bluuebunny/crossref_metadata_2025 huggingface dataset:
Not Enough: Efforts to Diversify Biogeosciences Benefit Limited Segment of Society
Authors: Barnes Rebecca T. , Wolford Michelle A. , Almaraz Maya , Cardarelli Emily L.
Published: July 2024

We examined data from the American Geophysical Union (AGU), the world's largest earth and space science society, to characterize demographics of multiple milestones in a biogeoscientists' career. Geoscientists of color and White women make up a smaller proportion of those participating in activities critical to transitioning from student to professional (submitting manuscripts, getting published, and receiving review invitations) in comparison to White men. Gender parity for biogeoscientists appears within reach at earlier career stages, with 37% of AGU Biogeosciences members and 41% of Biogeosciences attendees at the Fall Meeting identifying as women in 2020. The demographics of those successfully completing activities required for career advancement, that is, publishing and reviewing with Journal of Geophysical Research and Global Biogeochemical Cycles, two biogeoscience journals, illustrate more progress is needed. A large majority of manuscripts were submitted by men (73%), many of which have no co‐authors that identify as women or non‐binary geoscientists. Further, our communities' bias of who we suggest as reviewers, results in 85% of the reviewer invites going to White geoscientists and 63% going to men. Thus, while representation of diverse communities has improved in some areas, barriers to publishing result in authorship not reflective of society: only 25% of accepted manuscripts were led by self‐identified geoscientists of color and fewer than 5% were led by women geoscientists of color. It is critical that efforts to diversify move beyond gender, to ensure that scientists of color are also afforded the access and opportunity needed to thrive as biogeoscientists.
Bias Adjustment of Long‐Term (1961–2020) Daily Precipitation for China
Authors: Zhao Yanni , Chen Rensheng , Yang Zhiwei , Liu Yiwen , Zhao Linlin , Yang Yong , Wang Lei
Published: July 2024

The observation errors in precipitation gauges contribute to diminished precision in precipitation data sets. To reduce the impact of these errors, the World Meteorological Organization Solid Precipitation Intercomparison Experiments recommended the Double Fence Intercomparison Reference as a reference standard for precipitation measurements. This study proposed a new rain, snow, and mixed precipitation adjustment method for national standard precipitation gauges, using DFIR‐measured precipitation as the standard values. This method was used to adjust for systematic errors, including wind‐induced errors, wetting loss, and trace precipitation, in precipitation data collected by 785 stations in China from 1961 to 2020. After bias adjustment, the annual precipitation increased by 6.1–177.9 mm (with an average of 52.7 mm), accounting for 3.3%–52.1% (8.9%) of the total precipitation. The average annual error‐adjustment amounts for wind‐induced error, wetting loss, and trace precipitation were 21.9 (3.6% of total precipitation), 26.6 (4.7%), and 4.2 mm (1.3%), respectively. The adjustment percentage in winter was higher than that in summer, with the high‐adjusted‐percentage regions predominantly located in areas with drought, high proportion of snowfall, and strong wind speeds. Additionally, the annual average error‐adjustment amounts for rain, snow, and mixed precipitation respectively accounted for 5.2%, 38.2%, and 17.1% of their corresponding total amounts, indicating the significance of bias adjustment, particularly for snow and mixed precipitation, in the northern and Qinghai‐Tibet Plateau regions. Therefore, bias adjustment is necessary to enhance the accuracy of the precipitation data set in China.
Combined Inhibition of PI3K and STAT3 signaling effectively inhibits bladder cancer growth
Authors: Peng Weidong , Zhang Haojie , Yin Mingwei , Kong Dejie , Kang Liping , Teng Xinkun , Wang Jingjing , Chu Zhimin , Sun Yating , Long Pengpeng , Cui Chengying , Lyu Bin , Zhang Jinzhi , Xiao Han , Wu Mingqing , Wang Yongqiang , Li Yang
Published: July 2024

