Nasopharyngeal carcinoma(NPC) is a common head and neck malignancy. The incidence of NPC is higher in Southern China and Southeast Asia compared with Western countries. Given its high radiosensitivity, the standard tr...Nasopharyngeal carcinoma(NPC) is a common head and neck malignancy. The incidence of NPC is higher in Southern China and Southeast Asia compared with Western countries. Given its high radiosensitivity, the standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after treatment by radiation. Thus, special emphasis has been given to the discovery of effective radiosensitizers. This review aims to discuss the biomarkers, classified according to the main mechanisms of radiosensitization, which can enhance the sensitivity of NPC cells to ionizing radiation.展开更多
Objective: To study the effects of transferred wild type p73α gene on the sensitivity to the chemotherapeutic agents and the growth of p53-null H1299 cells of human lung adenocarcinoma. Methods: The pcDNA3-HA-p73α p...Objective: To study the effects of transferred wild type p73α gene on the sensitivity to the chemotherapeutic agents and the growth of p53-null H1299 cells of human lung adenocarcinoma. Methods: The pcDNA3-HA-p73α plasmid was transferred into the cultured p53-null H1299 cells of human lung adenocarcinoma with the mediation of Dosper liposome; The cells resistant to G418 were selected. The expression of p73α gene in the cells was examined with Western blot. MTT assay was used to analyze the response of the transfected cells to cis-dichlorodiamine platinum (cDDP) and adriamycin (ADM). The rate of drug-induced apoptosis of the transfected cells was determined with flow cytometry and DNA fragmentation assay. The changes of the biological behaviors were observed with colony formation assay. Results: The transfected H1299 cells of human lung adenocarcinoma over-expressed p73α protein stably. MTT assay showed that the IC 50 values of cDDP and ADM were reduced by approximately 7 fold and 130 fold respectively in the transfected cells as compared with the untransfected ones. Lower concentration of the chemotherapeutic agents (1.25 μmol/L of cDDP and 0.05 μmol/L of ADM) could be employed to suppress markedly the growth of the transfected H1299 cells. The apoptotic rate induced by cDDP was increased from 10.1% to 38 4% (P<0.01) and that of ADM from 12.1% to 49.3% (P<0.01). The clonogenecity after the administration of chemotherapeutic agents was significantly lower in the transfected H1299 cells than in the parental cells (P<0.01). The sensitive enhancement ratios were 1.8 and 2.6 for cDDP and ADM respectively. Conclusion: The transfection of H1299 cells with wild type p73α gene results in an increase of the sensitivity of the cells to chemotherapeutic agents.展开更多
Based on a series of aqua-planet and air–sea coupled experiments,the influence of unrealistic treatment of water substance in the Flexible Global Ocean–Atmosphere–Land System Model,spectral version 2（FGOALS-s2）,o...Based on a series of aqua-planet and air–sea coupled experiments,the influence of unrealistic treatment of water substance in the Flexible Global Ocean–Atmosphere–Land System Model,spectral version 2（FGOALS-s2）,on the model＇s climate sensitivity is investigated in this paper.Because the model does not adopt an explicit microphysics scheme,the detrained water substance from the convection scheme is converted back to the humidity.This procedure could lead to an additional increase of water vapor in the atmosphere,which could strengthen the model＇s climate sensitivity.Further sensitivity experiments confirm this deduction.After removing the water vapor converted from the detrained water substance,the water vapor reduced significantly in the upper troposphere and the high clouds also reduced.Quantitative calculations show that the water vapor reduced almost 10% of the total water vapor,and 50% at 150 h Pa,when the detrained water substance was removed,contributing to the 30% atmospheric surface temperature increase.This study calls for an explicit microphysics scheme to be introduced into the model in order to handle the detrained water vapor and thus improve the model＇s simulation skill.展开更多
