Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental arrest.Many studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure ...Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental arrest.Many studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains unknown.Whole-exome sequencing(WES)was performed to identify candidate mutations in couples with primary infertility.Sanger sequencing was used to validate the mutations.Multiple PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced.Assisted oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte activation.We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,p.R385Q.PN formation failure was observed during the ICSI cycle.However,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN formation.AOA after ICSI enabled normal fertilization,and all patients achieved successful pregnancies.These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy.Furthermore,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.展开更多
It has been reported that hyperspectral data could be employed to qualitatively elucidate the spatial composition of tablets of Chinese medicinal plants.To gain more insights into this technology,a quantitative profil...It has been reported that hyperspectral data could be employed to qualitatively elucidate the spatial composition of tablets of Chinese medicinal plants.To gain more insights into this technology,a quantitative profile provided by near infrared(NIR)spectromicroscopy was further studied by determining the glycyrrhizic acid content in licorice,Glycyrrhiza uralensis.Thirty-nine samples from twenty-four different origins were analyzed using NIR spectromicroscopy.Partial least squares,interval partial least square(iPLS),and least squares support vector regression(LS-SVR) methods were used to develop linear and non-linear calibration models,with optimal calibration parameters(number of interval numbers,kernel parameter,etc.) being explored.The root mean square error of prediction(RMSEP) and the coefficient of determination(R^2) of the iPLS model were 0.717 7% and 0.936 1 in the prediction set,respectively.The RMSEP and R^2 of LS-SVR model were 0.515 5%and 0.951 4 in the prediction set,respectively.These results demonstrated that the glycyrrhizic acid content in licorice could barely be analyzed by NIR spectromicroscopy,suggesting that good quality quantitative data are difficult to obtain from microscopic NIR spectra for complicated Chinese medicinal plant materials.展开更多
Reactive stromal changes in prostate cancer （PCa） are likely involved in the emergence of castration-resistant PCa （CRPC）. This study was designed to investigate stromal changes in patients with clinically advance...Reactive stromal changes in prostate cancer （PCa） are likely involved in the emergence of castration-resistant PCa （CRPC）. This study was designed to investigate stromal changes in patients with clinically advanced PCa and analyze their prognostic significance. Prostate needle biopsies obtained from 148 patients before castration therapy were analyzed by Masson trichrome staining and immunohistochemical analysis of vimentin and desmin. Reactive stroma grading was inversely correlated with Gleason score. Stroma grade （Masson stain 82.8% vs 45.6%, P 〈 0.001） and vimentin expression （P = 0.005） were significantly higher, and desmin expression （P = 0.004） significantly lower, in reactive stroma of tumors with a Gleason score of 6-7 than in adjacent peritumoral tissue. Kaplan-Meier analysis showed a significant association between reactive stroma grade in tumors and the occurrence of CRPC in patients with a Gleason score of 6-7 （P= 0.009）. Furthermore, patients with higher vimentin or lower desmin expression had a shorter disease-free period. In multivariate analysis, only vimentin expression was a significant predictor of tumor relapse （hazard ratio 1.78, 95% confidence interval 1.12-10.26, P = 0.012）. These findings indicate that the intensity of reactive stroma is associated with castration responsiveness, especially in patients with a lower Gleason score where the abundant stroma component is most frequently found. High expression of vimentin in tumor stroma was independently associated with poor outcomes in patients with Gleason scores of 6-7, and may serve as a new prognostic marker in daily practice.展开更多
Electrorheological(ER)fluids based on nanorods of calcium and titanium precipitate(CTP)possess good ER performance.We investigate the shear stress and leaking current of CTP suspension from-15 to 230℃,and it is found...Electrorheological(ER)fluids based on nanorods of calcium and titanium precipitate(CTP)possess good ER performance.We investigate the shear stress and leaking current of CTP suspension from-15 to 230℃,and it is found that the ER effect increases at up to 150℃.Dielectric spectra of the CTP suspension at different temperatures indicate that the change of interface polarization can perfectly interpret the increment of ER effect and leaking current.The Fourier transform infrared(FTIR)spectroscopy test shows that some compositions of the CTP particles decompose at temperature of 180℃,which leads to a consequential decrease of ER effect.Through thermogravimetric and differential thermal analyses(TG-DTA),we find that TiOC_(2)O_(4)(H_(2)O)_(2) plays a key role in the dielectric property and ER effect of CTP suspension.展开更多
