bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise derived myokine irisin as mediator of cardiorespiratory, metabolic and thermal adjustments during central and peripheral chemoreflex activation
Authors: Bernardes-Ribeiro Mariana , Patrone Luis Gustavo A. , Cristina-Silva Caroline , Bícego Kênia C. , Gargaglioni Luciane H. 
Published: May 2024

AbstractExercise elicits physiological adaptations, including hyperpnea. However, the mechanisms underlying exercise-induced hyperpnea remain unresolved. Skeletal muscle acts as a secretory organ, releasing irisin (IR) during exercise. Irisin can cross the blood–brain barrier, influencing muscle and tissue metabolism, as well as signaling in the central nervous system (CNS). We evaluated the effect of intracerebroventricular or intraperitoneal injection of IR in adult male rats on the cardiorespiratory and metabolic function during sleep–wake cycle under room air, hypercapnia and hypoxia. Central IR injection caused an inhibition on ventilation (VE) during wakefulness under normoxia, while peripheral IR reduced VE during sleep. Additionally, central IR exacerbates hypercapnic hyperventilation by increasing VE and reducing oxygen consumption. As to cardiovascular regulation, central IR caused an increase in heart rate (HR) across all conditions, while no change was observed following peripheral administration. Finally, central IR attenuated the hypoxia-induced regulated hypothermia and increase sleep episodes, while peripheral IR augmented CO2-induced hypothermia, during wakefulness. Overall, our results suggest that IR act mostly on CNS exerting an inhibitory effect on breathing under resting conditions, while stimulating the hypercapnic ventilatory response and increasing HR. Therefore, IR seems not to be responsible for the exercise-induced hyperpnea, but contributes to the increase in HR.
Imidazole[1,5-a]pyridine derivatives as EGFR tyrosine kinase inhibitors unraveled by umbrella sampling and steered molecular dynamics simulations
Authors: Truong Duc Toan , Ho Kiet , Nhi Huynh Thi Yen , Nguyen Van Ha , Dang Tuan Thanh , Nguyen Minh Tho 
Published: May 2024

AbstractAlthough the use of the tyrosine kinase inhibitors (TKIs) has been proved that it can save live in a cancer treatment, the currently used drugs bring in many undesirable side-effects. Therefore, the search for new drugs and an evaluation of their efficiency are intensively carried out. Recently, a series of eighteen imidazole[1,5-a]pyridine derivatives were synthetized by us, and preliminary analyses pointed out their potential to be an important platform for pharmaceutical development owing to their promising actions as anticancer agents and enzyme (kinase, HIV-protease,…) inhibitors. In the present theoretical study, we further analyzed their efficiency in using a realistic scenario of computational drug design. Our protocol has been developed to not only observe the atomistic interaction between the EGFR protein and our 18 novel compounds using both umbrella sampling and steered molecular dynamics simulations, but also determine their absolute binding free energies. Calculated properties of the 18 novel compounds were in detail compared with those of two known drugs, erlotinib and osimertinib, currently used in cancer treatment. Inspiringly the simulation results promote three imidazole[1,5-a]pyridine derivatives as promising inhibitors into a further step of clinical trials.
Spatiotemporal variations of ecosystem services in the Aral Sea basin under different CMIP6 projections
Authors: He Jing , Yu Yang , Sun Lingxiao , Li Chunlan , Zhang Haiyan , Malik Ireneusz , Wistuba Malgorzata , Yu Ruide 
Published: May 2024

