bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine triggers early astrocyte reactivity that provokes microglial responses and drives the pathogenesis of sepsis-associated encephalopathy in mice
Authors: Guo Qilin , Gobbo Davide , Zhao Na , Zhang Hong , Awuku Nana-Oye , Liu Qing , Fang Li-Pao , Gampfer Tanja M. , Meyer Markus R. , Zhao Renping , Bai Xianshu , Bian Shan , Scheller Anja , Kirchhoff Frank , Huang Wenhui 
Published: July 2024

AbstractMolecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. Here, we report that in mice during the first 6 hours of peripheral lipopolysaccharide (LPS)-evoked systemic inflammation (6 hpi), the plasma level of adenosine quickly increased and enhanced the tone of central extracellular adenosine which then provoked neuroinflammation by triggering early astrocyte reactivity. Specific ablation of astrocytic Gi protein-coupled A1 adenosine receptors (A1ARs) prevented this early reactivity and reduced the levels of inflammatory factors (e.g., CCL2, CCL5, and CXCL1) in astrocytes, thereby alleviating microglial reaction, ameliorating blood-brain barrier disruption, peripheral immune cell infiltration, neuronal dysfunction, and depression-like behaviour in the mice. Chemogenetic stimulation of Gi signaling in A1AR-deficent astrocytes at 2 and 4 hpi of LPS injection could restore neuroinflammation and depression-like behaviour, highlighting astrocytes rather than microglia as early drivers of neuroinflammation. Our results identify early astrocyte reactivity towards peripheral and central levels of adenosine as an important pathway driving SAE and highlight the potential of targeting A1ARs for therapeutic intervention.
Tunable anti-ambipolar vertical bilayer organic electrochemical transistor enable neuromorphic retinal pathway
Authors: Laswick Zachary , Wu Xihu , Surendran Abhijith , Zhou Zhongliang , Ji Xudong , Matrone Giovanni Maria , Leong Wei Lin , Rivnay Jonathan 
Published: July 2024

AbstractIncreasing demand for bio-interfaced human-machine interfaces propels the development of organic neuromorphic electronics with small form factors leveraging both ionic and electronic processes. Ion-based organic electrochemical transistors (OECTs) showing anti-ambipolarity (OFF-ON-OFF states) reduce the complexity and size of bio-realistic Hodgkin-Huxley(HH) spiking circuits and logic circuits. However, limited stable anti-ambipolar organic materials prevent the design of integrated, tunable, and multifunctional neuromorphic and logic-based systems. In this work, a general approach for tuning anti-ambipolar characteristics is presented through assembly of a p-n bilayer in a vertical OECT (vOECT) architecture. The vertical OECT design reduces device footprint, while the bilayer material tuning controls the anti-ambipolarity characteristics, allowing control of the device’s on and off threshold voltages, and peak position, while reducing size thereby enabling tunable threshold spiking neurons and logic gates. Combining these components, a mimic of the retinal pathway reproducing the wavelength and light intensity encoding of horizontal cells to spiking retinal ganglion cells is demonstrated. This work enables further incorporation of conformable and adaptive OECT electronics into biointegrated devices featuring sensory coding through parallel processing for diverse artificial intelligence and computing applications.
Reaching the precision limit with tensor-based wavefront shaping
Authors: Gutiérrez-Cuevas Rodrigo , Bouchet Dorian , de Rosny Julien , Popoff Sébastien M. 
Published: July 2024

AbstractPerturbations in complex media, due to their own dynamical evolution or to external effects, are often seen as detrimental. Therefore, a common strategy, especially for telecommunication and imaging applications, is to limit the sensitivity to those perturbations in order to avoid them. Here, instead, we consider enhancing the interaction between light and perturbations to produce the largest change in the output intensity distribution. Our work hinges on the use of tensor-based techniques, presently at the forefront of machine learning explorations, to study intensity-based measurements where its quadratic relationship to the field prevents the use of standard matrix methods. With this tensor-based framework, we can identify the maximum-information intensity channel which maximizes the change in its output intensity distribution and the Fisher information encoded in it about a given perturbation. We further demonstrate experimentally its superiority for robust and precise sensing applications. Additionally, we derive the appropriate strategy to reach the precision limit for intensity-based measurements, leading to an increase in Fisher information by more than four orders of magnitude compared to the mean for random wavefronts when measured with the pixels of a camera.
Single cell transcriptomic profiling identifies tumor-acquired and therapy-resistant cell states in pediatric rhabdomyosarcoma
Authors: Danielli Sara G. , Wei Yun , Dyer Michael A. , Stewart Elizabeth , Sheppard Heather , Wachtel Marco , Schäfer Beat W. , Patel Anand G. , Langenau David M. 
Published: July 2024

