bluuebunny/crossref_metadata_2025_split huggingface dataset:
USP1 modulates hepatocellular carcinoma progression via the Hippo/TAZ axis
Authors: Liu Dongyi , Li Quanhui , Zang Yifeng , Li Xin , Li Zhongbo , Zhang Peng , Feng Chang , Yang Penghe , Cui Jiayao , Sun Yanan , Wei Tian , Su Peng , Zhao Xin , Yang Huijie , Ding Yinlu 
Published: April 2023

AbstractHepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. The Hippo signaling pathway has emerged as a significant suppressive pathway for hepatocellular carcinogenesis. The core components of the Hippo pathway constitute a kinase cascade, which inhibits the functional activation of YAP/TAZ. Interestingly, the overactivation of YAP/TAZ is commonly observed in hepatocellular carcinoma, although the inhibitory kinase cascade of the Hippo pathway is still functional. Recent studies have indicated that the ubiquitin‒proteasome system also plays important roles in modulating Hippo signaling activity. Our DUB (deubiquitinase) siRNA screen showed that USP1 is a critical regulator of Hippo signaling activity. Analysis of TCGA data demonstrated that USP1 expression is elevated in HCC and associated with poor survival in HCC patients. RNA sequencing analysis revealed that USP1 depletion affects Hippo signaling activity in HCC cell lines. Mechanistic assays revealed that USP1 is required for Hippo/TAZ axis activity and HCC progression. USP1 interacted with the WW domain of TAZ, which subsequently enhanced TAZ stability by suppressing K11-linked polyubiquitination of TAZ. Our study identifies a novel mechanism linking USP1 and TAZ in regulating the Hippo pathway and one possible therapeutic target for HCC.
IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling
Authors: Bachus Holly , McLaughlin Erin , Lewis Crystal , Papillion Amber M. , Benveniste Etty N. , Hill Dave Durell , Rosenberg Alexander F. , Ballesteros-Tato André , León Beatriz 
Published: April 2023

AbstractDefective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. We found that IL-6 turned off IL-2 signaling during early T-cell activation and thus inhibited Th2 priming. Mechanistically, IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.
Inflammatory signals from fatty bone marrow support DNMT3A driven clonal hematopoiesis
Authors: Zioni N. , Bercovich A. Akhiad , Chapal-Ilani N. , Bacharach Tal , Rappoport N. , Solomon A. , Avraham R. , Kopitman E. , Porat Z. , Sacma M. , Hartmut G. , Scheller M. , Muller-Tidow C. , Lipka D. , Shlush E. , Minden M. , Kaushansky N. , Shlush Liran I. 
Published: April 2023

AbstractBoth fatty bone marrow (FBM) and somatic mutations in hematopoietic stem cells (HSCs), also termed clonal hematopoiesis (CH) accumulate with human aging. However it remains unclear whether FBM can modify the evolution of CH. To address this question, we herein present the interaction between CH and FBM in two preclinical male mouse models: after sub-lethal irradiation or after castration. An adipogenesis inhibitor (PPARγ inhibitor) is used in both models as a control. A significant increase in self-renewal can be detected in both human and rodent DNMT3AMut-HSCs when exposed to FBM. DNMT3AMut-HSCs derived from older mice interacting with FBM have even higher self-renewal in comparison to DNMT3AMut-HSCs derived from younger mice. Single cell RNA-sequencing on rodent HSCs after exposing them to FBM reveal a 6-10 fold increase in DNMT3AMut-HSCs and an activated inflammatory signaling. Cytokine analysis of BM fluid and BM derived adipocytes grown in vitro demonstrates an increased IL-6 levels under FBM conditions. Anti-IL-6 neutralizing antibodies significantly reduce the selective advantage of DNMT3AMut-HSCs exposed to FBM. Overall, paracrine FBM inflammatory signals promote DNMT3A-driven clonal hematopoiesis, which can be inhibited by blocking the IL-6 pathway.
Combining data and theory for derivable scientific discovery with AI-Descartes
Authors: Cornelio Cristina , Dash Sanjeeb , Austel Vernon , Josephson Tyler R. , Goncalves Joao , Clarkson Kenneth L. , Megiddo Nimrod , El Khadir Bachir , Horesh Lior 
Published: April 2023

