Science Advances

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ISSN / EISSN : 2375-2548 / 2375-2548
Total articles ≅ 7,252
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Jingen Zhu, Neeti Ananthaswamy, Swati Jain, Himanshu Batra, Wei-Chun Tang, Douglass A. Lewry, Michael L. Richards, , Paul B. Kilgore, Jian Sha, et al.
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abh1547

Abstract:
A “universal” platform that can rapidly generate multiplex vaccine candidates is critically needed to control pandemics. Using the severe acute respiratory syndrome coronavirus 2 as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates was engineered by incorporating various viral components into appropriate compartments of phage nanoparticle structure. These include expressible spike genes in genome, spike and envelope epitopes as surface decorations, and nucleocapsid proteins in packaged core. Phage decorated with spike trimers was found to be the most potent vaccine candidate in animal models. Without any adjuvant, this vaccine stimulated robust immune responses, both T helper cell 1 (TH1) and TH2 immunoglobulin G subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new nanovaccine design framework might allow the rapid deployment of effective adjuvant-free phage-based vaccines against any emerging pathogen in the future.
Reem B. Rashid, Weiyuan Du, Sophie Griggs, , ,
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abh1055

Abstract:
On-site signal amplification for bioelectronic sensing is a desirable approach to improving recorded signal quality and to reducing the burden on signal transmission and back-end electronics. While organic electrochemical transistors (OECTs) have been used as local transducers of bioelectronic signals, their current output presents challenges for implementation. OECT-based circuits offer new opportunities for high-performance signal processing. In this work, we introduce an active sensing node based on cofacial vertical OECTs forming an ambipolar complementary inverter. The inverter, which shows a voltage gain of 28, is composed of two OECTs on opposite side walls of a single active area, resulting in a footprint identical to a planar OECT. The inverter is used as an analog voltage preamplifier for recording electrocardiogram signals when biased at the input voltage corresponding to peak gain. We further demonstrate compatibility with nontraditional fabrication methods with potential benefits for rapid prototyping and large-area printed electronics.
Xiaoling Qiu, Xiaoling Wang, Yunxiang He, Jieying Liang, , , Joseph J. Richardson, , , , et al.
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abh3482

Abstract:
Soft structures in nature, such as supercoiled DNA and proteins, can organize into complex hierarchical architectures through multiple noncovalent molecular interactions. Identifying new classes of natural building blocks capable of facilitating long-range hierarchical structuring has remained an elusive goal. We report the bottom-up synthesis of a hierarchical metal-phenolic mesocrystal where self-assembly proceeds on different length scales in a spatiotemporally controlled manner. Phenolic-based coordination complexes organize into supramolecular threads that assemble into tertiary nanoscale filaments, lastly packing into quaternary mesocrystals. The hierarchically ordered structures are preserved after thermal conversion into a metal-carbon hybrid framework and can impart outstanding performance to sodium ion batteries, which affords a capability of 72.5 milliampere hours per gram at an ultrahigh rate of 200 amperes per gram and a 90% capacity retention over 15,000 cycles at a current density of 5.0 amperes per gram. This hierarchical structuring of natural polyphenols is expected to find widespread applications.
, Annaïse J. Jauch, , Sedat Dilbaz, Peter Rhein, Stefan A. Steurer, , Radek C. Skoda,
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abi4852

Abstract:
A considerable number of patients with cancer suffer from anemia, which has detrimental effects on quality of life and survival. The mechanisms underlying tumor-associated anemia are multifactorial and poorly understood. Therefore, we aimed at systematically assessing the patho-etiology of tumor-associated anemia in mice. We demonstrate that reduced red blood cell (RBC) survival rather than altered erythropoiesis is driving the development of anemia. The tumor-induced inflammatory and metabolic remodeling affect RBC integrity and augment splenic phagocyte activity promoting erythrophagocytosis. Exercise training normalizes these tumor-associated abnormal metabolic profiles and inflammation and thereby ameliorates anemia, in part, by promoting RBC survival. Fatigue was prevented in exercising tumor-bearing mice. Thus, exercise has the unique potential to substantially modulate metabolism and inflammation and thereby counteracts pathological remodeling of these parameters by the tumor microenvironment. Translation of this finding to patients with cancer could have a major impact on quality of life and potentially survival.
Srinivas Allanki, Boris Strilic, Lilly Scheinberger, Yeszamin L. Onderwater, Alora Marks, Stefan Günther, , Khrievono Kikhi, , , et al.
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abg6497

Abstract:
Damage-induced fibrotic scarring limits tissue regeneration in mammals and is a leading cause of morbidity. In contrast, species like zebrafish can regenerate damaged tissues without excessive fibrosis. However, whether specific signaling pathways can both limit fibrosis and promote regeneration is unclear. Here, we show that interleukin-11 (Il-11)/Stat3 signaling has such a dual function. Zebrafish lacking Il-11 receptor function display severely compromised heart, fin, and scale regeneration. Deep phenotyping and transcriptional analysis of adult hearts and fins show that Il-11 signaling drives cellular reprogramming to orchestrate global and tissue-specific regenerative programs and broadly antagonizes hallmarks of adult mammalian scarring. Mechanistically, our data indicate that IL-11 signaling in endothelial cells antagonizes profibrotic transforming growth factor–β signaling and endothelial-to-mesenchymal transition, limiting scarring and promoting cardiomyocyte repopulation, after injury. Overall, our findings position damage-induced Il-11/Stat3 signaling in a key role limiting fibrosis and promoting regeneration, revealing novel targets for regenerative therapies.
Hongchen Chu, Xiang Xiong, Ya-Jun Gao, , Hao Jing, Cheng-Yao Li, , ,
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abj0935

