Mimicking an Enzyme-Based Colorimetric Aptasensor for Antibiotic Residue Detection in Milk Combining Magnetic Loop-DNA Probes and CHA-Assisted Target Recycling Amplification

A mimicking-enzyme-based colorimetric aptasensor was developed for the detection of kanamycin (KANA) in milk using magnetic loop-DNA-NMOF-Pt (m-L-DNA) probes and catalytic hairpin assembly (CHA)-assisted target recycling for signal amplification. The m-L-DNA probes were constructed via hybridization of hairpin DNA H1 (containing aptamer sequence) immobilized magnetic beads (m-H1) and signal DNA (sDNA, partial hybridization with H1) labeled nano Fe-MIL-88NH₂-Pt (NMOF-Pt-sDNA). In the presence of KANA and complementary hairpin DNA H2, the m-L-DNA probes decomposed and formed an m-H1/KANA intermediate, which triggered the CHA reaction to form a stable duplex strand (m-H1-H2) while releasing KANA again for recycling. Consequently, numerous NMOF-Pt-sDNA as mimicking enzymes can synergistically catalyze 3,3′,5,5′-tetramethylbenzidine (TMB) for color development. The aptasensor exhibited high selectivity and sensitivity for KANA in milk with a detection limit of 0.2 pg mL^–1 within 30 min. The assay can be conveniently extended for on-site screening of other antibiotics in foods by simply changing the base sequence of the probes

Tensor Factorization with Sparse and Graph Regularization for Fake News Detection on Social Networks

Social media has a significant influence, which greatly facilitates people to stay up-to-date with information. Unfortunately, a great deal of fake news on social media misleads people and causes a lot of losses. Therefore, fake news detection is necessary to address this issue. Recently, social content category-based methods have become a crucial component of fake news detection. Different from news context-based category, which focuses on word embedding, it tends to explore the potential relationships and structures between users and news. In this article, a third-order tensor, which obtains massive information and connections, is constructed by the social links and engagements of social networks. Then, a sparse and graph-regularized CANDECOMP/PARAFAC (SGCP) tensor decomposition learning method is proposed for fake news detection on social network. In SGCP, a news factor matrix is constructed by CP decomposition of the tensor, which reflects the complex connections among users and news. Furthermore, SGCP retains sparsity of the news factor matrix and preserves the manifold structures from the original space. In addition, an efficient optimization algorithm, which is proven to be monotonically nonincreasing, is proposed to solve SGCP. Finally, abundant experiments are conducted on real-world datasets and demonstrate the effectiveness of the proposed SGCP.</p

Dual-Mode Gold Nanocluster-Based Nanoprobe Platform for Two-Photon Fluorescence Imaging and Fluorescence Lifetime Imaging of Intracellular Endogenous miRNA

Bioimaging is widely used in various fields of modern medicine. Fluorescence imaging has the advantages of high sensitivity, high selectivity, noninvasiveness, in situ imaging, and so on. However, one-photon (OP) fluorescence imaging has problems, such as low tissue penetration depth and low spatiotemporal resolution. These disadvantages can be solved by two-photon (TP) fluorescence imaging. However, TP imaging still uses fluorescence intensity as a signal. The complexity of organisms will inevitably affect the change of fluorescence intensity, cause false-positive signals, and affect the accuracy of the results obtained. Fluorescence lifetime imaging (FLIM) is different from other kinds of fluorescence imaging, which is an intrinsic property of the material and independent of the material concentration and fluorescence intensity. FLIM can effectively avoid the fluctuation of TP imaging based on fluorescence intensity and the interference of autofluorescence. Therefore, based on silica-coated gold nanoclusters (AuNCs@SiO2) combined with nucleic acid probes, the dual-mode nanoprobe platform was constructed for TP and FLIM imaging of intracellular endogenous miRNA-21 for the first time. First, the dual-mode nanoprobe used a dual fluorescence quencher of BHQ2 and graphene oxide (GO), which has a high signal-to-noise ratio and anti-interference. Second, the dual-mode nanoprobe can detect miR-21 with high sensitivity and selectivity in vitro, with a detection limit of 0.91 nM. Finally, the dual-mode nanoprobes performed satisfactory TP fluorescence imaging (330.0 μm penetration depth) and FLIM (τave = 50.0 ns) of endogenous miR-21 in living cells and tissues. The dual-mode platforms have promising applications in miRNA-based early detection and therapy and hold much promise for improving clinical efficacy

