Advanced Science

Journal Information
ISSN / EISSN : 2198-3844 / 2198-3844
Published by: Wiley (10.1002)
Total articles ≅ 3,352
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Susmriti Das Mahapatra, Preetam Chandan Mohapatra, Adrianus Indrat Aria, Graham Christie, , Stephan Hofmann,
Published: 13 July 2021
Advanced Science; doi:10.1002/advs.202100864

Piezoelectric materials are widely referred to as “smart” materials because they can transduce mechanical pressure acting on them to electrical signals and vice versa. They are extensively utilized in harvesting mechanical energy from vibrations, human motion, mechanical loads, etc., and converting them into electrical energy for low power devices. Piezoelectric transduction offers high scalability, simple device designs, and high-power densities compared to electro-magnetic/static and triboelectric transducers. This review aims to give a holistic overview of recent developments in piezoelectric nanostructured materials, polymers, polymer nanocomposites, and piezoelectric films for implementation in energy harvesting. The progress in fabrication techniques, morphology, piezoelectric properties, energy harvesting performance, and underpinning fundamental mechanisms for each class of materials, including polymer nanocomposites using conducting, non-conducting, and hybrid fillers are discussed. The emergent application horizon of piezoelectric energy harvesters particularly for wireless devices and self-powered sensors is highlighted, and the current challenges and future prospects are critically discussed.
Lizhen Xu, Heng Zhang, Yunfei Wang, Xiancui Lu, Zhenye Zhao, Cheng Ma, Shilong Yang, Vladimir Yarov‐Yarovoy, Yuhua Tian, , et al.
Published: 11 July 2021
Advanced Science; doi:10.1002/advs.202101716

Transient receptor potential vanilloid 1 (TRPV1) ion channel is a nociceptor critically involved in pain sensation. Direct blockade of TRPV1 exhibits significant analgesic effects but also incurs severe side effects such as hyperthermia, causing failures of TRPV1 inhibitors in clinical trials. In order to selectively target TRPV1 channels that are actively involved in pain-sensing, peptidic positive allosteric modulators (PAMs) based on the high-resolution structure of the TRPV1 intracellular ankyrin-repeat like domain are de novo designed. The hotspot centric approach is optimized for protein design; its usage in Rosetta increases the success rate in protein binder design. It is demonstrated experimentally, with a combination of fluorescence resonance energy transfer (FRET) imaging, surface plasmon resonance, and patch-clamp recording, that the designed PAMs bind to TRPV1 with nanomolar affinity and allosterically enhance its response to ligand activation as it is designed. It is further demonstrated that the designed PAM exhibits long-lasting in vivo analgesic effects in rats without changing their body temperature, suggesting that they have potentials for developing into novel analgesics.
Ying Zhang, Qi Shen, Qi Li, Panpan He, Jinyan Li, , Jing Wang, Yefan Duan, Chuang Shen, , et al.
Published: 11 July 2021
Advanced Science; doi:10.1002/advs.202100386

Broadband near-infrared (NIR) photothermal and photoacoustic agents covering from the first NIR (NIR-I) to the second NIR (NIR-II) biowindow are of great significance for imaging and therapy of cancers. In this work, ultrathin two-dimensional plasmonic PtAg nanosheets are discovered with strong broadband light absorption from NIR-I to NIR-II biowindow, which exhibit outstanding photothermal and photoacoustic effects under both 785 and 1064 nm lasers. Photothermal conversion efficiencies (PCEs) of PtAg nanosheets reach 19.2% under 785 nm laser and 45.7% under 1064 nm laser. The PCE under 1064 nm laser is higher than those of most reported inorganic NIR-II photothermal nanoagents. After functionalization with folic acid modified thiol-poly(ethylene glycol) (SH-PEG-FA), PtAg nanosheets endowed with good biocompatibility and 4T1 tumor-targeted function give high performances for photoacoustic imaging (PAI) and photothermal therapy (PTT) in vivo under both 785 and 1064 nm lasers. The effective ablation of tumors in mice can be realized without side effects and tumor metastasis by PAI-guided PTT of PtAg nanosheets under 785 or 1064 nm laser. The results demonstrate that the prepared PtAg nanosheets with ultrathin thickness and small size can serve as a promising phototheranostic nanoplatform for PAI-guided PTT of tumors in both NIR-I and NIR-II biowindows.
Cecilia Colombero, David Remy, Sandra Antoine‐Bally, Anne‐Sophie Macé, Pedro Monteiro, Nadia ElKhatib, Margot Fournier, Ahmed Dahmani, Elodie Montaudon, Guillaume Montagnac, et al.
Published: 11 July 2021
Advanced Science; doi:10.1002/advs.202101614

