Ultrasensitive solid-state electrochemiluminescence sensor based on lotus root shaped carbon fiber, CdSe QDs and Fe3O4 synergically amplify Ru(bpy)32+ luminophore signal for detection of cyfluthrin.

An efficient and innovative electrochemiluminescence (ECL) sensor was developed for trace detection of cyfluthrin. The sensor utilized materials such as lotus root shaped carbon fiber (Co CNFs), cadmium selenide quantum dots (CdSe QDs), and Fe3O4 to amplify Ru(bpy)32+ signals. Co CNFs, with its large specific surface area and porosity, served the purpose of not only enhancing the stability of the sensor by fixing CdSe QDs and Ru(bpy)32+ on the Co CNFs/GCE, but also facilitating electron transfer. CdSe QDs was involved in the luminescence reaction and collaborated with Ru(bpy)32+ to enhance the sensor's sensitivity, while Fe3O4 promoted electron transfer in the system due to its large surface area. The solid-state ECL sensor achieved satisfactory signal under the synergistic action of these components. The ECL signal of the sensor was quenched by cyfluthrin, and a favorable linear relationship was observed between the sensor and cyfluthrin in the concentration range 1 × 10-12 to 1 × 10-6 M. The detection limit of the sensor was 3.3 × 10-13 M (S/N = 3). The utilization of lotus root shaped carbon fiber, CdSe QDs, and Fe3O4 in the Ru(bpy)32+ system demonstrated a synergistic effect for cyfluthrin detection, presenting a new approach for the rapid determination analysis of pesticide residues in foods.

A molecule-imprinted electrochemiluminescence sensor based on CdS@MWCNTs for ultrasensitive detection of fenpropathrin.

A molecularly-imprinted electrochemiluminescence sensor was constructed for the determination of fenpropathrin (FPT) by molecular imprinting technology. In this sensing platform, the introduction of CdS@MWCNTs significantly enhanced the initial ECL signal of the luminol-O2 system. Specifically, MWCNTs was used as a carrier to adsorb more CdS, in which CdS acted as a co-reaction promoter for luminescence. Molecularly imprinted polymer (MIP) containing specific recognition sites of FPT was used as the material for selective recognition. With increasing amount of FPT the ECL signal decreased. Under the optimum conditions, the ECL response was linearly related to the logarithm of FPT concentration. The developed ECL sensor allowed for sensitive determination of FPT and exhibited a wide linear range from 1.0 × 10- 10 mol L- 1 to 1.0 × 10- 6 mol L- 1. The limit of detection was 3.3 × 10- 11 mol L- 1 (S/N = 3). It can be used for the detection of FPT in vegetable samples.

Natural protoberberine alkaloids, identified as potent selective LSD1 inhibitors, induce AML cell differentiation.

Natural protoberberine alkaloids were first identified and characterized as potent, selective and cellular active lysine specific demethylase 1 (LSD1) inhibitors. Due to our study, isoquinoline-based tetracyclic scaffold was identified as the key structural element for their anti-LSD1 activity, subtle changes of substituents attached to the core structure led to dramatic changes of the activity. Among these protoberberine alkaloids, epiberberine potently inhibited LSD1 (IC50 = 0.14 ± 0.01 µM) and was highly selective to LSD1 over MAO-A/B. Furthermore, epiberberine could induce the expression of CD86, CD11b and CD14 in THP-1 and HL-60 cells, confirming its cellular activity of inducing acute myeloid leukemia (AML) cells differentiation. Moreover, epiberberine prolonged the survival of THP-1 cells bearing mice and inhibited the growth of AML cells in vivo without obvious global toxicity. These findings give the potential application of epiberberine in AML treatment, and the isoquinoline-based tetracyclic scaffold could be used for further development of LSD1 inhibitors.

Identification of osimertinib (AZD9291) as a lysine specific demethylase 1 inhibitor.

Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). In this study, osimertinib was characterized as a LSD1 inhibitor for the first time with an IC50 of 3.98 ±â€¯0.3 µM and showed LSD1 inhibitory effect at cellular level. These findings provide new molecular skeleton for dual inhibitor for LSD1 and EGFR. Osimertinib could serve as a lead compound for further development for anti-NSCLC drug discovery with dual targeting.

