The development of communication technology will promote the application of Internet of Things,and Beyond 5G will become a new technology promoter.At the same time,Beyond 5G will become one of the important supports f...The development of communication technology will promote the application of Internet of Things,and Beyond 5G will become a new technology promoter.At the same time,Beyond 5G will become one of the important supports for the development of edge computing technology.This paper proposes a communication task allocation algorithm based on deep reinforcement learning for vehicle-to-pedestrian communication scenarios in edge computing.Through trial and error learning of agent,the optimal spectrum and power can be determined for transmission without global information,so as to balance the communication between vehicle-to-pedestrian and vehicle-to-infrastructure.The results show that the agent can effectively improve vehicle-to-infrastructure communication rate as well as meeting the delay constraints on the vehicle-to-pedestrian link.展开更多
Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also ...Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also conducted an initial examination of the underlying molecular mechanisms.Methods:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding treatment.After DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day 8.Mice in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut implantation.Severity was assessed using SCORAD on treatment days 1,10,and 20.On day 18,nine mice per group were euthanized,and the remaining on day 28.Histopathological changes were observed using hematoxylin-eosin and immunohistochemistry staining.TNF-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western blot.Results:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like mice.Significant decreases occurred in serum IL-4,IL-6,IL-13,and TNF-αlevels.Skin analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein levels.Conclusion:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.展开更多
Background:In this research,we investigated the anti-cancer effect and the related mechanism of 2-[2-(4-chlorobenzamidomethylthio)-1,3,4-thiadiazol-5-yl]-1,2-benziselenazol-3(2H)-one compound(CTBO)and 2-[2-(4-nitroben...Background:In this research,we investigated the anti-cancer effect and the related mechanism of 2-[2-(4-chlorobenzamidomethylthio)-1,3,4-thiadiazol-5-yl]-1,2-benziselenazol-3(2H)-one compound(CTBO)and 2-[2-(4-nitrobenzamidomethylthio)-1,3,4-thiadiazol-5-yl]-1,2-benziselenazol-3(2H)-one compound(NTBO),which we synthesized in our lab previously.Methods:We applied the human lung cancer adenocarcinoma A549 cells to investigate the anti-tumor effect of CTBO and NTBO.The following methods were used in the research,including methylthiazolyldiphenyl-tetrazolium bromide assay,one-step terminal-deoxynucleotidyl transferase mediated nick end labeling,transcriptome sequencing analysis,quantitative reverse transcription polymerase chain reaction and western blot.Results:The results showed that both CTBO and NTBO significantly inhibited the A549 cells proliferation and induced the A549 cells apoptosis.The transcriptome sequencing analysis results illustrated that the two derivatives might exert the apoptotic effects through mitogen-activated protein kinase and tumor necrosis factor signaling pathways activation.Further,the western blot results suggested that CTBO and NTBO exerted anti-cancer effect through different molecular mechanisms.Conclusion:The results above provided fundamental research evidence for the further application of benziselenazolone derivatives in clinical.展开更多
3D Bioprinting plays an irreplaceable role in bone tissue engineering. Shellac and curcumin are two natural compounds that are widely used in the food and pharmaceutical sectors. In this study, a new composite scaffol...3D Bioprinting plays an irreplaceable role in bone tissue engineering. Shellac and curcumin are two natural compounds that are widely used in the food and pharmaceutical sectors. In this study, a new composite scaffold with good biocompatibility and antibacterial ability was manufactured by adding shellac and curcumin into the traditional bone scaffold through low-temperature three-dimensional printing (LT-3DP), and its impact on the osteoimmune microenvironment was evaluated.展开更多
The Accelerator Driven Sub-critical(ADS)system is a strategic plan to solve the nuclear waste problem for nuclear power plants in China.High-energy particle accelerators and colliders contain long strings of supercond...The Accelerator Driven Sub-critical(ADS)system is a strategic plan to solve the nuclear waste problem for nuclear power plants in China.High-energy particle accelerators and colliders contain long strings of superconducting devices,superconducting radio frequency cavities,and magnets,which may require cooling by 2 K superfluid helium(HeliumⅡ).2 K superfluid helium cryogenic system has become a research hot spot in the field of superconducting accelerators.In this study,the ADS Injector-I 2 K cryogenic system is examined in detail.The cryogenic system scheme design,key equipment,and technology design,such as the 2 K Joule–Thomson(J–T)heat exchanger and cryomodules CM1+CM2 design,are examined,in addition to the commissioning and operation of the cryogenic system.The ADS Injector-I 2 K cryogenic system is the first 100 W superfluid helium system designed and built independently in China.The ADS proton beam reached 10 Me V at 10 m A in July 2016 and 10 Me V at 2 m A in continuous mode in January 2017 and has been operated reliably for over 15,000 h,proving that the design of ADS Injector-I 2 K cryogenic system,the key equipment,and technology research are reasonable,reliable,and meet the requirements.The research into key technologies provides valuable engineering experience that can be helpful for future projects such as CI-ADS(China Initiative Accelerator-Driven System),SHINE(Shanghai High Repetition Rate XFEL and Extreme Light Facility),PAPS(Platform of Advanced Photon Source Technology),and CEPC(Circular Electron-Positron Collider),thereby developing national expertise in the field of superfluid helium cryogenic systems.展开更多
Isotopic and chemical compositions of pore water(PW) are highly relevant to environmental and forensic study. Five lake water(LW)samples and five sediment samples were collected to investigate the effects of pore size...Isotopic and chemical compositions of pore water(PW) are highly relevant to environmental and forensic study. Five lake water(LW)samples and five sediment samples were collected to investigate the effects of pore sizes of sediments on PW chemistry and stable isotopes and determine mechanisms controlling their variations. Six pore water fractions were extracted from different-sized pores in each sediment sample at six sequential centrifugal speeds for chemical and isotopic analysis. The sediments consisted mainly of quartz, feldspar, and clay minerals. The hydrogen and oxygen isotopic compositions of PW are mainly controlled by the overlying LW, although the lag effect of exchange between overlying LW and PW results in isotopic differences when recharge of LW is quicker than isotopic exchange in PW. Identical isotopic compositions of PW from sediments with different pore sizes indicate that isotopic exchange of water molecules with different pore sizes is a quick process. The ratio of average total dissolved solid(TDS) concentration of PW to TDS concentration of LW shows a strong relationship with adsorption capacity of sediments, demonstrating that remobilization of ions bound to sediments mainly causes a chemical shift from LW to PW.Concentrations of Ca^(2+), Mg^(2+),and Cl^-in PW remain unchanged,while concentrations of Na^+,K^+,and SO_4^(2-) slightly increase with decreasing pore size. Chemical differences of PW from sediments with different pore sizes are governed by ion adsorption properties and surface characteristics of different-si zed particles.展开更多
