The heavy-ion accelerator facility(HIAF)under construction in China will produce various stable and intense radioactive beams with energies ranging from MeV/u to GeV/u.The ion-linac(iLinac)accelerator,which will serve...The heavy-ion accelerator facility(HIAF)under construction in China will produce various stable and intense radioactive beams with energies ranging from MeV/u to GeV/u.The ion-linac(iLinac)accelerator,which will serve as the injector for the HIAF,is a superconducting heavy-ion accelerator containing 13 cryomodules.It will operate in either continuous wave mode or pulsed mode,with a beam current ranging from 0.01 to 1 emA.The beam position monitor(BPM)is crucial for this high-beam-power machine,which requires precise beam control and a very small beam loss of less than 1 W/m,especially inside the cryomodules of this unique beam instrument.Nearly 70 BPMs will be installed on the iLinac.New digital beam position and phase measurement(DBPPM)electronics based on a heterogeneous multiprocessing platform system-on-chip(MPSoC)has been developed to provide accurate beam trajectory and phase measurements as well as beam interlocking signals for a fast machine protection system(MPS).The DBPPM comprises an analog front-end(AFE)board in field programmable gate array(FPGA)mezzanine-connector(FMC)form factor,along with a digital signal processing board housed within a “2U 19”chassis.To mitigate radio frequency(RF)leakage effects from high-power RF systems in certain scenarios,beam signals undergo simultaneous processing at both fundamental and second-harmonic frequencies.A dynamic range from-65 dBm to 0 dBm was established to accommodate both weak beam commissioning and high-intensity operational demands.Laboratory tests demonstrated that at input power levels exceeding-45 d Bm,the phase resolution surpasses 0.05°,and the position resolution exceeds 5μm.These results align well with the stipulated measurement requirements.Moreover,the newly developed DBPPM has self-testing and self-calibration functions that are highly helpful for the systematic evaluation of numerous electronic components and fault diagnosis equipment.In addition,the DBPPM electronics implements a 2D nonlinear polynomial correction on the FPGA and can collect accurate real-time position measurements at large beam offsets.This newly developed DBPPM electronics has been applied to several Linac machines,and the results from beam measurements show high performance,good long-term stability,and high reliability.In this paper,a detailed overview of the architecture,performance,and proof-of-principle measurement of the beams is presented.展开更多
Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes in...Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.展开更多
Inspired by sophisticated biological structures and their physiological processes, supramolecular chemistry has been developed for understanding and mimicking the behaviors of natural species. Through spontaneous self...Inspired by sophisticated biological structures and their physiological processes, supramolecular chemistry has been developed for understanding and mimicking the behaviors of natural species. Through spontaneous self-assembly of functional building blocks, we are able to control the structures and regulate the functions of resulting supramolecular assemblies. Up to now, numerous functional supramolecular assemblies have been constructed and successfully employed as molecular devices, machines and biological diagnostic platforms. This review will focus on molecular structures of functional molecular building blocks and their assembled superstructures for biological detection and delivery.展开更多
Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant pr...Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes(TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.展开更多
FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM...FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam2OA-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM2OA. By breeding K14-Cre mice with Fam20An^x/fl^x mice, we created K14-Cre;Fam20Af/flox/flox （conditional knock out, cKO） mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography： histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam2OA-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice, The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.展开更多
A noninvasive Ionization profile monitor(IPM)consisting of micro-channel plates,a phosphor screen and the optical-signal acquisition has been developed at the cooling storage ring of Heavy Ion Research Facility in Lan...A noninvasive Ionization profile monitor(IPM)consisting of micro-channel plates,a phosphor screen and the optical-signal acquisition has been developed at the cooling storage ring of Heavy Ion Research Facility in Lanzhou(HIRFL-CSR).It makes the real-time profile measurements for the transverse beam cooling and orbit oscillation possible and efficient.This paper firstly describes all the IPM design criterions including the theoretical signal yield calculation,the space charge field and initial momentum evaluation,and the electrostatic field distortion simulation as well.In order to investigate the IPM performance,the beam profile measurements are done with different high voltage settings.Subsequently,some valuable beam experiments about the transverse electron cooling and orbit oscillation study are also presented.In the end,fast turn-by-turn profile measurements for the emittance blow-up research in a synchrotron are discussed.In cooperation with the newly deployed emittance instruments at the HIRFL-CSR injector,the IPM shows great prospects for the injection mismatch study,and potential values for the tune,dispersion and chromaticity measurements as well.展开更多
