The contribution of heme propionate groups to the conformational dynamics associated with CO photodissociation from horse heart myoglobin

Photoacoustic calorimetry and transient absorption spectroscopy were used to study conformational dynamics associated with CO photodissociation from horse heart myoglobin (Mb) reconstituted with either Fe protoporphyrin IX dimethylester (FePPDME), Fe octaethylporphyrin (FeOEP), or with native Fe protoporphyrin IX (FePPIX). The volume and enthalpy changes associated with the Fe-CO bond dissociation and formation of a transient deoxyMb intermediate for the reconstituted Mbs were found to be similar to those determined for native Mb (DeltaV1 = -2.5+/-0.6 ml mol(-1) and DeltaH1 = 8.1+/-3.0 kcal mol(-1)). The replacement of FePPIX by FeOEP significantly alters the conformational dynamics associated with CO release from protein. Ligand escape from FeOEP reconstituted Mb was determined to be roughly a factor of two faster (tau=330 ns) relative to native protein (tau=700 ns) and accompanying reaction volume and enthalpy changes were also found to be smaller (DeltaV2 = 5.4+/-2.5 ml mol(-1) and DeltaH2 = 0.7+/-2.2 kcal mol(-1)) than those for native Mb (DeltaV2 = 14.3+/-0.8 ml mol(-1) and DeltaH2 = 7.8+/-3.5 kcal mol(-1)). On the other hand, volume and enthalpy changes for CO release from FePPIX or FePPDME reconstituted Mb were nearly identical to those of the native protein. These results suggest that the hydrogen bonding network between heme propionate groups and nearby amino acid residues likely play an important role in regulating ligand diffusion through protein matrix. Disruption of this network leads to a partially open conformation of protein with less restricted ligand access to the heme binding pocket.     

On the photophysics of metallophthalocyanine-based photothermal sensitizers: synergism between theory and experiment

A comprehensive understanding of the factors governing the efficiency of metallophthalocyanine-based photothermal sensitizers requires the knowledge of their excited-state dynamics. This can only be properly gained when the nature and energy of the excited states (often spectroscopically silent) lying between the photogenerated state and the ground state are known. Here the excited state deactivation mechanism of two very promising metallophthalocyanine-based photothermal sensitizers, NiPc(OBu)(8) and NiNc(OBu)(8), is reviewed. It is shown that time dependent density functional theory (TDDFT) methods are capable to provide reliable information on the nature and energies of the low-lying excited states along the relaxation pathways. TDDFT calculations and ultrafast experiments consistently show that benzoannulation of the Pc ring modifies the photodeactivation mechanism of the photogenerated S(1)(pi,pi*) state by inducing substantial changes in the relative energies of the excited states lying between the S(1)(pi,pi*) state and the ground state.     

Detection of tetanus-induced effects in linearly lined-up micropatterned neuronal networks: application of a multi-electrode array chip combined with agarose microstructures

K-7174, a GATA-specific inhibitor, is a putative anti-inflammatory agent that attenuates effects of inflammatory cytokines in certain cell types. However, molecular mechanisms involved have not been elucidated. We found that, in glomerular podocytes, induction of monocyte chemoattractant protein 1 (MCP-1) and inducible nitric oxide synthase (iNOS) by TNF-alpha was abrogated by K-7174. It was correlated with unexpected induction of unfolded protein response (UPR) evidenced by: (1) induction of endogenous indicators 78 kDa glucose-regulated protein and CCAAT/enhancer-binding protein-homologous protein, and (2) suppression of an exogenous indicator, endoplasmic reticulum stress-repressive alkaline phosphatase. In podocytes, induction of UPR by either tunicamycin, thapsigargin, A23187 or AB5 subtilase cytotoxin completely reproduced the suppressive effect of K-7174. Furthermore, K-7174-elicited UPR abrogated induction of MCP-1 and iNOS not only by TNF-alpha but also by medium conditioned by activated macrophages. These results suggested a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of K-7174.     