IL-23/IL-17 axis is an important regulator in various inflammatory diseases. However, the role of IL-23 in allergic airway inflammation is not well understood. In this study, we show that in an allergen-induced asthma...IL-23/IL-17 axis is an important regulator in various inflammatory diseases. However, the role of IL-23 in allergic airway inflammation is not well understood. In this study, we show that in an allergen-induced asthma model, mice with transgenic overexpression of IL-23R exhibited increased airway infiltration of eosinophils and Th2 cytokine production, whereas those deficient in IL-23 displayed reduced airway inflammation. In vitro, IL-23-IL-23R signaling promoted GATA-3 expression and enhanced Th2 cytokine expression. Conversely, in the absence of this signal, Th2 cell differentiation was partially inhibited. Therefore, IL-23 signaling may regulate allergic asthma through modulation of Th2 cell differentiation.展开更多
Objective： To investigate the expressions of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （Ki-67） in patients with rectal adenocarcinoma and their associations with neoadjuvant...Objective： To investigate the expressions of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （Ki-67） in patients with rectal adenocarcinoma and their associations with neoadjuvant therapy. Methods： The expressions of Ki-67 and VEGF in 32 cases of rectal adenocarcinoma, including both pretreatment tumor biopsies and postoperative specimen, were detected by immunohistochemistry using specific antibodies, and were correlated with clinicopathological factors. Results： The intensity of VEGF staining was significantly correlated with lymph nodal metastasis （P =0.033）, depth of tumor invasion （P =0.007） and tumor stage （P= 0.016）, but not with histological types, tumor sizes, patients＇ ages and genders （P 〉 0.05）. Low level of VEGF expression had significant correlation with the high sensitivity of response to neoadjuvant therapy （P = 0.016）. The transient increase of VEGF expression could be seen after neoadjuvant therapy （P = 0.035）. Ki-67 labeling index （Ki-67-LI） was significantly correlated with lymph node metastasis （P = 0.028）, but not correlated to tumor sizes, patients＇ ages and genders （P 〉 0.05）. Tumors with lower Ki-67-LI were more sensitive to neoadjuvant therapy （P = 0.032）. The Ki-67 level decreased after neoadjuvant therapy, but no statistical significance was found （P 〉 0.05）. Conclusion： Our results demonstrate that the expression of VEGF and Ki-67 in pretreatment rectal adenocarcinoma biopsies may be predictive of tumor response to neoadjuvant therapy.展开更多
The fluorescence quenching of inclusion complex of neutral red （NR） and hydroxypropyl-β-cyclodextrin （HP-β-CD） carried by chlorobenzene was investigated. The fluorescence intensity of NR increased due to the for...The fluorescence quenching of inclusion complex of neutral red （NR） and hydroxypropyl-β-cyclodextrin （HP-β-CD） carried by chlorobenzene was investigated. The fluorescence intensity of NR increased due to the formed inclusion complex of HP-β-CD and NR. But the fluorescence intensity of NR-HP-β-CD diminished when chlorobenzene was added, and there was a linear relationship between the fluorescence quenching value of the system （△IF = IF, NR-HP-β-CD - IF, CB-NB-NR-HP-β-CD） and the concentration of chlorobenzene. Based on this, a novel fluorescence quenching method for the determination of chlorobenzene with NR as a fluorescence probe has been developed. Under the optimal conditions, the linear range of calibration curve for the determination of chlorobenzene was 5.0 × 10^-8 - 8.0 × 10^-6 mol/L and the detection limit was 1.0 × 10^-8 mol/L. It has been applied to determination ofchlorobenzene in synthetic waste water samples with satisfactory results.展开更多
In this paper,we reported the differences in susceptibility to insecticides between adults and larvae of housefly, Musca domestica (L.),and the mechanisms for the differences.The larvae of housefly were much more to...In this paper,we reported the differences in susceptibility to insecticides between adults and larvae of housefly, Musca domestica (L.),and the mechanisms for the differences.The larvae of housefly were much more tolerant to insecticides than the adults,and the tolerance ratio to cyhalothrin was as high as 205.5 for susceptible strain.Mechanism studies showed that higher GST activity was associated with higher insecticide tolerance in the larvae.The co\|toxicity coefficient of the mixture of cyhalothrin and methylene dithiocyanate(4∶1) on pyrethroid\|resistant houseflies was 188.展开更多