BACKGROUND Human-derived mesenchymal stromal cells have been shown to improve cognitive function following experimental stroke.The activity of exosomes has been verified to be comparable to the therapeutic effects of ...BACKGROUND Human-derived mesenchymal stromal cells have been shown to improve cognitive function following experimental stroke.The activity of exosomes has been verified to be comparable to the therapeutic effects of mesenchymal stromal cells.However,the effects of exosomes derived from human umbilical cord mesenchymal stem cells(HUC-MSCs)(ExoCtrl)on post-stroke cognitive impairment(PSCI)have rarely been reported.Moreover,whether exosomes derived from C-C chemokine receptor type 2(CCR2)-overexpressing HUC-MSCs(ExoCCR2)can enhance the therapeutic effects on PSCI and the possible underlying mechanisms have not been studied.AIM To investigate the effects of ExoCtrl on PSCI and whether ExoCCR2 can enhance therapeutic effects on PSCI.METHODS Transmission electron microscopy,qNano®particles analyzer,and Western blotting were employed to determine the morphology and CCR2 expression of ExoCtrl or ExoCCR2.ELISA was used to study the binding capacity of exosomes to CC chemokine ligand 2(CCL2)in vivo.After the intravenous injection of ExoCtrl or ExoCCR2 into experimental rats,the effect of ExoCtrl and ExoCCR2 on PSCI was assessed by Morris water maze.Remyelination and oligodendrogenesis were analyzed by Western blotting and immunofluorescence microscopy.QRT-PCR and immunofluorescence microscopy were conducted to compare the microglia/macrophage polarization.The infiltration and activation of hematogenous macrophages were analyzed by Western blotting and transwell migration analysis.RESULTS CCR2-overexpressing HUC-MSCs loaded the CCR2 receptor into their exosomes.The morphology and diameter distribution between ExoCtrl and ExoCCR2 showed no significant difference.ExoCCR2 bound significantly to CCL2 but ExoCtrl showed little CCL2 binding.Although both ExoCCR2 and ExoCtrl showed beneficial effects on PSCI,oligodendrogenesis,remyelination,and microglia/macrophage polarization,ExoCCR2 exhibited a significantly superior beneficial effect.We also found that ExoCCR2 could suppress the CCL2-induced macrophage migration and activation in vivo and in vitro,compared with ExoCtrl treated group.CONCLUSION CCR2 over-expression enhanced the therapeutic effects of exosomes on the experimental PSCI by promoting M2 microglia/macrophage polarization,enhancing oligodendrogenesis and remyelination.These therapeutic effects are likely through suppressing the CCL2-induced hematogenous macrophage migration and activation.Key words:Cognitive impairment;Stroke;Exosomes;C-C chemokine receptor type 2;Microglia/macrophage polarization;Remyelination.展开更多
The transverse momentum spectra of different types of particles produced in central and peripheral gold–gold(Au–Au)and inelastic proton–proton(pp)collisions at the Relativistic Heavy Ion Collider,as well as in cent...The transverse momentum spectra of different types of particles produced in central and peripheral gold–gold(Au–Au)and inelastic proton–proton(pp)collisions at the Relativistic Heavy Ion Collider,as well as in central and peripheral lead-lead(Pb–Pb)and pp collisions at the Large Hadron Collider,are analyzed by the multi-component standard(Boltzmann–Gibbs,Fermi–Dirac,and Bose–Einstein)distributions.The obtained results from the standard distribution give an approximate agreement with the measured experimental data by the STAR,PHENIX,and ALICE Collaborations.The behavior of the effective(kinetic freeze-out)temperature,transverse flow velocity,and kinetic freeze-out volume for particles with different masses is obtained,which observes the early kinetic freezeout of heavier particles as compared to the lighter particles.The parameters of emissions of different particles are observed to be different,which reveals a direct signature of the mass-dependent differential kinetic freeze-out.It is also observed that the peripheral nucleus–nucleus(AA)and pp collisions at the same center-of-mass energy per nucleon pair are in good agreement in terms of the extracted parameters.展开更多
Esophageal squamous cell carcinoma(ESCC)is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs)is critical to ESCC initiation and progression.Recentl...Esophageal squamous cell carcinoma(ESCC)is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs)is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.展开更多
Alloying is a good approach to increasing its strength but leads to a reduction of damping to pure magnesium.Classifying the alloying characteristics of various alloying elements in magnesium alloys and their combined...Alloying is a good approach to increasing its strength but leads to a reduction of damping to pure magnesium.Classifying the alloying characteristics of various alloying elements in magnesium alloys and their combined effects on the damping and mechanical properties of magnesium alloys is important.In this paper,the properties of the Mg-0.6wt%X binary alloys were analyzed through strength measurements and dynamic mechanical analysis.The effects of foreign atoms on solid-solution strengthening and dislocation damping were studied comprehensively.The effect of solid solubility on damping capacity can be considered from two perspectives:the effect of single solid-solution atoms on the damping capacities of the alloy,and the effect of solubility on the damping capacities of the alloy.The results provide significant information that is useful in developing high-strength,high-damping magnesium alloys.This study will provide scientific guidance regarding the development of new types of damping magnesium alloys.展开更多
