Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in China.In this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)in...Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in China.In this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)injury of isolated cerebral basilar artery(BA)and erebral ischemia reperfusion(CIR)injury in rat models.In isolated rat BA rings,HR causes endothelial dysfunction(ED)and acetylcholine(ACh)induces endothelium-dependent vasodilation.The myography result showed that SCU(100μM)was able to significantly improve the endothelium-dependent vasodilation induced by Ach.However,SCU did not affect the ACh-induced relaxation in normal BA.Further studies suggested that SCU(10-1000μM)dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase(PKG)inhibitor Rp-8-Br-cGMPs(PKGI-rp,4μM).Pre-incubation with SCU(500μM)reversed the impairment of endothelium-dependent vasodilation induced by HR,but the reversing effect was blocked if PKGI-rp(4μM)was added.The brain slice staining test in rats’model of middle cerebral artery occlusion(MCAO)induced CIR proved that the administration of SCU(45,90 mg/kg,iv)significantly reduced the area of cerebral infarction.The Western blot assay result showed that SCU(45 mg/kg,iv)increased brain PKG activity and PKG protein level after CIR surgery.In conclusion,our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.展开更多
Downy mildew of grapevine(Vitis vinifera L.),caused by the oomycete pathogen Plasmopara viticola,is one of the most serious concerns for grape production worldwide.It has been widely reported that the pathogenesis-rel...Downy mildew of grapevine(Vitis vinifera L.),caused by the oomycete pathogen Plasmopara viticola,is one of the most serious concerns for grape production worldwide.It has been widely reported that the pathogenesis-related 4(PR4)protein plays important roles in plant resistance to diseases.However,little is known about the role of PR4 in the defense of grapevine against P.viticola.In this study,we engineered loss-of-function mutations in the VvPR4b gene from the cultivar“Thompson Seedless”using the CRISPR/Cas9 system and evaluated the consequences for downy mildew resistance.Sequencing results showed that deletions were the main type of mutation introduced and that no off-target events occurred.Infection assays using leaf discs showed that,compared to wild-type plants,the VvPR4b knockout lines had increased susceptibility to P.viticola.This was accompanied by reduced accumulation of reactive oxygen species around stomata.Measurement of the relative genomic abundance of P.viticola in VvPR4b knockout lines also demonstrated that the mutants had increased susceptibility to the pathogen.Our results confirm that VvPR4b plays an active role in the defense of grapevine against downy mildew.展开更多
AIM： To report the surgical result of pars plana vitrectomy（PPV） with air tamponade for rhegmatogenous retinal detachment（RRD） by ultra-widefield fundus imaging system. METHODS： Of 25 consecutive patients（25 e...AIM： To report the surgical result of pars plana vitrectomy（PPV） with air tamponade for rhegmatogenous retinal detachment（RRD） by ultra-widefield fundus imaging system. METHODS： Of 25 consecutive patients（25 eyes） with fresh primary RRD and causative retinal break and vitreous traction were presented. All the patients underwent PPV with air tamponade. Visual acuity（VA） was examined postoperatively and images were captured by ultrawidefield scanning laser ophthalmoscope system（Optos）. RESULTS： Initial reattachment was achieved in 25 cases（100%）. The air volume was 〉60% on the postoperative day（POD） 1. The ultra-widefield images showed that the retina was reattached in all air-filled eyes postoperatively. The retinal break and laser burns in the superior were detected in 22 of 25 eyes（88%）. A missed retinal hole was found under intravitreal air bubble in 1 case（4%）. The air volume was range from 40% to 60% on POD 3. A doublelayered image was seen in 25 of 25 eyes with intravitreal gas. Retinal breaks and laser burns around were seen in the intravitreal air. On POD 7, small bubble without effect was seen in 6 cases（24%） and bubble was completely disappeared in 4 cases（16%）. Small oval bubble in the superior area was observed in 15 cases（60%）. There were no missed and new retinal breaks and no retinal detachment in all cases on the POD 14 and 1 mo and last follow-up. Air disappeared completely on a mean of 9.84 d postoperatively. The mean final postoperative bestcorrected visual acuity（BCVA） was 0.35 log MAR. Mean final postoperative BCVA improved significantly relative to mean preoperative（P〈0.05）. Final VA of 0.3 log MAR or better was seen in 13 eyes. CONCLUSION： PPV with air tamponade is an effective management for fresh RRD with superior retinal breaks. The ultra-widefield fundus imaging can detect postoperative retinal breaks in air-filled eyes. It would be a useful facility for follow-up after PPV with air tamponade. Facedown position and acquired visual rehabilitation may be shorten.展开更多