DataSheet1_Low-intensity focused ultrasound targeted microbubble destruction reduces tumor blood supply and sensitizes anti-PD-L1 immunotherapy.docx

Immune checkpoint blockade (ICB) typified by anti-PD-1/PD-L1 antibodies as a revolutionary treatment for solid malignancies has been limited to a subset of patients due to poor immunogenicity and inadequate T cell infiltration. Unfortunately, no effective strategies combined with ICB therapy are available to overcome low therapeutic efficiency and severe side effects. Ultrasound-targeted microbubble destruction (UTMD) is an effective and safe technique holding the promise to decrease tumor blood perfusion and activate anti-tumor immune response based on the cavitation effect. Herein, we demonstrated a novel combinatorial therapeutic modality combining low-intensity focused ultrasound-targeted microbubble destruction (LIFU-TMD) with PD-L1 blockade. LIFU-TMD caused the rupture of abnormal blood vessels to deplete tumor blood perfusion and induced the tumor microenvironment (TME) transformation to sensitize anti-PD-L1 immunotherapy, which markedly inhibited 4T1 breast cancer’s growth in mice. We discovered immunogenic cell death (ICD) in a portion of cells induced by the cavitation effect from LIFU-TMD, characterized by the increased expression of calreticulin (CRT) on the tumor cell surface. Additionally, flow cytometry revealed substantially higher levels of dendritic cells (DCs) and CD8+ T cells in draining lymph nodes and tumor tissue, as induced by pro-inflammatory molecules like IL-12 and TNF-α. These suggest that LIFU-TMD as a simple, effective, and safe treatment option provides a clinically translatable strategy for enhancing ICB therapy.</p

α‑Alkylation of Chiral Sulfinimines for Constructing Quaternary Chiral Carbons by Introducing Removable Directing Groups

This study developed a facile and efficient synthetic strategy to construct quaternary chiral centers at the α-position of imines and ketones. High regioselectivity and diastereoselectivity were achieved through the synergetic effect of electron-withdrawing directing groups and <i>N</i>-<i>tert</i>-butyl sulfinamide as chiral auxiliaries. Either of them could be removed under the optimized conditions without any epimerization

Additional file 1 of LIFU/MMP-2 dual-responsive release of repurposed drug disulfiram from nanodroplets for inhibiting vasculogenic mimicry and lung metastasis in triple-negative breast cancer

Additional file 1: Fig. S1. Drug Loading Efficacy of Nanodroplets with Varying Feeding Ratios of DSF and PLGA-MMP-2-PEG. Fig. S2. Detection of conjugation efficiency of the FITC-labelled MMP-2-PEG and PLGA-COOH. Fig. S3. HPLC chromatograms of DSF. Table S1. Average particle size, zeta potential, drug loading and encapsulation efficiency of PFP@PD and PFP@PDM-PEG. (n=3, mean ± SD). Fig. S4. In vitro drug release profiles of PFP@PD and PFP@PDM-PEG. (n=3, mean ± SD). Fig. S5. Antitumor efficacy of PFP@PDM-PEG in vitro. Fig. S6. Representative images of the 4T1 tumors after different treatment at day 14. Fig. S7. Representative H&E staining of the liver in each group. The scale bar: 10 μm. Fig. S8. Calculation of the mean density of endothelium-dependent microvessels in each group. Fig. S9. Calculation of the fluorescence intensity of COL1 in each group. (n=3, t-test, *p < 0.05, **p < 0.01, ***p < 0.001). Fig. S10. Calculation of the fluorescence intensity of activated MMP-2 in each group. (n=3, t-test, **p < 0.01, ***p < 0.001, ****p < 0.0001). Fig. S11. All mouse hematologic and serum biomedical indices. Fig. S12. H&E staining of the vital organs (heart, liver, spleen, lungs, and kidneys). Fig. S13. Variations in body weight of 4T1 tumor-bearing mice in various groups