Development of a Two‐Photon Fluorescent Probe for Imaging of Endogenous Formaldehyde in Living Tissues

Investigation of the physiological and pathological functions of formaldehyde (FA) are largely restricted by a lack of useful FA imaging agents, in particular, those that allow detection of FA in the context of living tissues. Herein, we present the rational design, synthesis, and photophysical property studies of the first two‐photon fluorescent FA probe, Na‐FA . Importantly, the highly desirable attributes of the probe Na‐FA (such as a very large turn‐on signal (up to 900‐fold), a low detection limit, and a very fast onset imparted by the unique design aspects of the probe), make it possible to monitor endogenous FA in living tissues for the first time. Furthermore, sodium bisulfite was identified as a simple and convenient inhibitor of FA within biological environments.     

样品制备方法对高效液相色谱-串联质谱分析人乳内源肽的影响

人乳内源肽是乳蛋白在乳腺中被降解形成的具有生理功能的肽,是人乳的重要组成部分,研究人乳内源肽对于婴儿健康具有重要的意义。高效液相色谱-串联质谱(LC-MS/MS)联用技术的应用,促使人乳内源肽的研究取得了突破性的进展。人乳中内源肽含量低、干扰组分多,样品制备方法是影响分析结果的关键步骤。为了研究样品制备方法对分析结果的影响,分别采用不变性超滤法(UF 1)、热变性超滤法(UF 2)、化学变性超滤法(UF 3)、三氯乙酸沉淀法(PCPN 1)、乙醇沉淀法(PCPN 2)、强疏水性碳介孔材料(highly ordered mesoporous carbon, OMC)富集法等6种方法从人乳中提取内源肽,利用LC-MS/MS研究样品制备方法对人乳内源肽分析结果的影响。结果表明,UF 1和UF 2法制备的样品中可鉴定到的肽段数目分别为1161±8条和1017±91条,两种方法制备的样品中肽序列的重合率大于70%, UF 1在所有方法中鉴定到的肽的数目最多。UF 3法制备的样品所能鉴定到的肽段数目最少,仅为366±18条。PCPN 1和PCPN 2两种沉淀法制备样品中的内源肽分别为779±69和876±55条,但内源肽差异较大,仅有约50%肽段序列重合。OMC法制备样品中肽的数目为549±151条,与其他方法相比,虽然鉴定的肽数量上没有优势,但该方法制备的样品中肽在等电点(pI)和亲水性平均系数(GRAVY)等性质上没有偏倚,说明该法可用于制备特定人乳内源肽。6种方法制备的样品中鉴定到来源于β-酪蛋白、免疫球蛋白受体、骨桥蛋白、α_S1-酪蛋白、κ-酪蛋白和胆盐激活脂肪酶的肽,并且源于以上蛋白质的肽段总数在该样品中均超过88%,说明6种方法制备的样品都可以满足鉴定一般人乳内源肽的需求。UF 2、UF 3和OMC法制备的样品中鉴定到源于乳铁蛋白的内源肽的数目分别为21、38和19条,内源肽在乳铁蛋白上的覆盖率分别为14%、16%和19%,而文献常用的PCPN 1法制备的样品则会丢失此类内源肽。综上,UF 2法制备的样品不仅肽段数量多、母体蛋白质种类丰富,还可鉴定到源于乳铁蛋白的肽,可作为人乳内源肽组学研究中的首选方法。     

Comparative Chemical Profiles of the Essential Oils from Different Varieties of Psidium guajava L.

Guava (Psidium guajava) leaves are commonly used in the treatment of diseases. They are considered a waste product resulting from guava cultivation. The leaves are very rich in essential oils (EOs) and volatiles. This work represents the detailed comparative chemical profiles of EOs derived from the leaves of six guava varieties cultivated in Egypt, including Red Malaysian (RM), El-Qanater (EQ), White Indian (WI), Early (E), El-Sabahya El-Gedida (ESEG), and Red Indian (RI), cultivated on the same farm in Egypt. The EOs from the leaves of guava varieties were extracted by hydro-distillation and analyzed with GC-MS. The EOs were categorized in a holistic manner using chemometric tools. The hydro-distillation of the samples yielded 0.11–0.48% of the EO (v/w). The GC-MS analysis of the extracted EOs showed the presence of 38 identified compounds from the six varieties. The sesquiterpene compounds were recorded as main compounds of E, EQ, ESEG, RI, and WI varieties, while the RM variety attained the highest content of monoterpenes (56.87%). The sesquiterpenes, β-caryophyllene (11.21–43.20%), and globulol (76.17–26.42%) were detected as the major compounds of all studied guava varieties, while trans-nerolidol (0.53–10.14) was reported as a plentiful compound in all of the varieties except for the RM variety. A high concentration of D-limonene was detected in the EOs of the RM (33.96%), WI (27.04%), and ESEG (9.10%) varieties. These major compounds were consistent with those reported for other genotypes from different countries. Overall, the EOs’ composition and the chemometric analysis revealed substantial variations among the studied varieties that might be ascribed to genetic variability, considering the stability of the cultivation and climate conditions. Therefore, this chemical polymorphism of the studied varieties supports that these varieties could be considered as genotypes of P. guajava. It is worth mentioning here that the EOs, derived from leaves considered to be agricultural waste, of the studied varieties showed that they are rich in biologically active compounds, particularly β-caryophyllene, trans-nerolidol, globulol, and D-limonene. These could be considered as added value for pharmacological and industrial applications. Further study is recommended to confirm the chemical variations of the studied varieties at a molecular level, as well as their possible medicinal and industrial uses.     