Bladder cancer is characterized by aberrant activation of the phosphatidylinositol-3-OH kinase (PI3K) signaling, underscoring the significance of directing therapeutic efforts toward the PI3K pathway as a promising strategy. In this study, we discovered that PI3K serves as a potent therapeutic target for bladder cancer through a high-throughput screening of inhibitory molecules. The PI3K inhibitor demonstrated a robust anti-tumor efficacy, validated both in vitro and in vivo settings. Nevertheless, the feedback activation of JAK1-STAT3 signaling reinstated cell and organoid survival, leading to resistance against the PI3K inhibitor. Mechanistically, the PI3K inhibitor suppresses PTPN11 expression, a negative regulator of the JAK-STAT pathway, thereby activating STAT3. Conversely, restoration of PTPN11 enhances the sensitivity of cancer cells to the PI3K inhibitor. Simultaneous inhibition of both PI3K and STAT3 with small-molecule inhibitors resulted in sustained tumor regression in patient-derived bladder cancer xenografts. These findings advocate for a combinational therapeutic approach targeting both PI3K and STAT3 pathways to achieve enduring cancer eradication in vitro and in vivo, underscoring their promising therapeutic efficacy for treating bladder cancer.
High-order brain interactions in ketamine during rest and task: a double-blinded cross-over design using portable EEG on male participants
Authors: Herzog Rubén , Barbey Florentine Marie , Islam Md Nurul , Rueda-Delgado Laura , Nolan Hugh , Prado Pavel , Krylova Marina , Izyurov Igor , Javaheripour Nooshin , Danyeli Lena Vera , Sen Zümrüt Duygu , Walter Martin , O’Donnell Patricio , Buhl Derek L. , Murphy Brian , Ibanez Agustin
Published: July 2024

Ketamine is a dissociative anesthetic that induces a shift in global consciousness states and related brain dynamics. Portable low-density EEG systems could be used to monitor these effects. However, previous evidence is almost null and lacks adequate methods to address global dynamics with a small number of electrodes. This study delves into brain high-order interactions (HOI) to explore the effects of ketamine using portable EEG. In a double-blinded cross-over design, 30 male adults (mean age = 25.57, SD = 3.74) were administered racemic ketamine and compared against saline infusion as a control. Both task-driven (auditory oddball paradigm) and resting-state EEG were recorded. HOI were computed using advanced multivariate information theory tools, allowing us to quantify nonlinear statistical dependencies between all possible electrode combinations. Ketamine induced an increase in redundancy in brain dynamics (copies of the same information that can be retrieved from 3 or more electrodes), most significantly in the alpha frequency band. Redundancy was more evident during resting state, associated with a shift in conscious states towards more dissociative tendencies. Furthermore, in the task-driven context (auditory oddball), the impact of ketamine on redundancy was more significant for predictable (standard stimuli) compared to deviant ones. Finally, associations were observed between ketamine’s HOI and experiences of derealization. Ketamine appears to increase redundancy and HOI across psychometric measures, suggesting these effects are correlated with alterations in consciousness towards dissociation. In comparisons with event-related potential (ERP) or standard functional connectivity metrics, HOI represent an innovative method to combine all signal spatial interactions obtained from low-density dry EEG in drug interventions, as it is the only approach that exploits all possible combinations between electrodes. This research emphasizes the potential of complexity measures coupled with portable EEG devices in monitoring shifts in consciousness, especially when paired with low-density configurations, paving the way for better understanding and monitoring of pharmacological-induced changes.
Olivar: towards automated variant aware primer design for multiplex tiled amplicon sequencing of pathogens
Authors: Wang Michael X. , Lou Esther G. , Sapoval Nicolae , Kim Eddie , Kalvapalle Prashant , Kille Bryce , Elworth R. A. Leo , Liu Yunxi , Fu Yilei , Stadler Lauren B. , Treangen Todd J.
Published: July 2024

Tiled amplicon sequencing has served as an essential tool for tracking the spread and evolution of pathogens. Over 15 million complete SARS-CoV-2 genomes are now publicly available, most sequenced and assembled via tiled amplicon sequencing. While computational tools for tiled amplicon design exist, they require downstream manual optimization both computationally and experimentally, which is slow and costly. Here we present Olivar, a first step towards a fully automated, variant-aware design of tiled amplicons for pathogen genomes. Olivar converts each nucleotide of the target genome into a numeric risk score, capturing undesired sequence features that should be avoided. In a direct comparison with PrimalScheme, we show that Olivar has fewer mismatches overlapping with primers and predicted PCR byproducts. We also compare Olivar head-to-head with ARTIC v4.1, the most widely used primer set for SARS-CoV-2 sequencing, and show Olivar yields similar read mapping rates (~90%) and better coverage to the manually designed ARTIC v4.1 amplicons. We also evaluate Olivar on real wastewater samples and found that Olivar has up to 3-fold higher mapping rates while retaining similar coverage. In summary, Olivar automates and accelerates the generation of tiled amplicons, even in situations of high mutation frequency and/or density. Olivar is available online as a web application at https://olivar.rice.edu and can be installed locally as a command line tool with Bioconda. Source code, installation guide, and usage are available at https://github.com/treangenlab/Olivar.
Overcoming laser phase noise for low-cost coherent optical communication
Authors: Fang Xiansong , Zhu Yixiao , Cai Xiang , Hu Weisheng , He Zhixue , Yu Shaohua , Zhang Fan
Published: July 2024

