bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer
Authors: Casacuberta-Serra Sílvia , González-Larreategui Íñigo , Capitán-Leo Daniel , Soucek Laura 
Published: August 2024

AbstractRAS and MYC rank amongst the most commonly altered oncogenes in cancer, with RAS being the most frequently mutated and MYC the most amplified. The cooperative interplay between RAS and MYC constitutes a complex and multifaceted phenomenon, profoundly influencing tumor development. Together and individually, these two oncogenes regulate most, if not all, hallmarks of cancer, including cell death escape, replicative immortality, tumor-associated angiogenesis, cell invasion and metastasis, metabolic adaptation, and immune evasion. Due to their frequent alteration and role in tumorigenesis, MYC and RAS emerge as highly appealing targets in cancer therapy. However, due to their complex nature, both oncogenes have been long considered “undruggable” and, until recently, no drugs directly targeting them had reached the clinic. This review aims to shed light on their complex partnership, with special attention to their active collaboration in fostering an immunosuppressive milieu and driving immunotherapeutic resistance in cancer. Within this review, we also present an update on the different inhibitors targeting RAS and MYC currently undergoing clinical trials, along with their clinical outcomes and the different combination strategies being explored to overcome drug resistance. This recent clinical development suggests a paradigm shift in the long-standing belief of RAS and MYC “undruggability”, hinting at a new era in their therapeutic targeting.
The JAK-STAT pathway: from structural biology to cytokine engineering
Authors: Lv You , Qi Jianxun , Babon Jeffrey J. , Cao Longxing , Fan Guohuang , Lang Jiajia , Zhang Jin , Mi Pengbing , Kobe Bostjan , Wang Faming 
Published: August 2024

AbstractThe Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway serves as a paradigm for signal transduction from the extracellular environment to the nucleus. It plays a pivotal role in physiological functions, such as hematopoiesis, immune balance, tissue homeostasis, and surveillance against tumors. Dysregulation of this pathway may lead to various disease conditions such as immune deficiencies, autoimmune diseases, hematologic disorders, and cancer. Due to its critical role in maintaining human health and involvement in disease, extensive studies have been conducted on this pathway, ranging from basic research to medical applications. Advances in the structural biology of this pathway have enabled us to gain insights into how the signaling cascade operates at the molecular level, laying the groundwork for therapeutic development targeting this pathway. Various strategies have been developed to restore its normal function, with promising therapeutic potential. Enhanced comprehension of these molecular mechanisms, combined with advances in protein engineering methodologies, has allowed us to engineer cytokines with tailored properties for targeted therapeutic applications, thereby enhancing their efficiency and safety. In this review, we outline the structural basis that governs key nodes in this pathway, offering a comprehensive overview of the signal transduction process. Furthermore, we explore recent advances in cytokine engineering for therapeutic development in this pathway.
Twenty-year trends of potentially avoidable hospitalizations for hypertension in Switzerland
Authors: Marques-Vidal Pedro , Maung Ko Ko , Gouveia Alexandre 
Published: August 2024

AbstractWe assessed the trends, characteristics, and consequences of potentially avoidable hospitalizations (PAH) for hypertension in Switzerland, for the period 1998 to 2018. Data from 117,507 hospitalizations (62.1% women), minimum age 20 years. Hospitalizations with hypertension as the main cause for admission were eligible. PAH for hypertension was defined according to the Organization for Economic Cooperation and Development criteria. The age-standardized rates of PAH for hypertension increased from 43 in 1998 to 81 per 100,000 in 2004, to decrease to 57 per 100,000 inhabitants in 2018. Compared to non-PAH, patients with PAH for hypertension were younger, more frequently women (66.9% vs. 56.7%), non-Swiss nationals (15.9% vs. 10.9%), were more frequently admitted as an emergency (78.9% vs. 59.5%), and by the patient’s initiative (33.1% vs. 14.1%). Patients with PAH had also fewer comorbidities, as per the Charlson’s index. Patients with PAH for hypertension were more frequently hospitalized in a semi-private or private setting, stayed less frequently in the intensive care unit (4.6% vs. 7.3%), were discharged more frequently home (91.4% vs. 73.0%), and had a shorter length of stay than patients with non-PAH for hypertension: median and [interquartile range] 5 [3–8] vs. 9 [4–15] days. In 2018, the total costs of PAH were estimated at 16.5 million CHF, corresponding to a median cost of 4936 [4445–4961] Swiss Francs per stay. We conclude that in Switzerland, PAH have increased, represent a considerable fraction of hospitalizations for hypertension, and carry a non-negligible health cost.
Self-stacked small molecules for ultrasensitive, substrate-free Raman imaging in vivo
Authors: Gao Shuai , Zhang Yongming , Cui Kai , Zhang Sihang , Qiu Yuanyuan , Liao Yunhui , Wang Haoze , Yu Sheng , Ma Liyang , Chen Hongzhuan , Ji Minbiao , Fang Xiaohong , Lu Wei , Xiao Zeyu 
Published: August 2024