目的探讨以鼻腔滴注博来霉素(BLM)的方式诱导C57BL/6小鼠肺纤维化模型的最佳方法。方法 7~8周龄雄性小鼠30只,分为0.10 u BLM组、0.25 u BLM组、0.40 u BLM组,每组8只,麻醉后分别一次性滴鼻0.10、0.25及0.40 u BLM;对照组6只,给予等体...目的探讨以鼻腔滴注博来霉素(BLM)的方式诱导C57BL/6小鼠肺纤维化模型的最佳方法。方法 7~8周龄雄性小鼠30只,分为0.10 u BLM组、0.25 u BLM组、0.40 u BLM组,每组8只,麻醉后分别一次性滴鼻0.10、0.25及0.40 u BLM;对照组6只,给予等体积的磷酸盐缓冲液。观察并记录小鼠体重变化与生存率,实验结束后处死小鼠。用甲醛固定肺组织,苏木精-伊红染色评价肺组织炎症变化;Masson染色评价肺纤维化变化。结果给药后小鼠体重逐渐下降,并在第8和9天再次上升,第14天逐渐趋近于对照组,第28天BLM组所有小鼠肺部组织产生纤维化。各组肺纤维化评分比较,差异无统计学意义(P >0.05)。但给药0.25与0.40 u BLM的小鼠死亡率高,个体间差异较大,不利于实验样本的收集与数据的统计分析。结论 0.10 u BLM滴鼻给药是复制C57BL/6小鼠肺纤维化模型便捷、理想的实验方法。展开更多
Objective:To investigate the status quo of fear of disease progressi on in postoperative patients’spouse of bladder cancer and analyze its influencing factors.Methods:Postoperative patients’spouse of bladder cancer ...Objective:To investigate the status quo of fear of disease progressi on in postoperative patients’spouse of bladder cancer and analyze its influencing factors.Methods:Postoperative patients’spouse of bladder cancer of a cancer hospital in Tianjin were selected as the research objects by the convenience sampling method.The general data questionnaire,spouse fear of disease progression scale and self-efficacy scale were used to investigate.Multiple linear regression was used to analyze the influencing factors of the fear of the disease progression in the postoperative pa tients’spouse of bladder cancer.Results:The score of fear of disease progression was(35.75±9.86).The results of multiple linear regression analysis showed that the spouse’s age,medical payment method,occupational status and self-efficacy were the main influencing factors for the spouse’s fear of disease progression after bladder cancer(P<0.05),which accounted for 55%of the total variation.Conclusion:The spouse’s fear of disease progression in patients with bladder cancer is at a moderate lev el,and age,medical payment method,occupational status and self-efficacy are the main influencing factors.It is suggested that clinical medical staff focus on young,rural cooperative medical care,self-financed,in-service,and unemployed,low self-eff icacy of postoperative bladder cancer patients'spouses.A series of psychological counseling and health education should be given to help the patient spouse correctly understand and deal with diseases,reduce the patients’spouses of negative emotions,im prove the patients’spouses of self-efficacy,and reduce the spouse fear level of disease progression.展开更多
Utilizing delayed expansion cemented paste backfill materials(DECPB) in mine backfill operations offers an effective solution to the challenge of achieving proper contact between the in-situ cemented backfill mass and...Utilizing delayed expansion cemented paste backfill materials(DECPB) in mine backfill operations offers an effective solution to the challenge of achieving proper contact between the in-situ cemented backfill mass and the roof in mined-out areas(backfill-roof contact).This article presents recent progress in both theoretical and experimental research concerning DECPB.The types and mechanisms of expansive additives,including expansive agents,foaming agents,and expansive mineral materials relevant to DECPB,are explained,along with their impact on the expansive properties and mechanical characteristics of DECPB.The composition,material characteristics,preparation methods,and controlled release mechanisms of microcapsules are analyzed.Two methods for measuring the volume change rate of paste backfill slurries are discussed.Research indicates that an appropriate content of expansive additives not only enhances the expansive properties of cemented paste backfill materials but also contributes to improving their mechanical properties.Chemical foaming agents and bentonite are found to be more suitable for preparing DECPB compared to expansive agents.The delayed expansion of cemented paste backfill material is influenced by microcapsules,with their wall materials,preparation parameters,and the alkaline slurry environment affecting their controlled release mechanism.Developing and optimizing precise measurement devices and methods forfor the volume change rate of cemented paste backfill materials is essential requirement for studying the performance of DECPB.Combining delayed expansion technology with retarding techniques in cemented paste backfill materials can provide a reliable solution for achieving proper backfill-roof contact in the future.展开更多
