国际标准CIE S 026:2018为时间生物学领域的照明专业人员和现场研究人员提供了一种方法来表征非视觉光感受与响应方面的光照量。该标准定义了五种光谱灵敏度函数,以描述光辐射刺激五种α响应视网膜光感受器的能力,这些光感受器通过内在...国际标准CIE S 026:2018为时间生物学领域的照明专业人员和现场研究人员提供了一种方法来表征非视觉光感受与响应方面的光照量。该标准定义了五种光谱灵敏度函数,以描述光辐射刺激五种α响应视网膜光感受器的能力,这些光感受器通过内在光敏视网膜神经节细胞(ipRGCs)对人类产生非视觉效应。CIE最近还发布了一个开放获取的α响应工具箱,基于测量(用户自定义)的光谱或工具箱中内置的标准照明体(A、D65、E、FL11、LED-B3),计算光度量、辐射度量和光子系统中α响应计量的数量和比率。基于视黑素蛋白的ipRGCs光感受已被广泛证明可以解释非视觉响应的光谱敏感性,包括改变夜间睡眠的时间、褪黑素分泌和调节稳态瞳孔直径。最近的研究结果表明,感光色素视黑素蛋白也在视觉响应中发挥作用,并且基于视黑素蛋白的光感受可能对亮度感知和空间视觉方面有重要影响。虽然在非视觉效应方面,关于视杆细胞、视锥细胞与ipRGCs如何交互的认识不断发展,最近CIE的一份关于应用“在合适的时间推荐合适的光照”的立场声明中使用了视黑素响应日光(D65)等效照度来指导调节非视觉响应。关于这种方法的详细说明,可以通过第二届昼夜节律和神经生理光度学国际研讨会(曼彻斯特,2019年8月)的同行评审出版物了解*。CIE S 026新的α响应计量方法实现了可追踪测量,并对个人光照量、光干预和照明设计进行了正式的量化规范。通过使用这个工具箱,将这种计量方法应用于日常光源,包括动态变化的日光、LED照明光源以及智能手机屏幕等。这些示例展示了如何利用视黑素含量随时间变化的光照,以更好地支持人类健康与福祉。展开更多
Photodynamic therapy（PDT） is a new medical technology, the study on photodynamic therapy was in full swing in the past two decade. Scientists have made great progress in it. Photosensitizer,oxygen and light source p...Photodynamic therapy（PDT） is a new medical technology, the study on photodynamic therapy was in full swing in the past two decade. Scientists have made great progress in it. Photosensitizer,oxygen and light source play important role in photodynamic therapy. PDT is a light activated chemotherapy. A photon is adsorbed by a photosensitizer which moves the drug into an excited state. The excited drug can then pass its energy to oxygen to create a chemical radical called “singlet oxygen”. Singlet oxygen attacks cellular structures by oxidation. Such oxidative damage might be oxidation of cell membranes or proteins. When the accumulation of oxidative damage exceeds a threshold level,the cell begins to die. Photodynamic therapy allows selective treatment of localized cancer. PDT involves administration of a photosensitizer to the patients, followed by delivery of light to the cancerous region. The light activates the agent which kills the cancer cells. Without light,the agent is harmless. As a new therapy,photodynamic Therapy has great Advantage in treating cancers. 1. PDT avoids systemic treatment. The treatment occurs only where light is delivered, hence the patient does not undergo go needless systemic treatment when treating localized disease. Side-effects are avoided, from losing hair or suffering nausea to more serious complications. 2. PDT is selective. The photosensitizing agent will selectively accumulate in cancer cells and not in surrounding normal tissues. Hence ,there is selective targeting of the cancer and sparing of surrounding tissues. 3. when surgery is not possible. PDT kills cancer cells but does not damage collagenous tissue structures,and normal cells will repopulate these structures. Hence,if a patient has cancer in a structure that cannot be removed surgicaily（eg. ,the upper bronchi of the lung） ,PDT can still treat the site. 4. PDT is repeatable. Uniike radiation therapy,PDT can be used again and again. Hence,it offers a means of longterm management of cancer even if complete cure is not attainable.展开更多
Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH （low） insertion peptide （pHLIP） with a disulfide bond which imparts extracellular pH （pHe）-driven tumor targeting ability, has b...Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH （low） insertion peptide （pHLIP） with a disulfide bond which imparts extracellular pH （pHe）-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 （Ce6）, a second-generation photosensitizer （PS）, is used for photodynamic therapy （PDT）. Gold nanorods （AuNRs） are used as a hyperthermia agent for photothermal therapy （PTT） and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pile-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6- pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPs^-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione （GSH）, and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention （EPR） effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.展开更多
GCaMP is one of the most widely used calcium indicators in neuronal imaging and calcium cell biology. The newly developed GCaMP6 shows superior brightness and ultrasensitivity to calcium concentration change. In this ...GCaMP is one of the most widely used calcium indicators in neuronal imaging and calcium cell biology. The newly developed GCaMP6 shows superior brightness and ultrasensitivity to calcium concentration change. In this study, we determined crystal structures of CaZ＋-bound GCaMP6 monomer and dimer and presented detailed structural analyses in comparison with its par- ent version GCaMP5G. Our analyses reveal the structural basis for the outperformance of this newly developed Ca2＋ indicator. Three substitution mutations and the resulting changes of local structure and interaction explain the ultrasensitivity and in- creased fluorescence intensity common to all three versions of GCaMP6. Each particular substitution in the three GCaMP6 is also structurally consistent with their differential sensitivity and intensity, maximizing the potential of using GCaMP6 in solving diverse problems in neuronal research and calcium signaling. Our studies shall also be beneficial to further structure-guided optimization of GCaMP and facilitate the design of novel calcium indicators.展开更多
