bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake
Authors: Cheng Yawen , Zhu Yuan , Liu Yaoshan , Liu Xuenan , Ding Yanan , Li Deli , Zhang Xiao , Liu Yunsong 
Published: April 2024

AbstractAccumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.
Mucopolysaccharidosis type II zebrafish model exhibits early impaired proteasomal-mediated degradation of the axon guidance receptor Dcc
Authors: Manzoli Rosa , Badenetti Lorenzo , Bruzzone Matteo , Macario Maria Carla , Rubin Michela , Dal Maschio Marco , Roveri Antonella , Moro Enrico 
Published: April 2024

AbstractMost of the patients affected by neuronopathic forms of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder caused by defects in iduronate-2-sulfatase (IDS) activity, exhibit early neurological defects associated with white matter lesions and progressive behavioural abnormalities. While neuronal degeneration has been largely described in experimental models and human patients, more subtle neuronal pathogenic defects remain still underexplored. In this work, we discovered that the axon guidance receptor Deleted in Colorectal Cancer (Dcc) is significantly dysregulated in the brain of ids mutant zebrafish since embryonic stages. In addition, thanks to the establishment of neuronal-enriched primary cell cultures, we identified defective proteasomal degradation as one of the main pathways underlying Dcc upregulation in ids mutant conditions. Furthermore, ids mutant fish-derived primary neurons displayed higher levels of polyubiquitinated proteins and P62, suggesting a wider defect in protein degradation. Finally, we show that ids mutant larvae display an atypical response to anxiety-inducing stimuli, hence mimicking one of the characteristic features of MPS II patients. Our study provides an additional relevant frame to MPS II pathogenesis, supporting the concept that multiple developmental defects concur with early childhood behavioural abnormalities.
POLE2 promotes osteosarcoma progression by enhancing the stability of CD44
Authors: Wang Baichuan , Hu Hongzhi , Wang Xiaohui , Shao Zengwu , Shi Deyao , Wu Fashuai , Liu Jianxiang , Zhang Zhicai , Li Juan , Xia Zhidao , Liu Weijian , Wu Qiang 
Published: April 2024

AbstractOsteosarcoma (OS) is the most prevalent primary malignancy of bone in children and adolescents. It is extremely urgent to develop a new therapy for OS. In this study, the GSE14359 chip from the GEO database was used to screen differentially expressed genes in OS. DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibited the proliferation and migration of OS cells in vitro, as well as the growth of tumors in vivo, while the apoptosis rate was increased. Bioinformatics analysis revealed that CD44 and Rac signaling pathway were the downstream molecule and pathway of POLE2, which were inhibited by knockdown of POLE2. POLE2 reduced the ubiquitination degradation of CD44 by acting on MDM2. Moreover, knockdown of CD44 inhibited the tumor-promoting effects of POLE2 overexpression on OS cells. In conclusion, POLE2 augmented the expression of CD44 via inhibiting MDM2-mediated ubiquitination, and then activated Rac signaling pathway to influence the progression of OS, indicating that POLE2/CD44 might be potential targets for OS treatment.
ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores
Authors: Wei Bin , Fu Yuhui , Li Xiuzhi , Chen Fang , Zhang Yiqing , Chen Hanmo , Tong Mindan , Li Linsen , Pan Yi , Zhang Shen , Chen She , Liu Xiaoxia , Zhong Qing 
Published: April 2024

AbstractMacroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1. Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux, which largely phenocopied ATG2A/B depletion. A pool of ANKFY1 co-localized with ATG2A between endosomes and phagophores and depletion of UVRAG, ANKFY1 or ATG2A/B led to reduction of PI3P distribution on phagophores. Purified recombinant ANKFY1 bound to PI3P on membrane through its FYVE domain and enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes. Therefore, we propose that ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores. This finding implicates a new lipid source for ATG2A-mediated phagophore expansion, where endosomes donate PI3P and other lipids to phagophores via lipid transfer.
Bioadhesive interface for marine sensors on diverse soft fragile species
Authors: Duque Londono Camilo , Cones Seth F. , Deng Jue , Wu Jingjing , Yuk Hyunwoo , Guza David E. , Mooney T. Aran , Zhao Xuanhe 
Published: April 2024

