Ferroptosis is a type of programmed cell death dependent on iron.It is different from other forms of cell death such as apoptosis,classic necrosis and autophagy.Ferroptosis is involved in many neurodegenerative diseas...Ferroptosis is a type of programmed cell death dependent on iron.It is different from other forms of cell death such as apoptosis,classic necrosis and autophagy.Ferroptosis is involved in many neurodegenerative diseases.The role of ferroptosis in glutamate-induced neuronal toxicity is not fully understood.To test its toxicity,glutamate(1.25–20 mM)was applied to HT-22 cells for 12 to 48 hours.The optimal experimental conditions occurred at 12 hours after incubation with 5 mM glutamate.Cells were cultured with 3–12μM ferrostatin-1,an inhibitor of ferroptosis,for 12 hours before exposure to glutamate.The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Autophagy was determined by monodansylcadaverine staining and apoptosis by caspase 3 activity.Damage to cell structures was observed under light and by transmission electron microscopy.The release of lactate dehydrogenase was detected by the commercial kit.Reactive oxygen species were measured by flow cytometry.Glutathione peroxidase activity,superoxide dismutase activity and malondialdehyde level were detected by the appropriate commercial kit.Prostaglandin peroxidase synthase 2 and glutathione peroxidase 4 gene expression was detected by real-time quantitative polymerase chain reaction.Glutathione peroxidase 4 and nuclear factor erythroid-derived-like 2 protein expression was detected by western blot analysis.Results showed that ferrostatin-1 can significantly counter the effects of glutamate on HT-22 cells,improving the survival rate,reducing the release of lactate dehydrogenase and reducing the damage to mitochondrial ultrastructure.However,it did not affect the caspase-3 expression and monodansylcadaverine-positive staining in glutamate-injured HT-22 cells.Ferrostatin-1 reduced the levels of reactive oxygen species and malondialdehyde and enhanced superoxide dismutase activity.It decreased gene expression of prostaglandin peroxidase synthase 2 and increased gene expression of glutathione peroxidase 4 and protein expressions of glutathione peroxidase 4 and nuclear factor(erythroid-derived)-like 2 in glutamate-injured HT-22 cells.Treatment of cultured cells with the apoptosis inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone(2–8μM),autophagy inhibitor 3-methyladenine(100–400μM)or necrosis inhibitor necrostatin-1(10–40μM)had no effect on glutamate induced cell damage.However,the iron chelator deferoxamine mesylate salt inhibited glutamate induced cell death.Thus,the results suggested that ferroptosis is caused by glutamate-induced toxicity and that ferrostatin-1 protects HT-22 cells from glutamate-induced oxidative toxicity by inhibiting the oxidative stress.展开更多
BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-...BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.展开更多
Totally implantable access ports(TIAPs)are used for patients with poor peripheral vascular support requiring central venous access.In recent years,TIAPs have been gradually accepted and promoted by patients,doctors,an...Totally implantable access ports(TIAPs)are used for patients with poor peripheral vascular support requiring central venous access.In recent years,TIAPs have been gradually accepted and promoted by patients,doctors,and nurses owing to their advantages of convenient carrying,a long maintenance period,low complications,and a high quality of life for patients.Currently,medical personnel that handle TIAP implantation and management in China are from different areas of healthcare,including surgery,internal medicine,radiology,nurse anesthesia,vascular access,etc.,and many only handle TIAP as a part of their duties.Therefore,the operating procedures and steps for the diagnosis and treatment of complications of TIAP vary from person to person,resulting in different incidence and treatment methods for complications in the implantation and use of TIAP in different medical units.Based on this,we have updated the Shanghai expert consensus on TIAPs from 2015 and explored the diagnosis and treatment procedures of related complications while continuing to emphasize standardized implantation and maintenance.展开更多
Taking the advantage of reduced scattering and low autofluorescence background, the NIR fluorescence probes, such as fluorescence proteins, organic molecules and nanoparticles, not only hold the promise of in vivo ima...Taking the advantage of reduced scattering and low autofluorescence background, the NIR fluorescence probes, such as fluorescence proteins, organic molecules and nanoparticles, not only hold the promise of in vivo imaging of biological processes in physiology and pathology with high signal-to-noise ratio, but also for clinical diagnosis. In this review, we provide an overview of the recent progress on NIR probes,focusing on fundamental mechanisms of NIR dyes and nanoparticles, and protein engineering strategies for NIR proteins.展开更多