AbstractThe Aral Sea, located in Central Asia, has undergone significant reduction in surface area owing to the combined impacts of climate change and human activities. This reduction has led to a regional ecological crisis and profound repercussions on ecosystem services. Investigating the spatiotemporal variations and synergistic trade-offs of ESs in the Aral Sea basin is crucial for fostering the integrated development of the region’s socioeconomic ecology. This study utilizes the Future Land-Use Simulation and InVEST models to analyze future land-use scenarios, integrating CMIP6 projections to assess the quality of four key ecosystem services: water production, soil conservation, carbon storage, and habitat quality over two timeframes: the historical period (1995–2020) and the projected future (2021–2100). Employing Spearman correlation, the study explores the trade-offs and synergies among these ecosystem services. Findings reveal that the primary forms of land-use change in the Aral Sea basin are the reduction in water area (− 49.59%) and the rapid expansion of urban areas (+ 504.65%). Temporally, habitat quality exhibits a declining trend, while carbon storage shows an increasing trend, and water production and soil retention fluctuate initially decreasing and then increasing. Spatially, water production and carbon storage demonstrate an increasing trend from the northwest to the southeast. Habitat quality exhibits a higher spatial pattern in the southeast and south, contrasting with lower spatial patterns in the north and west. Low-level soil conservation is predominantly distributed in the northwest, while medium to low-level soil conservation is prevalent in the east of the basin. The trade-off and synergy analysis indicates that between 1995 and 2020, a trade-off relationship existed between carbon storage and habitat quality and water production, whereas synergies were observed between soil conservation and carbon storage, water production and habitat quality, and soil conservation. The correlation between water production and soil conservation emerges as the strongest, whereas the correlation between carbon storage and habitat quality appears to be the weakest. The dynamic spatiotemporal changes, trade-offs, and collaborative relationships of ESs constitute major aspects of ecosystem service research, holding substantial implications for the effective management of the regional ecological environment.
Integration of single-cell sequencing and bulk RNA-seq to identify and develop a prognostic signature related to colorectal cancer stem cells
Authors: Wu Jiale , Li Wanyu , Su Junyu , Zheng Jiamin , Liang Yanwen , Lin Jiansuo , Xu Bilian , Liu Yi 
Published: May 2024

AbstractThe prognosis for patients with colorectal cancer (CRC) remains worse than expected due to metastasis, recurrence, and resistance to chemotherapy. Colorectal cancer stem cells (CRCSCs) play a vital role in tumor metastasis, recurrence, and chemotherapy resistance. However, there are currently no prognostic markers based on CRCSCs-related genes available for clinical use. In this study, single-cell transcriptome sequencing was employed to distinguish cancer stem cells (CSCs) in the CRC microenvironment and analyze their properties at the single-cell level. Subsequently, data from TCGA and GEO databases were utilized to develop a prognostic risk model for CRCSCs-related genes and validate its diagnostic performance. Additionally, functional enrichment, immune response, and chemotherapeutic drug sensitivity of the relevant genes in the risk model were investigated. Lastly, the key gene RPS17 in the risk model was identified as a potential prognostic marker and therapeutic target for further comprehensive studies. Our findings provide new insights into the prognostic treatment of CRC and offer novel perspectives for a systematic and comprehensive understanding of CRC development.
Clear surgical margins as a prognostic indicator for disease recurrence, with no impact on survival rates in patients with myxofibrosarcoma
Authors: Tomáš Tomáš , Apostolopoulos Vasileios , Pazourek Lukáš , Kubíček Marián , Staniczková Zambo Iva , Adámková Dagmar , Šlampa Pavel , Mahdal Michal 
Published: May 2024

AbstractMyxofibrosarcoma presents an infiltrating growth pattern that results in a high tendency for local recurrence. Clear margin resection is challenging because of microscopic infiltration. The purpose of the present study was to analyze the overall and disease-free survival rates of patients with myxofibrosarcoma and the prognostic factors that determine both survival and disease recurrence. Among the 111 patients included in our study, the 5-year overall survival rate was 65.5%. An age of more than 65 years (hazard ratio [HR] 1.9 [95% confidence interval (CI) 1.4–5.6]; p < 0.001), a tumor size of more than 5 cm (HR 2.8 [95% CI 0.9–8.1]; p = 0.049) and the G3 tumor grade (HR 14.1 [95% CI 2.1–105.0]; p < 0.001) negatively affected overall survival. The 5-year recurrence-free survival rate was 49.4%. R1/R2-type resection (HR 2.4 [95% CI 1.0–5.6]; p = 0.048) had a detrimental effect on tumor recurrence. Clear margins had a positive impact on recurrence-free survival, but did not significantly affect overall patient survival, suggesting that other factors may play a more significant role in determining patient outcomes. A surgical margin of 2 mm was not sufficient to significantly influence the incidence of recurrence. Consequently, a wider surgical margin may be necessary to reduce the risk of myxofibrosarcoma recurrence.
Proteomics and metabolic burden analysis to understand the impact of recombinant protein production in E. coli
Authors: Rajacharya Girish H. , Sharma Ashima , Yazdani Syed Shams 
Published: May 2024

