A Dual Fluorescence Turn-On Sensor Array Formed by Poly(para-aryleneethynylene) and Aggregation-Induced Emission Fluorophores for Sensitive Multiplexed Bacterial Recognition.

Bacterial infections have emerged as the leading causes of mortality and morbidity worldwide. Herein, we developed a dual-channel fluorescence "turn-on" sensor array, comprising six electrostatic complexes formed from one negatively charged poly(para-aryleneethynylene) (PPE) and six positively charged aggregation-induced emission (AIE) fluorophores. The 6-element array enabled the simultaneous identification of 20 bacteria (OD600=0.005) within 30s (99.0 % accuracy), demonstrating significant advantages over the array constituted by the 7 separate elements that constitute the complexes. Meanwhile, the array realized different mixing ratios and quantitative detection of prevalent bacteria associated with urinary tract infection (UTI). It also excelled in distinguishing six simulated bacteria samples in artificial urine. Remarkably, the limit of detection for E. coli and E. faecalis was notably low, at 0.000295 and 0.000329 (OD600), respectively. Finally, optimized by diverse machine learning algorithms, the designed array achieved 96.7 % accuracy in differentiating UTI clinical samples from healthy individuals using a random forest model, demonstrating the great potential for medical diagnostic applications.

A Multichannel Fluorescent Tongue for Amyloid-ß Aggregates Detection.

Attention has been paid to the early diagnosis of Alzheimer's disease, due to the maximum benefit acquired from the early-stage intervention and treatment. However, the sensing techniques primarily depended upon for neuroimaging and immunological assays for the detection of AD biomarkers are expensive, time-consuming and instrument dependent. Here, we developed a multichannel fluorescent tongue consisting of four fluorescent dyes and GO through electrostatic and π-π interaction. The array distinguished multiple aggregation states of 1 µM Aß40/Aß42 with 100% prediction accuracy via 10-channel signal outputs, illustrating the rationality of the array design. Screening vital sensor elements for the simplified sensor array and the optimization of sensing system was achieved by machine learning algorithms. Moreover, our sensing tongue was able to detect the aggregation states of Aß40/Aß42 in serum, demonstrating the great potential of multichannel array in diagnosing the Alzheimer's diseases.

One-Component Multichannel Sensor Array for Rapid Identification of Bacteria.

Bacterial infections routinely cause serious problems to public health. To mitigate the impact of bacterial infections, sensing systems are urgently required for the detection and subsequent epidemiological control of pathogenic organisms. Most conventional approaches are time-consuming and highly instrument- and professional operator-dependent. Here, we developed a novel one-component multichannel array constructed with complex systems made from three modified polyethyleneimine as well as negatively charged graphene oxide, which provided an information-rich multimode response to successfully identify 10 bacteria within minutes via electrostatic interactions and hydrophobic interactions. Furthermore, the concentration of bacteria (from OD600 = 0.025 to 1) and the ratio of mixed bacteria were successfully achieved with our smart sensing system. Our designed sensor array also exhibited huge potential in biological samples, such as in urine (OD600 = 0.125, 94% accuracy). The way to construct a sensor array with minimal sensor element with abundant signal outputs tremendously saves cost and time, providing a powerful tool for the diagnosis and assessment of bacterial infections in the clinic.

Discovery of thiapyran-pyrimidine derivatives as potential EGFR inhibitors.

A series of novel thiapyran-pyrimidine derivatives (10a-10h, 11a-11g, 12a-12f, 13a-13f, 14a-14f) were synthesized and their antiproliferative activities were tested. Most of the target compounds showed good activity on one or more cancer cell lines but low activity on human normal cell LO2. The most promising compound 13a exhibited the similar IC50 values on A549 and H1975 cell lines to the lead drug Olmutinib, and exhibited excellent activity and selectivity on EGFRT790M/L858R in the kinase experiment. AO and Hoechst33258 staining indicated that 13a could effectively induce H1975 cells apoptosis. Cell cycle and apoptosis analysis suggested that 13a could block cancer cells in G2/M phase and induce into late apoptosis in a manner of concentration-dependent. The structure-activity relationship of 13a was analyzed to explore its mechanism. All the results showed that 13a was a promising EGFR inhibitor.

Design, synthesis and antitumor activity of novel thiophene-pyrimidine derivatives as EGFR inhibitors overcoming T790M and L858R/T790M mutations.

Five series of novel thiophene-pyrimidine derivatives (9a-h, 10a-f, 11a-f, 12a-f, 13a-f) have been synthesized and tested for their anti-proliferative activity against several cancer cell lines in which EGF is highly expressed. Most of the target compounds showed excellent activity against one or more cancer cell lines. The most promising compound 13a, of which IC50 values on of cell lines A549 and A431 (4.34 ± 0.60 µM and 3.79 ± 0.57 µM) were similar to the lead compound Olmutinib, showed strong activity and selectivity to EGFRT790M and EGFRT790M/L858R. Inhibition data of human normal hepatoma cell line LO2 indicated that most target compounds were less toxic to normal cells and had selective inhibitory effects on cancer cells. In addition, the structure-activity relationship was analyzed and the mechanism of apoptosis induced by the 13a was studied. The results showed that compound 13a induced late apoptosis of A431 cancer cells in a dose-dependent manner.