CaBi_(4)Ti_(4)O_(15)(CBT)-based Aurivillius high-temperature piezoceramics with different Sb-Mn co-doping amounts were synthesized via the conventional sintering technique.The influences of doping amount on the produc...CaBi_(4)Ti_(4)O_(15)(CBT)-based Aurivillius high-temperature piezoceramics with different Sb-Mn co-doping amounts were synthesized via the conventional sintering technique.The influences of doping amount on the product were studied via their crystal structure,microstructure,and piezoelectric performance.It is found that an appropriate Sb-Mn co-doping amount can effectively optimize the crystal structure and decrease the oxygen vacancy concentration in CBT ceramics,leading to enhanced electrical properties.Optimized electrical performance with a high Curie temperature(TC)of 792℃and a remarkable piezoelectric coefficient(d33)of 25 p C/N were achieved at a doping amount(x)of 0.05.Furthermore,this ceramic is found to exhibit an excellent thermal stability,with d33 retaining 88%of its original value after annealing at 600℃for 2 h.Moreover,this ceramic shows a high electrical resistivity(ρ)of 1.35×10^(8)Ω·cm with a small dielectric loss(tanδ)of 1.7%at 400℃.Because of such outstanding piezoelectric performance,it is believed that these Sb-Mn co-doped CBT ceramics could be potential candidates for high-temperature piezoelectric applications.展开更多
Schiff-base metal complexes as efficient catalysts are widely used in ring-opening polymerization of cycle esters. The salen Fe complexes were formed with their excellent biocompatibility and less toxicity. A series o...Schiff-base metal complexes as efficient catalysts are widely used in ring-opening polymerization of cycle esters. The salen Fe complexes were formed with their excellent biocompatibility and less toxicity. A series of salen Fe complexes were designed in this work in order to study the activity and control of polymerization of lactide. The salen Fe complexes＇ activities changed with the ligands configuration and substituent groups.展开更多
Background： Soybean isoflavones are structurally similar to mammalian estrogens and therefore may act as estrogen agonists or antagonists. However, it has not been determined if they have any negative effects on repr...Background： Soybean isoflavones are structurally similar to mammalian estrogens and therefore may act as estrogen agonists or antagonists. However, it has not been determined if they have any negative effects on reproductive parameters in male livestock. Therefore, the objective of this study was to evaluate the effects of soybean isofiavones on male reproduction using Chinese mini-pig boars as a model. Fifty Xiang boars were randomly divided into five groups and fed diets containing 0, 125, 250, or 500 ppm soybean isoflavones or 0.5 ppm diethylstilbestrol for 60 days. Results： Dietary supplementation with 250 ppm of soy isoflavones markedly increased the testis index （P 〈 0.05）, fructose content （P 〈 0.05）, and o-glycosidase content in testicular tissue （P 〈 0.01）, as well as increased the number of viable germ cells （P 〈 0.01） and the level of Bcl-2 protein （P 〈 0.01）. However, 500 ppm of soybean isoflavones significantly reduced both testis and epididymis indexes （P 〈 0.0S） and lactate dehydrogenase levels （P 〈 0.01）, as well as reduced serum LH and testosterone levels （P 〈 0.05）. High levels of soybean isoflavones also increased malondialdehyde levels （P 〈 0.05）, as well as increased the numbers of early and late apoptotic germ cells （P 〈 0.01） and the level of Bax proteins （P 〈 0.05） in the testis. Conclusions： The results of this study indicate that consumption of soy isoflavones at dietary levels up to 250 ppm did not adversely affect reproductive parameters in Chinese mini-pig boars whereas higher levels of soy isoflavones may adversely affect male reproduction.展开更多
The energy homeostasis-associated（Enho） gene encodes a secreted protein, adropin, which regulates the expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor γ, a major r...The energy homeostasis-associated（Enho） gene encodes a secreted protein, adropin, which regulates the expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor γ, a major regulator of lipogenesis. In the present study, the porcine（Sus scrofa） homologue of the Enho gene, which was named p Enho, was amplified by reverse transcriptase polymerase chain reaction（RT-PCR） using oligonucleotide primers derived from in silico sequences. The gene sequence was submitted into the Gen Bank of NCBI, and the access number is GQ414763. The p Enho encodes a protein of 76 amino acids which shows 75% similarity to Homo sapiens adropin. The expression profile of p Enho in tissues（liver, muscle, anterior jejunum, posterior jejunum, and ileum） was determined by quantitative real-time RT-PCR. p Enho was localized on porcine chromosome 10 and no introns were found. In conclusion, p Enho was cloned and analysed with the aim of increasing knowledge about glucose and lipid metabolism in piglets and helping to promote the health and growth of piglets through adropin regulation.展开更多
The emergence of fluorescent light-up molecular probe,which can specifically turn on their fluorescent in the presence of stimulation factors,has open up a new opportunity to advance biosensing and bioimaging.In this ...The emergence of fluorescent light-up molecular probe,which can specifically turn on their fluorescent in the presence of stimulation factors,has open up a new opportunity to advance biosensing and bioimaging.In this work,we designed and synthesized a peptide-AIE conjugate probe for cell imaging with controlled in situ assembled nanostructures.The modular designed probe is consisted of a selfassembled peptide-tetraphenylethene(TPE)motif,a fibroblast activation protein alpha(FAP-α)responsive motif,a hydrophilic motif and a targeting motif.The probe exhibits typically turn-on fluorescence property specifically triggered by FAP-α,which is a significant overexpressed membrane protein on pancreatic tumor cells.Interestingly,the peptide modified the TPE dramatically impacts the assembled nanostructure,which can be modulated by peptide sequences.As a result,the peptide FF(PhePhe)modification of TPE as the self-assembled motif provides a suitable balance of the probe with lightup property and nanofiber assembled structure in situ.Finally,our probe could effectively detect the FAP-αon tumor cells with high specificity.Meantime,the nanofibers in situ assembled on the surface of CAFs enhanced the probe accumulation and prolonged the retention for cell imaging.We envision that this study may inspire new insights into the design of nanostructure controlled AIE light-up bio-probe.展开更多
OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospina...OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospinal fluid on the rats with cerebral ischemic injury.METHODS Cerebral ischemia rats were induced by middle cerebral artery occlusion(MCAO).Adult male sprague-dawley(SD)rats were randomly divided into seven groups:sham-group;model group;nimodipine(NMP)-treated group and nao mai tai(NMT)-treated group were set as positive drug control groups;TQHXD-treated group(3,6 and 12g·kg-1body weight);The neurological function of rats was estimated by neurological defect scoring after the 1,7and 15 dafter administration.Histological structure of the brain in rats were observed by hematoxylin and eosin(H&E)staining.Ultramicrostructural features of hippocampus neurons and the opening of tight junction(TJ)of BBB in rats were observed by transmission electron microscope(TEM).Western blotting was performed to detect the expression of ZO-1,occludin,claudin-5,AQP-4 and MMP-9 in BBB after cerebral ischemia injury.Component analysis experiments:adult male SD rats were randomly divided into four groups:Distilled water was administered intragastrically sham-operated rats;Distilled water was administered intragastrically model rats by MCAO;TQHXD was administered intragatrically to rats in sham-operated group;TQHXD was administered intragestrically to rats in model group by MCAO.GC and HPLC was used to detect three compounds,namely,muscone,ligustilide and hydroxysafflor yellow A,in rats cerebrospinal fluid(CSF)after oral administration of TQHXD.Finally,samples of cerebrospinal fluid of rats in each group were compared with single medicine so as to explicit the three compounds come from which herb.RESULTS TQHXD significantly reduced the neurological defect scores.Histological examination indicated that dense neuropil and largely surviving neurons had been seen in TQHXD-treated rats.TEM observation revealed that TQHXD could significantly inhibit the damage of hippocampal neurons and reduce the opening of TJ.The decreased protein expression levels of claudin-5,occludin,ZO-1 and the increased protein expression levels of AQP-4 and MMP-9in cerebral ischemia tissue were significantly prevented by treatment of TQHXD.Analysis of experimental results showed that muscone,ligustilide and hydroxysafflor yellow A could penetrate the BBB into the CSF,and the content of the model group was lower than that of sham group after intragastric administration of TQHXD.CONCLUSION These results demonstrated that TQHXD may act as a potential neuroprotective agent against BBB damage for cerebral ischemia through protecting of hippocampus neurons,reducing the opening of TJ and decreasing the permeability of BBB by up-regulating ZO-1,occludin,claudin-5 expressions,down-regulating AQP-4 and MMP-9 expressions.The effect of TQHXD on the decrease of the opening of TJ also reduced the content of muscone,ligustilide and hydroxysafflor yellow A in cerebrospinal fluid.展开更多
Objective:To investigate the effects of gastrodin on neurotransmitter effect, stress response, blood vessel and nerve function in migraine patients.Methods:A total of90 patients with migraine admitted to our hospital ...Objective:To investigate the effects of gastrodin on neurotransmitter effect, stress response, blood vessel and nerve function in migraine patients.Methods:A total of90 patients with migraine admitted to our hospital from September 2016 to December 2017 were randomly divided into observation group and control group with 45 cases in each group. The control group was treated with flunarizine hydrochloride, while the observation group was treated with gastrodin based on the control group. The levels of neurotransmitter effect[including 5-serotonin (5-HT) and tumor necrosis factor alpha (TNF-alpha)], stress response[oxidized low density lipoprotein (ox-LDL) and paraoxonase-1 (PON-1)], vascular function[including nitric oxide (NO), endothelin-1 (ET-1)] and neurological function[including high brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP)] related indexes were observed and compared between the two groups.Results: The two groups showed significant changes in transmitter effect, stress response, blood vessel and nerve function. Before treatment, there was no significant difference in the levels between the two groups. After treatment, the levels of TNF-a, ox-LDL, NO, ET-1, BDNF and CGRP in the two groups were significantly lower than those before treatment, while the levels of 5-HT and PON-1 were significantly higher than those before treatment. And after treatment, the levels of TNF-a, ox-LDL, NO, ET-1, BDNF and CGRP in the observation group were significantly lower than those in the control group, while the levels of 5-HT and PON-1 were significantly higher than those in the control group.Conclusions:Gastrodin treatment can regulate oxidative stress level and improve vascular and neurological function in migraine patients.展开更多
基金supported by the National Natural Science Foundation of China(No.11975290)。
