bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent transcriptomic signatures from putative mesenchymal stimuli in glioblastoma cells
Authors: Hart William S. , Myers Paul J. , Purow Benjamin W. , Lazzara Matthew J. 
Published: February 2024

AbstractIn glioblastoma, a mesenchymal phenotype is associated with especially poor patient outcomes. Various glioblastoma microenvironmental factors and therapeutic interventions are purported drivers of the mesenchymal transition, but the degree to which these cues promote the same mesenchymal transitions and the uniformity of those transitions, as defined by molecular subtyping systems, is unknown. Here, we investigate this question by analyzing publicly available patient data, surveying commonly measured transcripts for mesenchymal transitions in glioma-initiating cells (GIC), and performing next-generation RNA sequencing of GICs. Analysis of patient tumor data reveals that TGFβ, TNFα, and hypoxia signaling correlate with the mesenchymal subtype more than the proneural subtype. In cultured GICs, the microenvironment-relevant growth factors TGFβ and TNFα and the chemotherapeutic temozolomide promote expression of commonly measured mesenchymal transcripts. However, next-generation RNA sequencing reveals that growth factors and temozolomide broadly promote expression of both mesenchymal and proneural transcripts, in some cases with equal frequency. These results suggest that glioblastoma mesenchymal transitions do not occur as distinctly as in epithelial-derived cancers, at least as determined using common subtyping ontologies and measuring response to growth factors or chemotherapeutics. Further understanding of these issues may identify improved methods for pharmacologically targeting the mesenchymal phenotype in glioblastoma.
MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma
Authors: Guan Jinqiu , Li Mengzhen , Wang Yi , Zhang Yu , Que Yi , Lu Suying , Wang Juan , Zhu Jia , Huang Junting , Zhen Zijun , Sun Feifei , Song Mengjia , Zhang Yizhuo 
Published: February 2024

AbstractMYCN amplification is an independent poor prognostic factor in patients with high-risk neuroblastoma (NB). Further exploring the molecular regulatory mechanisms in MYCN-amplified NB will help to develop novel therapy targets. In this study, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) was identified as the differentially expressed gene (DEG) highly expressed in MYCN-amplified NB, and it showed a positive correlation with MYCN and was associated with a poor prognosis of NB patients. Knockdown of MTHFD1 inhibited proliferation and migration, and induced apoptosis of NB cells in vitro. Mouse model experiments validated the tumorigenic effect of MTHFD1 in NB in vivo. In terms of the mechanism, ChIP-qPCR and dual-luciferase reporter assays demonstrated that MTHFD1 was directly activated by MYCN at the transcriptional level. As an important enzyme in the folic acid metabolism pathway, MTHFD1 maintained the NADPH redox homeostasis in MYCN-amplified NB. Knockdown of MTHFD1 reduced cellular NADPH/NADP+ and GSH/GSSG ratios, increased cellular reactive oxygen species (ROS) and triggered the apoptosis of NB cells. Moreover, genetic knockdown of MTHFD1 or application of the anti-folic acid metabolism drug methotrexate (MTX) potentiated the anti-tumor effect of JQ1 both in vitro and in vivo. Taken together, MTHFD1 as an oncogene is a potential therapeutic target for MYCN-amplified NB. The combination of MTX with JQ1 is of important clinical translational significance for the treatment of patients with MYCN-amplified NB.
SOX on tumors, a comfort or a constraint?
Authors: Jiang Junqing , Wang Yufei , Sun Mengyu , Luo Xiangyuan , Zhang Zerui , Wang Yijun , Li Siwen , Hu Dian , Zhang Jiaqian , Wu Zhangfan , Chen Xiaoping , Zhang Bixiang , Xu Xiao , Wang Shuai , Xu Shengjun , Huang Wenjie , Xia Limin 
Published: February 2024

