principle of combining the hydrophone and geophone data. This new process was applied to the OBC data acquired in Bohai area. The actual processing results show that the ghost and the reverberation are attenuated effectively. The frequency energy of the first notch point of the hydrophone data increased from −22 dB to −13 dB, and the frequency energy of the first notch point of the geophone data increased from −18 dB to −10 dB. The spectral characteristics of the dual-sensor data are more reasonable. The frequency spectrum is broadened and richer, and the resolution of the stack profile is improved greatly.
基金supported by the National Natural Science Foundation of China(grant no.81372404)the Postdoctoral Foundation of China(grant no.2012M521018)to Yueying Lithe Zhenjiang Social Development Project(No.SH2015072)to Yaxiang Shi
文摘Ginkgol C17:1 has been shown to inhibit apoptosis and migration of cancer cells,but the underlying mechanisms are not fully elucidated.In this study,we explored whether the inhibitory effects of Ginkgol C17:1 were associated with epidermal growth factor receptor(EGFR) and PI3K/Akt signaling.The results showed that EGF treatment increased the phosphorylation of EGFR,PI3 K,Akt,mTOR and NF-κB,and also enhanced the proliferation,migration and invasion of HepG2 cells.Ginkgol C17:1 dose-dependently inhibited EGF-induced phosphorylation/activation of all the key components including EGFR,PI3 K,Akt,mTOR and NF-kB,leading to a significant reduction either of proliferation or migration and invasion of HepG2 cells.Notably,treatment with Ginkgol C17:1 in mice suppressed the growth of tumor mass in vivo,and expression of EGFR in the tumor tissue.The results suggest that Ginkgol C17:1 is a potent tumor inhibiting compound that acts on EGF-induced signal transduction of the PI3K/Akt signaling pathways,and may represent a clinically interesting candidate for cancer therapy.
基金This research was funded by(the National Natural Science Foundation of China)Grant Number(71704016),(the Key Scientific Research Fund of Hunan Provincial Education Department of China)Grant Number(19A006),and(the Enterprise Strategic Management and Investment Decision Research Base of Hunan Province)Grant Number(19qyzd03).
文摘Big data knowledge,such as customer demands and consumer preferences,is among the crucial external knowledge that firms need for new product development in the big data environment.Prior research has focused on the profit of big data knowledge providers rather than the profit and pricing schemes of knowledge recipients.This research addresses this theoretical gap and uses theoretical and numerical analysis to compare the profitability of two pricing schemes commonly used by knowledge recipients:subscription pricing and pay-per-use pricing.We find that:(1)the subscription price of big data knowledge has no effect on the optimal time of knowledge transaction in the same pricing scheme,but the usage ratio of the big data knowledge affects the optimal time of knowledge transaction,and the smaller the usage ratio of big data knowledge the earlier the big data knowledge transaction conducts;(2)big data knowledge with a higher update rate can bring greater profits to the firm both in subscription pricing scheme and pay-per-use pricing scheme;(3)a knowledge recipient will choose the knowledge that can bring a higher market share growth rate regardless of what price scheme it adopts,and firms can choose more efficient knowledge in the pay-per-use pricing scheme by adjusting the usage ratio of knowledge usage according to their economic conditions.The model and findings in this paper can help knowledge recipient firms select optimal pricing method and enhance future new product development performance.
文摘Background:To investigate the underlying molecular mechanisms of radiofrequency hyperthermia(RFH)-enhanced direct chemotherapy of pancreatic cancers.Method:Rat ductal PaCa cell line DSL-6A/C1 and orthotopic pancreatic cancers of Lewis rats were divided into four study groups with various treatments:i)phosphate-buffered saline(PBS)as a control;ii)RFH alone;iii)intratumoral chemotherapy alone(gemcitabine);and(iv)combination therapy of gemcitabine plus intratumoral RFH at 42°C for30 min.In the in-vitro confirmation experiments,the viability and apoptosis of DSL-6A/C1 cells in each treatment group were evaluated using cell live/dead staining,flow cytometry,and Western blot.In the in vivo validation experiments,related proteins were evaluated by immunohistochemistry(IHC)staining of tumors.Results:Of the in-vitro experiments,the lowest cell viability and more apoptotic cells were shown in the group with combination therapy compared to other treatments.Western blot data showed elevated Bax/Bcl-2,Caspase-3,and HSP70 expressions in DSL cells with combination therapy,compared to other treatments.Of the in vivo experiments,IHC staining detected the significantly increased expressions of HSP70,IL-1β,TNF-ɑ,Bax,and Caspase-3 in pancreatic cancer tissues of the animal group treated by combination therapy of gemcitabine with RFH.Conclusion:Molecular imaging-guided interventional RFH can significantly enhance the chemotherapeutic effect on pancreatic cancers via potential molecular mechanisms of up-regulating Bax/caspase-3-dependent apoptosis pathways.