文摘The heavy-ion accelerator facility(HIAF)under construction in China will produce various stable and intense radioactive beams with energies ranging from MeV/u to GeV/u.The ion-linac(iLinac)accelerator,which will serve as the injector for the HIAF,is a superconducting heavy-ion accelerator containing 13 cryomodules.It will operate in either continuous wave mode or pulsed mode,with a beam current ranging from 0.01 to 1 emA.The beam position monitor(BPM)is crucial for this high-beam-power machine,which requires precise beam control and a very small beam loss of less than 1 W/m,especially inside the cryomodules of this unique beam instrument.Nearly 70 BPMs will be installed on the iLinac.New digital beam position and phase measurement(DBPPM)electronics based on a heterogeneous multiprocessing platform system-on-chip(MPSoC)has been developed to provide accurate beam trajectory and phase measurements as well as beam interlocking signals for a fast machine protection system(MPS).The DBPPM comprises an analog front-end(AFE)board in field programmable gate array(FPGA)mezzanine-connector(FMC)form factor,along with a digital signal processing board housed within a “2U 19”chassis.To mitigate radio frequency(RF)leakage effects from high-power RF systems in certain scenarios,beam signals undergo simultaneous processing at both fundamental and second-harmonic frequencies.A dynamic range from-65 dBm to 0 dBm was established to accommodate both weak beam commissioning and high-intensity operational demands.Laboratory tests demonstrated that at input power levels exceeding-45 d Bm,the phase resolution surpasses 0.05°,and the position resolution exceeds 5μm.These results align well with the stipulated measurement requirements.Moreover,the newly developed DBPPM has self-testing and self-calibration functions that are highly helpful for the systematic evaluation of numerous electronic components and fault diagnosis equipment.In addition,the DBPPM electronics implements a 2D nonlinear polynomial correction on the FPGA and can collect accurate real-time position measurements at large beam offsets.This newly developed DBPPM electronics has been applied to several Linac machines,and the results from beam measurements show high performance,good long-term stability,and high reliability.In this paper,a detailed overview of the architecture,performance,and proof-of-principle measurement of the beams is presented.
基金supported by grants from Hong Kong RGC (GRF #473908 and #475009)National Natural Science Foundation of China (No. 81071634)
文摘Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.
基金supported by National Basic Research Program of China(973 Program,No.2013CB932701 )the 100-Talent program of the Chinese Academy of Sciences,Beijing Natural Science Foundation(No.2132053)Young Scientists Fund of National Natural Science Foundation(No.51102014)
文摘Inspired by sophisticated biological structures and their physiological processes, supramolecular chemistry has been developed for understanding and mimicking the behaviors of natural species. Through spontaneous self-assembly of functional building blocks, we are able to control the structures and regulate the functions of resulting supramolecular assemblies. Up to now, numerous functional supramolecular assemblies have been constructed and successfully employed as molecular devices, machines and biological diagnostic platforms. This review will focus on molecular structures of functional molecular building blocks and their assembled superstructures for biological detection and delivery.
基金supported by grants from the National Natural Science Foundation of China(NSFC)(No.#81072148,#81071634and#30928012)Natural Science Foundation of Chongqing(No.2010BB5101)Shenzhen Science Fund for Distinguished Young Scholars(No.JC201005270328A)
文摘Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes(TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.
基金supported by the National Natural Science Foundation of China (Grant No. 81171744)the Natural Science Foundation of Heilongjiang Province of China (Grant H201418)
文摘FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam2OA-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM2OA. By breeding K14-Cre mice with Fam20An^x/fl^x mice, we created K14-Cre;Fam20Af/flox/flox （conditional knock out, cKO） mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography： histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam2OA-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice, The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.
基金This work was supported by the National Natural Science Foundation of China(No.11805250).
文摘A noninvasive Ionization profile monitor(IPM)consisting of micro-channel plates,a phosphor screen and the optical-signal acquisition has been developed at the cooling storage ring of Heavy Ion Research Facility in Lanzhou(HIRFL-CSR).It makes the real-time profile measurements for the transverse beam cooling and orbit oscillation possible and efficient.This paper firstly describes all the IPM design criterions including the theoretical signal yield calculation,the space charge field and initial momentum evaluation,and the electrostatic field distortion simulation as well.In order to investigate the IPM performance,the beam profile measurements are done with different high voltage settings.Subsequently,some valuable beam experiments about the transverse electron cooling and orbit oscillation study are also presented.In the end,fast turn-by-turn profile measurements for the emittance blow-up research in a synchrotron are discussed.In cooperation with the newly deployed emittance instruments at the HIRFL-CSR injector,the IPM shows great prospects for the injection mismatch study,and potential values for the tune,dispersion and chromaticity measurements as well.