AbstractRaman spectroscopy using surface-enhanced Raman scattering (SERS) nanoprobes represents an ultrasensitive and high-precision technique for in vivo imaging. Clinical translation of SERS nanoprobes has been hampered by biosafety concerns about the metal substrates used to enhance Raman signals. We report a set of small molecules with bis-thienyl-substituted benzobisthiadiazole structures that enhance Raman signal through self-stacking rather than external substrates. In our technique, called stacking-induced charge transfer-enhanced Raman scattering (SICTERS), the self-stacked small molecules form an ordered spatial arrangement that enables three-dimensional charge transfer between neighboring molecules. The Raman scattering cross-section of SICTERS nanoprobes is 1350 times higher than that of conventional SERS gold nanoprobes of similar particle size. SICTERS outperforms SERS in terms of in vivo imaging sensitivity, resolution and depth. SICTERS is capable of noninvasive Raman imaging of blood and lymphatic vasculatures, which has not been achieved by SERS. SICTERS represents an alternative technique to enhance Raman scattering for guiding the design of ultrasensitive substrate-free Raman imaging probes.
Mechanism for controlled assembly of transcriptional condensates by Aire
Authors: Huoh Yu-San , Zhang Qianxia , Törner Ricarda , Baca Sylvan C. , Arthanari Haribabu , Hur Sun 
Published: August 2024

AbstractTranscriptional condensates play a crucial role in gene expression and regulation, yet their assembly mechanisms remain poorly understood. Here, we report a multi-layered mechanism for condensate assembly by autoimmune regulator (Aire), an essential transcriptional regulator that orchestrates gene expression reprogramming for central T cell tolerance. Aire condensates assemble on enhancers, stimulating local transcriptional activities and connecting disparate inter-chromosomal loci. This functional condensate formation hinges upon the coordination between three Aire domains: polymerization domain caspase activation recruitment domain (CARD), histone-binding domain (first plant homeodomain (PHD1)), and C-terminal tail (CTT). Specifically, CTT binds coactivators CBP/p300, recruiting Aire to CBP/p300-rich enhancers and promoting CARD-mediated condensate assembly. Conversely, PHD1 binds to the ubiquitous histone mark H3K4me0, keeping Aire dispersed throughout the genome until Aire nucleates on enhancers. Our findings showed that the balance between PHD1-mediated suppression and CTT-mediated stimulation of Aire polymerization is crucial to form transcriptionally active condensates at target sites, providing new insights into controlled polymerization of transcriptional regulators.
Acyl-CoA synthetase 6 controls rod photoreceptor function and survival by shaping the phospholipid composition of retinal membranes
Authors: Wang Yixiao , Becker Silke , Finkelstein Stella , Dyka Frank M. , Liu Haitao , Eminhizer Mark , Hao Ying , Brush Richard S. , Spencer William J. , Arshavsky Vadim Y. , Ash John D. , Du Jianhai , Agbaga Martin-Paul , Vinberg Frans , Ellis Jessica M. , Lobanova Ekaterina S. 
Published: August 2024

