bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nociceptive adenosine A2A receptor on trigeminal nerves orchestrates CGRP release to regulate the progression of oral squamous cell carcinoma
Authors: Jiang Lanxin , Zhou Ying , Tang Shijie , Yang Dan , Zhang Yixin , Zhang Jiuge , Yang Fan , Zhou Tong , Xia Xiaoqiang , Chen Qianming , Jiang Lu , Jiang Yuchen , Feng Xiaodong 
Published: June 2024

AbstractOral squamous cell carcinoma (OSCC) associated pain commonly predicts adverse events among patients. This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy. However, it is yet to be determined if targeting oncometabolite-associated nociception processes can hinder OSCC progression. In this study, we reported that nociceptive endings infiltrating both clinical samples and mouse tumor xenografts were associated with poorer clinical outcomes and drove tumor progression in vivo, as evidenced by clinical tissue microarray analysis and murine lingual denervation. We observed that the OSCC microenvironment was characteristic of excessive adenosine due to CD73 upregulation which negatively predicted clinical outcomes in the TCGA-HNSC patient cohort. Notably, such adenosine concentrative OSCC niche was associated with the stimulation of adenosine A2A receptor (A2AR) on trigeminal ganglia. Antagonism of trigeminal A2AR with a selective A2AR inhibitor SCH58261 resulted in impeded OSCC growth in vivo. We showed that trigeminal A2AR overstimulation in OSCC xenograft did not entail any changes in the transcription level of CGRP in trigeminal ganglia but significantly triggered the release of CGRP, an effect counteracted by SCH58261. We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP. Finally, we diminished the impact of CGRP on OSCC with istradefylline, a clinically available drug that targets neuronal A2AR. Therefore, we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.
Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex
Authors: Gärtner Matti , Weigand Anne , Meiering Marvin Sören , Weigner David , Carstens Luisa , Keicher Christian , Hertrampf Rita , Beckmann Christian , Mennes Maarten , Wunder Andreas , Grimm Simone 
Published: June 2024

AbstractNeuroimaging studies have identified the anterior cingulate cortex (ACC) as one of the major targets of ketamine in the human brain, which may be related to ketamine’s antidepressant (AD) mechanisms of action. However, due to different methodological approaches, different investigated populations, and varying measurement timepoints, results are not consistent, and the functional significance of the observed brain changes remains a matter of open debate. Inhibition of glutamate release during acute ketamine administration by lamotrigine provides the opportunity to gain additional insight into the functional significance of ketamine-induced brain changes. Furthermore, the assessment of trait negative emotionality holds promise to link findings in healthy participants to potential AD mechanisms of ketamine. In this double-blind, placebo-controlled, randomized, single dose, parallel-group study, we collected resting-state fMRI data before, during, and 24 h after ketamine administration in a sample of 75 healthy male and female participants who were randomly allocated to one of three treatment conditions (ketamine, ketamine with lamotrigine pre- treatment, placebo). Spontaneous brain activity was extracted from two ventral and one dorsal subregions of the ACC. Our results showed activity decreases during the administration of ketamine in all three ACC subregions. However, only in the ventral subregions of the ACC this effect was attenuated by lamotrigine. 24 h after administration, ACC activity returned to baseline levels, but group differences were observed between the lamotrigine and the ketamine group. Trait negative emotionality was closely linked to activity changes in the subgenual ACC after ketamine administration. These results contribute to an understanding of the functional significance of ketamine effects in different subregions of the ACC by combining an approach to modulate glutamate release with the assessment of multiple timepoints and associations with trait negative emotionality in healthy participants.
Chemerin attracts neutrophil reverse migration by interacting with C–C motif chemokine receptor-like 2
Authors: Ji Jingjing , Zhong Hanhui , Wang Yawen , Liu Jinghua , Tang Jing , Liu Zhifeng 
Published: June 2024