基金the National Natural Science Foundation of China,No.81871847 and No.81672261
文摘BACKGROUND Human-derived mesenchymal stromal cells have been shown to improve cognitive function following experimental stroke.The activity of exosomes has been verified to be comparable to the therapeutic effects of mesenchymal stromal cells.However,the effects of exosomes derived from human umbilical cord mesenchymal stem cells(HUC-MSCs)(ExoCtrl)on post-stroke cognitive impairment(PSCI)have rarely been reported.Moreover,whether exosomes derived from C-C chemokine receptor type 2(CCR2)-overexpressing HUC-MSCs(ExoCCR2)can enhance the therapeutic effects on PSCI and the possible underlying mechanisms have not been studied.AIM To investigate the effects of ExoCtrl on PSCI and whether ExoCCR2 can enhance therapeutic effects on PSCI.METHODS Transmission electron microscopy,qNano®particles analyzer,and Western blotting were employed to determine the morphology and CCR2 expression of ExoCtrl or ExoCCR2.ELISA was used to study the binding capacity of exosomes to CC chemokine ligand 2(CCL2)in vivo.After the intravenous injection of ExoCtrl or ExoCCR2 into experimental rats,the effect of ExoCtrl and ExoCCR2 on PSCI was assessed by Morris water maze.Remyelination and oligodendrogenesis were analyzed by Western blotting and immunofluorescence microscopy.QRT-PCR and immunofluorescence microscopy were conducted to compare the microglia/macrophage polarization.The infiltration and activation of hematogenous macrophages were analyzed by Western blotting and transwell migration analysis.RESULTS CCR2-overexpressing HUC-MSCs loaded the CCR2 receptor into their exosomes.The morphology and diameter distribution between ExoCtrl and ExoCCR2 showed no significant difference.ExoCCR2 bound significantly to CCL2 but ExoCtrl showed little CCL2 binding.Although both ExoCCR2 and ExoCtrl showed beneficial effects on PSCI,oligodendrogenesis,remyelination,and microglia/macrophage polarization,ExoCCR2 exhibited a significantly superior beneficial effect.We also found that ExoCCR2 could suppress the CCL2-induced macrophage migration and activation in vivo and in vitro,compared with ExoCtrl treated group.CONCLUSION CCR2 over-expression enhanced the therapeutic effects of exosomes on the experimental PSCI by promoting M2 microglia/macrophage polarization,enhancing oligodendrogenesis and remyelination.These therapeutic effects are likely through suppressing the CCL2-induced hematogenous macrophage migration and activation.Key words:Cognitive impairment;Stroke;Exosomes;C-C chemokine receptor type 2;Microglia/macrophage polarization;Remyelination.
基金supported by the National Natural Science Foundation of China(Nos.11575103 and 11947418)the Chinese Government Scholarship(China Scholarship Council)+2 种基金the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(STIP)(No.201802017)the Shanxi Provincial Natural Science Foundation(No.201901D111043)the Fund for Shanxi‘‘1331 Project’’Key Subjects Construction。
文摘The transverse momentum spectra of different types of particles produced in central and peripheral gold–gold(Au–Au)and inelastic proton–proton(pp)collisions at the Relativistic Heavy Ion Collider,as well as in central and peripheral lead-lead(Pb–Pb)and pp collisions at the Large Hadron Collider,are analyzed by the multi-component standard(Boltzmann–Gibbs,Fermi–Dirac,and Bose–Einstein)distributions.The obtained results from the standard distribution give an approximate agreement with the measured experimental data by the STAR,PHENIX,and ALICE Collaborations.The behavior of the effective(kinetic freeze-out)temperature,transverse flow velocity,and kinetic freeze-out volume for particles with different masses is obtained,which observes the early kinetic freezeout of heavier particles as compared to the lighter particles.The parameters of emissions of different particles are observed to be different,which reveals a direct signature of the mass-dependent differential kinetic freeze-out.It is also observed that the peripheral nucleus–nucleus(AA)and pp collisions at the same center-of-mass energy per nucleon pair are in good agreement in terms of the extracted parameters.
基金supported by NSFC Joint Research Fund for Hong Kong and Macao Young Scholars(No.30928012)National Natural Science Foundation of China(No.81071634,81172582,and 30801344)Shenzhen Science Fund for Distinguished Young Scholars(No.JC201005270328A)
文摘Esophageal squamous cell carcinoma(ESCC)is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs)is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.
基金financially supported by the National Natural Science Foundation of China(Nos.51361010 and 51665012)the Jiangxi Province Science Fund for Distinguished Young Scholars(Nos.20171BCB23061 and 2018ACB21020)
文摘Alloying is a good approach to increasing its strength but leads to a reduction of damping to pure magnesium.Classifying the alloying characteristics of various alloying elements in magnesium alloys and their combined effects on the damping and mechanical properties of magnesium alloys is important.In this paper,the properties of the Mg-0.6wt%X binary alloys were analyzed through strength measurements and dynamic mechanical analysis.The effects of foreign atoms on solid-solution strengthening and dislocation damping were studied comprehensively.The effect of solid solubility on damping capacity can be considered from two perspectives:the effect of single solid-solution atoms on the damping capacities of the alloy,and the effect of solubility on the damping capacities of the alloy.The results provide significant information that is useful in developing high-strength,high-damping magnesium alloys.This study will provide scientific guidance regarding the development of new types of damping magnesium alloys.