AbstractThe retina is light-sensitive neuronal tissue in the back of the eye. The phospholipid composition of the retina is unique and highly enriched in polyunsaturated fatty acids, including docosahexaenoic fatty acid (DHA). While it is generally accepted that a high DHA content is important for vision, surprisingly little is known about the mechanisms of DHA enrichment in the retina. Furthermore, the biological processes controlled by DHA in the eye remain poorly defined as well. Here, we combined genetic manipulations with lipidomic analysis in mice to demonstrate that acyl-CoA synthetase 6 (Acsl6) serves as a regulator of the unique composition of retinal membranes. Inactivation of Acsl6 reduced the levels of DHA-containing phospholipids, led to progressive loss of light-sensitive rod photoreceptor neurons, attenuated the light responses of these cells, and evoked distinct transcriptional response in the retina involving the Srebf1/2 (sterol regulatory element binding transcription factors 1/2) pathway. This study identifies one of the major enzymes responsible for DHA enrichment in the retinal membranes and introduces a model allowing an evaluation of rod functioning and pathology caused by impaired DHA incorporation/retention in the retina.
Endometriotic lesions exhibit distinct metabolic signature compared to paired eutopic endometrium at the single-cell level
Authors: Sarsenova Meruert , Lawarde Ankita , Pathare Amruta D. S. , Saare Merli , Modhukur Vijayachitra , Soplepmann Pille , Terasmaa Anton , Käämbre Tuuli , Gemzell-Danielsson Kristina , Lalitkumar Parameswaran Grace Luther , Salumets Andres , Peters Maire 
Published: August 2024

AbstractCurrent therapeutics of endometriosis focus on hormonal disruption of endometriotic lesions (ectopic endometrium, EcE). Recent findings show higher glycolysis utilization in EcE, suggesting non-hormonal strategy for disease treatment that addresses cellular metabolism. Identifying metabolically altered cell types in EcE is important for targeted metabolic drug therapy without affecting eutopic endometrium (EuE). Here, using single-cell RNA-sequencing, we examine twelve metabolic pathways in paired samples of EuE and EcE from women with confirmed endometriosis. We detect nine major cell types in both EuE and EcE. Metabolic pathways are most differentially regulated in perivascular, stromal, and endothelial cells, with the highest changes in AMPK signaling, HIF-1 signaling, glutathione metabolism, oxidative phosphorylation, and glycolysis. We identify transcriptomic co-activation of glycolytic and oxidative metabolism in perivascular and stromal cells of EcE, indicating a critical role of metabolic reprogramming in maintaining endometriotic lesion growth. Perivascular cells, involved in endometrial stroma repair and angiogenesis, may be potential targets for non-hormonal treatment of endometriosis.
Amorphous shear band formation in crystalline Si-anodes governs lithiation and capacity fading in Li-ion batteries
Authors: Häusler Michael , Stamati Olga , Gammer Christoph , Moitzi Franco , Sinojiya Rahulkumar Jagdishbhai , Villanova Julie , Sartory Bernhard , Scheiber Daniel , Keckes Jozef , Fuchsbichler Bernd , Koller Stefan , Brunner Roland 
Published: August 2024

AbstractThe cycling stability of Li-ion batteries is commonly attributed to the formation of the solid electrolyte interphase (SEI) layer, which is generated on the active material surface during electrochemical reactions in battery operation. Silicon experiences large volume changes upon the Li-insertion and extraction, leading to the amorphization of the silicon-interface due to the permeation of the Li-ions into the silicon. Here, we discover how generated non-hydrostatic strain upon electrochemical cycling further triggers dislocation and eventually shear band formation within the crystalline silicon core. The latter boosts the non-uniform lithiation at the silicon interface affecting the SEI reformation process and ultimately the capacity. Our findings are based on a comprehensive multiscale structural and chemical experimental characterization, complemented by molecular dynamics modelling. This approach highlights the importance of considering electrochemical, microstructural and mechanical mechanisms, offering a strategy for developing improved anode materials with enhanced cycling stability and reduced capacity loss.
Sharp-peaked lanthanide nanocrystals for near-infrared photoacoustic multiplexed differential imaging
Authors: Loh Kang Yong , Li Lei S. , Fan Jingyue , Goh Yi Yiing , Liew Weng Heng , Davis Samuel , Zhang Yide , Li Kai , Liu Jie , Liang Liangliang , Feng Minjun , Yang Ming , Zhang Hang , Ma Ping’an , Feng Guangxue , Mu Zhao , Gao Weibo , Sum Tze Chien , Liu Bin , Lin Jun , Yao Kui , Wang Lihong V. , Liu Xiaogang 
Published: August 2024

