bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma
Authors: Wang Ning , Tan Hor-Yue , Lu Yuanjun , Chan Yau-Tuen , Wang Di , Guo Wei , Xu Yu , Zhang Cheng , Chen Feiyu , Tang Guoyi , Feng Yibin 
Published: February 2021

AbstractAltered energy metabolism of cancer cells shapes the immune cell response in the tumor microenvironment that facilitates tumor progression. Herein, we reported the novel of tumor cell-expressed Piwi Like RNA-Mediated Gene Silencing 1 (PIWIL1) in mediating the crosstalk of fatty acid metabolism and immune response of human hepatocellular carcinoma (HCC). PIWIL1 expression in HCC was increased compared to normal hepatic tissues and was positively correlated with the proliferation rate of HCC cell lines. PIWIL1 overexpression accelerated in vitro proliferation and in vivo growth of HCC tumors, while PIWIL1 knockdown showed opposite effects. PIWIL1 increased oxygen consumption and energy production via fatty acid metabolism without altering aerobic glycolysis. Inhibition of fatty acid metabolism abolished PIWIL1-induced HCC proliferation and growth. RNA-seq analysis revealed that immune system regulation might be involved, which was echoed by the experimental observation that PIWIL1-overexpressing HCC cells attracted myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment. MDSCs depletion reduced the proliferation and growth of PIWIL1-overexpressing HCC tumors. Complement C3, whose secretion was induced by PIWIL1 in HCC cells, mediates the interaction of HCC cells with MDSCs by activated p38 MAPK signaling in MDSCs, which in turn initiated expression of immunosuppressive cytokine IL10. Neutralizing IL10 secretion reduced the immunosuppressive activity of MDSCs in the microenvironment of PIWIL1-overexpressing HCC. Taken together, our study unraveled the critical role of PIWIL1 in initiating the interaction of cancer cell metabolism and immune cell response in HCC. Tumor cells-expressed PIWIL1 may be a potential target for the development of novel HCC treatment.
Long non-coding RNA Lnc-LALC facilitates colorectal cancer liver metastasis via epigenetically silencing LZTS1
Authors: Zhang Chuan , Wang Lu , Jin Chi , Zhou Jiahui , Peng Chaofan , Wang Yong , Xu Ziwei , Zhang Dongsheng , Huang Yuanjian , Zhang Yue , Ji Dongjian , Peng Wen , Jin Kangpeng , Tang Junwei , Feng Yifei , Sun Yueming 
Published: February 2021

AbstractColorectal cancer (CRC) is one of the most common cancers around the world and endangers human health seriously. Liver metastasis is an important factor affecting the long-term prognosis of CRC and the specific mechanism of CRLM (colorectal cancer with liver metastasis) is not fully understood. LZTS1 has been found dysregulated in many cancers, especially in CRC. Theories suggested that hypermethylation of the promoter regions of LZTS1 was responsible for LZTS1 abnormal expression in multiple malignant tumors. Although the role of LZTS1 in CRC cell proliferation has been reported, its role in CRLM remains unclear. Numerous studies reported Long non-coding RNA (lncRNA) could regulate the gene expression level by regulating gene methylation status in many tumors. However, whether there were lncRNAs could change the methylation status of LZTS1 or not in CRLM was unknown. In this study, we aimed to investigate whether there are lncRNAs can regulate the expression of LZTS1 through affecting DNA methylation in CRLM. We found that upregulated Lnc-LALC in CRC was negatively correlated with LZTS1 expression, and Lnc-LALC could regulate LZTS1 expression in both mRNA and protein level in our study. Functionally, Lnc-LALC enhanced the CRC cells metastasis ability in vitro and vivo through inhibiting the expression of LZTS1. Furthermore, the precise mechanisms exploration showed that lnc-LALC could recruit DNA methyltransferases (DNMTs) to the LZTS1 promoter by combining with Enhancer of zeste homolog 2(EZH2) and then altered the expression of LZTS1 via DNMTs-mediated DNA methylation. Collectively, our data demonstrated the important role of Lnc-LALC/ LZTS1 axis in CRLM development.
The crosstalk between HIFs and mitochondrial dysfunctions in cancer development
Authors: Bao Xingting , Zhang Jinhua , Huang Guomin , Yan Junfang , Xu Caipeng , Dou Zhihui , Sun Chao , Zhang Hong 
Published: February 2021