可控释放一氧化碳的纳米材料及其生物医学应用

一氧化碳（CO）是一种内源性气体信使分子,具有广泛而复杂的生理学功能.CO分子的生理学效应与其浓度、位置和作用时间密切相关.而现有的一氧化碳供体普遍存在着稳定性较差,剂量难以把控,缺乏靶向性以及对正常细胞和组织器官具有潜在的毒副作用等问题,限制了其进一步的应用.随着纳米科学技术的迅速发展,国内外研究者们构建出一系列能够实现可控释放CO的多功能纳米材料,并将其用于生物医学领域.结合纳米材料自身独特的性能优势,分类介绍了多种内源性/外源性刺激响应型CO控释纳米材料,并概述了可控释放CO的纳米药物在抑制炎症反应、抗菌和肿瘤治疗等生物医学领域的应用,最后对CO控释纳米材料在生物医学领域面临的挑战和发展前景进行了总结和讨论.     

三苯胺取代的苯并咪唑的两种晶体:具有不同颜色的摩擦发光与相反发射位移的力致荧光变色

通过芳香亲核取代、还原以及DMSO/空气条件下的氧化成环反应合成了（4-二苯氨基苯基）-1H-苯并咪唑基苯腈（TBIM）,化合物的溶液经挥发获得两种晶体TBIM_B与TBIM_G,前者具有深蓝色荧光（435 nm）而后者则具有绿色荧光（505 nm）.受力后两者均成为具有青色荧光（457 nm）的无定形粉末,在溶剂熏蒸或热退火条件下前者的荧光可完全恢复,而后者只能转变为前者的荧光.此外,TBIM_B与TBIM_G晶体受力后可分别发出蓝色（432 nm）和绿色（500 nm）的闪光.两种晶体都属于中心对称空间群且晶体内分子对的净偶极矩几乎为零,压电效应与破碎晶体表面分子对间的放电激发理论并不适用于解释两种晶体的摩擦发光.分子的链状堆积结构使晶体在受力下很容易发生解理并引起解理面之间的相对运动导致内生摩擦放电,从而激发解理面上的分子使之产生荧光辐射,这种机制很有可能是该两种晶体出现摩擦发光活性的主要原因.     

同位素稀释-气相色谱-质谱法检测大鼠血浆中的内源性胍丁胺

建立了大鼠血浆中内源性胍丁胺的同位素稀释-气相色谱-负化学电离质谱定量分析方法。大鼠血浆样品经蛋白沉淀并蒸干后,用六氟乙酰丙酮衍生化,采用Florisil固相萃取柱净化,以稳定同位素标记的d₈-胍丁胺为内标,在气相色谱-质谱仪上采用负化学电离方式电离,选择离子模式检测。胍丁胺标准溶液的检出限为0.0057 ng/mL。血浆中添加的胍丁胺在1.14~57.0 ng/mL范围内呈良好的线性关系（r=0.997）,方法回收率介于92.3%~109.8%之间,日内和日间精密度均小于15%。大鼠血浆中胍丁胺平均含量水平为（22±9）ng/mL,雌、雄大鼠血浆中的胍丁胺水平未见显著性差异（p>0.05）。该方法特异性好、灵敏度高,为生物体内胍丁胺的生理功能研究提供了高灵敏的分析方法。     

Endogenous Biomarkers for SLC Transporter-Mediated Drug-Drug Interaction Evaluation

Membrane transporters play an important role in the absorption, distribution, metabolism, and excretion of xenobiotic substrates, as well as endogenous compounds. The evaluation of transporter-mediated drug-drug interactions (DDIs) is an important consideration during the drug development process and can guide the safe use of polypharmacy regimens in clinical practice. In recent years, several endogenous substrates of drug transporters have been identified as potential biomarkers for predicting changes in drug transport function and the potential for DDIs associated with drug candidates in early phases of drug development. These biomarker-driven investigations have been applied in both preclinical and clinical studies and proposed as a predictive strategy that can be supplanted in order to conduct prospective DDIs trials. Here we provide an overview of this rapidly emerging field, with particular emphasis on endogenous biomarkers recently proposed for clinically relevant uptake transporters.     

香豆素类荧光探针对硫化氢检测的研究进展

硫化氢(H2S)是目前人们发现的第三类生物内源性“气体信使分子”。其及时检测对人类的健康有着非常大的意义。随着荧光探针技术的发展,有机小分子荧光探针受到广大学者的关注。其中,香豆素因其结构简单,荧光量子产率高以及易于功能化而备受青睐。本文根据探针的识别机理综述近三年来报道的香豆素类H2S荧光探针代表性研究成果,并对其进行了展望,为后续设计开发更具实用价值的H2S荧光探针提供一点有益的参考。     

固相萃取富集-高效液相色谱法测定长春花中的3种内源激素

植物内源激素直接参与植物生命的所有活动。激素在植物中的含量极低,且性质不稳定,加上长春花（Catharan．thusroseus（L_）G．Don）中文多灵（vindoline）、长春质碱（catharanthine）等众多生物碱类的干扰,使得长春花植物内源激素的测定十分困难。目前对于长春花中内源激素的分离和检测尚未见报道。本文以固相萃取和高效液相色谱法测定了长春花中的3种内源激素含量,取得了理想的效果。     

促红细胞生成素和人生长激素兴奋剂检测方法的研究进展

在2008年世界反兴奋剂组织颁布的兴奋剂目录中,S2项肽类激素及相关品种均属于内源性生物大分子物质,如何区分所检测物质属于外界摄入还是机体分泌是此项检测的重点与难点。本文针对其中应用最为普遍、研究较为深入的促红细胞生成素(EPO)和人生长激素(hGH)的检测,从间接血液指标检测、直接检测途径等方面进行了分类评述,侧重于从理化分析方法、免疫分析方法角度阐述识别及区分重组蛋白与内源性蛋白的新途径。