The Luanhe River Delta is located in the center of the Circum-Bohai Sea Economic Zone.It enjoys rapid economic and social development while suffering relatively water scarcity.The overexploitation of groundwater in th...The Luanhe River Delta is located in the center of the Circum-Bohai Sea Economic Zone.It enjoys rapid economic and social development while suffering relatively water scarcity.The overexploitation of groundwater in the Luanhe River Delta in recent years has caused the continuous drop of groundwater level and serious environmental and geological problems.This study systematically analyzes the evolution characteristics of the population,economy,and groundwater exploitation in the Luanhe River Delta and summarizes the change patterns of the groundwater flow regime in different aquifers in the Luanhe River Delta according to previous water resource assessment data as well as the latest groundwater survey results.Through comparison of major source/sink terms and groundwater resources,the study reveals the impacts of human activities on the groundwater resources and ecological environment in the study area over the past 30 years from 1990 to 2020.The results are as follows.The average annual drop rate of shallow groundwater and the deep groundwater in the centers of depression cones is 0.4 m and 1.64 m,respectively in the Luanhe River Delta in the past 30 years.The depression cones of shallow and deep groundwater in the study area cover an area of 545.32 km^(2)and 548.79 km^(2),respectively,accounting for more than 10%of the total area of the Luanhe River Delta.Overexploitation of groundwater has further aggravated land subsidence.As a result,two large-scale subsidence centers have formed,with a maximum subsidence rate of up to 120 mm/a.The drop of groundwater level has induced some ecological problems in the Luanhe River Delta area,such as the zero flow and water quality deterioration of rivers and continuous shrinkage of natural wetlands and water.Meanwhile,the proportion of natural wetland area to the total wetland area has been decreased from 99%to 8%and the water area from 1776 km^(2)to 263 km^(2).These results will provide data for groundwater overexploitation control,land subsidence prevention,and ecological restoration in plains and provide services for water resources management and national land space planning.展开更多
Plant viruses are mainly transmitted by insect vectors in the non-persistent,semi-persistent,or persistent modes.In the non-persistent mode,plant viruses are retained in the stylets of their insect vectors.In the semi...Plant viruses are mainly transmitted by insect vectors in the non-persistent,semi-persistent,or persistent modes.In the non-persistent mode,plant viruses are retained in the stylets of their insect vectors.In the semi-persistent mode,plant viruses are carried to vector foreguts or salivary glands,but they cannot spread to salivary glands.In the persistent mode,plant viruses are retained in vector guts and can spread to salivary glands.In the non-persistent and semi-persistent modes,plant viruses are retained for a short time and cannot enter the hemolymph of insect vectors,whereas in the persistent mode,plant viruses are retained for a relatively long time and can be found in the hemolymph.Here,we reviewed recent studies that uncovered molecular mechanisms of how plant viruses manipulate host traits for efficient transmission by insect vectors.Normally,plants that are infected with viruses,regardless of the transmission mode,tend to release more attractive volatiles to vectors.However,plant defensive systems are regulated differently by viruses in these three modes.In the non-persistent mode,virus infections significantly induce plant defense responses,which probably trigger vectors(e.g.,winged aphids)to disperse and transmit viruses in a short time.In the semi-persistent mode,virus infections frequently suppress plant defense responses,resulting in an increase of vector population and facilitating viral transmissions during vector outbreaks.In the persistent mode,virus infections reduce plant defense responses and manipulate plant traits to become suitable feeding sites in a relatively long period of time.Understanding the underlying mechanisms of virus–vector–plant interactions will lay a foundation for preventing virus transmission.展开更多
Main quadrupole magnets are critical for the Circular Electron and Positron Collider(CEPC)and are specifically designed as dual aperture quadrupole(DAQ)magnets.However,the field crosstalk between the two apertures pre...Main quadrupole magnets are critical for the Circular Electron and Positron Collider(CEPC)and are specifically designed as dual aperture quadrupole(DAQ)magnets.However,the field crosstalk between the two apertures presents challenges.As the CEPC will work at four beam energies of Z,W,Higgs and ttbar mode,the DAQ magnets will operate at four field gradients spanning from 3.18 to 12.63 T/m.The first short quadrupole magnet prototype with the bore diameter of 76 mm and magnetic length of 1.0 m revealed the problems of large magnetic field harmonics and a magnetic center shift within the beam energy range.Accordingly,a compensation method was proposed in this work to solve the field crosstalk effect.By adjusting the gap height at the middle of the two apertures,the field harmonics and magnetic center shift are significantly reduced.After optimization,the short prototype was modified using a new scheme.The field simulations are validated from the magnetic measurement results.Further,the multipole field meets the requirements of the four beam energies.The detailed magnetic field optimization,field harmonics adjustment,and measurement results are presented herein.展开更多
A 16-pole superconducting multipole wiggler with a large gap of 68 mm was designed and fabricated to serve as a multipole wiggler for HEPS-TF.The wiggler consists of 16 pairs of NbTi superconducting coils with a perio...A 16-pole superconducting multipole wiggler with a large gap of 68 mm was designed and fabricated to serve as a multipole wiggler for HEPS-TF.The wiggler consists of 16 pairs of NbTi superconducting coils with a period length of 170 mm,and its maximum peak field is 2.6 Tesla.In magnet design,magnet poles were optimized.Furthermore,the Lorentz force on the coils and electromagnetic force between the upper and lower halves were computed and analyzed along with the stored energy and inductance at different currents.To enhance the critical current of the magnet coil,all the pole coils selected for the magnet exhibited excellent performance,and appropriate prestress derived from the coil force analysis was applied to the pole coils during magnet assembly.The entire magnet structure was immersed in 4.2-K liquid helium in the cryostat cooled solely by four two-stage cryocoolers,and the performance test of the superconducting wiggler was appropriately completed.Based on the measured results,the first and second field integrals on the axis of the superconducting wiggler were significantly improved at different field levels after the compensation of the corrector coils.Subsequently,the wiggler was successfully installed in the storage ring of BEPCII operation with beams.展开更多
