Gint4.T-siHDGF chimera-capped mesoporous silica nanoparticles encapsulating temozolomide for synergistic glioblastoma therapy.

Due to glioblastoma (GBM) being the most intractable brain tumor, the continuous improvement of effective treatment methods is indispensable. The combination of siRNA-based gene therapy and chemotherapy for GBM treatment has now manifested great promise. Herein, Gint4.T-siHDGF chimera-capped mesoporous silica nanoparticles (MSN) encapsulating chemotherapy drug temozolomide (TMZ), termed as TMSN@siHDGF-Gint4.T, is developed to co-deliver gene-drug siHDGF and TMZ for synergistic GBM therapy. TMSN@siHDGF-Gint4.T possesses spherical nucleic acid-like architecture that can improve the enzyme resistance of siHDGF and increase the blood-brain barrier (BBB) permeability of the nanovehicle. The aptamer Gint4.T of chimera endows the nanovehicle with GBM cell-specific binding ability. When administered systemically, TMSN@siHDGF-Gint4.T can traverse BBB and enter GBM cells. In the acidic lysosome environment, the cleavage of benzoic-imine bond on MSN surface leads to an initial rapid release of chimera, followed by a slow release of TMZ encapsulated in MSN. The sequential release of siHDGF and TMZ first allows siHDGF to exert its gene-silencing effect, and the downregulation of HDGF expression further enhances the cytotoxicity of TMZ. In vivo experimental results have demonstrated that TMSN@siHDGF-Gint4.T significantly inhibits tumor growth and extends the survival time of GBM-bearing mice. Thus, the as-developed TMSN@siHDGF-Gint4.T affords a potential approach for the combination treatment of GBM.

Moroidin, a Cyclopeptide from the Seeds of Celosia cristata That Induces Apoptosis in A549 Human Lung Cancer Cells.

Interference of microtubule dynamics with tubulin-targeted drugs is a validated approach for cancer chemotherapy. Moroidin (1) is an Urticaceae-type cyclopeptide having a potent inhibitory effect on purified tubulin polymerization. So far, moroidin has not been chemically synthesized, and its effect on cancer cells remains unknown. Herein, the cyclopeptide moroidin was isolated and identified from the seeds of Celosia cristata, and a revised assignment of its NMR data was presented. For the first time, moroidin (1) was demonstrated as having cytotoxic effects for several cancer cells, especially A549 lung cancer cells. The cellular evidence obtained showed that moroidin disrupts microtubule polymerization and decreases ß-tubulin protein levels, but is not as potent as colchicine. Molecular docking indicated that 1 has a high binding potential to the vinca alkaloid site on tubulin. Moreover, moroidin arrested A549 cells in the G2/M phase and induced cell apoptosis. The intrinsic mitochondrial pathway and AKT were involved in the moroidin-induced cell apoptosis. In addition, moroidin (1) inhibited the migration and invasion of A549 cells at sublethal concentrations.

Integrated ratiometric fluorescence probe-based acoustofluidic platform for visual detection of anthrax biomarker.

The sensitive detection of dipicolinic acid (DPA) as an excellent biomarker of Bacillus anthracis, especially through visual point-of-care testing, is significant for accurate and rapid diagnosis of anthrax to timely prevent anthrax disease or biological terrorist attack. Herein, an acoustofluidics-based colorimetric platform with the integrated ratiometric fluorescence probe (INT-probe) was fabricated, which improved the sensitivity of visual detection for DPA and overcame the poor reproducibility of the existing acoustofluidics-assisted colorimetric analysis. For the design of INT-probe, Eu3+-EDTA complex as sensing moiety was grafted onto the surface of blue organosilane-functionalized carbon dots (SiCDs)-doped SiO2 nanoparticles (NPs). Upon exposure to DPA, Eu3+ was sensitized by DPA to emit red luminescence, while the SiCDs as reference inside the SiO2 NPs still kept the blue fluorescence unchanged. Attributed to the acoustic radiation force-driven enrichment of the INT-probe, slight color changes caused by low concentration of DPA could be amplified and distinguished by naked-eyes/smartphone. With the increase of DPA concentration, obvious color variations of INT-probe/DPA aggregates from blue to pink could be observed, and the color information of the fluorescent aggregates was converted to red, green and blue values for quantitative analysis, whose lowest detectable concentration reached 100 nM that is about 2-3 orders of magnitude lower than the infectious dosage of Bacillus anthracis spores (60 µM). Importantly, benefiting from the great color signal enhancement by acoustofluidic sensing platform, the usage of Eu3+ reduced to as low as 0.273 µmol per gram of SiO2 NPs, providing a meaningful way to utilize lanthanide resource efficiently.