AbstractThe sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes the physiological function of the SOX family and their multiple roles in tumors, with a focus on the relationship between the SOX family and TIME, aiming to propose their potential role in cancer and promising methods for treatment.
T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms
Authors: Rauch Eileen , Amendt Timm , Lopez Krol Aleksandra , Lang Fabian B. , Linse Vincent , Hohmann Michelle , Keim Ann-Christin , Kreutzer Susanne , Kawengian Kevin , Buchholz Malte , Duschner Philipp , Grauer Saskia , Schnierle Barbara , Ruhl Andreas , Burtscher Ingo , Dehnert Sonja , Kuria Chege , Kupke Alexandra , Paul Stephanie , Liehr Thomas , Lechner Marcus , Schnare Markus , Kaufmann Andreas , Huber Magdalena , Winkler Thomas H. , Bauer Stefan , Yu Philipp 
Published: February 2024

AbstractEndogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the mouse germline. This enables us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identify an autoreactive B cell response against the neo-self/ERV antigen GFP as a key mechanism of ERV control. Hallmarks of this response are spontaneous ERV-GFP+ germinal center formation, elevated serum IFN-γ levels and a dependency on Age-associated B cells (ABCs) a subclass of T-bet+ memory B cells. Impairment of IgM B cell receptor-signal in nucleic-acid sensing TLR-deficient mice contributes to defective ERV control. Although ERVs are a part of the genome they break immune tolerance, induce immune surveillance against ERV-derived self-antigens and shape the host immune response.
A method to estimate the contribution of rare coding variants to complex trait heritability
Authors: Pathan Nazia , Deng Wei Q. , Di Scipio Matteo , Khan Mohammad , Mao Shihong , Morton Robert W. , Lali Ricky , Pigeyre Marie , Chong Michael R. , Paré Guillaume 
Published: February 2024

AbstractIt has been postulated that rare coding variants (RVs; MAF < 0.01) contribute to the “missing” heritability of complex traits. We developed a framework, the Rare variant heritability (RARity) estimator, to assess RV heritability (h2RV) without assuming a particular genetic architecture. We applied RARity to 31 complex traits in the UK Biobank (n = 167,348) and showed that gene-level RV aggregation suffers from 79% (95% CI: 68-93%) loss of h2RV. Using unaggregated variants, 27 traits had h2RV > 5%, with height having the highest h2RV at 21.9% (95% CI: 19.0-24.8%). The total heritability, including common and rare variants, recovered pedigree-based estimates for 11 traits. RARity can estimate gene-level h2RV, enabling the assessment of gene-level characteristics and revealing 11, previously unreported, gene-phenotype relationships. Finally, we demonstrated that in silico pathogenicity prediction (variant-level) and gene-level annotations do not generally enrich for RVs that over-contribute to complex trait variance, and thus, innovative methods are needed to predict RV functionality.
Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndrome
Authors: Xu Jun , Liu Ying , Yang Fangying , Cao Yurou , Chen Weihang , Li Joshua Shing Shun , Zhang Shuai , Comjean Aram , Hu Yanhui , Perrimon Norbert 
Published: February 2024

AbstractParaneoplastic syndromes occur in cancer patients and originate from dysfunction of organs at a distance from the tumor or its metastasis. A wide range of organs can be affected in paraneoplastic syndromes; however, the pathological mechanisms by which tumors influence host organs are poorly understood. Recent studies in the fly uncovered that tumor secreted factors target host organs, leading to pathological effects. In this study, using a Drosophila gut tumor model, we characterize a mechanism of tumor-induced kidney dysfunction. Specifically, we find that Pvf1, a PDGF/VEGF signaling ligand, secreted by gut tumors activates the PvR/JNK/Jra signaling pathway in the principal cells of the kidney, leading to mis-expression of renal genes and paraneoplastic renal syndrome-like phenotypes. Our study describes an important mechanism by which gut tumors perturb the function of the kidney, which might be of clinical relevance for the treatment of paraneoplastic syndromes.
Acidic media enables oxygen-tolerant electrosynthesis of multicarbon products from simulated flue gas
Authors: Wang Meng , Wang Bingqing , Zhang Jiguang , Xi Shibo , Ling Ning , Mi Ziyu , Yang Qin , Zhang Mingsheng , Leow Wan Ru , Zhang Jia , Lum Yanwei 
Published: February 2024

