bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD2AP promotes the progression of glioblastoma multiforme via TRIM5-mediated NF-kB signaling
Authors: Zhang Liang , He Jiawei , Zhao Wentao , Zhou Yuhang , Li Jin , Li Shaobo , Zhao Wenpeng , Zhang Lingliang , Tang Ziqian , Tan Guowei , Chen Sifang , Zhang Bingchang , Zhang Yun-wu , Wang Zhanxiang 
Published: October 2024

AbstractCD2-associated protein (CD2AP) is a scaffolding/adaptive protein that regulates intercellular adhesion and multiple signaling pathways. Although emerging evidence suggests that CD2AP is associated with several malignant tumors, there is no study investigating the expression and biological significance of CD2AP in glioblastoma multiforme (GBM). Here by studying public datasets, we found that CD2AP expression was significantly elevated in GBM and that glioma patients with increased CD2AP expression had a worse prognosis. We also confirmed the increase of CD2AP expression in clinical GBM samples and GBM cell lines. CD2AP overexpression in GBM cells promoted their proliferation, colony formation, migration, and invasion in vitro and their tumorigenesis in vivo, and reduced cell apoptosis both at basal levels and in response to temozolomide. While CD2AP knockdown had the opposite effects. Mechanistically, we revealed that CD2AP interacted with TRIM5, an NF-κB modulator. CD2AP overexpression and knockdown increased and decreased TRIM5 levels as well as the NF-κB activity, respectively. Moreover, downregulation of TRIM5 reversed elevated NF-κB activity in GBM cells with CD2AP overexpression; and inhibition of the NF-κB activity attenuated malignant features of GBM cells with CD2AP overexpression. Our findings demonstrate that CD2AP promotes GBM progression through activating TRIM5-mediated NF-κB signaling and that downregulation of CD2AP can attenuate GBM malignancy, suggesting that CD2AP may become a biomarker and the CD2AP-TRIM5-NF-κB axis may become a therapeutic target for GBM.
NOD2 reduces the chemoresistance of melanoma by inhibiting the TYMS/PLK1 signaling axis
Authors: Yun Fang , Wu Na , Yi Xiaojia , Zhang Xuedan , Feng Yu , Ni Qinxuan , Gai Yanlong , Li Enjiang , Yang Zhe , Zhang Qiao , Sai Buqing , Kuang Yingmin , Zhu Yuechun 
Published: October 2024

AbstractNucleotide-binding oligomerization domain 2 (NOD2) is an immune sensor crucial for eliciting the innate immune responses. Nevertheless, discrepancies exist regarding the effect of NOD2 on different types of cancer. This study aimed to investigate these function of NOD2 in melanoma and its underlying mechanisms. We have validated the tumor suppressor effect of NOD2 in melanoma. NOD2 inhibited the proliferation of melanoma cells, hindering their migration and invasion while promoting the onset of apoptosis. Our study showed that NOD2 expression is closely related to pyrimidine and folate metabolism. NOD2 inhibits thymidylate synthase (TYMS) expression by promoting K48-type ubiquitination modification of TYMS, thereby decreasing the resistance of melanoma cells to 5-fluorouracil (5-FU) and capecitabine (CAP). TYMS was identified to form a complex with Polo-like Kinase 1 (PLK1) and activate the PLK1 signaling pathway. Furthermore, we revealed that the combination of the PLK1 inhibitor volasertib (BI6727) with 5-FU or CAP had a synergistic effect repressing the proliferation, migration, and autophagy of melanoma cells. Overall, our research highlights the protective role of NOD2 in melanoma and suggests that targeting NOD2 and the TYMS/PLK1 signaling axis is a high-profile therapy that could be a prospect for melanoma treatment.
Aberrant activation of a miR-101–UBE2D1 axis contributes to the advanced progression and chemotherapy sensitivity in human hepatocellular carcinoma
Authors: Mu Xiuli , Wei Yuchen , Fan Xin , Zhang Rui , Xi Wenjin , Zheng Guoxu , Yang An-gang 
Published: October 2024

AbstractChemotherapeutic drugs, such as cisplatin (cis-dichlorodiamineplatinum [II], cDDP) and 5-fluorouracil (5Fu), are widely used in transarterial chemoembolization (TACE), which is a standard therapy for patients with hepatocellular carcinoma (HCC). Chemoresistance is a major cause of TACE treatment failure in HCC patients. Our previous studies have identified the expression levels of miR-101 responsive genes, such as EED, EZH2, STMN1 and JUNB, exhibit significant correlation with the occurrence and progression of HCC, while the role of miR-101 responsive gene signatures in the chemoresistance of HCC treatment remains unclear. In this study, we identified ubiquitin-coupled enzyme E2D1 (UBE2D1) as a crucial regulatory factor in the chemoresistance of HCC, which is a direct target of miR-101 and exhibits significant correlation with miR-101-responsive gene signatures. The bioinformatics analysis showed the expression of UBE2D1 was significantly increased in HCC tissues and was closely correlated with the poor prognosis. In addition, we analyzed the role of miR-101/UBE2D1 axis in regulating chemo-sensitive of HCC cells. Our results showed that miR-101 increases the DNA damage and apoptosis of HCC cells by inhibiting the expression of UBE2D1, which in turn increases the sensitivity of HCC cells to cDDP and 5Fu both in vitro and in vivo. Therefore, simultaneous assessment of miR-101 and UBE2D1 expression levels might provide an effective approach in preselecting HCC patients with survival benefit from TACE treatment. Moreover, further elucidation of the underlying molecular mechanisms of the miR-101/UBE2D1 axis could provide novel insight for targeted therapy of HCC.
Tapasin assembly surveillance by the RNF185/Membralin ubiquitin ligase complex regulates MHC-I surface expression
Authors: van de Weijer Michael L. , Samanta Krishna , Sergejevs Nikita , Jiang LuLin , Dueñas Maria Emilia , