bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Low‐Altitude Ionosphere of the Ice Giant Planets
Authors: Molina‐Cuberos G. J. , Witasse O. , Toledo D. , Tripathi S. N. 
Published: March 2023

AbstractThe study of atmospheric electricity of the lower stratosphere and upper troposphere of the ice giant planets can help to understand several physical phenomena such as cloud formation, lightning generation, aerosols growth, or chemical composition. At these depths, galactic radiation is the main energy source able to ionize the atmospheric constituents and to produce a low altitude ionospheric layer that can be similar in magnitude to the upper ionosphere produced by solar radiation and auroral electrons. The presence of aerosols affects the ion‐neutral chemistry by capturing electrons and ions depending on the aerosol size and number density. Here, we present a new one dimensional ionospheric model of Uranus and Neptune able to calculate the number densities of electrons and ions as well as the charging of aerosols between 100 Pa and 4 × 105 Pa. Since the results depends upon the amount and size of the atmospheric aerosols, as well as on the flux of the incoming cosmic radiation, several aerosol models, solar‐cycle conditions, and the effect of the intrinsic magnetic field are considered.
Shaping the Huara Intrusive Complex in the Hyperarid Atacama Desert—Erosional Near‐Stasis Contrasting High Topographic Gradients
Authors: Ritter Benedikt , Mohren Joel , Binnie Steven A. , Wennrich Volker , Dunkl István , Albert Richard , Gerdes Axel , LoBue Sandro , Dunai Tibor J. 
Published: March 2023

AbstractThe Atacama Desert is one of the driest and oldest deserts on Earth, with extremely low precipitation rates (<2 mm/yr). Mostly abiotic hyperarid environmental conditions prevail, and surface processes act at extremely low rates over the long‐term. To gain knowledge about the rate of surface processes and age of landscapes in desert environments, terrestrial cosmogenic nuclide derived erosion rate estimates can be used. Within the Huara Intrusive Complex, situated in the hyperarid core of the Atacama Desert, basin‐averaged bedrock erosion rates from channel sediments are extremely low, that is, less than 1 m/Myr. Such low rates indicate that fluvial processes operate very slowly or are almost absent. Bedrock erosion rates of channel knickpoints, however, reveal one to two orders of magnitude higher erosion rates (2–12 m/Myr). Erosion rates are remarkably low when compared to the steep surrounding topography. Tectonic uplift creates higher gravitational potentials for surface processes, controlling the overall erosion rate capacity. However, erosion itself is taking place by local precipitation capable of exceeding thresholds for surface activity. In the Atacama Desert, this happens only due to rare severe precipitation events, explaining the extremely low erosion rates. The efficiency of these events is modulated by local intrinsic processes and conditions, such as high infiltration capacities of Atacama soils and/or large channel boulder accumulations. Due to the virtual absence of these precipitation events capable of erosion, the landscape appears to be in hibernation.
Exploring Icehouse Cyclicity Pattern and Seawater Dynamics on an Ancient Carbonate Platform With Nd Isotopes (Carboniferous, Southern Kazakhstan)
Authors: Belka Z. , Skompski S. , Jakubowicz M. , Dopieralska J. , Walczak A. , Mustapayeva S. 
Published: March 2023

AbstractOver the past decades, neodymium (Nd) isotopes have received considerable attention in paleoceanography as a tool for reconstructing past seawater circulation, local weathering inputs, and sea‐level change. In this study, we have investigated the Nd isotope composition of a shallow‐water Serpukhovian (Carboniferous) carbonate succession to explore icehouse cyclicity pattern and seawater dynamics on the Karatau carbonate platform in southern Kazakhstan. The cyclic succession formed in response to glacio‐eustasy and composed of subtidal and intertidal limestones displays a large variation in εNd(326 Ma) values from −1.6 to +4.3, corresponding to differences in the isotopic composition of two seawater masses present in the Uralian–Turkestan Ocean during the Serpukhovian: (a) highly radiogenic deep waters and (b) less radiogenic surface waters. The Nd isotope excursions within the icehouse cycles are more complex than simple transgressive‐regressive cycles. They probably reflect a temporal pattern of the sub‐Milankovitch climatic perturbations during Carboniferous interglacial intervals. The episodic appearance of rich brachiopod communities was forced by the inflow of highly radiogenic, nutrient‐enriched waters, presumably driven by upwelling. Nd isotope analyses of cyclic intertidal and subtidal carbonates have great potential to produce high‐resolution records of seawater dynamics on shallow‐water carbonate platforms.
Surface-layer protein is a public-good matrix exopolymer for microbial community organisation in environmental anammox biofilms
Authors: Li Wong Lan , Lu Yang , Ho James Chin Shing , Mugunthan Sudarsan , Law Yingyu , Conway Patricia , Kjelleberg Staffan , Seviour Thomas 
Published: March 2023

Abstract
Extracellular polymeric substances (EPS) are core biofilm components, yet how they mediate interactions within and contribute to the structuring of biofilms is largely unknown, particularly for non-culturable microbial communities that predominate in environmental habitats. To address this knowledge gap, we explored the role of EPS in an anaerobic ammonium oxidation (anammox) biofilm. An extracellular glycoprotein, BROSI_A1236, from an anammox bacterium, formed envelopes around the anammox cells, supporting its identification as a surface (S-) layer protein. However, the S-layer protein also appeared at the edge of the biofilm, in close proximity to the polysaccharide-coated filamentous Chloroflexi bacteria but distal to the anammox bacterial cells. The Chloroflexi bacteria assembled into a cross-linked network at the edge of the granules and surrounding anammox cell clusters, with the S-layer protein occupying the space around the Chloroflexi. The anammox S-layer protein was also abundant at junctions between Chloroflexi cells. Thus, the S-layer protein is likely transported through the matrix as an EPS and also acts as an adhesive to facilitate the assembly of filamentous Chloroflexi into a three-dimensional biofilm lattice. The spatial distribution of the S-layer protein within the mixed species biofilm suggests that it is a “public-good” EPS, which facilitates the assembly of other bacteria into a framework for the benefit of the biofilm community, and enables key syntrophic relationships, including anammox.
Ecological divergence of syntopic marine bacterial species is shaped by gene content and expression
Authors: Nowinski Brent , Feng Xiaoyuan , Preston Christina M , Birch James M , Luo Haiwei , Whitman William B , Moran Mary Ann 
Published: March 2023

Abstract
Identifying mechanisms by which bacterial species evolve and maintain genomic diversity is particularly challenging for the uncultured lineages that dominate the surface ocean. A longitudinal analysis of bacterial genes, genomes, and transcripts during a coastal phytoplankton bloom revealed two co-occurring, highly related Rhodobacteraceae species from the deeply branching and uncultured NAC11-7 lineage. These have identical 16S rRNA gene amplicon sequences, yet their genome contents assembled from metagenomes and single cells indicate species-level divergence. Moreover, shifts in relative dominance of the species during dynamic bloom conditions over 7 weeks confirmed the syntopic species’ divergent responses to the same microenvironment at the same time. Genes unique to each species and genes shared but divergent in per-cell inventories of mRNAs accounted for 5% of the species’ pangenome content. These analyses uncover physiological and ecological features that differentiate the species, including capacities for organic carbon utilization, attributes of the cell surface, metal requirements, and vitamin biosynthesis. Such insights into the coexistence of highly related and ecologically similar bacterial species in their shared natural habitat are rare.
Azithromycin, a potent autophagy inhibitor for cancer therapy, perturbs cytoskeletal protein dynamics
Authors: Takano Naoharu , Hiramoto Masaki , Yamada Yumiko , Kokuba Hiroko , Tokuhisa Mayumi , Hino Hirotsugu , Miyazawa Keisuke 
Published: March 2023

Abstract
Background
Autophagy plays an important role in tumour cell growth and survival and also promotes resistance to chemotherapy. Hence, autophagy has been targeted for cancer therapy. We previously reported that macrolide antibiotics including azithromycin (AZM) inhibit autophagy in various types of cancer cells in vitro. However, the underlying molecular mechanism for autophagy inhibition remains unclear. Here, we aimed to identify the molecular target of AZM for inhibiting autophagy.

Methods
We identified the AZM-binding proteins using AZM-conjugated magnetic nanobeads for high-throughput affinity purification. Autophagy inhibitory mechanism of AZM was analysed by confocal microscopic and transmission electron microscopic observation. The anti-tumour effect with autophagy inhibition by oral AZM administration was assessed in the xenografted mice model.

Results
We elucidated that keratin-18 (KRT18) and α/β-tubulin specifically bind to AZM. Treatment of the cells with AZM disrupts intracellular KRT18 dynamics, and KRT18 knockdown resulted in autophagy inhibition. Additionally, AZM treatment suppresses intracellular lysosomal trafficking along the microtubules for blocking autophagic flux. Oral AZM administration suppressed tumour growth while inhibiting autophagy in tumour tissue.

