Analyzing urinary hippuric acid as a metabolic health biomarker through a supramolecular architecture.

The prevalence of metabolic disorders has been found to increase concomitantly with alternations in habitual diet and lifestyle, indicating the importance of metabolic health monitoring for early warning of high-risk status and suggesting effective intervention strategies. Hippuric acid (HA), as one of the most abundant metabolites from the gut microbiota, holds potential as a regulator of metabolic health. Accordingly, it is imperative to establish an efficient, sensitive, and affordable method for large-scale population monitoring, revealing the association between HA level and metabolic disorders. Upon systematic screening of macrocycle•dye reporter pair, a supramolecular architecture (guanidinomethyl-modified calix[5]arene, GMC5A) was employed to sense urinary HA by employing fluorescein (Fl), whose complexation behavior was demonstrated by theoretical calculations, accomplishing quantification of HA in urine from 249 volunteers in the range of 0.10 mM and 10.93 mM. Excitedly, by restricted cubic spline, urinary HA concentration was found to have a significantly negative correlation with the risk of metabolic disorders when it exceeded 0.76 mM, suggesting the importance of dietary habits, especially the consumption of fruits, coffee, and tea, which was unveiled from a simple questionnaire survey. In this study, we accomplished a high throughput and sensitive detection of urinary HA based on supramolecular sensing with the GMC5A•Fl reporter pair, which sheds light on the rapid quantification of urinary HA as an indicator of metabolic health status and early intervention by balancing the daily diet.

Progress in research on health literate schools / 中国学校卫生

Abstract@#Health literate schools (HeLit-Schools) play a significant role in fostering students health literacy. The paper elucidates the background and conceptual connotations of HeLit-Schools, and analyzes how HeLit-Schools effectively integrate and enhance the health literacy of schools in three aspects: philosophy and core drivers, strategy and method implementation, as well as evaluation mechanisms and standard setting. Furthermore, the paper explores the implications of foreign HeLit-Schools research and practice for China under the context of "Healthy China" construction, as well as the key strategies for Chinese schools in the implementation of HeLit-Schools, aiming to provide a new perspective and theoretical support for Chinese schools to practice the "Healthy China initiative" and strengthen school construction from the perspective of health literacy.

Guest adaptative supramolecular sensing strategy for warning the risky aflatoxins in contaminated cereals.

In the face of diversified analytes, it is a great challenge and infeasible task to design and synthesize corresponding macrocyclic hosts to realize the ideal supramolecular sensing. Herein, we proposed a novel supramolecular sensing strategy, guest adaptative assay (GAA), in which analyte was quantitatively transformed under mild conditions to perfectly adapt to macrocyclic host. As a health-threatening "landmine" in cereals, aflatoxins were converted by the aid of alkali hydrolysis to satisfactorily obtain aflatoxins transformants in ionic state, resulting in sensitive response by the guanidinocalix[5]arene•fluorescein reporter pair. Surprisingly, the established strategy not only exhibited effective practicality in screening out high-risk cereals contaminated with aflatoxins, but also relieved the laborious task of macrocycle design and screening in supramolecular sensing.

Coordination-induced self-assembly based carbon dot dendrimers as efficient signal labels for electrochemiluminescent immunosensor construction.

In this work, an "on-off" electrochemiluminescent immunosensor for bone alkaline phosphatase (BALP) detection was constructed based on the carbon dot dendrimers (CD DRs) as signal labels and Pt nanoparticles functionalized Ni-phenolic coordination spheres (Pt@Ni-PCS) as quenching labels. The prepared CD DRs with low cytotoxicity were synthesized via coordination-induced self-assembly of carboxyl groups-rich N-doped carbon dots and zirconium oxygen clusters, of which the ECL efficiency was 2-fold enhancement than that of discrete N-doped carbon dots. Benefiting from the efficient quenching effect of Pt@Ni-PCS toward Zr-CD DRs/triethylamine-based ECL system, the prepared immunoassay for BALP detection exhibited a broad linear range with 1 pg/mL to 50 ng/mL and a low limit of detection of 24.9 fg/mL. Importantly, this highlights coordination-induced self-assembly as a tool for carbon dots enrichment to construct efficient ECL nanocomposites, which conceptualizes a pathway to expand the application of carbon dots in clinical ECL analysis technology.

Self-Stirring Microcatalysts: Large-Scale, High-Throughput, and Controllable Preparation and Application.

