bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fusion gene LRP1–SNRNP25 drives invasion and migration by activating the pJNK/37LRP/MMP2 signaling pathway in osteosarcoma
Authors: Xing Peipei , Liu Haotian , Xiao Wanyi , Zhang Gengpu , Zhang Chao , Liao Zhichao , Li Ting , Yang Jilong 
Published: April 2024

AbstractThrough transcriptome sequencing, we previously identified a new osteosarcoma-specific, frequent fusion gene, LRP1–SNRNP25, and found that it played an important role in tumor cell invasion and migration. However, the specific mechanism remains unclear. In this article, whole-genome sequencing further confirmed that the LRP1–SNRNP25 fusion gene is formed by fusion of LRP1 exon 8 and SNRNP25 exon 2. In vitro, scratch and Transwell assays demonstrated that the migration and invasion abilities of LRP1–SNRNP25-overexpressing osteosarcoma cells were significantly increased. To explore the molecular mechanism of the LRP1–SNRNP25 fusion in affecting osteosarcoma cell migration and invasion, we evaluated the migration and invasion-related molecular signaling pathways by western blotting. Some migration- and invasion-related genes, including pJNK and MMP2, were upregulated. Coimmunoprecipitation–mass spectrometry showed that 37LRP can interact with pJNK. Western blotting confirmed that LRP1–SNRNP25 overexpression upregulates 37LRP protein expression. Immunofluorescence staining showed the intracellular colocalization of LRP1–SNRNP25 with pJNK and 37LRP proteins and that LRP1–SNRNP25 expression increased the pJNK and 37LRP levels. Coimmunoprecipitation (co-IP) confirmed that LRP1–SNRNP25 interacted with pJNK and 37LRP proteins. The pJNK inhibitor SP600125 dose-dependently decreased the pJNK/37LRP/MMP2 levels. After siRNA-mediated 37LRP knockdown, the MMP2 protein level decreased. These two experiments proved the upstream/downstream relationship among pJNK, 37LRP, and MMP2, with pJNK the farthest upstream and MMP2 the farthest downstream. These results proved that the LRP1–SNRNP25 fusion gene exerts biological effects through the pJNK/37LRP/MMP2 signaling pathway. In vivo, LRP1–SNRNP25 promoted osteosarcoma cell growth. Tumor growth was significantly inhibited after SP600125 treatment. Immunohistochemical analysis showed that the pJNK, MMP2, and Ki-67 protein levels were significantly increased in tumor tissues of LRP1–SNRNP25-overexpressing cell-injected nude mice. Furthermore, lung and liver metastasis were more prevalent in these mice. In a word, LRP1–SNRNP25 promotes invasion, migration, and metastasis via pJNK/37LRP/MMP2 pathway. LRP1–SNRNP25 is a potential therapeutic target for LRP1–SNRNP25-positive osteosarcoma.
Negotiating severity behind the scenes: prenatal testing in Germany
Authors: Nov-Klaiman Tamar , Bowman-Smart Hilary , Horn Ruth 
Published: April 2024

Abstract
Foetal-related severity is a key concept in policy and legislation relating to access to both reproductive technologies and selective abortions in many countries around the world, but not in Germany. This study sheds light on how ‘severity’ in the context of prenatal testing is understood and negotiated within the particular socio-cultural and legal context of Germany, where ‘severity’ relating to foetal clinical findings neither counts as a justification to implement population prenatal screening programs, nor as a legal ground to terminate pregnancy. This study explores the views of women who undergo prenatal testing, as well as of professionals who encounter them, through semi-structured interviews. It showcases how they frame severity and questions whether the existing legal and regulatory framework relating to prenatal testing and termination of pregnancy addresses their concerns and needs regarding reproductive decision-making. The interviews (n = 27) reveal that despite it being legally outside the explicit reasons for testing and termination of pregnancy, both women and professionals negotiate severity behind the scenes. Their interpretation of severity is highly context-dependent and relies on clinical, social and familial facets. Their perceptions of severity guide them in their handling of and decision-making around pregnancy management. Acknowledging the personal nature of severity assessment and providing professional or legal guidance which explicitly mentions foetal anomaly as a legitimate factor in pregnancy management could provide healthcare professionals and patients with the room needed to manage the pregnancy favourably.
A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin
Authors: Gu Wei , Huang Xiaofeng , Singh Pratik N. P. , Li Sanlan , Lan Ying , Deng Min , Lacko Lauretta A. , Gomez-Salinero Jesus M. , Rafii Shahin , Verzi Michael P. , Shivdasani Ramesh A. , Zhou Qiao 
Published: April 2024