Preparing a highly textured,flawless YBa_（2-）Cu_3O_7（YBCO）layer by ion-beam-as sis ted deposition（IBAD）requires a substrate with a smooth surface.In this paper,smooth tapes of Hastelloy C-276,a common template a...Preparing a highly textured,flawless YBa_（2-）Cu_3O_7（YBCO）layer by ion-beam-as sis ted deposition（IBAD）requires a substrate with a smooth surface.In this paper,smooth tapes of Hastelloy C-276,a common template alloy,were prepared by electrochemical polishing,and the surface roughness the tapes was investigating by atomic force microscopy and scanning electron microscopy.By analyzing these results,it was discussed how the processing parameters affect the surface roughness,and it is found the following optimized processing parameters：current density of 0.104 A·cm^（-2）,temperature of 50℃,plate spacing of 9 cm and time of 150 s.With these optimized parameters,the substrate roughness decreases to less than 5 nm,meeting the requirements of IBAD.展开更多
Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer.In this study,we describe the design,synthesis,and biological evaluation of a series of O-lin...Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer.In this study,we describe the design,synthesis,and biological evaluation of a series of O-linked indoles as potent inhibitors of VEGFR-2.Among these compounds,18 showed significant anti-angiogenesis activities via VEGFR-2 in enzymatic proliferation assays,with IC50 value of3.8 nmol/L Kinase selectivity profiling revealed that 18 was a multitargeted inhibitor,and it also exhibited good potency against VEGFR-1,PDCFR-α and β.展开更多
Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SAR...Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SARS-CoV-2,which is the virus causing coronavirus disease 2019(COVID-19),uses the angiotensin-converting enzyme 2(ACE2)as a cell receptor to invade human cells.Thus,ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection.This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger(ages≤49 years)and older(ages>49 years)persons using two-sided Student's t test.We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine,testis,kidneys,heart,thyroid,and adipose tissue,and were the lowest in the blood,spleen,bone marrow,brain,blood vessels,and muscle.ACE2 showed medium expression levels in the lungs,colon,liver,bladder,and adrenal gland.ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue.In the skin,digestive system,brain,and blood vessels,ACE2 expression levels were positively associated with immune signatures in both males and females.In the thyroid and lungs,ACE2 expression levels were positively and negatively associated with immune signatures in males and females,respectively,and in the lungs they had a positive and a negative correlation in the older and younger groups,respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes,ages,and races equally.The different host immune responses to SARS-CoV-2 infection may partially explain why males and females,young and old persons infected with this virus have markedly distinct disease severity.This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.展开更多
Inhibition of VEGFR-2 signaling pathway is one of the most promising approaches for the treatment of cancer. In this paper, we reported the design, synthesis, and biological evaluation of a series of biphenylurea deri...Inhibition of VEGFR-2 signaling pathway is one of the most promising approaches for the treatment of cancer. In this paper, we reported the design, synthesis, and biological evaluation of a series of biphenylurea derivatives as VEGFR-2 inhibitors. Among these compounds, 39 exhibited potent inhibitory activity against VEGFR-2 both in vitro and in vivo. The antiangiogenesis activity of 39 was further confirmed by both tube formation assay and chick chorioallantoic membrane assay.展开更多
基金the National Natural Science Foundation of China(Nos.81560589,30960450,81173110 and 81560072)Yunnan Provincial Science and Technology Department(Nos.202105AF150015,202102AA310030,2018FE001(-026),2017FE467(-019),2014BC012,and 2017IC041)Yunnan Provincial Educational Department(Nos.2018JS161).