AbstractRenewable electricity powered electrochemical CO2 reduction (CO2R) offers a valuable method to close the carbon cycle and reduce our overreliance on fossil fuels. However, high purity CO2 is usually required as feedstock, which potentially decreases the feasibility and economic viability of the process. Direct conversion of flue gas is an attractive option but is challenging due to the low CO2 concentration and the presence of O2 impurities. As a result, up to 99% of the applied current can be lost towards the undesired oxygen reduction reaction (ORR). Here, we show that acidic electrolyte can significantly suppress ORR on Cu, enabling generation of multicarbon products from simulated flue gas. Using a composite Cu and carbon supported single-atom Ni tandem electrocatalyst, we achieved a multicarbon Faradaic efficiency of 46.5% at 200 mA cm-2, which is ~20 times higher than bare Cu under alkaline conditions. We also demonstrate stable performance for 24 h with a multicarbon product full-cell energy efficiency of 14.6%. Strikingly, this result is comparable to previously reported acidic CO2R systems using pure CO2. Our findings demonstrate a potential pathway towards designing efficient electrolyzers for direct conversion of flue gas to value-added chemicals and fuels.
Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase
Authors: Han Xiaofeng , Chen Fuqiang , Li Huanhuan , Ge Ran , Shen Qianqian , Duan Peigao , Sheng Xiang , Zhang Wuyuan 
Published: February 2024

AbstractHemiacetal compounds are valuable building blocks in synthetic chemistry, but their enzymatic synthesis is limited and often hindered by the instability of hemiacetals in aqueous environments. Here, we show that this challenge can be addressed through reaction engineering by using immobilized peroxygenase from Agrocybe aegerita (AaeUPO) under neat reaction conditions, which allows for the selective C-H bond oxyfunctionalization of environmentally significant cyclic ethers to cyclic hemiacetals. A wide range of chiral cyclic hemiacetal products are prepared in >99% enantiomeric excess and 95170 turnover numbers of AaeUPO. Furthermore, by changing the reaction medium from pure organic solvent to alkaline aqueous conditions, cyclic hemiacetals are in situ transformed into lactones. Lactams are obtained under the applied conditions, albeit with low enzyme activity. These findings showcase the synthetic potential of AaeUPO and offer a practical enzymatic approach to produce chiral cyclic hemiacetals through C-H oxyfunctionalization under mild conditions.
Phosphorylation of Arabidopsis UVR8 photoreceptor modulates protein interactions and responses to UV-B radiation
Authors: Liu Wei , Giuriani Giovanni , Havlikova Anezka , Li Dezhi , Lamont Douglas J. , Neugart Susanne , Velanis Christos N. , Petersen Jan , Hoecker Ute , Christie John M. , Jenkins Gareth I. 
Published: February 2024

AbstractExposure of plants to ultraviolet-B (UV-B) radiation initiates transcriptional responses that modify metabolism, physiology and development to enhance viability in sunlight. Many of these regulatory responses to UV-B radiation are mediated by the photoreceptor UV RESISTANCE LOCUS 8 (UVR8). Following photoreception, UVR8 interacts directly with multiple proteins to regulate gene expression, but the mechanisms that control differential protein binding to initiate distinct responses are unknown. Here we show that UVR8 is phosphorylated at several sites and that UV-B stimulates phosphorylation at Serine 402. Site-directed mutagenesis to mimic Serine 402 phosphorylation promotes binding of UVR8 to REPRESSOR OF UV-B PHOTOMORPHOGENESIS (RUP) proteins, which negatively regulate UVR8 action. Complementation of the uvr8 mutant with phosphonull or phosphomimetic variants suggests that phosphorylation of Serine 402 modifies UVR8 activity and promotes flavonoid biosynthesis, a key UV-B-stimulated response that enhances plant protection and crop nutritional quality. This research provides a basis to understand how UVR8 interacts differentially with effector proteins to regulate plant responses to UV-B radiation.
Large-area, untethered, metamorphic, and omnidirectionally stretchable multiplexing self-powered triboelectric skins
Authors: Shao Beibei , Lu Ming-Han , Wu Tai-Chen , Peng Wei-Chen , Ko Tien-Yu , Hsiao Yung-Chi , Chen Jiann-Yeu , Sun Baoquan , Liu Ruiyuan , Lai Ying-Chih 
Published: February 2024