As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of ...As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production.Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.展开更多
Based on the LINAC of BEPCII, a high-polarized, high bightness, energy-tunable, monoenergetic laser compton backscattering (LCS)gamma-ray source is under construction at IHEP. The gamma-ray energy range is from 1 MeV ...Based on the LINAC of BEPCII, a high-polarized, high bightness, energy-tunable, monoenergetic laser compton backscattering (LCS)gamma-ray source is under construction at IHEP. The gamma-ray energy range is from 1 MeV to 111 MeV. It is a powerful and hopeful researchplatform to reveal the underlying physics of the nuclear, the basic particles and the vacuum or to check the exist basic physical models, quantumelectrodynamic (QED) theories. In the platform, a 1.064 mm Nd:YAG laser system and a 10.6 mm CO_(2) laser system are employed. All the triggersignals to the laser system and the electron control system are from the only reference clock at the very beginning of the LINAC to make sure thetemporal synchronization. Two optical transition radiation (OTR) targets and two charged-couple devices (CCD) are used to monitor and to alignthe electron beam and the laser beam. With the LCS gamma-ray source, it is proposed to experimentally check the gamma-ray calibrations, thephoton-nuclear physics, nuclear astrophysics and some basic QED phenomena.展开更多
BACKGROUND: Stroke prevention guidelines should be made available application to aid in uniformity, timing, preciseness, and acceptance of disease. OBJECTIVE: To investigate the awareness of neurologists in some Bei...BACKGROUND: Stroke prevention guidelines should be made available application to aid in uniformity, timing, preciseness, and acceptance of disease. OBJECTIVE: To investigate the awareness of neurologists in some Beijing secondary prevention of cerebral infarction/transient ischemia. DESIGN: Cross-sectional study. to neurologists for clinical hospitals of intervention in SETTING: Beijing Tiantan Hospital, Beijing Anzhen Hospital, General Hospital of Beijing Military Area, Command of Chinese PLA, Beijing Chuiyangliu Hospital, Beijing 6^th Hospital, Beijing Hepingli Hospital, and Beijing Daxing District Hospital. PARTICIPANTS: A total of 28 (associate) chief physicians, 58 attending physicians, and 54 resident physicians who engaged in clinical treatment of cerebrovascular diseases were selected from 8 hospitals in Beijing from March to April 2007. All physicians provided informed consent. METHODS: Self-made closed questionnaires were provided for data collection, consisting of 16 questions that were single choice or multiple choice. Specifically, questions 1-7 focused on awareness of blood pressure regulation in different patients and first choice of decompression drug; questions 8-12 focused on awareness of lipid regulation; and questions 13-16 focused on awareness of anti-blood platelet drugs applied in secondary prevention. The scores ranged from 0-100 points, and each question was worth 6.25 points. The scores positively correlated with the awareness rate. To test leveling real-time, the survey lasted for a maximum of 20 minutes. One questionnaire was independently finished by each subject in the survey. MAIN OUTCOME MEASURES: Awareness intervention among neurologists during secondary prevention of cerebral infarction/transient ischemia and questionnaire scores. RESULTS: 140 subjects were included in the final analysis. ① The awareness rate among neurologists for intervention during secondary prevention of cerebral infarction/transient ischemia ranged from 0.7-57.9%, the scores ranged between 0-56 points, and the mean score was 26 points.② Scores of resident physicians were 0-56 points with a mean score of 26 points; attending physicians scored 6-50 points, with a mean score of 26 points; and chief physicians scored 6-50 points, with a mean score of 23 points. There were no significant differences among the various physicians (F = 0.771, t = 0.465, P 〉 0.05). CONCLUSION: Awareness among neurologists of intervention during secondary prevention of cerebral infarction/transient ischemia is not ideal. However, there was no significant difference between professional titles.展开更多
A growing number of children and adolescents are being diagnosed as Chiari malformation type I (CM- I ) for behavioral disorders, developmental delay, seizures, or abnormal orpharyngeal function. The aim of this stu...A growing number of children and adolescents are being diagnosed as Chiari malformation type I (CM- I ) for behavioral disorders, developmental delay, seizures, or abnormal orpharyngeal function. The aim of this study was to compare the clinical characteristics, imaging findings and surgical outcomes of CM- I in pediatric and adult patients. Between January 2014 and June 2017, 84 patients with CM- I underwent surgical treatment in our department. We divided the patients into two groups: pediatric group (n=l 1, age 〈18 years) and adult group (n=73, age 〉18 years). Data on clinical characteristics, imaging findings, surgical outcomes, and prognosis were retrospectively reviewed and compared between these two groups. For clinical presentation, scoliosis (36.4%) and developmental delay (36.4%) were more common in pediatric patients, whereas, sensory disturbance (58.9%) and motor weakness (41. 1%) were more common in adult patients. Imaging findings showed that the incidence of hydrocephalus and craniovertebral junctional abnormalities was significantly higher in pediatric group than in adult group (P〈0.05). Compared to adult group, pediatric group showed a better improvement or resolution of syrinx and tonsillar herniation after surgical treatments (P〈0.05). The total Chicago Chiari Outcome Scale (CCOS) score in pediatric patients at the last follow- up was significantly higher than that in adult patients (P=0.002). In conclusion, the clinical characteristics and imaging findings appeared to be different in pediatric and adult patients with CM- I. The surgical outcomes of pediatric patients were shown to be significantly better than those of adult patients.展开更多