Conclusions
As drug-repurposing, our results indicate that AZM is a potent autophagy inhibitor for cancer treatment, which acts by directly interacting with cytoskeletal proteins and perturbing their dynamics.
Trifluridine/tipiracil+bevacizumab (BEV) vs. fluoropyrimidine-irinotecan+BEV as second-line therapy for metastatic colorectal cancer: a randomised noninferiority trial
Authors: Kuboki Yasutoshi , Terazawa Tetsuji , Masuishi Toshiki , Nakamura Masato , Watanabe Jun , Ojima Hitoshi , Makiyama Akitaka , Kotaka Masahito , Hara Hiroki , Kagawa Yoshinori , Sugimoto Naotoshi , Kawakami Hisato , Takashima Atsuo , Kajiwara Takeshi , Oki Eiji , Sunakawa Yu , Ishihara Soichiro , Taniguchi Hiroya , Nakajima Takako Eguchi , Morita Satoshi , Shirao Kuniaki , Takenaka Naruhito , Ozawa Daisuke , Yoshino Takayuki 
Published: March 2023

Abstract
Background
This open-label, multicentre, phase II/III trial assessed the noninferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab vs. fluoropyrimidine and irinotecan plus bevacizumab (control) as second-line treatment for metastatic colorectal cancer (mCRC).

Methods
Patients were randomised (1:1) to receive FTD/TPI (35 mg/m2 twice daily, days 1–5 and days 8–12, 28-day cycle) plus bevacizumab (5 mg/kg, days 1 and 15) or control. The primary endpoint was overall survival (OS). The noninferiority margin of the hazard ratio (HR) was set to 1.33.

Results
Overall, 397 patients were enrolled. Baseline characteristics were similar between the groups. Median OS was 14.8 vs. 18.1 months (FTD/TPI plus bevacizumab vs. control; HR 1.38; 95% confidence interval [CI] 0.99–1.93; Pnoninferiority = 0.5920). In patients with a baseline sum of the diameter of target lesions of <60 mm (n = 216, post hoc analyses), the adjusted median OS was similar between groups (FTD/TPI plus bevacizumab vs. control, 21.4 vs. 20.7 months; HR 0.92; 95% CI 0.55–1.55). Grade ≥3 adverse events (FTD/TPI plus bevacizumab vs. control) included neutropenia (65.8% vs. 41.6%) and diarrhoea (1.5% vs. 7.1%).

Conclusions
FTD/TPI plus bevacizumab did not demonstrate noninferiority to fluoropyrimidine and irinotecan plus bevacizumab as second-line treatment for mCRC.

Clinical trial registration
JapicCTI-173618, jRCTs031180122.
TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion
Authors: Zhang Qing , Zheng Jianglin , Wu Wenjie , Lian Haiyan , Iranzad Natasha , Wang Endi , Yang Lianhe , Wang Xuan , Jiang Xiaobing 
Published: March 2023

AbstractDiffuse invasion is an important factor leading to treatment resistance and a poor prognosis in gliomas. Herein, we found that expression of the tripartite motif containing 56 (TRIM56), a RING-finger domain containing E3 ubiquitin ligase, was markedly higher in glioma than in normal brain tissue, and was significantly correlated with malignant phenotypes and a poor prognosis. In vitro and in vivo experimental studies revealed that TRIM56 promoted the migration and invasion of glioma cells. Mechanistically, TRIM56 was transcriptionally regulated by SP1 and promoted the K48-K63-linked poly-ubiquitination transition of IQGAP1 at Lys-1230 by interacting with it, which in turn promoted CDC42 activation. This mechanism was confirmed to mediate glioma migration and invasion. In conclusion, our study provides insights into the mechanisms through which TRIM56 promotes glioma motility, i.e., by regulating IQGAP1 ubiquitination to promote CDC42 activation, which might be clinically targeted for the treatment of glioma.
Likely accelerated weakening of Atlantic overturning circulation emerges in optimal salinity fingerprint
Authors: Zhu Chenyu , Liu Zhengyu , Zhang Shaoqing , Wu Lixin 
Published: March 2023