AbstractPlasticity among cell lineages is a fundamental, but poorly understood, property of regenerative tissues. In the gut tube, the small intestine absorbs nutrients, whereas the colon absorbs electrolytes. In a striking display of inherent plasticity, adult colonic mucosa lacking the chromatin factor SATB2 is converted to small intestine. Using proteomics and CRISPR-Cas9 screening, we identify MTA2 as a crucial component of the molecular machinery that, together with SATB2, restrains colonic plasticity. MTA2 loss in the adult mouse colon activated lipid absorptive genes and functional lipid uptake. Mechanistically, MTA2 co-occupies DNA with HNF4A, an activating pan-intestinal transcription factor (TF), on colonic chromatin. MTA2 loss leads to HNF4A release from colonic chromatin, and accumulation on small intestinal chromatin. SATB2 similarly restrains colonic plasticity through an HNF4A-dependent mechanism. Our study provides a generalizable model of lineage plasticity in which broadly-expressed TFs are retained on tissue-specific enhancers to maintain cell identity and prevent activation of alternative lineages, and their release unleashes plasticity.
Current-sensitive Hall effect in a chiral-orbital-current state
Authors: Zhang Yu , Ni Yifei , Schlottmann Pedro , Nandkishore Rahul , DeLong Lance E. , Cao Gang 
Published: April 2024

AbstractChiral orbital currents (COC) underpin a novel colossal magnetoresistance in ferrimagnetic Mn3Si2Te6. Here we report the Hall effect in the COC state which exhibits the following unprecedented features: (1) A sharp, current-sensitive peak in the magnetic field dependence of the Hall resistivity, and (2) A current-sensitive scaling relation between the Hall conductivity σxy and the longitudinal conductivity σxx, namely, σxy ∝ σxxα with α reaching up to 5, which is exceptionally large compared to α ≤ 2 typical of all solids. The novel Hall responses along with a current-sensitive carrier density and a large Hall angle of 15% point to a giant, current-sensitive Hall effect that is unique to the COC state. Here, we show that a magnetic field induced by the fully developed COC combines with the applied magnetic field to exert the greatly enhanced transverse force on charge carriers, which dictates the COC Hall responses.
Staggered structural dynamic-mediated selective adsorption of H2O/D2O on flexible graphene oxide nanosheets
Authors: Futamura Ryusuke , Iiyama Taku , Ueda Takahiro , Bonnaud Patrick A. , Coudert François-Xavier , Furuse Ayumi , Tanaka Hideki , Pellenq Roland J. -M. , Kaneko Katsumi 
Published: April 2024

AbstractGraphene oxide (GO) is the one of the most promising family of materials as atomically thin membranes for water-related molecular separation technologies due to its amphipathic nature and layered structure. Here, we show important aspects of GO on water adsorption from molecular dynamics (MD) simulations, in-situ X-ray diffraction (XRD) measurements, and ex-situ nuclear magnetic resonance (NMR) measurements. Although the MD simulations for GO and the reduced GO models revealed that the flexibility of the interlayer spacing could be attributed to the oxygen-functional groups of GO, the ultra-large GO model cannot well explain the observed swelling of GO from XRD experiments. Our MD simulations propose a realistic GO interlayer structure constructed by staggered stacking of flexible GO sheets, which can explain very well the swelling nature upon water adsorption. The transmission electron microscopic (TEM) observation also supports the non-regular staggered stacking structure of GO. Furthermore, we demonstrate the existence of the two distinct types of adsorbed water molecules in the staggered stacking: water bonded with hydrophilic functional groups and “free” mobile water. Finally, we show that the staggered stacking of GO plays a crucial role in H/D isotopic recognition in water adsorption, as well as the high mobility of water molecules.
Climate-forced Hg-remobilization associated with fern mutagenesis in the aftermath of the end-Triassic extinction
Authors: Bos Remco , Zheng Wang , Lindström Sofie , Sanei Hamed , Waajen Irene , Fendley Isabel M. , Mather Tamsin A. , Wang Yang , Rohovec Jan , Navrátil Tomáš , Sluijs Appy , van de Schootbrugge Bas 
Published: April 2024

