Field-effect-transistor type C-reactive protein sensor using cysteine-tagged protein G

A BioFET (biological field effect transisor) for detection of C-reactive protein has been characterised using cysteine-tagged protein G capable of site-specific immobilisation of antibody to enhance antigen detection. Drain current of the BioFET with immobilised protein G on the gate surface has been measured in different pH solutions to investigate charge effect of the protein. Antibody-antigen interaction was observed through variation of the drain current of the BioFET. The current differential ratio was linearly related to the concentration of the C-reactive protein in the range 3-20 mug/ml.     

An Inkjet‐Printed Field‐Effect Transistor for Label‐Free Biosensing

A flexible, biological field‐effect transistor (BioFET) for use in biosensing is reported. The BioFET is based on an organic thin‐film transistor (OTFT) fabricated mainly by inkjet printing and subsequently functionalized with antibodies for protein recognition. The BioFET is assessed for label‐free detection of a model protein, human immunoglobulin G (HIgG). It is characterized electrically to evaluate the contribution of each step in the functionalization of the OTFT and to detect the presence of the target protein. The fabrication, structure, materials optimization, electrical characteristics, and functionality of the starting OTFT and final BioFET are also discussed. Different materials are evaluated for the top insulator layer, with the aim of protecting the lower layers from the electrolyte and preserving the BioFET electrical performance.     

A Mannosylated,PEGylated Albumin as a Drug Delivery System for the Treatment of Cancer Stroma Cells

Mannose receptors that are expressed on macrophages and fibroblasts in cancer stroma are promising therapeutic targets for cancer treatment. Albumin can be used as a drug carrier in chemotherapeutics due to its accumulation in the tumor tissue by the enhanced permeability and retention effects. A mannosylated albumin was recently developed as a new drug carrier targeting cells that express mannose receptors such as macrophages and fibroblasts in cancer stroma. The mannosylated albumin is specifically distributed to hepatic macrophages in vivo, leading to an extremely short residence time in the blood. Here, a dual-modified albumin, i.e., mannosylated and polyethylene glycosylated (PEGylated) is reported, to improve its blood circulating time and stromal cell targeting. The product efficiently delivers paclitaxel to stromal cells in a mouse melanoma model, thus resulting in the disruption of stromal cells and suppressed tumor growth, which is seven times stronger than that for PEGylated albumin. The findings suggest that the dual-modified albumin has the potential to provide maximal therapeutic efficacies of chemotherapeutics for the treatment of intractable cancer.     

牛血清蛋白在亲水硅片表面吸附的原子力显微成像

本文用原子力显微术（AFM）研究了牛血清白蛋白（BSA）在亲水硅片表面的吸附，硅片表面经亲水处理后，将牛血清蛋白（BSA）吸附在表面，采用轻敲模式，可获得清晰的AFM图像，牛血清蛋白（BSA）的AFM图像表明：BSA在亲水硅片表面是单分子，水平吸附在硅片表面，且吸颗粒状；1mg/ml的BSA在吸附30min后为饱和吸附。BSA到达硅表面后，蛋白中可移动的带正电荷的基团可以趋向亲水表面，使BSA与硅表面的静电相互作用由斥力变为吸引力，BSA可以稳定地吸附在亲水硅片表面。     

Intracellular Bottom-up Synthesis of Ultrasmall CuS Nanodots in Cancer Cells for Simultaneous Photothermal Therapy and COX-2 Inactivation

