bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway
Authors: Han Tao , Chen Tingsong , Chen Lujun , Li Kerui , Xiang Daimin , Dou Lei , Li Hengyu , Gu Yubei 
Published: September 2023

AbstractHepatic leukemia factor (HLF) is aberrantly expressed in human malignancies. However, the role of HLF in the regulation of ovarian cancer (OC) remains unknown. Herein, we reported that HLF expression was upregulated in OC tissues and ovarian cancer stem cells (CSCs). Functional studies have revealed that HLF regulates OC cell stemness, proliferation, and metastasis. Mechanistically, HLF transcriptionally activated Yes-associated protein 1 (YAP1) expression and subsequently modulated the Hippo signaling pathway. Moreover, we found that miR-520e directly targeted HLF 3′-UTR in OC cells. miR-520e expression was negatively correlated with HLF and YAP1 expression in OC tissues. The combined immunohistochemical (IHC) panels exhibited a better prognostic value for OC patients than any of these components alone. Importantly, the HLF/YAP1 axis determines the response of OC cells to carboplatin treatment and HLF depletion or the YAP1 inhibitor verteporfin abrogated carboplatin resistance. Analysis of patient-derived xenografts (PDXs) further suggested that HLF might predict carboplatin benefits in OC patients. In conclusion, these findings suggest a crucial role of the miR-520e/HLF/YAP1 axis in OC progression and chemoresistance, suggesting potential therapeutic targets for OC.
CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation
Authors: Zhuang Wei , Zhou Jinfeng , Zhong Lan , Lv Jie , Zhong Xuan , Liu Guangyu , Xie Ling , Wang Chun , Saimaier Kaidireya , Han Sanxing , Shi Changjie , Hua Qiuhong , Zhang Ru , Xie Xin , Du Changsheng 
Published: September 2023

AbstractChemokines secreted by dendritic cells (DCs) play a key role in the regulation of inflammation and autoimmunity through chemokine receptors. However, the role of chemokine receptor CXCR1 in inflammation-inducing experimental autoimmune encephalomyelitis (EAE) and acute respiratory distress syndrome (ARDS) remains largely enigmatic. Here we reported that compared with healthy controls, the level of CXCR1 was aberrantly increased in multiple sclerosis (MS) patients. Knockout of CXCR1 not only ameliorated disease severity in EAE mice but also suppressed the secretion of inflammatory factors (IL-6/IL-12p70) production. We observed the same results in EAE mice with DCs-specific deletion of CXCR1 and antibody neutralization of the ligand CXCL5. Mechanically, we demonstrated a positive feedback loop composed of CXCL5/CXCR1/HIF-1α direct regulating of IL-6/IL-12p70 production in DCs. Meanwhile, we found CXCR1 deficiency in DCs limited IL-6/IL-12p70 production and lung injury in LPS-induced ARDS, a disease model caused by inflammation. Overall, our study reveals CXCR1 governs DCs-mediated inflammation and autoimmune disorders and its potential as a therapeutic target for related diseases.
The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family
Authors: Kundu Prasun , Naskar Deboki , McKie Shannon J. , Dass Sheena , Kanjee Usheer , Introini Viola , Ferreira Marcelo U. , Cicuta Pietro , Duraisingh Manoj , Deane Janet E. , Rayner Julian C. 
Published: September 2023

AbstractTryptophan Rich Antigens (TRAgs) are encoded by a multi-gene family found in all Plasmodium species, but are significantly expanded in P. vivax and closely related parasites. We show that multiple P. vivax TRAgs are expressed on the merozoite surface and that one, PVP01_0000100 binds red blood cells with a strong preference for reticulocytes. Using X-ray crystallography, we solved the structure of the PVP01_0000100 C-terminal tryptophan rich domain, which defines the TRAg family, revealing a three-helical bundle that is conserved across Plasmodium and has structural homology with lipid-binding BAR domains involved in membrane remodelling. Biochemical assays confirm that the PVP01_0000100 C-terminal domain has lipid binding activity with preference for sulfatide, a glycosphingolipid present in the outer leaflet of plasma membranes. Deletion of the putative orthologue in P. knowlesi, PKNH_1300500, impacts invasion in reticulocytes, suggesting a role during this essential process. Together, this work defines an emerging molecular function for the Plasmodium TRAg family.
DNA methylation profiling to determine the primary sites of metastatic cancers using formalin-fixed paraffin-embedded tissues
Authors: Zhang Shirong , He Shutao , Zhu Xin , Wang Yunfei , Xie Qionghuan , Song Xianrang , Xu Chunwei , Wang Wenxian , Xing Ligang , Xia Chengqing , Wang Qian , Li Wenfeng , Zhang Xiaochen , Yu Jinming , Ma Shenglin , Shi Jiantao , Gu Hongcang 
Published: September 2023