AbstractThe long-term response of the Atlantic meridional overturning circulation (AMOC) to anthropogenic forcing has been difficult to detect from the short direct measurements available due to strong interdecadal variability. Here, we present observational and modeling evidence for a likely accelerated weakening of the AMOC since the 1980s under the combined forcing of anthropogenic greenhouse gases and aerosols. This likely accelerated AMOC weakening signal can be detected in the AMOC fingerprint of salinity pileup remotely in the South Atlantic, but not in the classic warming hole fingerprint locally in the North Atlantic, because the latter is contaminated by the “noise” of interdecadal variability. Our optimal salinity fingerprint retains much of the signal of the long-term AMOC trend response to anthropogenic forcing, while dynamically filtering out shorter climate variability. Given the ongoing anthropogenic forcing, our study indicates a potential further acceleration of AMOC weakening with associated climate impacts in the coming decades.
Structural basis of HIV-1 maturation inhibitor binding and activity
Authors: Sarkar Sucharita , Zadrozny Kaneil K. , Zadorozhnyi Roman , Russell Ryan W. , Quinn Caitlin M. , Kleinpeter Alex , Ablan Sherimay , Meshkin Hamed , Perilla Juan R. , Freed Eric O. , Ganser-Pornillos Barbie K. , Pornillos Owen , Gronenborn Angela M. , Polenova Tatyana 
Published: March 2023

AbstractHIV-1 maturation inhibitors (MIs), Bevirimat (BVM) and its analogs interfere with the catalytic cleavage of spacer peptide 1 (SP1) from the capsid protein C-terminal domain (CACTD), by binding to and stabilizing the CACTD-SP1 region. MIs are under development as alternative drugs to augment current antiretroviral therapies. Although promising, their mechanism of action and associated virus resistance pathways remain poorly understood at the molecular, biochemical, and structural levels. We report atomic-resolution magic-angle-spinning NMR structures of microcrystalline assemblies of CACTD-SP1 complexed with BVM and/or the assembly cofactor inositol hexakisphosphate (IP6). Our results reveal a mechanism by which BVM disrupts maturation, tightening the 6-helix bundle pore and quenching the motions of SP1 and the simultaneously bound IP6. In addition, BVM-resistant SP1-A1V and SP1-V7A variants exhibit distinct conformational and binding characteristics. Taken together, our study provides a structural explanation for BVM resistance as well as guidance for the design of new MIs.
Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage
Authors: Nappi Annarita , Miro Caterina , Pezone Antonio , Tramontano Alfonso , Di Cicco Emery , Sagliocchi Serena , Cicatiello Annunziata Gaetana , Murolo Melania , Torabinejad Sepehr , Abbotto Elena , Caiazzo Giuseppina , Raia Maddalena , Stornaiuolo Mariano , Antonini Dario , Fabbrocini Gabriella , Salvatore Domenico , Avvedimento Vittorio Enrico , Dentice Monica 
Published: March 2023

AbstractThe Thyroid Hormone (TH) activating enzyme, type 2 Deiodinase (D2), is functionally required to elevate the TH concentration during cancer progression to advanced stages. However, the mechanisms regulating D2 expression in cancer still remain poorly understood. Here, we show that the cell stress sensor and tumor suppressor p53 silences D2 expression, thereby lowering the intracellular THs availability. Conversely, even partial loss of p53 elevates D2/TH resulting in stimulation and increased fitness of tumor cells by boosting a significant transcriptional program leading to modulation of genes involved in DNA damage and repair and redox signaling. In vivo genetic deletion of D2 significantly reduces cancer progression and suggests that targeting THs may represent a general tool reducing invasiveness in p53-mutated neoplasms.
Iridium oxide nanoribbons with metastable monoclinic phase for highly efficient electrocatalytic oxygen evolution
Authors: Liao Fan , Yin Kui , Ji Yujin , Zhu Wenxiang , Fan Zhenglong , Li Youyong , Zhong Jun , Shao Mingwang , Kang Zhenhui , Shao Qi 
Published: March 2023

AbstractMetastable metal oxides with ribbon morphologies have promising applications for energy conversion catalysis, however they are largely restricted by their limited synthesis methods. In this study, a monoclinic phase iridium oxide nanoribbon with a space group of C2/m is successfully obtained, which is distinct from rutile iridium oxide with a stable tetragonal phase (P42/mnm). A molten-alkali mechanochemical method provides a unique strategy for achieving this layered nanoribbon structure via a conversion from a monoclinic phase K0.25IrO2 (I2/m (12)) precursor. The formation mechanism of IrO2 nanoribbon is clearly revealed, with its further conversion to IrO2 nanosheet with a trigonal phase. When applied as an electrocatalyst for the oxygen evolution reaction in acidic condition, the intrinsic catalytic activity of IrO2 nanoribbon is higher than that of tetragonal phase IrO2 due to the low d band centre of Ir in this special monoclinic phase structure, as confirmed by density functional theory calculations.
Controlling extrudate volume fraction through poroelastic extrusion of entangled looped fibers
Authors: Pan Zehao , Nunes Janine K. , Duprat Camille , Shum Ho Cheung , Stone Howard A. 
Published: March 2023