Multifunctional Hybrid Fe2O3-Au Nanoparticles for Efficient Plasmonic Heating

One of the most widely used methods for manufacturing colloidal gold nanospherical particles involves the reduction of chloroauric acid (HAuCl₄) to neutral gold Au(0) by reducing agents, such as sodium citrate or sodium borohydride. The extension of this method to decorate iron oxide or similar nanoparticles with gold nanoparticles to create multifunctional hybrid Fe₂O₃-Au nanoparticles is straightforward. This approach yields fairly good control over Au nanoparticle dimensions and loading onto Fe₂O₃. Additionally, the Au metal size, shape, and loading can easily be tuned by changing experimental parameters (e.g., reactant concentrations, reducing agents, surfactants, etc.). An advantage of this procedure is that the reaction can be done in air or water, and, in principle, is amenable to scaling up. The use of such optically tunable Fe₂O₃-Au nanoparticles for hyperthermia studies is an attractive option as it capitalizes on plasmonic heating of gold nanoparticles tuned to absorb light strongly in the VIS-NIR region. In addition to its plasmonic effects, nanoscale Au provides a unique surface for interesting chemistries and catalysis. The Fe₂O₃ material provides additional functionality due to its magnetic property. For example, an external magnetic field could be used to collect and recycle the hybrid Fe₂O₃-Au nanoparticles after a catalytic experiment, or alternatively, the magnetic Fe₂O₃ can be used for hyperthermia studies through magnetic heat induction. The photothermal experiment described in this report measures bulk temperature change and nanoparticle solution mass loss as functions of time using infrared thermocouples and a balance, respectively. The ease of sample preparation and the use of readily available equipment are distinct advantages of this technique. A caveat is that these photothermal measurements assess the bulk solution temperature and not the surface of the nanoparticle where the heat is transduced and the temperature is likely to be higher.     

In vivo measurement of spectroscopic and photochemical properties of intact leaves using the ‘mirage effect’

This paper describes a new, highly sensitive, method for in vivo studies of photosynthesis based on the ‘mirage effect’ in which thermal energy dissipation from intact leaves, illuminated with intensity-modulated light, is sensed through the periodic deflection of a laser beam propagating along the leaf surface. The photothermal deflection technique allows one to rapidly estimate the gross efficiency of photochemical energy storage by comparing the heat emission signal with and without an additional strong, photosynthetically saturating, non-modulated light. In pea leaves, the maximal storage efficiency at low light intensities was shown to approach 55%. The general utility of this simple photothermal method is illustrated by examining the variation of the deflection signal under different conditions. The spectral resolution of this new method is shown to be much higher than that of the photoacoustic method.     

基于巨噬细胞的诊疗一体化系统

目的:建立一种可以同时实现显像诊断与主动靶向到肿瘤部位进行治疗的纳米药物模型。方法:包载了1,1'-二十八烷基-3,3,3',3'-四甲基吲哚三碳花青碘(1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide, Di R)荧光染料的聚乳酸-羟基乙酸共聚物(Polylactic-co-glycolic acid, PLGA)纳米粒表面被金属离子与酚羟基络合形成的网状结构涂布后可稳定连接在巨噬细胞表面,Di R可以在近红外激光下实现荧光成像,并经波长为808 nm的近红外激光器以2 W/cm2功率照射,产生光热作用。结果:构建了粒径在100 nm左右的包载了Di R的PLGA纳米粒,表面涂布金属多酚网状结构后,纳米粒连接到巨噬细胞表面,Di R发挥既可荧光成像,经808 nm激光照射后又可高效升温至46℃以上,使用CCK8试剂检测证明此种连接了纳米粒的功能化细胞(Functional Cell)发挥光热作用后可杀死近70%的小鼠乳腺癌细胞4T1。结论:成功建立了一种基于巨噬细胞递送的诊疗一体化系统,将荧光成像与光热治疗有机结合到一起,达到有效杀伤肿瘤细胞的功效。     