AbstractIdentifying the primary site of metastatic cancer is critical to guiding the subsequent treatment. Approximately 3–9% of metastatic patients are diagnosed with cancer of unknown primary sites (CUP) even after a comprehensive diagnostic workup. However, a widely accepted molecular test is still not available. Here, we report a method that applies formalin-fixed, paraffin-embedded tissues to construct reduced representation bisulfite sequencing libraries (FFPE-RRBS). We then generate and systematically evaluate 28 molecular classifiers, built on four DNA methylation scoring methods and seven machine learning approaches, using the RRBS library dataset of 498 fresh-frozen tumor tissues from primary cancer patients. Among these classifiers, the beta value-based linear support vector (BELIVE) performs the best, achieving overall accuracies of 81-93% for identifying the primary sites in 215 metastatic patients using top-k predictions (k = 1, 2, 3). Coincidentally, BELIVE also successfully predicts the tissue of origin in 81-93% of CUP patients (n = 68).
Action initiation and punishment learning differ from childhood to adolescence while reward learning remains stable
Authors: Pauli Ruth , Brazil Inti A. , Kohls Gregor , Klein-Flügge Miriam C. , Rogers Jack C. , Dikeos Dimitris , Dochnal Roberta , Fairchild Graeme , Fernández-Rivas Aranzazu , Herpertz-Dahlmann Beate , Hervas Amaia , Konrad Kerstin , Popma Arne , Stadler Christina , Freitag Christine M. , De Brito Stephane A. , Lockwood Patricia L. 
Published: September 2023

AbstractTheoretical and empirical accounts suggest that adolescence is associated with heightened reward learning and impulsivity. Experimental tasks and computational models that can dissociate reward learning from the tendency to initiate actions impulsively (action initiation bias) are thus critical to characterise the mechanisms that drive developmental differences. However, existing work has rarely quantified both learning ability and action initiation, or it has relied on small samples. Here, using computational modelling of a learning task collected from a large sample (N = 742, 9-18 years, 11 countries), we test differences in reward and punishment learning and action initiation from childhood to adolescence. Computational modelling reveals that whilst punishment learning rates increase with age, reward learning remains stable. In parallel, action initiation biases decrease with age. Results are similar when considering pubertal stage instead of chronological age. We conclude that heightened reward responsivity in adolescence can reflect differences in action initiation rather than enhanced reward learning.
Decarboxylation of β-boryl NHPI esters enables radical 1,2-boron shift for the assembly of versatile organoborons
Authors: Guo Yu , Wang Xiaosha , Li Chengbo , Su Jianke , Xu Jian , Song Qiuling 
Published: September 2023

AbstractIn recent years, numerous 1,2-R shift (R = aliphatic or aryl) based on tetracoordinate boron species have been well investigated. In the contrary, the corresponding radical migrations, especially 1,2-boryl radical shift for the construction of organoborons is still in its infancy. Given the paucity and significance of such strategies in boron chemistry, it is urgent to develop other efficient and alternative synthetic protocols to enrich these underdeveloped radical 1,2-boron migrations, before their fundamental potential applications could be fully explored at will. Herein, we have demonstrated a visible-light-induced photoredox neutral decarboxylative radical cross-coupling reaction, which undergoes a radical 1,2-boron shift to give a translocated C-radical for further capture of versatile radical acceptors. The mild reaction conditions, good functional-group tolerance, and broad β-boryl NHPI esters scope as well as versatile radical acceptors make this protocol applicable in modification of bioactive molecules. It can be expected that this methodology will be a very useful tool and an alternative strategy for the construction of primary organoborons via a novel radical 1,2-boron shift mode.
A landscape of complex tandem repeats within individual human genomes
Authors: Ichikawa Kazuki , Kawahara Riki , Asano Takeshi , Morishita Shinichi 
Published: September 2023