AbstractThe long-term effects of the Central Atlantic Magmatic Province, a large igneous province connected to the end-Triassic mass-extinction (201.5 Ma), remain largely elusive. Here, we document the persistence of volcanic-induced mercury (Hg) pollution and its effects on the biosphere for ~1.3 million years after the extinction event. In sediments recovered in Germany (Schandelah-1 core), we record not only high abundances of malformed fern spores at the Triassic-Jurassic boundary, but also during the lower Jurassic Hettangian, indicating repeated vegetation disturbance and stress that was eccentricity-forced. Crucially, these abundances correspond to increases in sedimentary Hg-concentrations. Hg-isotope ratios (δ202Hg, Δ199Hg) suggest a volcanic source of Hg-enrichment at the Triassic-Jurassic boundary but a terrestrial source for the early Jurassic peaks. We conclude that volcanically injected Hg across the extinction was repeatedly remobilized from coastal wetlands and hinterland areas during eccentricity-forced phases of severe hydrological upheaval and erosion, focusing Hg-pollution in the Central European Basin.
Loss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer
Authors: Papakyriacou Irineos , Kutkaite Ginte , Rúbies Bedós Marta , Nagarajan Divya , Alford Liam P. , Menden Michael P. , Mao Yumeng 
Published: April 2024

AbstractImmune checkpoint blockade therapy aims to activate the immune system to eliminate cancer cells. However, clinical benefits are only recorded in a subset of patients. Here, we leverage genome-wide CRISPR/Cas9 screens in a Tumor-Immune co-Culture System focusing on triple-negative breast cancer (TNBC). We reveal that NEDD8 loss in cancer cells causes a vulnerability to nivolumab (anti-PD-1). Genetic deletion of NEDD8 only delays cell division initially but cell proliferation is unaffected after recovery. Since the NEDD8 gene is commonly essential, we validate this observation with additional CRISPR screens and uncover enhanced immunogenicity in NEDD8 deficient cells using proteomics. In female immunocompetent mice, PD-1 blockade lacks efficacy against established EO771 breast cancer tumors. In contrast, we observe tumor regression mediated by CD8+ T cells against Nedd8 deficient EO771 tumors after PD-1 blockade. In essence, we provide evidence that NEDD8 is conditionally essential in TNBC and presents as a synergistic drug target for PD-1/L1 blockade therapy.
Reservoir displacement by an invasive rodent reduces Lassa virus zoonotic spillover risk
Authors: Eskew Evan A. , Bird Brian H. , Ghersi Bruno M. , Bangura James , Basinski Andrew J. , Amara Emmanuel , Bah Mohamed A. , Kanu Marilyn C. , Kanu Osman T. , Lavalie Edwin G. , Lungay Victor , Robert Willie , Vandi Mohamed A. , Fichet-Calvet Elisabeth , Nuismer Scott L. 
Published: April 2024

AbstractThe black rat (Rattus rattus) is a globally invasive species that has been widely introduced across Africa. Within its invasive range in West Africa,R. rattusmay compete with the native rodentMastomys natalensis, the primary reservoir host of Lassa virus, a zoonotic pathogen that kills thousands annually. Here, we use rodent trapping data from Sierra Leone and Guinea to show thatR. rattuspresence reducesM. natalensisdensity within the human dwellings where Lassa virus exposure is most likely to occur. Further, we integrate infection data fromM. natalensisto demonstrate that Lassa virus zoonotic spillover risk is lower at sites withR. rattus. While non-native species can have numerous negative effects on ecosystems, our results suggest thatR. rattusinvasion has the indirect benefit of decreasing zoonotic spillover of an endemic pathogen, with important implications for invasive species control across West Africa.
Timescale correlation of shallow trap states increases electrochemiluminescence efficiency in carbon nitrides
Authors: Fang Yanfeng , Yang Hong , Hou Yuhua , Li Wang , Shen Yanfei , Liu Songqin , Zhang Yuanjian 
Published: April 2024

