bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microtubule associated protein 4 (MAP4) phosphorylation reduces cardiac microvascular density through NLRP3-related pyroptosis
Authors: Feng Yan-hai , Li Ling-fei , Zhang Qiong , Zhang Jun-hui , Huang Yao , Lv Yan-ling , Jia Jie-Zhi , Zhang Dongxia , Hu Jiong-Yu , Huang Yue-Sheng 
Published: August 2021

AbstractPhosphorylation of MAP4 (p-MAP4) causes cardiac remodeling, with the cardiac microvascular endothelium being considered a vital mediator of this process. In the current study, we investigated the mechanism underlying p-MAP4 influences on cardiac microvascular density. We firstly confirmed elevated MAP4 phosphorylation in the myocardium of MAP4 knock-in (KI) mice. When compared with the corresponding control group, we detected the decreased expression of CD31, CD34, VEGFA, VEGFR2, ANG2, and TIE2 in the myocardium of MAP4 KI mice, accompanied by a reduced plasma concentration of VEGF. Moreover, we observed apoptosis and mitochondrial disruption in the cardiac microvascular endothelium of MAP4 KI animals. Consistently, we noted a decreased cardiac microvascular density, measured by CD31 and lectin staining, in MAP4 KI mice. To explore the underlying mechanism, we targeted the NLRP3-related pyroptosis and found increased expression of the corresponding proteins, including NLRP3, ASC, mature IL-1β, IL-18, and GSDMD-N in the myocardium of MAP4 KI mice. Furthermore, we utilized a MAP4 (Glu) adenovirus to mimic cellular p-MAP4. After incubating HUVECs with MAP4 (Glu) adenovirus, the angiogenic ability was inhibited, and NLRP3-related pyroptosis were significantly activated. Moreover, both cytotoxicity and PI signal were upregulated by the MAP4 (Glu) adenovirus. Finally, NLRP3 inflammasome blockage alleviated the inhibited angiogenic ability induced by MAP4 (Glu) adenovirus. These results demonstrated that p-MAP4 reduced cardiac microvascular density by activating NLRP3-related pyroptosis in both young and aged mice. We thus managed to provide clues explaining MAP4 phosphorylation-induced cardiac remodeling and enriched current knowledge regarding the role of MAP4.
Climate change modulates the stratospheric volcanic sulfate aerosol lifecycle and radiative forcing from tropical eruptions
Authors: Aubry Thomas J. , Staunton-Sykes John , Marshall Lauren R. , Haywood Jim , Abraham Nathan Luke , Schmidt Anja 
Published: August 2021

AbstractExplosive volcanic eruptions affect climate, but how climate change affects the stratospheric volcanic sulfate aerosol lifecycle and radiative forcing remains unexplored. We combine an eruptive column model with an aerosol-climate model to show that the stratospheric aerosol optical depth perturbation from frequent moderate-magnitude tropical eruptions (e.g. Nabro 2011) will be reduced by 75% in a high-end warming scenario compared to today, a consequence of future tropopause height rise and unchanged eruptive column height. In contrast, global-mean radiative forcing, stratospheric warming and surface cooling from infrequent large-magnitude tropical eruptions (e.g. Mt. Pinatubo 1991) will be exacerbated by 30%, 52 and 15% in the future, respectively. These changes are driven by an aerosol size decrease, mainly caused by the acceleration of the Brewer-Dobson circulation, and an increase in eruptive column height. Quantifying changes in both eruptive column dynamics and aerosol lifecycle is therefore key to assessing the climate response to future eruptions.
Topological isolation of developmental regulators in mammalian genomes
Authors: Wu Hua-Jun , Landshammer Alexandro , Stamenova Elena K. , Bolondi Adriano , Kretzmer Helene , Meissner Alexander , Michor Franziska 
Published: August 2021

