bluuebunny/crossref_metadata_2025_split huggingface dataset:
ORP5 promotes tumor metastasis via stabilizing c-Met in renal cell carcinoma
Authors: Song Li , Zhang Lin , Zhou Yun , Shao Xiaotong , Xu Yuting , Pei Dongsheng , Wang Qingling 
Published: April 2022

AbstractORP5, a lipid transporter, has been reported to increase the metastasis of several cancers. However, the potential mechanisms of ORP5 in renal cell carcinoma (RCC) remain unclear. In this study, we demonstrated that ORP5 was commonly overexpressed in tumor cells and tissues of RCC, and associated with tumor progression. Overexpression of ORP5 could promote RCC cells migration and invasion. In addition, the results suggested that the expression of ORP5 was favorably associated with c-Met expression, and ORP5 promoted RCC cells metastasis by upregulating c-Met in vitro and in vivo. Mechanistically, ORP5 facilitated the ubiquitination and degradation of c-Cbl (the E3 ligase of c-Met), and thus inhibited c-Met lysosomal degradation, which resulted in the stabilization of c-Met. In general, these findings revealed the role of ORP5 in contributing to tumorigenesis via upregulating c-Met in RCC.
Ferroptosis is involved in PGPS-induced otitis media in C57BL/6 mice
Authors: Yan Bin , Xie Daoli , Wu Yuancheng , Wang Shuli , Zhang Xiaolin , Zhao Tong , Liu Luying , Ma Peng , Li Guqiang , Yang Ying , Zhao Yucheng , Zheng Tihua , Geng Ruishuang , Li Bo , Zheng Qingyin 
Published: April 2022

AbstractOtitis media (OM) is a common disease that can cause hearing loss in children. Currently, the main clinical treatment for OM is antibiotics, but the overuse of antibiotics might lead to bacterial resistance, which is a worldwide public health challenge. Studying the pathogenesis of OM will help us develop new effective treatments. Ferroptosis is one type of programmed cell death characterized by the occurrence of lipid peroxidation driven by iron ions. Many studies have shown that ferroptosis is associated with infectious diseases. It is presently unclear whether ferroptosis is involved in the pathogenesis of OM. In this study, we explored the relationship between ferroptosis and OM by PGPS-induced OM in C57BL/6 mice and treating the induced OM with ferroptosis inhibitors deferoxamine (DFO), Ferrostatin-1 (Fer-1), and Liperoxstatin-1 (Lip-1). We examined the expression of ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and prostaglandin-endoperoxide synthase 2 (Cox2), glutathione peroxidase 4 (GPX4) protein as well as lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). The results showed that in PGPS-induced OM model mice, several ferroptosis-related proteins including ACSL4 and Cox2 were up-regulated compared to mice treated with saline. Meanwhile, a ferroptosis-related protein GPX4 was down-regulated upon PGPS treatment. The DFO treatment in PGPS-inoculated mice effectively inhibited the development of OM. The inhibitors treatment caused a significant decrease in the expression of ACSL4, Cox2, 4 HNE, MDA, reduction in free iron. Meanwhile, the ferroptosis inhibitors treatment caused increase in the expression of inflammation-related factors tumor necrosis factor-α (TNF-α) and antioxidant protein GPX4. Our results suggest that there is a crosstalk between ferroptosis signaling pathway and the pathogenesis of OM. Ferroptosis inhibition can alleviate PGPS-induced OM.
Microscale carbon distribution around pores and particulate organic matter varies with soil moisture regime
Authors: Schlüter Steffen , Leuther Frederic , Albrecht Lukas , Hoeschen Carmen , Kilian Rüdiger , Surey Ronny , Mikutta Robert , Kaiser Klaus , Mueller Carsten W. , Vogel Hans-Jörg 
Published: April 2022

AbstractSoil carbon sequestration arises from the interplay of carbon input and stabilization, which vary in space and time. Assessing the resulting microscale carbon distribution in an intact pore space, however, has so far eluded methodological accessibility. Here, we explore the role of soil moisture regimes in shaping microscale carbon gradients by a novel mapping protocol for particulate organic matter and carbon in the soil matrix based on a combination of Osmium staining, X-ray computed tomography, and machine learning. With three different soil types we show that the moisture regime governs C losses from particulate organic matter and the microscale carbon redistribution and stabilization patterns in the soil matrix. Carbon depletion around pores (aperture > 10 µm) occurs in a much larger soil volume (19–74%) than carbon enrichment around particulate organic matter (1%). Thus, interacting microscale processes shaped by the moisture regime are a decisive factor for overall soil carbon persistence.
Emergence of novel cephalopod gene regulation and expression through large-scale genome reorganization
Authors: Schmidbaur Hannah , Kawaguchi Akane , Clarence Tereza , Fu Xiao , Hoang Oi Pui , Zimmermann Bob , Ritschard Elena A. , Weissenbacher Anton , Foster Jamie S. , Nyholm Spencer V. , Bates Paul A. , Albertin Caroline B. , Tanaka Elly , Simakov Oleg 
Published: April 2022

AbstractColeoid cephalopods (squid, cuttlefish, octopus) have the largest nervous system among invertebrates that together with many lineage-specific morphological traits enables complex behaviors. The genomic basis underlying these innovations remains unknown. Using comparative and functional genomics in the model squid Euprymna scolopes, we reveal the unique genomic, topological, and regulatory organization of cephalopod genomes. We show that coleoid cephalopod genomes have been extensively restructured compared to other animals, leading to the emergence of hundreds of tightly linked and evolutionary unique gene clusters (microsyntenies). Such novel microsyntenies correspond to topological compartments with a distinct regulatory structure and contribute to complex expression patterns. In particular, we identify a set of microsyntenies associated with cephalopod innovations (MACIs) broadly enriched in cephalopod nervous system expression. We posit that the emergence of MACIs was instrumental to cephalopod nervous system evolution and propose that microsyntenic profiling will be central to understanding cephalopod innovations.
Single-layer spatial analog meta-processor for imaging processing
Authors: Wang Zhuochao , Hu Guangwei , Wang Xinwei , Ding Xumin , Zhang Kuang , Li Haoyu , Burokur Shah Nawaz , Wu Qun , Liu Jian , Tan Jiubin , Qiu Cheng-Wei 
Published: April 2022

AbstractComputational meta-optics brings a twist on the accelerating hardware with the benefits of ultrafast speed, ultra-low power consumption, and parallel information processing in versatile applications. Recent advent of metasurfaces have enabled the full manipulation of electromagnetic waves within subwavelength scales, promising the multifunctional, high-throughput, compact and flat optical processors. In this trend, metasurfaces with nonlocality or multi-layer structures are proposed to perform analog optical computations based on Green’s function or Fourier transform, intrinsically constrained by limited operations or large footprints/volume. Here, we showcase a Fourier-based metaprocessor to impart customized highly flexible transfer functions for analog computing upon our single-layer Huygens’ metasurface. Basic mathematical operations, including differentiation and cross-correlation, are performed by directly modulating complex wavefronts in spatial Fourier domain, facilitating edge detection and pattern recognition of various image processing. Our work substantiates an ultracompact and powerful kernel processor, which could find important applications for optical analog computing and image processing.
High-entropy induced a glass-to-glass transition in a metallic glass
Authors: Luan Hengwei , Zhang Xin , Ding Hongyu , Zhang Fei , Luan J. H. , Jiao Z. B. , Yang Yi-Chieh , Bu Hengtong , Wang Ranbin , Gu Jialun , Shao Chunlin , Yu Qing , Shao Yang , Zeng Qiaoshi , Chen Na , Liu C. T. , Yao Ke-Fu 
Published: April 2022

AbstractGlass-to-glass transitions are useful for us to understand the glass nature, but it remains difficult to tune the metallic glass into significantly different glass states. Here, we have demonstrated that the high-entropy can enhance the degree of disorder in an equiatomic high-entropy metallic glass NbNiZrTiCo and elevate it to a high-energy glass state. An unusual glass-to-glass phase transition is discovered during heating with an enormous heat release even larger than that of the following crystallization at higher temperatures. Dramatic atomic rearrangement with a short- and medium-range ordering is revealed by in-situ synchrotron X-ray diffraction analyses. This glass-to-glass transition leads to a significant improvement in the modulus, hardness, and thermal stability, all of which could promote their applications. Based on the proposed high-entropy effect, two high-entropy metallic glasses are developed and they show similar glass-to-glass transitions. These findings uncover a high-entropy effect in metallic glasses and create a pathway for tuning the glass states and properties.
Single-cell transcriptomics identifies Mcl-1 as a target for senolytic therapy in cancer
Authors: Troiani Martina , Colucci Manuel , D’Ambrosio Mariantonietta , Guccini Ilaria , Pasquini Emiliano , Varesi Angelica , Valdata Aurora , Mosole Simone , Revandkar Ajinkya , Attanasio Giuseppe , Rinaldi Andrea , Rinaldi Anna , Bolis Marco , Cippà Pietro , Alimonti Andrea 
Published: April 2022