Monitoring allergic reaction to penicillin based on ultrasensitive detection of penicilloyl protein using alkyne response SERS immunosensor.

The evaluation of true penicillin allergy is significant to reduce its occurrence and the overdiagnosis before anti-infective treatment. However, the currently available methods with high specificity still face the problem of low sensitivity, thereby easily leading to false negatives. Herein, an alkyne responsive surface-enhanced Raman scattering (SERS) immunosensor is reported for ultrasensitive detection of penicillin allergen penicilloyl protein (P-protein) by using Au-Ag alloy nanoparticles@(antibody + alkyne probe) (as SERS immunoprobe) together with Ag nanofilm modified by antibody (as SERS capture substrate). The SERS immunoassay integrates the interference-free Raman response of high wavenumber region (2212 cm-1) and specific capture antibody with high affinity to selectively recognize P-protein from complicated sample. Meanwhile, the target-induced near-field coupling effect between localized surface plasmon resonances of individual SERS immunoprobe and capture substrate enables the detection of P-protein as low as pg/mL level, and the limit of detection can reach 0.329 pg/mL that is about 6 orders of magnitude lower than the limit defined protein residue (causing penicillin allergy). With the ultrasensitivity and specific selectivity, the proposed SERS immunoassay platform can precisely evaluate the content of P-protein in blood sample or penicillin drugs. It will be a potential tool to monitor allergic reaction to penicillin and better understand the mechanism of penicillin hypersensitivity.

Intrinsic Raman signal amplification for rapid identification and detection of methylglyoxal in manuka honey.

Methylglyoxal (MGO) is the primary material basis for the non-peroxide antibacterial activity (NPA) of manuka honey from New Zealand. Therefore, it is necessary to identify the quality or discriminate the grade of honey because no all manuka honeys on the market display the NPA. The current routine method employed for the detection of MGO involves high-performance liquid chromatography (HPLC) test. However, it requires long time (∼8 h) for sample derivatization. Herein, we report an intrinsic Raman signal amplification strategy for the rapid identification and detection of MGO by using silver-coated gold nanoparticles (Au@Ag NPs) along with a high selective surface-enhanced Raman scattering (SERS) probe 8-thioguanosine (8-TG). 8-TG is synthesized via the derivatization of 8-bromoguanosine (8-BG) with thiourea, and its Raman peak assignments were confirmed by computer simulation. The detection is performed through the Raman intensity ratio (I631/I700) variation of N2-(1-carboxyethyl)-thioguanosine (CETG) formed by the reaction between 8-TG and MGO on surface of Au@Ag NPs, where one CETG Raman intensity at 631 cm-1 increases while the other one at 700 cm-1 decreases oppositely. The opposite change not only yields an intrinsic Raman signal amplification, but also provides built-in correction. As a result, the proposed SERS method exhibits high sensitivity and accuracy. In addition, the whole analytical test is achieved within ∼20 min. The method can be used for the fast detection of MGO in manuka honey and discrimination of the honey grade.

A multimer-based SERS aptasensor for highly sensitive and homogeneous assay of carcinoembryonic antigens.

Carcinoembryonic antigens (CEAs) are known as one of the most common tumor markers. Their facile and affordable detection is critical for early diagnosis of malignant tumors, especially in resource-constrained settings. Here, we report a novel multimer-based surface-enhanced Raman scattering (SERS) aptasensor for a specific CEA assay. The aptasensor is fabricated through aptamer-assisted self-assembly of silver-coated gold nanoparticles (Au@Ag NPs), and the self-assembled multimeric structure possesses abundant hot-spots to provide high SERS response. When CEA is introduced, the specific recognition of CEA by aptamers will lead to the disassembly of Au@Ag multimers due to the lack of a bridging aptamer between Au@Ag NPs. As a result, the number of hot-spots in the multimeric system is decreased, and the intensity at 1585 cm-1 of the SERS reporter (4-mercaptobenzoic acid, 4-MBA) on the surface of NPs will also be decreased. The Raman intensity is proportional to the logarithm of the concentration of CEA. The detection sensitivity can be down to the pg mL-1 level. The analytical method only needs a droplet of 2 µL of sample, and the detection time is less than 20 min. The multimer-based SERS aptasensor can be applied in sensitive and inexpensive detection of CEA in serum samples.