AbstractNeutrophil reverse migration (rM) is a recently identified phenomenon in which neutrophils migrate away from the inflammatory site back into the vasculature following initial infiltration, which involved in the resolution of loci inflammatory response or dissemination of inflammation. Present study was aimed to explore the mechanisms in neutrophil rM. By scRNA-seq on the white blood cells in acute lung injury model, we found rM-ed neutrophils exhibited increased gene expression of C–C motif chemokine receptor-like 2 (Ccrl2), an atypical chemokine receptor. Furthermore, an air pouch model was established to directly track rM-ed neutrophils in vivo. Air pouches were generated by 3 ml filtered sterile air injected subcutaneously for 3 days, and then LPS (2 mg/kg) was injected into the pouches to mimic the inflammatory state. For the rM-ed neutrophil tracking system, cell tracker CMFDA were injected into the air pouch to stain the inflammatory loci cells, and after 6 h, stained cells in blood were regarded as the rM-ed neutrophil. Based on this tracking system, we confirmed that rM-ed neutrophils showed increased CCRL2. We also found that the concentrations of the CCRL2 ligand chemerin in plasma was increased in the late stage. Neutralizing chemerin decreased the rM-ed neutrophil ratio in the blood. These results suggest that circulating chemerin attracts neutrophils to leave inflammatory sites by interacting with CCRL2, which might involve in the dissemination of inflammation.
Continuous sterane and phytane δ13C record reveals a substantial pCO2 decline since the mid-Miocene
Authors: Witkowski Caitlyn R. , von der Heydt Anna S. , Valdes Paul J. , van der Meer Marcel T. J. , Schouten Stefan , Sinninghe Damsté Jaap S. 
Published: June 2024

AbstractConstraining the relationship between temperature and atmospheric concentrations of carbon dioxide (pCO2) is essential to model near-future climate. Here, we reconstruct pCO2 values over the past 15 million years (Myr), providing a series of analogues for possible near-future temperatures and pCO2, from a single continuous site (DSDP Site 467, California coast). We reconstruct pCO2 values using sterane and phytane, compounds that many phytoplankton produce and then become fossilised in sediment. From 15.0-0.3 Myr ago, our reconstructed pCO2 values steadily decline from 650 ± 150 to 280 ± 75 ppmv, mirroring global temperature decline. Using our new range of pCO2 values, we calculate average Earth system sensitivity and equilibrium climate sensitivity, resulting in 13.9 °C and 7.2 °C per doubling of pCO2, respectively. These values are significantly higher than IPCC global warming estimations, consistent or higher than some recent state-of-the-art climate models, and consistent with other proxy-based estimates.
A matched case-control analysis of autonomous vs human-driven vehicle accidents
Authors: Abdel-Aty Mohamed , Ding Shengxuan 
Published: June 2024

AbstractDespite the recent advancements that Autonomous Vehicles have shown in their potential to improve safety and operation, considering differences between Autonomous Vehicles and Human-Driven Vehicles in accidents remain unidentified due to the scarcity of real-world Autonomous Vehicles accident data. We investigated the difference in accident occurrence between Autonomous Vehicles’ levels and Human-Driven Vehicles by utilizing 2100 Advanced Driving Systems and Advanced Driver Assistance Systems and 35,113 Human-Driven Vehicles accident data. A matched case-control design was conducted to investigate the differential characteristics involving Autonomous’ versus Human-Driven Vehicles’ accidents. The analysis suggests that accidents of vehicles equipped with Advanced Driving Systems generally have a lower chance of occurring than Human-Driven Vehicles in most of the similar accident scenarios. However, accidents involving Advanced Driving Systems occur more frequently than Human-Driven Vehicle accidents under dawn/dusk or turning conditions, which is 5.25 and 1.98 times higher, respectively. Our research reveals the accident risk disparities between Autonomous Vehicles and Human-Driven Vehicles, informing future development in Autonomous technology and safety enhancements.
Free-standing two-dimensional ferro-ionic memristor
Authors: Lee Jinhyoung , Woo Gunhoo , Cho Jinill , Son Sihoon , Shin Hyelim , Seok Hyunho , Kim Min-Jae , Kim Eungchul , Wang Ziyang , Kang Boseok , Jang Won-Jun , Kim Taesung 
Published: June 2024

