Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetrati...Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore,in this study,taking fluorescent labeled PLGA(poly(lactic-co-glycolic acid)) nanoparticles as a tool,the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method(MPT).Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2–3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate(SDS) increased the complex viscosity and viscoelastic properties of mucus,but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants,the penetration of nanoparticles in intestinal villus was obviously increased. In summary,the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile.展开更多
Long non-coding RNAs(lncRNAs), gradually being paid attention to, have been found playing a critical role in regulation of cellular processes such as cell growth and apoptosis, what is more, accumulating evidence indi...Long non-coding RNAs(lncRNAs), gradually being paid attention to, have been found playing a critical role in regulation of cellular processes such as cell growth and apoptosis, what is more, accumulating evidence indicates that lncRNAs also play a critical role in regulation of carcinogenesis and cancer progression. Here, we will summarize the recent researches about some lncRNAs in the development of cancers, hoping to give a new view about the study in the mechanisms involved in carcinogenesis and tumor progression.展开更多
Combined with actual situation of Fengxian power Supply Company, the neutral grounding modes of Fengxian 35 kV and 10 kV power grid are studied in the paper. The different frequencies injected method is used to measur...Combined with actual situation of Fengxian power Supply Company, the neutral grounding modes of Fengxian 35 kV and 10 kV power grid are studied in the paper. The different frequencies injected method is used to measure the capacitive current of Fengxian 28 substations, and the neutral grounding modes of the 28 substations are determined based on the measured values of capacitive current.展开更多
Human and mouse orthologs are expected to have similar biological functions; however, many discrepancies have also been reported. We systematically compared human and mouse orthologs in terms of alternative splicing p...Human and mouse orthologs are expected to have similar biological functions; however, many discrepancies have also been reported. We systematically compared human and mouse orthologs in terms of alternative splicing patterns and expression profiles. Human-mouse orthologs are divergent in alternative splicing, as human orthologs could generally encode more isoforms than their mouse orthologs. In early embryos, exon skipping is far more common with human orthologs, whereas constitutive exons are more prevalent with mouse orthologs. This may correlate with divergence in expression of splicing regulators. Orthologous expression similarities are different in distinct embryonic stages, with the highest in morula. Expression differences for orthologous transcription factor genes could play an important role in orthologous expression discordance. We further detected largely orthologous divergence in differential expression between distinct embryonic stages. Collectively, our study uncovers significant orthologous divergence from multiple aspects, which may result in functional differences and dynamics between human-mouse orthologs during embryonic development.展开更多
Aims We aim to investigate variations in the resorption efficiencies of 10 mineral nutrients[i.e.nitrogen(N),phosphorus(P),potassium(K),magnesium(Mg),calcium(Ca),manganese(Mn),zinc(Zn),alu-minum(Al),iron(Fe)and copper...Aims We aim to investigate variations in the resorption efficiencies of 10 mineral nutrients[i.e.nitrogen(N),phosphorus(P),potassium(K),magnesium(Mg),calcium(Ca),manganese(Mn),zinc(Zn),alu-minum(Al),iron(Fe)and copper(Cu)]in leaves of desert shrubs and to explore effects of aridity on resorption efficiency of these nutrients.Methods Plant samples were collected from 10 sites in northern Xinjiang Uygur Autonomous Region of China.Samples of green and senesced leaves were analysed to determine concentrations of N,P,K,Mg,Ca,Mn,Zn,Al,Fe and Cu and thus the nutrient resorption efficiency.Important Findings The mean nutrient concentrations in the desert shrubs varied,with the stoichiometric ratio Ca:N(19.3 mg g−1):K(10.5 mg g−1):Mg:P(1.01 mg g−1):Al:Fe:Mn:Zn:Cu(4.78 mg kg−1)=4038:2950:2199:1816:211:37:32:11:2:1 in green leaves;and Ca:N(12.6 mg g−1):Mg:K(7.6 mg g−1):P(0.56 mg g−1):Fe:Al:Mn:Zn:Cu(2.85 mg kg−1)=5583:3710:2943:2523:178:133:119:19:3.7:1 in senesced leaves.Resorption generally occurred for six elements(N,P,K,Cu,Mg and Mn,with average