Artificial-intelligence-generated content has driven explosive data traffic growth in data-center interconnects. Traditional direct detection solutions struggle with limited spectral efficiency and distance, prompting the shift to coherent optics for cost-sensitive short-reach links. One specific challenge is integrating low-cost lasers while overcoming severe phase noise on high-order modulation formats. Here, we propose a residual carrier modulation scheme for precise and efficient carrier frequency and phase recovery. The residual optical carrier can continuously track phase fluctuations without redundancy compared with discrete time-domain pilots, and address the digital-to-analog convertor resolution reduction issue of frequency-domain digital pilots. In proof-of-concept experiments, we transmit a net 1-Tb/s probabilistic-shaped 256-ary quadrature amplitude modulated (PS-256-QAM) signal using a 3 MHz distributed feedback (DFB) laser. Our scheme improves bitrate by 41% compared to conventional time-domain pilots, achieving a record laser linewidth sum and symbol duration product of 6.89 × 10−5. This approach supports MHz linewidth DFB lasers in low-cost coherent optical communications.
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

Molecular 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

Increasing 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

Perturbations 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

Rhabdomyosarcoma (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

Spinal 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

Light-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

Bacteriocins 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

Homomorphic 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

Existing 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

Azole 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

Pollinator-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

In 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

Respiratory 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

Genomic 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

Spaceflight 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

The 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.
Organ systems of a Cambrian euarthropod larva
Authors: Smith Martin R. , Long Emma J. , Dhungana Alavya , Dobson Katherine J. , Yang Jie , Zhang Xiguang
Published: July 2024

The Cambrian radiation of euarthropods can be attributed to an adaptable body plan. Sophisticated brains and specialized feeding appendages, which are elaborations of serially repeated organ systems and jointed appendages, underpin the dominance of Euarthropoda in a broad suite of ecological settings. The origin of the euarthropod body plan from a grade of vermiform taxa with hydrostatic lobopodous appendages (‘lobopodian worms’)1,2 is founded on data from Burgess Shale-type fossils. However, the compaction associated with such preservation obscures internal anatomy3–6. Phosphatized microfossils provide a complementary three-dimensional perspective on early crown group euarthropods7, but few lobopodians8,9. Here we describe the internal and external anatomy of a three-dimensionally preserved euarthropod larva with lobopods, midgut glands and a sophisticated head. The architecture of the nervous system informs the early configuration of the euarthropod brain and its associated appendages and sensory organs, clarifying homologies across Panarthropoda. The deep evolutionary position of Youti yuanshi gen. et sp. nov. informs the sequence of character acquisition during arthropod evolution, demonstrating a deep origin of sophisticated haemolymph circulatory systems, and illuminating the internal anatomical changes that propelled the rise and diversification of this enduringly successful group.
A dataset of synthetic art dialogues with ChatGPT
Authors: Gil-Martín Manuel , Luna-Jiménez Cristina , Esteban-Romero Sergio , Estecha-Garitagoitia Marcos , Fernández-Martínez Fernando , D’Haro Luis Fernando
Published: July 2024

This paper introduces Art_GenEvalGPT, a novel dataset of synthetic dialogues centered on art generated through ChatGPT. Unlike existing datasets focused on conventional art-related tasks, Art_GenEvalGPT delves into nuanced conversations about art, encompassing a wide variety of artworks, artists, and genres, and incorporating emotional interventions, integrating speakers’ subjective opinions and different roles for the conversational agents (e.g., teacher-student, expert guide, anthropic behavior or handling toxic users). Generation and evaluation stages of GenEvalGPT platform are used to create the dataset, which includes 13,870 synthetic dialogues, covering 799 distinct artworks, 378 different artists, and 26 art styles. Automatic and manual assessment proof the high quality of the synthetic dialogues generated. For the profile recovery, promising lexical and semantic metrics for objective and factual attributes are offered. For subjective attributes, the evaluation for detecting emotions or subjectivity in the interventions achieves 92% of accuracy using LLM-self assessment metrics.
A peer-and self-group competitive behavior-based socio-inspired approach for household electricity conservation
Authors: Ramnath Gaikwad Sachin , Harikrishnan R. , Muyeen S. M. , Kukker Amit , Pohekar S. D. , Kotecha Ketan
Published: July 2024