Herein, we introduce a strategy to develop a kind of unprecedented microcatalyst, which owns self-stirring and catalytic performance based on pneumatic printing and magnetic field induction technology. A spindle-shaped microcatalyst based on metal-organic frameworks (MOFs) with a certain aspect ratio and size can be obtained by tuning the printing parameters and the intensity of the magnetic field. One nozzle can print 18 000 microcatalysts per hour, which provides a prerequisite for the realization of large-scale production in the industrial field. Furthermore, this strategy can be widely applied to a variety of other heterogeneous catalysts, such as mesoporous SiO2, zeolite, metallic oxide, and so on. To demonstrate the superiority of the printed catalyst, the series of printed microcatalysts were evaluated by various catalytic reactions including liquid-phase hydrogenation, microdroplet dye-fading, and photocatalytic degradation in microreactor, all of which exhibited excellent catalytic performance.

Hierarchical self-uncloaking CRISPR-Cas13a-customized RNA nanococoons for spatial-controlled genome editing and precise cancer therapy.

CRISPR-Cas13a holds enormous potential for developing precise RNA editing. However, spatial manipulation of CRISPR-Cas13a activity remains a daunting challenge for elaborately regulating localized RNase function. Here, we designed hierarchical self-uncloaking CRISPR-Cas13a-customized RNA nanococoons (RNCOs-D), featuring tumor-specific recognition and spatial-controlled activation of Cas13a, for precise cancer synergistic therapy. RNCOs-D consists of programmable RNA nanosponges (RNSs) capable of targeted delivery and caging chemotherapeutic drug, and nanocapsules (NCs) anchored on RNSs for cloaking Cas13a/crRNA ribonucleoprotein (Cas13a RNP) activity. The acidic endo/lysosomal microenvironment stimulates the outer decomposition of NCs with concomitant Cas13a RNP activity revitalization, while the inner disassembly through trans-cleavage of RNSs initiated by cis-recognition and cleavage of EGFR variant III (EGFRvIII) mRNA. RNCOs-D demonstrates the effective EGFRvIII mRNA silencing for synergistic therapy of glioblastoma cancer cells in vitro and in vivo. The engineering of RNSs, together with efficient Cas13a activity regulation, holds immense prospect for multimodal and synergistic cancer therapy.

CeO2/MXene heterojunction-based ultrasensitive electrochemiluminescence biosensing for BCR-ABL fusion gene detection combined with dual-toehold strand displacement reaction for signal amplification.

An "on-off" nonenzymatic and ultrasensitive electrochemiluminescence (ECL) biosensing platform has been constructed to detect BCR-ABL fusion gene based on CeO2/MXene heterojunction and configuration-entropy driven dual-toehold strand displacement reaction (DT-SDR) for signal amplification. The CeO2/MXene heterojunction were prepared via one-step hydrothermal method through in situ synthesis of CeO2 nanocubes on the surface of Ti3C2-MXene nanosheets. Surprisingly, the prepared CeO2/MXene heterojunction with good dispersion and excellent conductivity not only significantly enhanced ECL emission of S2O82-/O2 system, but also acted as good electrode modification materials to provide massive active sites for three-stranded ST/AS/BK complex immobilization. In the presence of target BCR-ABL fusion gene and Bio-FS, target BCR-ABL fusion gene bound to dual-toehold exposed at the ends of ST, replacing AS and BK and obtaining ST/target with a loop. Subsequently, Bio-FS bound to the loop (as toehold) in ST strand of ST/target to form ST/Bio-FS, replacing the target to further trigger a new SDA cycle. This configuration-entropy driven DT-SDR made three-stranded ST/AS/BK complex transform into dual-stranded ST/Bio-FS in the electrode interface. Ultimately, the quenching labels of streptavidin modified Pt nanoparticles functionalized polydopamine composites (SA-Pt@PDA) were introduced via biotin and streptavidin recognition, realizing ECL emission quenching of S2O82-/O2 system for "on-off" detection of BCR-ABL fusion gene. The developed ECL biosensor for BCR-ABL fusion gene detection achieves the wide concentration variation from 1 fM to 100 pM with low limit of detection down to 0.27 fM, which provides new enlightenment and basis for molecular diagnosis of chronic myelogenous leukemia in clinical practice.

Dispersion-to-localization of catalytic hairpin assembly for sensitive sensing and imaging microRNAs in living cells from whole blood.