基金financial support from the Key Research and Development Project of Zhejiang Province,China(No.2017C01056)。
文摘CaBi_(4)Ti_(4)O_(15)(CBT)-based Aurivillius high-temperature piezoceramics with different Sb-Mn co-doping amounts were synthesized via the conventional sintering technique.The influences of doping amount on the product were studied via their crystal structure,microstructure,and piezoelectric performance.It is found that an appropriate Sb-Mn co-doping amount can effectively optimize the crystal structure and decrease the oxygen vacancy concentration in CBT ceramics,leading to enhanced electrical properties.Optimized electrical performance with a high Curie temperature(TC)of 792℃and a remarkable piezoelectric coefficient(d33)of 25 p C/N were achieved at a doping amount(x)of 0.05.Furthermore,this ceramic is found to exhibit an excellent thermal stability,with d33 retaining 88%of its original value after annealing at 600℃for 2 h.Moreover,this ceramic shows a high electrical resistivity(ρ)of 1.35×10^(8)Ω·cm with a small dielectric loss(tanδ)of 1.7%at 400℃.Because of such outstanding piezoelectric performance,it is believed that these Sb-Mn co-doped CBT ceramics could be potential candidates for high-temperature piezoelectric applications.
基金financially supported by the National Natural Science Foundation of China (Nos. 21574124 and 51503203)
文摘Schiff-base metal complexes as efficient catalysts are widely used in ring-opening polymerization of cycle esters. The salen Fe complexes were formed with their excellent biocompatibility and less toxicity. A series of salen Fe complexes were designed in this work in order to study the activity and control of polymerization of lactide. The salen Fe complexes＇ activities changed with the ligands configuration and substituent groups.
文摘Background： Soybean isoflavones are structurally similar to mammalian estrogens and therefore may act as estrogen agonists or antagonists. However, it has not been determined if they have any negative effects on reproductive parameters in male livestock. Therefore, the objective of this study was to evaluate the effects of soybean isofiavones on male reproduction using Chinese mini-pig boars as a model. Fifty Xiang boars were randomly divided into five groups and fed diets containing 0, 125, 250, or 500 ppm soybean isoflavones or 0.5 ppm diethylstilbestrol for 60 days. Results： Dietary supplementation with 250 ppm of soy isoflavones markedly increased the testis index （P 〈 0.05）, fructose content （P 〈 0.05）, and o-glycosidase content in testicular tissue （P 〈 0.01）, as well as increased the number of viable germ cells （P 〈 0.01） and the level of Bcl-2 protein （P 〈 0.01）. However, 500 ppm of soybean isoflavones significantly reduced both testis and epididymis indexes （P 〈 0.0S） and lactate dehydrogenase levels （P 〈 0.01）, as well as reduced serum LH and testosterone levels （P 〈 0.05）. High levels of soybean isoflavones also increased malondialdehyde levels （P 〈 0.05）, as well as increased the numbers of early and late apoptotic germ cells （P 〈 0.01） and the level of Bax proteins （P 〈 0.05） in the testis. Conclusions： The results of this study indicate that consumption of soy isoflavones at dietary levels up to 250 ppm did not adversely affect reproductive parameters in Chinese mini-pig boars whereas higher levels of soy isoflavones may adversely affect male reproduction.
基金Project supported by the National Natural Science Foundation of China(No.31302003)the Key Program of Hunan Province Scientific and Technology Planning Project(No.2100CK2006)+1 种基金the Special Fund for Innovative and Entrepreneurship Talents of Changsha City(No.K1307006-21)the Key Program of Changsha Scientific and Technology Planning Project(No.K1201108-21),China
文摘The energy homeostasis-associated（Enho） gene encodes a secreted protein, adropin, which regulates the expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor γ, a major regulator of lipogenesis. In the present study, the porcine（Sus scrofa） homologue of the Enho gene, which was named p Enho, was amplified by reverse transcriptase polymerase chain reaction（RT-PCR） using oligonucleotide primers derived from in silico sequences. The gene sequence was submitted into the Gen Bank of NCBI, and the access number is GQ414763. The p Enho encodes a protein of 76 amino acids which shows 75% similarity to Homo sapiens adropin. The expression profile of p Enho in tissues（liver, muscle, anterior jejunum, posterior jejunum, and ileum） was determined by quantitative real-time RT-PCR. p Enho was localized on porcine chromosome 10 and no introns were found. In conclusion, p Enho was cloned and analysed with the aim of increasing knowledge about glucose and lipid metabolism in piglets and helping to promote the health and growth of piglets through adropin regulation.