Interaction of a drug molecule with human serum albumin （HSA） is usually studied by fluorescence responses of the ligand or/and the single tryptophan residue （Trp-214） of the protein, but qualitative spectral info...Interaction of a drug molecule with human serum albumin （HSA） is usually studied by fluorescence responses of the ligand or/and the single tryptophan residue （Trp-214） of the protein, but qualitative spectral information may lead to multiple conclusions. In this work, we report a study on the interaction of hematoporphyrin monomethyl ether （HMME） with human serum albumin （HSA）, using the environment-sensitive spectra of HMME and reaction-induced fluorescence response of Trp-214. Particularly, the single kinetic parameter, the linear slope, was derived from the concentration-dependent absorbance or fluorescence of HMME in a certain solvent. A quantitative change in the slope at [HMME]/[HSA] = 1 ： 1 clearly demonstrated a specific binding of HMME to site I. The microenvironment in site I may be comparable to that in DMSO solvent, because of the similarity of the slope. Linear correlation of the fluorescence to the absorbance of HMME in site I indicates that the energy transfer is not responsible for Trp-214 fluorescence quenching but an electron transfer may be possible. In addition, much higher rate observed for the binding of HMME or 2-taurine-substituted HB （THB） with HSA than that of hypocrellin B was due to the electrostatic attraction under physiological condition.展开更多
Is Chinese urbanization going to take a long time, or can its development goal be achieved by the government in a short time? What is the highest stable urbanization level that China can reach? When can China complete...Is Chinese urbanization going to take a long time, or can its development goal be achieved by the government in a short time? What is the highest stable urbanization level that China can reach? When can China complete its urbanization? To answer these questions, this paper presents a system dynamic(SD) model of Chinese urbanization, and its validity and simulation are justified by a stock-flow test and a sensitivity analysis using real data from 1998 to 2013. Setting the initial conditions of the simulation by referring to the real data of 2013, the multi-scenario analysis from 2013 to 2050 reveals that Chinese urbanization will reach a level higher than 70% in 2035 and then proceed to a slow urbanization stage regardless of the population policy and GDP growth rate settings; in 2050, Chinese urbanization levels will reach approximately 75%, which is a stable and equilibrium level for China. Thus, it can be argued that Chinese urbanization is a long social development process that will require approximately20 years to complete and that the ultimate urbanization level will be 75–80%, which means that in the distant future, 20–25% of China's population will still settle in rural regions of China.展开更多
Thiazolidinediones(TZDs),such as rosiglitazone(RSG),which activates peroxisome proliferator activated receptor-y(PPARy),are a potent class of oral antidiabetic agents with good durability.However,the clinical use of T...Thiazolidinediones(TZDs),such as rosiglitazone(RSG),which activates peroxisome proliferator activated receptor-y(PPARy),are a potent class of oral antidiabetic agents with good durability.However,the clinical use of TZDs is challenging because of their side effects,including weight gain and hepatotoxicity.Here,we found that bavachinin(BVC),a lead natural product,additively activates PPARγ with lowdose RSG to preserve the maximum antidiabetic effects while reducing weight gain and hepatotoxicity in db/db mice caused by RSG monotherapy.Structural and biochemical assays demonstrated that an unexplored hotspot around Met329 and Ser332 in helix 5 is triggered by BVC cobinding to RSG-bound PPARy,thereby allosterically stabilizing the active state of the activation-function 2 motif responsible for additive activation with RSG.Based on this hotspot,we discovered a series of new classes of allosteric agonists inducing the activity of TZDs in the same manner as BVC.Together,our data illustrate that the hotspot of PPARγ is druggable for the discovery of new allosteric synergists,and the combination thera py of allosteric synergists and TZD drugs may provide a potential alternative approach to the treatment of type 2 diabetes mellitus.展开更多
文摘Nasopharyngeal carcinoma(NPC) is a common head and neck malignancy. The incidence of NPC is higher in Southern China and Southeast Asia compared with Western countries. Given its high radiosensitivity, the standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after treatment by radiation. Thus, special emphasis has been given to the discovery of effective radiosensitizers. This review aims to discuss the biomarkers, classified according to the main mechanisms of radiosensitization, which can enhance the sensitivity of NPC cells to ionizing radiation.