The clinical application of photothermal therapy (PTT) is limited by the accuracy of thermal damage and the risk of tumor metastasis and relapse induced by hyperthermia-related inflammation. Intracellular bottom-up synthesis (iBuS) of CuS nanoparticles from small-molecule precursors inside tumor cells triggered by tumor specific stimuli is a promising strategy to enhance the precision of PTT treatment and reduce the risk of nondegradable metal nanoparticles. Herein, monolocking nanoparticles (MLNPs) with Cu-meloxicam complexes encapsulated by human serum albumin (HSA) are reported, which efficiently form CuS nanodots via the elevated concentration of endogenous H₂S inside tumor cells and meanwhile release meloxicam for anti-inflammatory effects. The intracellular bottom-up fabrication of CuS nanodots is directly visualized by TEM. An enhanced PTT effect is observed with 4T1 cells caused by additional meloxicam-induced inactivation of the COX-2 enzyme. After systemic administration, MLNPs completely ablate tumors under laser exposure, simultaneously inhibiting the inflammation induced by photothermal damage, and can be cleared via the kidney into urine. This strategy provides a new route for activated multimodal therapy, which could be applicable to precisely combat cancer.     

基于小波熵的白蛋白热变性动态散斑研究

利用基于小波熵的动态散斑方法研究了白蛋白的热变性过程.采用CCD相机得到了白蛋白热变性过程中的动态散斑图序列;用动态散斑图序列生成了时序散斑图(THSP),再以小波熵为参数,将THSP的每一行分为8个时间窗口,利用db4正交小波对每个窗口进行了三级小波分解,得到了256×256×8的三维小波熵值矩阵.对小波熵值矩阵图像化为8幅256×256的灰度图,直观分析了动态散斑信号的变化规律,进而分析了白蛋白热变性过程中蛋白质分子系综的运动特性.结果表明,利用基于小波熵的动态散斑方法,能对白蛋白热变性过程中蛋白质分子的运动及凝聚过程进行初步的定量分析和研究.该方法是研究溶液中微粒运动的有力手段.     

支持向量机在尿沉渣有形成分分类中的应用

计算机显微图像尿沉渣分析仪，是运用图像处理技术和统计学习理论中支持向量机（SVM）技术，对尿沉渣的有形成分进行自动分类和识别，并从形态学方面对其进行了特征描述。在应用SVM分类方法的过程中，首先建立已知分类的图像，进而提取图像的特征，再对这些特征进行训练，同时交叉验证确定最优的SVM核函数和参数。最后根据训练过程建立的模型来对测试图像分类．结果表明，选用了支持向量机来实现沉渣识别，与传统的方法相比，取得了更高的识别率。     

Pharmacokinetics of Nanoscale Quantum Dots: In Vivo Distribution,Sequestration, and Clearance in the Rat

Advances in nanotechnology research on quantum dots (QDs)—water soluble ZnS‐capped, CdSe fluorescent semiconductor nanocrystals—for in vivo biomedical applications have prompted a close scrutiny of the behavior of nanostructures in vivo. Data pertaining to pharmacokinetics and toxicity will undoubtedly assist in designing better in vivo nanostructure contrast agents or therapies. In vivo kinetics, clearance, and metabolism of semiconductor QDs are characterized following their intravenous dosing in Sprague–Dawley rats. The QDs coated with the organic molecule mercaptoundecanoic acid and crosslinked with lysine (denoted as QD‐LM) are cleared from plasma with a clearance of 0.59 ± 0.16 mL min^–1 kg^–1. A higher clearance (1.23 ± 0.22 mL min^–1 kg^–1) exists when the QDs are conjugated to bovine serum albumin (denoted as QD‐BSA, P < .05 (P = statistical significance). The biodistribution between these two QDs is also different. The liver takes up 40 % of the QD‐LM dose and 99 % of QD‐BSA dose after 90 min. Small amounts of both QDs appear in the spleen, kidney, and bone marrow. However, QDs are not detected in feces or urine for up to ten days after intravenous dosing.     

The Thermal-Chemical Damage in Biological Material under Laser Irradiation

A mathematical model for thermal-chemical damage to biological materials excited by laser irradiation is described. The chemical rate equations for protein denaturization are used to predict radii of damage for cases where the input-laser-energy distribution results in the uniform heating of a small sphere or a disk. These rate equations are limited to a single-hit process. Experimental checks on this model are presented for ruby-laser irradiation of small carbon particles in egg albumin and for CO2?laser surface heating of egg albumin.     

