bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum apolipoprotein H determines ferroptosis resistance by modulating cellular lipid composition
Authors: He Xiang , Zhang Jiahui , Huang Masha , Wang Jie , Yang Simin , Yu Xiang , Xu Yingjie , Yang Wen 
Published: October 2024

AbstractFerroptosis is a regulated cell death process dependent on iron, triggered by the accumulation of lipid peroxidation. The environmental context significantly impacts cellular sensitivities to ferroptosis. Serum, constituting the extracellular fluid composition in vivo, provides crucial environmental biomolecules. In this study, we investigated the influence of sera on ferroptosis induction, pinpointing the serum protein apolipoprotein H (APOH) as a pivotal inhibitor of ferroptosis. Moreover, we elucidated that APOH suppresses ferroptosis by activating the phosphoinositide 3-kinase (PI3K)-AKT-sterol regulatory element-binding proteins (SREBPs) pathway, thereby elevating stearoyl-CoA desaturase (SCD) levels and augmenting cellular monounsaturated fatty acid-containing phospholipids (MUFA-PLs). Furthermore, ApoHinfer, the peptide derivative of the active region of APOH, mimics its ferroptosis inhibitory activity. Our findings underscore the critical role of serum protein APOH in the inhibition of ferroptosis and indicates potential therapeutic applications in treating cancer and diseases associated with ferroptosis.
Developing an erythrocyte‒MHC-I conjugate for cancer treatment
Authors: Liu Yuehua , Nie Xiaoqian , Yao Xingyun , Shou Huafeng , Yuan Yang , Ge Yun , Tong Xiangmin , Lee Hsiang-Ying , Gao Xiaofei 
Published: October 2024

AbstractMature erythrocytes are known to lack major histocompatibility complex (MHC) proteins. However, the presence of MHC molecules on erythrocytes has been occasionally reported, though without a defined function. In this study, we designed erythrocyte conjugated solely with a fusion protein consisting of an antigenic peptide linked to MHC class I (MHC-I) protein, termed MHC-I‒Ery. The modified erythrocyte, decorated with the peptide derived from human papillomavirus (HPV) 16 oncoprotein E6/E7, effectively activated antigen-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from HPV16+ cervical cancer patients. Additionally, MHC-I‒Ery monotherapy was shown to inhibit antigen-positive tumor growth in mice. This treatment immediately activated CD8+ T cells and reduced suppressive myeloid cells in the spleen, leading to systemic anti-tumor activity. Safety and tolerability evaluations of MHC-I‒Ery in non-human primates further supported its clinical potential. Our results first demonstrated that erythrocytes equipped solely with antigen peptide‒MHC-I complexes can robustly stimulate the immune system, suggesting a novel and promising approach for advancing cancer immunotherapy.
Palladium-catalyzed difluorocarbene transfer enables access to enantioenriched chiral spirooxindoles
Authors: Nie Zhiwen , Wu Keqin , Zhan Xiaohang , Yang Weiran , Lian Zhong , Lin Shaoquan , Wang Shou-Guo , Yin Qin 
Published: October 2024

AbstractWe disclose herein an unprecedented Pd-catalyzed difluorocarbene transfer reaction, which assembles a series of structurally interesting chiral spiro ketones with generally over 90% ee. Commercially available BrCF2CO2K serves as the difluorocarbene precursor, which is harnessed as a user-friendly and safe carbonyl source in this transformation. Preliminary mechanistic studies exclude the formation of free CO in the reaction process, and importantly, we also find that BrCF2CO2K outcompete gaseous CO and several common CO surrogates in this asymmetric process. The reaction mechanism, including the in-situ progressive release of the difluorocarbene, the rapid migratory insertion of ArPd(II) = CF2 species, and subsequent defluorination hydrolysis by water to introduce the carbonyl group, accounts for the overall high efficiency and uniqueness. This work clearly showcases the advantage and potential of the difluorocarbene in synthesis and supplies a mechanistically distinct route for asymmetric carbonylative cyclization reactions.
Technology availability, sector policies and behavioral change are complementary strategies for achieving net-zero emissions
Authors: Strefler Jessica , Merfort Leon , Bauer Nico , Stevanović Miodrag , Tänzler Dennis , Humpenöder Florian , Klein David , Luderer Gunnar , Pehl Michaja , Pietzcker Robert C. , Popp Alexander , Rodrigues Renato , Rottoli Marianna , Kriegler Elmar 
Published: October 2024