Objective Pituitary adenomas(PAs)can adapt an aggressive phenotype by invading adjacent brain structures with rapid cellular proliferation.Previous studies demonstrated that excessive expression of metalloproteases AD...Objective Pituitary adenomas(PAs)can adapt an aggressive phenotype by invading adjacent brain structures with rapid cellular proliferation.Previous studies demonstrated that excessive expression of metalloproteases ADAM12 and MMP-14 is instrumental for the active proliferation and invasiveness of PA cells in vitro and of tumors in vivo.However,the mechanisms regulating ADAM12 and MMP-14 expression in PAs remain unclear.Methods Target gene prediction and transcriptomic profiling of invasive vs.noninvasive human PA samples were performed to identify miRNA species potentially involved in the regulation of ADAM12 and MMP14.For cellular analyses of miRNA functions,two mouse PA cell lines(AtT20 and TtT/GF)were transfected with miR-149-3p and miR-149-5p,respectively.The effects of miR-149(3p and 5p)on expression levels of ADAM12 and MMP14 were determined by Western blotting followed by an analysis of proliferation and colony formation assays,scratch migration assays,and invasion assays.Results A significant downregulation of miRNA-149 was observed in invasive vs.noninvasive PA(0.32 vs.0.09,P<0.0001).In AtT-20 and TtT/GF mouse PAs cells,transfection of mimic miRNA-149(3p and 5p)caused a significantly reduced cell proliferation and matrigel invasion,whilst the effect on cell migration was less pronounced.Both strands of miRNA-149(3p and 5p)markedly reduced protein levels of ADAM12 and MMP-14 by at least 40%in both cell lines.Conclusion This study proved that the invasiveness of PA cells is,at least partly,regulated by miRNA-149-dependent expression of ADAM12 and MMP-14.展开更多
The purpose of the present study was to investigate the impact of genetic polymorphism on fluvastatin pharmacokinetics.In addition,we compared the fluvastatin pharmacokinetics differences between extended-release(ER)8...The purpose of the present study was to investigate the impact of genetic polymorphism on fluvastatin pharmacokinetics.In addition,we compared the fluvastatin pharmacokinetics differences between extended-release(ER)80 mg tablet and immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter genetic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study(n=24),effects of ABCG2,SLCO1B1,ABCB1,CYP2C9 and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed.The administration dosage for IR 40 mg and ER 80 mg were twice and once daily,respectively,for total 7 d.Blood samples for pharmacokinetic evaluation were taken on the 1st and 7th d.The lower exposure following ER was observed.For ER tablets,SLCO1B1 T521C genotype correlated with AUC 0-24 of repeat doses(P=0.010).SLCO1B1 T521C genotype had no statistically significant effect on AUC 0-24 of IR capsule of fluvastatin after single or repeated doses.In vitro study demonstrated that when the concentration of fluvastatin was low(<1μmol/l),the uptake of fluvastatin in the HEK293-OATP1B1 with SLCO1B1521TT(K m=0.18μmol/l)was faster than that with SLCO1B1521CC(K m=0.49μmol/l),On the other hand,when concentration reached to higher level(>1μmol/l),transport velocity of fluvastatin by HEK293-OATP1B1 with SLCO1B1521TT(K m=11.4μmol/l)and with SLCO1B1521TCC(K m=15.1μmol/l)tend to be the same.It suggests that the increased effect of SLCO1B1 T521C genotype on ER formulation of fluvastatin was mainly caused by lower blood concentrations.We recommend that formulation should be incorporated into future pharmacogenomics studies.展开更多
With the fast development of business logic and information technology, today's best solutions are tomorrow's legacy systems. In China, the situation in the education domain follows the same path. Currently, there e...With the fast development of business logic and information technology, today's best solutions are tomorrow's legacy systems. In China, the situation in the education domain follows the same path. Currently, there exists a number of e-learning legacy assets with accumulated practical business experience, such as program resource, usage behaviour data resource, and so on. In order to use these legacy assets adequately and efficiently, we should not only utilize the explicit assets but also discover the hidden assets. The usage behaviour data resource is the set of practical operation sequences requested by all users. The hidden patterns in this data resource will provide users' practical experiences, which can benefit the service composition in service-oriented architecture (SOA) migration. Namely, these discovered patterns will be the candidate composite services (coarse-grained) in SOA systems. Although data mining techniques have been used for software engineering tasks, little is known about how they can be used for service composition of migrating an e-learning legacy system (MELS) to SOA. In this paper, we propose a service composition approach based on sequence mining techniques for MELS. Composite services found by this approach will be the complementation of business logic analysis results of MELS. The core of this approach is to develop an appropriate sequence mining algorithm for mining related data collected from an e-learning legacy system. According to the features of execution trace data on usage behaviour from this e-learning legacy system and needs of further pattern analysis, we propose a sequential mining algorithm to mine this kind of data of tile legacy system. For validation, this approach has been applied to the corresponding real data, which was collected from the e-learning legacy system; meanwhile, some investigation questionnaires were set up to collect satisfaction data. The investigation result is 90% the same with the result obtained through our approach.展开更多
Prunus pusilliflora is a wild cherry germplasm resource distributed mainly in Southwest China.Despite its ornamental and economic value,a high-quality assembled P.pusilliflora genome is unavailable,hindering our under...Prunus pusilliflora is a wild cherry germplasm resource distributed mainly in Southwest China.Despite its ornamental and economic value,a high-quality assembled P.pusilliflora genome is unavailable,hindering our understanding of its genetic background,population diversity,and evolutionary processes.Here,we de novo assembled a chromosome-scale P.pusilliflora genome using Oxford Nanopore,Illumina,and chromosome conformation capture sequencing.The assembled genome size was 309.62 Mb,with 76 scaffolds anchored to eight pseudochromosomes.We predicted 33035 protein-coding genes,functionally annotated 98.27%of them,and identified repetitive sequences covering 49.08%of the genome.We found that P.pusilliflora is closely related to Prunus serrulata and Prunus yedoensis,having diverged from them∼41.8 million years ago.A comparative genomic analysis revealed that P.pusilliflora has 643 expanded and 1128 contracted gene families.Furthermore,we found that P.pusilliflora is more resistant to Colletotrichum viniferum,Phytophthora capsici,and Pseudomonas syringae pv.tomato(Pst)DC3000 infections than cultivated Prunus avium.P.pusilliflora also has considerably more nucleotide-binding site-type resistance gene analogs than P.avium,which explains its stronger disease resistance.The cytochrome P450 and WRKY families of 263 and 61 proteins were divided into 42 and 8 subfamilies respectively in P.pusilliflora.Furthermore,81 MADS-box genes were identified in P.pusilliflora,accompanying expansions of the SVP and AGL15 subfamilies and loss of the TM3 subfamily.Our assembly of a high-quality P.pusilliflora genome will be valuable for further research on cherries and molecular breeding.展开更多
基金supported by National Natural Science Foundation of China(No.61871283)the Foundation of Pre-Research on Equipment of China(No.61400010304)Major Civil-Military Integration Project in Tianjin,China(No.18ZXJMTG00170).