AbstractMarkedly expanded tandem repeats (TRs) have been correlated with ~60 diseases. TR diversity has been considered a clue toward understanding missing heritability. However, haplotype-resolved long TRs remain mostly hidden or blacked out because their complex structures (TRs composed of various units and minisatellites containing >10-bp units) make them difficult to determine accurately with existing methods. Here, using a high-precision algorithm to determine complex TR structures from long, accurate reads of PacBio HiFi, an investigation of 270 Japanese control samples yields several genome-wide findings. Approximately 322,000 TRs are difficult to impute from the surrounding single-nucleotide variants. Greater genetic divergence of TR loci is significantly correlated with more events of younger replication slippage. Complex TRs are more abundant than single-unit TRs, and a tendency for complex TRs to consist of <10-bp units and single-unit TRs to be minisatellites is statistically significant at loci with ≥500-bp TRs. Of note, 8909 loci with extended TRs (>100b longer than the mode) contain several known disease-associated TRs and are considered candidates for association with disorders. Overall, complex TRs and minisatellites are found to be abundant and diverse, even in genetically small Japanese populations, yielding insights into the landscape of long TRs.
Class III hybrid cluster protein homodimeric architecture shows evolutionary relationship with Ni, Fe-carbon monoxide dehydrogenases
Authors: Fujishiro Takashi , Takaoka Kyosei 
Published: September 2023

AbstractHybrid cluster proteins (HCPs) are Fe-S-O cluster-containing metalloenzymes in three distinct classes (class I and II: monomer, III: homodimer), all of which structurally related to homodimeric Ni, Fe-carbon monoxide dehydrogenases (CODHs). Here we show X-ray crystal structure of class III HCP from Methanothermobacter marburgensis (Mm HCP), demonstrating its homodimeric architecture structurally resembles those of CODHs. Also, despite the different architectures of class III and I/II HCPs, [4Fe-4S] and hybrid clusters are found in equivalent positions in all HCPs. Structural comparison of Mm HCP and CODHs unveils some distinct features such as the environments of their homodimeric interfaces and the active site metalloclusters. Furthermore, structural analysis of Mm HCP C67Y and characterization of several Mm HCP variants with a Cys67 mutation reveal the significance of Cys67 in protein structure, metallocluster binding and hydroxylamine reductase activity. Structure-based bioinformatics analysis of HCPs and CODHs provides insights into the structural evolution of the HCP/CODH superfamily.
KMT2A associates with PHF5A-PHF14-HMG20A-RAI1 subcomplex in pancreatic cancer stem cells and epigenetically regulates their characteristics
Authors: Mouti Mai Abdel , Deng Siwei , Pook Martin , Malzahn Jessica , Rendek Aniko , Militi Stefania , Nibhani Reshma , Soonawalla Zahir , Oppermann Udo , Hwang Chang-il , Pauklin Siim 
Published: September 2023

AbstractPancreatic cancer (PC), one of the most aggressive and life-threatening human malignancies, is known for its resistance to cytotoxic therapies. This is increasingly ascribed to the subpopulation of undifferentiated cells, known as pancreatic cancer stem cells (PCSCs), which display greater evolutionary fitness than other tumor cells to evade the cytotoxic effects of chemotherapy. PCSCs are crucial for tumor relapse as they possess ‘stem cell-like’ features that are characterized by self-renewal and differentiation. However, the molecular mechanisms that maintain the unique characteristics of PCSCs are poorly understood. Here, we identify the histone methyltransferase KMT2A as a physical binding partner of an RNA polymerase-associated PHF5A-PHF14-HMG20A-RAI1 protein subcomplex and an epigenetic regulator of PCSC properties and functions. Targeting the protein subcomplex in PCSCs with a KMT2A-WDR5 inhibitor attenuates their self-renewal capacity, cell viability, and in vivo tumorigenicity.
Pre-activated nanoparticles with persistent luminescence for deep tumor photodynamic therapy in gallbladder cancer
Authors: Juengpanich Sarun , Li Shijie , Yang Taorui , Xie Tianao , Chen Jiadong , Shan Yukai , Lee Jiyoung , Lu Ziyi , Chen Tianen , Zhang Bin , Cao Jiasheng , Hu Jiahao , Yu Jicheng , Wang Yanfang , Topatana Win , Gu Zhen , Cai Xiujun , Chen Mingyu 
Published: September 2023

AbstractPhototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.
Atomically dispersed Cu coordinated Rh metallene arrays for simultaneously electrochemical aniline synthesis and biomass upgrading
Authors: Mao Qiqi , Mu Xu , Wang Wenxin , Deng Kai , Yu Hongjie , Wang Ziqiang , Xu You , Wang Liang , Wang Hongjing 
Published: September 2023

AbstractOrganic electrocatalytic conversion is an essential pathway for the green conversion of low-cost organic compounds to high-value chemicals, which urgently demands the development of efficient electrocatalysts. Here, we report a Cu single-atom dispersed Rh metallene arrays on Cu foam for cathodic nitrobenzene electroreduction reaction and anodic methanol oxidation reaction. In the coupled electrocatalytic system, the Cusingle-atom-Rh metallene arrays on Cu foam requires only the low voltages of 1.18 V to reach current densities of 100 mA cm−2 for generating aniline and formate, with up to ~100% of nitrobenzene conversion/ aniline selectivity and over ~90% of formate Faraday efficiency, achieving synthesis of high-value chemicals. Density functional theory calculations reveal the electron effect between Cu single-atom and Rh host and catalytic reaction mechanism. The synergistic catalytic effect and H*-spillover effect can improve catalytic reaction process and reduce energy barrier for reaction process, thus enhancing electrocatalytic reaction activity and target product selectivity.
Growth phase estimation for abundant bacterial populations sampled longitudinally from human stool metagenomes
Authors: Lim Joe J. , Diener Christian , Wilson James , Valenzuela Jacob J. , Baliga Nitin S. , Gibbons Sean M. 
Published: September 2023

AbstractLongitudinal sampling of the stool has yielded important insights into the ecological dynamics of the human gut microbiome. However, human stool samples are available approximately once per day, while commensal population doubling times are likely on the order of minutes-to-hours. Despite this mismatch in timescales, much of the prior work on human gut microbiome time series modeling has assumed that day-to-day fluctuations in taxon abundances are related to population growth or death rates, which is likely not the case. Here, we propose an alternative model of the human gut as a stationary system, where population dynamics occur internally and the bacterial population sizes measured in a bolus of stool represent a steady-state endpoint of these dynamics. We formalize this idea as stochastic logistic growth. We show how this model provides a path toward estimating the growth phases of gut bacterial populations in situ. We validate our model predictions using an in vitro Escherichia coli growth experiment. Finally, we show how this method can be applied to densely-sampled human stool metagenomic time series data. We discuss how these growth phase estimates may be used to better inform metabolic modeling in flow-through ecosystems, like animal guts or industrial bioreactors.
Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation
Authors: Wang Ran , Yang Xianfa , Chen Jiehui , Zhang Lin , Griffiths Jonathan A. , Cui Guizhong , Chen Yingying , Qian Yun , Peng Guangdun , Li Jinsong , Wang Liantang , Marioni John C. , Tam Patrick P. L. , Jing Naihe 
Published: September 2023