文摘Objective: To study the effects of transferred wild type p73α gene on the sensitivity to the chemotherapeutic agents and the growth of p53-null H1299 cells of human lung adenocarcinoma. Methods: The pcDNA3-HA-p73α plasmid was transferred into the cultured p53-null H1299 cells of human lung adenocarcinoma with the mediation of Dosper liposome; The cells resistant to G418 were selected. The expression of p73α gene in the cells was examined with Western blot. MTT assay was used to analyze the response of the transfected cells to cis-dichlorodiamine platinum (cDDP) and adriamycin (ADM). The rate of drug-induced apoptosis of the transfected cells was determined with flow cytometry and DNA fragmentation assay. The changes of the biological behaviors were observed with colony formation assay. Results: The transfected H1299 cells of human lung adenocarcinoma over-expressed p73α protein stably. MTT assay showed that the IC 50 values of cDDP and ADM were reduced by approximately 7 fold and 130 fold respectively in the transfected cells as compared with the untransfected ones. Lower concentration of the chemotherapeutic agents (1.25 μmol/L of cDDP and 0.05 μmol/L of ADM) could be employed to suppress markedly the growth of the transfected H1299 cells. The apoptotic rate induced by cDDP was increased from 10.1% to 38 4% (P<0.01) and that of ADM from 12.1% to 49.3% (P<0.01). The clonogenecity after the administration of chemotherapeutic agents was significantly lower in the transfected H1299 cells than in the parental cells (P<0.01). The sensitive enhancement ratios were 1.8 and 2.6 for cDDP and ADM respectively. Conclusion: The transfection of H1299 cells with wild type p73α gene results in an increase of the sensitivity of the cells to chemotherapeutic agents.
基金jointly supported by the National Basic Research Program of China[grant number 2014CB953904]the National Natural Science Foundation of China[grant numbers 41405091 and 91337110]+1 种基金the Open Projects of the Key Laboratory of Meteorological Disaster of the Ministry of Education[grant number KLME1405]the Strategic Leading Science Projects of the Chinese Academy of Sciences[grant number XDA11010402]
文摘Based on a series of aqua-planet and air–sea coupled experiments,the influence of unrealistic treatment of water substance in the Flexible Global Ocean–Atmosphere–Land System Model,spectral version 2（FGOALS-s2）,on the model＇s climate sensitivity is investigated in this paper.Because the model does not adopt an explicit microphysics scheme,the detrained water substance from the convection scheme is converted back to the humidity.This procedure could lead to an additional increase of water vapor in the atmosphere,which could strengthen the model＇s climate sensitivity.Further sensitivity experiments confirm this deduction.After removing the water vapor converted from the detrained water substance,the water vapor reduced significantly in the upper troposphere and the high clouds also reduced.Quantitative calculations show that the water vapor reduced almost 10% of the total water vapor,and 50% at 150 h Pa,when the detrained water substance was removed,contributing to the 30% atmospheric surface temperature increase.This study calls for an explicit microphysics scheme to be introduced into the model in order to handle the detrained water vapor and thus improve the model＇s simulation skill.
