bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastrodin promotes CNS myelinogenesis and alleviates demyelinating injury by activating the PI3K/AKT/mTOR signaling
Authors: Shi Xiao-yu , He Yi-xi , Ge Man-yue , Liu Peng , Zheng Ping , Li Zheng-hao 
Published: February 2025

Abstract
Demyelination is a common feature of numerous neurological disorders including multiple sclerosis and leukodystrophies. Although myelin can be regenerated spontaneously following injury, this process is often inadequate, potentially resulting in neurodegeneration and exacerbating neurological dysfunction. Several drugs aimed at promoting the differentiation of oligodendrocyte precursor cells (OPCs) have yielded unsatisfactory clinical effects. A recent study has shifted the strategy of pro-OPC differentiation towards enhancing myelinogenesis. In this study we identified the pro-myelinating drug using a zebrafish model. Five traditional Chinese medicine monomers including gastrodin, paeoniflorin, puerarin, salidroside and scutellarin were assessed by bath-application in Tg (MBP:eGFP-CAAX) transgenic line at 1–5 dpf. Among the 5 monomers, only gastrodin exhibited significant pro-myelination activity. We showed that gastrodin (10 µM) enhanced myelin sheath formation and oligodendrocyte (OL) maturation without affecting the number of OLs. Gastrodin markedly increased the phosphorylation levels of PI3K, AKT, and mTOR in primary cultured OLs via direct interaction with PI3K. Co-treatment with the PI3K inhibitor LY294002 (5 µM) mitigated gastrodin-induced OL maturation. Furthermore, injection of gastrodin (100 mg·kg−1·d−1, i.p.) effectively facilitated remyelination in a lysophosphatidylcholine-induced demyelinating mouse model and alleviated demyelination in the experimental autoimmune encephalomyelitis mice. These results identify gastrodin as a promising therapeutic agent for demyelinating diseases and highlight the potential of the zebrafish model for screening pro-myelinogenic pharmacotherapy.
Atlas of expression of acyl CoA binding protein/diazepam binding inhibitor (ACBP/DBI) in human and mouse
Authors: Li Sijing , Mingoia Silvia , Montégut Léa , Lambertucci Flavia , Chen Hui , Dong Yanbing , De Palma Fatima Domenica Elisa , Scuderi Sarah Adriana , Rong Yan , Carbonnier Vincent , Martins Isabelle , Maiuri Maria Chiara , Kroemer Guido 
Published: February 2025

Abstract
Acyl CoA binding protein encoded by diazepam binding inhibitor (ACBP/DBI) is a tissue hormone that stimulates lipo-anabolic responses and inhibits autophagy, thus contributing to aging and age-related diseases. Protein expression profiling of ACBP/DBI was performed on mouse tissues to identify organs in which this major tissue hormone is expressed. Transcriptomic and proteomic data bases corroborated a high level of human-mouse interspecies conservation of ACBP/DBI expression in different organs. Single-cell RNA-seq data confirmed that ACBP/DBI was strongly expressed by parenchymatous cells from specific human and mouse organs (e.g., kidney, large intestine, liver, lung) as well as by myeloid or glial cells from other organs (e.g., adipose tissue, brain, eye) following a pattern that was conserved among the two species. We identified a panel of 44 mRNAs that are strongly co-expressed with ACBP/DBI mRNA in normal and malignant human and normal mouse tissues. Of note, 22 (50%) of these co-expressed mRNAs encode proteins localized at mitochondria, and mRNAs with metabolism-related functions are strongly overrepresented (66%). Systematic data mining was performed to identify transcription factors that regulate ACBP/DBI expression in human and mouse. Several transcription factors, including growth response 1 (EGR1), E2F Transcription Factor 1 (E2F1, which interacts with retinoblastoma, RB) and transformation-related protein 53 (TRP53, best known as p53), which are endowed with oncosuppressive effects, consistently repress ACBP/DBI expression as well as its co-expressed mRNAs across multiple datasets, suggesting a mechanistic basis for a coregulation network. Furthermore, we identified multiple transcription factors that transactivate ACBP/DBI gene expression together with its coregulation network. Altogether, this study indicates the existence of conserved mechanisms determining the expression of ACBP/DBI in specific cell types of the mammalian organism.
Cryo-EM structure of the human THIK-1 K2P K+ channel reveals a lower Y gate regulated by lipids and anesthetics
Authors: Rödström Karin E. J. , Eymsh Bisher , Proks Peter , Hayre Mehtab S. , Cordeiro Sönke , Mendez-Otalvaro Edward , Madry Christian , Rowland Anna , Kopec Wojciech , Newstead Simon , Baukrowitz Thomas , Schewe Marcus , Tucker Stephen J. 
Published: February 2025