AbstractPhotoacoustic tomography offers a powerful tool to visualize biologically relevant molecules and understand processes within living systems at high resolution in deep tissue, facilitated by the conversion of incident photons into low-scattering acoustic waves through non-radiative relaxation. Although current endogenous and exogenous photoacoustic contrast agents effectively enable molecular imaging within deep tissues, their broad absorption spectra in the visible to near-infrared (NIR) range limit photoacoustic multiplexed imaging. Here, we exploit the distinct ultrasharp NIR absorption peaks of lanthanides to engineer a series of NIR photoacoustic nanocrystals. This engineering involves precise host and dopant material composition, yielding nanocrystals with sharply peaked photoacoustic absorption spectra (~3.2 nm width) and a ~10-fold enhancement in NIR optical absorption for efficient deep tissue imaging. By combining photoacoustic tomography with these engineered nanocrystals, we demonstrate photoacoustic multiplexed differential imaging with substantially decreased background signals and enhanced precision and contrast.
Renewed insights into Ackermannviridae phage biology and applications
Authors: Sørensen Anders Nørgaard , Brøndsted Lone 
Published: August 2024

AbstractThe Ackermannviridae family was established in 2017, containing phages previously classified within the Myoviridae family under the Viunalikevirus genus. Ackermannviridae phages have been increasingly studied due to their broad range of hosts among Enterobacteriaceae, and currently, 174 complete genomes are available on NCBI. Instrumental for their wide host infectivity, Ackermannviridae phages display a branched complex of multiple Tail Spike Proteins (TSPs). These TSPs recognize diverse surface polysaccharide receptors, allowing the phages to target strains with distinct lipopolysaccharides or capsular polysaccharides. This review gives an updated overview of the taxonomy and hosts of the expanding Ackermannviridae family with significant emphasis on recent advances in structural and computational biology for elucidating TSP diversity, structural domains, and assembly of the branched TSP complex. Furthermore, we explore the potential of engineering Ackermannviridae phages and discuss the challenges of using transducing wildtype phages for biocontrol. Finally, this review identifies bottlenecks hindering further advances in understanding Ackermannviridae phage biology and applications.
Stress grading system optimisation for an inverter‐fed rotating machine
Authors: Wang Peng , Zhao Wenhuan , Zhang Yue , Yang Shuai , Cavallini Andrea , Yu Chaofan , Cheng Chizhou , Zhu Yingwei 
Published: August 2024

AbstractStress grading systems using non‐linear resistive coatings are a key component to suppress surface corona in the end‐windings of rotating machine. Compared to a sinusoidal‐fed motor, the high slew rate of the voltage at the flanks of the repetitive square voltages from the inverter cause large capacitive currents to flow in the main wall insulation. These large currents, if not properly considered in the design phase, lead to severe electrothermal stress of the grading system. Experiments and simulations were conducted on a stress grading system whose structure arises from limitation posed by the motor structure. Measurements performed with different rise times show that the maximum potential along the conductive armour tape (CAT) increases non‐linearly with increasing axial distance, and the potential at the edge of the CAT reached nearly twice the peak‐to‐peak voltage at 500 ns rise time, leading to corona inception. As metal plates are used in the machine to dampen vibrations in the end‐winding, similar plates were also fastened to the stress grading system, worsening the already inadequate corona suppression performance. The stress grading system was therefore modified, avoiding the surface corona while, at the same time, reducing the temperature in the grading system to acceptable levels.
The Three Hundred project: Radio luminosity evolution from merger-induced shock fronts in simulated galaxy clusters
Authors: Nuza S. E. , Hoeft M. , Contreras-Santos A. , Knebe A. , Yepes G. 
Published: August 2024