文摘IL-23/IL-17 axis is an important regulator in various inflammatory diseases. However, the role of IL-23 in allergic airway inflammation is not well understood. In this study, we show that in an allergen-induced asthma model, mice with transgenic overexpression of IL-23R exhibited increased airway infiltration of eosinophils and Th2 cytokine production, whereas those deficient in IL-23 displayed reduced airway inflammation. In vitro, IL-23-IL-23R signaling promoted GATA-3 expression and enhanced Th2 cytokine expression. Conversely, in the absence of this signal, Th2 cell differentiation was partially inhibited. Therefore, IL-23 signaling may regulate allergic asthma through modulation of Th2 cell differentiation.
文摘Objective： To investigate the expressions of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （Ki-67） in patients with rectal adenocarcinoma and their associations with neoadjuvant therapy. Methods： The expressions of Ki-67 and VEGF in 32 cases of rectal adenocarcinoma, including both pretreatment tumor biopsies and postoperative specimen, were detected by immunohistochemistry using specific antibodies, and were correlated with clinicopathological factors. Results： The intensity of VEGF staining was significantly correlated with lymph nodal metastasis （P =0.033）, depth of tumor invasion （P =0.007） and tumor stage （P= 0.016）, but not with histological types, tumor sizes, patients＇ ages and genders （P 〉 0.05）. Low level of VEGF expression had significant correlation with the high sensitivity of response to neoadjuvant therapy （P = 0.016）. The transient increase of VEGF expression could be seen after neoadjuvant therapy （P = 0.035）. Ki-67 labeling index （Ki-67-LI） was significantly correlated with lymph node metastasis （P = 0.028）, but not correlated to tumor sizes, patients＇ ages and genders （P 〉 0.05）. Tumors with lower Ki-67-LI were more sensitive to neoadjuvant therapy （P = 0.032）. The Ki-67 level decreased after neoadjuvant therapy, but no statistical significance was found （P 〉 0.05）. Conclusion： Our results demonstrate that the expression of VEGF and Ki-67 in pretreatment rectal adenocarcinoma biopsies may be predictive of tumor response to neoadjuvant therapy.
基金This project was supported by the National Basic Research Program of China （No. 2007CB936602） and the Natural Science Foundation of Shandong Province in China （No. Y2008B20）.
文摘The fluorescence quenching of inclusion complex of neutral red （NR） and hydroxypropyl-β-cyclodextrin （HP-β-CD） carried by chlorobenzene was investigated. The fluorescence intensity of NR increased due to the formed inclusion complex of HP-β-CD and NR. But the fluorescence intensity of NR-HP-β-CD diminished when chlorobenzene was added, and there was a linear relationship between the fluorescence quenching value of the system （△IF = IF, NR-HP-β-CD - IF, CB-NB-NR-HP-β-CD） and the concentration of chlorobenzene. Based on this, a novel fluorescence quenching method for the determination of chlorobenzene with NR as a fluorescence probe has been developed. Under the optimal conditions, the linear range of calibration curve for the determination of chlorobenzene was 5.0 × 10^-8 - 8.0 × 10^-6 mol/L and the detection limit was 1.0 × 10^-8 mol/L. It has been applied to determination ofchlorobenzene in synthetic waste water samples with satisfactory results.
文摘In this paper,we reported the differences in susceptibility to insecticides between adults and larvae of housefly, Musca domestica (L.),and the mechanisms for the differences.The larvae of housefly were much more tolerant to insecticides than the adults,and the tolerance ratio to cyhalothrin was as high as 205.5 for susceptible strain.Mechanism studies showed that higher GST activity was associated with higher insecticide tolerance in the larvae.The co\|toxicity coefficient of the mixture of cyhalothrin and methylene dithiocyanate(4∶1) on pyrethroid\|resistant houseflies was 188.