AbstractPrecise control of mammalian gene expression is facilitated through epigenetic mechanisms and nuclear organization. In particular, insulated chromosome structures are important for regulatory control, but the phenotypic consequences of their boundary disruption on developmental processes are complex and remain insufficiently understood. Here, we generated deeply sequenced Hi-C data for human pluripotent stem cells (hPSCs) that allowed us to identify CTCF loop domains that have highly conserved boundary CTCF sites and show a notable enrichment of individual developmental regulators. Importantly, perturbation of such a boundary in hPSCs interfered with proper differentiation through deregulated distal enhancer-promoter activity. Finally, we found that germline variations affecting such boundaries are subject to purifying selection and are underrepresented in the human population. Taken together, our findings highlight the importance of developmental gene isolation through chromosomal folding structures as a mechanism to ensure their proper expression.
Mobile ions determine the luminescence yield of perovskite light-emitting diodes under pulsed operation
Authors: Kumawat Naresh Kumar , Tress Wolfgang , Gao Feng 
Published: August 2021

AbstractThe external quantum efficiency of perovskite light-emitting diodes (PeLEDs) has advanced quickly during the past few years. However, under pulsed operation, an operation mode which is important for display and visible light communication, the performance of PeLEDs changes a lot and requires in-depth understanding to facilitate these applications. Here, we report the response of PeLEDs under pulsed operation in the range of 10 Hz to 20 kHz. Beyond transient effects in the low frequencies, we find that for higher frequencies (>500 Hz) the transient electroluminescence intensity depends strongly on the duty cycle. This feature is much more pronounced and of different origin than that in conventional LEDs. We rationalise our experimental observations using a mathematical model and assign these features to the effect of mobile ionic charges in the perovskite. Our work also provides important implications for the operation of PeLEDs under the steady state, where accumulation of mobile ions at the interfaces could be beneficial for high electroluminescence yields but harmful for the long-term stability.
A non-printed integrated-circuit textile for wireless theranostics
Authors: Yang Yuxin , Wei Xiaofei , Zhang Nannan , Zheng Juanjuan , Chen Xing , Wen Qian , Luo Xinxin , Lee Chong-Yew , Liu Xiaohong , Zhang Xingcai , Chen Jun , Tao Changyuan , Zhang Wei , Fan Xing 
Published: August 2021

AbstractWhile the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI “nurse” for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.
An N-Cadherin 2 expressing epithelial cell subpopulation predicts response to surgery, chemotherapy and immunotherapy in bladder cancer
Authors: Gouin Kenneth H. , Ing Nathan , Plummer Jasmine T. , Rosser Charles J. , Ben Cheikh Bassem , Oh Catherine , Chen Stephanie S. , Chan Keith Syson , Furuya Hideki , Tourtellotte Warren G. , Knott Simon R. V. , Theodorescu Dan 
Published: August 2021

AbstractNeoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) have revolutionized bladder cancer management. However, stratification of patients that would benefit most from these modalities remains a major clinical challenge. Here, we combine single nuclei RNA sequencing with spatial transcriptomics and single-cell resolution spatial proteomic analysis of human bladder cancer to identify an epithelial subpopulation with therapeutic response prediction ability. These cells express Cadherin 12 (CDH12, N-Cadherin 2), catenins, and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without NAC. In contrast, CDH12-enriched tumors exhibit superior response to ICT. In all settings, patient stratification by tumor CDH12 enrichment offers better prediction of outcome than currently established bladder cancer subtypes. Molecularly, the CDH12 population resembles an undifferentiated state with inherently aggressive biology including chemoresistance, likely mediated through progenitor-like gene expression and fibroblast activation. CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), providing one explanation for ICT efficacy in these tumors. Altogether, this study describes a cancer cell population with an intriguing diametric response to major bladder cancer therapeutics. Importantly, it also provides a compelling framework for designing biomarker-guided clinical trials.
Cryo-EM structures of the TTYH family reveal a novel architecture for lipid interactions
Authors: Sukalskaia Anastasiia , Straub Monique S. , Deneka Dawid , Sawicka Marta , Dutzler Raimund 
Published: August 2021