Under conditions of starvation, normal and tumor epithelial cells can rewire their metabolism toward the consumption of extracellular proteins, including extracellular matrix-derived components as nutrient sources. The mechanism of pericellular matrix degradation by starved cells has been largely overlooked. Here it is shown that matrix degradation by breast and pancreatic tumor cells and patient-derived xenograft explants increases by one order of magnitude upon amino acid and growth factor deprivation. In addition, it is found that collagenolysis requires the invadopodia components, TKS5, and the transmembrane metalloproteinase, MT1-MMP, which are key to the tumor invasion program. Increased collagenolysis is controlled by mTOR repression upon nutrient depletion or pharmacological inhibition by rapamycin. The results reveal that starvation hampers clathrin-mediated endocytosis, resulting in MT1-MMP accumulation in arrested clathrin-coated pits. The study uncovers a new mechanism whereby mTOR repression in starved cells leads to the repurposing of abundant plasma membrane clathrin-coated pits into robust ECM-degradative assemblies.
Hyeokjun Seo, Sunghyun Yoon, Banseok Oh, Yongchul G. Chung,
Published: 11 July 2021
Advanced Science; doi:10.1002/advs.202004999

Liquid-phase chemical separations from complex mixtures of hydrocarbon molecules into singular components are large-scale and energy-intensive processes. Membranes with molecular specificity that efficiently separate molecules of similar size and shape can avoid phase changes, thereby reducing the energy intensity of the process. Here, forward osmosis molecular differentiation of hexane isomers through a combination of size- and shape-based separation of molecules is demonstrated. An ultramicroporous carbon membrane produced with 6FDA-polyimides realized the separation of isomers for different shapes of di-branched, mono-branched, and linear molecules. The draw solvents provide the driving force for fractionation of hexane isomers with a sub-0.1 nm size difference at room temperature without liquid-phase pressurization. Such membranes could perform bulk chemical separations of organic liquids to achieve major reductions in the energy intensity of the separation processes.
Xiao Xiang, Ziyang Liu, Chong Zhang, Zhao Li, Jie Gao, Changkun Zhang, Qi Cao, Jinghui Cheng, Hengkang Liu, Dingbao Chen, et al.
Published: 11 July 2021
Advanced Science; doi:10.1002/advs.202101230

Intrahepatic cholangiocarcinoma (ICC) is highly heterogeneous. Here, the authors perform exome sequencing and bulk RNA sequencing on 73 tumor regions from 14 ICC patients to portray the multi-faceted intratumor heterogeneity (ITH) landscape of ICC. The authors show that ITH is highly concordant across genomic, transcriptomic, and immune levels. Comparison of these data to 8 published datasets reveals significantly higher degrees of ITH in ICC than hepatocellular carcinoma. Remarkably, the authors find that high-ITH tumors highly overlap with the IDH (isocitrate dehydrogenase)-mutant subgroup (IDH-SG), comprising of IDH-mutated tumors and IDH-like tumors, that is, those IDH-wildtype tumors that exhibit similar molecular profiles to the IDH-mutated ones. Furthermore, IDH-SG exhibits less T cell infiltration and lower T cell cytotoxicity, indicating a colder tumor microenvironment (TME). The higher ITH and colder TME of IDH-SG are successfully validated by single-cell RNA sequencing on 17 503 cells from 4 patients. Collectively, the study shows that IDH mutant subgroup status, rather than IDH mutation alone, is associated with ITH and the TME of ICC tumors. The results highlight that IDH-like patients may also benefit from IDH targeted therapies and provide important implications for the diagnosis and treatment of ICC.
Sizhan Liu, Alexander R. DeFilippo, Mahalingam Balasubramanian, Zhenxian Liu, SuYin Grass Wang, Yu‐Sheng Chen, Stella Chariton, Vitali Prakapenka, Xiangpeng Luo, Liuyan Zhao, et al.
Published: 11 July 2021
Advanced Science; doi:10.1002/advs.202003046

Perovskite photovoltaic ABX3 systems are being studied due to their high energy-conversion efficiencies with current emphasis placed on pure inorganic systems. In this work, synchrotron single-crystal diffraction measurements combined with second harmonic generation measurements reveal the absence of inversion symmetry below room temperature in CsPbBr3. Local structural analysis by pair distribution function and X-ray absorption fine structure methods are performed to ascertain the local ordering, atomic pair correlations, and phase evolution in a broad range of temperatures. The currently accepted space group assignments for CsPbBr3 are found to be incorrect in a manner that profoundly impacts physical properties. New assignments are obtained for the bulk structure: I m 3 ¯ (above ≈410 K), P21/m (between ≈300 K and ≈410 K), and the polar group Pm (below ≈300 K), respectively. The newly observed structural distortions exist in the bulk structure consistent with the expectation of previous photoluminescence and Raman measurements. High-pressure measurements reveal multiple low-pressure phases, one of which exists as a metastable phase at ambient pressure. This work should help guide research in the perovskite photovoltaic community to better control the structure under operational conditions and further improve transport and optical properties.
Di Chen, Yiran Zhang, Wen Wang, Huan Chen, Ting Ling, Renyu Yang, Yawei Wang, Chao Duan, Yu Liu, Xin Guo, et al.
Published: 11 July 2021
Advanced Science; doi:10.1002/advs.202100311

