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.

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.

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.

Blue-LED-excitable NIR-Ⅱluminescent lanthanide-doped SrS nanoprobes for ratiometric thermal sensing

Lanthanide(Ln^(3+))-doped near infrared(NIR)-II luminescent nanoprobes have shown great promise in many technological fields,but are currently limited by the low absorption efficiency of Ln^(3+)due to the forbidden 4f→4f transition.Herein,we report a novel NIR-II luminescent nanoprobe based on efficient energy transfer from Ce^(3+)to Er^(3+)and Nd^(3+)in sub-10 nm SrS nanocrystals(NCs),which are excitable by using a commercial blue light-emitting diode(LED).Through sensitization by the allowed 4f→5d transition of Ce^(3+),the NCs exhibit strong NIR-II luminescence from Er^(3+)and Nd^(3+)with quantum yields of 2.9%and 2.3%,respectively.Furthermore,by utilizing the intense NIR-II luminescence of Er^(3+)from the thermally coupled Stark sublevels of ^(4)I_(13/2),we demonstrate the application of SrS:Ce^(3+)/Er^(3+)NCs as blue-LED-excitable NIR-II luminescent nanoprobes for ratiometric thermal sensing.These findings reveal the unique advantages of SrS:Ln^(3+)NCs in NIR-II luminescence,which may open up a new avenue for exploring novel and versatile luminescent nanoprobes based on Ln^(3+)-doped sulphide NCs.

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.

Mn^(2+)-activated calcium fluoride nanoprobes for time-resolved photoluminescence biosensing

Time-resolved (TR)photoluminescence (PL) technique has shown great promise in ultrasensitive biodetection and high-resolution bioimaging.Hitherto,almost all the TRPL bioprobes are based on the parity-forbidden f→f transition of lanthanide ions.Herein,we report TRPL biosensing by taking advantage of the d→d transition of transition metal (TM)Mn^2+ ion.We demonstrate that the Forster resonance energy transfer (FRET)signal can be distinguished from that of radiative reabsorption process through measuring the PL lifetime of Mn^2+,thus establishing a reliable method for Mn^2+ in homogeneous TR-FRET biodetection.We also demonstrate the biotin receptor-targeted cancer cell imaging by utilizing biotinylated CaF2:Ce,Mn nanoprobes.Furthermore,we show in a proof-of-concept experiment the appli- cation of the long-lived PL of Mn^2+ for TRPL bioimaging through the burst shot with a cell phone.These findings provide a general approach for exploiting the long-lived PL of TM ions for TRPL biosensing,thereby opening up a new avenue for the exploration of novel and versatile applications of TM ions.