AbstractIn this study, we analyze the effects of technology availability, political coordination, and behavioral change on transformation pathways toward net-zero greenhouse gas emissions in the European Union by 2050. We implemented an iterative stakeholder dialogue to co-design the scenarios that were calculated using a global multi-regional energy-economy-land-climate model. We find that in scenarios without behavioral change and with restriction of technologies, the target of greenhouse gas neutrality in the European Union cannot be reached. Already a target of 200 Mt CO2eq/yr requires CO2 prices above 100 €/tCO2 in 2030 across all sectors in all scenarios. The required CO2 price can increase to up to 450 €/tCO2 by 2030 if technologies are constrained, if no complementary regulatory measures are implemented, and if changes in consumer behavior towards a more sustainable lifestyle do not materialize.
A reconfigurable and conformal liquid sensor for ambulatory cardiac monitoring
Authors: Zhao Xun , Zhou Yihao , Kwak William , Li Aaron , Wang Shaolei , Dallenger Marklin , Chen Songyue , Zhang Yuqi , Lium Allison , Chen Jun 
Published: October 2024

AbstractThe severe mismatch between solid bioelectronics and dynamic biological tissues has posed enduring challenges in the biomonitoring community. Here, we developed a reconfigurable liquid cardiac sensor capable of adapting to dynamic biological tissues, facilitating ambulatory cardiac monitoring unhindered by motion artifacts or interference from other biological activities. We employed an ultrahigh-resolution 3D scanning technique to capture tomographic images of the skin on the wrist. Then, we established a theoretical model to gain a deep understanding of the intricate interaction between our reconfigurable sensor and dynamic biological tissues. To properly elucidate the advantages of this sensor, we conducted cardiac monitoring alongside benchmarks such as the electrocardiogram. The liquid cardiac sensor was demonstrated to produce stable signals of high quality (23.1 dB) in ambulatory settings.
Cryo-EM structures of the human P2X1 receptor reveal subtype-specific architecture and antagonism by supramolecular ligand-binding
Authors: Oken Adam C. , Lisi Nicolas E. , Ditter Ismayn A. , Shi Haoyuan , Nechiporuk Nadia A. , Mansoor Steven E. 
Published: October 2024

AbstractP2X receptors are a family of seven trimeric non-selective cation channels that are activated by extracellular ATP to play roles in the cardiovascular, neuronal, and immune systems. Although it is known that the P2X1 receptor subtype has increased sensitivity to ATP and fast desensitization kinetics, an underlying molecular explanation for these subtype-selective features is lacking. Here we report high-resolution cryo-EM structures of the human P2X1 receptor in the apo closed, ATP-bound desensitized, and the high-affinity antagonist NF449-bound inhibited states. The apo closed and ATP-bound desensitized state structures of human P2X1 define subtype-specific properties such as distinct pore architecture and ATP-interacting residues. The NF449-bound inhibited state structure of human P2X1 reveals that NF449 has a unique dual-ligand supramolecular binding mode at the interface of neighboring protomers, inhibiting channel activation by overlapping with the canonical P2X receptor ATP-binding site. Altogether, these data define the molecular pharmacology of the human P2X1 receptor laying the foundation for structure-based drug design.
Flexible electronic-photonic 3D integration from ultrathin polymer chiplets
Authors: Huang Yunxiang , Li Gen , Bai Tianyu , Shin Yieljae , Wang Xiaoxin , More Alexander Ian , Boucher Pierre , Chandrasekaran Chandramouli , Liu Jifeng , Fang Hui 
Published: October 2024

AbstractIntegrating flexible electronics and photonics can create revolutionary technologies, but combining these components on a single polymer device has been difficult, particularly for high-volume manufacturing. Here, we present a robust chiplet-level heterogeneous integration of polymer-based circuits (CHIP), where ultrathin polymer electronic and optoelectronic chiplets are vertically bonded at room temperature and shaped into application-specific forms with monolithic Input/Output (I/O). This process was used to develop a flexible 3D integrated optrode with high-density microelectrodes for electrical recording, micro light-emitting diodes (μLEDs) for optogenetic stimulation, temperature sensors for bio-safe operations, and shielding designs to prevent optoelectronic artifacts. CHIP enables simple, high-yield, and scalable 3D integration, double-sided area utilization, and miniaturization of connection I/O. Systematic characterization demonstrated the scheme’s success and also identified frequency-dependent origins of optoelectronic artifacts. We envision CHIP being applied to numerous polymer-based devices for a wide range of applications.
Protective effects of cilostazol via the HNF1α/FXR signalling pathway and anti-apoptotic mechanisms in a rat model of estrogen-induced intrahepatic cholestasis
Authors: Hassan Marwa , Salem Maha B. , Hammam Olfat A. , ElZallat Mohamed 
Published: October 2024