AbstractMitochondria are essential cellular organelles that are involved in regulating cellular energy, metabolism, survival, and proliferation. To some extent, cancer is a genetic and metabolic disease that is closely associated with mitochondrial dysfunction. Hypoxia-inducible factors (HIFs), which are major molecules that respond to hypoxia, play important roles in cancer development by participating in multiple processes, such as metabolism, proliferation, and angiogenesis. The Warburg phenomenon reflects a pseudo-hypoxic state that activates HIF-1α. In addition, a product of the Warburg effect, lactate, also induces HIF-1α. However, Warburg proposed that aerobic glycolysis occurs due to a defect in mitochondria. Moreover, both HIFs and mitochondrial dysfunction can lead to complex reprogramming of energy metabolism, including reduced mitochondrial oxidative metabolism, increased glucose uptake, and enhanced anaerobic glycolysis. Thus, there may be a connection between HIFs and mitochondrial dysfunction. In this review, we systematically discuss the crosstalk between HIFs and mitochondrial dysfunctions in cancer development. Above all, the stability and activity of HIFs are closely influenced by mitochondrial dysfunction related to tricarboxylic acid cycle, electron transport chain components, mitochondrial respiration, and mitochondrial-related proteins. Furthermore, activation of HIFs can lead to mitochondrial dysfunction by affecting multiple mitochondrial functions, including mitochondrial oxidative capacity, biogenesis, apoptosis, fission, and autophagy. In general, the regulation of tumorigenesis and development by HIFs and mitochondrial dysfunction are part of an extensive and cooperative network.
Gab2 deficiency suppresses high-fat diet-induced obesity by reducing adipose tissue inflammation and increasing brown adipose function in mice
Authors: Wang Xinhui , Zhao Yinan , Zhou Dekun , Tian Yingpu , Feng Gensheng , Lu Zhongxian 
Published: February 2021

AbstractObesity is caused by a long-term imbalance between energy intake and consumption and is regulated by multiple signals. This study investigated the effect of signaling scaffolding protein Gab2 on obesity and its relevant regulation mechanism. Gab2 knockout (KO) and wild-type (WT) mice were fed with a standard diet (SD) or high-fat diet (HFD) for 12 weeks. The results showed that the a high-fat diet-induced Gab2 expression in adipose tissues, but deletion of Gab2 attenuated weight gain and improved glucose tolerance in mice fed with a high-fat diet. White adipose tissue and systemic inflammations were reduced in HFD-fed Gab2 deficiency mice. Gab2 deficiency increased the expression of Ucp1 and other thermogenic genes in brown adipose tissue. Furthermore, the regulation of Gab2 on the mature differentiation and function of adipocytes was investigated in vitro using primary or immortalized brown preadipocytes. The expression of brown fat-selective genes was found to be elevated in differentiated adipocytes without Gab2. The mechanism of Gab2 regulating Ucp1 expression in brown adipocytes involved with its downstream PI3K (p85)-Akt-FoxO1 signaling pathway. Our research suggests that deletion of Gab2 suppresses diet-induced obesity by multiple pathways and Gab2 may be a novel therapeutic target for the treatment of obesity and associated complications.
Facile synthesis of nickel cobaltite quasi-hexagonal nanosheets for multilevel resistive switching and synaptic learning applications
Authors: Dongale Tukaram D. , Khot Atul C. , Takaloo Ashkan Vakilipour , Kim Tae Geun 
Published: February 2021

AbstractHigh-density memory devices are essential to sustain growth in information technology (IT). Furthermore, brain-inspired computing devices are the future of IT businesses such as artificial intelligence, deep learning, and big data. Herein, we propose a facile and hierarchical nickel cobaltite (NCO) quasi-hexagonal nanosheet-based memristive device for multilevel resistive switching (RS) and synaptic learning applications. Electrical measurements of the Pt/NCO/Pt device show the electroforming free pinched hysteresis loops at different voltages, suggesting the multilevel RS capability of the device. The detailed memristive properties of the device were calculated using the time-dependent current–voltage data. The two-valued charge-flux properties indicate the memristive and multilevel RS characteristics of the device. Interestingly, the Pt/NCO/Pt memristive device shows a compliance current (CC)-dependent RS property; compliance-free RS was observed from 10−2 to 10−4 A, and the compliance effect dominated in the range of 10−5–10−6 A. In CC control mode, the device demonstrated three resistance states during endurance and retention measurements. In addition, the device was successful in mimicking biological synaptic properties such as potentiation-depression- and spike-timing-dependent plasticity rules. The results of the present investigation demonstrated that solution-processable NCO nanosheets are potential switching materials for high-density memory and brain-inspired computing applications.
A computational reward learning account of social media engagement
Authors: Lindström Björn , Bellander Martin , Schultner David T. , Chang Allen , Tobler Philippe N. , Amodio David M. 
Published: February 2021