AbstractRhabdomyosarcoma (RMS) is a pediatric tumor that resembles undifferentiated muscle cells; yet the extent to which cell state heterogeneity is shared with human development has not been described. Using single-cell/nucleus RNA sequencing from patient tumors, patient-derived xenografts, primary in vitro cultures, and cell lines, we identify four dominant muscle-lineage cell states: progenitor, proliferative, differentiated, and ground cells. We stratify these RMS cells/nuclei along the continuum of human muscle development and show that they share expression patterns with fetal/embryonal myogenic precursors rather than postnatal satellite cells. Fusion-negative RMS (FN-RMS) have a discrete stem cell hierarchy that recapitulates fetal muscle development and contain therapy-resistant FN-RMS progenitors that share transcriptomic similarity with bipotent skeletal mesenchymal cells. Fusion-positive RMS have tumor-acquired cells states, including a neuronal cell state, that are not found in myogenic development. This work identifies previously underappreciated cell state heterogeneity including unique treatment-resistant and tumor-acquired cell states that differ across RMS subtypes.
Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys
Authors: Xue Xiaoyu , Wu Xianming , Fan Yongheng , Han Shuyu , Zhang Haipeng , Sun Yuting , Yin Yanyun , Yin Man , Chen Bing , Sun Zheng , Zhao Shuaijing , Zhang Qi , Liu Weiyuan , Zhang Jiaojiao , Li Jiayin , Shi Ya , Xiao Zhifeng , Dai Jianwu , Zhao Yannan 
Published: July 2024

AbstractSpinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.
Room-temperature quantum nanoplasmonic coherent perfect absorption
Authors: Lai Yiming , Clarke Daniel D. A. , Grimm Philipp , Devi Asha , Wigger Daniel , Helbig Tobias , Hofmann Tobias , Thomale Ronny , Huang Jer-Shing , Hecht Bert , Hess Ortwin 
Published: July 2024

AbstractLight-matter superposition states obtained via strong coupling play a decisive role in quantum information processing, but the deleterious effects of material dissipation and environment-induced decoherence inevitably destroy coherent light-matter polaritons over time. Here, we propose the use of coherent perfect absorption under near-field driving to prepare and protect the polaritonic states of a single quantum emitter interacting with a plasmonic nanocavity at room temperature. Our scheme of quantum nanoplasmonic coherent perfect absorption leverages an inherent frequency specificity to selectively initialize the coupled system in a chosen plasmon-emitter dressed state, while the coherent, unidirectional and non-perturbing near-field energy transfer from a proximal plasmonic waveguide can in principle render the dressed state robust against dynamic dissipation under ambient conditions. Our study establishes a previously unexplored paradigm for quantum state preparation and coherence preservation in plasmonic cavity quantum electrodynamics, offering compelling prospects for elevating quantum nanophotonic technologies to ambient temperatures.
A bacteriocin expression platform for targeting pathogenic bacterial species
Authors: Rutter Jack W. , Dekker Linda , Clare Chania , Slendebroek Zoe F. , Owen Kimberley A. , McDonald Julie A. K. , Nair Sean P. , Fedorec Alex J. H. , Barnes Chris P. 
Published: July 2024

AbstractBacteriocins are antimicrobial peptides that are naturally produced by many bacteria. They hold great potential in the fight against antibiotic resistant bacteria, including ESKAPE pathogens. Engineered live biotherapeutic products (eLBPs) that secrete bacteriocins can be created to deliver targeted bacteriocin production. Here we develop a modular bacteriocin secretion platform that can be used to express and secrete multiple bacteriocins from non-pathogenic Escherichia coli host strains. As a proof of concept we create Enterocin A (EntA) and Enterocin B (EntB) secreting strains that show strong antimicrobial activity against Enterococcus faecalis and Enterococcus faecium in vitro, and characterise this activity in both solid culture and liquid co-culture. We then develop a Lotka-Volterra model that can be used to capture the interactions of these competitor strains. We show that simultaneous exposure to EntA and EntB can delay Enterococcus growth. Our system has the potential to be used as an eLBP to secrete additional bacteriocins for the targeted killing of pathogenic bacteria.
Stochastic switching and analog-state programmable memristor and its utilization for homomorphic encryption hardware
Authors: Cheong Woon Hyung , In Jae Hyun , Jeon Jae Bum , Kim Geunyoung , Kim Kyung Min 
Published: July 2024