AbstractCurrently, there is a lack of targeted medications for estrogen-induced intrahepatic cholestasis (EIC) and the primary objective in managing this condition is to safeguard liver function. Consequently, this study was conducted to examine the pharmacological efficacy of cilostazol (CTZ) in the management of EIC and explore its underlying mechanisms through the use of an animal model. Thirty female Sprague-Dawley rats were divided into five groups of six animals each: Normal group, 17-ethinylestradiol (EE)-induced intrahepatic cholestasis group, EE + ursodeoxycholic acid (UDCA)-treated group, EE + CTZ (5 mg/kg)-treated group, and EE + CTZ (10 mg/kg)-treated group. It was found that the therapeutic efficacy of UDCA and low dosage of CTZ (5 mg/kg) was comparable. Nevertheless, when CTZ was administered at a dose of 10 mg/kg, it resulted in the normalization of all liver function parameters, oxidative stress, and pro-inflammatory markers, together with improvement in the histopathological derangements and hepatocytic apoptosis. These effects were mediated through the activation of the hepatocyte nuclear factor-1 alpha (HNF1α)/Farnesoid X receptor (FXR) pathway with subsequent down-regulation of the bile acids (BAs) synthesis enzyme; cholesterol 7α-hydroxylase (CYP7A1), and up-regulation of the BAs-metabolizing enzyme; cytochrome P450 (CYP)3A1 and the bile salt export pump; BSEP. Therefore, the administration of CTZ in a dose-dependent manner can protect against EIC through regulating the HNF1α/FXR pathway and anti-apoptotic mechanisms. This implies that CTZ exhibits considerable promise as a therapeutic agent for the treatment of cholestatic liver disorders.
Structural characterization of green fluorescent protein in the I-state
Authors: Takeda Ryota , Tsutsumi Erika , Okatsu Kei , Fukai Shuya , Takeda Kazuki 
Published: October 2024

AbstractGreen fluorescent protein (GFP) is widely utilized as a fluorescent tag in biochemical fields. Whereas the intermediate (I) state has been proposed in the photoreaction cycle in addition to the A and B states, until now the structure of I has only been estimated by computational studies. In this paper, we report the crystal structures of the I stabilizing variants of GFP at high resolutions where respective atoms can be observed separately. Comparison with the structures in the other states highlights the structural feature of the I state. The side chain of one of the substituted residues, Val203, adopts the gauche- conformation observed for Thr203 in the A state, which is different from the B state. On the other hand, His148 interacts with the chromophore by ordinary hydrogen bonding with a distance of 2.85 Å, while the weaker interaction by longer distances is observed in the A state. Therefore, it was indicated that it is possible to distinguish three states A, B and I by the two hydrogen bond distances Oγ-Thr203···Oη-chromophore and Nδ1-His148···Oη-chromophore. We discuss the characteristics of the I intermediate of wild-type GFP on the bases of the structure estimated from the variant structures by quantum chemical calculations.
Assessing the effect of therapeutic level of oxytetracycline dihydrate on pharmacokinetics and biosafety in Oncorhynchus mykiss (Walbaum, 1792)
Authors: Pathak Richa , Mallik Sumanta Kumar , Patil Prasanna Kumar , Kala Krishna , Shahi Neetu , Nadella Ranjit Kumar , Pandey Nityanand , Kunal Kishor , Pandey Pramod Kumar 
Published: October 2024