Context. Galaxy cluster mergers are believed to generate large-scale shock waves that are ideal sites for cosmic ray production. In these so-called radio relic shocks, synchrotron radiation is produced mainly as a result of electron acceleration in the presence of intracluster magnetic fields.
Aims. We aim to compute radio emission light curves for a sample of galaxy group and cluster mergers simulated in a cosmological context in order to study the dependence of radio luminosity on cluster mass, redshift, and impact parameter.
Methods. We used model galaxy clusters from THE THREE HUNDRED project, a sample of 324 simulated high-density regions of radius 15 h−1 Mpc extracted from a cosmological volume, to identify cluster mergers characterised by the two main merging structures, construct their light curves, and follow their evolution throughout the complete simulated cosmic history.
Results. We found that the median non-thermal radio relic luminosity light curve produced in galaxy cluster mergers can be described by a skewed Gaussian function abruptly rising after core-passage of the secondary cluster that peaks after ~0.1–0.8 Gyr as a function of M200,1, the mass of the primary, displaying a mass-dependent luminosity output increase of ≲10 to about ≳10–50 times relative to the radio emission measured at core-passage for galaxy groups and clusters, respectively. In general, most merger orbits are fairly radial with a median opening angle of ~20º before the collision. We also found that, independent of the cluster mass, less radial mergers tend to last longer, although the trend is weak. Finally, in agreement with previous works, we found that the peak radio luminosity shows a significant correlation with mass, P1.4 ∝ M200,12.05 demonstrating that this relation holds all the way up from galaxy group scales to the most massive galaxy clusters.
Conclusions. We conclude that cluster mass is the primary driver for radio ‘gischt’ median luminosity, although there are significant variations for a given cluster mass related to the specifics of each merging process. In general, binary mergers are responsible for many of the well-known observed radio relic structures but complex situations involving three or more substructures are also common. Our simulations suggest that the shock-driven, non-thermal radio emission observed on cluster outskirts are the result of massive galaxy cluster mergers at ɀ ≲ 1, peaking at ɀ ~ 0–0.5.
Retrieving stellar parameters and dynamics of AGB stars with Gaia parallax measurements and CO5BOLD RHD simulations
Authors: Béguin E. , Chiavassa A. , Ahmad A. , Freytag B. , Uttenthaler S. 
Published: August 2024

Context. The complex dynamics of asymptotic giant branch (AGB) stars and the resulting stellar winds have a significant impact on the measurements of stellar parameters and amplify their uncertainties. Three-dimensional (3D) radiative hydrodynamic (RHD) simulations of convection suggest that convection-related structures at the surface of AGB star affect the photocentre displacement and the parallax uncertainty measured by Gaia.
Aims. We explore the impact of the convection on the photocentre variability and aim to establish analytical laws between the photo-centre displacement and stellar parameters to retrieve such parameters from the parallax uncertainty.
Methods. We used a selection of 31 RHD simulations with CO5BOLD and the post-processing radiative transfer code OPTIM3D to compute intensity maps in the Gaia G band [320–1050 nm]. From these maps, we calculated the photocentre position and temporal fluctuations. We then compared the synthetic standard deviation to the parallax uncertainty of a sample of 53 Mira stars observed with Gaia.
Results. The simulations show a displacement of the photocentre across the surface ranging from 4 to 13% of the corresponding stellar radius, in agreement with previous studies. We provide an analytical law relating the pulsation period of the simulations and the photocentre displacement as well as the pulsation period and stellar parameters. By combining these laws, we retrieve the surface gravity, the effective temperature, and the radius for the stars in our sample.
Conclusions. Our analysis highlights an original procedure to retrieve stellar parameters by using both state-of-the-art 3D numerical simulations of AGB stellar convection and parallax observations of AGB stars. This will help us refine our understanding of these giants.