Cervical cancer(CC),has been identified as one of the most frequent malignant tumors all over the world,with high mortality in females.A growing number of investigations have confirmed that long noncoding RNAs(lncRNAs...Cervical cancer(CC),has been identified as one of the most frequent malignant tumors all over the world,with high mortality in females.A growing number of investigations have confirmed that long noncoding RNAs(lncRNAs)play a crucial role in the progression of multiple cancers.Nonetheless,the biological function and regulatory mechanism of LINC01772 in CC haven’t been explored so far.In this study,LINC01772 expression was found to be upregulated in tissues and cells of CC.Knocking down LINC01772 suppressed CC cell proliferation,migration and epithelial-mesenchymal transition(EMT)process.Through molecular mechanism assays,LINC01772 was verified to be bound with miR-3611 and LINC01772 acted as a sponge for miR-3611.Zinc finger E-box binding homeobox 1(ZEB1)was a downstream target gene of miR-3611.ZEB1 was negatively regulated by miR-3611 but positively regulated by LINC01772.Rescue assays confirmed that miR-3611 inhibitor or ZEB1 overexpression offset the inhibitive effect of LINC01772 depletion on cell proliferation,migration and EMT process in CC.In a word,our study validated that LINC01772 promoted cell metastasis and EMT process in CC by sponging miR-3611 to upregulate ZEB1 expression,indicating that LINC01772 could serve as a new therapeutic target for patients with CC.展开更多
Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prev...Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.展开更多
To investigate the cause of fine particulate matter(particles with an aerodynamic diameter less than 2.5 um,PM2.5) pollution in the heating season in the North China Plain(specifically Beijing,Tianjin,and Langfang),wa...To investigate the cause of fine particulate matter(particles with an aerodynamic diameter less than 2.5 um,PM2.5) pollution in the heating season in the North China Plain(specifically Beijing,Tianjin,and Langfang),water-soluble ions and carbonaceous components in PM2.5were simultaneously measured by online instruments with 1-hr resolution,from November 15,2016 to March 15,2017.The results showed extreme severity of PM2.5 pollution on a regional scale.Secondary inorganic ions(SNA,i.e.,NO3-+So42+NH4+) dominated the water-soluble ions,accounting for 30%-40% of PM2.5,while the total carbon(TC,i.e.,OC+EC) contributed to 26.5%-30.1% of PM2.5 IN the three cities.SNA were mainly responsible for the increasing PM2.5 pollution compared with organic matter(OM).NO3-was the most abundant species among water-soluble ions,but SO42- played a much more important role in driving the elevated PM2.5 concentrations.The relative humidity(RH) and its precursor SO2 were the key factors affecting the formation of sulfate.Homogeneous reactions dominated the formation of nitrate which was mainly limited by HNO3 in ammonia-rich conditions.Secondary formation and regional transport from the heavily polluted region promoted the growth of PM2.5 concentrations in the formation stage of PM2.5 pollution in Beijing and Langfang.Regional transport or local emissions,along with secondary formation,made great contributions to the PM2.5 pollution in the evolution stage of PM2.5 pollution in Beijing and Langfang.The favourable meteorological conditions and regional transport from a relatively clean region both favored the diffusion of pollutants in all three cities.展开更多
Long-term and synchronous monitoring of PMIo and PM2.s was conducted in Chengdu in China from 2007 to 2013. The levels, variations, compositions and size distributions were investigated. The sources were quantified by...Long-term and synchronous monitoring of PMIo and PM2.s was conducted in Chengdu in China from 2007 to 2013. The levels, variations, compositions and size distributions were investigated. The sources were quantified by two-way and three-way receptor models （PMF2, ME2-2way and ME2-3way）, Consistent results were found： the primary source categories contributed 63.4% （PMF2）, 64.8% （ME2-2way） and 66.8% （ME2-Bway） to PMIo, and contributed 60.9% （PMF2）, 65.5% （ME2-2way） and 61.0% （ME2-3way） to PM2.s. Secondary sources contributed 31.8% （PMF2）, 32.9% （ME2-2way） and 31.7% （ME2-3way） to PMIo, and 35.0% （PMF2）, 33.8% （ME2-2way） and 36.0% （ME2-3way） to PM2.s. The size distribution of source categories was estimated better by the ME2-3way method. The three-way model can simultaneously consider chemical species, temporal variability and PM sizes, while a two-way model independently computes datasets of different sizes. A method called source directional apportionment （SDA） was employed to quantify the contributions from various directions for each source category. Crustal dust from east-north-east （ENE） contributed the highest to both PM^o （12.7%） and PMzs （9.7%） in Chengdu, followed by the crustal dust from south-east （SE） for PMao （9.8%） and secondary nitrate ＆ secondary organic carbon from ENE for PMzs （9.6%）. Source contributions from different directions are associated with meteorological conditions, source locations and emission patterns during the sampling period. These findings and methods provide useful tools to better understand PM pollution status and tn dovolon offoctive nolhltion control gtrateMeg.展开更多