AbstractMarine animals equipped with sensors provide vital information for understanding their ecophysiology and collect oceanographic data on climate change and for resource management. Existing methods for attaching sensors to marine animals mostly rely on invasive physical anchors, suction cups, and rigid glues. These methods can suffer from limitations, particularly for adhering to soft fragile marine species such as squid and jellyfish, including slow complex operations, unreliable fixation, tissue trauma, and behavior changes of the animals. However, soft fragile marine species constitute a significant portion of ocean biomass (>38.3 teragrams of carbon) and global commercial fisheries. Here we introduce a soft hydrogel-based bioadhesive interface for marine sensors that can provide rapid (time <22 s), robust (interfacial toughness >160 J m−2), and non-invasive adhesion on various marine animals. Reliable and rapid adhesion enables large-scale, multi-animal sensor deployments to study biomechanics, collective behaviors, interspecific interactions, and concurrent multi-species activity. These findings provide a promising method to expand a burgeoning research field of marine bio-sensing from large marine mammals and fishes to small, soft, and fragile marine animals.
Resolved magnetohydrodynamic wave lensing in the solar corona
Authors: Zhou Xinping , Shen Yuandeng , Yuan Ding , Keppens Rony , Zhao Xiaozhou , Fu Libo , Tang Zehao , Wang Jiaoyang , Zhou Chengrui 
Published: April 2024

AbstractElectromagnetic wave lensing, a common physical phenomenon recognized in visible light for centuries, finds extensive applications in manipulating light in optical systems such as telescopes and cameras. Magnetohydrodynamic wave is a common perturbation phenomenon in the corona. By using high spatio-temporal resolution observations from the Solar Dynamics Observatory, here, we report the observation of a magnetohydrodynamic wave lensing in the highly ionized and magnetized coronal plasma, where quasi-periodic wavefronts emanated from a flare converged at a specific point after traversing a coronal hole. The entire process resembles an electromagnetic wave lensing from the source to the focus. Meanwhile, the magnetohydrodynamic wave lensing is well reproduced through a magnetohydrodynamic numerical simulation with full spatio-temporal resolution. We further investigate potential applications for coronal seismology, as the lensing process encodes information on the Alfvén speed, in conjunction with favorable geometric and density variations.
The physiological interactome of TCR-like antibody therapeutics in human tissues
Authors: Marrer-Berger Estelle , Nicastri Annalisa , Augustin Angelique , Kramar Vesna , Liao Hanqing , Hanisch Lydia Jasmin , Carpy Alejandro , Weinzierl Tina , Durr Evelyne , Schaub Nathalie , Nudischer Ramona , Ortiz-Franyuti Daniela , Breous-Nystrom Ekaterina , Stucki Janick , Hobi Nina , Raggi Giulia , Cabon Lauriane , Lezan Emmanuelle , Umaña Pablo , Woodhouse Isaac , Bujotzek Alexander , Klein Christian , Ternette Nicola 
Published: April 2024

AbstractSelective binding of TCR-like antibodies that target a single tumour-specific peptide antigen presented by human leukocyte antigens (HLA) is the absolute prerequisite for their therapeutic suitability and patient safety. To date, selectivity assessment has been limited to peptide library screening and predictive modeling. We developed an experimental platform to de novo identify interactomes of TCR-like antibodies directly in human tissues using mass spectrometry. As proof of concept, we confirm the target epitope of a MAGE-A4-specific TCR-like antibody. We further determine cross-reactive peptide sequences for ESK1, a TCR-like antibody with known off-target activity, in human liver tissue. We confirm off-target-induced T cell activation and ESK1-mediated liver spheroid killing. Off-target sequences feature an amino acid motif that allows a structural groove-coordination mimicking that of the target peptide, therefore allowing the interaction with the engager molecule. We conclude that our strategy offers an accurate, scalable route for evaluating the non-clinical safety profile of TCR-like antibody therapeutics prior to first-in-human clinical application.
Orbital hybridization of donor and acceptor to enhance the conductivity of mixed-stack complexes
Authors: Fujino Tomoko , Kameyama Ryohei , Onozuka Kota , Matsuo Kazuki , Dekura Shun , Miyamoto Tatsuya , Guo Zijing , Okamoto Hiroshi , Nakamura Toshikazu , Yoshimi Kazuyoshi , Kitou Shunsuke , Arima Taka-hisa , Sato Hiroyasu , Yamamoto Kaoru , Takahashi Akira , Sawa Hiroshi , Nakamura Yuiga , Mori Hatsumi 
Published: April 2024

AbstractMixed-stack complexes which comprise columns of alternating donors and acceptors are organic conductors with typically poor electrical conductivity because they are either in a neutral or highly ionic state. This indicates that conductive carriers are insufficient or are mainly localized. In this study, mixed-stack complexes that uniquely exist at the neutral–ionic boundary were synthesized by combining donors (bis(3,4-ethylenedichalcogenothiophene)) and acceptors (fluorinated tetracyanoquinodimethanes) with similar energy levels and orbital symmetry between the highest occupied molecular orbital of the donor and the lowest unoccupied molecular orbital of the acceptor. Surprisingly, the orbitals were highly hybridized in the single-crystal complexes, enhancing the room-temperature conductivity (10−4–0.1 S cm−1) of mixed-stack complexes. Specifically, the maximum conductivity was the highest reported for single-crystal mixed-stack complexes under ambient pressures. The unique electronic structures at the neutral–ionic boundary exhibited structural perturbations between their electron-itinerant and localized states, causing abrupt temperature-dependent changes in their electrical, optical, dielectric, and magnetic properties.
Using strain to uncover the interplay between two- and three-dimensional charge density waves in high-temperature superconducting YBa2Cu3Oy
Authors: Vinograd I. , Souliou S. M. , Haghighirad A.-A. , Lacmann T. , Caplan Y. , Frachet M. , Merz M. , Garbarino G. , Liu Y. , Nakata S. , Ishida K. , Noad H. M. L. , Minola M. , Keimer B. , Orgad D. , Hicks C. W. , Le Tacon M. 
Published: April 2024

