bluuebunny/crossref_metadata_2025 huggingface dataset:
Ab Initio Melting Temperatures of Bcc and Hcp Iron Under the Earth’s Inner Core Condition
Authors: Sun Yang , Mendelev Mikhail I. , Zhang Feng , Liu Xun , Da Bo , Wang Cai‐Zhuang , Wentzcovitch Renata M. , Ho Kai‐Ming
Published: March 2023

There has been a long debate on the stable phase of iron under the Earth’s inner core conditions. Because of the solid‐liquid coexistence at the inner core boundary, the thermodynamic stability of solid phases directly relates to their melting temperatures, which remains considerable uncertainty. In the present study, we utilized a semi‐empirical potential fitted to high‐temperature ab initio data to perform a thermodynamic integration from classical systems described by this potential to ab initio systems. This method provides a smooth path for thermodynamic integration and significantly reduces the uncertainty caused by the finite‐size effect. Our results suggest the hcp phase is the stable phase of pure iron under the inner core conditions, while the free energy difference between the hcp and bcc phases is tiny, on the order of 10 s meV/atom near the melting temperature.
Distinct Role of a Spring Atmospheric Circulation Mode in the Arctic Sea Ice Decline in Summer
Authors: Bi Haibo , Liang Yu , Chen Xianyao
Published: March 2023

A distinguishing feature of Arctic sea ice is the rapid declining in the Pacific Arctic Sector (PAS) in recent years. The atmospheric variability during spring (March‐May) plays a critical role in determining the sea ice extent (SIE) during the following summer. The summertime (June‐August) SIE reduction in the eastern part of PAS, including the East Siberian Sea and the Laptev Sea, is strongly related to the first two leading atmospheric circulation modes in spring, the Arctic Oscillation and the Arctic Dipole, retrieved from empirical orthogonal function analysis. Here, we show that the third leading mode of atmospheric circulation in spring, namely the Barents‐Beaufort Oscillation (BBO), can also change the summer SIE, especially on the western regime of the PAS across the Beaufort and Chukchi Seas. We find that a positive phase of springtime BBO (i.e., BBO+), relative to the BBO−, acts to decrease sea ice thickness via advection and generate sea ice deformation through divergence and shear processes, thereby preconditioning for a rapid sea ice loss within the PAS in the following summer. Furthermore, the occurrence of BBO is state‐dependent and potentially modulated by the phase shift of the Atlantic Multidecadal Oscillation (AMO) and the Pacific Decadal Oscillation (PDO). Since the mid‐1990s, the AMO (PDO) index has changed from a dominant negative (positive) to a positive (negative) phase. These phase shifts in AMO and PDO would have contributed to the subsequently increased appearance of anomalous BBO+ after 2000 and enhanced the summertime sea ice loss in the western regions of the PAS in recent years.
Morphology and Fractal Dimension of Size‐Resolved Soot Particles Emitted From Combustion Sources
Authors: Pang Yuner , Chen Minghao , Wang Yuanyuan , Chen Xiyao , Teng Xiaomi , Kong Shaofei , Zheng Zhonghua , Li Weijun
Published: March 2023

Databases of the morphological parameters of fresh size‐resolved soot particles and their systematic comparisons among various combustion sources are important to trace the soot aging process and evaluate their optical properties. Here, the mixing state, effective density (ρeff), monomer number and diameter (N and dp), and fractal dimension (Df) of size‐resolved soot particles from vehicle emissions (VE), biomass burning (BB), coal combustion (CC), tunnel air (TA) and urban air (UA) were characterized based on electron microscopy observations and analysis. We determined that freshly‐emitted soot particles from combustion sources contain not only bare‐like soot but also some coated‐soot particles. ρeff (157–689 kg/m3) decreased while N (46–1,500) and dp (24–42 nm) increased with the increased diameter of soot particles. The Df of BB and CC were independent of the diameter changes and fluctuated between 1.65 and 1.80, while the Df of VE and TA (1.62–1.71) increased and UA Df (1.87–1.80) decreased with increasing diameter. Based on Df obtained in this study, we found that the ensemble Df of VE, BB, CC, TA, and UA could not represent the finer (<150 nm) soot particles and coarser soot particles (>600 nm) in VE, TA, and UA. This study highlights that the morphological parameters of freshly‐emitted soot particles vary among different combustion sources and have a size effect, particularly for finer and coarser soot particles. The database of size‐resolved soot particles will be helpful to improve soot models based on numerical simulation and better evaluate atmospheric optical properties.
The Low‐Altitude Ionosphere of the Ice Giant Planets
Authors: Molina‐Cuberos G. J. , Witasse O. , Toledo D. , Tripathi S. N.
Published: March 2023