Localized DNA circuits have shown good performance regarding reaction rate and sensitivity for sensing intracellular microRNAs (miRNAs). However, these methods reported recently require large kinds of DNA strands and suffer from low signal-to-background (S/B) ratio, which hinder their clinical application. To circumvent these issues, we herein developed a novel strategy for sensitive sensing and imaging miRNAs in living cells based on dispersion-to-localization of catalytic hairpin assembly (DL-CHA). This strategy consists of only three classes of DNA strands (two hairpins and a linker strand), which largely reduces sequence design complexity. Additionally, owing to the unique engineering of the substrate transformation from dispersion to localization, the DL-CHA exhibits not only minimal background leakage but also intensive signal amplification, thus significantly improving the S/B ratio. In particular, the simple sensing method is capable of imaging miRNAs in cells from clinical blood samples for the diagnosis of breast cancer. Therefore, this work provides a powerful tool for intracellular molecules detection and gives a much broader design space for constructing high-performance DNA circuits.

Surface plasmon resonance biosensor for exosome detection based on reformative tyramine signal amplification activated by molecular aptamer beacon.

Human epidermal growth factor receptor 2 (HER2)-positive exosomes play an extremely important role in the diagnosis and treatment options of breast cancers. Herein, based on the reformative tyramine signal amplification (TSA) enabled by molecular aptamer beacon (MAB) conversion, a label-free surface plasmon resonance (SPR) biosensor was proposed for highly sensitive and specific detection of HER2-positive exosomes. The exosomes were captured by the HER2 aptamer region of MAB immobilized on the chip surface, which enabled the exposure of the G-quadruplex DNA (G4 DNA) that could form peroxidase-like G4-hemin. In turn, the formed G4-hemin catalyzed the deposition of plentiful tyramine-coated gold nanoparticles (AuNPs-Ty) on the exosome membrane with the help of H2O2, generating a significantly enhanced SPR signal. In the reformative TSA system, the horseradish peroxidase (HRP) as a major component was replaced with nonenzymic G4-hemin, bypassing the defects of natural enzymes. Moreover, the dual-recognition of the surface proteins and lipid membrane of the desired exosomes endowed the sensing strategy with high specificity without the interruption of free proteins. As a result, this developed SPR biosensor exhibited a wide linear range from 1.0 × 104 to 1.0 × 107 particles/mL. Importantly, this strategy was able to accurately distinguish HER2-positive breast cancer patients from healthy individuals, exhibiting great potential clinical application.

Efficient DNA Walker Guided with Well-Regulated Interfacial Tracks for Ultrasensitive Electrochemiluminescence Biosensing.

Herein, highly efficient deoxyribonucleic acid (DNA) walking on electrode surfaces was realized by regulating DNA tracks, which was applied to construct an ultrasensitive electrochemiluminescent (ECL) biosensor for BCR/ABL fusion gene detection. The well-regulated DNA tracks were constructed via supersandwich hybridization chain reaction of two DNA strands (L1 and L2) to generate periodic linear dsDNA concatemers, where an exposed L1 domain closed with blocking strands (BS). The prepared DNA tracks were further assembled onto the surface of the Au nanoparticle-functionalized g-C3N4 nanohybrid (Au@g-C3N4 NHs)-modified electrode, achieving well-regulated interfacial tracks for the DNA walker. On this state, folic acid-labeled BS (FA-BS) were close to Au@g-C3N4 NHs, performing a quenched ECL emission. With existence of the BCR/ABL fusion gene, the target combined two walking DNA strands (WD1 and WD2) to form the bipedal DNA walkers, which walked on the well-regulated interfacial DNA tracks and replaced the FA-BS to light up the ECL emission, realizing DNA walker-based signal amplification. Compared to randomly constructed DNA tracks, the well-regulated DNA tracks reduced the kinetics barrier and fitted the step size of the DNA walker, thus promoting the DNA walking efficiency and decreasing the risk of interruption in the walking process. As a result, the designed DNA walker presented higher efficiency and capacity in signal amplification. Benefiting from this efficient DNA walker strategy, the ECL biosensor achieved sensitive detection of the BCR/ABL fusion gene with a detection limit of 0.18 fM. This smart strategy proposed a brief strategy to promote the working efficiency of the biosensor, which presented great application potential in clinical molecular diagnosis.