AbstractThe Tweety homologs (TTYHs) are members of a conserved family of eukaryotic membrane proteins that are abundant in the brain. The three human paralogs were assigned to function as anion channels that are either activated by Ca2+ or cell swelling. To uncover their unknown architecture and its relationship to function, we have determined the structures of human TTYH1–3 by cryo-electron microscopy. All structures display equivalent features of a dimeric membrane protein that contains five transmembrane segments and an extended extracellular domain. As none of the proteins shows attributes reminiscent of an anion channel, we revisited functional experiments and did not find any indication of ion conduction. Instead, we find density in an extended hydrophobic pocket contained in the extracellular domain that emerges from the lipid bilayer, which suggests a role of TTYH proteins in the interaction with lipid-like compounds residing in the membrane.
Ultrafast femtosecond pressure modulation of structure and exciton kinetics in 2D halide perovskites for enhanced light response and stability
Authors: Song Chunpeng , Yang Huanrui , Liu Feng , Cheng Gary J. 
Published: August 2021

AbstractThe carriers’ transportation between layers of two-dimensional (2D) perovskites is inhibited by dielectric confinement. Here, for the first time, we employ a femtosecond laser to introduce ultrafast shock pressure in the range of 0~15.45 GPa to reduce dielectric confinement by modulating the structure and exciton dynamics in a perovskite single crystal (PSCs), e.g. (F-PEA)2PbI4 (4-fluorophenethylammonium, F-PEA). The density functional theory (DFT) simulation and experimental results show that the inorganic framework distortion results in a bandgap reduction. It was found that the exciton-optical phonon coupling and free excitons (FEs) binding energy are minimized at 2.75 GPa shock pressure due to a reduction in dielectric confinement. The stability testing under various harsh light and humid thermal conditions shows that femtosecond laser shocking improves the stability of (F-PEA)2PbI4 PSCs. Femtosecond laser shock processing provides a new approach for regulating the structure and enhancing halide perovskite properties.
Ultra-conformal skin electrodes with synergistically enhanced conductivity for long-time and low-motion artifact epidermal electrophysiology
Authors: Zhao Yan , Zhang Song , Yu Tianhao , Zhang Yan , Ye Guo , Cui Han , He Chengzhi , Jiang Wenchao , Zhai Yu , Lu Chunming , Gu Xiaodan , Liu Nan 
Published: August 2021

AbstractAccurate and imperceptible monitoring of electrophysiological signals is of primary importance for wearable healthcare. Stiff and bulky pregelled electrodes are now commonly used in clinical diagnosis, causing severe discomfort to users for long-time using as well as artifact signals in motion. Here, we report a ~100 nm ultra-thin dry epidermal electrode that is able to conformably adhere to skin and accurately measure electrophysiological signals. It showed low sheet resistance (~24 Ω/sq, 4142 S/cm), high transparency, and mechano-electrical stability. The enhanced optoelectronic performance was due to the synergistic effect between graphene and poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), which induced a high degree of molecular ordering on PEDOT and charge transfer on graphene by strong π-π interaction. Together with ultra-thin nature, this dry epidermal electrode is able to accurately monitor electrophysiological signals such as facial skin and brain activity with low-motion artifact, enabling human-machine interfacing and long-time mental/physical health monitoring.
Rational design of pyrrole derivatives with aggregation-induced phosphorescence characteristics for time-resolved and two-photon luminescence imaging
Authors: Yang Jianhui , Zhang Yahui , Wu Xinghui , Dai Wenbo , Chen Dan , Shi Jianbing , Tong Bin , Peng Qian , Xie Haiyan , Cai Zhengxu , Dong Yuping , Zhang Xin 
Published: August 2021

AbstractPure organic room-temperature phosphorescent (RTP) materials have been suggested to be promising bioimaging materials due to their good biocompatibility and long emission lifetime. Herein, we report a class of RTP materials. These materials are developed through the simple introduction of an aromatic carbonyl to a tetraphenylpyrrole molecule and also exhibit aggregation-induced emission (AIE) properties. These molecules show non-emission in solution and purely phosphorescent emission in the aggregated state, which are desirable properties for biological imaging. Highly crystalline nanoparticles can be easily fabricated with a long emission lifetime (20 μs), which eliminate background fluorescence interference from cells and tissues. The prepared nanoparticles demonstrate two-photon absorption characteristics and can be excited by near infrared (NIR) light, making them promising materials for deep-tissue optical imaging. This integrated aggregation-induced phosphorescence (AIP) strategy diversifies the existing pool of bioimaging agents to inspire the development of bioprobes in the future.
Polarized X-ray scattering measures molecular orientation in polymer-grafted nanoparticles
Authors: Mukherjee Subhrangsu , Streit Jason K. , Gann Eliot , Saurabh Kumar , Sunday Daniel F. , Krishnamurthy Adarsh , Ganapathysubramanian Baskar , Richter Lee J. , Vaia Richard A. , DeLongchamp Dean M. 
Published: August 2021