The 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

The 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

Over 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.
Quaoar’s Ring Defies Gravity
Authors: Cartier Kimberly
Published: March 2023

The dwarf planet’s ring makes astronomers question whether a long-held theory about ring and moon formation needs tweaking.
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

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

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

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

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

Diffuse 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

The 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

HIV-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

The 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

Metastable 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

When 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

Fibroblast 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

Reducing 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.
Lifetime over 10000 hours for organic solar cells with Ir/IrOx electron-transporting layer
Authors: Li Yanxun , Huang Bo , Zhang Xuning , Ding Jianwei , Zhang Yingyu , Xiao Linge , Wang Boxin , Cheng Qian , Huang Gaosheng , Zhang Hong , Yang Yingguo , Qi Xiaoying , Zheng Qiang , Zhang Yuan , Qiu Xiaohui , Liang Minghui , Zhou Huiqiong
Published: March 2023

The stability of organic solar cells is a key issue to promote practical applications. Herein, we demonstrate that the device performance of organic solar cells is enhanced by an Ir/IrOx electron-transporting layer, benefiting from its suitable work function and heterogeneous distribution of surface energy in nanoscale. Notably, the champion Ir/IrOx-based devices exhibit superior stabilities under shelf storing (T80 = 56696 h), thermal aging (T70 = 13920 h), and maximum power point tracking (T80 = 1058 h), compared to the ZnO-based devices. It can be attributed to the stable morphology of photoactive layer resulting from the optimized molecular distribution of the donor and acceptor and the absence of photocatalysis in the Ir/IrOx-based devices, which helps to maintain the improved charge extraction and inhibited charge recombination in the aged devices. This work provides a reliable and efficient electron-transporting material toward stable organic solar cells.
China’s electric vehicle and climate ambitions jeopardized by surging critical material prices
Authors: Wang Hetong , Feng Kuishuang , Wang Peng , Yang Yuyao , Sun Laixiang , Yang Fan , Chen Wei-Qiang , Zhang Yiyi , Li Jiashuo
Published: March 2023

The adoption of electric vehicles (EVs) on a large scale is crucial for meeting the desired climate commitments, where affordability plays a vital role. However, the expected surge in prices of lithium, cobalt, nickel, and manganese, four critical materials in EV batteries, could hinder EV uptake. To explore these impacts in the context of China, the world’s largest EV market, we expand and enrich an integrated assessment model. We find that under a high material cost surge scenario, EVs would account for 35% (2030) and 51% (2060) of the total number of vehicles in China, significantly lower than 49% (2030) and 67% (2060) share in the base-line, leading to a 28% increase in cumulative carbon emissions (2020-2060) from road transportation. While material recycling and technical battery innovation are effective long-term countermeasures, securing the supply chains of critical materials through international cooperation is highly recommended, given geopolitical and environmental fragilities.
Micro-electrochemical insights into pit initiation site on aged UNS S32750 super duplex stainless steel
Authors: Amatsuka Shuichiro , Nishimoto Masashi , Muto Izumi , Kawamori Makoto , Takara Yuya , Sugawara Yu
Published: March 2023