AbstractHighly efficient interconversion of different types of energy plays a crucial role in both science and technology. Among them, electrochemiluminescence, an emission of light excited by electrochemical reactions, has drawn attention as a powerful tool for bioassays. Nonetheless, the large differences in timescale among diverse charge-transfer pathways from picoseconds to seconds significantly limit the electrochemiluminescence efficiency and hamper their broad applications. Here, we report a timescale coordination strategy to improve the electrochemiluminescence efficiency of carbon nitrides by engineering shallow electron trap states via Au-N bond functionalization. Quantitative electrochemiluminescence kinetics measurements and theoretic calculations jointly disclose that Au-N bonds endow shallow electron trap states, which coordinate the timescale of the fast electron transfer in the bulk emitter and the slow redox reaction of co-reagent at diffusion layers. The shallow electron trap states ultimately accelerate the rate and kinetics of emissive electron-hole recombination, setting a new cathodic electrochemiluminescence efficiency record of carbon nitrides, and empowering a visual electrochemiluminescence sensor for nitrite ion, a typical environmental contaminant, with superior detection range and limit.
Near-strain-free anode architecture enabled by interfacial diffusion creep for initial-anode-free quasi-solid-state batteries
Authors: Kim Kwang Hee , Lee Myung-Jin , Ryu Minje , Liu Tae-Kyung , Lee Jung Hwan , Jung Changhoon , Kim Ju-Sik , Park Jong Hyeok 
Published: April 2024

AbstractAnode-free (or lithium-metal-free) batteries with garnet-type solid-state electrolytes are considered a promising path in the development of safe and high-energy-density batteries. However, their practical implementation has been hindered by the internal strain that arises from the repeated plating and stripping of lithium metal at the interlayer between the solid electrolyte and negative electrode. Herein, we utilize the titanium nitrate nanotube architecture and a silver-carbon interlayer to mitigate the anisotropic stress caused by the recurring formation of lithium deposition layers during the cycling process. The mixed ionic-electronic conducting nature of the titanium nitrate nanotubes effectively accommodates the entry of reduced Li into its free volume space via interfacial diffusion creep, achieving near-strain-free operation with nearly tenfold volume suppressing capability compared to a conventional Cu anode counterpart during the lithiation process. Notably, the fabricated Li6.4La3Zr1.7Ta0.3O12 (LLZTO)-based initial-anode-free quasi-solid-state battery full cell, coupled with an ionic liquid catholyte infused high voltage LiNi0.33Co0.33Mn0.33O2-based cathode with an areal capacity of 3.2 mA cm−2, exhibits remarkable room temperature (25 °C) cyclability of over 600 cycles at 1 mA cm−2 with an average coulombic efficiency of 99.8%.
Positive-unlabeled learning identifies vaccine candidate antigens in the malaria parasite Plasmodium falciparum
Authors: Chou Renee Ti , Ouattara Amed , Adams Matthew , Berry Andrea A. , Takala-Harrison Shannon , Cummings Michael P. 
Published: April 2024

AbstractMalaria vaccine development is hampered by extensive antigenic variation and complex life stages of Plasmodium species. Vaccine development has focused on a small number of antigens, many of which were identified without utilizing systematic genome-level approaches. In this study, we implement a machine learning-based reverse vaccinology approach to predict potential new malaria vaccine candidate antigens. We assemble and analyze P. falciparum proteomic, structural, functional, immunological, genomic, and transcriptomic data, and use positive-unlabeled learning to predict potential antigens based on the properties of known antigens and remaining proteins. We prioritize candidate antigens based on model performance on reference antigens with different genetic diversity and quantify the protein properties that contribute most to identifying top candidates. Candidate antigens are characterized by gene essentiality, gene ontology, and gene expression in different life stages to inform future vaccine development. This approach provides a framework for identifying and prioritizing candidate vaccine antigens for a broad range of pathogens.
Computational modeling reveals key factors driving treatment-free remission in chronic myeloid leukemia patients
Authors: Lai Xiulan , Jiao Xiaopei , Zhang Haojian , Lei Jinzhi 
Published: April 2024

AbstractPatients with chronic myeloid leukemia (CML) who receive tyrosine kinase inhibitors (TKIs) have been known to achieve treatment-free remission (TFR) upon discontinuing treatment. However, the underlying mechanisms of this phenomenon remain incompletely understood. This study aims to elucidate the mechanism of TFR in CML patients, focusing on the feedback interaction between leukemia stem cells and the bone marrow microenvironment. We have developed a mathematical model to explore the interplay between leukemia stem cells and the bone marrow microenvironment, allowing for the simulation of CML progression dynamics. Our proposed model reveals a dichotomous response following TKI discontinuation, with two distinct patient groups emerging: one prone to early molecular relapse and the other capable of achieving long-term TFR after treatment cessation. This finding aligns with clinical observations and underscores the essential role of feedback interaction between leukemic cells and the tumor microenvironment in sustaining TFR. Notably, we have shown that the ratio of leukemia cells in peripheral blood (PBLC) and the tumor microenvironment (TME) index can be a valuable predictive tool for identifying patients likely to achieve TFR after discontinuing treatment. This study provides fresh insights into the mechanism of TFR in CML patients and underscores the significance of microenvironmental control in achieving TFR.
A system dynamics-based model for the evolution of environmental group events
Authors: Qi Xue-ting , Bu Fanliang 
Published: April 2024