AbstractSocial media has become a modern arena for human life, with billions of daily users worldwide. The intense popularity of social media is often attributed to a psychological need for social rewards (likes), portraying the online world as a Skinner Box for the modern human. Yet despite such portrayals, empirical evidence for social media engagement as reward-based behavior remains scant. Here, we apply a computational approach to directly test whether reward learning mechanisms contribute to social media behavior. We analyze over one million posts from over 4000 individuals on multiple social media platforms, using computational models based on reinforcement learning theory. Our results consistently show that human behavior on social media conforms qualitatively and quantitatively to the principles of reward learning. Specifically, social media users spaced their posts to maximize the average rate of accrued social rewards, in a manner subject to both the effort cost of posting and the opportunity cost of inaction. Results further reveal meaningful individual difference profiles in social reward learning on social media. Finally, an online experiment (n = 176), mimicking key aspects of social media, verifies that social rewards causally influence behavior as posited by our computational account. Together, these findings support a reward learning account of social media engagement and offer new insights into this emergent mode of modern human behavior.
The contribution of water radiolysis to marine sedimentary life
Authors: Sauvage Justine F. , Flinders Ashton , Spivack Arthur J. , Pockalny Robert , Dunlea Ann G. , Anderson Chloe H. , Smith David C. , Murray Richard W. , D’Hondt Steven 
Published: February 2021

AbstractWater radiolysis continuously produces H2and oxidized chemicals in wet sediment and rock. Radiolytic H2has been identified as the primary electron donor (food) for microorganisms in continental aquifers kilometers below Earth’s surface. Radiolytic products may also be significant for sustaining life in subseafloor sediment and subsurface environments of other planets. However, the extent to which most subsurface ecosystems rely on radiolytic products has been poorly constrained, due to incomplete understanding of radiolytic chemical yields in natural environments. Here we show that all common marine sediment types catalyse radiolytic H2production, amplifying yields by up to 27X relative to pure water. In electron equivalents, the global rate of radiolytic H2production in marine sediment appears to be 1-2% of the global organic flux to the seafloor. However, most organic matter is consumed at or near the seafloor, whereas radiolytic H2is produced at all sediment depths. Comparison of radiolytic H2consumption rates to organic oxidation rates suggests that water radiolysis is the principal source of biologically accessible energy for microbial communities in marine sediment older than a few million years. Where water permeates similarly catalytic material on other worlds, life may also be sustained by water radiolysis.
A tailored multi-functional catalyst for ultra-efficient styrene production under a cyclic redox scheme
Authors: Zhu Xing , Gao Yunfei , Wang Xijun , Haribal Vasudev , Liu Junchen , Neal Luke M. , Bao Zhenghong , Wu Zili , Wang Hua , Li Fanxing 
Published: February 2021

AbstractStyrene is an important commodity chemical that is highly energy and CO2 intensive to produce. We report a redox oxidative dehydrogenation (redox-ODH) strategy to efficiently produce styrene. Facilitated by a multifunctional (Ca/Mn)1−xO@KFeO2 core-shell redox catalyst which acts as (i) a heterogeneous catalyst, (ii) an oxygen separation agent, and (iii) a selective hydrogen combustion material, redox-ODH auto-thermally converts ethylbenzene to styrene with up to 97% single-pass conversion and >94% selectivity. This represents a 72% yield increase compared to commercial dehydrogenation on a relative basis, leading to 82% energy savings and 79% CO2 emission reduction. The redox catalyst is composed of a catalytically active KFeO2 shell and a (Ca/Mn)1−xO core for reversible lattice oxygen storage and donation. The lattice oxygen donation from (Ca/Mn)1−xO sacrificially stabilizes Fe3+ in the shell to maintain high catalytic activity and coke resistance. From a practical standpoint, the redox catalyst exhibits excellent long-term performance under industrially compatible conditions.
The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis
Authors: Scheer Hélène , de Almeida Caroline , Ferrier Emilie , Simonnot Quentin , Poirier Laure , Pflieger David , Sement François M. , Koechler Sandrine , Piermaria Christina , Krawczyk Paweł , Mroczek Seweryn , Chicher Johana , Kuhn Lauriane , Dziembowski Andrzej , Hammann Philippe , Zuber Hélène , Gagliardi Dominique 
Published: February 2021