Specific and visual assay of iodide ion in human urine via redox pretreatment using ratiometric fluorescent test paper printed with dimer DNA silver nanoclusters and carbon dots.

The fluorescence-based assay of iodide ion (I-) has been extensively studied by the use of different sensing probes and techniques, but it remains a tricky task to eliminate the interference of chloride ion (Cl-) for the analysis of low-level I- in complex genuine samples. Herein, we develop a redox pretreatment strategy for specific separating I- from human urine. Simultaneously, a novel ratiometric fluorescent probe is constructed by a simple mixing of dimer DNA silver nanoclusters (dDNA-AgNCs) and carbon dots (CDs) with the ratio of 5:1 in fluorescent intensity, and used for visual assay of I-. After addition of I-, the fluorescence of orange dDNA-AgNCs can be quenched by I- as the result of I--induced oxidative etching and aggregation of dDNA-AgNCs, while blue CDs as the stable internal standard are unresponsive to I-. With the increase of I-, the fluorescence intensity ratio (I577/I446) of binary-color probe gradually decreased, which leads to color variation from salmon pink to lighter salmon pink to lilac to light steel blue to final deep sky blue (under a UV lamp) with a sensitive detection limit of 19.8 nM. The assay for I- can also be convenient to implement for visual monitoring of I- by observing color change of test paper printed with the ratiometric probe, responding to 50 nM that is about 1 order of magnitude lower than the median urinary I- concentration defined by the World Health Organization (WHO) for school-age children. The sensitive test paper can provide an advanced platform for colorimetric and visual monitoring of I- in human urine.

Fluorescent turn-on assay of C-type natriuretic peptide using a molecularly imprinted ratiometric fluorescent probe with high selectivity and sensitivity.

A novel molecularly imprinted ratiometric fluorescent probe was fabricated by simple sol-gel polymerization for selective and sensitive assay of C-type natriuretic peptide (CNP) in biosamples. Both the nitrobenzoxadiazole (NBD) and carbon dots (CDs) were located on the surface of silica, used as the detection signal and reference signal, respectively. For the turn-on-based probe, the fluorescence intensity of NBD could be quantitatively enhanced by CNP based on the strategy of photo-induced electron transfer (PET), while the fluorescence of CDs remained unchanged. The obtained probe exhibited excellent recognition selectivity and fast kinetics to CNP templates, and also showed good stability. The linear range of CNP determination was 5-80 pg mL-1 with a low detection limit of 2.87 pg mL-1. Finally, the probe was successfully applied to determine CNP in human serum samples and attained high recoveries between 97.3 and 104% with precisions below 4.7%. The result indicates that the proposed method has promising potential for the assay of trace peptides in complex matrices. Schematic illustration for the formation and determination mechanism of the probe.

Base amount-dependent fluorescence enhancement for the assay of vascular endothelial growth factor 165 in human serum using hairpin DNA-silver nanoclusters and oxidized carbon nanoparticles.

A base amount-dependent fluorescence enhancement-based strategy is put forward to determine vascular endothelial growth factor 165 (VEGF165) in human serum by the use of hairpin DNA-silver nanoclusters (hDNA-AgNCs) and oxidized carbon nanoparticles (CNPs). The hDNA-AgNCs aptasensing probe consists of AgNCs-contained hairpin loop (that generates a fluorescence signal), hairpin stem (that makes the structure stable), and the terminal aptamer 1 (that recognizes the target together with aptamer 2). It has been demonstrated that the fluorescence intensity of hDNA-AgNCs is ~ 3-fold stronger than that of single-stranded DNA-AgNCs (ssDNA-AgNCs), and hDNA-AgNCs have a strong dependence of fluorescence enhancement on the base amount in hairpin stem and loop. Upon the addition of oxidized CNPs, the terminal aptamer 1 of hDNA-AgNCs can adsorb onto the surface of oxidized CNPs via π-π stacking, and the fluorescence of hDNA-AgNCs (with excitation/emission maxima at 490/567 nm) is quenched via fluorescence resonance energy transfer (FRET). When aptamer 2 and VEGF165 are subsequently added, aptamer 1, VEGF165, and aptamer 2 reassemble into an intact tertiary structure, and the fluorescence is recovered because hDNA-AgNCs are far away from the surface of oxidized CNPs and the FRET efficiency decreases. Under the optimized conditions, the aptasensing probe can selectively assay VEGF165 with a detection limit of 14 pM. The results provide a label-free and sensitive method to monitor VEGF165 in human serum. Schematic representation of the strong dependence of fluorescence enhancement on base amount in stem and loop of hairpin DNA-silver nanoclusters. The probe can be used to assay vascular endothelial growth factor 165 (VEGF165) and give a judgment whether human serum VEGF165 is at a normal or abnormal level for clinical diagnosis.