文摘The development of communication technology will promote the application of Internet of Things,and Beyond 5G will become a new technology promoter.At the same time,Beyond 5G will become one of the important supports for the development of edge computing technology.This paper proposes a communication task allocation algorithm based on deep reinforcement learning for vehicle-to-pedestrian communication scenarios in edge computing.Through trial and error learning of agent,the optimal spectrum and power can be determined for transmission without global information,so as to balance the communication between vehicle-to-pedestrian and vehicle-to-infrastructure.The results show that the agent can effectively improve vehicle-to-infrastructure communication rate as well as meeting the delay constraints on the vehicle-to-pedestrian link.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82260940)the Yunnan Provincial(Traditional Chinese Medicine)Clinical Dermatology Center,12th Five-year Key Construction Discipline of State Administration of Traditional Chinese Medicine“Dai Pharmacy”+1 种基金Open Project of Yunnan Key Laboratory of Dai and Yi Medicines(No.30971101100)Key Laboratory of Chemistry in Ethnic Medicinal Resources,State Ethnic Affairs Commission&Ministry of Education,Yunnan Minzu University.
文摘Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also conducted an initial examination of the underlying molecular mechanisms.Methods:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding treatment.After DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day 8.Mice in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut implantation.Severity was assessed using SCORAD on treatment days 1,10,and 20.On day 18,nine mice per group were euthanized,and the remaining on day 28.Histopathological changes were observed using hematoxylin-eosin and immunohistochemistry staining.TNF-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western blot.Results:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like mice.Significant decreases occurred in serum IL-4,IL-6,IL-13,and TNF-αlevels.Skin analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein levels.Conclusion:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.
基金supported by the National Natural Science Foundation of China(NSFC)Youth Project(No.82204397).
文摘Background:In this research,we investigated the anti-cancer effect and the related mechanism of 2-[2-(4-chlorobenzamidomethylthio)-1,3,4-thiadiazol-5-yl]-1,2-benziselenazol-3(2H)-one compound(CTBO)and 2-[2-(4-nitrobenzamidomethylthio)-1,3,4-thiadiazol-5-yl]-1,2-benziselenazol-3(2H)-one compound(NTBO),which we synthesized in our lab previously.Methods:We applied the human lung cancer adenocarcinoma A549 cells to investigate the anti-tumor effect of CTBO and NTBO.The following methods were used in the research,including methylthiazolyldiphenyl-tetrazolium bromide assay,one-step terminal-deoxynucleotidyl transferase mediated nick end labeling,transcriptome sequencing analysis,quantitative reverse transcription polymerase chain reaction and western blot.Results:The results showed that both CTBO and NTBO significantly inhibited the A549 cells proliferation and induced the A549 cells apoptosis.The transcriptome sequencing analysis results illustrated that the two derivatives might exert the apoptotic effects through mitogen-activated protein kinase and tumor necrosis factor signaling pathways activation.Further,the western blot results suggested that CTBO and NTBO exerted anti-cancer effect through different molecular mechanisms.Conclusion:The results above provided fundamental research evidence for the further application of benziselenazolone derivatives in clinical.
文摘3D Bioprinting plays an irreplaceable role in bone tissue engineering. Shellac and curcumin are two natural compounds that are widely used in the food and pharmaceutical sectors. In this study, a new composite scaffold with good biocompatibility and antibacterial ability was manufactured by adding shellac and curcumin into the traditional bone scaffold through low-temperature three-dimensional printing (LT-3DP), and its impact on the osteoimmune microenvironment was evaluated.
文摘The Accelerator Driven Sub-critical(ADS)system is a strategic plan to solve the nuclear waste problem for nuclear power plants in China.High-energy particle accelerators and colliders contain long strings of superconducting devices,superconducting radio frequency cavities,and magnets,which may require cooling by 2 K superfluid helium(HeliumⅡ).2 K superfluid helium cryogenic system has become a research hot spot in the field of superconducting accelerators.In this study,the ADS Injector-I 2 K cryogenic system is examined in detail.The cryogenic system scheme design,key equipment,and technology design,such as the 2 K Joule–Thomson(J–T)heat exchanger and cryomodules CM1+CM2 design,are examined,in addition to the commissioning and operation of the cryogenic system.The ADS Injector-I 2 K cryogenic system is the first 100 W superfluid helium system designed and built independently in China.The ADS proton beam reached 10 Me V at 10 m A in July 2016 and 10 Me V at 2 m A in continuous mode in January 2017 and has been operated reliably for over 15,000 h,proving that the design of ADS Injector-I 2 K cryogenic system,the key equipment,and technology research are reasonable,reliable,and meet the requirements.The research into key technologies provides valuable engineering experience that can be helpful for future projects such as CI-ADS(China Initiative Accelerator-Driven System),SHINE(Shanghai High Repetition Rate XFEL and Extreme Light Facility),PAPS(Platform of Advanced Photon Source Technology),and CEPC(Circular Electron-Positron Collider),thereby developing national expertise in the field of superfluid helium cryogenic systems.
基金supported by the National Natural Science Foundation of China(Grants No.41672225 and 41222020)the Program of the China Geology Survey(Grant No.12120113103700)the Fundamental Research Funds for the Central Universities(Grant No.2652013028)
文摘Isotopic and chemical compositions of pore water(PW) are highly relevant to environmental and forensic study. Five lake water(LW)samples and five sediment samples were collected to investigate the effects of pore sizes of sediments on PW chemistry and stable isotopes and determine mechanisms controlling their variations. Six pore water fractions were extracted from different-sized pores in each sediment sample at six sequential centrifugal speeds for chemical and isotopic analysis. The sediments consisted mainly of quartz, feldspar, and clay minerals. The hydrogen and oxygen isotopic compositions of PW are mainly controlled by the overlying LW, although the lag effect of exchange between overlying LW and PW results in isotopic differences when recharge of LW is quicker than isotopic exchange in PW. Identical isotopic compositions of PW from sediments with different pore sizes indicate that isotopic exchange of water molecules with different pore sizes is a quick process. The ratio of average total dissolved solid(TDS) concentration of PW to TDS concentration of LW shows a strong relationship with adsorption capacity of sediments, demonstrating that remobilization of ions bound to sediments mainly causes a chemical shift from LW to PW.Concentrations of Ca^(2+), Mg^(2+),and Cl^-in PW remain unchanged,while concentrations of Na^+,K^+,and SO_4^(2-) slightly increase with decreasing pore size. Chemical differences of PW from sediments with different pore sizes are governed by ion adsorption properties and surface characteristics of different-si zed particles.
