BACKGROUND Gastric cancer is a prevalent malignant cancer with a high incidence and significantly affects the health of modern people globally.Cisplatin(DDP)is one of the most common and effective chemotherapies for p...BACKGROUND Gastric cancer is a prevalent malignant cancer with a high incidence and significantly affects the health of modern people globally.Cisplatin(DDP)is one of the most common and effective chemotherapies for patients with gastric cancer,but DDP resistance remains a severe clinical challenge.AIM To explore the function of M2 polarized macrophages-derived exosomal microRNA(miR)-588 in the modulation of DDP resistance of gastric cancer cells.METHODS M2 polarized macrophages were isolated and identified by specific markers using flow cytometry analysis.The exosomes from M2 macrophages were identified by transmission electron microscopy and related markers.The uptake of the PKH67-labelled M2 macrophages-derived exosomes was detected in SGC7901 cells.The function and mechanism of exosomal miR-588 from M2 macrophages in the modulation of DDP resistance of gastric cancer cells was analyzed by CCK-8 assay,apoptosis analysis,colony formation assay,Western blot analysis,qPCR analysis,and luciferase reporter assay in SGC7901 and SGC7901/DDP cells,and by tumorigenicity analysis in nude mice.RESULTS M2 polarized macrophages were isolated from mouse bone marrow stimulated with interleukin(IL)-13 and IL-4.Co-cultivation of gastric cancer cells with M2 polarized macrophages promoted DDP resistance.M2 polarized macrophagesderived exosomes could transfer in gastric cancer cells to enhance DDP resistance.Exosomal miR-588 from M2 macrophages contributed to DDP resistance of gastric cancer cells.miR-588 promoted DDP-resistant gastric cancer cell growth in vivo.miR-588 was able to target cylindromatosis(CYLD)in gastric cancer cells.The depletion of CYLD reversed miR-588 inhibition-regulated cell proliferation and apoptosis of gastric cancer cells exposed to DDP.CONCLUSION In conclusion,we uncovered that exosomal miR-588 from M2 macrophages contributes to DDP resistance of gastric cancer cells by partly targeting CYLD.miR-588 may be applied as a potential therapeutic target for the treatment of gastric cancer.展开更多
For conservative linear homogeneous nonholonomic systems, there exists a cotangent bundle with the symplectic structure dπμ∧ dξμ, in which the motion equations of the system can be written into the form of the ca...For conservative linear homogeneous nonholonomic systems, there exists a cotangent bundle with the symplectic structure dπμ∧ dξμ, in which the motion equations of the system can be written into the form of the canonical equations by the set of quasi-coordinates πμand quasi-momenta ξμ. The key to construct this cotangent bundle is to define a set of suitable quasi-coordinates πμby a first-order linear mapping, so that the reduced configuration space of the system is a Riemann space with no torsion. The Hamilton–Jacobi method for linear homogeneous nonholonomic systems is studied as an application of the quasi-canonicalization. The Hamilton–Jacobi method can be applied not only to Chaplygin nonholonomic systems, but also to non-Chaplygin nonholonomic systems. Two examples are given to illustrate the effectiveness of the quasi-canonicalization and the Hamilton–Jacobi method.展开更多
The recent observation of high critical temperature T_(c) in lanthanum and Yttrium hydrides confirms the key role of hydrogen cage(H-cage)in determining high superconductivity.Here,we present a new class of metastable...The recent observation of high critical temperature T_(c) in lanthanum and Yttrium hydrides confirms the key role of hydrogen cage(H-cage)in determining high superconductivity.Here,we present a new class of metastable H_(12) clathrate structures based on the icosahedral cI 24-Na that can be stabilized by incorporation of metal elements.Analysis shows that the charge transfer from metal atoms to H atoms contributes to forming the H_(12) clathrate.Nine dynamically stable structures are identified to exhibit superconductivity,and a maximum T_(c) of 28K is found in voids-doped Mo_(6)H_(24).Calculations reveal that the low T_(c) is attributed to the weak interaction between H atoms in each cage due to the long H–H distance.The current results provide a possible route to design H-cage containing superconductors.展开更多