AbstractUridylation is a widespread modification destabilizing eukaryotic mRNAs. Yet, molecular mechanisms underlying TUTase-mediated mRNA degradation remain mostly unresolved. Here, we report that the Arabidopsis TUTase URT1 participates in a molecular network connecting several translational repressors/decapping activators. URT1 directly interacts with DECAPPING 5 (DCP5), the Arabidopsis ortholog of human LSM14 and yeast Scd6, and this interaction connects URT1 to additional decay factors like DDX6/Dhh1-like RNA helicases. Nanopore direct RNA sequencing reveals a global role of URT1 in shaping poly(A) tail length, notably by preventing the accumulation of excessively deadenylated mRNAs. Based on in vitro and in planta data, we propose a model that explains how URT1 could reduce the accumulation of oligo(A)-tailed mRNAs both by favoring their degradation and because 3’ terminal uridines intrinsically hinder deadenylation. Importantly, preventing the accumulation of excessively deadenylated mRNAs avoids the biogenesis of illegitimate siRNAs that silence endogenous mRNAs and perturb Arabidopsis growth and development.
Combinatorial CRISPR screen identifies fitness effects of gene paralogues
Authors: Thompson Nicola A. , Ranzani Marco , van der Weyden Louise , Iyer Vivek , Offord Victoria , Droop Alastair , Behan Fiona , Gonçalves Emanuel , Speak Anneliese , Iorio Francesco , Hewinson James , Harle Victoria , Robertson Holly , Anderson Elizabeth , Fu Beiyuan , Yang Fengtang , Zagnoli-Vieira Guido , Chapman Phil , Del Castillo Velasco-Herrera Martin , Garnett Mathew J. , Jackson Stephen P. , Adams David J. 
Published: February 2021

AbstractGenetic redundancy has evolved as a way for human cells to survive the loss of genes that are single copy and essential in other organisms, but also allows tumours to survive despite having highly rearranged genomes. In this study we CRISPR screen 1191 gene pairs, including paralogues and known and predicted synthetic lethal interactions to identify 105 gene combinations whose co-disruption results in a loss of cellular fitness. 27 pairs influence fitness across multiple cell lines including the paralogues FAM50A/FAM50B, two genes of unknown function. Silencing of FAM50B occurs across a range of tumour types and in this context disruption of FAM50A reduces cellular fitness whilst promoting micronucleus formation and extensive perturbation of transcriptional programmes. Our studies reveal the fitness effects of FAM50A/FAM50B in cancer cells.
Improved protein structure refinement guided by deep learning based accuracy estimation
Authors: Hiranuma Naozumi , Park Hahnbeom , Baek Minkyung , Anishchenko Ivan , Dauparas Justas , Baker David 
Published: February 2021

AbstractWe develop a deep learning framework (DeepAccNet) that estimates per-residue accuracy and residue-residue distance signed error in protein models and uses these predictions to guide Rosetta protein structure refinement. The network uses 3D convolutions to evaluate local atomic environments followed by 2D convolutions to provide their global contexts and outperforms other methods that similarly predict the accuracy of protein structure models. Overall accuracy predictions for X-ray and cryoEM structures in the PDB correlate with their resolution, and the network should be broadly useful for assessing the accuracy of both predicted structure models and experimentally determined structures and identifying specific regions likely to be in error. Incorporation of the accuracy predictions at multiple stages in the Rosetta refinement protocol considerably increased the accuracy of the resulting protein structure models, illustrating how deep learning can improve search for global energy minima of biomolecules.
Boosting photocatalytic hydrogen production from water by photothermally induced biphase systems
Authors: Guo Shaohui , Li Xuanhua , Li Ju , Wei Bingqing 
Published: February 2021

