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.

We present a new strategy to engineer human iPSC-derived liver organoids by combining stem cell biology with a microfluidic chip system.

Epigenetic alteration has been implicated in aging. However, the mechanism by which epigenetic change impacts aging remains to be understood. H3K27me3, a highly conserved histone modification signifying transcriptional repression, is marked and maintained by Polycomb Repressive Complexes (PRCs). Here, we explore the mechanism by which age-modulated increase of H3K27me3 impacts adult lifespan. Using Drosophila, we reveal that aging leads to loss of fidelity in epigenetic marking and drift of H3K27me3 and consequential reduction in the expression of glycolytic genes with negative effects on energy production and redox state. We show that a reduction of H3K27me3 by PRCs-deficiency promotes glycolysis and healthy lifespan. While perturbing glycolysis diminishes the pro-lifespan benefits mediated by PRCs-deficiency, transgenic increase of glycolytic genes in wild-type animals extends longevity. Together, we propose that epigenetic drift of H3K27me3 is one of the molecular mechanisms that contribute to aging and that stimulation of glycolysis promotes metabolic health and longevity.

No abstract

Hydrogel fibers are promising carriers for biological applications due to their flexible mechanical properties, well-defined spatial distribution, and excellent biocompatibility. In particular, the droplet-filled hydrogel fibers with the controllable dimension and location of droplets display great advantages to enhance the loading capacity of multiple components and biofunctions. In this work, we proposed a new all-in-water microfluidic system that allows for one-step fabrication of aqueous-droplet-filled hydrogel fibers (ADHFs) with unique morphology and tunable configurations. In the system, the aqueous droplets with equidistance are successfully arranged within the alginate calcium fibers, relying on the design of the pump valve cycle and the select of two immiscible liquids with a stable aqueous interface. The architecture of the ADHF can be flexibly controlled by adjusting the three phase flow rates and the valve switch cycle. The produced ADHFs exhibit high controllability, uniformity, biocompatibility, and stability. The established system enabled the formation of functional human islet organoids in situ through encapsulating pancreatic endocrine progenitor cells within microfibers. The generated islet organoids within droplets exhibit high cell viability and islet-specific function of insulin secretion. The proposed approach provides a new way to fabricate multifunctional hydrogel fibers for materials sciences, tissue engineering, and regenerative medicine.

Hepatitis IMPORTANCE Hepatitis B virus (HBV)is an important human pathogen. HBV quasispecies with genetically heterogenous variants are thought to play a role in the progression of HBV-associated liver diseases. So far, direct evidence is available in only a few cases to confirm the proposed role of HBV variants in the pathogenesis. We report here that the coexistence of two naturally occurring HBV variants at a ratio of 1 to 4 increased HBV replication and induced significantly stronger intrahepatic cytotoxic T lymphocyte responses and antibody responses specific to HBV surface antigen (HBsAg) in mice. Our discovery uncovered an unexpected aspect of HBV quasispecies: the coexistence of different variants can significantly modulate specific host immune responses and may enhance immune-mediated liver damage under some circumstances, representing a novel mechanism for the immunopathogenesis of HBV infection.

Hydrogel microfibers are widely applied in tissue engineering and regenerative medicine due to the tunable morphologies, componential anisotropy, and good biocompatibility. Specially, grooved microfibers with unique advantages can facilitate cell...