AbstractScientists aim to discover meaningful formulae that accurately describe experimental data. Mathematical models of natural phenomena can be manually created from domain knowledge and fitted to data, or, in contrast, created automatically from large datasets with machine-learning algorithms. The problem of incorporating prior knowledge expressed as constraints on the functional form of a learned model has been studied before, while finding models that are consistent with prior knowledge expressed via general logical axioms is an open problem. We develop a method to enable principled derivations of models of natural phenomena from axiomatic knowledge and experimental data by combining logical reasoning with symbolic regression. We demonstrate these concepts for Kepler’s third law of planetary motion, Einstein’s relativistic time-dilation law, and Langmuir’s theory of adsorption. We show we can discover governing laws from few data points when logical reasoning is used to distinguish between candidate formulae having similar error on the data.
All-optical control of high-purity trions in nanoscale waveguide
Authors: Lee Hyeongwoo , Koo Yeonjeong , Kumar Shailabh , Jeong Yunjo , Heo Dong Gwon , Choi Soo Ho , Joo Huitae , Kang Mingu , Siddique Radwanul Hasan , Kim Ki Kang , Lee Hong Seok , An Sangmin , Choo Hyuck , Park Kyoung-Duck 
Published: April 2023

AbstractThe generation of high-purity localized trions, dynamic exciton–trion interconversion, and their spatial modulation in two-dimensional (2D) semiconductors are building blocks for the realization of trion-based optoelectronic devices. Here, we present a method for the all-optical control of the exciton-to-trion conversion process and its spatial distributions in a MoS2 monolayer. We induce a nanoscale strain gradient in a 2D crystal transferred on a lateral metal–insulator–metal (MIM) waveguide and exploit propagating surface plasmon polaritons (SPPs) to localize hot electrons. These significantly increase the electrons and efficiently funnel excitons in the lateral MIM waveguide, facilitating complete exciton-to-trion conversion even at ambient conditions. Additionally, we modulate the SPP mode using adaptive wavefront shaping, enabling all-optical control of the exciton-to-trion conversion rate and trion distribution in a reversible manner. Our work provides a platform for harnessing excitonic quasiparticles efficiently in the form of trions at ambient conditions, enabling high-efficiency photoconversion.
A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi
Authors: dos Reis Thaila Fernanda , de Castro Patrícia Alves , Bastos Rafael Wesley , Pinzan Camila Figueiredo , Souza Pedro F. N. , Ackloo Suzanne , Hossain Mohammad Anwar , Drewry David Harold , Alkhazraji Sondus , Ibrahim Ashraf S. , Jo Hyunil , Lightfoot Jorge D. , Adams Emily M. , Fuller Kevin K. , deGrado William F. , Goldman Gustavo H. 
Published: April 2023

AbstractFungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases. Here, we identify the host defense peptide mimetic, brilacidin (BRI) as a synergizer with caspofungin (CAS) against CAS-sensitive and CAS-resistant isolates of Aspergillus fumigatus, Candida albicans, C. auris, and CAS-intrinsically resistant Cryptococcus neoformans. BRI also potentiates azoles against A. fumigatus and several Mucorales fungi. BRI acts in A. fumigatus by affecting cell wall integrity pathway and cell membrane potential. BRI combined with CAS significantly clears A. fumigatus lung infection in an immunosuppressed murine model of invasive pulmonary aspergillosis. BRI alone also decreases A. fumigatus fungal burden and ablates disease development in a murine model of fungal keratitis. Our results indicate that combinations of BRI and antifungal drugs in clinical use are likely to improve the treatment outcome of aspergillosis and other fungal infections.
Characterization of genome-wide STR variation in 6487 human genomes
Authors: Shi Yirong , Niu Yiwei , Zhang Peng , Luo Huaxia , Liu Shuai , Zhang Sijia , Wang Jiajia , Li Yanyan , Liu Xinyue , Song Tingrui , Xu Tao , He Shunmin 
Published: April 2023