CMOS electrochemical measurement circuit for biomolecular detection

This paper presents a three-electrode potentiostat transducer circuit for electrochemical sensing system designed for biomolecular detection. Melatonin has been found to be used as a significant index of potential breast cancer risk. The proposed chip automatically measures the redox current which depends on the concentration of melatonin in the analyte solution. Moreover, a current-to-time converter is designed to convert the sensed current into the proportional digitized time signal for back-end signal processing. Cyclic voltammetry and molecularly imprinted polymers were used in the experiments. The sensing electrodes were coated with a thin film imprinted with the target molecule. Fabricated in the TSMC CMOS 0.18 μm 1P6M technology, the proposed chip has a core chip size of 0.083 mm² and a power consumption of 1.143 mW with a 1.8 V supply voltage. This chip can measure the sensed current from ±15 to ±1500 µA with a linearity of R² = 0.999. In the cyclic voltammetry measurement, this chip has an error of less than 0.7%. The urine measurement results of the proposed chip were compared with that of enzyme-linked immune sorbent assay. Verified by melatonin concentration measurement, the proposed chip with high sensitivity demonstrates the feasibility of melatonin concentration detection, which contributes to the examination of breast cancer.     

Determining Protein Size Using an Electrochemically Machined Pore Gradient in Silicon

Porous silicon films displaying a distribution of pore dimensions can be generated by electrochemically etching silicon in aqueous ethanolic HF using an asymmetric electrode configuration. The median pore size and breadth of the size‐distribution in the film can be set by adjusting the HF concentration, current density, and position of the counter electrode relative to the silicon electrode. Films with pore sizes in the range of a few nanometers are used as size‐exclusion matrices to perform an on‐chip determination of macromolecule dimensions. The test molecule used in this study is bovine serum albumin (BSA). Optical reflectivity spectra of the thin porous Si films display distinctive shifts in the Fabry–Perot fringes in regions of the film where the pore dimensions are larger than a critical size, interpreted to be the characteristic dimensions of the protein. Gating of the protein in and out of the porous films is demonstrated by adjustment of the solution pH below and above the pI (isoelectric point) value, respectively.     

Nd：YAG激光治疗前列腺增生症（附82例临床报告）

使用Ｎｄ：ＹＡＧ激光经尿道治疗前列腺增生症８２例。术后病人排尿通畅，夜尿减少，残余尿、尿流率较术前显著改善（Ｐ＜０．０１），有效率１００％，临床治愈率８３．８％，无特殊并发症，无明显水中毒现象，是一种简单、安全、有效的治疗方法，尤其适用于高危患者．     

Infrared spectra of urine from cancerous bladders

The infrared spectra of organic constituents of urine from cancerous bladders of some patients were recorded. The spectra of the organic part of the samples were classified into five types according to the bulk constituents. Samples with type A spectra consisted mainly of proteins with only trace amounts of lipids. Their spectra were characterized mainly by the absorption bands of proteins at the frequencies 3330, 3075, 2960, 2850, 1650, 1530, 1450, 1400 and 1320 cm^?1, in addition to a weak band at 1720 cm^?1 due to the absorption of lipids. Samples with type B spectra were characterized by high amounts of proteins and low amounts of lipids and phosphate compounds. The presence of phosphate compounds was indicated by the absorption bands at the frequencies 1100 and 1030 cm^?1. Samples giving spectral type C were characterized by high urea contents as indicated by the presence of two strong bands at 1670 and 1630 cm^?1. Samples with the spectral type D consisted of urea and phosphate compounds whereas the last spectral type E consisted mainly of calcium oxalates, uric acids and phosphate compounds. The presence of calcium oxalates was indicated by the presence of its diagnostic bands at the frequencies 1630 and 1330 cm^?1, while the presence of uric acid was indicated by the bands at the frequencies 1360, 1130, 1020 and 880 cm^?1. On the other hand, the spectra of the organic part of urine from some normal bladders exhibited the characteristic bands of urea only. Careful examination of the spectra of the inorganic part of urine revealed that some samples consisted mainly of hydroxyapatite. The absorption bands of hydroxyapatite appeared at the frequencies 568, 603, 985, 1037 and 1128 cm^?1. The spectra of other samples showed that the bands of basic phosphates at the frequencies 568, 620, 727, 890, 1035 and 1140 cm^?1. The spectra of the inorganic part of urine from a number of normal bladders displayed the bands of basic phosphates. The relationship between urine constituents and pathological types of bladder tumor tissue was discussed.     