Objective:Metabolic disorders are markedly common in women with polycystic ovary syndrome(PCOS),and nonalcoholic fatty liver disease(NAFLD)is observed in 30%-55%of all PCOS patients.Many studies have reported that aut...Objective:Metabolic disorders are markedly common in women with polycystic ovary syndrome(PCOS),and nonalcoholic fatty liver disease(NAFLD)is observed in 30%-55%of all PCOS patients.Many studies have reported that autophagy and apoptosis,which are closely related to mitochondrial function,play important roles in the development of NAFLD.Therefore,in this study,we aimed to explore the role of mitochondrial dysfunction caused by liver apoptosis and autophagy imbalance in the development of NAFLD in a PCOS mouse model.Methods:We used a dihydrotestosterone(DHT)-induced PCOS model to mimic the pathological process of hyperandrogenism.Hematoxylin and eosin and Oil Red O staining assays were used to observe the pathological changes in the liver.Western blotting and quantitative real-time polymerase chain reaction were used to perform mitochondrion-related assays.Results:Hepatic steatosis and different degrees of inflammation were observed in the DHT-treated mice.The expression of molecules involved in the respiratory chain and aerobic respiration process was altered.The levels of the key molecules associated with apoptosis and autophagy were abnormal.Conclusions:Androgens may play a role in the process of hepatic steatosis development by affecting mitochondrial function and subsequently inducing apoptosis and autophagy.Such phenomena might be involved in the pathogenesis of NAFLD in women with PCOS.展开更多
文摘Cervical cancer(CC),has been identified as one of the most frequent malignant tumors all over the world,with high mortality in females.A growing number of investigations have confirmed that long noncoding RNAs(lncRNAs)play a crucial role in the progression of multiple cancers.Nonetheless,the biological function and regulatory mechanism of LINC01772 in CC haven’t been explored so far.In this study,LINC01772 expression was found to be upregulated in tissues and cells of CC.Knocking down LINC01772 suppressed CC cell proliferation,migration and epithelial-mesenchymal transition(EMT)process.Through molecular mechanism assays,LINC01772 was verified to be bound with miR-3611 and LINC01772 acted as a sponge for miR-3611.Zinc finger E-box binding homeobox 1(ZEB1)was a downstream target gene of miR-3611.ZEB1 was negatively regulated by miR-3611 but positively regulated by LINC01772.Rescue assays confirmed that miR-3611 inhibitor or ZEB1 overexpression offset the inhibitive effect of LINC01772 depletion on cell proliferation,migration and EMT process in CC.In a word,our study validated that LINC01772 promoted cell metastasis and EMT process in CC by sponging miR-3611 to upregulate ZEB1 expression,indicating that LINC01772 could serve as a new therapeutic target for patients with CC.
基金supported by the National Natural Science Foundation of China(NSFC)(81991494 and 82122031)the National Key R&D Program of China(2020YFA0907100)+3 种基金the Chinese Academy of Sciences(YSBR-010)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-026)Beijing Natural Science Foundation(L222076)L.D.is supported by the Youth Innovation Promotion Association CAS,China(2018113).
文摘Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.
基金supported by the National Natural Science Foundation of China(No.91544226)the National Key Research and Development Plan of China(Nos.2017YFC0209503 and 2016YFC0206202)+1 种基金the National Research Program for Key Issues in Air Pollution Control in China(No.DQGG0107-03)the financial support from CSC(Chinese Scholorship Council)
文摘To investigate the cause of fine particulate matter(particles with an aerodynamic diameter less than 2.5 um,PM2.5) pollution in the heating season in the North China Plain(specifically Beijing,Tianjin,and Langfang),water-soluble ions and carbonaceous components in PM2.5were simultaneously measured by online instruments with 1-hr resolution,from November 15,2016 to March 15,2017.The results showed extreme severity of PM2.5 pollution on a regional scale.Secondary inorganic ions(SNA,i.e.,NO3-+So42+NH4+) dominated the water-soluble ions,accounting for 30%-40% of PM2.5,while the total carbon(TC,i.e.,OC+EC) contributed to 26.5%-30.1% of PM2.5 IN the three cities.SNA were mainly responsible for the increasing PM2.5 pollution compared with organic matter(OM).NO3-was the most abundant species among water-soluble ions,but SO42- played a much more important role in driving the elevated PM2.5 concentrations.The relative humidity(RH) and its precursor SO2 were the key factors affecting the formation of sulfate.Homogeneous reactions dominated the formation of nitrate which was mainly limited by HNO3 in ammonia-rich conditions.Secondary formation and regional transport from the heavily polluted region promoted the growth of PM2.5 concentrations in the formation stage of PM2.5 pollution in Beijing and Langfang.Regional transport or local emissions,along with secondary formation,made great contributions to the PM2.5 pollution in the evolution stage of PM2.5 pollution in Beijing and Langfang.The favourable meteorological conditions and regional transport from a relatively clean region both favored the diffusion of pollutants in all three cities.