resorption efficiency 47.8%,52.0%,38.6%,41.0%,12.7%and 7.89%,respectively)during leaf senescence,while the other four nutrients tended to accumulate in senesced leaves,showing averagely negative resorption efficiencies[Ca(-3.87%),Al(−57.1%),Zn(−62.6%),Fe(−89.6%)].Aridity showed strikingly different effects on the resorption process of the 10 nutri-ents.Of the four elements with totally(N/P/K)or mostly(Cu)posi-tive observations of resorption efficiency,their resorption generally decreased with aridity,suggesting that drought stress had negative effects on the resorption efficiencies of these elements.In contrast,with at least one-third observations of resorption efficiency being negative,the other elements(Mg/Mn/Ca/Zn/Al/Fe)showed gener-ally increasing resorptive tendency with aridity,except for Zn.This research provided a systematic analysis on the large variation and contrasting responses of the resorption of multi-elements to aridity in typical desert shrubs.Our findings foster the understanding of nutrient resorption patterns of desert plants and enable us to better predict the contrastive effects of drought stress on the cycling of diverse nutrients and the consequent stoichiometric decoupling in plants of desert ecosystems.展开更多
Anterior segment eye diseases account for a significant proportion of presentations to eye clinics worldwide,including diseases associated with corneal pathologies,anterior chamber abnormalities(e.g.blood or inflammat...Anterior segment eye diseases account for a significant proportion of presentations to eye clinics worldwide,including diseases associated with corneal pathologies,anterior chamber abnormalities(e.g.blood or inflammation),and lens diseases.The construction of an automatic tool for segmentation of anterior segment eye lesions would greatly improve the efficiency of clinical care.With research on artificial intelligence progressing in recent years,deep learning models have shown their superiority in image classification and segmentation.The training and evaluation of deep learning models should be based on a large amount of data annotated with expertise;however,such data are relatively scarce in the domain of medicine.Herein,the authors developed a new medical image annotation system,called EyeHealer.It is a large-scale anterior eye segment dataset with both eye structures and lesions annotated at the pixel level.Comprehensive experiments were conducted to verify its performance in disease classification and eye lesion segmentation.The results showed that semantic segmentation models outperformed medical segmentation models.This paper describes the establishment of the system for automated classification and segmentation tasks.The dataset will be made publicly available to encourage future research in this area.展开更多
Uveal melanoma is the most common intraocular cancer in the adult eye.R183 and Q209 were found to be mutational hotspots in exon 4 and exon 5 of GNAQ and GNA11 in Caucasians.However,only a few studies have reported so...Uveal melanoma is the most common intraocular cancer in the adult eye.R183 and Q209 were found to be mutational hotspots in exon 4 and exon 5 of GNAQ and GNA11 in Caucasians.However,only a few studies have reported somaticmutations in GNAQ or GNA11 in uveal melanoma in Chinese.We extracted somatic DNA from paraffin-embedded biopsies of 63 Chinese uveal melanoma samples and sequenced the entire coding regions of exons 4 and 5 in GNAQ and GNA11.The results showed that 33%of Chinese uveal melanoma samples carried Q209 mutations while none had R183 mutation in GNAQ or GNA11.In addition,seven novel missense somatic mutations in GNAQ(Y192C,F194L,P170S,D236N,L232F,V230A,and M227I)and four novel missense somatic mutations in GNA11(R166C,I200T,S225F,and V206M)were found in our study.The high mutation frequency of Q209 and the novel missense mutations detected in this study suggest that GNAQ and GNA11 are common targets for somatic mutations in Chinese uveal melanoma.展开更多
基金financially supported by the National Natural Science Foundation of China (Grant No. 31870987)
文摘Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore,in this study,taking fluorescent labeled PLGA(poly(lactic-co-glycolic acid)) nanoparticles as a tool,the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method(MPT).Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2–3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate(SDS) increased the complex viscosity and viscoelastic properties of mucus,but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants,the penetration of nanoparticles in intestinal villus was obviously increased. In summary,the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile.