AbstractCells subjected to treatment with anti-cancer therapies can evade apoptosis through cellular senescence. Persistent senescent tumor cells remain metabolically active, possess a secretory phenotype, and can promote tumor proliferation and metastatic dissemination. Removal of senescent tumor cells (senolytic therapy) has therefore emerged as a promising therapeutic strategy. Here, using single-cell RNA-sequencing, we find that senescent tumor cells rely on the anti-apoptotic gene Mcl-1 for their survival. Mcl-1 is upregulated in senescent tumor cells, including cells expressing low levels of Bcl-2, an established target for senolytic therapy. While treatment with the Bcl-2 inhibitor Navitoclax results in the reduction of metastases in tumor bearing mice, treatment with the Mcl-1 inhibitor S63845 leads to complete elimination of senescent tumor cells and metastases. These findings provide insights on the mechanism by which senescent tumor cells survive and reveal a vulnerability that can be exploited for cancer therapy.
Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy
Authors: Liu Minglun , Chen Yuncong , Guo Yan , Yuan Hao , Cui Tongxiao , Yao Shankun , Jin Suxing , Fan Huanhuan , Wang Chengjun , Xie Ran , He Weijiang , Guo Zijian 
Published: April 2022

AbstractGolgi apparatus (GA) oxidative stress induced by in situ reactive oxygen species (ROS) could severely damage the morphology and function of GA, which may open up an avenue for effective photodynamic therapy (PDT). However, due to the lack of effective design strategy, photosensitizers (PSs) with specific GA targeting ability are in high demand and yet quite challenging. Herein, we report an aggregation-induced emission luminogen (AIEgen) based PS (TPE-PyT-CPS) that can effectively target the GA via caveolin/raft mediated endocytosis with a Pearson correlation coefficient up to 0.98. Additionally, the introduction of pyrene into TPE-PyT-CPS can reduce the energy gap between the lowest singlet state (S1) and the lowest triplet state (T1) (ΔEST) and exhibits enhanced singlet oxygen generation capability. GA fragmentation and cleavage of GA proteins (p115/GM130) are observed upon light irradiation. Meanwhile, the apoptotic pathway is activated through a crosstalk between GA oxidative stress and mitochondria in HeLa cells. More importantly, GA targeting TPE-T-CPS show better PDT effect than its non-GA-targeting counterpart TPE-PyT-PS, even though they possess very close ROS generation rate. This work provides a strategy for the development of PSs with specific GA targeting ability, which is of great importance for precise and effective PDT.
AI-enabled, implantable, multichannel wireless telemetry for photodynamic therapy
Authors: Kim Woo Seok , Khot M. Ibrahim , Woo Hyun-Myung , Hong Sungcheol , Baek Dong-Hyun , Maisey Thomas , Daniels Brandon , Coletta P. Louise , Yoon Byung-Jun , Jayne David G. , Park Sung Il 
Published: April 2022

AbstractPhotodynamic therapy (PDT) offers several advantages for treating cancers, but its efficacy is highly dependent on light delivery to activate a photosensitizer. Advances in wireless technologies enable remote delivery of light to tumors, but suffer from key limitations, including low levels of tissue penetration and photosensitizer activation. Here, we introduce DeepLabCut (DLC)-informed low-power wireless telemetry with an integrated thermal/light simulation platform that overcomes the above constraints. The simulator produces an optimized combination of wavelengths and light sources, and DLC-assisted wireless telemetry uses the parameters from the simulator to enable adequate illumination of tumors through high-throughput (<20 mice) and multi-wavelength operation. Together, they establish a range of guidelines for effective PDT regimen design. In vivo Hypericin and Foscan mediated PDT, using cancer xenograft models, demonstrates substantial suppression of tumor growth, warranting further investigation in research and/or clinical settings.
Effect of electrode and oxide properties on the filament kinetics during electroforming in metal-oxide-based memories
Authors: Zhang Kena , Ren Yao , Ganesh Panchapakesan , Cao Ye 
Published: April 2022