An aging treatment of UNS S32750 super duplex stainless steel at 1173 K for 1.0 ks produced σ and secondary austenite (γ2) phases in the α and γ phase boundary regions. Small amount of Mn-Cr oxide and MnS complex inclusions were present in the steel. No pitting was observed during the potentiodynamic polarization of a small area (200 × 200 µm) without inclusions in 1 M MgCl2 at 348 K. Because the electrode area included α, γ, σ, and γ2 phases, these phases and their boundaries alone could not act as initiation sites for pitting. The electrode area size was gradually reduced from 3 × 3 mm to 1 × 1 mm, and pitting corrosion was observed to occur at the Mn-Cr oxide and MnS complex inclusions in a region that appeared to be the γ2 phase near the σ phase.
The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data
Authors: Leonard Hampton L. , Murtadha Ruqaya , Martinez-Carrasco Alejandro , Jama Alina , Müller-Nedebock Amica Corda , Gil-Martinez Ana-Luisa , Illarionova Anastasia , Moore Anni , Bustos Bernabe I. , Jadhav Bharati , Huxford Brook , Storm Catherine , Towns Clodagh , Vitale Dan , Chetty Devina , Yu Eric , Grenn Francis P. , Salazar Gabriela , Rateau Geoffrey , Iwaki Hirotaka , Elsayed Inas , Foote Isabelle Francesca , Jansen van Rensburg Zuné , Kim Jonggeol Jeff , Yuan Jie , Lake Julie , Brolin Kajsa , Senkevich Konstantin , Wu Lesley , Tan Manuela M. X. , Periñán María Teresa , Makarious Mary B. , Ta Michael , Pillay Nikita Simone , Betancor Oswaldo Lorenzo , Reyes-Pérez Paula R. , Alvarez Jerez Pilar , Saini Prabhjyot , al-Ouran Rami , Sivakumar Ramiya , Real Raquel , Reynolds Regina H. , Hu Ruifneg , Abrahams Shameemah , Rao Shilpa C. , Antar Tarek , Leal Thiago Peixoto , Iankova Vassilena , Scotton William J. , Song Yeajin , Singleton Andrew , Nalls Mike A. , Dey Sumit , Bandres-Ciga Sara , Blauwendraat Cornelis , Noyce Alastair J. ,   on behalf of The International Parkinson Disease Genomics Consortium (IPDGC) and The Global Parkinson’s Genetics Program (GP2)
Published: March 2023

Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.
Immunogenicity and protective activity of mRNA vaccine candidates against yellow fever virus in animal models
Authors: Medina-Magües Lex G. , Mühe Janine , Jasny Edith , Medina-Magües Emily S. , Roth Nicole , Lopera-Madrid Jaime , Salas-Quinchucua Cristhian , Knuese Cole , Petsch Benjamin , Osorio Jorge E.
Published: March 2023

Despite the success of the widely used attenuated yellow fever (YF) vaccine, its global supply remains a substantial barrier to implementing vaccination campaigns in endemic regions and combating emerging epidemics. In A129 mice and rhesus macaques, we evaluated the immunogenicity and protective activity of messenger RNA (mRNA) vaccine candidates encapsulated in lipid nanoparticles, expressing the pre-membrane and envelope proteins or the non-structural protein 1 of YF virus. Vaccine constructs induced humoral and cell-mediated immune responses in mice, resulting in protection against lethal YF virus infection after passive administration of serum or splenocytes from vaccinated mice. Vaccination of macaques induced sustained high humoral and cellular immune responses for at least 5 months after the second dose. Our data demonstrate that these mRNA vaccine candidates can be considered an attractive addition to the licensed YF vaccine supply based on the induction of functional antibodies correlating with protection and T-cell responses; they could alleviate the limited supply of current YF vaccines, mitigating future YF epidemics.
Predicting indirect effects of rotavirus vaccination programs on rotavirus mortality among children in 112 countries
Authors: Kraay A. N. M. , Chaney D. M. , Deshpande A. , Pitzer V. E. , Lopman B. A.
Published: March 2023

Rotavirus is a leading cause of diarrhea deaths in children, particularly in low-to-middle income countries (LMICs). Licensed rotavirus vaccines provide strong direct protection, but their indirect effect—the protection due to reduced transmission—is not fully understood. We aimed to quantify the population-level effects of rotavirus vaccination and identify factors that drive indirect protection. We used an SIR-like transmission model to estimate the indirect effects of vaccination on rotavirus deaths in 112 LMICs. We performed a regression analysis to identify predictors of indirect effect magnitude (linear regression) and the occurrence of negative indirect effects (logistic regression). Indirect effects contributed to vaccine impacts in all regions, with effect sizes 8-years post-vaccine introduction ranging from 16.9% in the WHO European region to 1.0% in the Western Pacific region. Indirect effect estimates were higher in countries with higher under-5 mortality, higher vaccine coverage, and lower birth rates. Of the 112 countries analyzed, 18 (16%) had at least 1 year with a predicted negative indirect effect. Negative indirect effects were more common in countries with higher birth rate, lower under-5 mortality and lower vaccine coverage. Rotavirus vaccination may have a larger impact than would be expected from direct effects alone, but the impact of these indirect effects is expected to vary by country.
Molecular-evaluated and explainable drug repurposing for COVID-19 using ensemble knowledge graph embedding
Authors: Islam Md Kamrul , Amaya-Ramirez Diego , Maigret Bernard , Devignes Marie-Dominique , Aridhi Sabeur , Smaïl-Tabbone Malika
Published: March 2023