Sanggenon O induced apoptosis of A549 cells is counterbalanced by protective autophagy.

Sanggenon O (SO) is a Diels-Alder type adduct extracted fromMorus alba, which has been used for its anti-inflammatory action in the Oriental medicine. However, whether it has regulatory effect on human cancer cell proliferation and what the underlying mechanism remains unknown. Here, we found that SO could significantly inhibit the growth and proliferation of A549 cells and induce its pro-apoptotic action through a caspase-dependent pathway. It could also impair the mitochondria which can be reflected by mitochondrial membrane permeabilization. Besides, SQSTM1 up-regulation and autophagic flux measurement demonstrated that exposure to SO led to autophagosome accumulation, which plays a protective role in SO-treated cells. In addition, knocking down of LC3B increased SO triggered apoptotic cell rates. These results indicated that SO has great potential as a promising candidate combined with autophagy inhibitor for the treatment of NSCLC. In conclusion, our results identified a novel mechanism by which SO exerts potent anticancer activity.

Optically Active Ultrafine Au-Ag Alloy Nanoparticles Used for Colorimetric Chiral Recognition and Circular Dichroism Sensing of Enantiomers.

Despite a significant surge in the number of investigations into chirality at the nanoscale, especially thiolated chiral molecules capping gold clusters, only limited knowledge is currently available to elaborate the alloying effect on chiroptical behavior of bimetallic nanoparticles (NPs). Also, few successful cases as to the efforts toward the development of chirality-dependent applications on the optically active nanomaterial have been made. Herein, as a positive test case for chiral alloy nanoparticle synthesis, the stable and large chiroptical ultrafine Au-Ag alloy NPs were prepared by reduction of different molar fractions of HAuCl4 and AgNO3 with NaBH4 in the presence of d/l-penicillamine (d/l-Pen). Compared with those of monometallic Au and Ag counterparts with comparable size, the Au-Ag alloy NPs (Ag mole fraction, 70%) obviously displayed the largest optical activities with the maximum g-factors of ∼1.6 × 10-3. Impressively, the Pen-mediated synthesis of chiral Au-Ag alloy NPs possesses a colorimetric self-recognition function and can be used as an incisive circular dichroism (CD) probe toward d- and l-Pen enantiomers. The plasmonic CD signal amplification (ΔICD) shows good linearity with the amount of Pen over the range of 5.0-80.0 µM with a detection limit (3σ) of 1.7 µM for l-Pen and 1.5 µM for d-Pen, respectively. In addition, the sensing system exhibits good selectivity toward d- and l-Pen in the presence of other enantiomers; therefore, it is highly expected that the approach described here would open new opportunities for design of more novel enantioselective analyses of important species related to biological processes.

An ultrasensitive solid-state electrochemiluminescence sensor based on Ni-MOF@Ru(bpy)32+ and Au NPs@TiO2 for determination of permethrin.

The novel TiO2 and Ni-MOF materials were synthesized and utilized for the detection of permethrin (PET). A highly sensitive solid-state electrochemiluminescence (ECL) sensor was developed based on Ni-MOF@Ru(bpy)32+ and Au NPs@TiO2. In this sensing platform, Ru(bpy)32+-Tripropyl Amine (TPrA) was used as a luminescent signal, Ni-MOF acted as a carrier to carry more luminescent reagents Ru(bpy)32+. Au NPs acted as promoters facilitated electron transport and TiO2 could further enhance the luminescence intensity of the system by synergistical interaction with Au NPs. The possible mechanisms of signal amplification were investigated. The ECL intensity decreased significantly with increasing PET concentration, enabling the determination of PET amount through the observation of the change in ECL signal intensity (ΔI). Under optimal experimental conditions, the linear range of PET concentration from 1.0 × 10-11 mol L-1 to 1.0 × 10-6 mol L-1, with a detection limit of 3.3 × 10-12 mol L-1 (3S/N). This method was successfully applied to determine PET in various vegetable samples.