Two-photon excitation fluorescence microscopy(TPM),owing to its capacity for subcellular resolution,intrinsic optical sectioning,and superior penetration depth in turbid samples,has revolutionized biomedical research....Two-photon excitation fluorescence microscopy(TPM),owing to its capacity for subcellular resolution,intrinsic optical sectioning,and superior penetration depth in turbid samples,has revolutionized biomedical research.However,its layer-by-layer scanning to form a three-dimensional image inherently limits the volumetric imaging speed and increases phototoxicity significantly.In this study,we develop a gradient excitation technique to accelerate TPM volumetric imaging.The axial positions of the fluorophores can be decoded from the intensity ratio of the paired images obtained by sequentially exciting the specimen with two axially elongated two-photon beams of complementary gradient intensities.We achieved a 0.63μm axial localization precision and demonstrate the flexibility of the gradient TPM on various sparsely labeled samples,including bead phantoms,mouse brain tissues,and live macrophages.Compared with traditional TPM,our technique improves volumetric imaging speed(by at least sixfold),decreases photobleaching(i.e.,less than 2.07±2.89%in 25 min),and minimizes photodamages.展开更多
Osteogenic differentiation is the basis of bone growth and repair related to many diseases,in which evaluating the degree and ability of osteogenic transformation is quite important and highly desirable.However,fixing...Osteogenic differentiation is the basis of bone growth and repair related to many diseases,in which evaluating the degree and ability of osteogenic transformation is quite important and highly desirable.However,fixing or stopping the growth of cells is required for conventional methods to monitor osteogenic differentiation,which cannot realize the full investigation of the dynamic process.Herein,a new anion conjugated polymer featuring aggregation-induced emission(AIE)characteristics is developed with excellent solubility for in-situ monitoring the process of osteogenic differentiation.This novel polymer can bind with osteogenic differentiated cells,and the intracellular fluorescence increases gradually with the enhancement of osteogenic differentiation.Moreover,it possesses good biosafety with negligible effect on cell activity and osteogenic differentiation,which cannot be realized by the typical method of Alizarin Red S staining.Further study shows that the polymer crosses the cell membrane through endocytosis and enriches in lysosomes,whereas no obvious fluorescence is detected with other cells,including non-differentiated osteoblast cells,under the same conditions,demonstrating the high selectivity.This is the first fluorescent probe with excellent specificity to realize real-time observation of the process of osteogenic differentiation.Therefore,PTB-EDTA shows great promise in the study of osteogenic differentiation and related applications.展开更多
For many government departments,uncertainty aversion is a source of barriers in the advancement of data openness.A more active response to potential risks is needed and necessitates an in-depth examination of risks re...For many government departments,uncertainty aversion is a source of barriers in the advancement of data openness.A more active response to potential risks is needed and necessitates an in-depth examination of risks related to open government data(OGD).With a cross-case study in which three cases from the United Kingdom,the United States and China are examined,this study identifies potential risks that might emerge at different stages of the lifecycle of OGD programs and constructs a taxonomy model for them.The taxonomy model distinguishes the“risks from OGD”from the“risks to OGD”,which can help government departments make better responses.Finally,risk response strategies are suggested based on the research results.展开更多
The synthesis of amphiphilic aggregation-induced emission （ALE） dyes based organic nanoparticles has recently attracted in- creasing attention in the biomedical fields. These AlE dyes based nanoparticles could effec...The synthesis of amphiphilic aggregation-induced emission （ALE） dyes based organic nanoparticles has recently attracted in- creasing attention in the biomedical fields. These AlE dyes based nanoparticles could effectively overcome the aggregation caused quenching effect of conventional organic dyes, making them promising candidates for fabrication of ultrabright organic luminescent nanomaterials. In this work, AIE-active luminescent polymeric nanoparticles （4-NH2-PEG-TPE-E LPNs） were facilely fabricated through Michael addition reaction between tetraphenylethene acrylate （TPE-E） and 4-arm-poly（ethylene glycol）-amine （4-NH2-PEG） in rather mild ambient. The 4-NH2-PEG can not only endow these AlE-active LPNs good water dispersibility, but also provide functional groups for further conjugation reaction. The size, morphology and luminescent prop- erties of 4-NH2-PEG-TPE-E LPNs were characterized by a series of techniques in detail. Results suggested that these AlE-active LPNs showed spherical morphology with diameter about 100-200 nm. The obtained 4-NH2-PEG-TPE-E LPNs display high water dispersibility and strong fluorescence intensity because of their self assembly and AlE properties of TPE-E. Biological evaluation results demonstrated that 4-NH2-PEG-TPE-E LPNs showed negative toxicity toward cancer cells and good fluorescent imaging performance. All of these features make 4-NHz-PEG-TPE-E LPNs promising candidates for biolog- ical imaging and therapeutic applications.展开更多