AbstractWe developed a physical model to fundamentally understand the conductive filament (CF) formation and growth behavior in the switching layer during electroforming process in the metal-oxide-based resistive random-access memories (RRAM). The effects of the electrode and oxide layer properties on the CF morphology evolution, current-voltage characteristic, local temperature, and electrical potential distribution have been systematically explored. It is found that choosing active electrodes with lower oxygen vacancy formation energy and oxides with small Lorenz number (ratio of thermal and electrical conductivity) enables CF formation at a smaller electroforming voltage and creates a CF with more homogeneous morphology. This work advances our understanding of the kinetic behaviors of the CF formation and growth during the electroforming process and could potentially guide the oxide and electrode materials selection to realize a more stable and functional RRAM.
Snapshots of actin and tubulin folding inside the TRiC chaperonin
Authors: Kelly John J. , Tranter Dale , Pardon Els , Chi Gamma , Kramer Holger , Happonen Lotta , Knee Kelly M. , Janz Jay M. , Steyaert Jan , Bulawa Christine , Paavilainen Ville O. , Huiskonen Juha T. , Yue Wyatt W. 
Published: April 2022

AbstractThe integrity of a cell’s proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture and how it recognizes folding substrates are emerging from structural studies, the subsequent fate of substrates inside the TRiC chamber is not defined. We trapped endogenous human TRiC with substrates (actin, tubulin) and cochaperone (PhLP2A) at different folding stages, for structure determination by cryo-EM. The already-folded regions of client proteins are anchored at the chamber wall, positioning unstructured regions toward the central space to achieve their native fold. Substrates engage with different sections of the chamber during the folding cycle, coupled to TRiC open-and-close transitions. Further, the cochaperone PhLP2A modulates folding, acting as a molecular strut between substrate and TRiC chamber. Our structural snapshots piece together an emerging model of client protein folding within TRiC.
Comparative analysis of long noncoding RNA and mRNA expression provides insights into adaptation to hypoxia in Tibetan sheep
Authors: Wang Fan , Liu Jianbin , Zeng Qiaoying , Zhuoga Deqing 
Published: April 2022

AbstractTibetan sheep have lived on the Qinghai-Tibetan Plateau for thousands of years and have good adaptability to the hypoxic environment and strong disease resistance. However, the molecular mechanism by which Tibetan sheep adapt to this extreme environment, especially the role of genetic regulation, is still unknown. Emerging evidence suggests that long noncoding RNAs (lncRNAs) participate in the regulation of a diverse range of biological processes. To explore the potential lncRNAs involved in the adaptation to high-altitude hypoxia of Tibetan sheep, we analysed the expression profile of lncRNAs and mRNAs in the liver and lung tissues of sheep using comparative transcriptome analysis between four Tibetan sheep populations (high altitude) and one Hu sheep population (low altitude). The results showed a total of 7848 differentially expressed (DE) lncRNA transcripts, and 22,971 DE mRNA transcripts were detected by pairwise comparison. The expression patterns of selected mRNAs and lncRNAs were validated by qRT-PCR, and the results correlated well with the transcriptome data. Moreover, the functional annotation analysis based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases showed that DE mRNAs and the target genes of the lncRNAs were significantly enriched in organ morphogenesis, response to stimulus, haem binding, the immune system, arginine and proline metabolism, and fatty acid biosynthesis. The prediction of mRNA–mRNA and lncRNA–mRNA interaction networks further revealed transcripts potentially involved in adaptation to high-altitude hypoxia, and the hub genes DDX24, PDCD11, EIF4A3, NDUFA11, SART1, PRPF8 and TCONS_00306477, TCONS_00306029, TCONS_00139593, TCONS_00293272, and TCONS_00313398 were selected. Additionally, a set of target genes, PIK3R1, IGF1R, FZD6, IFNB2, ATF3, MB, CYP2B4, PSMD13, and TGFB1, were also identified as candidate genes associated with high-altitude hypoxia adaptation. In conclusion, a collection of novel expressed lncRNAs, a set of target genes and biological pathways known to be relevant for altitude adaptation were identified by comparative transcriptome analysis between Tibetan sheep and Hu sheep. Our results are the first to identify the characterization and expression profile of lncRNAs between Tibetan sheep and Hu sheep and provide insights into the genetic regulation mechanisms by which Tibetan sheep adapt to high-altitude hypoxic environments.
Evaluating the job shop scheduling problem on a D-wave quantum annealer
Authors: Carugno Costantino , Ferrari Dacrema Maurizio , Cremonesi Paolo 
Published: April 2022