Metabolite-protein interactions (MPIs) play key roles in cancer metabolism. However, our current knowledge about MPIs in cancers remains limited due to the complexity of cancer cells. Herein, the authors construct an integrative MPI network and propose a MPI network based hepatocellular carcinoma (HCC) subtyping and mechanism exploration workflow. Based on the expressions of hub proteins on the MPI network, two prognosis-distinctive HCC subtypes are identified. Meanwhile, multiple interdependent features of the poor prognostic subtype are observed, including hypoxia, DNA hypermethylation of metabolic pathways, fatty acid accumulation, immune pathway up-regulation, and exhausted T-cell infiltration. Notably, the immune pathway up-regulation is probably induced by accumulated unsaturated fatty acids which are predicted to interact with multiple immune regulators like SRC and TGFB1. Moreover, based on tumor microenvironment compositions, the poor prognostic subtype is further divided into two sub-populations showing remarkable differences in metabolism. The subtyping shows a strong consistency across multiple HCC cohorts including early-stage HCC. Overall, the authors redefine robust HCC prognosis subtypes and identify potential MPIs linking metabolism to immune regulations, thus promoting understanding and clinical applications about HCC metabolism heterogeneity.
Wuming Wang, , Hong‐Bin Liu, Zhiqiang Xiong, Ho‐Duen Leung, Ruican Cao, Alan Lap‐Yin Pang, Xianwei Su, Patrick Wai Nok Law, Zhiju Zhao, et al.
Published: 11 July 2021
Advanced Science; doi:10.1002/advs.202100849

The regulation of cardiomyocyte differentiation is a fundamental aspect of cardiac development and regenerative medicine. PTEN plays important roles during embryonic development. However, its role in cardiomyocyte differentiation remains unknown. In this study, a low-cost protocol for cardiomyocyte differentiation from mouse embryonic stem cells (ESCs) is presented and it is shown that Pten deletion potently suppresses cardiomyocyte differentiation. Transcriptome analysis shows that the expression of a series of cardiomyocyte marker genes is downregulated in Pten−/− cardiomyocytes. Pten ablation induces Dnmt3b expression via the AKT/FoxO3a pathway and regulates the expression of a series of imprinted genes, including Igf2. Double knockout of Dnmt3l and Dnmt3b rescues the deficiency of cardiomyocyte differentiation of Pten−/− ESCs. The DNA methylomes from wild-type and Pten−/− embryoid bodies and cardiomyocytes are analyzed by whole-genome bisulfite sequencing. Pten deletion significantly promotes the non-CG (CHG and CHH) methylation levels of genomic DNA during cardiomyocyte differentiation, and the non-CG methylation levels of cardiomyocyte genes and Igf2 are increased in Pten−/− cardiomyocytes. Igf2 or Igf1r deletion also suppresses cardiomyocyte differentiation through the MAPK/ERK signaling pathway, and IGF2 supplementation partially rescues the cardiomyocyte differentiation. Finally, Pten conditional knockout mice are generated and the role of PTEN in cardiomyocyte differentiation is verified in vivo.
Yupeng Chen, Zhongpeng Zhu, Xiangyu Jiang,
Published: 10 July 2021
Advanced Science; doi:10.1002/advs.202100949

Patterned conducting polymer films with unique structures have promising prospects for application in various fields, such as actuation, water purification, sensing, and bioelectronics. However, their practical application is hindered because of the limitations of existing construction methods. Herein, a strategy is proposed for the superhydrophobic-substrate-assisted construction of free-standing 3D microcavity-patterned conducting polymer films (McPCPFs) at micrometer resolution. Easy-peeling and nondestructive transfer properties are achieved through electrochemical polymerization along the solid/liquid/gas triphase interface on micropillar-structured substrates. The effects of the wettability and geometrical parameters of the substrates on the construction of McPCPFs are systematically investigated in addition to the evolution of the epitaxial growth along the triphase interface at different polymerization times. The McPCPFs can be easily peeled from superhydrophobic surfaces using ethanol because of weak adhesion and nondestructively transferred to various substrates taking advantage of the capillarity. Furthermore, sensitive light-driven McPCPF locomotion on organic liquid surfaces is demonstrated. Ultimately, a facile strategy for the construction of free-standing 3D microstructure-patterned conducting polymer films is proposed, which can improve productivity and applicability of the films in different fields and expand the application scope of superwettable interfaces.
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