AbstractThe aim of the experiment was to investigate the pharmacokinetics of oxytetracycline dihydrate after a single oral administration of 80 mg kg−1 day−1 in rainbow trout and assess its biosafety at concentration of 80, 240, 400, and 800 mg kg−1 day−1 over 30 days, focusing on various aspects such as effective feed consumption, physiological responses, drug tolerance, and detection of low drug concentrations in rainbow trout. The pharmacokinetics study spanned a duration of 5 days, while the assessment of biosafety extended for a 30-day safety margin, followed by a subsequent 10-day residual analysis. Pharmacokinetic analysis revealed slow absorption with low-rate constant in tissues. Absorption rates vary among tissues, with the gill showing the highest rate (0.011 h−1) and plasma exhibiting the slowest (0.0002 h−1). According to pharmacokinetic analysis, the highest concentration, Cmax (µg kg−1) was observed in the kidney (9380 µg kg−1) and gill (8710 µg kg−1), and lowest in muscle (2460 µg kg−1). The time (Tmax) to reach peak concentration (Cmax) varied among tissues, ranging from 3 h in the gill to 32 h in the muscle, with 24 h in plasma, 32 h in the kidney, and 16 h in both the liver and skin. The liver and kidney had the highest area under the concentration-time curve (AUC(0−128)), indicating widespread drug distribution. Prolonged elimination occurred at varying rates across tissues, with the gill showing the highest rate. The study found that OTC concentrations exceeded the LOD and LOQ values. Biosafety evaluation showed effective feed consumption, physiological responses, and low drug concentrations in muscle at the recommended dosage of 80 mg kg−1 fish day−1.
Single-cell phenotypic profiling and backtracing exposes and predicts clinically relevant subpopulations in isogenic Staphylococcus aureus communities
Authors: Hira Jonathan , Singh Bhupender , Halder Tirthankar , Mahmutovic Anel , Ajayi Clement , Sekh Arif Ahmed , Hegstad Kristin , Johannessen Mona , Lentz Christian S. 
Published: October 2024

AbstractIsogenic bacterial cell populations are phenotypically heterogenous and may include subpopulations of antibiotic tolerant or heteroresistant cells. The reversibility of these phenotypes and lack of biomarkers to differentiate functionally different, but morphologically identical cells is a challenge for research and clinical detection. To overcome this, we present ´Cellular Phenotypic Profiling and backTracing (CPPT)´, a fluorescence-activated cell sorting platform that uses fluorescent probes to visualize and quantify cellular traits and connects this phenotypic profile with a cell´s experimentally determined fate in single cell-derived growth and antibiotic susceptibility analysis. By applying CPPT on Staphylococcus aureus we phenotypically characterized dormant cells, exposed bimodal growth patterns in colony-derived cells and revealed different culturability of single cells on solid compared to liquid media. We demonstrate that a fluorescent vancomycin conjugate marks cellular subpopulations of vancomycin-intermediate S. aureus with increased likelihood to survive antibiotic exposure, showcasing the value of CPPT for discovery of clinically relevant biomarkers.
The interaction between plastics and microalgae affects community assembly and nutrient availability
Authors: Binda Gilberto , Carnati Stefano , Costa Margarida , Hostyeva Vladyslava , Leu Eva , Skjelbred Birger , Spanu Davide , Šupraha Luka , Trotta Sara , Vogelsang Christian , Nizzetto Luca 
Published: October 2024

AbstractThe presence of plastics and microplastics in water environments has raised concerns for potential negative impacts. The broader ecological implications for ecosystem functioning are, however, still unknown. The interaction between phytoplankton community and plastics has, for example, been overlooked. Here, we investigated the role of plastic as a substrate for biofilm growth and how this affects the dispersal of terrestrial microalgae, potentially altering the assembly of pelagic communities. When exposing an artificially assembled microalgae community to pristine and biofouled plastic under laboratory-controlled conditions, we found that only biofouled plastic affected the final community structure and the content of available nutrients in water. This is due to the exchanged algal species between the biofilm and the pelagic community. The results from this batchwise pilot scale study indicate that plastic can act as a substrate for benthic and pelagic species, potentially affecting ecosystem functions, which have been overlooked so far.
Genome-wide analysis tracks the emergence of intraspecific polyploids in Phragmites australis
Authors: Wang Cui , Liu Lele , Yin Meiqi , Eller Franziska , Brix Hans , Wang Tong , Salojärvi Jarkko , Guo Weihua 
Published: October 2024