AbstractThe impact of recombinant protein production (RPP) on host cells and the metabolic burden associated with it undermine the efficiency of the production system. This study utilized proteomics to investigate the dynamics of parent and recombinant cells induced at different time points for RPP. The results revealed significant changes in both transcriptional and translational machinery that may have impacted the metabolic burden, growth rate of the culture and the RPP. The timing of protein synthesis induction also played a critical role in the fate of the recombinant protein within the host cell, affecting protein and product yield. The study identified significant differences in the expression of proteins involved in fatty acid and lipid biosynthesis pathways between two E. coli host strains (M15 and DH5⍺), with the E. coli M15 strain demonstrating superior expression characteristics for the recombinant protein. Overall, these findings contribute to the knowledge base for rational strain engineering for optimized recombinant protein production.
A cooperative control method and application for series multivariable coupled system
Authors: Yu Yongchuan , Yang Haonan , Wan Shuo , Liu Qiusheng , Yan Jianzhuo 
Published: May 2024

AbstractSeries multivariable coupled system is a typical controlled object in process control industry. The interaction of various state variables between multiple inputs and outputs in the system forms a complex series multivariable coupled structure. This coupled structure makes the control of a controlled object in the system affect the controlled object in the upper and lower control loop. As a result, it is difficult to control one or more control loops in the system without changing the state of other links in the system. In this paper, a cooperative control method for series multivariable coupled system is proposed. A decoupling controller is designed to remove the coupling effect caused by the interaction between stages, and the system is decoupled into several independent control loops. Differential leading PI (proportional-integral) error compensation method is introduced to ensure the following performance of the controller without static error. The proposed cooperative control method satisfies the Lyapunov stability, and has been successfully applied in the simulation experiment of cascade pumping station system of Beijing East-to-West water transfer project. The proposed method reduces the difficulty to controlling the water level of forebay of each pumping station and ensures the efficient operation of the cascade pumping station system.
Temperature-dependent differences in mouse gut motility are mediated by stress
Authors: Han Alvin , Hudson-Paz Courtney , Robinson Beatriz G. , Becker Laren , Jacobson Amanda , Kaltschmidt Julia A. , Garrison Jennifer L. , Bhatt Ami S. , Monack Denise M. 
Published: May 2024

AbstractResearchers have advocated elevating mouse housing temperatures from the conventional ~22 °C to the mouse thermoneutral point of 30 °C to enhance translational research. However, the impact of environmental temperature on mouse gastrointestinal physiology remains largely unexplored. Here we show that mice raised at 22 °C exhibit whole gut transit speed nearly twice as fast as those raised at 30 °C, primarily driven by a threefold increase in colon transit speed. Furthermore, gut microbiota composition differs between the two temperatures but does not dictate temperature-dependent differences in gut motility. Notably, increased stress signals from the hypothalamic–pituitary–adrenal axis at 22 °C have a pivotal role in mediating temperature-dependent differences in gut motility. Pharmacological and genetic depletion of the stress hormone corticotropin-releasing hormone slows gut motility in stressed 22 °C mice but has no comparable effect in relatively unstressed 30 °C mice. In conclusion, our findings highlight that colder mouse facility temperatures significantly increase gut motility through hormonal stress pathways.
Bacillamide D produced by Bacillus cereus from the mouse intestinal bacterial collection (miBC) is a potent cytotoxin in vitro
Authors: Hohmann Maximilian , Brunner Valentina , Johannes Widya , Schum Dominik , Carroll Laura M. , Liu Tianzhe , Sasaki Daisuke , Bosch Johanna , Clavel Thomas , Sieber Stephan A. , Zeller Georg , Tschurtschenthaler Markus , Janßen Klaus-Peter , Gulder Tobias A. M. 
Published: May 2024

