In this work, highly photoluminescent (PL) self-assembled copper nanoclusters (Cu NCs) capable of rapid, sensitive, and selective detection of histamine were developed. Cu NCs were synthesized in facile conditions by using 2,3,5,6-tetrafluorothiophenol (TFTP) as both the reducing agent and the protecting ligand, which exhibited intense saffron yellow (590 nm) PL via self-assembled induced emission (SAIE), and the absolute quantum yield (QY) of assembly was as high as 43.0%. The size, electronic states, and morphologies of the assembled nanoribbons were characterized, and the geometric structure and spectral properties of the Cu NCs were investigated by theoretical study. Furthermore, the mechanism of the excellent sensing performance of Cu NCs toward histamine was demonstrated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and energy dispersive X-ray analysis (EDX). With this sensing system, the amount of histamine in fish, shrimp, and red wine were analyzed, and experiment results verified the application of the sensor. Importantly, the luminescent test strips based on Cu NCs were fabricated for colorimetric detection of histamine in foods. This proposed technique may provide an alternative to traditional methods for histamine detection.

Intracellular Fenton reaction-based mitochondria-targeted copper(ii)–peptide complex and Asc is developed for cancer cell treatment.

Background Ovarian cancer has the highest mortality among gynecological cancers due to late diagnosis and lack of effective targeted therapy. Although the study of interplay between cancer cells with their microenvironment is emerging, how ovarian cancer triggers signaling that coordinates with immune cells to promote metastasis is still elusive. Methods Microarray and bioinformatics analysis of low and highly invasive ovarian cancer cell lines were used to reveal periostin (POSTN), a matrix protein with multifunctions in cancer, with elevated expression in the highly invasive cells. Anchorage independent assay, Western blot, RNA interference, confocal analysis and neutralizing antibody treatment were performed to analyze the effects of POSTN on tumor promotion and to explore the underlying mechanism. Chemotaxis, flow cytometry and cytokine array analyses were undertaken to analyze the involvement of POSTN in cancer-associated fibroblast (CAF) and macrophage modulation. Correlations between POSTN expression levels and clinical characteristics were analyzed using the Oncomine, commercial ovarian cancer cDNA and China Medical University Hospital patient cohort. In vivo effect of POSTN on metastasis was studied using a mouse xenograft model. Results Expression of POSTN was found to be elevated in highly invasive ovarian cancer cells. We observed that POSTN was co-localized with integrin β3 and integrin β5, which was important for POSTN-mediated activation of ERK and NF-κB. Ectopic expression of POSTN enhanced whereas knockdown of POSTN decreased cancer cell migration and invasion in vitro, as well as tumor growth and metastasis in vivo. POSTN enhanced integrin/ERK/NF-κB signaling through an autocrine effect on cancer cells to produce macrophage attracting and mobilizing cytokines including MIP-1β, MCP-1, TNFα and RANTES resulting in increased chemotaxis of THP-1 monocytes and their polarization to M2 macrophages in vitro. In agreement, tumors derived from POSTN-overexpressing SKOV3 harbored more tumor-associated macrophages than the control tumors. POSTN induced TGF-β2 expression from ovarian cancer cells to promote activation of adipose-derived stromal cells to become CAF-like cells expressing alpha smooth muscle actin and fibroblast activation protein alpha. Consistently, increased CAFs were observed in POSTN overexpressing SKOV3 cells-derived metastatic tumors. In clinical relevance, we found that expression of POSTN was positively correlated with advanced-stage diseases and poor overall survival of patients. Conclusions Our study revealed a POSTN-integrin-NF-κB-mediated signaling and its involvement in enhancing M2 macrophages and CAFs, which could potentially participate in promoting tumor growth. Our results suggest that POSTN could be a useful prognosis marker and potential therapeutic target.