Abstract
THIK-1 (KCNK13) is a halothane-inhibited and anionic-lipid-activated two-pore domain (K2P) K+ channel implicated in microglial activation and neuroinflammation, and a current target for the treatment of neurodegenerative disorders, for example Alzheimer’s disease and amyothropic lateral sclerosis (ALS). However, compared to other K2P channels, little is known about the structural and functional properties of THIK-1. Here we present a 3.16-Å-resolution cryo-EM structure of human THIK-1 that reveals several distinct features, in particular, a tyrosine in M4 that contributes to a lower ‘Y gate’ that opens upon activation by physiologically relevant G-protein-coupled receptor and lipid signaling pathways. We demonstrate that linoleic acid bound within a modulatory pocket adjacent to the filter influences channel activity, and that halothane inhibition involves a binding site within the inner cavity, both resulting in conformational changes to the Y gate. Finally, the extracellular cap domain contains positively charged residues that line the ion exit pathway and contribute to the distinct biophysical properties of this channel. Overall, our results provide structural insights into THIK-1 function and identify distinct regulatory sites that expand its potential as a drug target for the modulation of microglial function.
Multinational modelling of PM2.5 and CO exposures from household air pollution in peri-urban Cameroon, Ghana and Kenya
Authors: Williams Harry , Baame Miranda , Lorenzetti Federico , Mangeni Judith , Nix Emily , Betang Emmanuel , Chartier Ryan , Sang Edna , Wilson Daniel , Tawiah Theresa , Quansah Reginald , Puzzolo Elisa , Menya Diana , Ngahane Bertrand Hugo Mbatchou , Pope Daniel , Asante Kwaku Poku , Shupler Matthew 
Published: February 2025

Abstract
In sub-Saharan Africa, approximately 85% of the population uses polluting cooking fuels (e.g. wood, charcoal). Incomplete combustion of these fuels generates household air pollution (HAP), containing fine particulate matter (PM2.5 ) and carbon monoxide (CO). Due to large spatial variability, increased quantification of HAP levels is needed to improve exposure assessment in sub-Saharan Africa. The CLEAN-Air(Africa) study included 24-h monitoring of PM2.5 and CO kitchen concentrations (npm2.5 = 248/nCO = 207) and female primary cook exposures (npm2.5 = 245/nCO = 222) in peri-urban households in Obuasi (Ghana), Mbalmayo (Cameroon) and Eldoret (Kenya). HAP measurements were combined with survey data on cooking patterns, socioeconomic characteristics and ambient exposure proxies (e.g. walking time to nearest road) in separate PM2.5 and CO mixed-effect log-linear regression models. Model coefficients were applied to a larger study population (n = 937) with only survey data to quantitatively scale up PM2.5 and CO exposures. The final models moderately explained variation in mean 24-h PM2.5 (R2 = 0.40) and CO (R2 = 0.26) kitchen concentration measurements, and PM2.5 (R2 = 0.27) and CO (R2 = 0.14) female cook exposures. Primary/secondary cooking fuel type was the only significant predictor in all four models. Other significant predictors of PM2.5 and CO kitchen concentrations were cooking location and household size; household financial security and rental status were only predictive of PM2.5 concentrations. Cooking location, household financial security and proxies of ambient air pollution exposure were significant predictors of PM2.5 cook exposures. Including objective cooking time measurements (from temperature sensors) from (n = 143) households substantially improved (by 52%) the explained variability of the CO kitchen concentration model, but not the PM2.5 model. Socioeconomic characteristics and markers of ambient air pollution exposure were strongly associated with mean PM2.5 measurements, while cooking environment variables were more predictive of mean CO levels.
Evaluation the toxic effects of Cobalt-Zinc Ferrite nanoparticles in experimental mice
Authors: El-Nahass Eman E. , Salem B. I. , El-Naggar Sabry A. , Elwan Mona M. 
Published: February 2025