AbstractShort tandem repeats (STRs) are abundant and highly mutagenic in the human genome. Many STR loci have been associated with a range of human genetic disorders. However, most population-scale studies on STR variation in humans have focused on European ancestry cohorts or are limited by sequencing depth. Here, we depicted a comprehensive map of 366,013 polymorphic STRs (pSTRs) constructed from 6487 deeply sequenced genomes, comprising 3983 Chinese samples (~31.5x, NyuWa) and 2504 samples from the 1000 Genomes Project (~33.3x, 1KGP). We found that STR mutations were affected by motif length, chromosome context and epigenetic features. We identified 3273 and 1117 pSTRs whose repeat numbers were associated with gene expression and 3′UTR alternative polyadenylation, respectively. We also implemented population analysis, investigated population differentiated signatures, and genotyped 60 known disease-causing STRs. Overall, this study further extends the scale of STR variation in humans and propels our understanding of the semantics of STRs.
Ghost-arc geochemical anomaly at a spreading ridge caused by supersized flat subduction
Authors: Gianni Guido M. , Likerman Jeremías , Navarrete César R. , Gianni Conrado R. , Zlotnik Sergio 
Published: April 2023

AbstractThe Southern Atlantic-Southwest Indian ridges (SASWIR) host mid-ocean ridge basalts with a residual subduction-related geochemical fingerprint (i.e., a ghost-arc signature) of unclear origin. Here, we show through an analysis of plate kinematic reconstructions and seismic tomography models that the SASWIR subduction-modified mantle source formed in the Jurassic close to the Georgia Islands slab (GI) and remained near-stationary in the mantle reference frame. In this analysis, the GI lies far inboard the Jurassic Patagonian-Antarctic Peninsula active margin. This was formerly attributed to a large-scale flat subduction event in the Late Triassic-Early Jurassic. We propose that during this flat slab stage, the subduction-modified mantle areas beneath the Mesozoic active margin and surrounding sutures zones may have been bulldozed inland by >2280 km. After the demise of the flat slab, this mantle anomaly remained near-stationary and was sampled by the Karoo mantle plume 183 Million years (Myr) ago and again since 55 Myr ago by the SASWIR. We refer to this process as asthenospheric anomaly telescoping. This study provides a hitherto unrecognized geodynamic effect of flat subduction, the viability of which we support through numerical modeling.
Particle-sounding of the spatial structure of kinetic Alfvén waves
Authors: Liu Z.-Y. , Zong Q.-G. , Rankin R. , Zhang H. , Hao Y.-X. , He J.-S. , Fu S.-Y. , Wu H.-H. , Yue C. , Pollock C. J. , Le G. 
Published: April 2023

AbstractKinetic Alfvén waves (KAWs) are ubiquitous throughout the plasma universe. Although they are broadly believed to provide a potential approach for energy exchange between electromagnetic fields and plasma particles, neither the detail nor the efficiency of the interactions has been well-determined yet. The primary difficulty has been the paucity of knowledge of KAWs’ spatial structure in observation. Here, we apply a particle-sounding technique to Magnetospheric Multiscale mission data to quantitatively determine the perpendicular wavelength of KAWs from ion gyrophase-distribution observations. Our results show that KAWs’ perpendicular wavelength is statistically 2.4$$\pm 0.7$$±0.7times proton thermal gyro-radius. This observation yields an upper bound of the energy the majority proton population can reach in coherent interactions with KAWs, that is, roughly 5.76 times proton perpendicular thermal energy. Therefore, the method and results shown here provide a basis for unraveling the effects of KAWs in dissipating energy and accelerating particles in a number of astrophysical systems, e.g., planetary magnetosphere, astrophysical shocks, stellar corona and wind, and the interstellar medium.
A novel nomogram model of breast cancer-based imaging for predicting the status of axillary lymph nodes after neoadjuvant therapy
Authors: Zhang Pengyu , Song Xiang , Sun Luhao , Li Chao , Liu Xiaoyu , Bao Jiaying , Tian Zhaokun , Wang Xinzhao , Yu Zhiyong 
Published: April 2023