AbstractPolyploidization plays an important role in plant speciation and adaptation. To address the role of polyploidization in grass diversification, we studied Phragmites australis, an invasive species with intraspecific variation in chromosome numbers ranging from 2n = 36 to 144. We utilized a combined analysis of ploidy estimation, phylogeny, population genetics and model simulations to investigate the evolution of P. australis. Using restriction site-associated DNA sequencing (RAD-seq), we conducted a genome-wide analysis of 88 individuals sourced from diverse populations worldwide, revealing the presence of six distinct intraspecific lineages with extensive genetic admixture. Each lineage was characterized by a specific ploidy level, predominantly tetraploid or octoploid, indicative of multiple independent polyploidization events. The population size of each lineage has declined moderately in history while remaining large, except for the North American native and the US Land types, which experienced constant population size contraction throughout their history. Our investigation did not identify direct association between polyploidization events and grass invasions. Nonetheless, we observed octoploid and hexaploid lineages at contact zones in Romania, Hungary, and South Africa, suggestively due to genomic conflicts arising from allotetraploid parental lineages.
Modeled temperature, mortality impact and external benefits of cool roofs and rooftop photovoltaics in London
Authors: Simpson Charles H. , Brousse Oscar , Taylor Tim , Grellier James , Taylor Jonathon , Fleming Lora E. , Davies Mike , Heaviside Clare 
Published: October 2024

AbstractPopulation exposure to high temperatures poses health risks and increases mortality. ‘Cool roofs’ (high-albedo roofs) and rooftop photovoltaics (RPV) may reduce temperatures in urban areas. Here, using advanced urban climate modeling, we model impacts of these measures on air temperature and heat-related mortality in London during the record-breaking hot summer of 2018. We estimate changes in mean near-surface air temperature of −0.3 °C in the RPV scenario and −0.8 °C in the cool roof scenario. We find that the heat-related mortality in this period (estimated 655–920) could have been reduced by 96 (12%) by RPV, or 249 (32%) by cool roofs, in scenarios where all roofs have these measures. Monetized using value of statistical life, we estimate benefits for RPV and cool roofs of £237 M and £615 M, respectively. We estimate that up to 20 TWh of electrical energy would be generated in the full RPV scenario. We show that, for conditions such as in London June–August 2018, RPV or cool roofs may reduce near-surface air temperatures and associated heat-related mortality, with cool roofs having a larger effect.
Scalability challenges of machine learning models for estimating walking and cycling volumes in large networks
Authors: Saberi Meead , Lilasathapornkit Tanapon 
Published: October 2024

AbstractThis study explores the scalability of machine learning models for estimating walking and cycling volumes across the extensive New South Wales (NSW) Six Cities Region in Australia using mobile phone and crowdsourced data. Previous research has focused on localized applications, missing the complexities of larger networks. The research addresses this gap by identifying unique challenges such as the scarcity and representativeness of observed count data, gaps in the crowdsourced and mobile phone data, and inconsistencies in link-level volume estimates. We propose and demonstrate the application of strategies like enhancing geographical diversity of observed count data and employing an extensive cross-validation approach in model training and testing. By leveraging various auxiliary datasets, the study demonstrates the effectiveness of these strategies in improving model performance. These findings provide valuable insights for transportation modelers, policymakers, and urban planners, offering a robust framework for supporting sustainable transportation infrastructure and policies with advanced data-driven methodologies.
Identification of dominant instability modes in power systems based on spatial‐temporal feature mining and TSOA optimization
Authors: Yu Miao , Sun Jianqun , Tian Shuoshuo , Zhang Shouzhi , Wei Jingjing , Wu Yixiao 
Published: October 2024

AbstractThe recognition of the transient dominant instability mode is of great significance for rapidly and accurately formulating transient emergency decisions in power systems. In response to the challenge of accurately distinguishing between angle instability and voltage instability, which are coupled in actual power grids, this paper explores the mapping relationship between simulation data and the stable state of the system, as well as the dominant instability mode. The method enables real‐time identification of the dominant instability mode, which bypasses complex physical mechanisms. Firstly, spatio‐temporal feature mining is conducted, where convolutional neural networks are employed to learn crucial local features of transient curves, and bidirectional gated recurrent unit s utilized to learn transient features over time sequences. Next, a multihead attention mechanism is introduced to enhance sensitivity to important time steps in the sequence data. Finally, the transit search optimization algorithm optimizes the global model parameters, further increasing the accuracy of the model. Using the IEEE 10‐machine and 39‐node system as an example for simulation, the results validate that the proposed method exhibits significant advantages in terms of accuracy and applicability compared with other machine learning methods.