Polymers with an abundant amorphous domain should facilitate energy dissipation upon stretching, making near amorphous π-conjugated polymers have immense potential in realizing intrinsically stretchable field-effect transistor (FET) devices. In this study, high mobility preservation under the stretched state is attempted by replacing typical alkyl-monothienyl (T-R) on a benzo­[1,2-b:4,5-b’]­dithiophene-difluorobenzothiadiazole backbone with three other biaxially extended side-chains, including alkyl-dithienyl (2T-R), branching alkyl-trithienyl (3T-R), and alkyl-benzotrithienyl (B3T-R) groups. Despite showing near amorphous features, the semi-2D BDT-based polymers with bulkier biaxially extended side chains (PBDT-2T, PBDT-3T, and PBDT-B3T) still present comparable mobility to the reference semicrystalline polymer (PBDT-T). Although these four polymers yield comparable mobility, they show distinctly different mobility retention in the stretched state. From the study of their mobility-stretchability relationship, the interdigitating and/or entanglement of these biaxially extended conjugated side chains are shown to play a nontrivial role in the resultant mechanical robustness against the stretching force. Owing to the proper spatial mobility and geometry, the branched 3T-R side chain possesses a more intense interdigitating and/or entanglement capability than the linear 2T-R one and the fused B3T-R one, providing better mechanical strength under stretched states. Meanwhile, it maintains sufficient interchain connectivity for intermittent interchain hopping to compensate for the 1D charge transport along the backbone, ensuring good charge transport even in the stretched state. As a result, the printed PBDT-3T film is demonstrated to deliver a high mobility retention of 73% at a 60% strain exerted parallel to the charge-transporting direction and a very stable mobility retention of 88% after 1000 stretching-releasing cycles at a 60% strain, being one of the best stretchable near amorphous conjugated polymers reported thus far. Our result underlines the effectiveness of using biaxially extended conjugated side chains to realize high-performance stretchable polymers.

Conjugated polymers synthesized through random terpolymerization have recently attracted great research interest due to the synergetic effect on the polymer’s crystallinity and semiconducting properties. Several studies have demonstrated the efficacy of random terpolymerization in fine-tuning the aggregation behavior and optoelectronic property of conjugated polymers to yield enhanced device performance. However, as an influential approach of backbone engineering, its efficacy in modulating the mobility–stretchability property of high-performance conjugated polymers has not been fuller explored to date. Herein, a series of random terpolymers based on the diketopyrrolopyrrole-bithiophene (DPP-2T) backbone incorporating different amounts of isoindigo (IID) unit are synthesized, and their structure–mobility–stretchability correlation is thoroughly investigated. Our results reveal that random terpolymers containing a low IID content (DPP95 and DPP90) show enhanced interchain packing and solid-state aggregation to result in improved charge-transporting performance (can reach 4 order higher) compared to the parent polymer DPP100. In addition, owing to the enriched amorphous feature, DPP95 and DPP90 deliver an improved orthogonal mobility (μh) of >0.01 cm2 V–1 s–1 under a 100% strain, higher than the value (∼0.002 cm2 V–1 s–1) of DPP100. Moreover, DPP95 even yields 20% enhanced orthogonal μh retention after 800 stretching–releasing cycles with 60% strain. As concluded from a series of analyses, the improved mobility–stretchability property exerted by random terpolymerization arises from the enriched amorphous feature and enhanced aggregation behavior imposed by the geometry mismatch between different acceptors (DPP and IID). This study demonstrates that backbone engineering through rational random terpolymerization not only enhances the mobility–stretchability of a conjugated polymer but also realizes a better mechanical endurance, providing a new perspective for the design of high-performance stretchable conjugated polymers.

Rationale: NRF2, a redox sensitive transcription factor, is up-regulated in head and neck squamous cell carcinoma (HNSCC), however, the associated impact and regulatory mechanisms remain unclear. Methods: The protein expression of NRF2 in HNSCC specimens was examined by IHC. The regulatory effect of c-MYC on NRF2 was validated by ChIP-qPCR, RT-qPCR and western blot. The impacts of NRF2 on malignant progression of HNSCC were determined through genetic manipulation and pharmacological inhibition in vitro and in vivo . The gene-set enrichment analysis (GSEA) on expression data of cDNA microarray combined with ChIP-qPCR, RT-qPCR, western blot, transwell migration/ invasion, cell proliferation and soft agar colony formation assays were used to investigate the regulatory mechanisms of NRF2. Results: NRF2 expression is positively correlated with malignant features of HNSCC. In addition, carcinogens, such as nicotine and arecoline, trigger c-MYC-directed NRF2 activation in HNSCC cells. NRF2 reprograms a wide range of cancer metabolic pathways and the most notable is the pentose phosphate pathway (PPP). Furthermore, glucose-6-phosphate dehydrogenase (G6PD) and transketolase (TKT) are critical downstream effectors of NRF2 that drive malignant progression of HNSCC; the coherently expressed signature NRF2/G6PD/TKT gene set is a potential prognostic biomarker for prediction of patient overall survival. Notably, G6PD- and TKT-regulated nucleotide biosynthesis is more important than redox regulation in determining malignant progression of HNSCC. Conclusions: Carcinogens trigger c-MYC-directed NRF2 activation. Over-activation of NRF2 promotes malignant progression of HNSCC through reprogramming G6PD- and TKT-mediated nucleotide biosynthesis. Targeting NRF2-directed cellular metabolism is an effective strategy for development of novel treatments for head and neck cancer.