AbstractUniaxial pressure provides an efficient approach to control charge density waves in YBa2Cu3Oy. It can enhance the correlation volume of ubiquitous short-range two-dimensional charge-density-wave correlations, and induces a long-range three-dimensional charge density wave, otherwise only accessible at large magnetic fields. Here, we use x-ray diffraction to study the strain dependence of these charge density waves and uncover direct evidence for a form of competition between them. We show that this interplay is qualitatively described by including strain effects in a nonlinear sigma model of competing superconducting and charge-density-wave orders. Our analysis suggests that strain stabilizes the 3D charge density wave in the regions between disorder-pinned domains of 2D charge density waves, and that the two orders compete at the boundaries of these domains. No signatures of discommensurations nor of pair density waves are observed. From a broader perspective, our results underscore the potential of strain tuning as a powerful tool for probing competing orders in quantum materials.
Distinct skyrmion phases at room temperature in two-dimensional ferromagnet Fe3GaTe2
Authors: Lv Xiaowei , Lv Hualiang , Huang Yalei , Zhang Ruixuan , Qin Guanhua , Dong Yihui , Liu Min , Pei Ke , Cao Guixin , Zhang Jincang , Lai Yuxiang , Che Renchao 
Published: April 2024

AbstractDistinct skyrmion phases at room temperature hosted by one material offer additional degree of freedom for the design of topology-based compact and energetically-efficient spintronic devices. The field has been extended to low-dimensional magnets with the discovery of magnetism in two-dimensional van der Waals magnets. However, creating multiple skyrmion phases in 2D magnets, especially above room temperature, remains a major challenge. Here, we report the experimental observation of mixed-type skyrmions, exhibiting both Bloch and hybrid characteristics, in a room-temperature ferromagnet Fe3GaTe2. Analysis of the magnetic intensities under varied imaging conditions coupled with complementary simulations reveal that spontaneous Bloch skyrmions exist as the magnetic ground state with the coexistence of hybrid stripes domain, on account of the interplay between the dipolar interaction and the Dzyaloshinskii-Moriya interaction. Moreover, hybrid skyrmions are created and their coexisting phases with Bloch skyrmions exhibit considerably high thermostability, enduring up to 328 K. The findings open perspectives for 2D spintronic devices incorporating distinct skyrmion phases at room temperature.
Weakened western Indian Ocean dominance on Antarctic sea ice variability in a changing climate
Authors: Zhang Li , Ren Xuya , Cai Wenju , Li Xichen , Wu Lixin 
Published: April 2024

AbstractPatterns of sea surface temperature (SST) anomalies of the Indian Ocean Dipole (IOD) exhibit strong diversity, ranging from being dominated by the western tropical Indian Ocean (WTIO) to the eastern tropical Indian Ocean (ETIO). Whether and how the different types of IOD variability patterns affect the variability of Antarctic sea ice is not known, nor is how the impact may change in a warming climate. Here, we find that the leading mode of austral spring Antarctic sea ice variability is dominated by WTIO SST variability rather than ETIO SST or El Niño–Southern Oscillation. WTIO warm SST anomalies excite a poleward-propagating Rossby wave, inducing a tri-polar anomaly pattern characterized by a decrease in sea ice near the Amundsen Sea but an increase in regions on both sides. Such impact has been weakening in the two decades post-2000, accompanied by weakened WTIO SST variability. Under greenhouse warming, climate models project a decrease in WTIO SST variability, suggesting that the reduced impact on Antarctic sea ice from the IOD will likely to continue, facilitating a fast decline of Antarctic sea ice.
Insights into the inhibition of protospacer integration via direct interaction between Cas2 and AcrVA5
Authors: Bi Mingfang , Su Wenjing , Li Jiafu , Mo Xiaobing 
Published: April 2024