基金This research is jointly funded by the“Project of Hydrogeological survey of Luanhe River Basin”of China Geological Survey(No.DD20190338)General Project of National Natural Science Foundation of China(No.41972196)+1 种基金Youth Fund of the National Natural Science Foundation of China(No.41907149)China Postdoctoral Foundation(No.2018M631732).
文摘The Luanhe River Delta is located in the center of the Circum-Bohai Sea Economic Zone.It enjoys rapid economic and social development while suffering relatively water scarcity.The overexploitation of groundwater in the Luanhe River Delta in recent years has caused the continuous drop of groundwater level and serious environmental and geological problems.This study systematically analyzes the evolution characteristics of the population,economy,and groundwater exploitation in the Luanhe River Delta and summarizes the change patterns of the groundwater flow regime in different aquifers in the Luanhe River Delta according to previous water resource assessment data as well as the latest groundwater survey results.Through comparison of major source/sink terms and groundwater resources,the study reveals the impacts of human activities on the groundwater resources and ecological environment in the study area over the past 30 years from 1990 to 2020.The results are as follows.The average annual drop rate of shallow groundwater and the deep groundwater in the centers of depression cones is 0.4 m and 1.64 m,respectively in the Luanhe River Delta in the past 30 years.The depression cones of shallow and deep groundwater in the study area cover an area of 545.32 km^(2)and 548.79 km^(2),respectively,accounting for more than 10%of the total area of the Luanhe River Delta.Overexploitation of groundwater has further aggravated land subsidence.As a result,two large-scale subsidence centers have formed,with a maximum subsidence rate of up to 120 mm/a.The drop of groundwater level has induced some ecological problems in the Luanhe River Delta area,such as the zero flow and water quality deterioration of rivers and continuous shrinkage of natural wetlands and water.Meanwhile,the proportion of natural wetland area to the total wetland area has been decreased from 99%to 8%and the water area from 1776 km^(2)to 263 km^(2).These results will provide data for groundwater overexploitation control,land subsidence prevention,and ecological restoration in plains and provide services for water resources management and national land space planning.
基金the Hunan Natural Science Foundation(Grant No.2019JJ30014)National Natural Science Foundation of China(Grant Nos.31872932 and 31571981)Agriculture Research System of China(Grant No.CARS-23-D-02)。
文摘Plant viruses are mainly transmitted by insect vectors in the non-persistent,semi-persistent,or persistent modes.In the non-persistent mode,plant viruses are retained in the stylets of their insect vectors.In the semi-persistent mode,plant viruses are carried to vector foreguts or salivary glands,but they cannot spread to salivary glands.In the persistent mode,plant viruses are retained in vector guts and can spread to salivary glands.In the non-persistent and semi-persistent modes,plant viruses are retained for a short time and cannot enter the hemolymph of insect vectors,whereas in the persistent mode,plant viruses are retained for a relatively long time and can be found in the hemolymph.Here,we reviewed recent studies that uncovered molecular mechanisms of how plant viruses manipulate host traits for efficient transmission by insect vectors.Normally,plants that are infected with viruses,regardless of the transmission mode,tend to release more attractive volatiles to vectors.However,plant defensive systems are regulated differently by viruses in these three modes.In the non-persistent mode,virus infections significantly induce plant defense responses,which probably trigger vectors(e.g.,winged aphids)to disperse and transmit viruses in a short time.In the semi-persistent mode,virus infections frequently suppress plant defense responses,resulting in an increase of vector population and facilitating viral transmissions during vector outbreaks.In the persistent mode,virus infections reduce plant defense responses and manipulate plant traits to become suitable feeding sites in a relatively long period of time.Understanding the underlying mechanisms of virus–vector–plant interactions will lay a foundation for preventing virus transmission.
文摘Main quadrupole magnets are critical for the Circular Electron and Positron Collider(CEPC)and are specifically designed as dual aperture quadrupole(DAQ)magnets.However,the field crosstalk between the two apertures presents challenges.As the CEPC will work at four beam energies of Z,W,Higgs and ttbar mode,the DAQ magnets will operate at four field gradients spanning from 3.18 to 12.63 T/m.The first short quadrupole magnet prototype with the bore diameter of 76 mm and magnetic length of 1.0 m revealed the problems of large magnetic field harmonics and a magnetic center shift within the beam energy range.Accordingly,a compensation method was proposed in this work to solve the field crosstalk effect.By adjusting the gap height at the middle of the two apertures,the field harmonics and magnetic center shift are significantly reduced.After optimization,the short prototype was modified using a new scheme.The field simulations are validated from the magnetic measurement results.Further,the multipole field meets the requirements of the four beam energies.The detailed magnetic field optimization,field harmonics adjustment,and measurement results are presented herein.
文摘A 16-pole superconducting multipole wiggler with a large gap of 68 mm was designed and fabricated to serve as a multipole wiggler for HEPS-TF.The wiggler consists of 16 pairs of NbTi superconducting coils with a period length of 170 mm,and its maximum peak field is 2.6 Tesla.In magnet design,magnet poles were optimized.Furthermore,the Lorentz force on the coils and electromagnetic force between the upper and lower halves were computed and analyzed along with the stored energy and inductance at different currents.To enhance the critical current of the magnet coil,all the pole coils selected for the magnet exhibited excellent performance,and appropriate prestress derived from the coil force analysis was applied to the pole coils during magnet assembly.The entire magnet structure was immersed in 4.2-K liquid helium in the cryostat cooled solely by four two-stage cryocoolers,and the performance test of the superconducting wiggler was appropriately completed.Based on the measured results,the first and second field integrals on the axis of the superconducting wiggler were significantly improved at different field levels after the compensation of the corrector coils.Subsequently,the wiggler was successfully installed in the storage ring of BEPCII operation with beams.
基金supported by the grants from the Sichuan Science and Technology Program,China(Grant Nos.:2023NSFSC0614 and 2022YFS0624)Southwest Medical University Science and Technology Program,China(Grant No.:2021ZKZD017)+2 种基金the Luzhou Science and Technology Program,China(Grant Nos.:2022-YJY-127,2022YFS0624-B1,2022YFS0624-C1,and 2022YFS0624-B3)the Open Research Project Program funded by the Science and Technology Development Fund(Grant No.:SKL-QRCM(UM)-2020-2022)the State Key Laboratory of Quality Research in Chinese Medicine(University of Macao,Macao,China)(Grant No.:SKL-QRCMOP21006).