AbstractUnderstanding of the molecular drivers of lineage diversification and tissue patterning during primary germ layer development requires in-depth knowledge of the dynamic molecular trajectories of cell lineages across a series of developmental stages of gastrulation. Through computational modeling, we constructed at single-cell resolution, a spatio-temporal transcriptome of cell populations in the germ-layers of gastrula-stage mouse embryos. This molecular atlas enables the inference of molecular network activity underpinning the specification and differentiation of the germ-layer tissue lineages. Heterogeneity analysis of cellular composition at defined positions in the epiblast revealed progressive diversification of cell types. The single-cell transcriptome revealed an enhanced BMP signaling activity in the right-side mesoderm of late-gastrulation embryo. Perturbation of asymmetric BMP signaling activity at late gastrulation led to randomization of left-right molecular asymmetry in the lateral mesoderm of early-somite-stage embryo. These findings indicate the asymmetric BMP activity during gastrulation may be critical for the symmetry breaking process.
Robotic-OCT guided inspection and microsurgery of monolithic storage devices
Authors: He Bin , Zhang Yuxin , Zhao Lu , Sun Zhenwen , Hu Xiyuan , Kang Yanrong , Wang Lei , Li Zhihui , Huang Wei , Li Zhigang , Xing Guidong , Hua Feng , Wang Chengming , Xue Ping , Zhang Ning 
Published: September 2023

AbstractData recovery from monolithic storage devices (MSDs) is in high demand for legal or business purposes. However, the conventional data recovery methods are destructive, complicated, and time-consuming. We develop a robotic-arm-assisted optical coherence tomography (robotic-OCT) for non-destructive inspection of MSDs, offering ~7 μm lateral resolution, ~4 μm axial resolution and an adjustable field-of-view to accommodate various MSD sizes. Using a continuous scanning strategy, robotic-OCT achieves automated volumetric imaging of a micro-SD card in ~37 seconds, significantly faster than the traditional stop-and-stare scanning that typically takes tens of minutes. We also demonstrate the robotic-OCT-guided laser ablation as a microsurgical tool for targeted area removal with precision of ±10 μm and accuracy of ~50 μm, eliminating the need to remove the entire insulating layer and operator intervention, thus greatly improving the data recovery efficiency. This work has diverse potential applications in digital forensics, failure analysis, materials testing, and quality control.
Topological data analysis of spatial patterning in heterogeneous cell populations: clustering and sorting with varying cell-cell adhesion
Authors: Bhaskar Dhananjay , Zhang William Y. , Volkening Alexandria , Sandstede Björn , Wong Ian Y. 
Published: September 2023

AbstractDifferent cell types aggregate and sort into hierarchical architectures during the formation of animal tissues. The resulting spatial organization depends (in part) on the strength of adhesion of one cell type to itself relative to other cell types. However, automated and unsupervised classification of these multicellular spatial patterns remains challenging, particularly given their structural diversity and biological variability. Recent developments based on topological data analysis are intriguing to reveal similarities in tissue architecture, but these methods remain computationally expensive. In this article, we show that multicellular patterns organized from two interacting cell types can be efficiently represented through persistence images. Our optimized combination of dimensionality reduction via autoencoders, combined with hierarchical clustering, achieved high classification accuracy for simulations with constant cell numbers. We further demonstrate that persistence images can be normalized to improve classification for simulations with varying cell numbers due to proliferation. Finally, we systematically consider the importance of incorporating different topological features as well as information about each cell type to improve classification accuracy. We envision that topological machine learning based on persistence images will enable versatile and robust classification of complex tissue architectures that occur in development and disease.
Protein–lipid charge interactions control the folding of outer membrane proteins into asymmetric membranes
Authors: Machin Jonathan M. , Kalli Antreas C. , Ranson Neil A. , Radford Sheena E. 
Published: September 2023

AbstractBiological membranes consist of two leaflets of phospholipid molecules that form a bilayer, each leaflet comprising a distinct lipid composition. This asymmetry is created and maintained in vivo by dedicated biochemical pathways, but difficulties in creating stable asymmetric membranes in vitro have restricted our understanding of how bilayer asymmetry modulates the folding, stability and function of membrane proteins. In this study, we used cyclodextrin-mediated lipid exchange to generate liposomes with asymmetric bilayers and characterize the stability and folding kinetics of two bacterial outer membrane proteins (OMPs), OmpA and BamA. We found that excess negative charge in the outer leaflet of a liposome impedes their insertion and folding, while excess negative charge in the inner leaflet accelerates their folding relative to symmetric liposomes with the same membrane composition. Using molecular dynamics, mutational analysis and bioinformatics, we identified a positively charged patch critical for folding and stability. These results rationalize the well-known ‘positive-outside’ rule of OMPs and suggest insights into the mechanisms that drive OMP folding and assembly in vitro and in vivo.