AbstractTwo-dimensional (2D) ferroelectric materials have emerged as significant platforms for multi-functional three-dimensional (3D) integrated electronic devices. Among 2D ferroelectric materials, ferro-ionic CuInP2S6 has the potential to achieve the versatile advances in neuromorphic computing systems due to its phase tunability and ferro-ionic characteristics. As CuInP2S6 exhibits a ferroelectric phase with insulating properties at room temperature, the external temperature and electrical field should be required to activate the ferro-ionic conduction. Nevertheless, such external conditions inevitably facilitate stochastic ionic conduction, which completely limits the practical applications of 2D ferro-ionic materials. Herein, free-standing 2D ferroelectric heterostructure is mechanically manipulated for nano-confined conductive filaments growth in free-standing 2D ferro-ionic memristor. The ultra-high mechanical bending is selectively facilitated at the free-standing area to spatially activate the ferro-ionic conduction, which allows the deterministic local positioning of Cu+ ion transport. According to the local flexoelectric engineering, 5.76×102-fold increased maximum current is observed within vertical shear strain 720 nN, which is theoretically supported by the 3D flexoelectric simulation. In conclusion, we envision that our universal free-standing platform can provide the extendable geometric solution for ultra-efficient self-powered system and reliable neuromorphic device.
High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer
Authors: Schmidt Tobias T. , Tyer Carly , Rughani Preeyesh , Haggblom Candy , Jones Jeffrey R. , Dai Xiaoguang , Frazer Kelly A. , Gage Fred H. , Juul Sissel , Hickey Scott , Karlseder Jan 
Published: June 2024

AbstractTelomeres are the protective nucleoprotein structures at the end of linear eukaryotic chromosomes. Telomeres’ repetitive nature and length have traditionally challenged the precise assessment of the composition and length of individual human telomeres. Here, we present Telo-seq to resolve bulk, chromosome arm-specific and allele-specific human telomere lengths using Oxford Nanopore Technologies’ native long-read sequencing. Telo-seq resolves telomere shortening in five population doubling increments and reveals intrasample, chromosome arm-specific, allele-specific telomere length heterogeneity. Telo-seq can reliably discriminate between telomerase- and ALT-positive cancer cell lines. Thus, Telo-seq is a tool to study telomere biology during development, aging, and cancer at unprecedented resolution.
Plasma proteomics identify biomarkers predicting Parkinson’s disease up to 7 years before symptom onset
Authors: Hällqvist Jenny , Bartl Michael , Dakna Mohammed , Schade Sebastian , Garagnani Paolo , Bacalini Maria-Giulia , Pirazzini Chiara , Bhatia Kailash , Schreglmann Sebastian , Xylaki Mary , Weber Sandrina , Ernst Marielle , Muntean Maria-Lucia , Sixel-Döring Friederike , Franceschi Claudio , Doykov Ivan , Śpiewak Justyna , Vinette Héloїse , Trenkwalder Claudia , Heywood Wendy E. , Mills Kevin , Mollenhauer Brit 
Published: June 2024

AbstractParkinson’s disease is increasingly prevalent. It progresses from the pre-motor stage (characterised by non-motor symptoms like REM sleep behaviour disorder), to the disabling motor stage. We need objective biomarkers for early/pre-motor disease stages to be able to intervene and slow the underlying neurodegenerative process. Here, we validate a targeted multiplexed mass spectrometry assay for blood samples from recently diagnosed motor Parkinson’s patients (n = 99), pre-motor individuals with isolated REM sleep behaviour disorder (two cohorts: n = 18 and n = 54 longitudinally), and healthy controls (n = 36). Our machine-learning model accurately identifies all Parkinson patients and classifies 79% of the pre-motor individuals up to 7 years before motor onset by analysing the expression of eight proteins—Granulin precursor, Mannan-binding-lectin-serine-peptidase-2, Endoplasmatic-reticulum-chaperone-BiP, Prostaglaindin-H2-D-isomaerase, Interceullular-adhesion-molecule-1, Complement C3, Dickkopf-WNT-signalling pathway-inhibitor-3, and Plasma-protease-C1-inhibitor. Many of these biomarkers correlate with symptom severity. This specific blood panel indicates molecular events in early stages and could help identify at-risk participants for clinical trials aimed at slowing/preventing motor Parkinson’s disease.
Climate change impacts on the extreme power shortage events of wind-solar supply systems worldwide during 1980–2022
Authors: Zheng Dongsheng , Tong Dan , Davis Steven J. , Qin Yue , Liu Yang , Xu Ruochong , Yang Jin , Yan Xizhe , Geng Guannan , Che Huizheng , Zhang Qiang 
Published: June 2024