AbstractHomomorphic encryption performs computations on encrypted data without decrypting, thereby eliminating security issues during the data communication between clouds and edges. As a result, there is a growing need for homomorphic encryption hardware (HE-HW) for the edges, where low power consumption and a compact form factor are desired. Here, a Pt/Ta2O5/Mo metallic cluster-type memristors (Mo-MCM) characterized by the Mo as a mobile species, and its utilization for the HE-HW via a 1-trasistor-1-memristor (1T1M) array as a prototype HE-HW is proposed. The Mo-MCM exhibits inherent stochastic set-switching behavior, which can be utilized for generating the random numbers required for encryption key generation. Furthermore, the device can accurately store analog conductance states after set-switching, which can be used as an analog non-volatile memristor. By simultaneously leveraging these two characteristics, encryption key generation, data encryption, and decryption are possible within a single device through an in-memory computing manner.
Deployment expectations of multi-gigatonne scale carbon removal could have adverse impacts on Asia’s energy-water-land nexus
Authors: Ampah Jeffrey Dankwa , Jin Chao , Liu Haifeng , Yao Mingfa , Afrane Sandylove , Adun Humphrey , Fuhrman Jay , Ho David T. , McJeon Haewon 
Published: July 2024

AbstractExisting studies indicate that future global carbon dioxide (CO2) removal (CDR) efforts could largely be concentrated in Asia. However, there is limited understanding of how individual Asian countries and regions will respond to varying and uncertain scales of future CDR concerning their energy-land-water system. We address this gap by modeling various levels of CDR-reliant pathways under climate change ambitions in Asia. We find that high CDR reliance leads to residual fossil fuel and industry emissions of about 8 Gigatonnes CO2yr−1 (GtCO2yr−1) by 2050, compared to less than 1 GtCO2yr−1 under moderate-to-low CDR reliance. Moreover, expectations of multi-gigatonne CDR could delay the achievement of domestic net zero CO2 emissions for several Asian countries and regions, and lead to higher land allocation and fertilizer demand for bioenergy crop cultivation. Here, we show that Asian countries and regions should prioritize emission reduction strategies while capitalizing on the advantages of carbon removal when it is most viable.
Toxic eburicol accumulation drives the antifungal activity of azoles against Aspergillus fumigatus
Authors: Elsaman Hesham , Golubtsov Evgeny , Brazil Sean , Ng Natanya , Klugherz Isabel , Martin Ronny , Dichtl Karl , Müller Christoph , Wagener Johannes 
Published: July 2024

AbstractAzole antifungals inhibit the sterol C14-demethylase (CYP51/Erg11) of the ergosterol biosynthesis pathway. Here we show that the azole-induced synthesis of fungicidal cell wall carbohydrate patches in the pathogenic mold Aspergillus fumigatus strictly correlates with the accumulation of the CYP51 substrate eburicol. A lack of other essential ergosterol biosynthesis enzymes, such as sterol C24-methyltransferase (Erg6A), squalene synthase (Erg9) or squalene epoxidase (Erg1) does not trigger comparable cell wall alterations. Partial repression of Erg6A, which converts lanosterol into eburicol, increases azole resistance. The sterol C5-desaturase (ERG3)-dependent conversion of eburicol into 14-methylergosta-8,24(28)-dien-3β,6α-diol, the “toxic diol” responsible for the fungistatic activity against yeasts, is not required for the fungicidal effects in A. fumigatus. While ERG3-lacking yeasts are azole resistant, ERG3-lacking A. fumigatus becomes more susceptible. Mutants lacking mitochondrial complex III functionality, which are much less effectively killed, but strongly inhibited in growth by azoles, convert eburicol more efficiently into the supposedly “toxic diol”. We propose that the mode of action of azoles against A. fumigatus relies on accumulation of eburicol which exerts fungicidal effects by triggering cell wall carbohydrate patch formation.
Genome of the early spider-orchid Ophrys sphegodes provides insights into sexual deception and pollinator adaptation
Authors: Russo Alessia , Alessandrini Mattia , El Baidouri Moaine , Frei Daniel , Galise Teresa Rosa , Gaidusch Lara , Oertel Hannah F. , Garcia Morales Sara E. , Potente Giacomo , Tian Qin , Smetanin Dmitry , Bertrand Joris A. M. , Onstein Renske E. , Panaud Olivier , Frey Jürg E. , Cozzolino Salvatore , Wicker Thomas , Xu Shuqing , Grossniklaus Ueli , Schlüter Philipp M. 
Published: July 2024

