We report the design, synthesis, and implemention in semiconducting polymers of a novel head-to-head linkage containing the TRTOR (3-alkyl-3′-alkoxy-2,2′-bithiophene) donor subunit having a single strategically optimized, planarizing noncovalent S•••O interaction. Diverse complementary thermal, optical, electrochemical, X-ray scattering, electrical, photovoltaic, and electron microscopic characterization techniques are applied to establish structure−property correlations in a TRTOR-based polymer series. In comparison to monomers having double S•••O interactions, replacing one alkoxy substituent with a less electron-donating alkyl one yields TRTOR-based polymers with significantly depressed (0.2−0.3 eV) HOMOs. Furthermore, the weaker single S•••O interaction and greater TRTOR steric encumberance enhances materials processability without sacrificing backbone planarity. From another perspective, TRTOR has comparable electronic properties to ring-fused 5Hdithieno[3,2-b:2′,3′-d]pyran (DTP) subunits, but a centrosymmetric geometry which promotes a more compact and ordered structure than bulkier, axisymmetric DTP. Compared to monosubstituted TTOR (3-alkoxy-2,2′-bithiophene), alkylation at the TRTOR bithiophene 3-position enhances conjugation and polymer crystallinity with contracted π−π stacking. Grazing incidence wide-angle X-ray scattering (GIWAXS) data reveal that the greater steric hindrance and the weaker single S•••O interaction are not detrimental to close packing and high crystallinity. As a proof of materials design, copolymerizing TRTOR with phthalimides yields copolymers with promising thin-film transistor mobility as high as 0.42 cm 2 /(V•s) and 6.3% power conversion efficiency in polymer solar cells, the highest of any phthalimide copolymers reported to date. The depressed TRTOR HOMOs imbue these polymers with substantially increased I on /I off ratios and V oc 's versus analogous subunits with multiple electron donating, planarizing alkoxy substituents. Implementing a head-to-head linkage with an alkyl/alkoxy substitution pattern and a single S•••O interaction is a promising strategy for organic electronics materials design.

Altered transforming growth factor-b (TGF-b) signalling has been implicated in tumour development and progression. However, the molecular mechanism behind this alteration is poorly understood. Here we show that profilin-2 (Pfn2) increases Smad2 and Smad3 expression via an epigenetic mechanism, and that profilin-2 and Smad expression correlate with an unfavourable prognosis of lung cancer patients. Profilin-2 overexpression promotes, whereas profilin-2 knockdown drastically reduces, lung cancer growth and metastasis. We show that profilin-2 suppresses the recruitment of HDAC1 to Smad2 and Smad3 promoters by preventing nuclear translocation of HDAC1 through protein-protein interaction at the C terminus of both proteins, leading to the transcriptional activation of Smad2 and Smad3. Increased Smad2 and Smad3 expression enhances TGF-b1-induced EMT and production of the angiogenic factors VEGF and CTGF. These findings reveal a new regulatory mechanism of TGF-b1/Smad signalling, and suggest a potential molecular target for the development of anticancer drugs.

Background-Recently, several new human coronaviruses have been identified.

YAP is a transcriptional co-regulator that plays important roles in various patho-physiological processes, including the survival and death of cells. However, the effect of YAP on apoptosis and EMT, simultaneously mediated by TGF-β1, is not known. In this study, we demonstrate that YAP can modulate cell fate of apoptosis versus EMT by acting as a surviving factor. Overexpression of YAP in mouse mammary epithelial (NMuMG) cells suppressed TGF-β1-induced apoptosis, which shifted the cellular response predominantly toward EMT. In contrast, knockdown of YAP induced spontaneous apoptosis and enhanced TGF-β1-induced apoptosis, leading to a sharp decrease in the proportion of surviving cells that underwent EMT. These data suggest that YAP is an essential factor for modulating cellular responses to TGF-β1. Further investigation showed that YAP could regulate the expression level and activation of EGFR. Knockdown or inhibition of EGFR abolished the suppressive effect of YAP on apoptosis, whereas activation of EGFR by EGF significantly reduced apoptosis caused by the knockdown of YAP. The results indicate that EGFR and its activation are critical for YAP-mediated suppression of TGF-β1-induced apoptosis. This study provides a new understanding of the regulatory mechanism underlying the determination of cell fate in response to TGF-β1-mediated simultaneous apoptosis and EMT.

Mitochondrial dysfunction and epithelial-to-mesenchymal transition (EMT) play important roles in cancer development and metastasis. However, very little is known about the connection between mitochondrial dysfunction and EMT. Tu translation elongation factor, mitochondrial (TUFM), a key factor in the translational expression of mitochondrial DNA, plays an important role in the control of mitochondrial function. Here, we show that TUFM is downregulated in human cancer tissues. TUFM expression level was positively correlated with that of E-cadherin and decreased significantly during the progression of human lung cancer. TUFM knockdown induced EMT, reduced mitochondrial respiratory chain activity, and increased glycolytic function and the production of reactive oxygen species (ROS). Mechanistically, TUFM knockdown activated AMPK and phosphorylated GSK3β and increased the nuclear accumulation of β-catenin, leading to the induction of EMT and increased migration and metastasis of A549 lung cancer cells. Although TUFM knockdown also induced EMT of MCF7 breast cancer cells, the underlying mechanism appeared somewhat different from that in lung cancer cells. Our work identifies TUFM as a novel regulator of EMT and suggests a molecular link between mitochondrial dysfunction and EMT induction.

Conventional microbial cell cultivation techniques are typically labor intensive, low throughput, and poorlyparallelized, rendering them inefficient. The development of automated, modular microbial cell micro‐cultivation systems, particularly those employing droplet microfluidics, have gained attention for their high‐throughput, highly paralellized and efficient cultivation capabilities. Here, we report the development of a microbial microdroplet culture system (MMC), which is an integrated platform for automated, high‐throughput cultivation and adaptive evolution of microorganisms. We demonstrated that the MMC yielded both accurate and reproducible results for the manipulation and detection of droplets. The superior performance of MMC for microbial cell cultivation was validated by comparing the growth curves of six microbial strains grown in MMC, conventional shake flasks or well plates. The highest incipient growth rate for all six microbial strains was achieved by using MMC. We also conducted an 18‐day process of adaptive evolution of methanol‐essential Escherichia coli strain in MMC and obtained two strains exhibiting higher growth rates compared with the parent strain. Our study demonstrates the power of MMC to provide an efficient and reliable approach for automated, high‐throughput microbial cultivation and adaptive evolution.

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Background:The role of HNF6 in lung cancer growth and progression remains to be characterized. Results: HNF6 up-regulates p53 and inhibits EMT, cell migration, and invasive growth in lung cancer cells. Conclusion: HNF6 suppresses EMT and invasive growth of lung adenocarcinoma cells through p53. Significance: HNF6 is potentially a molecular marker and target for diagnostic and therapeutic purpose for lung adenocarcinoma cancers.