Self-Limiting Assembly of Two-Dimensional Domains from Graphene Oxide at the Air/Water Interface

Self-assembly is a powerful approach to making new superstructures and high-level hierarchical structures with unique physical/chemical properties from nanosized building blocks. As-prepared graphene oxides (GOs) are in general highly polydisperse not only in size but also in shape. Yet we have demonstrated that such GO sheets tend to assemble into two-dimensional, nearly monodisperse aggregate domains at the air/water interface in a self-limiting fashion, which can be controlled. It was further shown that the self-limiting assembly was driven by the competing interactions between electrostatic repulsion between the negatively charged GO sheets and attractive potentials. This finding provides a convenient platform to understand the forces involved in the 2D assembly and opens a new direction for creating novel materials and structures at the air/water interface

DataSheet_1_BOS1 is a basic helix–loop–helix transcription factor involved in regulating panicle development in rice.pdf

Panicle development is crucial to increase the grain yield of rice (Oryza sativa). The molecular mechanisms of the control of panicle development in rice remain unclear. In this study, we identified a mutant with abnormal panicles, termed branch one seed 1-1 (bos1-1). The bos1-1 mutant showed pleiotropic defects in panicle development, such as the abortion of lateral spikelets and the decreased number of primary panicle branches and secondary panicle branches. A combined map-based cloning and MutMap approach was used to clone BOS1 gene. The bos1-1 mutation was located in chromosome 1. A T-to-A mutation in BOS1 was identified, which changed the codon from TAC to AAC, resulting in the amino acid change from tyrosine to asparagine. BOS1 gene encoded a grass-specific basic helix–loop–helix transcription factor, which is a novel allele of the previously cloned LAX PANICLE 1 (LAX1) gene. Spatial and temporal expression profile analyses showed that BOS1 was expressed in young panicles and was induced by phytohormones. BOS1 protein was mainly localized in the nucleus. The expression of panicle development-related genes, such as OsPIN2, OsPIN3, APO1, and FZP, was changed by bos1-1 mutation, suggesting that the genes may be the direct or indirect targets of BOS1 to regulate panicle development. The analysis of BOS1 genomic variation, haplotype, and haplotype network showed that BOS1 gene had several genomic variations and haplotypes. These results laid the foundation for us to further dissect the functions of BOS1.</p

Improving the Signal-to-Background Ratio during Catalytic Hairpin Assembly through Both-End-Blocked DNAzyme

Catalyzed hairpin assembly (CHA) is an important DNA engineering tool for a variety of applications such as DNA nanotechnology and biosensing. Here we report a hairpin-type of both-end-blocked DNAzyme to improve the signal-to-background ratio during the CHA process. In the design, the DNAzyme activity can be blocked efficiently via locking both ends of the G-rich DNAzyme sequence in the loop and stem (blocking efficiency = 96%) and can be easily recovered during the CHA process (activation efficiency = 94%). The both-end-blocked DNAzyme is by far the most sensitive optical detection mode for monitoring the CHA process that can be used for determination of 0.05 fmol miRNA-21. The fabricated CHA-DNAzyme sensing system was also able to discriminate miRNA-21 from single-/three-base mismatch miRNA-21. The feasibility of real application was also tested via detection of miRNA-21 levels in tumor cell samples. Therefore, the sensing system with the advantages of convenience, high sensitivity, and selectivity is an appealing strategy for miRNA detection

Ratiometric Phosphorescent Probe for Thallium in Serum, Water, and Soil Samples Based on Long-Lived, Spectrally Resolved, Mn-Doped ZnSe Quantum Dots and Carbon Dots