The detection of gravitational waves(GWs)by ground-based laser interferometer GW observatories(LIGO/Virgo)reveals a population of stellar binary black holes(sBBHs)with(total)masses up to~150 M⊙,which are potential so...The detection of gravitational waves(GWs)by ground-based laser interferometer GW observatories(LIGO/Virgo)reveals a population of stellar binary black holes(sBBHs)with(total)masses up to~150 M⊙,which are potential sources for space-based GW detectors,such as LISA and Taiji.In this paper,we investigate in details on the possibility of detecting sBBHs by the LISA-Taiji network in future.We adopt the sBBH merger rate density constrained by LIGO/VIRGO observations to randomly generate mock sBBHs samples.Assuming an observation period of 4 years,we find that the LISA-Taiji network may detect several tens(or at least several)sBBHs with signal-to-noise ratio(SNR)>8(or>15),a factor 2-3 times larger than that by only using LISA or Taiji observations.Among these sBBHs,no more than a few that can merge during the 4-year observation period.If extending the observation period to 10 years,then the LISA-Taiji network may detect about one hundred(or twenty)sBBHs with SNR>8(or>15),among them about twenty(or at least several)can merge within the observation period.Our results suggest that the LISA-Taiji network may be able to detect at least a handful to twenty or more sBBHs even if assuming a conservative SNR threshold(15)for"detection",which enables multi-band GW observations by space and ground-based GW detectors.We also further estimate the uncertainties in the parameter estimations of the sBBH systems"detected"by the LISA-Taiji network.We find that the relative errors in the luminosity distance measurements and sky localization are mostly in the range of 0.05-0.2 and 1-100 deg2,respectively,for these sBBHs.展开更多
Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted muc...Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted much attention in the treatment of bone,joint,neuropathic and other chronic pain and opioid use disorders in pregnant women.Considering that the unreasonable use of opioids by pregnant women will lead to risks such as drug accumulation and increased neural sensitivity in the fetus,the correct and reasonable use of opioids is the key to the treatment.In recent years,it has been found that opioids can cross the blood fetal barrier into the fetal circulation,and damage fetal nerve development to varying degrees.However,the studies on the typical diseases such as neonatal neural tube defects and neonatal abstinence syndrome are not comprehensive.Therefore,this article has clarified the unreasonable use of opioids during pregnancy and its effect on fetal nerve development,and put forward relevant measures in order to provide reference for clinicians/pharmacists in obstetrics and gynecology.展开更多
Gravitational wave(GW) signals from compact binary coalescences can be used as standard sirens to constrain cosmological parameters if their redshift can be measured independently by electromagnetic signals.However,me...Gravitational wave(GW) signals from compact binary coalescences can be used as standard sirens to constrain cosmological parameters if their redshift can be measured independently by electromagnetic signals.However,mergers of stellar binary black holes(BBHs) may not have electromagnetic counterparts and thus have no direct redshift measurements.These dark sirens may be still used to statistically constrain cosmological parameters by combining their GW measured luminosity distances and localization with deep redshift surveys of galaxies around it.We investigate this dark siren method to constrain cosmological parameters in detail by using mock BBH and galaxy samples.We find that the Hubble constant can be constrained well with an accuracy■ 1% with a few tens or more of BBH mergers at redshift up to 1 if GW observations can provide accurate estimates of their luminosity distance(with relative error of■ 0.01) and localization(■ 0.1 deg^(2)),though the constraint may be significantly biased if the luminosity distance and localization errors are larger.We also introduce a simple method to correct this bias and find it is valid when the luminosity distance and localization errors are modestly large.We further generate mock BBH samples,according to current constraints on BBH merger rate and the distributions of BBH properties,and find that the Deci-hertz Observatory(DO) in a half year observation period may detect about one hundred BBHs with signal-to-noise ratio■■30,relative luminosity distance error■ 0.02 and localization error ■0.01 deg^(2).By applying the dark standard siren method,we find that the Hubble constant can be constrained to the~0.1%-1% level using these DO BBHs,an accuracy comparable to the constraints obtained by using electromagnetic observations in the near future,thus it may provide insight into the Hubble tension.We also demonstrate that the constraint on the Hubble constant applying this dark siren method is robust and does not depend on the choice of the prior for the properties of BBH host galaxies.展开更多