AbstractThe gut microbiota influences human health and the development of chronic diseases. However, our understanding of potentially protective or harmful microbe-host interactions at the molecular level is still in its infancy. To gain further insights into the hidden gut metabolome and its impact, we identified a cryptic non-ribosomal peptide BGC in the genome of Bacillus cereus DSM 28590 from the mouse intestine (www.dsmz.de/miBC), which was predicted to encode a thiazol(in)e substructure. Cloning and heterologous expression of this BGC revealed that it produces bacillamide D. In-depth functional evaluation showed potent cytotoxicity and inhibition of cell migration using the human cell lines HCT116 and HEK293, which was validated using primary mouse organoids. This work establishes the bacillamides as selective cytotoxins from a bacterial gut isolate that affect mammalian cells. Our targeted structure-function-predictive approach is demonstrated to be a streamlined method to discover deleterious gut microbial metabolites with potential effects on human health.
Effect of nonsense-mediated mRNA decay factor SMG9 deficiency on premature aging in zebrafish
Authors: Lai Shaohong , Shiraishi Hiroshi , Sebastian Wulan Apridita , Shimizu Nobuyuki , Umeda Ryohei , Ikeuchi Mayo , Kiyota Kyoko , Takeno Takashi , Miyazaki Shuya , Yano Shinji , Shimada Tatsuo , Yoshimura Akihiko , Hanada Reiko , Hanada Toshikatsu 
Published: May 2024

AbstractSMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations in SMG9 are associated with heart and brain malformation syndrome (HBMS). However, the molecular mechanism underlying HBMS remains unclear. We generated smg9 mutant zebrafish (smg9oi7/oi7) that have a lifespan of approximately 6 months or longer, allowing for analysis of the in vivo function of Smg9 in adults in more detail. smg9oi7/oi7 zebrafish display congenital brain abnormalities and reduced cardiac contraction. Additionally, smg9oi7/oi7 zebrafish exhibit a premature aging phenotype. Analysis of NMD target mRNAs shows a trend toward increased mRNA levels in smg9oi7/oi7 zebrafish. Spermidine oxidase (Smox) is increased in smg9oi7/oi7 zebrafish, resulting in the accumulation of byproducts, reactive oxygen species, and acrolein. The accumulation of smox mRNA due to NMD dysregulation caused by Smg9 deficiency leads to increased oxidative stress, resulting in premature aging.
Chronic spindle assembly checkpoint activation causes myelosuppression and gastrointestinal atrophy
Authors: Karbon Gerlinde , Schuler Fabian , Braun Vincent Z , Eichin Felix , Haschka Manuel , Drach Mathias , Sotillo Rocio , Geley Stephan , Spierings Diana CJ , Tijhuis Andrea E , Foijer Floris , Villunger Andreas 
Published: May 2024

AbstractInterference with microtubule dynamics in mitosis activates the spindle assembly checkpoint (SAC) to prevent chromosome segregation errors. The SAC induces mitotic arrest by inhibiting the anaphase-promoting complex (APC) via the mitotic checkpoint complex (MCC). The MCC component MAD2 neutralizes the critical APC cofactor, CDC20, preventing exit from mitosis. Extended mitotic arrest can promote mitochondrial apoptosis and caspase activation. However, the impact of mitotic cell death on tissue homeostasis in vivo is ill-defined. By conditional MAD2 overexpression, we observe that chronic SAC activation triggers bone marrow aplasia and intestinal atrophy in mice. While myelosuppression can be compensated for, gastrointestinal atrophy is detrimental. Remarkably, deletion of pro-apoptotic Bim/Bcl2l11 prevents gastrointestinal syndrome, while neither loss of Noxa/Pmaip or co-deletion of Bid and Puma/Bbc3 has such a protective effect, identifying BIM as rate-limiting apoptosis effector in mitotic cell death of the gastrointestinal epithelium. In contrast, only overexpression of anti-apoptotic BCL2, but none of the BH3-only protein deficiencies mentioned above, can mitigate myelosuppression. Our findings highlight tissue and cell-type-specific survival dependencies in response to SAC perturbation in vivo.
Planetary nebulae of the Large Magellanic Cloud
Authors: Tosi S. , Dell’Agli F. , Kamath D. , Stanghellini L. , Ventura P. , Bianchi S. , Gómez-Muñoz M. A. , García-Hernández D. A. 
Published: May 2024