文摘Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in China.In this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)injury of isolated cerebral basilar artery(BA)and erebral ischemia reperfusion(CIR)injury in rat models.In isolated rat BA rings,HR causes endothelial dysfunction(ED)and acetylcholine(ACh)induces endothelium-dependent vasodilation.The myography result showed that SCU(100μM)was able to significantly improve the endothelium-dependent vasodilation induced by Ach.However,SCU did not affect the ACh-induced relaxation in normal BA.Further studies suggested that SCU(10-1000μM)dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase(PKG)inhibitor Rp-8-Br-cGMPs(PKGI-rp,4μM).Pre-incubation with SCU(500μM)reversed the impairment of endothelium-dependent vasodilation induced by HR,but the reversing effect was blocked if PKGI-rp(4μM)was added.The brain slice staining test in rats’model of middle cerebral artery occlusion(MCAO)induced CIR proved that the administration of SCU(45,90 mg/kg,iv)significantly reduced the area of cerebral infarction.The Western blot assay result showed that SCU(45 mg/kg,iv)increased brain PKG activity and PKG protein level after CIR surgery.In conclusion,our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.
基金supported by National Key Research and Development Program of China(2018YFD1000300)Natural Science Basic Research Plan in Shaanxi Province of China(grant no.2018JQ3012)+1 种基金National Natural Science Foundation of China(grant no.31672115,31601716)Shaanxi Province Key Research and Development Program(2018ZDXMNY053-1).
文摘Downy mildew of grapevine(Vitis vinifera L.),caused by the oomycete pathogen Plasmopara viticola,is one of the most serious concerns for grape production worldwide.It has been widely reported that the pathogenesis-related 4(PR4)protein plays important roles in plant resistance to diseases.However,little is known about the role of PR4 in the defense of grapevine against P.viticola.In this study,we engineered loss-of-function mutations in the VvPR4b gene from the cultivar“Thompson Seedless”using the CRISPR/Cas9 system and evaluated the consequences for downy mildew resistance.Sequencing results showed that deletions were the main type of mutation introduced and that no off-target events occurred.Infection assays using leaf discs showed that,compared to wild-type plants,the VvPR4b knockout lines had increased susceptibility to P.viticola.This was accompanied by reduced accumulation of reactive oxygen species around stomata.Measurement of the relative genomic abundance of P.viticola in VvPR4b knockout lines also demonstrated that the mutants had increased susceptibility to the pathogen.Our results confirm that VvPR4b plays an active role in the defense of grapevine against downy mildew.
文摘AIM： To report the surgical result of pars plana vitrectomy（PPV） with air tamponade for rhegmatogenous retinal detachment（RRD） by ultra-widefield fundus imaging system. METHODS： Of 25 consecutive patients（25 eyes） with fresh primary RRD and causative retinal break and vitreous traction were presented. All the patients underwent PPV with air tamponade. Visual acuity（VA） was examined postoperatively and images were captured by ultrawidefield scanning laser ophthalmoscope system（Optos）. RESULTS： Initial reattachment was achieved in 25 cases（100%）. The air volume was 〉60% on the postoperative day（POD） 1. The ultra-widefield images showed that the retina was reattached in all air-filled eyes postoperatively. The retinal break and laser burns in the superior were detected in 22 of 25 eyes（88%）. A missed retinal hole was found under intravitreal air bubble in 1 case（4%）. The air volume was range from 40% to 60% on POD 3. A doublelayered image was seen in 25 of 25 eyes with intravitreal gas. Retinal breaks and laser burns around were seen in the intravitreal air. On POD 7, small bubble without effect was seen in 6 cases（24%） and bubble was completely disappeared in 4 cases（16%）. Small oval bubble in the superior area was observed in 15 cases（60%）. There were no missed and new retinal breaks and no retinal detachment in all cases on the POD 14 and 1 mo and last follow-up. Air disappeared completely on a mean of 9.84 d postoperatively. The mean final postoperative bestcorrected visual acuity（BCVA） was 0.35 log MAR. Mean final postoperative BCVA improved significantly relative to mean preoperative（P〈0.05）. Final VA of 0.3 log MAR or better was seen in 13 eyes. CONCLUSION： PPV with air tamponade is an effective management for fresh RRD with superior retinal breaks. The ultra-widefield fundus imaging can detect postoperative retinal breaks in air-filled eyes. It would be a useful facility for follow-up after PPV with air tamponade. Facedown position and acquired visual rehabilitation may be shorten.