Metformin promotes the osseointegration of titanium implants under osteoporotic conditions by regulating BMSCs autophagy, and osteogenic differentiation.

Osteoporosis is a common bone disorder with adverse effects on oral osseointegration, and the effects of metformin on bone metabolism have received increasing attention. The aim of the present study was to test the hypothesis that metformin promoted osteogenesis of bone mesenchymal stem cells (BMSCs) and osseointegration of titanium implants. BMSCs were treated with metformin to assess autophagic capacity, reactive oxygen species (ROS) production, anti-aging ability, and osteogenic differentiation. To determine its potential application in peri-implant of the maxilla, metformin was injected around the implant each day, immediately after the implant was embedded into the tooth socket. The results showed that metformin increased the autophagic capacity and decreased ROS production of osteoporotic BMSCs under hypoxia and serum deprivation (H/SD) culturing conditions. Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP). Moreover, metformin substantially accelerated the formation of new bone, ameliorated the bone microarchitecture and promoted osseointegration of the dental implant. Collectively, metformin induces an osteogenic effect around the implant. Considering the widespread use of metformin, the results of the present study might promote a novel understanding of the positive effects of local metformin delivery on alveolar ridge defect, and have potential clinical application for the acceleration of osseointegration.

Salt-induced gold nanoparticles aggregation lights up fluorescence of DNA-silver nanoclusters to monitor dual cancer markers carcinoembryonic antigen and carbohydrate antigen 125.

In clinical diagnosis of cancer, the monitoring of single tumor marker may result in many false and missed results, while simultaneous detection of multiple tumor markers should be more accuracy and effective. Here, we report a new strategy that salt-induced gold nanoparticles (AuNPs) aggregation lights up fluorescence of dual-color DNA-silver nanoclusters-aptamer (DNA-AgNCs-apta) for the simultaneous monitoring of carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125). The dual-color aptasensor system is composed of green-emitting DNA-AgNCs with CEA aptamer (gDNA1-AgNCs-apta1) and red-emitting DNA-AgNCs with CA125 aptamer (rDNA2-AgNCs-apta2) in the ratio of 1:1 in volume. Upon addition of AuNPs, gDNA1-AgNCs-apta1 and/or rDNA2-AgNCs-apta2 are flexibly adsorbed onto the surface of AuNPs by terminal aptamer(s), which prevents salt-induced AuNPs aggregation under high salt condition and results in fluorescence quenching based on surface plasmon enhanced energy transfer (SPEET). With the addition of CEA and/or CA125, the target(s) and corresponding aptamer(s) coordinate to form the complex, keeping DNA-AgNCs-apta(s) far away from the surface of AuNPs and making AuNPs aggregated in high salt medium. The AuNPs aggregation leads to the recovery of fluorescence signals of DNA-AgNCs-apta(s) due to weakened SPEET. Utilizing the fluorescence aptasensor system, the limit of detection of CEA and CA125 are as low as 7.5 pg·mL-1 and 0.015 U·mL-1, respectively. The proposed method can be applied to the selective and simultaneous determination of CEA and CA125 in human serum.

Ratiometric fluorescent test pen filled with a mixing ink of carbon dots and CdTe quantum dots for portable assay of silver ion on paper.