The search for an effective drug is still urgent for COVID-19 as no drug with proven clinical efficacy is available. Finding the new purpose of an approved or investigational drug, known as drug repurposing, has become increasingly popular in recent years. We propose here a new drug repurposing approach for COVID-19, based on knowledge graph (KG) embeddings. Our approach learns “ensemble embeddings” of entities and relations in a COVID-19 centric KG, in order to get a better latent representation of the graph elements. Ensemble KG-embeddings are subsequently used in a deep neural network trained for discovering potential drugs for COVID-19. Compared to related works, we retrieve more in-trial drugs among our top-ranked predictions, thus giving greater confidence in our prediction for out-of-trial drugs. For the first time to our knowledge, molecular docking is then used to evaluate the predictions obtained from drug repurposing using KG embedding. We show that Fosinopril is a potential ligand for the SARS-CoV-2 nsp13 target. We also provide explanations of our predictions thanks to rules extracted from the KG and instanciated by KG-derived explanatory paths. Molecular evaluation and explanatory paths bring reliability to our results and constitute new complementary and reusable methods for assessing KG-based drug repurposing.
Development of a nomogram for predicting 90-day mortality in patients with sepsis-associated liver injury
Authors: Cui Liangwen , Bao Junjie , Yu Chao , Zhang Cheng , Huang Rui , Liu Lian , Shao Min
Published: March 2023

The high mortality rate in sepsis patients is related to sepsis-associated liver injury (SALI). We sought to develop an accurate forecasting nomogram to estimate individual 90-day mortality in SALI patients. Data from 34,329 patients were extracted from the public Medical Information Mart for Intensive Care (MIMIC-IV) database. SALI was defined by total bilirubin (TBIL) > 2 mg/dL and the occurrence of an international normalized ratio (INR) > 1.5 in the presence of sepsis. Logistic regression analysis was performed to establish a prediction model called the nomogram based on the training set (n = 727), which was subsequently subjected to internal validation. Multivariate logistic regression analysis showed that SALI was an independent risk factor for mortality in patients with sepsis. The Kaplan‒Meier curves for 90-day survival were different between the SALI and non-SALI groups after propensity score matching (PSM) (log rank: P < 0.001 versus P = 0.038), regardless of PSM balance. The nomogram demonstrated better discrimination than the sequential organ failure assessment (SOFA) score, logistic organ dysfunction system (LODS) score, simplified acute physiology II (SAPS II) score, and Albumin–Bilirubin (ALBI) score in the training and validation sets, with areas under the receiver operating characteristic curve (AUROC) of 0.778 (95% CI 0.730–0.799, P < 0.001) and 0.804 (95% CI 0.713–0.820, P < 0.001), respectively. The calibration plot showed that the nomogram was sufficiently successful to predict the probability of 90-day mortality in both groups. The DCA of the nomogram demonstrated a higher net benefit regarding clinical usefulness than SOFA, LODS, SAPSII, and ALBI scores in the two groups. The nomogram performs exceptionally well in predicting the 90-day mortality rate in SALI patients, which can be used to assess the prognosis of patients with SALI and may assist in guiding clinical practice to enhance patient outcomes.
Neural network based formation of cognitive maps of semantic spaces and the putative emergence of abstract concepts
Authors: Stoewer Paul , Schilling Achim , Maier Andreas , Krauss Patrick
Published: March 2023