Neddylation-dependent LSD1 destabilization inhibits the stemness and chemoresistance of gastric cancer.

Histone lysine-specific demethylase 1 (LSD1) expression has been evaluated in multiple tumors, including gastric cancer (GC). However, the mechanisms underlying LSD1 dysregulation in GC remain largely unclear. In this study, neural precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) was identified to be conjugated to LSD1 at K63 by ubiquitin-conjugating enzyme E2 M (UBE2M), and this neddylated LSD1 could promote LSD1 ubiquitination and degradation, leading to a decrease of GC cell stemness and chemoresistance. Herein, our findings revealed a novel mechanism of LSD1 neddylation and its contribution to decreasing GC cell stemness and chemoresistance. Taken together, our findings may whistle about the future application of neddylation inhibitors.

Targeting neddylation E2s: a novel therapeutic strategy in cancer.

Ubiquitin-conjugating enzyme E2 M (UBE2M) and ubiquitin-conjugating enzyme E2 F (UBE2F) are the two NEDD8-conjugating enzymes of the neddylation pathway that take part in posttranslational modification and change the activity of target proteins. The activity of E2 enzymes requires both a 26-residue N-terminal docking peptide and a conserved E2 catalytic core domain, which is the basis for the transfer of neural precursor cell-expressed developmentally downregulated 8 (NEDD8). By recruiting E3 ligases and targeting cullin and non-cullin substrates, UBE2M and UBE2F play diverse biological roles. Currently, there are several inhibitors that target the UBE2M-defective in cullin neddylation protein 1 (DCN1) interaction to treat cancer. As described above, this review provides insights into the mechanism of UBE2M and UBE2F and emphasizes these two E2 enzymes as appealing therapeutic targets for the treatment of cancers.

Polycondensation of a Perylene Bisimide Derivative and L-Malic Acid as Water-Soluble Conjugates for Fluorescent Labeling of Live Mammalian Cells.

Based on simple mixing and polymerization of a hydroxyl-containing derivative of perylene bisimide (PBI) and l-malic acid, here, we demonstrate a new type of dye-polymer conjugate, PBI-poly(α,ß-malic acid) (PBI⁻PMA). Benefiting from the excellent water-solubility of weak polyanionic PMA structure and the high fluorescence of PBI, the PBI-PMA conjugates readily dissolve in water, displaying strong pH-dependent fluorescence with the highest intensity at pH 6. Due to the excellent biocompatibility of PMA, those conjugates showed low cytotoxicity on L929 cells. Using L929 and HeLa cells, we also confirmed that the PBI-PMA-labeled cells display intense fluorescence. Overall, the PBI-PMA conjugate demonstrates high potential as a cell labeling agent with its synthesis ease, good solubility in aqueous medium, low cytotoxicity, and high fluorescence.

Optically active red-emitting Cu nanoclusters originating from complexation and redox reaction between copper(ii) and d/l-penicillamine.

Despite a significant surge in the number of investigations into both optically active Au and Ag nanostructures, there is currently only limited knowledge about optically active Cu nanoclusters (CuNCs) and their potential applications. Here, we have succeeded in preparing a pair of optically active red-emitting CuNCs on the basis of complexation and redox reaction between copper(ii) and penicillamine (Pen) enantiomers, in which Pen serves as both a reducing agent and a stabilizing ligand. Significantly, the CuNCs feature unique aggregation induced emission (AIE) characteristics and therefore can serve as pH stimuli-responsive functional materials. Impressively, the ligand chirality plays a dramatic role for the creation of brightly emissive CuNCs, attributed to the conformation of racemic Pen being unfavorable for the electrostatic interaction, and thus suppressing the formation of cluster aggregates. In addition, the clusters display potential toward cytoplasmic staining and labelling due to the high photoluminescence (PL) quantum yields (QYs) and remarkable cellular uptake, in spite that no chirality-dependent effects in autophagy and subcellular localization are observed in the application of chiral cluster enantiomer-based cell imaging.