AbstractWhen a suspension of spherical or near-spherical particles passes through a constriction the particle volume fraction either remains the same or decreases. In contrast to these particulate suspensions, here we observe that an entangled fiber suspension increases its volume fraction up to 14-fold after passing through a constriction. We attribute this response to the entanglements among the fibers that allows the network to move faster than the liquid. By changing the fiber geometry, we find that the entanglements originate from interlocking shapes or high fiber flexibility. A quantitative poroelastic model is used to explain the increase in velocity and extrudate volume fraction. These results provide a new strategy to use fiber volume fraction, flexibility, and shape to tune soft material properties, e.g., suspension concentration and porosity, during delivery, as occurs in healthcare, three-dimensional printing, and material repair.
Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice
Authors: Chen Gen , An Ning , Shen Jingling , Chen Huinan , Chen Yunjie , Sun Jia , Hu Zhicheng , Qiu Junhui , Jin Cheng , He Shengqu , Mei Lin , Sui Yanru , Li Wanqian , Chen Peng , Guan Xueqiang , Chu Maoping , Wang Yang , Jin Litai , Kim Kwonseop , Li Xiaokun , Cong Weitao , Wang Xu 
Published: March 2023

AbstractFibroblast growth factor-18 (FGF18) has diverse organ development and damage repair roles. However, its role in cardiac homeostasis following hypertrophic stimulation remains unknown. Here we investigate the regulation and function of the FGF18 in pressure overload (PO)-induced pathological cardiac hypertrophy. FGF18 heterozygous (Fgf18+/−) and inducible cardiomyocyte-specificFGF18knockout (Fgf18-CKO) male mice exposed to transverse aortic constriction (TAC) demonstrate exacerbated pathological cardiac hypertrophy with increased oxidative stress, cardiomyocyte death, fibrosis, and dysfunction. In contrast, cardiac-specific overexpression of FGF18 alleviates hypertrophy, decreased oxidative stress, attenuates cardiomyocyte apoptosis, and ameliorates fibrosis and cardiac function. Tyrosine-protein kinase FYN (FYN), the downstream factor of FGF18, was identified by bioinformatics analysis, LC-MS/MS and experiment validation. Mechanistic studies indicate that FGF18/FGFR3 promote FYN activity and expression and negatively regulate NADPH oxidase 4 (NOX4), thereby inhibiting reactive oxygen species (ROS) generation and alleviating pathological cardiac hypertrophy. This study uncovered the previously unknown cardioprotective effect of FGF18 mediated by the maintenance of redox homeostasis through the FYN/NOX4 signaling axis in male mice, suggesting a promising therapeutic target for the treatment of cardiac hypertrophy.
Near-infrared absorbing acceptor with suppressed triplet exciton generation enabling high performance tandem organic solar cells
Authors: Jia Zhenrong , Ma Qing , Chen Zeng , Meng Lei , Jain Nakul , Angunawela Indunil , Qin Shucheng , Kong Xiaolei , Li Xiaojun , Yang Yang , Zhu Haiming , Ade Harald , Gao Feng , Li Yongfang 
Published: March 2023

AbstractReducing the energy loss of sub-cells is critical for high performance tandem organic solar cells, while it is limited by the severe non-radiative voltage loss via the formation of non-emissive triplet excitons. Herein, we develop an ultra-narrow bandgap acceptor BTPSeV-4F through replacement of terminal thiophene by selenophene in the central fused ring of BTPSV-4F, for constructing efficient tandem organic solar cells. The selenophene substitution further decrease the optical bandgap of BTPSV-4F to 1.17 eV and suppress the formation of triplet exciton in the BTPSV-4F-based devices. The organic solar cells with BTPSeV-4F as acceptor demonstrate a higher power conversion efficiency of 14.2% with a record high short-circuit current density of 30.1 mA cm−2 and low energy loss of 0.55 eV benefitted from the low non-radiative energy loss due to the suppression of triplet exciton formation. We also develop a high-performance medium bandgap acceptor O1-Br for front cells. By integrating the PM6:O1-Br based front cells with the PTB7-Th:BTPSeV-4F based rear cells, the tandem organic solar cell demonstrates a power conversion efficiency of 19%. The results indicate that the suppression of triplet excitons formation in the near-infrared-absorbing acceptor by molecular design is an effective way to improve the photovoltaic performance of the tandem organic solar cells.