The shear banding is explored in a granular suspension driven by electric field and shear flow.We find that,given an imposed electric field,there is a critical shear rate determining whether shear banding emerges.A ph...The shear banding is explored in a granular suspension driven by electric field and shear flow.We find that,given an imposed electric field,there is a critical shear rate determining whether shear banding emerges.A phase diagram of shear banding and fluidization is constructed by using the present experimental data.The evolution in different shear banding phases constitutes an apparent shear thinning phenomenon,probably reflecting an underlying perspective of shear banding.Using the two-phase model,combining with mean field approach and the Onsager least dissipation principle,we give a qualitative explanation of our experimental findings.The results suggest that the stress heterogeneity plays a crucial role for the physical origin of shear banding in this system.展开更多
We apply electric fields at different frequencies of 0.1,1,10 and 100 kHz to the rat basophilic leukemia(RBL)mast cells in calcium-containing or calcium-free buffers.The stimuli cause changes of the intracellular calc...We apply electric fields at different frequencies of 0.1,1,10 and 100 kHz to the rat basophilic leukemia(RBL)mast cells in calcium-containing or calcium-free buffers.The stimuli cause changes of the intracellular calcium ion concentration[Ca^(2+)]i as well as the histamine.The[Ca^(2+)]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz,and then decreases when the frequency further increases from 10 kHz to 100 kHz,showing a peak at 100 kHz.A similar frequency dependence of the histamine release is also found.The[Ca^(2+)]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation.The ruthenium red(RR),an inhibitor to the TRPV(transient receptor potential(TRP)family V)channels across the cell membrane,is used in the experiment to check whether the electric field stimuli act on the TRPV channels.Under an electric field of 10 kHz,the[Ca^(2+)]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation,while the[Ca^(2+)]i in a calcium-free buffer is only about 2.2 times.Similar behavior is also found for the histamine release.RR blockage effect on the[Ca^(2+)]i decrease is statistically significant(~75%)when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment.This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli.Under this condition,the histamine is also released following a similar way.We suggest that,as far as an electric stimulation is concerned,an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells,and this would cause a significant calcium influx resulting in a significant histamine release,which could be one of the mechanisms for electric therapy.展开更多
基金the General Project of Chongqing Natural Science foundation of China(cstc2021jcyj-msxmX0877)the Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau,2023MSXM054)the General Project of Chongqing Health Center for Women and Children(2020YJMS01 and 2021YJMS05).
文摘Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental arrest.Many studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains unknown.Whole-exome sequencing(WES)was performed to identify candidate mutations in couples with primary infertility.Sanger sequencing was used to validate the mutations.Multiple PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced.Assisted oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte activation.We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,p.R385Q.PN formation failure was observed during the ICSI cycle.However,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN formation.AOA after ICSI enabled normal fertilization,and all patients achieved successful pregnancies.These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy.Furthermore,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.
基金supported by the National Natural Science Foundation of China(No.81303218)the Doctoral Fund of the Ministry of Education of China(No.20130013120006)Beijing University of Chinese Medicine Special Subject of Outstanding Young Teachers and Innovation Team Foundation
文摘It has been reported that hyperspectral data could be employed to qualitatively elucidate the spatial composition of tablets of Chinese medicinal plants.To gain more insights into this technology,a quantitative profile provided by near infrared(NIR)spectromicroscopy was further studied by determining the glycyrrhizic acid content in licorice,Glycyrrhiza uralensis.Thirty-nine samples from twenty-four different origins were analyzed using NIR spectromicroscopy.Partial least squares,interval partial least square(iPLS),and least squares support vector regression(LS-SVR) methods were used to develop linear and non-linear calibration models,with optimal calibration parameters(number of interval numbers,kernel parameter,etc.) being explored.The root mean square error of prediction(RMSEP) and the coefficient of determination(R^2) of the iPLS model were 0.717 7% and 0.936 1 in the prediction set,respectively.The RMSEP and R^2 of LS-SVR model were 0.515 5%and 0.951 4 in the prediction set,respectively.These results demonstrated that the glycyrrhizic acid content in licorice could barely be analyzed by NIR spectromicroscopy,suggesting that good quality quantitative data are difficult to obtain from microscopic NIR spectra for complicated Chinese medicinal plant materials.