The abnormal aggregation of amyloid beta (Aβ or A beta) from monomeric proteins into amyloid fibrils is an important pathological contact to Alzheimer’s disease (AD). Amyloid beta 40 (Aβ40), the pivotal biomarker of AD, aggregates to form amyloid plaques. For this reason, inhibition of amyloid fibrillation had become a crucial prevention and therapeutic strategy. Usually, LVFFA is the central hydrophobic fragment of Aβ and can inhibit the aggregation of Aβ40. In this work, in order to improve the inhibitory ability of LVFFA, hexapeptide CLVFFA were conjugated at the surface of Au clusters (AuNCs) to manufacture a nanosized inhibitor, AuNCs-CLVFFA. Thioflavin T fluorescence and transmission electron microscope results showed that AuNCs-CLVFFA inhibited Aβ40 fibrillogenesis, fibrils’ prolongation, and mature fibrils’ disaggregation. Furthermore, AuNCs as the backbone of the inhibitor showed extraordinary inhibition ability for Aβ40 aggregation at a low AuNCs-CLVFFA concentration. Free hexapeptide CLVFFA, at the same concentration, showed almost no inhibition. Additionally, the inhibitor could maintain the optical properties of nanoclusters, and the cell viability demonstrated that the inhibitor had good biocompatibility and may potentially be applied into AD therapy or treatment.

Background The development of drug resistance in oral squamous cell carcinoma (OSCC) that frequently leads to recurrence and metastasis after initial treatment remains an unresolved challenge. Presence of cancer stem cells (CSCs) has been increasingly reported to be a critical contributing factor in drug resistance, tumor recurrence and metastasis. Thus, unveiling of mechanisms regulating CSCs and potential targets for developing their inhibitors will be instrumental for improving OSCC therapy. Methods siRNA, shRNA and miRNA that specifically target keratin 17 (KRT17) were used for modulation of gene expression and functional analyses. Sphere-formation and invasion/migration assays were utilized to assess cancer cell stemness and epithelial mesenchymal transition (EMT) properties, respectively. Duolink proximity ligation assay (PLA) was used to examine molecular proximity between KRT17 and plectin, which is a large protein that binds cytoskeleton components. Cell proliferation assay was employed to evaluate growth rates and viability of oral cancer cells treated with cisplatin, carboplatin or dasatinib. Xenograft mouse tumor model was used to evaluate the effect of KRT17- knockdown in OSCC cells on tumor growth and drug sensitization. Results Significantly elevated expression of KRT17 in highly invasive OSCC cell lines and advanced tumor specimens were observed and high KRT17 expression was correlated with poor overall survival. KRT17 gene silencing in OSCC cells attenuated their stemness properties including markedly reduced sphere forming ability and expression of stemness and EMT markers. We identified a novel signaling cascade orchestrated by KRT17 where its association with plectin resulted in activation of integrin β4/α6, increased phosphorylation of FAK, Src and ERK, as well as stabilization and nuclear translocation of β-catenin. The activation of this signaling cascade was correlated with enhanced OSCC cancer stemness and elevated expression of CD44 and epidermal growth factor receptor (EGFR). We identified and demonstrated KRT17 to be a direct target of miRNA-485-5p. Ectopic expression of miRNA-485-5p inhibited OSCC sphere formation and caused sensitization of cancer cells towards cisplatin and carboplatin, which could be significantly rescued by KRT17 overexpression. Dasatinib treatment that inhibited KRT17-mediated Src activation also resulted in OSCC drug sensitization. In OSCC xenograft mouse model, KRT17 knockdown significantly inhibited tumor growth, and combinatorial treatment with cisplatin elicited a greater tumor inhibitory effect. Consistently, markedly reduced levels of integrin β4, active β-catenin, CD44 and EGFR were observed in the tumors induced by KRT17 knockdown OSCC cells. Conclusions A novel miRNA-485-5p/KRT17/integrin/FAK/Src/ERK/β-catenin signaling pathway is unveiled to modulate OSCC cancer stemness and drug resistance to the common first-line chemotherapeutics. This provides a potential new therapeutic strategy to inhibit OSCC stem cells and counter chemoresistance.