A ratiometric fluorescent test pen filled with a mixing ink of blue carbon dots (CDs) and red CdTe quantum dots (CdTe QDs) is introduced for portable assay of silver ion (Ag(I)) on paper. The mixing ink was tuned with ratiometric fluorescent intensity of 1:5, and then filled into a vacant commercial fluorescent pen core. Writing/painting a random word/figure on a blank paper can make the most portable nanoprobe determining Ag(I) by visualization. Ag(I) can adsorb onto the surface of CdTe QDs, which leads to the formation of surficial Ag2Te layer by an ion-exchanging reaction. This enables the red fluorescence of CdTe QDs (with excitation/emission maxima at 360/628 nm) to be quenched. Due to the unchanged blue fluorescence of CDs (with excitation/emission maxima at 360/440 nm) as internal standard, the solution color evolves gradually from red to blue with the increase of Ag(I) concentration with a detection limit of 3.48 nM. This is at least 2 orders of magnitude lower than the limit defined by World Health Organization (WHO) in drinkable water. The fluorescent test pen has also been used for the determination of Ag(I) in wastewater. Graphical abstract Ag(I) can adsorb on the surface of CdTe QDs to quench their fluorescence, while the fluorescent intensity of CDs keep constant, accompanying color change with the increase of Ag(I) concentration. The method offers a visual assay of Ag(I) in water.

A chemometric modeling-free near infrared barcode strategy for smart authentication and geographical origin discrimination of Chinese ginseng.

With the growing interest in alternative medicine, handy identification and differentiation of herbal medicines are becoming increasingly important. Here we report a chemometric modeling-free near infrared (NIR) barcode strategy for the smart identification and geographical origin discrimination of Chinese ginseng. The novel strategy demands the transformation of Chinese ginseng (standard and sample) NIR spectra into a barcode representation through assigning zero intensity to every NIR peak except the peaks having intensities greater than average peak intensity. Meanwhile, for Chinese ginseng standard NIR barcode, barcoding condition such as padding size was carefully optimized. It has been demonstrated that the padding size for each bar in the barcode is 8 cm-1. By comparing the percentage of nonzero overlap between Chinese ginseng standard barcode and sample barcodes, eight batches of samples (including Chinese ginseng, American ginseng and counterfeit) were successfully identified with 100% accuracy, respectively. Interestingly, the discrimination of the origin of ginsengs from three provinces (Jilin, Liaoning and Heilongjiang) of Northeastern China was achieved utilizing NIR barcode method. Two characteristic bars at 7750 and 8250 cm-1 were inspected in the ginseng sample from Jilin province, two specific bars at 6780 and 7015 cm-1 were displayed in the ginseng sample from Liaoning province and three distinct bars at 6560, 6910 and 7995 cm-1 were monitored in the ginseng sample from Heilongjiang province. The results indicate that the proposed method will be greatly expanded and applied as an inspecting platform for the on-site analysis and valid identification of Chinese ginseng in herbal markets by a handheld spectrometer or barcode scanner.

A split aptamer-labeled ratiometric fluorescent biosensor for specific detection of adenosine in human urine.

A dual-emission ratiometric fluorometric aptasensor is presented for highly specific detection of adenosine. An adenosine binding aptamer (ABA) was split into two halves (termed as ABA1 and ABA2). ABA1 was covalently bound to blue-emitting carbon dots (with excitation/emission maxima at 365/440 nm) as responsive fluorophore (referred to as ABA1-CDs). ABA2 was linked to red-emitting silica-coated CdTe quantum dots (with excitation/emission maxima at 365/613 nm) acting as internal reference and referred to as ABA2-QDs@SiO2. Upon addition of graphene oxide, the fluorescence of ABA1-CDs is quenched. After subsequent addition of ABA2-QDs@SiO2 and different amounts of adenosine, the blue fluorescence is recovered and causes a color change from red to royal blue. The method represents a ratiometric turn-on assay for visual, colorimetric and fluorometric determination of adenosine. The limit of detection is as low as 2.4 nM in case of ratiometric fluorometry. The method was successfully applied to the determination of adenosine in (spiked) human urine. Recoveries range from 98.8% to 102%. Graphical abstract Adenosine binding aptamer1-carbon dots (ABA1-CDs) can absorb on graphene oxide (GO) via π stacking. This causes fluorescence to be quenched by fluorescence resonance energy transfer (FRET). After addition of ABA2-silica-coated quantum dots (ABA2-QDs@SiO2) and adenosine, binding of adenosine to two pieces of aptamers forms a complex (ABA1-CD/adenosine/ABA2-QD@SiO2) which dissociates from GO. As a result, fluorescence is recovered.