文摘Reactive stromal changes in prostate cancer （PCa） are likely involved in the emergence of castration-resistant PCa （CRPC）. This study was designed to investigate stromal changes in patients with clinically advanced PCa and analyze their prognostic significance. Prostate needle biopsies obtained from 148 patients before castration therapy were analyzed by Masson trichrome staining and immunohistochemical analysis of vimentin and desmin. Reactive stroma grading was inversely correlated with Gleason score. Stroma grade （Masson stain 82.8% vs 45.6%, P 〈 0.001） and vimentin expression （P = 0.005） were significantly higher, and desmin expression （P = 0.004） significantly lower, in reactive stroma of tumors with a Gleason score of 6-7 than in adjacent peritumoral tissue. Kaplan-Meier analysis showed a significant association between reactive stroma grade in tumors and the occurrence of CRPC in patients with a Gleason score of 6-7 （P= 0.009）. Furthermore, patients with higher vimentin or lower desmin expression had a shorter disease-free period. In multivariate analysis, only vimentin expression was a significant predictor of tumor relapse （hazard ratio 1.78, 95% confidence interval 1.12-10.26, P = 0.012）. These findings indicate that the intensity of reactive stroma is associated with castration responsiveness, especially in patients with a lower Gleason score where the abundant stroma component is most frequently found. High expression of vimentin in tumor stroma was independently associated with poor outcomes in patients with Gleason scores of 6-7, and may serve as a new prognostic marker in daily practice.
基金Supported by the National Natural Science Foundation of China under Grant Nos 10334020,10974030 and 10574027.
文摘Electrorheological(ER)fluids based on nanorods of calcium and titanium precipitate(CTP)possess good ER performance.We investigate the shear stress and leaking current of CTP suspension from-15 to 230℃,and it is found that the ER effect increases at up to 150℃.Dielectric spectra of the CTP suspension at different temperatures indicate that the change of interface polarization can perfectly interpret the increment of ER effect and leaking current.The Fourier transform infrared(FTIR)spectroscopy test shows that some compositions of the CTP particles decompose at temperature of 180℃,which leads to a consequential decrease of ER effect.Through thermogravimetric and differential thermal analyses(TG-DTA),we find that TiOC_(2)O_(4)(H_(2)O)_(2) plays a key role in the dielectric property and ER effect of CTP suspension.
基金Supported by the National Natural Science Foundation of China under Grant Nos 10334020,10974030 and 10574027.
文摘The shear banding is explored in a granular suspension driven by electric field and shear flow.We find that,given an imposed electric field,there is a critical shear rate determining whether shear banding emerges.A phase diagram of shear banding and fluidization is constructed by using the present experimental data.The evolution in different shear banding phases constitutes an apparent shear thinning phenomenon,probably reflecting an underlying perspective of shear banding.Using the two-phase model,combining with mean field approach and the Onsager least dissipation principle,we give a qualitative explanation of our experimental findings.The results suggest that the stress heterogeneity plays a crucial role for the physical origin of shear banding in this system.
基金Supported by the Science and Technology Commission of Shanghai Municipality under Grant No 09DZ1976602the National Basic Research Program of China under Grant No 2006CB504509.
文摘We apply electric fields at different frequencies of 0.1,1,10 and 100 kHz to the rat basophilic leukemia(RBL)mast cells in calcium-containing or calcium-free buffers.The stimuli cause changes of the intracellular calcium ion concentration[Ca^(2+)]i as well as the histamine.The[Ca^(2+)]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz,and then decreases when the frequency further increases from 10 kHz to 100 kHz,showing a peak at 100 kHz.A similar frequency dependence of the histamine release is also found.The[Ca^(2+)]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation.The ruthenium red(RR),an inhibitor to the TRPV(transient receptor potential(TRP)family V)channels across the cell membrane,is used in the experiment to check whether the electric field stimuli act on the TRPV channels.Under an electric field of 10 kHz,the[Ca^(2+)]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation,while the[Ca^(2+)]i in a calcium-free buffer is only about 2.2 times.Similar behavior is also found for the histamine release.RR blockage effect on the[Ca^(2+)]i decrease is statistically significant(~75%)when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment.This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli.Under this condition,the histamine is also released following a similar way.We suggest that,as far as an electric stimulation is concerned,an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells,and this would cause a significant calcium influx resulting in a significant histamine release,which could be one of the mechanisms for electric therapy.