文摘BACKGROUND Gastric cancer is a prevalent malignant cancer with a high incidence and significantly affects the health of modern people globally.Cisplatin(DDP)is one of the most common and effective chemotherapies for patients with gastric cancer,but DDP resistance remains a severe clinical challenge.AIM To explore the function of M2 polarized macrophages-derived exosomal microRNA(miR)-588 in the modulation of DDP resistance of gastric cancer cells.METHODS M2 polarized macrophages were isolated and identified by specific markers using flow cytometry analysis.The exosomes from M2 macrophages were identified by transmission electron microscopy and related markers.The uptake of the PKH67-labelled M2 macrophages-derived exosomes was detected in SGC7901 cells.The function and mechanism of exosomal miR-588 from M2 macrophages in the modulation of DDP resistance of gastric cancer cells was analyzed by CCK-8 assay,apoptosis analysis,colony formation assay,Western blot analysis,qPCR analysis,and luciferase reporter assay in SGC7901 and SGC7901/DDP cells,and by tumorigenicity analysis in nude mice.RESULTS M2 polarized macrophages were isolated from mouse bone marrow stimulated with interleukin(IL)-13 and IL-4.Co-cultivation of gastric cancer cells with M2 polarized macrophages promoted DDP resistance.M2 polarized macrophagesderived exosomes could transfer in gastric cancer cells to enhance DDP resistance.Exosomal miR-588 from M2 macrophages contributed to DDP resistance of gastric cancer cells.miR-588 promoted DDP-resistant gastric cancer cell growth in vivo.miR-588 was able to target cylindromatosis(CYLD)in gastric cancer cells.The depletion of CYLD reversed miR-588 inhibition-regulated cell proliferation and apoptosis of gastric cancer cells exposed to DDP.CONCLUSION In conclusion,we uncovered that exosomal miR-588 from M2 macrophages contributes to DDP resistance of gastric cancer cells by partly targeting CYLD.miR-588 may be applied as a potential therapeutic target for the treatment of gastric cancer.
基金National Natural Science Foundation of China(Grant Nos.11972177,11972122,11802103,11772144,11872030,and 11572034)the Scientific Research Starting Foundation for Scholars with Doctoral Degree of Guangdong Medical University(Grant Nos.B2019042 and B2019021).
文摘For conservative linear homogeneous nonholonomic systems, there exists a cotangent bundle with the symplectic structure dπμ∧ dξμ, in which the motion equations of the system can be written into the form of the canonical equations by the set of quasi-coordinates πμand quasi-momenta ξμ. The key to construct this cotangent bundle is to define a set of suitable quasi-coordinates πμby a first-order linear mapping, so that the reduced configuration space of the system is a Riemann space with no torsion. The Hamilton–Jacobi method for linear homogeneous nonholonomic systems is studied as an application of the quasi-canonicalization. The Hamilton–Jacobi method can be applied not only to Chaplygin nonholonomic systems, but also to non-Chaplygin nonholonomic systems. Two examples are given to illustrate the effectiveness of the quasi-canonicalization and the Hamilton–Jacobi method.
基金Supported by the National Natural Science Foundation of China(Grant Nos.12074154,11722433,11804128,11804129,and 11904142)the Qing Lan Project of Jiangsu Province.
文摘The recent observation of high critical temperature T_(c) in lanthanum and Yttrium hydrides confirms the key role of hydrogen cage(H-cage)in determining high superconductivity.Here,we present a new class of metastable H_(12) clathrate structures based on the icosahedral cI 24-Na that can be stabilized by incorporation of metal elements.Analysis shows that the charge transfer from metal atoms to H atoms contributes to forming the H_(12) clathrate.Nine dynamically stable structures are identified to exhibit superconductivity,and a maximum T_(c) of 28K is found in voids-doped Mo_(6)H_(24).Calculations reveal that the low T_(c) is attributed to the weak interaction between H atoms in each cage due to the long H–H distance.The current results provide a possible route to design H-cage containing superconductors.