AbstractLarge-area metamorphic stretchable sensor networks are desirable in haptic sensing and next-generation electronics. Triboelectric nanogenerator-based self-powered tactile sensors in single-electrode mode constitute one of the best solutions with ideal attributes. However, their large-area multiplexing utilizations are restricted by severe misrecognition between sensing nodes and high-density internal circuits. Here, we provide an electrical signal shielding strategy delivering a large-area multiplexing self-powered untethered triboelectric electronic skin (UTE-skin) with an ultralow misrecognition rate (0.20%). An omnidirectionally stretchable carbon black-Ecoflex composite-based shielding layer is developed to effectively attenuate electrostatic interference from wirings, guaranteeing low-level noise in sensing matrices. UTE-skin operates reliably under 100% uniaxial, 100% biaxial, and 400% isotropic strains, achieving high-quality pressure imaging and multi-touch real-time visualization. Smart gloves for tactile recognition, intelligent insoles for gait analysis, and deformable human-machine interfaces are demonstrated. This work signifies a substantial breakthrough in haptic sensing, offering solutions for the previously challenging issue of large-area multiplexing sensing arrays.
A radius valley between migrated steam worlds and evaporated rocky cores
Authors: Burn Remo , Mordasini Christoph , Mishra Lokesh , Haldemann Jonas , Venturini Julia , Emsenhuber Alexandre , Henning Thomas 
Published: February 2024

AbstractThe radius valley (or gap) in the observed distribution of exoplanet radii, which separates smaller super-Earths from larger sub-Neptunes, is a key feature that theoretical models must explain. Conventionally, it is interpreted as the result of the loss of primordial hydrogen and helium (H/He) envelopes atop rocky cores. However, planet formation models predict that water-rich planets migrate from cold regions outside the snowline towards the star. Assuming water to be in the form of solid ice in their interior, many of these planets would be located in the radius gap contradicting observations. Here we use an advanced coupled formation and evolution model that describes the planets’ growth and evolution starting from solid, moon-sized bodies in the protoplanetary disk to mature Gyr-old planetary systems. Employing new equations of state and interior structure models to treat water as vapour mixed with H/He, we naturally reproduce the valley at the observed location. The model results demonstrate that the observed radius valley can be interpreted as the separation of less massive, rocky super-Earths formed in situ from more massive, ex situ, water-rich sub-Neptunes. Furthermore, the occurrence drop at larger radii, the so-called radius cliff, is matched by planets with water-dominated envelopes. Our statistical approach shows that the synthetic distribution of radii quantitatively agrees with observations for close-in planets, but only if low-mass planets initially containing H/He lose their atmosphere due to photoevaporation, which populates the super-Earth peak with evaporated rocky cores. Therefore, we provide a hybrid theoretical explanation of the radius gap and cliff caused by both planet formation (orbital migration) as well as evolution (atmospheric escape).
Newly formed dust within the circumstellar environment of SN Ia-CSM 2018evt
Authors: Wang王 Lingzhi 灵芝 , Hu Maokai , Wang Lifan , Yang 杨 Yi 轶 , Yang Jiawen , Gomez Haley , Chen Sijie , Hu Lei , Chen Ting-Wan , Mo Jun , Wang Xiaofeng , Baade Dietrich , Hoeflich Peter , Wheeler J. Craig , Pignata Giuliano , Burke Jamison , Hiramatsu Daichi , Howell D. Andrew , McCully Curtis , Pellegrino Craig , Galbany Lluís , Hsiao Eric Y. , Sand David J. , Zhang Jujia , Uddin Syed A. , Anderson J. P. , Ashall Chris , Cheng Cheng , Gromadzki Mariusz , Inserra Cosimo , Lin Han , Morrell N. , Morales-Garoffolo Antonia , Müller-Bravo T. E. , Nicholl Matt , Gonzalez Estefania Padilla , Phillips M. M. , Pineda-García J. , Sai Hanna , Smith Mathew , Shahbandeh M. , Srivastav Shubham , Stritzinger M. D. , Yang Sheng , Young D. R. , Yu Lixin , Zhang Xinghan 
Published: February 2024