AbstractSpacer acquisition step in CRISPR-Cas system involves the recognition and subsequent integration of protospacer by the Cas1-Cas2 complex in CRISPR-Cas systems. Here we report an anti-CRISPR protein, AcrVA5, and reveal the mechanisms by which it strongly inhibits protospacer integration. Our biochemical data shows that the integration by Cas1-Cas2 was abrogated in the presence of AcrVA5. AcrVA5 exhibits low binding affinity towards Cas2 and acetylates Cas2 at Lys55 on the binding interface of the Cas2 and AcrVA5 N-terminal peptide complex to inhibit the Cas2-mediated endonuclease activity. Moreover, a detailed structural comparison between our crystal structure and homolog structure shows that binding of AcrVA5 to Cas2 causes steric hindrance to the neighboring protospacer resulting in the partial disassembly of the Cas1-Cas2 and protospacer complex, as demonstrated by electrophoretic mobility shift assay. Our study focuses on this mechanism of spacer acquisition inhibition and provides insights into the biology of CRISPR-Cas systems.
Stroke-volume-allocation model enabling wearable sensors for vascular age and cardiovascular disease assessment
Authors: Qiu Shirong , Yan Bryan P. Y. , Zhao Ni 
Published: April 2024

AbstractFrequent and unobtrusive monitoring of cardiovascular conditions with consumer electronics is a widely pursued goal, since it provides the most economic and effective way of preventing and managing cardiovascular diseases (CVDs) ─ the leading causes of death worldwide. However, most current wearable and flexible devices can only support the measurement of one or two types of vital signs, such as heart rate and blood oxygen level, due to the lack of physiological models to link the measured signals to cardiovascular conditions. Here, we report a stroke-volume allocation (SVA) model to quantify the cushioning function of arteries and empower nearly all existing cardiac sensors with new functions, including arterial stiffness evaluation, dynamic blood pressure tracking and classification of CVD-related heart damage. Large-scale clinical data testing involving a hybrid dataset taken from 6 hospitals/research institutes (9 open databases and 4 self-built databases from 878 subjects in total) and diverse measurement approaches was carried out to validate the SVA model. The results show that the SVA-based parameters correlate well with the gold-standard measurements in arterial stiffness and blood pressure and outperform the commonly used vital sign (e.g., blood pressure) alone in detecting abnormalities in cardiovascular systems.
Single-mitosis dissection of acute and chronic DNA mutagenesis and repair
Authors: Ginno Paul Adrian , Borgers Helena , Ernst Christina , Schneider Anja , Behm Mikaela , Aitken Sarah J. , Taylor Martin S. , Odom Duncan T. 
Published: April 2024

AbstractHow chronic mutational processes and punctuated bursts of DNA damage drive evolution of the cancer genome is poorly understood. Here, we demonstrate a strategy to disentangle and quantify distinct mechanisms underlying genome evolution in single cells, during single mitoses and at single-strand resolution. To distinguish between chronic (reactive oxygen species (ROS)) and acute (ultraviolet light (UV)) mutagenesis, we microfluidically separate pairs of sister cells from the first mitosis following burst UV damage. Strikingly, UV mutations manifest as sister-specific events, revealing mirror-image mutation phasing genome-wide. In contrast, ROS mutagenesis in transcribed regions is reduced strand agnostically. Successive rounds of genome replication over persisting UV damage drives multiallelic variation at CC dinucleotides. Finally, we show that mutation phasing can be resolved to single strands across the entire genome of liver tumors from F1 mice. This strategy can be broadly used to distinguish the contributions of overlapping cancer relevant mutational processes.
TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma
Authors: Yi Heng , Yang Qijun , Repaci Charlie , Lee Cheolmin Matthew , Heo Gyujin , Timsina Jigyasha , Gorijala Priyanka , Yang Chengran , Budde John , Wang Lihua , Cruchaga Carlos , Sung Yun Ju 
Published: April 2024

AbstractComprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community.
A construction waste landfill dataset of two districts in Beijing, China from high resolution satellite images
Authors: Lin Shaofu , Huang Lei , Liu Xiliang , Chen Guihong , Fu Zhe 
Published: April 2024

AbstractConstruction waste is unavoidable in the process of urban development, causing serious environmental pollution. Accurate assessment of municipal construction waste generation requires building construction waste identification models using deep learning technology. However, this process requires high-quality public datasets for model training and validation. This study utilizes Google Earth and GF-2 images as the data source to construct a specific dataset of construction waste landfills in the Changping and Daxing districts of Beijing, China. This dataset contains 3,653 samples of the original image areas and provides mask-labeled images in the semantic segmentation domains. Each pixel within a construction waste landfill is classified into 4 categories of the image areas, including background area, vacant landfillable area, engineering facility area, and waste dumping area. The dataset contains 237,115,531 pixels of construction waste and 49,724,513 pixels of engineering facilities. The pixel-level semantic segmentation labels are provided to quantify the construction waste yield, which can serve as the basic data for construction waste extraction and yield estimation both for academic and industrial research.