This paper proposes a knowledge-based decision-making system for energy bill assessment and competitive energy consumption analysis for energy savings. As humans have a tendency toward comparison between peers and self-groups, the same concept of competitive behavior is utilized to design knowledge-based decision-making systems. A total of 225 house monthly energy consumption datasets are collected for Maharashtra state, along with a questionnaire-based survey that includes socio-demographic information, household appliances, family size, and some other parameters. After data collection, the pre-processing technique is applied for data normalization, and correlation technique-based key features are extracted. These features are used to classify different house categories based on consumption. A knowledge-based system is designed based on historical datasets for future energy consumption prediction and comparison with actual usage. These comparative studies provide a path for knowledgebase system design to generate monthly energy utilization reports for significant behavior changes for energy savings. Further, Linear Programming and Genetic Algorithms are used to optimize energy consumption for different household categories based on socio-demographic constraints. This will also benefit the consumers with an electricity bill evaluation range (i.e., normal, high, or very high) and find the energy conservation potential (kWh) as well as a cost-saving solution to solve real-world complex electricity conservation problem.
Progesterone modulates the immune microenvironment to suppress ovalbumin-induced airway inflammation by inhibiting NETosis
Authors: Wang Lin , Huang Feng-Ying , Dai Shu-Zhen , Fu Yongshu , Zhou Xiangdong , Wang Cai-Chun , Tan Guang-Hong , Li Qi
Published: July 2024

Studies have demonstrated that prior to puberty, girls have a lower incidence and severity of asthma symptoms compared to boys. This study aimed to explore the role of progesterone (P4), a sex hormone, in reducing inflammation and altering the immune microenvironment in a mouse model of allergic asthma induced by OVA. Female BALB/c mice with or without ovariectomy to remove the influence of sex hormones were used for the investigations. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue samples were collected for analysis. The results indicated that P4 treatment was effective in decreasing inflammation and mucus secretion in the lungs of OVA-induced allergic asthma mice. P4 treatment also reduced the influx of inflammatory cells into the BALF and increased the levels of Th1 and Th17 cytokines while decreasing the levels of Th2 and Treg cytokines in both BALF and lung microenvironment CD45+ T cells. Furthermore, P4 inhibited the infiltration of inflammatory cells into the lungs, suppressed NETosis, and reduced the number of pulmonary CD4+ T cells while increasing the number of regulatory T cells. The neutrophil elastase inhibitor GW311616A also suppressed airway inflammation and mucus production and modified the secretion of immune Th1, Th2, Th17, and Treg cytokines in lung CD45+ immune cells. These changes led to an alteration of the immunological milieu with increased Th1 and Th17 cells, accompanied by decreased Th2, Treg, and CD44+ T cells, similar to the effects of P4 treatment. Treatment with P4 inhibited NETosis by suppressing the p38 pathway activation, leading to reduced reactive oxygen species production. Moreover, P4 treatment hindered the release of double-stranded DNA during NETosis, thereby influencing the immune microenvironment in the lungs. These findings suggest that P4 treatment may be beneficial in reducing inflammation associated with allergic asthma by modulating the immune microenvironment. In conclusion, this research indicates the potential of P4 as a therapeutic agent for ameliorating inflammation in OVA-induced allergic asthma mice.
Identification and optimization of the key growth parameters involved in carotenoids production of the marine microalga Pavlova gyrans
Authors: Maciel Filipe , Berni Paulo , Geada Pedro , Teixeira José , Silva Joana , Vicente António
Published: July 2024

In this work, a multivariate analysis was carried out, using a Plackett–Burman (PB) design involving seventeen growth parameters, on carotenoids production of Pavlova gyrans (p < 0.10). Each assay was analysed regarding its content (mg g−1) of fucoxanthin (Fx), diatoxanthin, diadinoxanthin, β-carotene (βCar), α-carotene, and the sum of all carotenoids analysed individually (TCar). According to the statistical analysis, modified medium formulations were developed for the particular cases of Fx, βCar, and TCar. The study showed that Fx content was positively affected by nitrogen supplementation and lower light intensities. Higher concentrations of nitrogen and iron increased the final content of βCar as well. Similarly, salinity, light intensity, nitrogen, iron, and cobalt were identified as key factors in TCar production. The PB-based formulations showed significant improvements (p < 0.05) for TCar (11.794 mg g−1) and Fx (6.153 mg g−1) when compared to the control conditions (Walne’s medium—2.010 mg g−1). Furthermore, effective control of key variables (e.g., light intensity) throughout P. gyrans growth proved successful (p < 0.05), increasing the productivity of Fx (0.759 mg L−1 d−1) and TCar (1.615 mg L−1 d−1).
Readability analysis of ChatGPT's responses on lung cancer
Authors: Gencer Adem
Published: July 2024

