Individuals with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here we report the identification of somatic mutations for GBC in 57 tumor-normal pairs through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate (FDR)<0.05) of non-silent mutations include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multivariate analyses further show that cases with ErbB pathway mutations have a worse outcome (P=0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.
Stretchable conductors are the basic building blocks of advanced flexible electronic devices, such as flexible display, skin-like sensors, stretchable batteries, soft actuators and so forth. [1][2][3][4][5][6][7][8][9][10] They are used in a vast number of soft and stretchable devices developed in recent years, including biointerfacing electrodes, [11][12][13][14][15] transistors, [16][17][18] mechanical sensors, [19][20][21][22] energy devices [23][24][25][26] and many more. [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] To meet most application requirements, stretchable conductors need to remain conductive under tensile strain of more than 100%, and even more importantly, to show stable performance in terms of interfacial adhesion between conductive metal film and the supporting polymer substrate.[1] Current methods to achieve stretchable conductors generally fall into two categories. One involves a structural design strategy, where the conducting material is designed with specific structures/topographies including serpentines, [46][47][48][49][50][51][52] wrinkles, [53,54] meshes, [55][56][57][58] and microcracks. [59][60][61][62][63] The other strategy relies on intrinsic stretchability of Stretchable conductors are the basic units of advanced flexible electronic devices, such as skin-like sensors, stretchable batteries and soft actuators. Current fabrication strategies are mainly focused on the stretchability of the conductor with less emphasis on the huge mismatch of the conductive material and polymeric substrate, which results in stability issues during long-term use. Thermal-radiation-assisted metal encapsulation is reported to construct an interlocking layer between polydimethylsiloxane (PDMS) and gold by employing a semipolymerized PDMS substrate to encapsulate the gold clusters/atoms during thermal deposition. The stability of the stretchable conductor is significantly enhanced based on the interlocking effect of metal and polymer, with high interfacial adhesion (>2 MPa) and cyclic stability (>10 000 cycles). Also, the conductor exhibits superior properties such as high stretchability (>130%) and large active surface area (>5:1 effective surface area/geometrical area). It is noted that this method can be easily used to fabricate such a stretchable conductor in a wafer-scale format through a one-step process. As a proof of concept, both long-term implantation in an animal model to monitor intramuscular electric signals and on human skin for detection of biosignals are demonstrated. This design approach brings about a new perspective on the exploration of stretchable conductors for biomedical applications.
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