AbstractThis study is aimed to develop and validate a novel nomogram model that can preoperatively predict axillary lymph node pathological complete response (pCR) after NAT and avoid unnecessary axillary lymph node dissection (ALND) for breast cancer patients. A total of 410 patients who underwent NAT and were pathologically confirmed to be axillary lymph node positive after breast cancer surgery were included. They were divided into two groups: patients with axillary lymph node pCR and patients with residual node lesions after NAT. Then the nomogram prediction model was constructed by univariate and multivariate logistic regression. The result of multivariate logistic regression analysis showed that molecular subtypes, molybdenum target (MG) breast, computerized tomography (CT) breast, ultrasound (US) axilla, magnetic resonance imaging (MRI) axilla, and CT axilla (all p < 0.001) had a significant impact on the evaluation of axillary lymph node status after NAT. The nomogram score appeared that AUC was 0.832 (95% CI 0.786–0.878) in the training cohort and 0.947 (95% CI 0.906–0.988) in the validation cohort, respectively. The decision curve represented that the nomogram has a positive predictive ability, indicating its potential as a practical clinical tool.
Acoustic emission characteristics and damage evolution of basalt by microwave irradiation
Authors: Yang Jinqiang , Wang Chaolin , Zhao Yu , Bi Jing 
Published: April 2023

AbstractThe microwave-assisted rock breaking technology has been proven to be feasible, and has received considerable attention in the field of civil and mining engineering. A copper foil was used to wrap basalt to simulate rock excavation of practical application scenario in this paper. To this end, a multi-mode cavity with an operating frequency of 2.45 GHz was used to conduct microwave irradiation experiments on basalts with different irradiation times and different power. The thermal properties, AE characteristics, and damage evolution process of basalt were studied. The results show that the high heat generated by microwave leads to the development of cracks in the upper part of basalt. The higher the power level, the higher the degree of crack propagation in the sample, the lower the basalt strength, and the more active the AE activity. The fluctuation rule of the b value indicates that the basalt is dominated by small-scale microfractures before failure. High power levels or long irradiation time lead to more microwave-induced cracks participating in the failure process during loading. Compared with unheated basalt, microwave-heating basalt detects the characteristics of the precursor of failure in advance. The AE source location and the nephogram of the maximum principal stress of microwave-treated basalt reflected that the fracture path begins in the upper part of the rock. In addition, the combination of high power level and short irradiation time can achieve the purpose of energy saving.
High isolation circularly polarized in-band full-duplex anisotropic dielectric resonator antenna
Authors: Abedian Mohammad , Khalily Mohsen , Wang Fan , Xiao Pei , Tafazolli Rahim , Kishk Ahmed A. 
Published: April 2023

AbstractA novel high-isolation, monostatic, circularly polarized (CP) simultaneous transmit and receive (STAR) anisotropic dielectric resonator antenna (DRA) is presented. The Proposed antenna is composed of two identical but orthogonally positioned annular sectoral anisotropic dielectric resonators. Each circularly polarized (CP) resonator consists of alternating stacked dielectric layers of relative permittivities of 2 and 15 and is excited by a coaxial probe from the two opposite ends to have left and right-hand CP. Proper element spacing and a square absorber are placed between the resonators to maximize Tx/Rx isolation. Such a structure provides an in-band full-duplex (IBFD) CP-DRA system. Measurement results exhibit high Tx/Rx isolation better than 50 dB over the desired operating bandwidth (5.87–5.97 GHz) with a peak gain of 5.49 and 5.08 dBic for Ports 1 and 2, respectively.
Selection in coral mitogenomes, with insights into adaptations in the deep sea
Authors: Ramos Nina I. , DeLeo Danielle M. , Horowitz Jeremy , McFadden Catherine S. , Quattrini Andrea M. 
Published: April 2023

AbstractCorals are a dominant benthic fauna that occur across a vast range of depths from just below the ocean’s surface to the abyssopelagic zone. However, little is known about the evolutionary mechanisms that enable them to inhabit such a wide range of environments. The mitochondrial (mt) genome, which is involved in energetic pathways, may be subject to selection pressures at greater depths to meet the metabolic demands of that environment. Here, we use a phylogenomic framework combined with codon-based models to evaluate whether mt protein-coding genes (PCGs) associated with cellular energy functions are under positive selection across depth in three groups of corals: Octocorallia, Scleractinia, and Antipatharia. The results demonstrated that mt PCGs of deep- and shallow-water species of all three groups were primarily under strong purifying selection (0.0474 < ω < 0.3123), with the exception of positive selection in atp6 (ω = 1.3263) of deep-sea antipatharians. We also found evidence for positive selection at fifteen sites across cox1, mtMutS, and nad1 in deep-sea octocorals and nad3 of deep-sea antipatharians. These results contribute to our limited understanding of mt adaptations as a function of depth and provide insight into the molecular response of corals to the extreme deep-sea environment.
Effects of body size and countermeasure exercise on estimates of life support resources during all-female crewed exploration missions
Authors: Scott Jonathan P. R. , Green David A. , Weerts Guillaume , Cheuvront Samuel N. 
Published: April 2023