Abstract:
Rough surfaces lead to diffused light in both reflection and transmission, thereby blurring the reflected and transmitted images. Here, we merge the traditionally incompatible diffuse reflection and undistorted transmission by introducing the concept of random-flip metasurfaces made of randomly flipped components. These metasurfaces have a globally random phase in reflection that leads to diffuse reflection, while the local space inversion and reciprocity principle ensure distortion-free transmission. Notably, the metasurface reflects like a rough surface yet transmits like a smooth one in a broad spectrum. On the basis of complementary random arrays of gold nanorods, we verified this functionality by both optical spectroscopy and imaging experiments over a broad range of frequencies from the visible to the infrared regime. This feature, which originates from breaking the phase correlation between reflection and transmission by the metasurface, could enable a range of new optical materials and display technology.
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abj0786

Abstract:
Protein-mediated allosteric regulations are essential in biology, but their quantitative characterization continues to posit formidable challenges for both experiments and computations. Here, we combine coevolutionary information, multiscale molecular simulations, and free-energy methods to interrogate and quantify the allosteric regulation of functional changes in protein complexes. We apply this approach to investigate the regulation of adenylyl cyclase (AC) by stimulatory and inhibitory G proteins—a prototypical allosteric system that has long escaped from in-depth molecular characterization. We reveal a surprisingly simple ON/OFF regulation of AC functional dynamics through multiple pathways of information transfer. The binding of G proteins reshapes the free-energy landscape of AC following the classical population-shift paradigm. The model agrees with structural and biochemical data and reveals previously unknown experimentally consistent intermediates. Our approach showcases a general strategy to explore uncharted functional space in complex biomolecular regulations.
, Anugraha Mathew, Christian Jenul, Tobias Kohler, Max Bär, , , Urs Stalder, Ya-Chu Hsieh, , et al.
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abg2293

Abstract:
Pseudomonas syringae is an important plant pathogen of many valuable crops worldwide, with more than 60 identified pathovars. The phytotoxins produced by these organisms were related to the severity of the damage caused to the plant. An emerging strategy to treat bacterial infections relies on interference with their signaling systems. In this study, we investigated P. syringae pv. syringae, which produces the virulence factor mangotoxin that causes bacterial apical necrosis on mango leaves. A previously unknown signaling molecule named leudiazen was identified, determined to be unstable and volatile, and responsible for mangotoxin production. A strategy using potassium permanganate, compatible with organic farming, was developed to degrade leudiazen and thus to attenuate the pathogenicity of P. syringae pv. syringae.
, , Xiao Wang, Flaviano José dos Santos, Junda Song, , Karin Schmalzl, Wolfgang F. Schmidt, Alexandre Ivanov, , et al.
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abi7532

Abstract:
The bosonic analogs of topological insulators have been proposed in numerous theoretical works, but their experimental realization is still very rare, especially for spin systems. Recently, two-dimensional (2D) honeycomb van der Waals ferromagnets have emerged as a new platform for topological spin excitations. Here, via a comprehensive inelastic neutron scattering study and theoretical analysis of the spin-wave excitations, we report the realization of topological magnon insulators in CrXTe3 (X = Si, Ge) compounds. The nontrivial nature and intrinsic tunability of the gap opening at the magnon band-crossing Dirac points are confirmed, while the emergence of the corresponding in-gap topological edge states is demonstrated theoretically. The realization of topological magnon insulators with intrinsic gap-unability in this class of remarkable 2D materials will undoubtedly lead to new and fascinating technological applications in the domain of magnonics and topological spintronics.
Yu Zhao, Yu-Qing Xie, Simon Van Herck, Sina Nassiri, Min Gao, Yugang Guo,
Science Advances, Volume 7; https://doi.org/10.1126/sciadv.abg7291

Abstract:
Immune stimulatory antibodies and cytokines elicit potent antitumor immunity. However, the dose-limiting systemic toxicity greatly hinders their clinical applications. Here, we demonstrate a chemical approach, termed “switchable” immune modulator (Sw-IM), to limit the systemic exposure and therefore ameliorate their toxicities. Sw-IM is a biomacromolecular therapeutic reversibly masked by biocompatible polymers through chemical linkers that are responsive to tumor-specific stimuli, such as high reducing potential and acidic pH. Sw-IMs stay inert (switch off) in the circulation and healthy tissues but get reactivated (switch on) selectively in tumor via responsive removal of the polymer masks, thus focusing the immune boosting activities in the tumor microenvironment. Sw-IMs applied to anti–4-1BB agonistic antibody and IL-15 cytokine led to equivalent antitumor efficacy to the parental IMs with markedly reduced toxicities. Sw-IM provides a highly modular and generic approach to improve the therapeutic window and clinical applicability of potent IMs in mono- and combinational immunotherapies.
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