AbstractEconomic productivity depends on reliable access to electricity, but the extreme shortage events of variable wind-solar systems may be strongly affected by climate change. Here, hourly reanalysis climatological data are leveraged to examine historical trends in defined extreme shortage events worldwide. We find uptrends in extreme shortage events regardless of their frequency, duration, and intensity since 1980. For instance, duration of extreme low-reliability events worldwide has increased by 4.1 hours (0.392 hours per year on average) between 1980–2000 and 2001–2022. However, such ascending trends are unevenly distributed worldwide, with a greater variability in low- and middle-latitude developing countries. This uptrend in extreme shortage events is driven by extremely low wind speed and solar radiation, particularly compound wind and solar drought, which however are strongly disproportionated. Only average 12.5% change in compound extremely low wind speed and solar radiation events may give rise to over 30% variability in extreme shortage events, despite a mere average 1.0% change in average wind speed and solar radiation. Our findings underline that wind-solar systems will probably suffer from weakened power security if such uptrends persist in a warmer future.
Cassini spacecraft reveals global energy imbalance of Saturn
Authors: Wang Xinyue , Li Liming , Jiang Xun , Fry Patrick M. , West Robert A. , Nixon Conor A. , Guan Larry , Karandana G Thishan D. , Albright Ronald , Colwell Joshua E. , Guillot Tristan , Hofstadter Mark D. , Kenyon Matthew E. , Mallama Anthony , Perez-Hoyos Santiago , Sanchez-Lavega Agustin , Simon Amy A. , Wenkert Daniel , Zhang Xi 
Published: June 2024

AbstractThe global energy budget is pivotal to understanding planetary evolution and climate behaviors. Assessing the energy budget of giant planets, particularly those with large seasonal cycles, however, remains a challenge without long-term observations. Evolution models of Saturn cannot explain its estimated Bond albedo and internal heat flux, mainly because previous estimates were based on limited observations. Here, we analyze the long-term observations recorded by the Cassini spacecraft and find notably higher Bond albedo (0.41 ± 0.02) and internal heat flux (2.84 ± 0.20 Wm−2) values than previous estimates. Furthermore, Saturn’s global energy budget is not in a steady state and exhibits significant dynamical imbalances. The global radiant energy deficit at the top of the atmosphere, indicative of the planetary cooling of Saturn, reveals remarkable seasonal fluctuations with a magnitude of 16.0 ± 4.2%. Further analysis of the energy budget of the upper atmosphere including the internal heat suggests seasonal energy imbalances at both global and hemispheric scales, contributing to the development of giant convective storms on Saturn. Similar seasonal variabilities of planetary cooling and energy imbalance exist in other giant planets within and beyond the Solar System, a prospect currently overlooked in existing evolutional and atmospheric models.
Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to Mycobacterium tuberculosis
Authors: Dintwe One B. , Ballweber Fleming Lamar , Voillet Valentin , McNevin John , Seese Aaron , Naidoo Anneta , Omarjee Saleha , Bekker Linda-Gail , Kublin James G. , De Rosa Stephen C. , Newell Evan W. , Fiore-Gartland Andrew , Andersen-Nissen Erica , McElrath M. Juliana 
Published: June 2024