AbstractPolymer chains are attached to nanoparticle surfaces for many purposes, including altering solubility, influencing aggregation, dispersion, and even tailoring immune responses in drug delivery. The most unique structural motif of polymer-grafted nanoparticles (PGNs) is the high-density region in the corona where polymer chains are stretched under significant confinement, but orientation of these chains has never been measured because conventional nanoscale-resolved measurements lack sensitivity to polymer orientation in amorphous regions. Here, we directly measure local chain orientation in polystyrene grafted gold nanoparticles using polarized resonant soft X-ray scattering (P-RSoXS). Using a computational scattering pattern simulation approach, we measure the thickness of the anisotropic region of the corona and extent of chain orientation within it. These results demonstrate the power of P-RSoXS to discover and quantify orientational aspects of structure in amorphous soft materials and provide a framework for applying this emerging technique to more complex, chemically heterogeneous systems in the future.
Azobenzene-containing liquid crystalline composites for robust ultraviolet detectors based on conversion of illuminance-mechanical stress-electric signals
Authors: Zheng Xiaoxiong , Jia Yining , Chen Aihua 
Published: August 2021

AbstractWearable ultraviolet (UV) detectors have attracted considerable interest in the military and civilian realms. However, semiconductor-based UV detectors are easily interfered by elongation due to the elastic modulus incompatibility between rigid semiconductors and polymer matrix. Polymer detectors containing UV responsive moieties seriously suffer from slow response time. Herein, a UV illuminance–mechanical stress–electric signal conversion has been proposed based on well-defined ionic liquid (IL)-containing liquid crystalline polymer (ILCP) and highly elastic polyurethane (TPU) composite fabrics, to achieve a robust UV monitoring and shielding device with a fast response time of 5 s. Due to the electrostatic interactions and hydrogen bonds between ILs and LC networks, the ILCP-based device can effectively prevent the exudation of ILs and maintain stable performance upon stretching, bending, washing and 1000 testing cycles upon 365 nm UV irradiation. This work provides a generalizable approach toward the development of full polymer-based wearable electronics and soft robots.
Atomically dispersed Pb ionic sites in PbCdSe quantum dot gels enhance room-temperature NO2 sensing
Authors: Geng Xin , Li Shuwei , Mawella-Vithanage Lalani , Ma Tao , Kilani Mohamed , Wang Bingwen , Ma Lu , Hewa-Rahinduwage Chathuranga C. , Shafikova Alina , Nikolla Eranda , Mao Guangzhao , Brock Stephanie L. , Zhang Liang , Luo Long 
Published: August 2021

AbstractAtmospheric NO2 is of great concern due to its adverse effects on human health and the environment, motivating research on NO2 detection and remediation. Existing low-cost room-temperature NO2 sensors often suffer from low sensitivity at the ppb level or long recovery times, reflecting the trade-off between sensor response and recovery time. Here, we report an atomically dispersed metal ion strategy to address it. We discover that bimetallic PbCdSe quantum dot (QD) gels containing atomically dispersed Pb ionic sites achieve the optimal combination of strong sensor response and fast recovery, leading to a high-performance room-temperature p-type semiconductor NO2 sensor as characterized by a combination of ultra–low limit of detection, high sensitivity and stability, fast response and recovery. With the help of theoretical calculations, we reveal the high performance of the PbCdSe QD gel arises from the unique tuning effects of Pb ionic sites on NO2 binding at their neighboring Cd sites.
Targeting of eIF6-driven translation induces a metabolic rewiring that reduces NAFLD and the consequent evolution to hepatocellular carcinoma
Authors: Scagliola Alessandra , Miluzio Annarita , Ventura Gabriele , Oliveto Stefania , Cordiglieri Chiara , Manfrini Nicola , Cirino Delia , Ricciardi Sara , Valenti Luca , Baselli Guido , D’Ambrosio Roberta , Maggioni Marco , Brina Daniela , Bresciani Alberto , Biffo Stefano 
Published: August 2021