Objective： To study the role of dendritic cells （DCs） in initiating delayed-type hypersensitivity （DTH） to fluores- cein isothiocyanate （FITC） after trauma-hemorrhage in mice. Methods： Inbred BALB/c mice （6-...Objective： To study the role of dendritic cells （DCs） in initiating delayed-type hypersensitivity （DTH） to fluores- cein isothiocyanate （FITC） after trauma-hemorrhage in mice. Methods： Inbred BALB/c mice （6-8 weeks old, male） were epicutaneously sensitized with FITC 12 hours, 1 day, 2 days, 4 days and 7 days after closed bilateral femur fractures combined with hemorrhage. And 5 days after sensitization, DTH was evaluated by ear swelling after a challenge of FITC. Draining lymph node cells were examined for the percentages of FITC-positive cells, cluster of differentiation （CD）11c positive cells and major histocom- patibility complex II （MHC II）-positive cells by means of flow cytometry. In vitro proliferative responses of syngeneic lymphocytes and in vivo passive transfer of DTH to naive recipients induced by isolated DCs from the draining lymph nodes were determined. Results： The time of DTH to FITC decreased more significantly in the mice with trauma-hemorrhage （12 hours to 4 days） than in the mice with sham injury. After sensitization, the relative percentages of FITC^＋ cells, FITC^＋/ CD 11c^＋ cells and FITC^＋/CD 11c^＋/MHC II^＋ cells from the draining lymph nodes were all significantly reduced following injury. And the capacity of DCs from the draining lymph nodes in stimulating proliferative responses of lymphocytes and transferring DTH to naive recipients were also inhibited after injury. Conclusions： Trauma-hemorrhage induces repressive DTH in mice, which may be attributed, at least partially, to the reduced trafficking of DCs into the draining lymph nodes and insufficient maturation during DC migration.展开更多
文摘国际标准CIE S 026:2018为时间生物学领域的照明专业人员和现场研究人员提供了一种方法来表征非视觉光感受与响应方面的光照量。该标准定义了五种光谱灵敏度函数,以描述光辐射刺激五种α响应视网膜光感受器的能力,这些光感受器通过内在光敏视网膜神经节细胞(ipRGCs)对人类产生非视觉效应。CIE最近还发布了一个开放获取的α响应工具箱,基于测量(用户自定义)的光谱或工具箱中内置的标准照明体(A、D65、E、FL11、LED-B3),计算光度量、辐射度量和光子系统中α响应计量的数量和比率。基于视黑素蛋白的ipRGCs光感受已被广泛证明可以解释非视觉响应的光谱敏感性,包括改变夜间睡眠的时间、褪黑素分泌和调节稳态瞳孔直径。最近的研究结果表明,感光色素视黑素蛋白也在视觉响应中发挥作用,并且基于视黑素蛋白的光感受可能对亮度感知和空间视觉方面有重要影响。虽然在非视觉效应方面,关于视杆细胞、视锥细胞与ipRGCs如何交互的认识不断发展,最近CIE的一份关于应用“在合适的时间推荐合适的光照”的立场声明中使用了视黑素响应日光(D65)等效照度来指导调节非视觉响应。关于这种方法的详细说明,可以通过第二届昼夜节律和神经生理光度学国际研讨会(曼彻斯特,2019年8月)的同行评审出版物了解*。CIE S 026新的α响应计量方法实现了可追踪测量,并对个人光照量、光干预和照明设计进行了正式的量化规范。通过使用这个工具箱,将这种计量方法应用于日常光源,包括动态变化的日光、LED照明光源以及智能手机屏幕等。这些示例展示了如何利用视黑素含量随时间变化的光照,以更好地支持人类健康与福祉。
文摘Photodynamic therapy（PDT） is a new medical technology, the study on photodynamic therapy was in full swing in the past two decade. Scientists have made great progress in it. Photosensitizer,oxygen and light source play important role in photodynamic therapy. PDT is a light activated chemotherapy. A photon is adsorbed by a photosensitizer which moves the drug into an excited state. The excited drug can then pass its energy to oxygen to create a chemical radical called “singlet oxygen”. Singlet oxygen attacks cellular structures by oxidation. Such oxidative damage might be oxidation of cell membranes or proteins. When the accumulation of oxidative damage exceeds a threshold level,the cell begins to die. Photodynamic therapy allows selective treatment of localized cancer. PDT involves administration of a photosensitizer to the patients, followed by delivery of light to the cancerous region. The light activates the agent which kills the cancer cells. Without light,the agent is harmless. As a new therapy,photodynamic Therapy has great Advantage in treating cancers. 1. PDT avoids systemic treatment. The treatment occurs only where light is delivered, hence the patient does not undergo go needless systemic treatment when treating localized disease. Side-effects are avoided, from losing hair or suffering nausea to more serious complications. 2. PDT is selective. The photosensitizing agent will selectively accumulate in cancer cells and not in surrounding normal tissues. Hence ,there is selective targeting of the cancer and sparing of surrounding tissues. 3. when surgery is not possible. PDT kills cancer cells but does not damage collagenous tissue structures,and normal cells will repopulate these structures. Hence,if a patient has cancer in a structure that cannot be removed surgicaily（eg. ,the upper bronchi of the lung） ,PDT can still treat the site. 4. PDT is repeatable. Uniike radiation therapy,PDT can be used again and again. Hence,it offers a means of longterm management of cancer even if complete cure is not attainable.