文摘Ferroptosis is a type of programmed cell death dependent on iron.It is different from other forms of cell death such as apoptosis,classic necrosis and autophagy.Ferroptosis is involved in many neurodegenerative diseases.The role of ferroptosis in glutamate-induced neuronal toxicity is not fully understood.To test its toxicity,glutamate(1.25–20 mM)was applied to HT-22 cells for 12 to 48 hours.The optimal experimental conditions occurred at 12 hours after incubation with 5 mM glutamate.Cells were cultured with 3–12μM ferrostatin-1,an inhibitor of ferroptosis,for 12 hours before exposure to glutamate.The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Autophagy was determined by monodansylcadaverine staining and apoptosis by caspase 3 activity.Damage to cell structures was observed under light and by transmission electron microscopy.The release of lactate dehydrogenase was detected by the commercial kit.Reactive oxygen species were measured by flow cytometry.Glutathione peroxidase activity,superoxide dismutase activity and malondialdehyde level were detected by the appropriate commercial kit.Prostaglandin peroxidase synthase 2 and glutathione peroxidase 4 gene expression was detected by real-time quantitative polymerase chain reaction.Glutathione peroxidase 4 and nuclear factor erythroid-derived-like 2 protein expression was detected by western blot analysis.Results showed that ferrostatin-1 can significantly counter the effects of glutamate on HT-22 cells,improving the survival rate,reducing the release of lactate dehydrogenase and reducing the damage to mitochondrial ultrastructure.However,it did not affect the caspase-3 expression and monodansylcadaverine-positive staining in glutamate-injured HT-22 cells.Ferrostatin-1 reduced the levels of reactive oxygen species and malondialdehyde and enhanced superoxide dismutase activity.It decreased gene expression of prostaglandin peroxidase synthase 2 and increased gene expression of glutathione peroxidase 4 and protein expressions of glutathione peroxidase 4 and nuclear factor(erythroid-derived)-like 2 in glutamate-injured HT-22 cells.Treatment of cultured cells with the apoptosis inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone(2–8μM),autophagy inhibitor 3-methyladenine(100–400μM)or necrosis inhibitor necrostatin-1(10–40μM)had no effect on glutamate induced cell damage.However,the iron chelator deferoxamine mesylate salt inhibited glutamate induced cell death.Thus,the results suggested that ferroptosis is caused by glutamate-induced toxicity and that ferrostatin-1 protects HT-22 cells from glutamate-induced oxidative toxicity by inhibiting the oxidative stress.
基金Supported by the National Natural Science Foundation of China,No.81460124 and No.81860114
文摘BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.
文摘Totally implantable access ports(TIAPs)are used for patients with poor peripheral vascular support requiring central venous access.In recent years,TIAPs have been gradually accepted and promoted by patients,doctors,and nurses owing to their advantages of convenient carrying,a long maintenance period,low complications,and a high quality of life for patients.Currently,medical personnel that handle TIAP implantation and management in China are from different areas of healthcare,including surgery,internal medicine,radiology,nurse anesthesia,vascular access,etc.,and many only handle TIAP as a part of their duties.Therefore,the operating procedures and steps for the diagnosis and treatment of complications of TIAP vary from person to person,resulting in different incidence and treatment methods for complications in the implantation and use of TIAP in different medical units.Based on this,we have updated the Shanghai expert consensus on TIAPs from 2015 and explored the diagnosis and treatment procedures of related complications while continuing to emphasize standardized implantation and maintenance.
基金financially supported by the National Key Research and Development Program of China (No. 2017YFA0700403)National Natural Science Foundation of China (Nos. 31670872, 21874145, 2018M633180, 21905296)+1 种基金Shenzhen Science and Technology Innovation Committee (Nos. KQJSCX20170331161420421, JCYJ20170818163925063, JCYJ20170818164040422, GJHS2017031 4160302802)Chinese Academy of Sciences (No. GJJSTD20180002)
文摘Taking the advantage of reduced scattering and low autofluorescence background, the NIR fluorescence probes, such as fluorescence proteins, organic molecules and nanoparticles, not only hold the promise of in vivo imaging of biological processes in physiology and pathology with high signal-to-noise ratio, but also for clinical diagnosis. In this review, we provide an overview of the recent progress on NIR probes,focusing on fundamental mechanisms of NIR dyes and nanoparticles, and protein engineering strategies for NIR proteins.