AbstractJob Shop Scheduling is a combinatorial optimization problem of particular importance for production environments where the goal is to complete a production task in the shortest possible time given limitations in the resources available. Due to its computational complexity it quickly becomes intractable for problems of interesting size. The emerging technology of Quantum Annealing provides an alternative computational architecture that promises improved scalability and solution quality. However, several limitations as well as open research questions exist in this relatively new and rapidly developing technology. This paper studies the application of quantum annealing to solve the job shop scheduling problem, describing each step required from the problem formulation to the fine-tuning of the quantum annealer and compares the solution quality with various classical solvers. Particular attention is devoted to aspects that are often overlooked, such as the computational cost of representing the problem in the formulation required by the quantum annealer, the relative qubits requirements and how to mitigate chain breaks. Furthermore, the impact of advanced tools such as reverse annealing is presented and its effectiveness discussed. The results indicate several challenges emerging at various stages of the experimental pipeline which bring forward important research questions and directions of improvement.
Inhibitory effect of concomitantly administered rabies immunoglobulins on the immunogenicity of commercial and candidate human rabies vaccines in hamsters
Authors: Bernard Marie-Clotilde , Boudet Florence , Pineda-Peña Andrea-Clemencia , Guinet-Morlot Françoise 
Published: April 2022

AbstractThe World Health Organization protocol for rabies post-exposure prophylaxis (PEP) recommends extensive wound washing, immediate vaccination, and administration of rabies immunoglobulin (RIG) in severe category III exposures. Some studies have shown that RIG can interfere with rabies vaccine immunogenicity to some extent. We investigated the interference of RIG on a next generation highly purified Vero cell rabies vaccine candidate (PVRV-NG) versus standard-of-care vaccines in a previously described hamster model. The interference of either human (h) or equine (e) RIG on the immune response elicited by PVRV-NG, Verorab® (purified Vero cell rabies vaccine, PVRV), and Imovax® Rabies (human diploid cell rabies vaccine; HDCV) was evaluated using the 4-dose Essen PEP regimen. The anti-rabies seroneutralizing titers and specific serum IgM titers were measured by fluorescent antibody virus neutralization test and enzyme-linked immunosorbent assay, respectively, for the vaccines administered with or without RIG. The RIG interference on PVRV-NG, observed transiently at Day 7, was similar to that on PVRV and tended to be lower than that on HDCV using both read-outs. In summary, the results generated in the hamster model showed that RIG induced similar or less interference on PVRV-NG than the standard-of-care vaccines.
Data-driven computational intelligence applied to dengue outbreak forecasting: a case study at the scale of the city of Natal, RN-Brazil
Authors: Sanchez-Gendriz Ignacio , de Souza Gustavo Fontoura , de Andrade Ion G. M. , Neto Adrião Duarte Doria , de Medeiros Tavares Alessandre , Barros Daniele M. S. , de Morais Antonio Higor Freire , Galvão-Lima Leonardo J. , de Medeiros Valentim Ricardo Alexsandro 
Published: April 2022

AbstractDengue is recognized as a health problem that causes significant socioeconomic impacts throughout the world, affecting millions of people each year. A commonly used method for monitoring the dengue vector is to count the eggs that Aedes aegypti mosquitoes have laid in spatially distributed ovitraps. Given this approach, the present study uses a database collected from 397 ovitraps allocated across the city of Natal, RN—Brazil. The Egg Density Index for each neighborhood was computed weekly, over four complete years (from 2016 to 2019), and simultaneously analyzed with the dengue case incidence. Our results illustrate that the incidence of dengue is related to the socioeconomic level of the neighborhoods in the city of Natal. A deep learning algorithm was used to predict future dengue case incidence, either based on the previous weeks of dengue incidence or the number of eggs present in the ovitraps. The analysis reveals that ovitrap data allows earlier prediction (four to six weeks) compared to dengue incidence itself (one week). Therefore, the results validate that the quantification of Aedes aegypti eggs can be valuable for the early planning of public health interventions.