文摘Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH （low） insertion peptide （pHLIP） with a disulfide bond which imparts extracellular pH （pHe）-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 （Ce6）, a second-generation photosensitizer （PS）, is used for photodynamic therapy （PDT）. Gold nanorods （AuNRs） are used as a hyperthermia agent for photothermal therapy （PTT） and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pile-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6- pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPs^-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione （GSH）, and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention （EPR） effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.
基金supported in part by an International Early Career Scientist grant from the Howard Hughes Medical Institute to Shao Fenggrant from the National Basic Research Program of China (2011CB910304 and 2011CB911103) to Wang DaChengNational Natural Science Foundation of China (31100535) to Ding JingJin
文摘GCaMP is one of the most widely used calcium indicators in neuronal imaging and calcium cell biology. The newly developed GCaMP6 shows superior brightness and ultrasensitivity to calcium concentration change. In this study, we determined crystal structures of CaZ＋-bound GCaMP6 monomer and dimer and presented detailed structural analyses in comparison with its par- ent version GCaMP5G. Our analyses reveal the structural basis for the outperformance of this newly developed Ca2＋ indicator. Three substitution mutations and the resulting changes of local structure and interaction explain the ultrasensitivity and in- creased fluorescence intensity common to all three versions of GCaMP6. Each particular substitution in the three GCaMP6 is also structurally consistent with their differential sensitivity and intensity, maximizing the potential of using GCaMP6 in solving diverse problems in neuronal research and calcium signaling. Our studies shall also be beneficial to further structure-guided optimization of GCaMP and facilitate the design of novel calcium indicators.
基金This study was supported by the National Basic Research Program of China （No. 2005CB522602）, Natural Science Foundation of China （No.30772253） and Project of State Key Laboratory of Trauma, Burns, and Combined Injury （No. SKLZZ200802）.
文摘Objective： To study the role of dendritic cells （DCs） in initiating delayed-type hypersensitivity （DTH） to fluores- cein isothiocyanate （FITC） after trauma-hemorrhage in mice. Methods： Inbred BALB/c mice （6-8 weeks old, male） were epicutaneously sensitized with FITC 12 hours, 1 day, 2 days, 4 days and 7 days after closed bilateral femur fractures combined with hemorrhage. And 5 days after sensitization, DTH was evaluated by ear swelling after a challenge of FITC. Draining lymph node cells were examined for the percentages of FITC-positive cells, cluster of differentiation （CD）11c positive cells and major histocom- patibility complex II （MHC II）-positive cells by means of flow cytometry. In vitro proliferative responses of syngeneic lymphocytes and in vivo passive transfer of DTH to naive recipients induced by isolated DCs from the draining lymph nodes were determined. Results： The time of DTH to FITC decreased more significantly in the mice with trauma-hemorrhage （12 hours to 4 days） than in the mice with sham injury. After sensitization, the relative percentages of FITC^＋ cells, FITC^＋/ CD 11c^＋ cells and FITC^＋/CD 11c^＋/MHC II^＋ cells from the draining lymph nodes were all significantly reduced following injury. And the capacity of DCs from the draining lymph nodes in stimulating proliferative responses of lymphocytes and transferring DTH to naive recipients were also inhibited after injury. Conclusions： Trauma-hemorrhage induces repressive DTH in mice, which may be attributed, at least partially, to the reduced trafficking of DCs into the draining lymph nodes and insufficient maturation during DC migration.