Silver nanoparticles/activated carbon composite as a facile SERS substrate for highly sensitive detection of endogenous formaldehyde in human urine by catalytic reaction.

Most of efforts have been made to prepare high performance surface-enhanced Raman scattering (SERS) substrate for amplifying Raman signals. It still remains a grand challenging task in building a simple, conventional and low-cost SERS substrate with highly dense hotspots for improved sensitivity of the target analytes. Here, we report a very dexterous strategy to fabricate a distinctive SERS substrate with high density hotspots, using common adsorbent activated carbon (AC) as template to assemble silver nanoparticles (Ag NPs). It can be estimated that the enhancement effect of Ag NPs/AC composite is about 6.5-fold that of bare Ag NPs. Different from the resonant dyes, however, formaldehyde (FA) is a Raman-inactive molecule even though enhanced. Considering that, a novel method for quantitative analysis of FA using the Ag NPs/AC composite as SERS sensor has been developed, based on the catalytic effect of trace FA on the oxidation of malachite green (MG) through bromate under acidic condition. The change of MG from reduced form into oxidized leucomalachite green (LMG) results in the quench of Raman signals of MG, responding to 0.07 ppb FA that is about 2 orders of magnitude lower than the limit defined by the Nash's method as a standard procedure recommended in Europe, Japan and China. Moreover, SERS examinations of endogenous FA in human urine signify that the proposed method has high selectivity, reliability and accuracy. Thus, as-fabricated Ag NPs/AC composite is adequate as inexpensive and versatile SERS sensor utilized in the quantification of trace targets in various complicated matrices.

Colorimetric and visual detection of mercury(II) based on the suppression of the interaction of dithiothreitol with agar-stabilized silver-coated gold nanoparticles.

A colorimetric and visual method is described for the determination of mercury(II) ion. A gel consisting of agar-stabilized silver-coated gold nanoparticles (Au@Ag NPs) was prepared. The reaction with dithiothreitol (DTT) via thiol-Ag chemistry results in an orange to purple color change of the gel. However, in the presence of Hg(II), the reaction of DTT with the silver shells is suppressed due to the strong thiophilicity of Hg(II). The color of the gel changes from purple to red to orange in the presence of increasing concentrations of Hg(II). The Au@Ag NPs therefore are a viable optical probe for Hg(II) which can be detected in concentration as low as 78 nM via dual-wavelength ratiometric absorbance (A390/A520), and at 1 µM levels with bare eyes. The use of agar as a support is mandatory to prevent the aggregation of the NPs and also improves selectivity. The method was applied to the analysis of spiked samples, and recoveries ranged between 96.3 and 104%. The assay is easy, inexpensive, and in our perception represents an attractive tool for on-site visual detection of Hg(II). Graphical abstract Schematic of the assay. With increasing concentrations of Hg(II), the oxidative etching of silver shells caused by dithiothreitol (DTT) is gradually inhibited, and the color of agar-stabilized Au@Ag NP gel varies from purple to red, and finally to orange. This can be used for visual detection of Hg(II).

Toward rapid analysis, forecast and discovery of bioactive compounds from herbs by jointly using thin layer chromatography and ratiometric surface-enhanced Raman spectroscopy technique.

Conventional isolation and identification of active compounds from herbs have been extensively reported by using various chromatographic and spectroscopic techniques. However, how to quickly discover new bioactive ingredients from natural sources still remains a challenging task due to the interference of their similar structures or matrices. Here, we present a grand approach for rapid analysis, forecast and discovery of bioactive compounds from herbs based on a hyphenated strategy of thin layer chromatography and ratiometric surface-enhanced Raman spectroscopy. The performance of the hyphenated strategy is first evaluated by analyzing four protoberberine alkaloids, berberine (BER), coptisine (COP), palmatine (PAT) and jatrorrhizine (JAT), from a typical herb Coptidis Rhizoma as an example. It has been demonstrated that this coupling method can identify the four compounds by characteristic peaks at 728, 708, 736 and 732 cm-1, and especially discriminate BER and COP (with similar migration distances) by ratiometric Raman intensity (I708/I728). The corresponding limits of detection are 0.1, 0.05, 0.1 and 0.5 µM, respectively, which are about 1-2 orders of magnitude lower than those of direct observation method under 254 nm UV lamp. Based on these findings, the proposed method further guides forecast and discovery of unknown compounds from traditional Chinese herb Typhonii Rhizoma. Results infer that two trace alkaloids (BER and COP) from the n-butanol extract of Typhonii Rhizoma are found for the first time. Moreover, in vitro experiments manifest that BER can effectively decrease the viability of human glioma U87 cells by inducing cell cycle arrest in a concentration-dependent manner.