Thallium (Tl) is an extremely toxic heavy metal and exists in very low concentrations in the environment, but its sensing is largely underexplored as compared to its neighboring elements in the periodic table (especially mercury and lead). In this work, we developed a ratiometric phosphorescent nanoprobe for thallium detection based on Mn-doped ZnSe quantum dots (QDs) and water-soluble carbon dots (C-dots). Upon excitation with 360 nm, Mn-doped ZnSe QDs and C-dots can emit long-lived and spectrally resolved phosphorescence at 580 and 440 nm, respectively. In the presence of thallium, the phosphorescence emission from Mn-doped ZnSe QDs could be selectively quenched, while that from C-dots retained unchanged. Therefore, a ratiometric phosphorescent probe was thus developed, which can eliminate the potential influence from both background fluorescence and other analyte-independent external environment factors. Several other heavy metal ions caused interferences to thallium detection but could be efficiently masked with EDTA. The proposed method offered a detection limit of 1 μg/L, which is among the most sensitive probes ever reported. Successful application of this method for thallium detection in biological serum as well as in environmental water and soil samples was demonstrated

Label-Free and Separation-Free Atomic Fluorescence Spectrometry-Based Bioassay: Sensitive Determination of Single-Strand DNA, Protein, and Double-Strand DNA

Based on selective and sensitive determination of Hg²⁺ released from mercury complex by cold vapor generation (CVG) atomic fluorescence spectrometry (AFS) using SnCl₂ as a reductant, a novel label-free and separation-free strategy was proposed for DNA and protein bioassay. To construct the DNA bioassay platform, an Hg²⁺-mediated molecular beacon (hairpin) without labeling but possessing several thymine (T) bases at both ends was employed as the probe. It is well-known that Hg²⁺ could trigger the formation of the hairpin structure through T–Hg²⁺–T connection. In the presence of a specific target, the hairpin structure could be broken and the captured Hg²⁺ was released. Interestingly, it was found that SnCl₂ could selectively reduce only free Hg²⁺ to Hg⁰ vapor in the presence of T–Hg²⁺–T complex, which could be separated from sample matrices for sensitive AFS detection. Three different types of analyte, namely, single-strand DNA (ssDNA), protein, and double-strand DNA (dsDNA), were investigated as the target analytes. Under the optimized conditions, this bioassay provided high sensitivity for ssDNA, protein, and dsDNA determination with the limits of detection as low as 0.2, 0.08, and 0.3 nM and the linear dynamic ranges of 10–150, 5–175, and 1–250 nM, respectively. The analytical performance for these analytes compares favorably with those by previously reported methods, demonstrating the potential usefulness and versatility of this new AFS-based bioassay. Moreover, the bioassay retains advantages of simplicity, cost-effectiveness, and sensitivity compared to most of the conventional methods

In Situ Generation and Consumption of H₂O₂ by Bienzyme–Quantum Dots Bioconjugates for Improved Chemiluminescence Resonance Energy Transfer

Exploration of quantum dots (QDs) as energy acceptors revolutionizes the current chemiluminescence resonance energy transfer (CRET), since QDs possess large Stokes shifts and high luminescence efficiency. However, the strong and high concentration of oxidant (typically H₂O₂) needed for luminol chemiluminescence (CL) reaction could cause oxidative quenching to QDs, thereby decreasing the CRET performance. Here we proposed the use of bienzyme–QDs bioconjugate as the energy acceptor for improved CRET sensing. Two enzymes, one for H₂O₂ generation (oxidase) and another for H₂O₂ consumption (horseradish peroxidase, HRP), were bioconjugated onto the surface of QDs. The bienzyme allowed fast in situ cascaded H₂O₂ generation and consumption, thus alleviating fluorescence quenching of QDs. The nanosized QDs accommodate the two enzymes in a nanometric range, and the CL reaction was confined on the surface of QDs accordingly, thereby amplifying the CL reaction rate and improving CRET efficiency. As a result, CRET efficiency of 30–38% was obtained; the highest CRET efficiency by far was obtained using QDs as the energy acceptor. The proposed CRET system could be explored for ultrasensitive sensing of various oxidase substrates (here exemplified with cholesterol, glucose, and benzylamine), allowing for quantitative measurement of a spectrum of metabolites with high sensitivity and specificity. Limits of detection (LOD, 3σ) for cholesterol, glucose, and benzylamine were found to be 0.8, 3.4, and 10 nM, respectively. Furthermore, multiparametric blood analysis (glucose and cholesterol) is demonstrated