Context. Planetary nebulae (PNe) have three main components: a central star (CS), ionized gas, and dust in the nebula. Each contains critical chemical fingerprints of the PN’s evolution, which serve as tracers of the evolution, nucleosynthesis, and dust production that occurred during the preceding asymptotic giant branch (AGB) phase.
Aims. We aim to build a bridge to link the PN phase to the evolution of progenitors, to better understand the dust production and mass-loss mechanism during the final AGB phase. Here we present a comprehensive study of nine Large Magellanic Cloud spherical or elliptical PNe whose observations from the UV through the IR are available in the literature. We characterize nebulae and CSs, finding information necessary to reconstruct the evolutionary history of mass-loss and dust production, such as as the amount of gas that makes up the nebula and the dust that surrounds the CS.
Methods. We compared the observed energy distribution of the selected PNe to that obtained from photoionization modeling, taking the presence of dust into account. The physical and chemical parameters of the CSs were then compared with predictions from the evolutionary tracks.
Results. We characterize the source, assigning a progenitor, early-AGB mass to each CS. We estimate the mass of the nebula and the dust-to-gas ratio. For five objects, we find evidence for the presence of a near-IR bump, which would indicate the presence of hot dust.
Galaxy cluster virial-shock sources in eROSITA catalogs
Authors: Ilani Gideon , Hou Kuan-Chou , Nadler Gil , Keshet Uri 
Published: May 2024

Context.Virial shocks around galaxy clusters and groups are being mapped, thus tracing accretion onto large-scale structure.Aims.Following the recent identification of discrete ROSAT and radio sources associated with the virial shocks of MCXC clusters and groups, we examined the eROSITA-DE Early Data Release (EDR) to see whether it shows virial-shock X-ray sources within its 140 deg2field.Methods.EDR catalog sources were stacked and radially binned around EDR catalog clusters and groups. The properties of the excess virial-shock sources were inferred statistically by comparing the virial-shock region to the field.Results.We find an excess of X-ray sources narrowly localized at the 2.0 < r/R500 < 2.25 normalized radii, just inside the anticipated virial shocks, of the resolved 532 clusters, for samples of both extended sources (3σfor 534 sources) and bright sources (3.5σfor 5820 sources; 4σexcluding the low cluster-mass quartile). The excess sources are on average extended (∼100 kpc), luminous (LX ≃ 1043 − 44erg s−1), and hot (keV scales), consistent with infalling gaseous halos crossing the virial shock. The results agree with the stacked ROSAT–MCXC signal, showing the higherLXexpected at EDR redshifts and a possible dependence on host mass.Conclusions.Localized virial-shock spikes in the distributions of discrete radio, X-ray, and possibly alsoγ-ray sources are new powerful probes of accretion from the cosmic web. We expect that data from future all-sky catalogs will allow us to place strong constraints on virial shock physics.
Nomen est omen
Authors: Stern Cornelia 
Published: May 2024

SummaryDie Brechwurzel – Carapichea ipecacuanha (Brot.) L. Andersson – ist eine in Brasilien heimische, giftige Pflanze. Angebaut wird sie heute jedoch auch in mittelamerikanischen Staaten wie Costa Rica und Nicaragua sowie in Vorderindien. Schon ihr Artname deutet auf den brasilianischen Ursprung hin. Denn in der Tupissprache wurde die Brechwurzel pecaá-guéne genannt, was so viel wie „Kleines Kraut am Weg, das Brechen erregt“ heißen soll. Diese Wirkung hat sich dann auch in der deutschen Bezeichnung Brechwurzel beziehungsweise im portugiesischen und homöopathischen Namen Ipecacuanha niedergeschlagen. Weitere Bezeichnungen sind Speiwurzeln, Kopfbeere und Ruhrwurzel.
Schwere Metalle mit starker Wirkung
Authors: Blume Ralf 
Published: May 2024

SummaryNeben essenziellen Schwermetallen, die als lebenswichtige Spurenelemente zur Gesundheit des Menschen beitragen, gibt es pathogene Schwermetalle, die gesundheitliche Beschwerden verursachen können. Da sie oft nicht ausgeschieden werden können und sich im Körper anreichern, führt eine regelmäßige Aufnahme selbst geringer Mengen dieser Giftstoffe nicht selten zu chronischen Erkrankungen und schweren Pathologien. In der Klassischen Homöopathie stellen Schwermetalle und ihre Verbindungen in homöopathischer Aufbereitung aufgrund der langanhaltenden und starken Wirkung auf den Organismus eine wichtige Arzneimittelgruppe dar.