基金National Natural Science Foundation of China(Grant No.20872144)
文摘Interaction of a drug molecule with human serum albumin （HSA） is usually studied by fluorescence responses of the ligand or/and the single tryptophan residue （Trp-214） of the protein, but qualitative spectral information may lead to multiple conclusions. In this work, we report a study on the interaction of hematoporphyrin monomethyl ether （HMME） with human serum albumin （HSA）, using the environment-sensitive spectra of HMME and reaction-induced fluorescence response of Trp-214. Particularly, the single kinetic parameter, the linear slope, was derived from the concentration-dependent absorbance or fluorescence of HMME in a certain solvent. A quantitative change in the slope at [HMME]/[HSA] = 1 ： 1 clearly demonstrated a specific binding of HMME to site I. The microenvironment in site I may be comparable to that in DMSO solvent, because of the similarity of the slope. Linear correlation of the fluorescence to the absorbance of HMME in site I indicates that the energy transfer is not responsible for Trp-214 fluorescence quenching but an electron transfer may be possible. In addition, much higher rate observed for the binding of HMME or 2-taurine-substituted HB （THB） with HSA than that of hypocrellin B was due to the electrostatic attraction under physiological condition.
基金supported by the Key Project of the National Natural Science Foundation of China “the SD model and threshold value prediction of the interactive coupled effects between urbanization and eco-environment in mega-urban agglomerations” (Grant No. 41590844)the Independent Research Program of Tsinghua University (Grant No. 2015THZ01)
文摘Is Chinese urbanization going to take a long time, or can its development goal be achieved by the government in a short time? What is the highest stable urbanization level that China can reach? When can China complete its urbanization? To answer these questions, this paper presents a system dynamic(SD) model of Chinese urbanization, and its validity and simulation are justified by a stock-flow test and a sensitivity analysis using real data from 1998 to 2013. Setting the initial conditions of the simulation by referring to the real data of 2013, the multi-scenario analysis from 2013 to 2050 reveals that Chinese urbanization will reach a level higher than 70% in 2035 and then proceed to a slow urbanization stage regardless of the population policy and GDP growth rate settings; in 2050, Chinese urbanization levels will reach approximately 75%, which is a stable and equilibrium level for China. Thus, it can be argued that Chinese urbanization is a long social development process that will require approximately20 years to complete and that the ultimate urbanization level will be 75–80%, which means that in the distant future, 20–25% of China's population will still settle in rural regions of China.
基金the National Natural Science Foundation of China(21708025,81925034,91753117,and 81773793)the Open Fund of State Key Laboratory of Oncogenes and Related Genes,Shanghai Jiao Tong University School of Medicine+3 种基金the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-01-E00036)the Shanghai Science and Technology Innovation Foundation(19431901600)the China Postdoctoral Science Foundation(2016M601618 and 2017T100303)the National Science and Technology Major Project of China(2018ZX09711001-005-022)。
文摘Thiazolidinediones(TZDs),such as rosiglitazone(RSG),which activates peroxisome proliferator activated receptor-y(PPARy),are a potent class of oral antidiabetic agents with good durability.However,the clinical use of TZDs is challenging because of their side effects,including weight gain and hepatotoxicity.Here,we found that bavachinin(BVC),a lead natural product,additively activates PPARγ with lowdose RSG to preserve the maximum antidiabetic effects while reducing weight gain and hepatotoxicity in db/db mice caused by RSG monotherapy.Structural and biochemical assays demonstrated that an unexplored hotspot around Met329 and Ser332 in helix 5 is triggered by BVC cobinding to RSG-bound PPARy,thereby allosterically stabilizing the active state of the activation-function 2 motif responsible for additive activation with RSG.Based on this hotspot,we discovered a series of new classes of allosteric agonists inducing the activity of TZDs in the same manner as BVC.Together,our data illustrate that the hotspot of PPARγ is druggable for the discovery of new allosteric synergists,and the combination thera py of allosteric synergists and TZD drugs may provide a potential alternative approach to the treatment of type 2 diabetes mellitus.