AbstractDust associated with various stellar sources in galaxies at all cosmic epochs remains a controversial topic, particularly whether supernovae play an important role in dust production. We report evidence of dust formation in the cold, dense shell behind the ejecta–circumstellar medium (CSM) interaction in the Type Ia-CSM supernova (SN) 2018evt three years after the explosion, characterized by a rise in mid-infrared emission accompanied by an accelerated decline in the optical radiation of the SN. Such a dust-formation picture is also corroborated by the concurrent evolution of the profiles of the Hα emission line. Our model suggests enhanced CSM dust concentration at increasing distances from the SN as compared to what can be expected from the density profile of the mass loss from a steady stellar wind. By the time of the last mid-infrared observations at day +1,041, a total amount of 1.2 ± 0.2 × 10−2 M⊙ of new dust has been formed by SN 2018evt, making SN 2018evt one of the most prolific dust factories among supernovae with evidence of dust formation. The unprecedented witness of the intense production procedure of dust may shed light on the perceptions of dust formation in cosmic history.
VertXNet: an ensemble method for vertebral body segmentation and identification from cervical and lumbar spinal X-rays
Authors: Chen Yao , Mo Yuanhan , Readie Aimee , Ligozio Gregory , Mandal Indrajeet , Jabbar Faiz , Coroller Thibaud , Papież Bartłomiej W. 
Published: February 2024

AbstractAccurate annotation of vertebral bodies is crucial for automating the analysis of spinal X-ray images. However, manual annotation of these structures is a laborious and costly process due to their complex nature, including small sizes and varying shapes. To address this challenge and expedite the annotation process, we propose an ensemble pipeline called VertXNet. This pipeline currently combines two segmentation mechanisms, semantic segmentation using U-Net, and instance segmentation using Mask R-CNN, to automatically segment and label vertebral bodies in lateral cervical and lumbar spinal X-ray images. VertXNet enhances its effectiveness by adopting a rule-based strategy (termed the ensemble rule) for effectively combining segmentation outcomes from U-Net and Mask R-CNN. It determines vertebral body labels by recognizing specific reference vertebral instances, such as cervical vertebra 2 (‘C2’) in cervical spine X-rays and sacral vertebra 1 (‘S1’) in lumbar spine X-rays. Those references are commonly relatively easy to identify at the edge of the spine. To assess the performance of our proposed pipeline, we conducted evaluations on three spinal X-ray datasets, including two in-house datasets and one publicly available dataset. The ground truth annotations were provided by radiologists for comparison. Our experimental results have shown that the proposed pipeline outperformed two state-of-the-art (SOTA) segmentation models on our test dataset with a mean Dice of 0.90, vs. a mean Dice of 0.73 for Mask R-CNN and 0.72 for U-Net. We also demonstrated that VertXNet is a modular pipeline that enables using other SOTA model, like nnU-Net to further improve its performance. Furthermore, to evaluate the generalization ability of VertXNet on spinal X-rays, we directly tested the pre-trained pipeline on two additional datasets. A consistently strong performance was observed, with mean Dice coefficients of 0.89 and 0.88, respectively. In summary, VertXNet demonstrated significantly improved performance in vertebral body segmentation and labeling for spinal X-ray imaging. Its robustness and generalization were presented through the evaluation of both in-house clinical trial data and publicly available datasets.
Study of summer microclimate and PM2.5 concentration in campus plant communities
Authors: Jiang Yuan , Liu Congzhe , Wen Chenjie , Long Yuelin 
Published: February 2024

AbstractUnderstanding the influencing effect of meteorological factors and air pollutants in the campus plot and the relationship between them is an important topic in the planning and design of campus green space. The changes of pollutant concentrations and meteorological factors in campus green space have certain patterns and specific influencing factors. In this study, we selected four sample plots in Nanjing Forestry University as the research objects, and collected various environmental parameters of the four plots on July 25, 2022. The results showed that the main influences of meteorological factors are the type of the underlying surface of the site, the degree of plant canopy density and the shade coverage area of the building. These factors mainly have a great influence on the value of temperature and humidity. The comprehensive influencing factors can be concluded that the cooling and humidifying effect of the site is ranked as follows: forest > lawn > asphalt road > concrete Square. The main influencing factors of pollutants are: illumination, wind speed, temperature and relative humidity. Among them, illumination and temperature have a negative correlation with PM2.5, wind speed and relative humidity have a positive correlation with PM2.5. Our research shows that the adjustment of campus green space factors can reduce the concentration of pollutants by changing the meteorological factors.