文摘目的探讨以鼻腔滴注博来霉素(BLM)的方式诱导C57BL/6小鼠肺纤维化模型的最佳方法。方法 7~8周龄雄性小鼠30只,分为0.10 u BLM组、0.25 u BLM组、0.40 u BLM组,每组8只,麻醉后分别一次性滴鼻0.10、0.25及0.40 u BLM;对照组6只,给予等体积的磷酸盐缓冲液。观察并记录小鼠体重变化与生存率,实验结束后处死小鼠。用甲醛固定肺组织,苏木精-伊红染色评价肺组织炎症变化;Masson染色评价肺纤维化变化。结果给药后小鼠体重逐渐下降,并在第8和9天再次上升,第14天逐渐趋近于对照组,第28天BLM组所有小鼠肺部组织产生纤维化。各组肺纤维化评分比较,差异无统计学意义(P >0.05)。但给药0.25与0.40 u BLM的小鼠死亡率高,个体间差异较大,不利于实验样本的收集与数据的统计分析。结论 0.10 u BLM滴鼻给药是复制C57BL/6小鼠肺纤维化模型便捷、理想的实验方法。
文摘Objective:To investigate the status quo of fear of disease progressi on in postoperative patients’spouse of bladder cancer and analyze its influencing factors.Methods:Postoperative patients’spouse of bladder cancer of a cancer hospital in Tianjin were selected as the research objects by the convenience sampling method.The general data questionnaire,spouse fear of disease progression scale and self-efficacy scale were used to investigate.Multiple linear regression was used to analyze the influencing factors of the fear of the disease progression in the postoperative pa tients’spouse of bladder cancer.Results:The score of fear of disease progression was(35.75±9.86).The results of multiple linear regression analysis showed that the spouse’s age,medical payment method,occupational status and self-efficacy were the main influencing factors for the spouse’s fear of disease progression after bladder cancer(P<0.05),which accounted for 55%of the total variation.Conclusion:The spouse’s fear of disease progression in patients with bladder cancer is at a moderate lev el,and age,medical payment method,occupational status and self-efficacy are the main influencing factors.It is suggested that clinical medical staff focus on young,rural cooperative medical care,self-financed,in-service,and unemployed,low self-eff icacy of postoperative bladder cancer patients'spouses.A series of psychological counseling and health education should be given to help the patient spouse correctly understand and deal with diseases,reduce the patients’spouses of negative emotions,im prove the patients’spouses of self-efficacy,and reduce the spouse fear level of disease progression.
基金financially supported by the National Natural Science Foundation of China (No.52274122)the Research Fund of BGRIMM Technology Group (No.02-2136)the Youth Innovation Fund of BGRIMM Technology Group (Nos.04-2306,04-2342 and 04-2208)。
文摘Utilizing delayed expansion cemented paste backfill materials(DECPB) in mine backfill operations offers an effective solution to the challenge of achieving proper contact between the in-situ cemented backfill mass and the roof in mined-out areas(backfill-roof contact).This article presents recent progress in both theoretical and experimental research concerning DECPB.The types and mechanisms of expansive additives,including expansive agents,foaming agents,and expansive mineral materials relevant to DECPB,are explained,along with their impact on the expansive properties and mechanical characteristics of DECPB.The composition,material characteristics,preparation methods,and controlled release mechanisms of microcapsules are analyzed.Two methods for measuring the volume change rate of paste backfill slurries are discussed.Research indicates that an appropriate content of expansive additives not only enhances the expansive properties of cemented paste backfill materials but also contributes to improving their mechanical properties.Chemical foaming agents and bentonite are found to be more suitable for preparing DECPB compared to expansive agents.The delayed expansion of cemented paste backfill material is influenced by microcapsules,with their wall materials,preparation parameters,and the alkaline slurry environment affecting their controlled release mechanism.Developing and optimizing precise measurement devices and methods forfor the volume change rate of cemented paste backfill materials is essential requirement for studying the performance of DECPB.Combining delayed expansion technology with retarding techniques in cemented paste backfill materials can provide a reliable solution for achieving proper backfill-roof contact in the future.