As a promising fluorescent material, gold nanoclusters (Au NCs) have been used for biosensing and imaging. In metal ion sensing, the fluorescence of Au NCs is usually quenched in the presence of ions, but the reaction mechanism has not been clarified. In this work, mercaptan acids (3-mercaptopropanoic acid (3-MPA), 6-mercaptohexanoic acid (6-MHA), 11-mercaptoundecanoic acid (11-MUA) and 16-mercaptohexadecanoic acid (16-MHA)) were used as reductants and ligands to synthesize fluorescent Au NCs. The Au NCs had a core containing 18 atoms capped by 18 (3-MPA) or 10 (6-MHA, 11-MUA, 16-MHA) ligand molecules. The Au NCs prepared in this work had higher fluorescence quantum yields than those reported previously and the fluorescence showed a red-shift when varying the chain length of the mercaptan acids. It was found that in presence of ions (Mo(vi), Hg(ii)), the fluorescence of the Au NCs is dependent upon the ligands. The Au NCs with 3-MPA and 6-MHA ligands were sensitive to Mo(vi) and Hg(ii), while the Au NCs capped with 11-MUA and 16-MHA ligands were not sensitive to the ions. Various characterization techniques, including transmission electron microscopy, matrix-assisted laser-desorption ionization time of flight mass spectrometry, X-ray photoelectron spectroscopy, UV-Vis absorption spectroscopy and thermogravimetric analysis, were used to investigate the components and electronic structure of the clusters, as well as the emission and excitation properties before and after the reaction with metal ions. The structure of the Au NCs after the reaction with Mo(vi) and Hg(ii) was also studied. It was found that Mo(vi) and Hg(ii) both reacted with the gold atoms at the core site, but the reaction mechanisms were different.

The aggregation of amyloid-β protein (Aβ) is deemed a vital pathological feature of Alzheimer's disease (AD). Hence, inhibiting Aβ aggregation is noticed as a major tactic for the prevention and therapy of AD. Hydroxycinnamic acid, as a natural phenolic compound, is widely present in plant foods and has several biological activities including anti-inflammation, antioxidation, and neuroprotective effects. Here, it was found that hydroxycinnamic acid and its structural analogues (3hydroxycinnamic acid, 2-hydroxycinnamic acid, cinnamic acid, 3,4-dihydroxycinnamic acid, 2,4-dihydroxycinnamic acid, and 3,4,5trihydroxycinnamic acid) could inhibit Aβ40 fibrillogenesis and reduce Aβ40-induced cytotoxicity in a dose-dependent manner. Among these small molecules investigated, 3,4,5-trihydroxycinnamic acid is considered to be the most effective inhibitor, which reduces the ThT fluorescence intensity to 30.79% and increases cell viability from 49.47 to 84.78% at 200 μM. Also, the results with Caenorhabditis elegans verified that these small molecules can ameliorate AD-like symptoms of worm paralysis. Moreover, molecular docking studies showed that these small molecules interact with the Aβ40 mainly via hydrogen bonding. These results suggest that hydroxycinnamic acid and its structural analogues could inhibit Aβ40 fibrillogenesis and the inhibition activity is enhanced with the increase of phenolic hydroxyl groups of inhibitors. These small molecules have huge potential to be developed into novel aggregation inhibitors in neurodegenerative disorders.

As the highly toxic pollutants will seriously harm human health, it is particularly important to establish the analysis and detection technology of food pollutants. Compared with the traditional detection methods, fluorescent detection techniques based on nanomaterials trigger wide interesting because of reduced detection time, simple operation, high sensitivity and selectivity, and economic. In this review, the application of fluorescent sensors in food pollutants detection is presented. Firstly, conventional fluorescent nanomaterials including metal-based quantum dots, carbon dots, graphene quantum dots and metal nanoclusters were summarized, with emphasis on the photoluminescence mechanism. Then, the fluorescence sensors based on these nanomaterials for food pollutants detection were discussed, involving in the established methods, sensor mechanisms, sensitivity, selectivity, and practicability of fluorescence sensors. The selected analytes focus on five types of higher toxic food pollutants, including mycotoxins, foodborne pathogens, pesticide residues, antibiotic residues, and heavy metal ions. Finally, outlook on the future and potential development of fluorescence detection technology in the field of food science were proposed, including green synthesis and reusability of fluorescence probes, large-scale industrialization of sensors, nondestructive testing of samples and degradation of harmful substances.