Biocompatible Nanoparticles with Aggregation‐Induced Emission Characteristics as Far‐Red/Near‐Infrared Fluorescent Bioprobes for In Vitro and In Vivo Imaging Applications

Light emission of 2‐(2,6‐bis((E)‐4‐(diphenylamino)styryl)‐4H‐pyran‐4‐ylidene)malononitrile (TPA‐DCM) is weakened by aggregate formation. Attaching tetraphenylethene (TPE) units as terminals to TPA‐DCM dramatically changes its emission behavior: the resulting fluorogen, 2‐(2,6‐bis((E)‐4‐(phenyl(4′‐(1,2,2‐triphenylvinyl)‐[1,1′‐biphenyl]‐4‐yl)amino)styryl)‐4H‐pyran‐4‐ylidene)malononitrile (TPE‐TPA‐DCM), is more emissive in the aggregate state, showing the novel phenomenon of aggregation‐induced emission (AIE). Formulation of TPE‐TPA‐DCM using bovine serum albumin (BSA) as the polymer matrix yields uniformly sized protein nanoparticles (NPs) with high brightness and low cytotoxicity. Applications of the fluorogen‐loaded BSA NPs for in vitro and in vivo far‐red/near‐infrared (FR/NIR) bioimaging are successfully demonstrated using MCF‐7 breast‐cancer cells and a murine hepatoma‐22 (H₂₂)‐tumor‐bearing mouse model, respectively. The AIE‐active fluorogen‐loaded BSA NPs show an excellent cancer cell uptake and a prominent tumor‐targeting ability in vivo due to the enhanced permeability and retention effect.     

女性尿液荧光光谱学特性及机理分析

为了研究健康中青年女性尿液荧光光谱的差异,采用SP-3558多功能光谱测量系统对200nm～390nm紫外光激发的20岁～55岁女性尿液进行测量,并运用多种软件对光谱数据进行多峰拟合处理和理论分析,得到了健康女性尿液荧光光谱的特性和产生机理。结果表明,紫外光激发女性晨尿产生的较强荧光光谱,主要是由尿液中的肾脏代谢的中间物质氧化型烟酰胺腺嘌呤核苷酸(nicotinamide ade-nine nucleotide,NAD+)、核黄素、粪卟啉3种物质产生,其对应的中心波长分别为458nm,520nm,612nm和674nm,后两者均是由粪卟啉产生的;随着年龄的增大,肾脏代谢功能下降,导致其尿样中肾脏代谢的中间物质NAD+的含量增加,从而使458nm谱峰强度明显增强。     

A model for the apparent decrease in optical transmittance of thediabetic eye

This paper compares observed changes of ocular transmittance at short and long wavelengths in diabetic patients with values predicted by a model based on the Rayleigh light scattering properties of albumin. Selective chromatic adaptation was used to obtain critical flicker fusion (CFF) frequency thresholds from 21 subjects and 18 patients with insulin-dependent diabetes. The Ferry-Porter characteristic of each color-sensitive mechanism of each patient was compared to age-specific control values. For those eyes without an indication of neural injury, changes in optical density associated with the red- and blue-sensitive mechanisms were calculated and adjusted to reflect accelerated yellowing of the lens produced by increased duration of diabetes. The range of concentration of glycosylated albumin required to fit the model to the adjusted short-wavelength changes in optical density was determined and used to calculate the theoretical long-wavelength changes in optical density. The experimentally derived long-wavelength changes in optical density fell within the 95% confidence level of the values described by the model. These results support the premise that the apparent decrease in optical transmittance observed in patients with diabetes mellitus is caused by light scattering produced by dilute increase of plasma proteins within the retina.     