文摘Purpose To evaluate the performance of diffusion-weighted imaging(DWI) and variable flip angle(VFA) T1 mapping as a supplement to image-guided biopsy in follow-up analysis of liver fibrosis. Materials and Methods This prospective study was approved by the institution's committee on human research, and written informed consent was provided from the enrolled patients. We investigated five MRI parameters of DWI and VFA T1 mapping, collected from 11 patients who underwent serial ultrasound image-guided biopsy with follow-up MRI within 1.5 years after treatment for liver fibrosis/cirrhosis. For each patient, four consecutive MRI examinations were conducted, including baseline MRI before treatment and three follow-up MRI examinations after treatment at each 0.5-year interval. ADC values at four b values and T1 relaxation times were correlated to pathology-confirmed liver fibrosis stages, which were subsequently divided into two groups, stages F2–3 and F4. The receiver operating characteristic(ROC) analysis and repeated measurement analysis of variance were used for statistical analysis. Results Among these ADC parameters, ADC value(b = 500 s/mm^2) was the most consistent in differentiating between stage F2–3 and F4 liver fibrosis. Repeated measurement analysis showed that the intra-group and inter-group differences were 0.447 and 0.024, respectively. T1 relaxation time could not consistently differentiate between the F2–3 and F4 groups; however, it was repeatable, and the intra-group and inter-group differences were 0.410 and 0.042, respectively. Conclusion MRI-ADC value at a b value of 500 s/mm^2 can be a promising biomarker for differentiating stages F2–3 and F4 liver fibrosis. A combination of this biomarker with repeatable T1 relaxation time may function as a non-invasive tool for follow-up liver fibrosis in patients who reject repeated image-guided biopsy.
文摘In order to suppress the surface wave in three-component seismic exploration, according to the polarization characteristics of body wave and surface wave, a time-frequency domain polarization filtering method based on wavelet transform was studied. A covariance matrix was constructed in the time-frequency domain for the three-component seismic data, measured the polarization parameters of seismic waves. Combining the corresponding eigenvalues and eigenvectors of the matrix, the elliptic rate and elevation angle were used as constraints, and the polarization filter function was built to separate the surface waves. The separated surface waves were inversely transformed and then were adaptively subtracted from the original records. After the polarization filtering suppressed the surface wave, the signal-to-noise ratio of the converted wave was effectively improved. It laid a good foundation for the next seismic data processing and seismic exploration development. The actual data processing results show that the method can effectively extract surface waves from three-component seismic records and avoid the interference of surface waves on seismic signals.
文摘The fluid identification of carbonate reservoir is a key factor to hydrocarbon exploration and reservoir development. In order to simulate the seismic response characteristics of the cave in the carbonate reservoir, three sets of models were designed, including the caves varied in width, the caves filled with different solids, and the oil-gas-water model. The numerical simulation technique was used to carry out the forward modeling and the AVO (Amplitude varies with offset) response characteristics of the three groups of models were analyzed. The results show that the AVO characteristics can be observed when the cave reaches a certain extent in the horizontal direction. When the surrounding rock is constant, the absolute value of the intercept of the AVO curve increases with the Vp/Vs decrease. The AVO technology can effectively identify the gas cave. The effect is not obvious to water or oil cave.
基金supported by the National Natural Science Foundation of China(No.92068105,82172376,82072385).
文摘Mutation of the MAPK7 gene was related to human scoliosis.Mapk7 regulated the development of limb bones and skulls in mice.However,the role of MAPK7 in vertebral development is still unclear.In this study,we constructed Col2a1-cre;Mapk7 f/f transgenic mouse model to delete Mapk7 in cartilage,which displayed kyphosis and osteopenia.Mechanistically,Mapk7 loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes,which impaired chondrocyte hypertrophy and attenuated vertebral ossification.In vivo,systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by Mapk7 deficiency.Our study firstly clarified the mechanism by which MAPK7 was involved in vertebral development,which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.
基金supported by Natural Science Foundation of Chongqing,China(cstc2021jcyj-msxmx0027)Talent and Innovation Project of Beibei District in Chongqing(2022-11)Performance Incentive and Guidance Special Project of Scientific Research Organization,Chongqing Science and Technology(cstc2021jxjl130024).