Abstract
Cobalt Zinc ferrite nanoparticles (NPs) were synthesized utilizing the auto-combustion flash method, with the general formula Co1 − xZnxFe2O4 (x = 0,0.35). This study aimed to evaluate the hepato-renal and systemic toxicity of Cobalt Zinc Ferrite nanoparticles (CZF NPs). A total of eighty female mice were utilized to ascertain the median lethal dose (LD50) of CF NPs (100 mg/kg) and CZF NPs (100 mg/kg). Thirty female CD1 mice were placed into three groups, each containing ten animals. In Group 1 (Gp1), mice were administered a 200 µl injection of sterile saline intraperitoneally (i.p.). During a 6-day period, Gp2 and Gp3 received injections of CF NPs and CFZ NPs. On day 14 after injection, hematological, biochemical, and histopathological data were measured. CZF NPs were characterized using X-ray Diffraction Analysis (XRD), Transmission Electron Microscope (TEM) and Vibrating Sample Magnetometer (VSM). There was a significant alteration in the overall body weight of mice injected with CZF NPs. Injections of CF NPs did not significantly alter red blood cells (RBC) counts, hemoglobin concentration (Hb), hematocrit percentage (Hct%), total white blood cells (WBCs), and platelets. However, injections of CZF NPs resulted in an increase in WBC count and a decrease in platelet count. Furthermore, injection of CZF NPs altered the differential leukocyte percentages. The liver and kidney functions in mice injected with CF NPs did not show any notable changes. However, mice treated with CZF NPs had considerable increases in liver and kidney bio-markers. The administration of CF NPS did not modify the histological structure of hepatic and renal tissues; however, the hepatic and renal structures were disrupted in animals injected with CZF NPs. Overall, the findings indicated high toxicity of CZF NPs in the mice used for the experiment.
Molecular profiling of breast cancer methylation pattern in triple negative versus non- triple negative breast cancer
Authors: Mohanad Marwa , Hamza Hager M. , Bahnassy Abeer A. , Shaarawy Sabry , Ahmed Ola , EL-Mezayen Hatem A. , Ayad Eman G. , Tahoun Neveen , Abdellateif Mona S. 
Published: February 2025

Abstract
Epigenetic alterations, especially promotor methylation, have a significant impact on gene expression, molecular subtyping, prognosis, and outcome of breast cancer (BC). The methylation profile was assessed for 22 genes of the BC tissue using the EpiTect Methyl II PCR System in 40 triple-negative BC (TNBC) patients compared to 50 non-TNBC group. The data were corelated with the disease-free (DFS) and overall survival (OS) of the patients. Genes that were differentially hypermethylated in TNBC patients compared to those with non-TNBC included CCND2, CDKN2A, ESR1, CDH1, BRCA1, GSTP, RASSF1, SLIT2, MGMT, PTEN, TP73, and PRDM2. These panel achieved 95% sensitivity, 98% specificity, 97.44% positive predictive value (PPV), 94.23% negative predictive value (NPV), and AUC of 0.993. Hypermethylation of BRCA1, CDH1, CDKN2A, ESR1, GSTP, HIC1, MGMT, PRDM2, PTEN, PYCARDM, RASSF1M, THBS1, and TP73 associated significantly with worse OS and DFS in TNBC cohort. Meanwhile, CCNA1 and CDH1 hypermethylation demonstrated significant associations with poor DFS but did not show significant relationships with OS in TNBC patients. PTGS2 and TNFRSF10C methylation were associated with better DFS and OS rates in TNBC patients. On multivariate Cox regression, CCND2 and PTEN hypermethylation were independent predictors of DFS in the overall BC patients. The hypermethylation of BRCA1 and GSTP were independent predictors of DFS, while PTEN hypermethylation was an independent predictor of OS in the TNBC cohort. The identification of hypermethylated genes, such as BRCA1, CCND2, CDH1, ESR1, GSTP, RASSF1, SLIT2, MGMT, and PTEN may serve as potential biomarkers or therapeutic targets for TNBC.
Whole genome sequencing of promising Lactobacillus delbrueckii subsp. bulgaricus strains isolated from Egyptian dairy products for probiotic characteristics
Authors: El-Hosseny Mostafa F. , Hassan Mervat G. , Abdel-Monem M. O. , Seadawy Mohammed G. , Elhosseny Mostafa Fetoh 
Published: February 2025