Image1_TKI or TKI combined with PD-1 inhibitors as second-line treatment for HCC patients after sorafenib failure.jpeg

Background: Tyrosine kinase inhibitors (TKI) in combination with programmed cell death-1 (PD-1) inhibitors become the potential treatment modality for patients undergoing unresectable hepatocellular carcinoma (uHCC) in the first-line setting. However, the efficacy and safety of this combination regimen in patients after sorafenib failure remains unclear.Methods: Participants in this study included patients with uHCC after sorafenib failure who received TKI monotherapy (TKI group) or TKI combined with PD-1 inhibitors therapy (combination group) in our center from July 2018 to July 2021. The overall survival (OS) was used to be the primary efficacy endpoint, while progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were applied to be secondary endpoints. In addition, the adverse events are recorded and evaluated.Results: Among the 92 patients contained in this work, 50 patients were categorized into the TKI group, while 42 patients were in the combination group. There existed no evident differences between the two groups concerning the ORR (8.0% vs. 9.5%, p = 1.000). However, the DCR in the combined group was better in relative to that in the TKI group (71.4% vs. 50.0%, p = 0.037). In comparison with the TKI group, it was found that the combination group presented notably better median PFS (8.1 months vs. 4.7 months, p = 0.005) and median OS (21.9 months vs. 16.6 months, p = 0.042). According to multivariate analysis, PFS (HR 0.5, 95% CI: 0.3–0.8, p = 0.005) and OS (HR 0.5, 95% CI: 0.3–1.0, p = 0.051) were improved in the combination group in relative to the TKI group after the adjustment for some risk factors. Additionally, the incidence rates of grade ≥1 adverse event in the TKI group and the combination group were 96.0% and 97.6%, respectively. The most normal adverse event in the TKI group was neutropenia (n = 24,48.0%) and the combination group was hypoalbuminemia (n = 23,54.8%). All of these adverse events improved after symptomatic treatment, and no new toxic events were found to occur.Conclusion: TKI combined with PD-1 inhibitors showed better prognosis with manageable toxicity in uHCC patients after sorafenib failure compared with TKI monotherapy.</p

Presentation1_Taurohyocholic acid acts as a potential predictor of the efficacy of tyrosine kinase inhibitors combined with programmed cell death-1 inhibitors in hepatocellular carcinoma.PDF

Background and aims: Tyrosine kinase inhibitors (TKIs) combined with programmed cell death protein-1 (PD-1) have significantly improved survival in patients with unresectable hepatocellular carcinoma (uHCC), but effective biomarkers to predict treatment efficacy are lacking. Peripheral blood bile acids (BAs) are associated with tumor response to therapy, but their roles in HCC remain unclear.Methods: This retrospective study included HCC patients who received first-line TKIs combined with PD-1 inhibitors treatment (combination therapy) in our clinical center from November 2020 to June 2022. The aim of this study was to analyze the changes in plasma BA profiles before and after treatment in both the responding group (Res group) and the non-responding group (Non-Res group). We aimed to explore the potential role of BAs in predicting the response to combination therapy in HCC patients.Results: Fifty-six patients with HCC who underwent combination therapy were included in this study, with 28 designated as responders (Res group) and 28 as non-responders (Non-Res group). There were differences in plasma BA concentrations between the two groups before systemic therapy. Plasma taurohyocholic acid (THCA) levels in the Res group were significantly lower than those in the Non-Res group. Patients with low levels of THCA exhibited superior median progression-free survival (7.6 vs. 4.9 months, p = 0.027) and median overall survival (23.7 vs. 11.6 months, p = 0.006) compared to those of patients with high levels of THCA.Conclusion: Peripheral blood BA metabolism is significantly correlated with combination therapy response and survival in patients with HCC. Our findings emphasize the potential of plasma BAs as biomarkers for predicting combination therapy outcomes and offering novel therapeutic targets for modulating responses to systemic cancer therapy.</p