文摘Long non-coding RNAs(lncRNAs), gradually being paid attention to, have been found playing a critical role in regulation of cellular processes such as cell growth and apoptosis, what is more, accumulating evidence indicates that lncRNAs also play a critical role in regulation of carcinogenesis and cancer progression. Here, we will summarize the recent researches about some lncRNAs in the development of cancers, hoping to give a new view about the study in the mechanisms involved in carcinogenesis and tumor progression.
文摘Combined with actual situation of Fengxian power Supply Company, the neutral grounding modes of Fengxian 35 kV and 10 kV power grid are studied in the paper. The different frequencies injected method is used to measure the capacitive current of Fengxian 28 substations, and the neutral grounding modes of the 28 substations are determined based on the measured values of capacitive current.
基金supported by the China Human Proteomics Project (2014DFB30010)the National High Technology Research and Development Program of China (2015AA020104)+1 种基金the National Natural Science Foundation of China (31071162)the Graduate School of East China Normal University
文摘Human and mouse orthologs are expected to have similar biological functions; however, many discrepancies have also been reported. We systematically compared human and mouse orthologs in terms of alternative splicing patterns and expression profiles. Human-mouse orthologs are divergent in alternative splicing, as human orthologs could generally encode more isoforms than their mouse orthologs. In early embryos, exon skipping is far more common with human orthologs, whereas constitutive exons are more prevalent with mouse orthologs. This may correlate with divergence in expression of splicing regulators. Orthologous expression similarities are different in distinct embryonic stages, with the highest in morula. Expression differences for orthologous transcription factor genes could play an important role in orthologous expression discordance. We further detected largely orthologous divergence in differential expression between distinct embryonic stages. Collectively, our study uncovers significant orthologous divergence from multiple aspects, which may result in functional differences and dynamics between human-mouse orthologs during embryonic development.
基金The project was funded by the National Natural Science Foundation of China(#41473068)the‘Light of West China Program of the Chinese Academy of Sciences’and National Key Basic Research Program of China(#2014CB954202).
文摘Aims We aim to investigate variations in the resorption efficiencies of 10 mineral nutrients[i.e.nitrogen(N),phosphorus(P),potassium(K),magnesium(Mg),calcium(Ca),manganese(Mn),zinc(Zn),alu-minum(Al),iron(Fe)and copper(Cu)]in leaves of desert shrubs and to explore effects of aridity on resorption efficiency of these nutrients.Methods Plant samples were collected from 10 sites in northern Xinjiang Uygur Autonomous Region of China.Samples of green and senesced leaves were analysed to determine concentrations of N,P,K,Mg,Ca,Mn,Zn,Al,Fe and Cu and thus the nutrient resorption efficiency.Important Findings The mean nutrient concentrations in the desert shrubs varied,with the stoichiometric ratio Ca:N(19.3 mg g−1):K(10.5 mg g−1):Mg:P(1.01 mg g−1):Al:Fe:Mn:Zn:Cu(4.78 mg kg−1)=4038:2950:2199:1816:211:37:32:11:2:1 in green leaves;and Ca:N(12.6 mg g−1):Mg:K(7.6 mg g−1):P(0.56 mg g−1):Fe:Al:Mn:Zn:Cu(2.85 mg kg−1)=5583:3710:2943:2523:178:133:119:19:3.7:1 in senesced leaves.Resorption generally occurred for six elements(N,P,K,Cu,Mg and Mn,with average resorption efficiency 47.8%,52.0%,38.6%,41.0%,12.7%and 7.89%,respectively)during leaf senescence,while the other four nutrients tended to accumulate in senesced leaves,showing averagely negative resorption efficiencies[Ca(-3.87%),Al(−57.1%),Zn(−62.6%),Fe(−89.6%)].Aridity showed strikingly different effects on the resorption process of the 10 nutri-ents.Of the four elements with totally(N/P/K)or mostly(Cu)posi-tive observations of resorption efficiency,their resorption generally decreased with aridity,suggesting that drought stress had negative effects on the resorption efficiencies of these elements.In contrast,with at least one-third observations of resorption efficiency being negative,the other elements(Mg/Mn/Ca/Zn/Al/Fe)showed gener-ally increasing resorptive tendency with aridity,except for Zn.This research provided a systematic analysis on the large variation and contrasting responses of the resorption of multi-elements to aridity in typical desert shrubs.Our findings foster the understanding of nutrient resorption patterns of desert plants and enable us to better predict the contrastive effects of drought stress on the cycling of diverse nutrients and the consequent stoichiometric decoupling in plants of desert ecosystems.
