Direct Detection of Dilute Solid Chemicals with Responsive Lateral Organic Diodes

Organic field-effect transistors (OFETs) have emerged as promising sensors targeting chemical analytes in vapors and liquids. However, the direct detection of solid chemicals by OFETs has not been achieved. Here for the first time, we describe the direct detection of solid chemical analytes by organic electronics. An organic diode structure based on a horizontal side-by-side <i>p</i>–<i>n</i> junction was adopted and shown to be superior to OFETs for this purpose. The diodes showed more than 40% current decrease upon exposure to 1 ppm melamine powders. The estimated detection limit to melamine can potentially reach the ppb range. This is the first demonstration of an electronic signal from an interaction between a solid and an organic <i>p</i>–<i>n</i> junction directly, which suggests that our lateral organic diodes are excellent platforms for the development of future sensors when direct detection of solid chemicals is needed. The approach developed here is general and can be extended to chemical sensors targeting various analytes, opening unprecedented opportunities for the development of low-cost and high-performance solid chemical sensors

Disturbance of the let-7/LIN28 double-negative feedback loop is associated with radio- and chemo-resistance in non-small cell lung cancer

<div><p>Radio- and chemo-resistance represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC) and the underlying molecular mechanisms are not known. In the present study, during induction of radio- or chemo-resistance in NSCLC cells, dynamic analyses revealed that decreased expression of let-7 induced by irradiation or cisplatin resulted in increased expression of its target gene <i>LIN28</i>, and increased expression of LIN28 then contributed to further decreased expression of let-7 by inhibiting its maturation and biogenesis. Moreover, we showed that down-regulation of let-7 and up-regulation of LIN28 expression promoted resistance to irradiation or cisplatin by regulating the single-cell proliferative capability of NSCLC cells. Consequently, in NSCLC cells, let-7 and LIN28 can form a double-negative feedback loop through mutual inhibition, and disturbance of the let-7/LIN28 double-negative feedback loop induced by irradiation or chemotherapeutic drugs can result in radio- and chemo-resistance. In addition, low expression of let-7 and high expression of LIN28 in NSCLC patients was associated significantly with resistance to radiotherapy or chemotherapy. Therefore, our study demonstrated that disturbance of the let-7/LIN28 double-negative feedback loop is involved in the regulation of radio- and chemo-resistance, and that let-7 and LIN28 could be employed as predictive biomarkers of response to radiotherapy or chemotherapy in NSCLC patients.</p></div

Dynamic analyses of expression of let-7 and LIN28 during induction of radio- or chemo-resistance in A549 cells.

<p><b>(A)</b> To varying degrees, expression of let-7 miRNAs was down-regulated during induction of radio- or chemo-resistance. <b>(B)</b> To varying degrees, expression of LIN28A and LIN28B was up-regulated during induction of radio- or chemo-resistance.</p

Let-7 and LIN28 were putative regulators of single-cell proliferative capability.

<p><b>(A)</b> Colony-formation assay of A549/IR and A549/DDP cells transfected with let-7 mimics or si-LIN28A. <b>(B)</b> Colony-formation assay of A549 cells transfected with let-7 inhibitors or LIN28A plasmids (n = 3, *<i>P</i> < 0.05).</p

LIN28 blocked let-7 maturation specifically.

<p><b>(A)</b> si-LIN28 increased the maturation of let-7 in A549/IR and A549/DDP cells and LIN28 plasmid decreased the maturation of let-7 in A549 cells, respectively. <b>(B)</b> Inhibition of LIN28 decreased resistance to irradiation in A549/IR cells or to cisplatin in A549/DDP cells significantly. <b>(C)</b> Overexpression of LIN28 increased resistance to irradiation or cisplatin in A549 cells significantly (n = 3, *<i>P</i> < 0.05).</p

Let-7 family miRNAs regulated radio- and chemo-resistance by targeting <i>LIN28</i>.

<p><b>(A)</b> Luciferase assays of let-7 targeting effects on <i>LIN28</i>. Mutations were generated in the <i>LIN28A</i> 3′-UTR and <i>LIN28B</i> 3′-UTR sequence in the complementary site for the seed region of let-7 as indicated. <b>(B)</b> mRNA and protein levels of LIN28 were decreased in A549/IR and A549/DDP cells after transfection of let-7 mimics and increased in A549 cells after transfection of let-7 inhibitors, as detected by RT-PCR and western blotting. <b>(C)</b> Overexpression of let-7 decreased resistance to irradiation in A549/IR cells or to cisplatin in A549/DDP cells significantly. <b>(D)</b> Inhibition of let-7 increased resistance to irradiation or cisplatin in A549 cells significantly (n = 3, *<i>P</i> < 0.05).</p

Expression of let-7 family miRNAs was down-regulated in radio- or chemo-resistant cells.

<p><b>(A)</b> Members of the let-7 family (schematic). <b>(B)</b> Down-regulation of expression of let-7 family miRNAs in microarray experiments was validated by RT-PCR (n = 3, *<i>P</i> < 0.05).</p