AbstractBased on the system dynamics theory, this paper establishes an environmental mass event evolution model and explores the evolution law of mass events caused by environmental problems. From a methodological point of view, the mixed-strategy evolutionary game principle and dynamic punishment measures are combined, and simulation analysis is carried out by Anylogic software, and the results show that there is no stable evolutionary equilibrium solution for the two sides of the game in the traditional asymmetric mixed-strategy game model, and after adjusting the game payoff matrix and incorporating the dynamic punishment strategy, stable evolutionary equilibrium solutions appear in the evolutionary game model, and the system begins to tend to be stabilized. The process and conclusions of the simulation experiment provide methodological reference and theoretical support for the analysis of the evolution of environmental mass events.
Rapid Market Screening to assess lead concentrations in consumer products across 25 low- and middle-income countries
Authors: Sargsyan Aelita , Nash Emily , Binkhorst Gordon , Forsyth Jenna E. , Jones Barbara , Sanchez Ibarra Gabriel , Berg Sarah , McCartor Andrew , Fuller Richard , Bose-O’Reilly Stephan 
Published: April 2024

AbstractLead exposure can have serious consequences for health and development. The neurological and behavioral effects of lead are considered irreversible. Young children are particularly vulnerable to lead poisoning. In 2020, Pure Earth and UNICEF estimated that one in three children had elevated blood lead levels above 5 µg/dL. The sources of lead exposure vary around the world and can range from household products, such as spices or foodware, to environmental pollution from nearby industries. The aim of this study was to analyze common products from markets in low- and middle-income countries (LMICs) for their lead content to determine whether they are plausible sources of exposure. In 25 LMICs, the research teams systematically collected consumer products (metal foodware, ceramics, cosmetics, paints, toys, spices and other foods). The items were analyzed on site for detectable lead above 2 ppm using an X-ray fluorescence analyzer. For quality control purposes, a subset of the samples was analyzed in the USA using inductively coupled plasma mass spectrometry. The lead concentrations of the individual product types were compared with established regulatory thresholds. Out of 5007 analyzed products, threshold values (TV) were surpassed in 51% for metal foodware (TV 100 ppm), 45% for ceramics (TV 100 ppm), and 41% for paints (TV 90 ppm). Sources of exposure in LMICs can be diverse, and consumers in LMICs lack adequate protection from preventable sources of lead exposure. Rapid Market Screening is an innovative, simple, and useful tool to identify risky products that could be sources of lead exposure.
The burden of schizophrenia in the Middle East and North Africa region, 1990–2019
Authors: Safiri Saeid , Noori Maryam , Nejadghaderi Seyed Aria , Shamekh Ali , Sullman Mark J. M. , Collins Gary S. , Kolahi Ali-Asghar 
Published: April 2024

AbstractSchizophrenia ranks as the third-most common cause of disability among mental disorders globally. This study presents findings on the prevalence, incidence and years lived with disability (YLDs) as a result of schizophrenia in the Middle East and North Africa (MENA), stratified by age, sex and sociodemographic index (SDI). We collected publicly accessible data from the Global Burden of Disease (GBD) study 2019. This study reports the burden of schizophrenia, from 1990 to 2019, for the 21 countries that comprise MENA. In 2019, MENA exhibited an age-standardised point prevalence of 248.2, an incidence rate of 14.7 and an YLD rate of 158.7 per 100,000, which have not changed substantially between 1990 and 2019. In 2019, the age-standardised YLD rate was highest in Qatar and lowest in Afghanistan. No MENA countries demonstrated noteworthy changes in the burden of schizophrenia from 1990 to 2019. Furthermore, in 2019, the highest number of prevalent cases and the point prevalence were observed among those aged 35–39, with a higher prevalence among males in almost all age categories. Additionally, in 2019, the age-standardised YLD rates in MENA were below the worldwide average. Finally, there was a positive correlation between the burden of schizophrenia and the SDI from 1990 to 2019. The disease burden of schizophrenia has remained relatively stable over the past thirty years. Nevertheless, as the regional life-expectancy continues to increase, the burden of schizophrenia is also expected to rise. Therefore, early planning for the increase in the burden of the disease is urgently needed in the region.