AbstractSolar-driven hydrogen production from water using particulate photocatalysts is considered the most economical and effective approach to produce hydrogen fuel with little environmental concern. However, the efficiency of hydrogen production from water in particulate photocatalysis systems is still low. Here, we propose an efficient biphase photocatalytic system composed of integrated photothermal–photocatalytic materials that use charred wood substrates to convert liquid water to water steam, simultaneously splitting hydrogen under light illumination without additional energy. The photothermal–photocatalytic system exhibits biphase interfaces of photothermally-generated steam/photocatalyst/hydrogen, which significantly reduce the interface barrier and drastically lower the transport resistance of the hydrogen gas by nearly two orders of magnitude. In this work, an impressive hydrogen production rate up to 220.74 μmol h−1 cm−2 in the particulate photocatalytic systems has been achieved based on the wood/CoO system, demonstrating that the photothermal–photocatalytic biphase system is cost-effective and greatly advantageous for practical applications.
Chromatin information content landscapes inform transcription factor and DNA interactions
Authors: D’Oliveira Albanus Ricardo , Kyono Yasuhiro , Hensley John , Varshney Arushi , Orchard Peter , Kitzman Jacob O. , Parker Stephen C. J. 
Published: February 2021

AbstractInteractions between transcription factors and chromatin are fundamental to genome organization and regulation and, ultimately, cell state. Here, we use information theory to measure signatures of organized chromatin resulting from transcription factor-chromatin interactions encoded in the patterns of the accessible genome, which we term chromatin information enrichment (CIE). We calculate CIE for hundreds of transcription factor motifs across human samples and identify two classes: low and high CIE. The 10–20% of common and tissue-specific high CIE transcription factor motifs, associate with higher protein–DNA residence time, including different binding site subclasses of the same transcription factor, increased nucleosome phasing, specific protein domains, and the genetic control of both chromatin accessibility and gene expression. These results show that variations in the information encoded in chromatin architecture reflect functional biological variation, with implications for cell state dynamics and memory.
Optical tweezers-controlled hotspot for sensitive and reproducible surface-enhanced Raman spectroscopy characterization of native protein structures
Authors: Dai Xin , Fu Wenhao , Chi Huanyu , Mesias Vince St. Dollente , Zhu Hongni , Leung Cheuk Wai , Liu Wei , Huang Jinqing 
Published: February 2021

AbstractSurface-enhanced Raman spectroscopy (SERS) has emerged as a powerful tool to detect biomolecules in aqueous environments. However, it is challenging to identify protein structures at low concentrations, especially for the proteins existing in an equilibrium mixture of various conformations. Here, we develop an in situ optical tweezers-coupled Raman spectroscopy to visualize and control the hotspot between two Ag nanoparticle-coated silica beads, generating tunable and reproducible SERS enhancements with single-molecule level sensitivity. This dynamic SERS detection window is placed in a microfluidic flow chamber to detect the passing-by proteins, which precisely characterizes the structures of three globular proteins without perturbation to their native states. Moreover, it directly identifies the structural features of the transient species of alpha-synuclein among its predominant monomers at physiological concentration of 1 μM by reducing the ensemble averaging. Hence, this SERS platform holds the promise to resolve the structural details of dynamic, heterogeneous, and complex biological systems.
Functional regeneration and repair of tendons using biomimetic scaffolds loaded with recombinant periostin
Authors: Wang Yu , Jin Shanshan , Luo Dan , He Danqing , Shi Chunyan , Zhu Lisha , Guan Bo , Li Zixin , Zhang Ting , Zhou Yanheng , Wang Cun-Yu , Liu Yan 
Published: February 2021

AbstractTendon injuries disrupt the balance between stability and mobility, causing compromised functions and disabilities. The regeneration of mature, functional tendons remains a clinical challenge. Here, we perform transcriptional profiling of tendon developmental processes to show that the extracellular matrix-associated protein periostin (Postn) contributes to the maintenance of tendon stem/progenitor cell (TSPC) functions and promotes tendon regeneration. We show that recombinant periostin (rPOSTN) promotes the proliferation and stemness of TSPCs, and maintains the tenogenic potentials of TSPCs in vitro. We also find that rPOSTN protects TSPCs against functional impairment during long-term passage in vitro. For in vivo tendon formation, we construct a biomimetic parallel-aligned collagen scaffold to facilitate TSPC tenogenesis. Using a rat full-cut Achilles tendon defect model, we demonstrate that scaffolds loaded with rPOSTN promote endogenous TSPC recruitment, tendon regeneration and repair with native-like hierarchically organized collagen fibers. Moreover, newly regenerated tendons show recovery of mechanical properties and locomotion functions.