文摘As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production.Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.
基金This work was supported by National Natural Science Foundation of China(11655003)Innovation Project of IHEP(542017IHEPZZBS11820)This work was supported in part by the CAS Center for Excellence in Particle Physics(CCEPP).
文摘Based on the LINAC of BEPCII, a high-polarized, high bightness, energy-tunable, monoenergetic laser compton backscattering (LCS)gamma-ray source is under construction at IHEP. The gamma-ray energy range is from 1 MeV to 111 MeV. It is a powerful and hopeful researchplatform to reveal the underlying physics of the nuclear, the basic particles and the vacuum or to check the exist basic physical models, quantumelectrodynamic (QED) theories. In the platform, a 1.064 mm Nd:YAG laser system and a 10.6 mm CO_(2) laser system are employed. All the triggersignals to the laser system and the electron control system are from the only reference clock at the very beginning of the LINAC to make sure thetemporal synchronization. Two optical transition radiation (OTR) targets and two charged-couple devices (CCD) are used to monitor and to alignthe electron beam and the laser beam. With the LCS gamma-ray source, it is proposed to experimentally check the gamma-ray calibrations, thephoton-nuclear physics, nuclear astrophysics and some basic QED phenomena.
基金Key Research Task of Science and Technology Department of Beijing, No.D0905004000011
文摘BACKGROUND: Stroke prevention guidelines should be made available application to aid in uniformity, timing, preciseness, and acceptance of disease. OBJECTIVE: To investigate the awareness of neurologists in some Beijing secondary prevention of cerebral infarction/transient ischemia. DESIGN: Cross-sectional study. to neurologists for clinical hospitals of intervention in SETTING: Beijing Tiantan Hospital, Beijing Anzhen Hospital, General Hospital of Beijing Military Area, Command of Chinese PLA, Beijing Chuiyangliu Hospital, Beijing 6^th Hospital, Beijing Hepingli Hospital, and Beijing Daxing District Hospital. PARTICIPANTS: A total of 28 (associate) chief physicians, 58 attending physicians, and 54 resident physicians who engaged in clinical treatment of cerebrovascular diseases were selected from 8 hospitals in Beijing from March to April 2007. All physicians provided informed consent. METHODS: Self-made closed questionnaires were provided for data collection, consisting of 16 questions that were single choice or multiple choice. Specifically, questions 1-7 focused on awareness of blood pressure regulation in different patients and first choice of decompression drug; questions 8-12 focused on awareness of lipid regulation; and questions 13-16 focused on awareness of anti-blood platelet drugs applied in secondary prevention. The scores ranged from 0-100 points, and each question was worth 6.25 points. The scores positively correlated with the awareness rate. To test leveling real-time, the survey lasted for a maximum of 20 minutes. One questionnaire was independently finished by each subject in the survey. MAIN OUTCOME MEASURES: Awareness intervention among neurologists during secondary prevention of cerebral infarction/transient ischemia and questionnaire scores. RESULTS: 140 subjects were included in the final analysis. ① The awareness rate among neurologists for intervention during secondary prevention of cerebral infarction/transient ischemia ranged from 0.7-57.9%, the scores ranged between 0-56 points, and the mean score was 26 points.② Scores of resident physicians were 0-56 points with a mean score of 26 points; attending physicians scored 6-50 points, with a mean score of 26 points; and chief physicians scored 6-50 points, with a mean score of 23 points. There were no significant differences among the various physicians (F = 0.771, t = 0.465, P 〉 0.05). CONCLUSION: Awareness among neurologists of intervention during secondary prevention of cerebral infarction/transient ischemia is not ideal. However, there was no significant difference between professional titles.
基金This project was supported by grants from the National Natural Science Foundation of China (No. 81702478 and No. 81270865) and China Postdoctoral Science Foundation (No. 2016M600596).
文摘A growing number of children and adolescents are being diagnosed as Chiari malformation type I (CM- I ) for behavioral disorders, developmental delay, seizures, or abnormal orpharyngeal function. The aim of this study was to compare the clinical characteristics, imaging findings and surgical outcomes of CM- I in pediatric and adult patients. Between January 2014 and June 2017, 84 patients with CM- I underwent surgical treatment in our department. We divided the patients into two groups: pediatric group (n=l 1, age 〈18 years) and adult group (n=73, age 〉18 years). Data on clinical characteristics, imaging findings, surgical outcomes, and prognosis were retrospectively reviewed and compared between these two groups. For clinical presentation, scoliosis (36.4%) and developmental delay (36.4%) were more common in pediatric patients, whereas, sensory disturbance (58.9%) and motor weakness (41. 1%) were more common in adult patients. Imaging findings showed that the incidence of hydrocephalus and craniovertebral junctional abnormalities was significantly higher in pediatric group than in adult group (P〈0.05). Compared to adult group, pediatric group showed a better improvement or resolution of syrinx and tonsillar herniation after surgical treatments (P〈0.05). The total Chicago Chiari Outcome Scale (CCOS) score in pediatric patients at the last follow- up was significantly higher than that in adult patients (P=0.002). In conclusion, the clinical characteristics and imaging findings appeared to be different in pediatric and adult patients with CM- I. The surgical outcomes of pediatric patients were shown to be significantly better than those of adult patients.
基金This work was supported in part by the-National Natural Science Foundation of China (61403342, 61273286, U1509207, 61325019, 113 02195), and Hubei Key Laboratory of Intelligent Vision Based Monitoring for Hydroelectric Engineering (2014KLA09).
基金This research was funded in part by the ERANET PerMed consortium“PerProGlio”(to J.W.B.and A.S.).