Stretchable electronics have received great attention in recent years because they enable to accommodate large mechanical deformation without damaging electronic properties. These features are highly desirable for novel applications, including...

N-Glycosylation is an important co- and/or post-translational modification that occurs on the vast majority of the one-third of the mammalian proteome that traverses the cellular secretory pathway, regulating glycoprotein folding and functions. Previous studies on the sequence requirements for N-glycosylation have yielded the Asn-X-Ser/Thr (NXS/T) sequon and the enhanced aromatic sequons (Phe-X-Asn-X-Thr and Phe-X-X-Asn-X-Thr), which can be efficiently N-glycosylated. To further investigate the influence of sequence variation on N-glycosylation efficiency in the context of a five-residue enhanced aromatic sequon, we used the human CD2 adhesion domain (hCD2ad) to screen the i-2, i-1, i+1, and i+2 residues flanking Asn at the i position. We found that aromatic residues, especially Trp, and sulfur-containing residues at the i-2 position improved N-glycosylation efficiency, while positively charged residues such as Arg suppressed N-glycosylation. Thiol, hydroxyl, and aliphatic-based side chains at the i-1 position had higher N-glycosylation efficiency, and Cys, in particular, compensated for the negative effect of Arg at the i-2 position. Small residues and Ser at the i+1 position increased the likelihood of N-glycosylation, and Thr is better than Ser at the i+2 position. We devised an algorithm for prediction of N-glycosylation efficiency using the SAS software, employing the 120 sequences studied as a training set. We then introduced the optimized-enhanced aromatic sequons into other glycoproteins and observed an enhancement in N-glycan occupancy that was further supported by modeling the high-affinity interaction between the optimized sequence on hCD2ad and a human oligosaccharyltransferase (OST) subunit. The findings in this study provide useful information for enhancing or suppressing N-glycosylation at a site of interest and valuable data for a better understanding of OST-catalyzed N-glycosylation.

Semi-two-dimensional (semi-2D) benzo­[1,2-b:4,5-b′]­dithiophene (BDT)-based donor–acceptor copolymers have been regarded as one of the most successful organic semiconductors for photovoltaic applications. In this work, the structure–mobility relationship of four semi-2D BDT-based polymers bearing different kinds of conjugated side chains, including alkyl-monothienyl (T), alkyl-dithienyl (2T), branched alkyl-trithienyl (3T), and alkyl-benzotrithienyl (B3T), is thoroughly investigated. Because of the lower rigidity and the higher spatial mobility, the polymers owning lineally extended conjugated side chains, like PBDT-T and PBDT-2T, still possess certain crystallinity after thermal annealing. However, the crystallinity becomes evanescent as the side-chain conjugation further increases. PBDT-3T and PBDT-B3T bearing a large, branched conjugated side chain become nearly amorphous even after thermal annealing. Despite the low crystallinity, all these semi-2D polymers can still deliver decent hole mobility (μh) of >0.1 cm2 V–1 s–1 after thermal annealing. More interestingly, the amorphous PBDT-3T can deliver a maximum μh value of 0.4 cm2 V–1 s–1, outperforming the value of reference semicrystalline PBDT-T that owns a typical thienyl side chain. Based on the analyses of film morphology and solid-state crystallinity, the hyper-conjugated side chain with intense aggregation tendency is suggested to facilitate the intermittent interchain hopping between polymer chains, which compensates the short-range structural order of low-crystalline polymer to ensure the laudable charge carrier transport property. This work systematically explores the charge carrier transport behaviors of semi-2D polymers with varied biaxially extended conjugated side chains and enlightens a new design strategy to improve the charge carrier transport of low-crystalline polymers.

Aldol reaction is a green approach that is exclusively suitable for developing conjugated polymers (CPs) with ladder-type structures. Herein, electron-deficient non-fused and fused bis-isoindigo (bis-IID) are copolymerized with axisymmetric thiophene...

P3HT, as one of the most important conjugated polymers, has been reported to possess low mobility and poor stretchability. In this study, two polythiophenes are prepared by attaching ester-substituted, biaxially extended conjugated side chains with backbones of 3-(thiophen-2-yl)-6-(thiophen-3-yl)thieno-[3,2-b]thiophene-bithiophene (PDCTT2T) and 3-(thiophen-2-yl)-6-(thiophen-3-yl)thieno[3,2-b]thiophene-difluorobithiophene (PDCTT2T-F) and compared with their respective counterparts without the biaxially extended side chains (thieno[3,2b]thiophene-bithiophene and thieno[3,2-b]thiophene-difluorobithiophene backbonesfor PDCTT and PDCTT-F). Through investigating mobility−stretchability properties of these four polymers, the synergetic effect of ester-substituted, biaxially extended conjugation and backbone fluorination is demonstrated to improve mobility−stretchability properties of polythiophenes, especially in a highly stretched state. On the one hand, the biaxially extended side chains implant a more amorphous structure and reinforce the intramolecular charge transfer between polymer backbones. On the other hand, the backbone fluorination confers to a rigidified polymer backbone, facilitating effective intrachain charge transport. As a result, PDCTT2T-F delivers superior mobility (0.20 cm 2 V −1 s −1 ) to PDCTT-F (0.054 cm 2 V −1 s −1 ) alongside 11 times higher mobility retention at a 100% strain. In addition, both PDCTT2T and PDCTT2T-F encouragingly retain decent mobility throughout 800 stretching−releasing cycles (at a 60% strain), outperforming their respective parent polymers without side-chain conjugation that show a one-order decrease in mobility. The results shown in this work signify an effective design strategy to fine-tune mobility−stretchability properties of polythiophenes.