Targeted bile acids metabolomics in cholesterol gallbladder polyps and gallstones: From analytical method development towards application to clinical samples

Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Chenodeoxycholic acid,glycochenodeoxycholic acid,l-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

Highly efficient luminescent Ⅰ-Ⅲ-Ⅵ semiconductor nanoprobes based on template-synthesized CuInS2 nanocrystals

CuInS2 semiconductor nanocrystals (NCs) exhibit large absorption coefficient, size-dependent photoluminescence and low toxicity, making them excellent candidates in a variety of bioapplications. However, precise control of both their composition and morphology to improve the luminescent efficiency remains a great challenge via conventional direct synthesis. Herein, we present a novel low-temperature template synthesis of highly efficient luminescent CuInS2 nanoprobes from In2S3 NCs via a facile cation exchange strategy. The proposed strategy enables synthesis of a series of CuInS2 NCs with broad size tunability from 2.2 to 29.6 nm. Through rationally manipulating the stoichiometry of Cu/In, highly efficient luminescence of CuInS2 with the maximum quantum yield of 28.6% has been achieved, which is about one order of magnitude improvement relative to that of directly synthesized NCs. By virtue of the intense emission of CuInS2 nanoprobes, we exemplify their application in sensitive homogeneous biodetection for an important biomolecule of adenosine triphosphate (ATP) with the limit of detection down to 49.3 nM. Moreover, the CuInS2 nanoprobes are explored for ATP-targeted cancer cell imaging, thus revealing their great potentials in the field of cancer diagnosis and prognosis.

A new class of luminescent nanoprobes based on main-group Sb^(3+) emitters

Inorganic luminescent nanocrystals(NCs)doped with main-group ns^(2)-metal ions have evoked tremendous interest in many technological fields owing to their superior optical properties.Herein,we report a new class of luminescent nanoprobes based on 5s2-metal Sb3+-doped CaS NCs that are excitable by using a near ultraviolet light-emitting diode.The optical properties and excited-state dynamics of Sb3+in CaS NCs are comprehensively surveyed through temperature-dependent steady-state and transient photoluminescence(PL)spectroscopies.Owing to the strong electron-phonon coupling of Sb^(3+)in CaS NCs,Sb3+ions experience a dynamic Jahn-Taller distortion on the excited state,which results in bright green PL of Sb3+with a broad emission band,a large Stokes shift,and a high PL quantum yield up to 17.3%.By taking advantage of the intense PL of Sb^(3+),we show in proof-of-concept experiments the application of biotinylated CaS:Sb^(3+)NCs as sensitive luminescent nanoprobes for biotin receptor-targeted cancer cell imaging and zebrafish imaging with a high imaging contrast.These findings provide fundamental insights into the excited-state dynamics of Sb^(3+)in CaS NCs,thus laying a foundation for future design of novel and versatile luminescent nanoprobes via main-group ns2-metal doping.

蓝光LED可激发的稀土掺杂SrS近红外二区纳米荧光探针及温度传感

稀土掺杂近红外二区纳米荧光探针在许多技术领域都具有广泛的应用前景,但目前受限于稀土离子的4f→4f禁戒跃迁导致材料的吸收强度弱、发光效率低.本文报道了一种基于SrS纳米晶Ce^(3+)到Er^(3+)和Nd^(3+)高效能量传递的新型蓝光LED可激发的近红外二区纳米荧光探针.通过Ce^(3+)的4f→5d吸收允许跃迁敏化,该纳米晶可实现Er^(3+)和Nd^(3+)的高效近红外二区发光,其荧光量子产率分别为2.9%和2.3%.利用Er^(3+)的^(4)I_(13/2)热耦合晶体场子能级的近红外二区发光,该纳米晶可作为一种蓝光LED激发的近红外二区纳米荧光探针用于比率式温度传感.这些结果展示了SrS:Ln^(3+)纳米晶在近红外二区波段的发光优点,为多功能稀土硫化物基纳米荧光探针的设计开发提供了新思路.

Sub-10 nm lanthanide-doped SrFCl nanoprobes:Controlled synthesis,optical properties and bioimaging

Alkaline-earth dihalide nanocrystals(NCs) such as SrFCl, owing to their high chemical stability and low phonon energy, are excellent host materials for lanthanide(Ln3+) doping to achieve desirable optical properties for various bioapplications, Herein, we report a novel strategy for the synthesis of sub-10 nm Ln3+-doped SrFCl NCs with efficient upconverting and downshifting luminescence through a facile onestep hot-injection method. Utilizing the temperature-dependent upconverting luminescence(UCL) from the thermally coupled 2H11/2 and 4S3/2 levels of Er3+, we showed the potential of SrFCl:Yb,Er NCs as sensitive UCL nanoprobes for non-contact thermal sensing with a maximum detection sensitivity of 0.0066 K-1, which is among the highest values for thermal sensing based on Er3+-activated UCL nanoprobes. Furthermore, by employing the intense downshifting luminescence from Tb3+ and Eu3+, we demonstrated the successful use of biotinylated SrFCl:Ce,Tb and SrFCl:Eu3+ nanoprobes for biotin receptor-targeted cancer cell imaging, thus revealing the great promise of SrFCl:Ln3+ nanoprobes for versatile bioapplications.

基于Mn^(2+)激活氟化钙纳米荧光探针的时间分辨荧光生物分析（英文）

时间分辨荧光探测技术在超灵敏生物检测和高分辨生物成像领域具有广泛的应用前景.目前报道的时间分辨荧光生物探针大都是利用稀土离子4fN电子组态间的禁戒跃迁发光.本文报道了基于过渡金属Mn^(2+)离子d→d禁戒跃迁发光的时间分辨荧光生物分析.我们证明通过测试Mn^(2+)的荧光寿命变化可以将荧光共振能量传递与辐射再吸收信号区分开来,从而为Mn^(2+)发光在时间分辨荧光共振能量传递均相生物检测的应用提供了一种可靠的分析方法.利用生物素化的CaF_2:Ce,Mn纳米荧光探针,我们还实现了对生物素受体过表达癌细胞的靶向荧光成像.通过概念性验证并利用手机连拍功能,我们证明了Mn^(2+)的长寿命发光可用于时间分辨荧光生物成像.这些研究结果为过渡金属长寿命发光在时间分辨荧光生物分析领域的应用提供了普适方法,也为过渡金属离子的新型、多功能用途开辟了新的方向.