AbstractEmploying a methodology reported in a recent theoretical study on male astronauts, this study estimated the effects of body size and aerobic countermeasure (CM) exercise in a four-person, all-female crew composed of individuals drawn from a stature range (1.50- to 1.90-m) representative of current space agency requirements (which exist for stature, but not for body mass) upon total energy expenditure (TEE), oxygen (O2) consumption, carbon dioxide (CO2) and metabolic heat (Hprod) production, and water requirements for hydration, during space exploration missions. Assuming geometric similarity across the stature range, estimates were derived using available female astronaut data (mean age: 40-years; BMI: 22.7-kg·m−2; resting VO2 and VO2max: 3.3- and 40.5-mL·kg−1·min−1) on 30- and 1080-day missions, without and with, ISS-like countermeasure exercise (modelled as 2 × 30-min aerobic exercise at 75% VO2max, 6-day·week−1). Where spaceflight-specific data/equations were not available, terrestrial equivalents were used. Body size alone increased 24-h TEE (+ 30%), O2 consumption (+ 60%), CO2 (+ 60%) and Hprod (+ 60%) production, and water requirements (+ 17%). With CM exercise, the increases were + 25–31%, + 29%, + 32%, + 38% and + 17–25% across the stature range. Compared to the previous study of theoretical male astronauts, the effect of body size on TEE was markedly less in females, and, at equivalent statures, all parameter estimates were lower for females, with relative differences ranging from -5% to -29%. When compared at the 50th percentile for stature for US females and males, these differences increased to − 11% to − 41% and translated to larger reductions in TEE, O2 and water requirements, and less CO2 and Hprod during 1080-day missions using CM exercise. Differences between female and male theoretical astronauts result from lower resting and exercising O2 requirements (based on available astronaut data) of female astronauts, who are lighter than male astronauts at equivalent statures and have lower relative VO2max values. These data, combined with the current move towards smaller diameter space habitat modules, point to a number of potential advantages of all-female crews during future human space exploration missions.
Long COVID and risk of erectile dysfunction in recovered patients from mild to moderate COVID-19
Authors: Al-kuraishy Hayder M. , Al-Gareeb Ali I. , Alarfaj Sumaiah J. , Al-Akeel Rasha Khalifah , Faidah Hani , El-Bouseary Maisra M. , Sabatier Jean-Marc , De Waard Michel , El-Masry Thanaa A. , Batiha Gaber El-Saber 
Published: April 2023

AbstractPatients with coronavirus disease 2019 (COVID-19) were shown to have reduced serum testosterone levels compared to healthy individuals. Low testosterone levels are linked with the development of erectile dysfunction (ED). In this case-controlled study, 20 healthy controls and 39 patients with ED 3 months after recovering from mild-to-moderate COVID-19 pneumonia were studied. The patients ranged in age from 31 to 47 years. To identify early and late COVID-19 infections, real-time polymerase-chain reaction (RT-PCR) and COVID-19 antibody testing were done. The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), free testosterone (FT), free androgenic index (FAI), and sex hormone-binding globulin (SHBG) were measured. The sexual health inventory for patients (SHIM) score was used to measure the erectile function of the patients and controls. When compared to the controls, the TT serum level in long COVID-19 (LC) patients with ED was low (p = 0.01). In contrast to controls, FT and FAI were both lower in LC patients with ED. (p = 0.001). FSH serum levels did not significantly differ (p = 0.07), but in ED patients, LH serum levels were elevated. SHIM scores were associated with low TT (p = 0.30), FT (p = 0.09), and high LH (p = 0.76) in LC patients with ED. Male patients with decreased serum levels of LH and testosterone may have hypothalamic-pituitary–gonadal axis dysfunction, which could lead to the development of LC-induced ED. Therefore, an in-depth research is necessary to confirm the causal link between COVID-19 and ED in LC patients.