For common diseases such as lung cancer, patients often use the internet to obtain medical information. As a result of advances in artificial intelligence and large language models such as ChatGPT, patients and health professionals use these tools to obtain medical information. The aim of this study was to evaluate the readability of ChatGPT-generated responses with different readability scales in the context of lung cancer. The most common questions in the lung cancer section of Medscape® were reviewed, and questions on the definition, etiology, risk factors, diagnosis, treatment, and prognosis of lung cancer (both NSCLC and SCLC) were selected. A set of 80 questions were asked 10 times to ChatGPT via the OpenAI API. ChatGPT's responses were tested using various readability formulas. The mean Flesch Reading Ease, Flesch-Kincaid Grade Level, Gunning FOG Scale, SMOG Index, Automated Readability Index, Coleman-Liau Index, Linsear Write Formula, Dale-Chall Readability Score, and Spache Readability Formula scores are at a moderate level (mean and standard deviation: 40.52 ± 9.81, 12.56 ± 1.66, 13.63 ± 1.54, 14.61 ± 1.45, 15.04 ± 1.97, 14.24 ± 1.90, 11.96 ± 2.55, 10.03 ± 0.63 and 5.93 ± 0.50, respectively). The readability levels of the answers generated by ChatGPT are "collage" and above and are difficult to read. Perhaps in the near future, the ChatGPT can be programmed to produce responses that are appropriate for people of different educational and age groups.
A novel translational model of atherosclerosis, the ex vivo pump-perfused amputated human limb model
Authors: Hartley Adam , Afoke Jonathan , Liu Guiqing , Owen Samuel , Hajhosseiny Reza , Hassen Kimberly , Punjabi Prakash , Haskard Dorian , Shalhoub Joseph , Khamis Ramzi
Published: July 2024

The preclinical study of atherosclerosis has traditionally centred around the use of small animal models, translating to large animal models, prior to first-in-man studies. We propose to disrupt this paradigm by designing an ex vivo pump perfused human limb model. The novel model consists of taking a freshly amputated limb and incorporating it into an ex situ pump-perfused bypass system (akin to extracorporeal membrane oxygenation), circulating warmed, oxygenated blood. The circuit incorporates an introducer sheath and guiding catheter for intravascular imaging and X-ray angiography. Regular monitoring is performed using blood gas analysis, aiming for physiological parameters. The model maintains oxygen saturations > 99% for the length of perfusion (up to 6-h). Clinical grade X-ray angiography, intravascular ultrasound and optical coherence tomography have been successfully performed. Indocyanine green, a near-infrared fluorescent dye that localises to atherosclerotic plaque, has been injected into the system and left to circulate for 90-min. Fluorescence reflectance imaging of the dissected arterial bed confirmed uptake in areas of calcific atherosclerotic plaque on intravascular imaging. This is the first demonstration of an ex vivo pump-perfused “living” limb experimental model of atherosclerosis, which shows promise for future studies in translational interventional imaging and molecular targeting.
Cross-architecture tuning of silicon and SiGe-based quantum devices using machine learning
Authors: Severin B. , Lennon D. T. , Camenzind L. C. , Vigneau F. , Fedele F. , Jirovec D. , Ballabio A. , Chrastina D. , Isella G. , de Kruijf M. , Carballido M. J. , Svab S. , Kuhlmann A. V. , Geyer S. , Froning F. N. M. , Moon H. , Osborne M. A. , Sejdinovic D. , Katsaros G. , Zumbühl D. M. , Briggs G. A. D. , Ares N.
Published: July 2024

The potential of Si and SiGe-based devices for the scaling of quantum circuits is tainted by device variability. Each device needs to be tuned to operation conditions and each device realisation requires a different tuning protocol. We demonstrate that it is possible to automate the tuning of a 4-gate Si FinFET, a 5-gate GeSi nanowire and a 7-gate Ge/SiGe heterostructure double quantum dot device from scratch with the same algorithm. We achieve tuning times of 30, 10, and 92 min, respectively. The algorithm also provides insight into the parameter space landscape for each of these devices, allowing for the characterization of the regions where double quantum dot regimes are found. These results show that overarching solutions for the tuning of quantum devices are enabled by machine learning.