AbstractPollinator-driven evolution of floral traits is thought to be a major driver of angiosperm speciation and diversification. Ophrys orchids mimic female insects to lure male pollinators into pseudocopulation. This strategy, called sexual deception, is species-specific, thereby providing strong premating reproductive isolation. Identifying the genomic architecture underlying pollinator adaptation and speciation may shed light on the mechanisms of angiosperm diversification. Here, we report the 5.2 Gb chromosome-scale genome sequence of Ophrys sphegodes. We find evidence for transposable element expansion that preceded the radiation of the O. sphegodes group, and for gene duplication having contributed to the evolution of chemical mimicry. We report a highly differentiated genomic candidate region for pollinator-mediated evolution on chromosome 2. The Ophrys genome will prove useful for investigations into the repeated evolution of sexual deception, pollinator adaptation and the genomic architectures that facilitate evolutionary radiations.
Biomimetic synergistic effect of redox site and Lewis acid for construction of efficient artificial enzyme
Authors: Si Haibin , Du Dexin , Jiao Chengcheng , Sun Yan , Li Lu , Tang Bo 
Published: July 2024

AbstractIn enzymatic catalysis, the redox site and Lewis acid are the two main roles played by metal to assist amino acids. However, the reported enzyme mimics only focus on the redox-active metal as redox site, while the redox-inert metal as Lewis acid has, to the best of our knowledge, not been studied, presenting a bottleneck of enzyme mimics construction. Based on this, a series of highly efficient MxV2O5·nH2O peroxidase mimics with vanadium as redox site and alkaline-earth metal ion (M2+) as Lewis acid are reported. Experimental results and theoretical calculations indicate the peroxidase-mimicking activity of MxV2O5·nH2O show a periodic change with the Lewis acidity (ion potential) of M2+, revealing the mechanism of redox-inert M2+ regulating electron transfer of V-O through non-covalent polarization and thus promoting H2O2 adsorbate dissociation. The biomimetic synergetic effect of redox site and Lewis acid is expected to provide an inspiration for design of enzyme mimics.
Cholesterol-rich lysosomes induced by respiratory syncytial virus promote viral replication by blocking autophagy flux
Authors: Chen Lifeng , Zhang Jingjing , Xu Weibin , Chen Jiayi , Tang Yujun , Xiong Si , Li Yaolan , Zhang Hong , Li Manmei , Liu Zhong 
Published: July 2024

AbstractRespiratory syncytial virus (RSV) hijacks cholesterol or autophagy pathways to facilitate optimal replication. However, our understanding of the associated molecular mechanisms remains limited. Here, we show that RSV infection blocks cholesterol transport from lysosomes to the endoplasmic reticulum by downregulating the activity of lysosomal acid lipase, activates the SREBP2–LDLR axis, and promotes uptake and accumulation of exogenous cholesterol in lysosomes. High cholesterol levels impair the VAP-A-binding activity of ORP1L and promote the recruitment of dynein–dynactin, PLEKHM1, or HOPS VPS39 to Rab7–RILP, thereby facilitating minus-end transport of autophagosomes and autolysosome formation. Acidification inhibition and dysfunction of cholesterol-rich lysosomes impair autophagy flux by inhibiting autolysosome degradation, which promotes the accumulation of RSV fusion protein. RSV-F storage is nearly abolished after cholesterol depletion or knockdown of LDLR. Most importantly, the knockout of LDLR effectively inhibits RSV infection in vivo. These findings elucidate the molecular mechanism of how RSV co-regulates lysosomal cholesterol reprogramming and autophagy and reveal LDLR as a novel target for anti-RSV drug development.
Prognostic value of structural variants in early breast cancer patients
Authors: Kim Ji-Yeon , Park Kyunghee , Park Woong-Yang , Ahn Jin Seok , Im Young-Hyuck , Lee Jeong Eon , Kim Seok Won , Nam Seok Jin , Yu Jonghan , Park Yeon Hee 
Published: July 2024