基金partly supported by the National Key R&D Program of China (Grant Nos. 2020YFC2201400, 2020SKA0120102, and 2016YFA0400704)the National Natural Science Foundation of China (Grant Nos. 11690024, 11873056, and 11991052)+1 种基金the Strategic Priority Program of the Chinese Academy of Sciences (Grant No. XDB 23040100)the Beijing Municipal Natural Science Foundation (Grant No. 1204038)
文摘The detection of gravitational waves(GWs)by ground-based laser interferometer GW observatories(LIGO/Virgo)reveals a population of stellar binary black holes(sBBHs)with(total)masses up to~150 M⊙,which are potential sources for space-based GW detectors,such as LISA and Taiji.In this paper,we investigate in details on the possibility of detecting sBBHs by the LISA-Taiji network in future.We adopt the sBBH merger rate density constrained by LIGO/VIRGO observations to randomly generate mock sBBHs samples.Assuming an observation period of 4 years,we find that the LISA-Taiji network may detect several tens(or at least several)sBBHs with signal-to-noise ratio(SNR)>8(or>15),a factor 2-3 times larger than that by only using LISA or Taiji observations.Among these sBBHs,no more than a few that can merge during the 4-year observation period.If extending the observation period to 10 years,then the LISA-Taiji network may detect about one hundred(or twenty)sBBHs with SNR>8(or>15),among them about twenty(or at least several)can merge within the observation period.Our results suggest that the LISA-Taiji network may be able to detect at least a handful to twenty or more sBBHs even if assuming a conservative SNR threshold(15)for"detection",which enables multi-band GW observations by space and ground-based GW detectors.We also further estimate the uncertainties in the parameter estimations of the sBBH systems"detected"by the LISA-Taiji network.We find that the relative errors in the luminosity distance measurements and sky localization are mostly in the range of 0.05-0.2 and 1-100 deg2,respectively,for these sBBHs.
基金Key Research Base of Philosophy and Social Sciences in Shaanxi Province,Shaanxi Health Culture Research Center Projects(Grand JKWH2019-Q19).
文摘Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted much attention in the treatment of bone,joint,neuropathic and other chronic pain and opioid use disorders in pregnant women.Considering that the unreasonable use of opioids by pregnant women will lead to risks such as drug accumulation and increased neural sensitivity in the fetus,the correct and reasonable use of opioids is the key to the treatment.In recent years,it has been found that opioids can cross the blood fetal barrier into the fetal circulation,and damage fetal nerve development to varying degrees.However,the studies on the typical diseases such as neonatal neural tube defects and neonatal abstinence syndrome are not comprehensive.Therefore,this article has clarified the unreasonable use of opioids during pregnancy and its effect on fetal nerve development,and put forward relevant measures in order to provide reference for clinicians/pharmacists in obstetrics and gynecology.
基金partly supported by the National Key Program for Science and Technology Research and Development(Grant Nos. 2020YFC2201400, 2020SKA0120102 and 2016YFA0400704)the National Natural Science Foundation of China (Grant No. 11690024)the Strategic Priority Program of the Chinese Academy of Sciences (Grant XDB23040100)。
文摘Gravitational wave(GW) signals from compact binary coalescences can be used as standard sirens to constrain cosmological parameters if their redshift can be measured independently by electromagnetic signals.However,mergers of stellar binary black holes(BBHs) may not have electromagnetic counterparts and thus have no direct redshift measurements.These dark sirens may be still used to statistically constrain cosmological parameters by combining their GW measured luminosity distances and localization with deep redshift surveys of galaxies around it.We investigate this dark siren method to constrain cosmological parameters in detail by using mock BBH and galaxy samples.We find that the Hubble constant can be constrained well with an accuracy■ 1% with a few tens or more of BBH mergers at redshift up to 1 if GW observations can provide accurate estimates of their luminosity distance(with relative error of■ 0.01) and localization(■ 0.1 deg^(2)),though the constraint may be significantly biased if the luminosity distance and localization errors are larger.We also introduce a simple method to correct this bias and find it is valid when the luminosity distance and localization errors are modestly large.We further generate mock BBH samples,according to current constraints on BBH merger rate and the distributions of BBH properties,and find that the Deci-hertz Observatory(DO) in a half year observation period may detect about one hundred BBHs with signal-to-noise ratio■■30,relative luminosity distance error■ 0.02 and localization error ■0.01 deg^(2).By applying the dark standard siren method,we find that the Hubble constant can be constrained to the~0.1%-1% level using these DO BBHs,an accuracy comparable to the constraints obtained by using electromagnetic observations in the near future,thus it may provide insight into the Hubble tension.We also demonstrate that the constraint on the Hubble constant applying this dark siren method is robust and does not depend on the choice of the prior for the properties of BBH host galaxies.