基金supported by National Key R&D Program of China(No.2018YFE0205400)National Natural Science Foundation of China(Nos.31671028 and 51873045)Youth Innovation Promotion CAS(No.2017053)。
文摘The emergence of fluorescent light-up molecular probe,which can specifically turn on their fluorescent in the presence of stimulation factors,has open up a new opportunity to advance biosensing and bioimaging.In this work,we designed and synthesized a peptide-AIE conjugate probe for cell imaging with controlled in situ assembled nanostructures.The modular designed probe is consisted of a selfassembled peptide-tetraphenylethene(TPE)motif,a fibroblast activation protein alpha(FAP-α)responsive motif,a hydrophilic motif and a targeting motif.The probe exhibits typically turn-on fluorescence property specifically triggered by FAP-α,which is a significant overexpressed membrane protein on pancreatic tumor cells.Interestingly,the peptide modified the TPE dramatically impacts the assembled nanostructure,which can be modulated by peptide sequences.As a result,the peptide FF(PhePhe)modification of TPE as the self-assembled motif provides a suitable balance of the probe with lightup property and nanofiber assembled structure in situ.Finally,our probe could effectively detect the FAP-αon tumor cells with high specificity.Meantime,the nanofibers in situ assembled on the surface of CAFs enhanced the probe accumulation and prolonged the retention for cell imaging.We envision that this study may inspire new insights into the design of nanostructure controlled AIE light-up bio-probe.
基金The project supported by National Natural Science Foundation of China(81374005)″Twelfth Five Year″National Science and Technology Support Program(2012BAI26B03)
文摘OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospinal fluid on the rats with cerebral ischemic injury.METHODS Cerebral ischemia rats were induced by middle cerebral artery occlusion(MCAO).Adult male sprague-dawley(SD)rats were randomly divided into seven groups:sham-group;model group;nimodipine(NMP)-treated group and nao mai tai(NMT)-treated group were set as positive drug control groups;TQHXD-treated group(3,6 and 12g·kg-1body weight);The neurological function of rats was estimated by neurological defect scoring after the 1,7and 15 dafter administration.Histological structure of the brain in rats were observed by hematoxylin and eosin(H&E)staining.Ultramicrostructural features of hippocampus neurons and the opening of tight junction(TJ)of BBB in rats were observed by transmission electron microscope(TEM).Western blotting was performed to detect the expression of ZO-1,occludin,claudin-5,AQP-4 and MMP-9 in BBB after cerebral ischemia injury.Component analysis experiments:adult male SD rats were randomly divided into four groups:Distilled water was administered intragastrically sham-operated rats;Distilled water was administered intragastrically model rats by MCAO;TQHXD was administered intragatrically to rats in sham-operated group;TQHXD was administered intragestrically to rats in model group by MCAO.GC and HPLC was used to detect three compounds,namely,muscone,ligustilide and hydroxysafflor yellow A,in rats cerebrospinal fluid(CSF)after oral administration of TQHXD.Finally,samples of cerebrospinal fluid of rats in each group were compared with single medicine so as to explicit the three compounds come from which herb.RESULTS TQHXD significantly reduced the neurological defect scores.Histological examination indicated that dense neuropil and largely surviving neurons had been seen in TQHXD-treated rats.TEM observation revealed that TQHXD could significantly inhibit the damage of hippocampal neurons and reduce the opening of TJ.The decreased protein expression levels of claudin-5,occludin,ZO-1 and the increased protein expression levels of AQP-4 and MMP-9in cerebral ischemia tissue were significantly prevented by treatment of TQHXD.Analysis of experimental results showed that muscone,ligustilide and hydroxysafflor yellow A could penetrate the BBB into the CSF,and the content of the model group was lower than that of sham group after intragastric administration of TQHXD.CONCLUSION These results demonstrated that TQHXD may act as a potential neuroprotective agent against BBB damage for cerebral ischemia through protecting of hippocampus neurons,reducing the opening of TJ and decreasing the permeability of BBB by up-regulating ZO-1,occludin,claudin-5 expressions,down-regulating AQP-4 and MMP-9 expressions.The effect of TQHXD on the decrease of the opening of TJ also reduced the content of muscone,ligustilide and hydroxysafflor yellow A in cerebrospinal fluid.
文摘Objective:To investigate the effects of gastrodin on neurotransmitter effect, stress response, blood vessel and nerve function in migraine patients.Methods:A total of90 patients with migraine admitted to our hospital from September 2016 to December 2017 were randomly divided into observation group and control group with 45 cases in each group. The control group was treated with flunarizine hydrochloride, while the observation group was treated with gastrodin based on the control group. The levels of neurotransmitter effect[including 5-serotonin (5-HT) and tumor necrosis factor alpha (TNF-alpha)], stress response[oxidized low density lipoprotein (ox-LDL) and paraoxonase-1 (PON-1)], vascular function[including nitric oxide (NO), endothelin-1 (ET-1)] and neurological function[including high brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP)] related indexes were observed and compared between the two groups.Results: The two groups showed significant changes in transmitter effect, stress response, blood vessel and nerve function. Before treatment, there was no significant difference in the levels between the two groups. After treatment, the levels of TNF-a, ox-LDL, NO, ET-1, BDNF and CGRP in the two groups were significantly lower than those before treatment, while the levels of 5-HT and PON-1 were significantly higher than those before treatment. And after treatment, the levels of TNF-a, ox-LDL, NO, ET-1, BDNF and CGRP in the observation group were significantly lower than those in the control group, while the levels of 5-HT and PON-1 were significantly higher than those in the control group.Conclusions:Gastrodin treatment can regulate oxidative stress level and improve vascular and neurological function in migraine patients.