AbstractA postprandial increase of translation mediated by eukaryotic Initiation Factor 6 (eIF6) occurs in the liver. Its contribution to steatosis and disease is unknown. In this study we address whether eIF6-driven translation contributes to disease progression. eIF6 levels increase throughout the progression from Non-Alcoholic Fatty Liver Disease (NAFLD) to hepatocellular carcinoma. Reduction of eIF6 levels protects the liver from disease progression. eIF6 depletion blunts lipid accumulation, increases fatty acid oxidation (FAO) and reduces oncogenic transformation in vitro. In addition, eIF6 depletion delays the progression from NAFLD to hepatocellular carcinoma, in vivo. Mechanistically, eIF6 depletion reduces the translation of transcription factor C/EBPβ, leading to a drop in biomarkers associated with NAFLD progression to hepatocellular carcinoma and preserves mitochondrial respiration due to the maintenance of an alternative mTORC1-eIF4F translational branch that increases the expression of transcription factor YY1. We provide proof-of-concept that in vitro pharmacological inhibition of eIF6 activity recapitulates the protective effects of eIF6 depletion. We hypothesize the existence of a targetable, evolutionarily conserved translation circuit optimized for lipid accumulation and tumor progression.
Optimization of C-to-G base editors with sequence context preference predictable by machine learning methods
Authors: Yuan Tanglong , Yan Nana , Fei Tianyi , Zheng Jitan , Meng Juan , Li Nana , Liu Jing , Zhang Haihang , Xie Long , Ying Wenqin , Li Di , Shi Lei , Sun Yongsen , Li Yongyao , Li Yixue , Sun Yidi , Zuo Erwei 
Published: August 2021

AbstractEfficient and precise base editors (BEs) for C-to-G transversion are highly desirable. However, the sequence context affecting editing outcome largely remains unclear. Here we report engineered C-to-G BEs of high efficiency and fidelity, with the sequence context predictable via machine-learning methods. By changing the species origin and relative position of uracil-DNA glycosylase and deaminase, together with codon optimization, we obtain optimized C-to-G BEs (OPTI-CGBEs) for efficient C-to-G transversion. The motif preference of OPTI-CGBEs for editing 100 endogenous sites is determined in HEK293T cells. Using a sgRNA library comprising 41,388 sequences, we develop a deep-learning model that accurately predicts the OPTI-CGBE editing outcome for targeted sites with specific sequence context. These OPTI-CGBEs are further shown to be capable of efficient base editing in mouse embryos for generating Tyr-edited offspring. Thus, these engineered CGBEs are useful for efficient and precise base editing, with outcome predictable based on sequence context of targeted sites.
Deep learning-based transformation of H&E stained tissues into special stains
Authors: de Haan Kevin , Zhang Yijie , Zuckerman Jonathan E. , Liu Tairan , Sisk Anthony E. , Diaz Miguel F. P. , Jen Kuang-Yu , Nobori Alexander , Liou Sofia , Zhang Sarah , Riahi Rana , Rivenson Yair , Wallace W. Dean , Ozcan Aydogan 
Published: August 2021

AbstractPathology is practiced by visual inspection of histochemically stained tissue slides. While the hematoxylin and eosin (H&E) stain is most commonly used, special stains can provide additional contrast to different tissue components. Here, we demonstrate the utility of supervised learning-based computational stain transformation from H&E to special stains (Masson’s Trichrome, periodic acid-Schiff and Jones silver stain) using kidney needle core biopsy tissue sections. Based on the evaluation by three renal pathologists, followed by adjudication by a fourth pathologist, we show that the generation of virtual special stains from existing H&E images improves the diagnosis of several non-neoplastic kidney diseases, sampled from 58 unique subjects (P = 0.0095). A second study found that the quality of the computationally generated special stains was statistically equivalent to those which were histochemically stained. This stain-to-stain transformation framework can improve preliminary diagnoses when additional special stains are needed, also providing significant savings in time and cost.