基金This study was funded by the National Key Research and Development Program of China(Grant No.2017YFC1104600)Recruitment Program of Leading Talents of Guangdong Province(Grant No.2016LJ06Y375).
文摘Anterior segment eye diseases account for a significant proportion of presentations to eye clinics worldwide,including diseases associated with corneal pathologies,anterior chamber abnormalities(e.g.blood or inflammation),and lens diseases.The construction of an automatic tool for segmentation of anterior segment eye lesions would greatly improve the efficiency of clinical care.With research on artificial intelligence progressing in recent years,deep learning models have shown their superiority in image classification and segmentation.The training and evaluation of deep learning models should be based on a large amount of data annotated with expertise;however,such data are relatively scarce in the domain of medicine.Herein,the authors developed a new medical image annotation system,called EyeHealer.It is a large-scale anterior eye segment dataset with both eye structures and lesions annotated at the pixel level.Comprehensive experiments were conducted to verify its performance in disease classification and eye lesion segmentation.The results showed that semantic segmentation models outperformed medical segmentation models.This paper describes the establishment of the system for automated classification and segmentation tasks.The dataset will be made publicly available to encourage future research in this area.
基金TheNational Key Researchand Development Program of China(2018YFC0507204)"Strategic Priority Research Program"of the Chinese Academy of Sciences(XDA26040202)the National Natural Science Foundation of China(41473068).
基金This work was supported by State Key Laboratory of Ophthalmology(Zhongshan Ophthalmic Center,Sun Yat-Sen University),“100 talents plan”from Sun Yatsen University,the Open Research Funds of the State Key Laboratory of Ophthalmology(2017KF05)Funds of the Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science(2017B030314025)+1 种基金Medical Research Fund of Guangdong Province(No.A2018337)Guangzhou Institute of Pediatrics/GuangzhouWomen and Children’s Medical Center(No.IP-2018-002).
文摘Uveal melanoma is the most common intraocular cancer in the adult eye.R183 and Q209 were found to be mutational hotspots in exon 4 and exon 5 of GNAQ and GNA11 in Caucasians.However,only a few studies have reported somaticmutations in GNAQ or GNA11 in uveal melanoma in Chinese.We extracted somatic DNA from paraffin-embedded biopsies of 63 Chinese uveal melanoma samples and sequenced the entire coding regions of exons 4 and 5 in GNAQ and GNA11.The results showed that 33%of Chinese uveal melanoma samples carried Q209 mutations while none had R183 mutation in GNAQ or GNA11.In addition,seven novel missense somatic mutations in GNAQ(Y192C,F194L,P170S,D236N,L232F,V230A,and M227I)and four novel missense somatic mutations in GNA11(R166C,I200T,S225F,and V206M)were found in our study.The high mutation frequency of Q209 and the novel missense mutations detected in this study suggest that GNAQ and GNA11 are common targets for somatic mutations in Chinese uveal melanoma.