氦-氖激光穴位照射对广泛性子宫切除术后膀胱功能恢复的影响

目的：研究氦-氖激光穴位照射对广泛性子宫切除术后膀胱功能恢复的影响。方法：192例因宫颈癌IB~ⅡA期而行广泛性子宫切除及盆腔淋巴结清扫术的患者随机分为三组,即对照组,药物组和激光组,每组64例。对照组常规留置尿管和膀胱冲洗;药物组在对照组基础上,于术后第8-13天口服溴吡斯的明,第11~13天加服坦素罗辛;激光组在对照组基础上,于术后第8~13天采用氦—氖激光穴位照射治疗。所有患者于术后第14天拔除导尿管,第15天行残余尿量测定。结果：对照组、药物组和激光组的残余尿量分别是（154.67±73.83）ml、（77.23±38.54）ml和（62.33±39.27）ml,尿潴留发生率分别是37.5%、17.19%和12.5%,平均留置尿管时间分别为（21.73±4.52）天、（17.21±3.47）天和（16.98±2.24）天。药物组和激光组的残余尿量、尿潴留发生率和平均留置尿管时间均明显少于对照组（P〈0.01）,且激光组残余尿量还明显少于药物组（P〈0.05）。结论：氦—氖激光穴位照射能有效促进广泛性子宫切除术后膀胱功能的恢复,减少尿潴留的发生,缩短留置尿管时间。     

Albumin leakage into the brain and wireless-communication radiation

A series of reports from Lund, Sweden, based on observed leakages of endogenous serum albumin in blood, suggested that repeated exposure to microwave radiation from GSM cellular telephones could alter the permeability of the blood-brain barrier at SARs that were well below the maximum permissible level for cellular telephones. While an effort to confirm had failed at SARs of 0.3-1.5 W/kg, it had confirmed extravasation of serum albumin at 7.5 W/kg: a level about four times greater than the maximum permissible level for cellular telephones. Currently, there is considerable interest from several laboratories around the world in replicating the reported occurrence of abnormal neurons in the rat brain resulting from leakage of endogenous serum albumin.     

Effect of cyclophosphane on polyamine excretion in rats with Guérin's carcinoma and Pliss' lymphosarcoma

Polyamines were determined in the urine of rats with the Guerin carcinoma and Pliss lymphosarcoma treated with cyclophosphamide. Alterations in polyamine distribution and rise of the spermidine/putrescine ratio were caused by the tumor regression or partial inhibition of the tumor growth. Regression of the Guerin carcinoma was accompanied by a rise of spermidine concentration in urine. Delay of the Pliss lymphosarcoma growth led to the putrescine level stabilization. Exposition of the rat normal tissues and cells to the cytostatic caused the alteration in the urinary polyamine excretion. These data suggests that the polyamine test may be useful to evaluate the efficiency of the anticancer treatment soon after its beginning.     

Use of the polyamine test in the joint administration of 5-fluorouracil and indomethacin in stomach cancer patients

Excretion of polyamines (spermine, spermidine and putrescine) with the urine was studied in patients with carcinoma of the stomach of the III-IV stage after intravenous injection of 5-fluorouracil and indomethacin. A 40% increase of the polyamine level in the urine was observed at the beginning and towards the end of drug infusion course as well as a decrease of these indices at the top point of chemotherapy and towards the end of it. It is emphasized that an increase of the polyamine amount following the separate use of 5-fluorouracil is less expressed than following combined use of 5-fluorouracil and indomethacin.