Abstract
Probiotics are living microorganisms that, when given in an adequate dose, have a healthy impact on human well-being. With global interest in self-care, dietary supplements especially probiotics is expanding rapidly due to their supported health effects. In this study, a total of twenty-two samples were collected from dairy products in Egypt’s markets, firstly isolated then identified and screened for probiotic properties under stressful conditions as NaCl, acid and bile salt conditions. After evaluation of the antimicrobial effect against widespread gram negative and gram positive human infecting bacteria, besides the antiviral assessment against (SARS-CoV-2) virus which has disturbed the world, the antibiotic susceptibility test was done. Only three promising isolates were subjected for whole genome sequence with high-output next generation technology and the obtained data was subjected to a full bioinformatics analysis. The results obtained stated the advance of our isolates to tolerate the stress factors that can struggle in the human gut as well as the antimicrobial effects. All these bright characteristics were confirmed and illustrated in detail through different and reliable genome analysis tools. Our isolates were founded to have stable genome through containing mobile genetic elements like phages and CRISPR clusters that confirm the safety and quality for human health.
Conceptual design of airborne contra rotating VAWTs for rooftop wind energy
Authors: Radhakrishnan Jayakrishnan , Sridhar Surya , Zuber Mohammed , Ng Eddie Y. K. , Shenoy B. Satish 
Published: February 2025

Abstract
Co-rotating, counter, and contra-rotating Vertical Axis Wind Turbines (VAWTs) offer higher power yields than singular turbines due to synergetic interactions, making them ideal for rooftop applications. This study focuses on enhancing the efficiency of a Contra-Rotating VAWT (CR-VAWT) using a ducted airborne configuration. A wind gathering device (WGD), optimized via the Taguchi method, is integrated around the CR-VAWT, which is elevated using an oblate spheroid aerostat designed through a force-weight approach. CFD analyses reveal that incorporating the WGD boosts power output by 32% and increases instantaneous torque by 40% during dynamic stall. The WGD enhances flow redirection towards the rotor plane, achieving a 58% power gain at a 10°skew angle. By suppressing blade-tip vortex shedding, the WGD not only improves efficiency but may also reduce noise. This portable system is suitable for rooftops with limited space, requiring fewer turbines to meet energy demands while reducing noise and improving aesthetics. It also allows for integration with other renewable technologies like photovoltaics, promoting sustainability and lowering carbon footprints. A comprehensive implementation framework is presented to support future research on airborne VAWTs.
3D-printed gelled electrolytes for electroanalytical applications
Authors: Krempiński Andrzej , Rudnicki Konrad , Korzonek Weronika , Poltorak Lukasz 
Published: February 2025

Abstract
In this work, several gelators were employed to formulate a conducive gel phase (ionic conductivity) compatible with direct ink writing/bioprinting/robocasting (different names in the literature describe the same printing technology). The main goal of this work was to evaluate gelled phases being a mixture of background electrolyte (NaCl), redox probe (Fe(CN)6
3−/4−), and gel precursor (guar gum, gelatine, agarose, and agar-agar). The studied concentration of gelators ranged from 0.1 to 4% depending on the employed system. Each gelator required a customized formulation protocol. We have found that guar gum exhibits the best printing properties (lack of aggregates blocking the printing nozzle) while giving the least reproducible electrochemical results (when a glassy carbon electrode was employed as the working electrode). The study of two other gelators (agarose and gelatin) indicated significant changes in the electrochemical properties of the investigated surface as their concentration and number of voltammetric scans were varied. The best electrochemical performance was obtained for agar-agar however, this was also a gelator causing the most problems during 3D printing. Finally, we have employed six screen-printed electrodes displaying approximate properties, that were further covered with a 3D-printed conductive gelled cube (direct printing over the electrode surface). We have found that such a system allowed for a surprisingly good electroanalytical response when the model redox probe (Fe(CN)6
3−/4−) was considered. This work is a prelude to 3D-printed gel-based detection devices we are currently developing in our team.
Cytosolic CRISPR RNAs for efficient application of RNA-targeting CRISPR-Cas systems
Authors: Cheng Ezra C K , Lam Joe K C , Kwon S Chul 
Published: February 2025