文摘Objective Pituitary adenomas(PAs)can adapt an aggressive phenotype by invading adjacent brain structures with rapid cellular proliferation.Previous studies demonstrated that excessive expression of metalloproteases ADAM12 and MMP-14 is instrumental for the active proliferation and invasiveness of PA cells in vitro and of tumors in vivo.However,the mechanisms regulating ADAM12 and MMP-14 expression in PAs remain unclear.Methods Target gene prediction and transcriptomic profiling of invasive vs.noninvasive human PA samples were performed to identify miRNA species potentially involved in the regulation of ADAM12 and MMP14.For cellular analyses of miRNA functions,two mouse PA cell lines(AtT20 and TtT/GF)were transfected with miR-149-3p and miR-149-5p,respectively.The effects of miR-149(3p and 5p)on expression levels of ADAM12 and MMP14 were determined by Western blotting followed by an analysis of proliferation and colony formation assays,scratch migration assays,and invasion assays.Results A significant downregulation of miRNA-149 was observed in invasive vs.noninvasive PA(0.32 vs.0.09,P<0.0001).In AtT-20 and TtT/GF mouse PAs cells,transfection of mimic miRNA-149(3p and 5p)caused a significantly reduced cell proliferation and matrigel invasion,whilst the effect on cell migration was less pronounced.Both strands of miRNA-149(3p and 5p)markedly reduced protein levels of ADAM12 and MMP-14 by at least 40%in both cell lines.Conclusion This study proved that the invasiveness of PA cells is,at least partly,regulated by miRNA-149-dependent expression of ADAM12 and MMP-14.
基金This study was supported by grants from the National Key R&D Program of China(No.2016YFC0904900)National Natural Science Foundation(No.81673509 and No.81573504)of China+1 种基金Natural Science Foundation of Beijing Municipality(No.7171012)National Science and Technology Major Projects for“Major New Drugs Innovation and Development”of China(No.2017ZX09304028 and No.2017ZX09101001).
文摘The purpose of the present study was to investigate the impact of genetic polymorphism on fluvastatin pharmacokinetics.In addition,we compared the fluvastatin pharmacokinetics differences between extended-release(ER)80 mg tablet and immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter genetic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study(n=24),effects of ABCG2,SLCO1B1,ABCB1,CYP2C9 and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed.The administration dosage for IR 40 mg and ER 80 mg were twice and once daily,respectively,for total 7 d.Blood samples for pharmacokinetic evaluation were taken on the 1st and 7th d.The lower exposure following ER was observed.For ER tablets,SLCO1B1 T521C genotype correlated with AUC 0-24 of repeat doses(P=0.010).SLCO1B1 T521C genotype had no statistically significant effect on AUC 0-24 of IR capsule of fluvastatin after single or repeated doses.In vitro study demonstrated that when the concentration of fluvastatin was low(<1μmol/l),the uptake of fluvastatin in the HEK293-OATP1B1 with SLCO1B1521TT(K m=0.18μmol/l)was faster than that with SLCO1B1521CC(K m=0.49μmol/l),On the other hand,when concentration reached to higher level(>1μmol/l),transport velocity of fluvastatin by HEK293-OATP1B1 with SLCO1B1521TT(K m=11.4μmol/l)and with SLCO1B1521TCC(K m=15.1μmol/l)tend to be the same.It suggests that the increased effect of SLCO1B1 T521C genotype on ER formulation of fluvastatin was mainly caused by lower blood concentrations.We recommend that formulation should be incorporated into future pharmacogenomics studies.
基金supported by E-learning Platform, National Torch Project (No. z20040010)
文摘With the fast development of business logic and information technology, today's best solutions are tomorrow's legacy systems. In China, the situation in the education domain follows the same path. Currently, there exists a number of e-learning legacy assets with accumulated practical business experience, such as program resource, usage behaviour data resource, and so on. In order to use these legacy assets adequately and efficiently, we should not only utilize the explicit assets but also discover the hidden assets. The usage behaviour data resource is the set of practical operation sequences requested by all users. The hidden patterns in this data resource will provide users' practical experiences, which can benefit the service composition in service-oriented architecture (SOA) migration. Namely, these discovered patterns will be the candidate composite services (coarse-grained) in SOA systems. Although data mining techniques have been used for software engineering tasks, little is known about how they can be used for service composition of migrating an e-learning legacy system (MELS) to SOA. In this paper, we propose a service composition approach based on sequence mining techniques for MELS. Composite services found by this approach will be the complementation of business logic analysis results of MELS. The core of this approach is to develop an appropriate sequence mining algorithm for mining related data collected from an e-learning legacy system. According to the features of execution trace data on usage behaviour from this e-learning legacy system and needs of further pattern analysis, we propose a sequential mining algorithm to mine this kind of data of tile legacy system. For validation, this approach has been applied to the corresponding real data, which was collected from the e-learning legacy system; meanwhile, some investigation questionnaires were set up to collect satisfaction data. The investigation result is 90% the same with the result obtained through our approach.
基金This study was funded by the Shanghai Agriculture Applied Technology Development Program,China(grant no.2022-02-08-00-12-F01111)the China Agriculture Research System(grant no.CARS-30-2-08)+2 种基金the National Natural Science Foundation of China(grant no.32102347)the Shanghai Sailing Program(grant no.21YF1422100)the Startup Fund for Young Faculty at SJTU(grant no.21X010500643).
文摘Prunus pusilliflora is a wild cherry germplasm resource distributed mainly in Southwest China.Despite its ornamental and economic value,a high-quality assembled P.pusilliflora genome is unavailable,hindering our understanding of its genetic background,population diversity,and evolutionary processes.Here,we de novo assembled a chromosome-scale P.pusilliflora genome using Oxford Nanopore,Illumina,and chromosome conformation capture sequencing.The assembled genome size was 309.62 Mb,with 76 scaffolds anchored to eight pseudochromosomes.We predicted 33035 protein-coding genes,functionally annotated 98.27%of them,and identified repetitive sequences covering 49.08%of the genome.We found that P.pusilliflora is closely related to Prunus serrulata and Prunus yedoensis,having diverged from them∼41.8 million years ago.A comparative genomic analysis revealed that P.pusilliflora has 643 expanded and 1128 contracted gene families.Furthermore,we found that P.pusilliflora is more resistant to Colletotrichum viniferum,Phytophthora capsici,and Pseudomonas syringae pv.tomato(Pst)DC3000 infections than cultivated Prunus avium.P.pusilliflora also has considerably more nucleotide-binding site-type resistance gene analogs than P.avium,which explains its stronger disease resistance.The cytochrome P450 and WRKY families of 263 and 61 proteins were divided into 42 and 8 subfamilies respectively in P.pusilliflora.Furthermore,81 MADS-box genes were identified in P.pusilliflora,accompanying expansions of the SVP and AGL15 subfamilies and loss of the TM3 subfamily.Our assembly of a high-quality P.pusilliflora genome will be valuable for further research on cherries and molecular breeding.