文摘Long-wavelength fluorescence carbon dots (CDs) show great importance in multiple fields,especially for the biochemical sensing.Here,we proposed one type of CDs doped with nitrogen and sulfur through the hydrothermal method,which exhibited obvious yellow-fluorescence in aqueous solution.Importantly,the fluorescence intensity of CDs decreased with pH decreasing in the acidic range,thus a linear relationship between pH and fluorescence intensity was established,exhibiting the potential of pH sensing.Additionally,introducing tigecycline into CDs resulted in their decreased fluorescence,thus,we further established a strategy of detecting tigecycline with the concentration range of 200 μM to 7 nM.Meanwhile,we elucidated the static quenching as the major mechanism for CDs responding tigecycline,which was induced by the formed new complex between CDs and tigecycline.Furthermore,the practicality of the method was verified by examining the recovery of tigecycline in the actual lake-water samples.
基金supported by the National Key Research and Development Program of China(2017YFD0600701).
文摘Redwood trees(Sequoioideae),including Metasequoia glyptostroboides(dawn redwood),Sequoiadendron giganteum(giant sequoia),and Sequoia sempervirens(coast redwood),are threatened and widely recognized iconic tree species.Genomic resources for redwood trees could provide clues to their evolutionary relationships.Here,we report the 8-Gb reference genome of M.glyptostroboides and a comparative analysis with two related species.More than 62%of the M.glyptostroboides genome is composed of repetitive sequences.Clade-specific bursts of long terminal repeat retrotransposons may have contributed to genomic differentiation in the three species.The chromosomal synteny between M.glyptostroboides and S.giganteum is extremely high,whereas there has been significant chromosome reorganization in S.sempervirens.Phylogenetic analysis of marker genes indicates that S.sempervirens is an autopolyploid,and more than 48%of the gene trees are incongruent with the species tree.Results of multiple analyses suggest that incomplete lineage sorting(ILS)rather than hybridization explains the inconsistent phylogeny,indicating that genetic variation among redwoods may be due to random retention of polymorphisms in ancestral populations.Functional analysis of ortholog groups indicates that gene families of ion channels,tannin biosynthesis enzymes,and transcription factors for meristem maintenance have expanded in S.giganteum and S.sempervirens,which is consistent with their extreme height.As a wetland-tolerant species,M.glyptostroboides shows a transcriptional response to flooding stress that is conserved with that of analyzed angiosperm species.Our study offers insights into redwood evolution and adaptation and provides genomic resources to aid in their conservation and management.
文摘The epidemic of corona virus disease 2019(COVID-19)caused by severe acute respiratory syndrome Coronavirus 2 and its variants of concern(VOCs)has been ongoing for over 3 years.Antibody therapies encompassing convalescent plasma,hyperimmunoglobulin,and neutralizing monoclonal antibodies(mAbs)applied in passive immunotherapy have yielded positive outcomes and played a crucial role in the early COVID-19 treatment.In this review,the development path,action mechanism,clinical research results,challenges,and safety profile associated with the use of COVID-19 convalescent plasma,hyperimmunoglobulin,and mAbs were summarized.In addition,the prospects of applying antibody therapy against VOCs was assessed,offering insights into the coping strategies for facing new infectious disease outbreaks.
基金the National Health Committee of the People's Republic of China(grant number:2019ZX09302059).
文摘The oral hexavalent live human-bovine reassortant rotavirus vaccine(RV6)developed by Wuhan Institute of Biological Products Co.,Ltd(WIBP)has finished a randomized,placebo-controlled phase III clinical trial in four provinces of China in 2021.The trail demonstrated that RV6 has a high vaccine efficacy against the prevalent strains and is safe for use in infants.During the phase III clinical trial(2019–2021),200 rotavirus-positive fecal samples from children with RV gastroenteritis(RVGE)were further studied.Using reverse transcription-polymerase chain reaction and high-throughput sequencing,VP7 and VP4 sequences were obtained and their genetic characteristics,as well as the differences in antigenic epitopes of VP7,were analyzed in detail.Seven rotavirus genotypes were identified.The predominant rotavirus genotype was G9P[8](77.0%),followed by prevalent strains G8P[8](8.0%),G3P[8](3.5%),G3P[9](1.5%),G1P[8](1.0%),G2P[4](1.0%),and G4P[6](1.0%).The amino acid sequence identities of G1,G2,G3,G4,G8,and G9 genotypes of isolates compared to the vaccine strains were 98.8%,98.2%–99.7%,88.4%–99.4%,98.2%,94.2%–100%,and 93.9%–100%,respectively.Notably,the vaccine strains exhibited high similarity in amino acid sequence,with only minor differences in antigenic epitopes compared to the Chinese endemic strains.This supports the potential application of the vaccine in preventing diseases caused by rotaviruses.