Abstract
Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) technologies have evolved rapidly over the past decade with the continuous discovery of new Cas systems. In particular, RNA-targeting CRISPR-Cas13 proteins are promising single-effector systems to regulate target mRNAs without altering genomic DNA, yet the current Cas13 systems are restrained by suboptimal efficiencies. Here, we show that U1 promoter-driven CRISPR RNAs (crRNAs) increase the efficiency of various applications, including RNA knockdown and editing, without modifying the Cas13 protein effector. We confirm that U1-driven crRNAs are exported into the cytoplasm, while conventional U6 promoter-driven crRNAs are mostly confined to the nucleus. Furthermore, we reveal that the end positions of crRNAs expressed by the U1 promoter are consistent regardless of guide sequences and lengths. We also demonstrate that U1-driven crRNAs, but not U6-driven crRNAs, can efficiently repress the translation of target genes in combination with catalytically inactive Cas13 proteins. Finally, we show that U1-driven crRNAs can counteract the inhibitory effect of miRNAs. Our simple and effective engineering enables unprecedented cytosolic RNA-targeting applications.
The spirit of the times: historical conditions and market-seeking FDI strategies by U.S. alcohol firms
Authors: Chen Xuchang , Maksimov Vladislav , Mathias Blake Dustin , Wang Stephanie Lu 
Published: February 2025

Abstract
Market-seeking foreign direct investment (FDI) remains central for firms to expand their global presence and seize opportunities abroad. However, existing research often focuses on immediate or near-term drivers related to firms’ market-seeking FDI strategies, and thus neglects the valuable insights a historical perspective can provide. To address this gap, we draw insights from imprinting theory and propose a framework theorizing the dual-layered imprinting of historical conditions stemming from both extreme historical experiences and founding conditions. Using the U.S. alcohol industry as a research context, we employ a mixed-methods approach, integrating quantitative and qualitative techniques. Our findings reveal that firms’ experiences during extreme anti-alcohol conditions, such as Prohibition, positively correlate with regulation-driven market-seeking FDI, while firms founded in more pro-alcohol periods prioritize speed-driven market-seeking FDI. Moreover, we identify how unrelated diversification, a strategy consistent with the anti-alcohol imprint but inconsistent with the pro-alcohol imprint, affects the relationship between historical imprints and FDI strategies through imprint amplification or decay. Our qualitative analyses elucidate the role of founders’ and leaders’ strategic decision-making in reinforcing the mechanisms through which historical conditions shape FDI strategy. This longitudinal framework provides insights into imprint formation, transmission, and manifestation, accounting for contextual variations and implications for FDI strategy.
ℤ2 Topological Phase Transition in Twisted Plumbene
Authors: Gholamhosseinian Ayda , Modarresi Mohsen , Rezaee Roknabadi Mahmood , Mogulkoc Aybey 
Published: February 2025

Abstract
Since the discovery of superconductivity in twisted bilayer graphene, which initiated the field of twistronics, Moiré patterns caused by different twisting angles between stacked layers of van der Waals 2D materials show unique properties in these structures. In the present study, we examine the band structures at various rotation angles within the Density Functional Theory (DFT) framework to analyze the dependence of electronic and topological properties on the twisting angle in twisted bilayer plumbene structures. The results indicate the potential for a phase transition in the plumbene bilayer, where it can transition from a trivial insulator to a conductor. Furthermore, plumbene may exhibit characteristics of a topological insulator under specific angles. This research contains both topological insulator and conductor structures. Our study suggests an intriguing possibility for changes in electronic and topological properties in this two-dimensional material, which can have potential applications in spintronic devices.
Effects of different accident scenarios and sites on the reduction factor used for expressing sheltering effectiveness
Authors: HIROUCHI Jun , WATANABE Masatoshi , HAYASHI Naho , NAGAKUBO Azusa , TAKAHARA Shogo 
Published: February 2025

Abstract
Public living in areas contaminated by nuclear accidents is exposed to radiation in the early phase and over the long term. Even under similar accident scenarios, radiation doses and sheltering effectiveness, which is one of the protective measures, depend on meteorological conditions and the surrounding environment. Radiation doses and sheltering effectiveness in the early phase of nuclear accidents are crucial information for the public as well as national and local governments planning a nuclear emergency preparedness. In this study, we assessed radiation doses and sheltering effectiveness at sites with nuclear facilities in Japan using the Off-Site Consequence Analysis code for Atmospheric Release accidents, which is one of the level-3 probabilistic risk assessment codes, for five accident scenarios: three scenarios from past severe accident studies, a scenario defined by the Nuclear Regulation Authority in Japan, and a scenario corresponding to the Fukushima-Daiichi Nuclear Power Station accident. The sheltering effectiveness differed by up to approximately 50% among the accident scenarios at the same sites and by approximately 20%–50% among sites under the same accident scenario. Differences in the radionuclide composition among the accident scenarios and the differences in wind speeds among the sites primarily caused these differences in sheltering effectiveness.&#xD;