基金financially supported by the National Science Foundation of China(Nos.51571002,51171002 and 51401003)Beijing Municipal Natural Science Foundations(Nos.2132011 and KZ201310005003)
文摘Preparing a highly textured,flawless YBa_（2-）Cu_3O_7（YBCO）layer by ion-beam-as sis ted deposition（IBAD）requires a substrate with a smooth surface.In this paper,smooth tapes of Hastelloy C-276,a common template alloy,were prepared by electrochemical polishing,and the surface roughness the tapes was investigating by atomic force microscopy and scanning electron microscopy.By analyzing these results,it was discussed how the processing parameters affect the surface roughness,and it is found the following optimized processing parameters：current density of 0.104 A·cm^（-2）,temperature of 50℃,plate spacing of 9 cm and time of 150 s.With these optimized parameters,the substrate roughness decreases to less than 5 nm,meeting the requirements of IBAD.
基金the National Natural Science Foundation of China (Nos.81273365,81173080 and 81321092)National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"(Nos.2012ZX09103101-024 and 2014ZX09304002-008-001)+1 种基金Chinese National Programs for High Technology Research and Development(No.2012AA020302)the Shanghai Science and Technology Commission(No. 12DZ1930802) for their financial support
文摘Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer.In this study,we describe the design,synthesis,and biological evaluation of a series of O-linked indoles as potent inhibitors of VEGFR-2.Among these compounds,18 showed significant anti-angiogenesis activities via VEGFR-2 in enzymatic proliferation assays,with IC50 value of3.8 nmol/L Kinase selectivity profiling revealed that 18 was a multitargeted inhibitor,and it also exhibited good potency against VEGFR-1,PDCFR-α and β.
基金This work was supported by the China Pharmaceutical University(grant number 3150120001 to XW)。
文摘Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SARS-CoV-2,which is the virus causing coronavirus disease 2019(COVID-19),uses the angiotensin-converting enzyme 2(ACE2)as a cell receptor to invade human cells.Thus,ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection.This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger(ages≤49 years)and older(ages>49 years)persons using two-sided Student's t test.We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine,testis,kidneys,heart,thyroid,and adipose tissue,and were the lowest in the blood,spleen,bone marrow,brain,blood vessels,and muscle.ACE2 showed medium expression levels in the lungs,colon,liver,bladder,and adrenal gland.ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue.In the skin,digestive system,brain,and blood vessels,ACE2 expression levels were positively associated with immune signatures in both males and females.In the thyroid and lungs,ACE2 expression levels were positively and negatively associated with immune signatures in males and females,respectively,and in the lungs they had a positive and a negative correlation in the older and younger groups,respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes,ages,and races equally.The different host immune responses to SARS-CoV-2 infection may partially explain why males and females,young and old persons infected with this virus have markedly distinct disease severity.This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.
基金the National Natural Science Foundation of China (Nos. 81273365, 81173080, 81321092)National Science & Technology Major Project ‘‘Key New Drug Creation and Manufacturing Program’’ (Nos. 2012ZX09103101-024, 2014ZX09304002-008-001)+1 种基金Chinese National Programs for High Technology Research and Development (No. 2012AA020302)the Shanghai Science and Technology Commission (No. 12DZ1930802) for their financial support
文摘Inhibition of VEGFR-2 signaling pathway is one of the most promising approaches for the treatment of cancer. In this paper, we reported the design, synthesis, and biological evaluation of a series of biphenylurea derivatives as VEGFR-2 inhibitors. Among these compounds, 39 exhibited potent inhibitory activity against VEGFR-2 both in vitro and in vivo. The antiangiogenesis activity of 39 was further confirmed by both tube formation assay and chick chorioallantoic membrane assay.