AbstractA recent clinical trial demonstrated that Bacille Calmette-Guérin (BCG) revaccination of adolescents reduced the risk of sustained infection withMycobacterium tuberculosis(M.tb). In a companion phase 1b trial, HVTN 602/Aeras A-042, we characterize in-depth the cellular responses to BCG revaccination or to a H4:IC31 vaccine boost to identify T cell subsets that could be responsible for the protection observed. High-dimensional clustering analysis of cells profiled using a 26-color flow cytometric panel show marked increases in five effector memory CD4+T cell subpopulations (TEM) after BCG revaccination, two of which are highly polyfunctional. CITE-Seq single-cell analysis shows that the activated subsets include an abundant cluster of Th1 cells with migratory potential. Additionally, a small cluster of Th17 TEMcells induced by BCG revaccination expresses high levels of CD103; these may represent recirculating tissue-resident memory cells that could provide pulmonary immune protection. Together, these results identify unique populations of CD4+T cells with potential to be immune correlates of protection conferred by BCG revaccination.
Faecal microbiota of schoolchildren is associated with nutritional status and markers of inflammation: a double-blinded cluster-randomized controlled trial using multi-micronutrient fortified rice
Authors: Seyoum Yohannes , Greffeuille Valérie , Kouadio Dorgeles Kouakou Dje , Kuong Khov , Turpin Williams , M’Rabt Rachida , Chochois Vincent , Fortin Sonia , Perignon Marlène , Fiorentino Marion , Berger Jacques , Burja Kurt , Ponce Maiza Campos , Chamnan Chhoun , Wieringa Frank T. , Humblot Christèle 
Published: June 2024

AbstractFaecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419))
Immuno-protective vesicle-crosslinked hydrogel for allogenic transplantation
Authors: Wang Yuqian , Huang Renqi , Lu Yougong , Liu Mingqi , Mo Ran 
Published: June 2024

AbstractThe longevity of grafts remains a major challenge in allogeneic transplantation due to immune rejection. Systemic immunosuppression can impair graft function and can also cause severe adverse effects. Here, we report a local immuno-protective strategy to enhance post-transplant persistence of allografts using a mesenchymal stem cell membrane-derived vesicle (MMV)-crosslinked hydrogel (MMV-Gel). MMVs are engineered to upregulate expression of Fas ligand (FasL) and programmed death ligand 1 (PD-L1). The MMVs are retained within the hydrogel by crosslinking. The immuno-protective microenvironment of the hydrogel protects allografts by presenting FasL and PD-L1. The binding of these ligands to T effector cells, the dominant contributors to graft destruction and rejection, results in apoptosis of T effector cells and generation of regulatory T cells. We demonstrate that implantation with MMV-Gel prolongs the survival and function of grafts in mouse models of allogeneic pancreatic islet cells and skin transplantation.
Low-coordinated copper facilitates the *CH2CO affinity at enhanced rectifying interface of Cu/Cu2O for efficient CO2-to-multicarbon alcohols conversion
Authors: Zhang Yangyang , Chen Yanxu , Wang Xiaowen , Feng Yafei , Dai Zechuan , Cheng Mingyu , Zhang Genqiang 
Published: June 2024

AbstractThe carbon−carbon coupling at the Cu/Cu2O Schottky interface has been widely recognized as a promising approach for electrocatalytic CO2 conversion into value-added alcohols. However, the limited selectivity of C2+ alcohols persists due to the insufficient control over rectifying interface characteristics required for precise bonding of oxyhydrocarbons. Herein, we present an investigation into the manipulation of the coordination environment of Cu sites through an in-situ electrochemical reconstruction strategy, which indicates that the construction of low-coordinated Cu sites at the Cu/Cu2O interface facilitates the enhanced rectifying interfaces, and induces asymmetric electronic perturbation and faster electron exchange, thereby boosting C-C coupling and bonding oxyhydrocarbons towards the nucleophilic reaction process of *H2CCO-CO. Impressively, the low-coordinated Cu sites at the Cu/Cu2O interface exhibit superior faradic efficiency of 64.15  ±  1.92% and energy efficiency of ~39.32% for C2+ alcohols production, while maintaining stability for over 50 h (faradic efficiency >50%, total current density = 200 mA cm−2) in a flow-cell electrolyzer. Theoretical calculations, operando synchrotron radiation Fourier transform infrared spectroscopy, and Raman experiments decipher that the low-coordinated Cu sites at the Cu/Cu2O interface can enhance the coverage of *CO and adsorption of *CH2CO and CH2CHO, facilitating the formation of C2+ alcohols.