How do we make sense of the input from our sensory organs, and put the perceived information into context of our past experiences? The hippocampal-entorhinal complex plays a major role in the organization of memory and thought. The formation of and navigation in cognitive maps of arbitrary mental spaces via place and grid cells can serve as a representation of memories and experiences and their relations to each other. The multi-scale successor representation is proposed to be the mathematical principle underlying place and grid cell computations. Here, we present a neural network, which learns a cognitive map of a semantic space based on 32 different animal species encoded as feature vectors. The neural network successfully learns the similarities between different animal species, and constructs a cognitive map of ‘animal space’ based on the principle of successor representations with an accuracy of around 30% which is near to the theoretical maximum regarding the fact that all animal species have more than one possible successor, i.e. nearest neighbor in feature space. Furthermore, a hierarchical structure, i.e. different scales of cognitive maps, can be modeled based on multi-scale successor representations. We find that, in fine-grained cognitive maps, the animal vectors are evenly distributed in feature space. In contrast, in coarse-grained maps, animal vectors are highly clustered according to their biological class, i.e. amphibians, mammals and insects. This could be a putative mechanism enabling the emergence of new, abstract semantic concepts. Finally, even completely new or incomplete input can be represented by interpolation of the representations from the cognitive map with remarkable high accuracy of up to 95%. We conclude that the successor representation can serve as a weighted pointer to past memories and experiences, and may therefore be a crucial building block to include prior knowledge, and to derive context knowledge from novel input. Thus, our model provides a new tool to complement contemporary deep learning approaches on the road towards artificial general intelligence.
Hard optimization problems have soft edges
Authors: Marino Raffaele , Kirkpatrick Scott
Published: March 2023

Finding a Maximum Clique is a classic property test from graph theory; find any one of the largest complete subgraphs in an Erdös-Rényi G(N, p) random graph. We use Maximum Clique to explore the structure of the problem as a function of N, the graph size, and K, the clique size sought. It displays a complex phase boundary, a staircase of steps at each of which $$2 \log _2N$$

2

log
2

N

and $$K_{\text {max}}$$

K
max

, the maximum size of a clique that can be found, increases by 1. Each of its boundaries has a finite width, and these widths allow local algorithms to find cliques beyond the limits defined by the study of infinite systems. We explore the performance of a number of extensions of traditional fast local algorithms, and find that much of the “hard” space remains accessible at finite N. The “hidden clique” problem embeds a clique somewhat larger than those which occur naturally in a G(N, p) random graph. Since such a clique is unique, we find that local searches which stop early, once evidence for the hidden clique is found, may outperform the best message passing or spectral algorithms.
Organic carbon accumulation and aggregate formation in soils under organic and inorganic fertilizer management practices in a rice–wheat cropping system
Authors: Zhao Zhanhui , Mao Yanli , Gao Songfeng , Lu Chunyang , Pan Chuanjiao , Li Xiaoyu
Published: March 2023

Soil organic carbon (C) and aggregates are the important components of soil fertility and the foundation of sustainable agriculture. The storage and protection of SOC in aggregates is widely regarded as the material basis of soil organic C accumulation. However, current understanding of soil aggregate and its associated organic C is insufficient to elucidate the regulation mechanism of soil organic C. A nine-year field experiment including chemical fertilizer (FR) and organic manure (OM) treatments was set up in the eastern plain of Funiu Mountain, central China. Using chemical analysis, physical sieving as well as nuclear magnetic resonance (NMR) methods, we mainly probed into the response of soil organic C concentration and composition, and C functional groups, water-stable aggregates to different treatments. Furthermore, scanning electronic microscopy (SEM) and partial least square structural equation modelling (PLS-SEM) was conducted to characterise the different size aggregates and to analyse the mechanism of soil organic C accumulation and stabilisation at aggregate scales. After nine years of farming, OM treatment substantially increased soil organic C content (by 3.77 g kg−1) and significantly enhanced the formation of macro-aggregates (> 250 μm), while FR had no significant influence on soil organic C. At the aggregate scale, the amounts of soil organic C, C physical fractions (particulate and mineral-associated organic C), total nitrogen and microbial biomass carbon associated in macro-aggregates (> 250 μm) were obviously higher than that in micro-aggregates and silt + clay fraction, and OM treatment greatly increased the accumulation of soil organic C and its components in macro-aggregates. Moreover, microbial biomass carbon (MBC) amounts in aggregates were remarkably increased (27–116%) by the application of OM. And MBC had a positively effect on the physical fractions of SOC but not on the C chemical structure within aggregates. The present study indicated that soil organic C accumulation mainly rely on macro-aggregates (> 250 μm). Intra–particulate organic carbon (POC) and mineral-associated organic carbon (MOC) within macro-aggregates played an important role in soil organic C accumulation. Meanwhile, soil microbes were a driving force for the accumulation of soil organic C physical fractions (POC and MOC). We concluded that OM treatment accelerated the synergistic process between organic C sequestration and soil aggregation, and showed great potential to increase soil organic C accumulation.