AbstractGenomic analysis of structural variants(SVs) in breast cancer (BC) patients has been conducted, but the relationship between genomic alterations and BC prognosis remains unclear. We performed RNA sequencing of 297 early BC fresh-frozen tissues. We identified SVs using three tools (STAR.Arriba, STAR.fusion, and STAR.SEQR) with the COSMIC and Mitelman databases as guide references. We found a median of five to eight fusions per sample. In BC intrinsic subtypes, normal subtype had the fewest fusions (median: 1, interquartile range [IQR]: 0, 3) followed by luminal A (median: 5.5, IQR: 2.75, 10.25), luminal B (median: 9, IQR: 6, 16.5), HER2-enriched (median: 9, IQR: 6, 16.5) and basal (median 10, IQR: 6, 15.5) subtypes (p < 0.05). Intrachromosomal fusion was more frequent observed rather than interchromosomal fusion. In location, chromosome 17 had the most fusions followed by chromosome 1 and 11. When samples were divided into high and low fusion groups based on a cut-off value of 11 fusions, five-year event-free survival (5Y-EFS) was 68.1% in the high fusion group (n = 72) and 80.1% in the low fusion group (n = 125) (p = 0.024) while 75.6% among all patients (95% confidence interval: 0.699, 0.819). Among BC subtype, TNBCs with more fusions had shorter EFS compared to those with fewer fusions (5Y-EFS rate: 65.1% vs. 85.7%; p = 0.013) but no EFS differences were observed in other BC subtypes. ESTIMATE ImmuneScore was also associated with the number of fusions in TNBC (p < 0.005) and TNBCs with high ImmuneScore had better 5Y-EFS compared to those with low ImmuneScore (p = 0.041). In conclusion, diverse fusions were observed by BC subtype, and the number of fusions was associated with BC survival outcome and immune status in TNBC.
Advancing insights into microgravity induced muscle changes using Caenorhabditis elegans as a model organism
Authors: Beckett Laura J. , Williams Philip M. , Toh Li Shean , Hessel Volker , Gerstweiler Lukas , Fisk Ian , Toronjo-Urquiza Luis , Chauhan Veeren M. 
Published: July 2024

AbstractSpaceflight presents significant challenges to the physiological state of living organisms. This can be due to the microgravity environment experienced during long-term space missions, resulting in alterations in muscle structure and function, such as atrophy. However, a comprehensive understanding of the adaptive mechanisms of biological systems is required to devise potential solutions and therapeutic approaches for adapting to spaceflight conditions. This review examines the current understanding of the challenges posed by spaceflight on physiological changes, alterations in metabolism, dysregulation of pathways and the suitability and advantages of using the model organism Caenorhabditis elegans nematodes to study the effects of spaceflight. Research has shown that changes in the gene and protein composition of nematodes significantly occur across various larval stages and rearing environments, including both microgravity and Earth gravity settings, often mirroring changes observed in astronauts. Additionally, the review explores significant insights into the fundamental metabolic changes associated with muscle atrophy and growth, which could lead to the development of diagnostic biomarkers and innovative techniques to prevent and counteract muscle atrophy. These insights not only advance our understanding of microgravity-induced muscle atrophy but also lay the groundwork for the development of targeted interventions to mitigate its effects in the future.
Room temperature compressed air-stable conductive copper films for flexible electronics
Authors: Pereira H. Jessica , Makarovsky Oleg , Amabilino David. B. , Newton Graham N. 
Published: July 2024

AbstractThe state-of-the-art technology of fabricating printed copper electronics is focussed largely on thermal sintering restricting transition towards heat sensitive flexible substrates. Herein we report a pioneering technology which eliminates the need for conventional sintering. Biopolymer-stabilised copper particles are prepared such that they can be compressed at room temperature to generate air-stable films with very low resistivities (2.05 – 2.33 × 10−8 Ω m at 20 °C). A linear positive correlation of resistivity with temperature verifies excellent metallic character and electron microscopy confirms the formation of films with low porosity (< 4.6%). An aqueous ink formulation is used to fabricate conductive patterns on filter paper, first using a fountain/dip pen and then printing to deposit more defined patterns (R < 2 Ω). The remarkable conductivity and stability of the films, coupled with the sustainability of the approach could precipitate a paradigm-shift in the use of copper inks for printable electronics.