基金National Key Research and Development Program of China(2017YFC0110200)National Natural Science Foundation of China(81822023,81927803,91959121,92159104,82071972)+2 种基金Natural Science Foundation of Guangdong Province(2019A1515011746,2020B121201010)Scientific Instrument Innovation Team of Chinese Academy of Sciences(GJJSTD20180002)Shenzhen Basic Research Program(QCYJ20180507182432303,RCJC20200714114433058,ZDSY20130401165820357).
文摘Two-photon excitation fluorescence microscopy(TPM),owing to its capacity for subcellular resolution,intrinsic optical sectioning,and superior penetration depth in turbid samples,has revolutionized biomedical research.However,its layer-by-layer scanning to form a three-dimensional image inherently limits the volumetric imaging speed and increases phototoxicity significantly.In this study,we develop a gradient excitation technique to accelerate TPM volumetric imaging.The axial positions of the fluorophores can be decoded from the intensity ratio of the paired images obtained by sequentially exciting the specimen with two axially elongated two-photon beams of complementary gradient intensities.We achieved a 0.63μm axial localization precision and demonstrate the flexibility of the gradient TPM on various sparsely labeled samples,including bead phantoms,mouse brain tissues,and live macrophages.Compared with traditional TPM,our technique improves volumetric imaging speed(by at least sixfold),decreases photobleaching(i.e.,less than 2.07±2.89%in 25 min),and minimizes photodamages.
基金supported by the Natural Science Foundation of Guangdong Province(Grant No.2019A1515012074).
文摘Osteogenic differentiation is the basis of bone growth and repair related to many diseases,in which evaluating the degree and ability of osteogenic transformation is quite important and highly desirable.However,fixing or stopping the growth of cells is required for conventional methods to monitor osteogenic differentiation,which cannot realize the full investigation of the dynamic process.Herein,a new anion conjugated polymer featuring aggregation-induced emission(AIE)characteristics is developed with excellent solubility for in-situ monitoring the process of osteogenic differentiation.This novel polymer can bind with osteogenic differentiated cells,and the intracellular fluorescence increases gradually with the enhancement of osteogenic differentiation.Moreover,it possesses good biosafety with negligible effect on cell activity and osteogenic differentiation,which cannot be realized by the typical method of Alizarin Red S staining.Further study shows that the polymer crosses the cell membrane through endocytosis and enriches in lysosomes,whereas no obvious fluorescence is detected with other cells,including non-differentiated osteoblast cells,under the same conditions,demonstrating the high selectivity.This is the first fluorescent probe with excellent specificity to realize real-time observation of the process of osteogenic differentiation.Therefore,PTB-EDTA shows great promise in the study of osteogenic differentiation and related applications.
文摘For many government departments,uncertainty aversion is a source of barriers in the advancement of data openness.A more active response to potential risks is needed and necessitates an in-depth examination of risks related to open government data(OGD).With a cross-case study in which three cases from the United Kingdom,the United States and China are examined,this study identifies potential risks that might emerge at different stages of the lifecycle of OGD programs and constructs a taxonomy model for them.The taxonomy model distinguishes the“risks from OGD”from the“risks to OGD”,which can help government departments make better responses.Finally,risk response strategies are suggested based on the research results.
基金supported by the National Natural Science Foundation of China (21134004, 21201108, 51363016, 21474057, 21564006, 21561022)the National Basic Research Program (2011CB935700)
文摘The synthesis of amphiphilic aggregation-induced emission （ALE） dyes based organic nanoparticles has recently attracted in- creasing attention in the biomedical fields. These AlE dyes based nanoparticles could effectively overcome the aggregation caused quenching effect of conventional organic dyes, making them promising candidates for fabrication of ultrabright organic luminescent nanomaterials. In this work, AIE-active luminescent polymeric nanoparticles （4-NH2-PEG-TPE-E LPNs） were facilely fabricated through Michael addition reaction between tetraphenylethene acrylate （TPE-E） and 4-arm-poly（ethylene glycol）-amine （4-NH2-PEG） in rather mild ambient. The 4-NH2-PEG can not only endow these AlE-active LPNs good water dispersibility, but also provide functional groups for further conjugation reaction. The size, morphology and luminescent prop- erties of 4-NH2-PEG-TPE-E LPNs were characterized by a series of techniques in detail. Results suggested that these AlE-active LPNs showed spherical morphology with diameter about 100-200 nm. The obtained 4-NH2-PEG-TPE-E LPNs display high water dispersibility and strong fluorescence intensity because of their self assembly and AlE properties of TPE-E. Biological evaluation results demonstrated that 4-NH2-PEG-TPE-E LPNs showed negative toxicity toward cancer cells and good fluorescent imaging performance. All of these features make 4-NHz-PEG-TPE-E LPNs promising candidates for biolog- ical imaging and therapeutic applications.