动脉粥样硬化斑块中脂肪沉积的扫频光热波成像

动脉粥样硬化和易损斑块破裂在全球范围内具有最高的死亡率,超过传染病和癌症导致的死亡率的总和。动脉粥样硬化斑块是由一层很薄的”纤维帽”和导致血栓形成的脂质核心构成。光热波成像是基于对被目标发色团（本文中指脂肪沉积）吸收的光信号强度进行周期调制,从而实现对目标发色团释放的热（红外）信号的调制。这里,我们利用光热波成像来检测来自兔子动脉硬化模型的粥样硬化斑块中脂肪沉积的三维分布。波长为1210纳米的激光被用来靶向检测脂肪。动脉粥样硬化斑块组织在0．1到5赫兹连续扫频的激光的激发下发出光热波,光热波传播到样品表面形成红外辐射温度并被红外相机以25．6帧／秒的速度接收并录制20秒。红外相机上的每一个像素（总共256~256像素）在进行时域傅里叶变换以后得到强度和相位的频域光热波图像。某一特定频率的强度和相位光热波图像对应着脂肪沉积在动脉粥样硬化斑块样品中的横向和纵向分布。对强度和相位光热波图像的分析指出：光热波成像能够用来检测脂肪在动脉粥样硬化斑块中的三维分布,并且脂肪的分布和动脉粥样硬化斑块的形状特征有着紧密联系。     

A Series of Pyrene‐Substituted Silicon Phthalocyanines as Near‐IR Sensitizers in Organic Ternary Solar Cells

An attractive method to broaden the absorption bandwidth of polymer/fullerene‐based bulk heterojunction (BHJ) solar cells is to blend near infrared (near‐IR) sensitizers into the host system. Axial substitution of silicon phthalocyanines (Pcs) opens a possibility to modify the chemical, thermodynamic, electronic, and optical properties. Different axial substitutions are already designed to modify the thermodynamic properties of Pcs, but the impact of extending the π‐conjugation of the axial ligand on the opto‐electronic properties, as a function of the length of the alkyl spacer, has not been investigated yet. For this purpose, a novel series of pyrene‐substituted silicon phthalocyanines (SiPc‐Pys) with varying lengths of alkyl chain tethers are synthesized. The UV–vis and external quantum efficiency (EQE) results exhibit an efficient near IR sensitization up to 800 nm, clearly establishing the impact of the pyrene substitution. This yields an increase of over 20% in the short circuit current density (J _SC) and over 50% in the power conversion efficiency (PCE) for the dye‐sensitized ternary device. Charge generation, transport properties, and microstructure are studied using different advanced technologies. Remarkably, these results provide guidance for the diverse and judicious selection of dye sensitizers to overcome the absorption limitation and achieve high efficiency ternary solar cells.     

In vivo studies of gross photosynthesis in attached leaves by means of photothermal radiometry

In photothermal radiometry, heat radiation from an illuminated object, in synchronism with incident chopped light, is observed using an infrared detector with suitable electronics. By thus measuring the heat released during pulse-wise irradiation of leaves, conclusions can be drawn as to the gross efficiency of photosynthesis: More heat means less photochemically stored energy. Saturation of photosynthesis, by employing additional strong continuous-wave background light, affords an internal photothermal radiometry signal reference corresponding to the photochemical zero efficiency level, against which the signal in the absence of saturation can be compared. Through such means, gross energy storage efficiencies approaching 30% have been observed in Caragana arborescens Lam. at low light intensities. Several other examples are given, including measurements on dark-adapted leaves and leaves infiltrated with 3-(3,4-dichlorophenyl)-1,1-dimethylurea, to support our conclusion that photothermal radiometry provides a powerful new method for in vivo studies of photosynthesis in whole, attached leaves.