Profuse color-evolution-based fluorescent test paper sensor for rapid and visual monitoring of endogenous Cu2+ in human urine.

The fluorescent paper for colorimetric detection of metal ions has been widely fabricated using various sensing probes, but it still remains an elusive task to design a test paper with multicolor variation with target dosages for accurate determination. Herein, we report a profuse color-evolution-based fluorescent test paper sensor for rapid and visual monitoring of Cu2+ in human urine by printing tricolor probe onto filter paper. The tricolor probe consists of blue-emission carbon dots (bCDs), green-emission quantum dots (gQDs) and red-emission quantum dots (rQDs), which is based on the principle that the fluorescence of gQDs and rQDs are simultaneously quenched by Cu2+, whereas the bCDs as the photostable internal standard is insensitive to Cu2+. Upon the addition of different amounts of Cu2+, the ratiometric fluorescence intensity of the tricolor probe continuously varied, leading to color changes from shallow pink to blue with a detection limit of 1.3nM. When the tricolor probe solution was printed onto a sheet of filter paper, as-obtained test paper displayed a more profuse color evolution from shallow pink to light salmon to dark orange to olive drab to dark olive green to slate blue to royal blue and to final dark blue with the increase of Cu2+ concentration compared with dual-color probe-based test paper, and dosage scale as low as 6.0nM was clearly discriminated. The sensing test paper is simple, rapid and inexpensive, and serves as a visual platform for ultrasensitive monitoring of endogenous Cu2+ in human urine.

Ehrlich Reaction Evoked Multiple Spectral Resonances and Gold Nanoparticle Hotspots for Raman Detection of Plant Hormone.

Surface-enhanced Raman scattering (SERS) by use of noble metal nanoparticles has become a powerful tool to determine a low-concentration target by unique spectral fingerprints, but it is still limited to the Raman-inactive and nonresonant biomolecules such as amine acids, proteins, and hormones. Here, we report an Ehrlich reaction based derivative strategy in combination with gold nanoparticles (Au NPs) hotspots for the selective detection of indole-like plant hormones by SERS spectroscopy. Ehrlich reaction of p-(dimethylamino)benzaldehyde (PDAB) with the indole ring chemically transformed plant hormone indole-3-butyric acid (IBA) into a Raman-active and resonant derivative with an extended π-conjugated system in the form of a cation, which produced a new absorption band at 626 nm. On the other hand, cationic IBA-PDAB highly evoked the aggregation of Au NPs with negative citrate ligands to form the effective Raman hotspots and gave rise to the new absorption ranging from 600 to 800 nm. Significantly, the spectral overlap among IBA-PDAB, aggregated Au NPs, and the exciting laser initiated the multiple optical resonances to generate the ultrahigh Raman scattering with a sensitive limit of 2.0 nM IBA. The IBA in the whole sprouts and various parts of pea, mungbean, soybean, and black bean has been identified and quantified. The reported method opens a novel avenue for the SERS detection of Raman-inactive analyte by a proper derivation.

Neuroprotective Activity of Cerebrosides from Typhonium giganteum by Regulating Caspase-3 and Bax/Bcl-2 Signaling Pathways in PC12 Cells.

An investigation of the potential neuroprotective natural product constituents of the rhizomes of Typhonium giganteum led to the isolation of two new cerebrosides, typhonosides E (1) and F (2), along with 11 known analogues (3-13). The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. The activity of these compounds against glutamate-induced cell apoptosis was investigated in PC12 cells. All compounds exhibited such activity, which was related to the length of the fatty acyl chain. Among them, longan cerebroside II (11), with the longest fatty acyl chain, showed the most potent protective effect in PC12 cells from glutamate injury, with an EC50 value of 2.5 µM. Moreover, at the molecular level, longan cerebroside II (11) downregulated the expression of caspase-9, caspase-3, and Bax, upregulated the expression of Bcl-2, and decreased the level of cytosolic cytochrome c in a concentration-dependent manner.