基金supported by the Tianjin Natural Science Foundation(No.16JCQNJC08700)the Fundamental Research Funds for the Central Universities+4 种基金National Key Research and Development Program of China(No.2016YFC0208500)the National Natural Science Foundation of China(No.21407174)the Tianjin Research Program of Application Foundation(No.14JCQNJC08100)the Tianjin Science and Technology Project(Nos.16YFZCSF00260,14ZCDGSF00027,14ZCDGSF00029)the Special Funds for Research on Public Welfares of the Ministry of Environmental Protection of China(201309072)
文摘Long-term and synchronous monitoring of PMIo and PM2.s was conducted in Chengdu in China from 2007 to 2013. The levels, variations, compositions and size distributions were investigated. The sources were quantified by two-way and three-way receptor models （PMF2, ME2-2way and ME2-3way）, Consistent results were found： the primary source categories contributed 63.4% （PMF2）, 64.8% （ME2-2way） and 66.8% （ME2-Bway） to PMIo, and contributed 60.9% （PMF2）, 65.5% （ME2-2way） and 61.0% （ME2-3way） to PM2.s. Secondary sources contributed 31.8% （PMF2）, 32.9% （ME2-2way） and 31.7% （ME2-3way） to PMIo, and 35.0% （PMF2）, 33.8% （ME2-2way） and 36.0% （ME2-3way） to PM2.s. The size distribution of source categories was estimated better by the ME2-3way method. The three-way model can simultaneously consider chemical species, temporal variability and PM sizes, while a two-way model independently computes datasets of different sizes. A method called source directional apportionment （SDA） was employed to quantify the contributions from various directions for each source category. Crustal dust from east-north-east （ENE） contributed the highest to both PM^o （12.7%） and PMzs （9.7%） in Chengdu, followed by the crustal dust from south-east （SE） for PMao （9.8%） and secondary nitrate ＆ secondary organic carbon from ENE for PMzs （9.6%）. Source contributions from different directions are associated with meteorological conditions, source locations and emission patterns during the sampling period. These findings and methods provide useful tools to better understand PM pollution status and tn dovolon offoctive nolhltion control gtrateMeg.
基金This work was supported by the National Natural Science Foundation of China(No.81673766 and 81973945 to YF,No.81572555 to XL)the Chinese Special Fund for Postdocs(No.2014T70392)+1 种基金the Swedish Medical Research Council(No.10380)the Swedish Federal Government under the LUA/ALF agreement(No.ALFGBG-147791 to HB and LS).
文摘Objective:Metabolic disorders are markedly common in women with polycystic ovary syndrome(PCOS),and nonalcoholic fatty liver disease(NAFLD)is observed in 30%-55%of all PCOS patients.Many studies have reported that autophagy and apoptosis,which are closely related to mitochondrial function,play important roles in the development of NAFLD.Therefore,in this study,we aimed to explore the role of mitochondrial dysfunction caused by liver apoptosis and autophagy imbalance in the development of NAFLD in a PCOS mouse model.Methods:We used a dihydrotestosterone(DHT)-induced PCOS model to mimic the pathological process of hyperandrogenism.Hematoxylin and eosin and Oil Red O staining assays were used to observe the pathological changes in the liver.Western blotting and quantitative real-time polymerase chain reaction were used to perform mitochondrion-related assays.Results:Hepatic steatosis and different degrees of inflammation were observed in the DHT-treated mice.The expression of molecules involved in the respiratory chain and aerobic respiration process was altered.The levels of the key molecules associated with apoptosis and autophagy were abnormal.Conclusions:Androgens may play a role in the process of hepatic steatosis development by affecting mitochondrial function and subsequently inducing apoptosis and autophagy.Such phenomena might be involved in the pathogenesis of NAFLD in women with PCOS.
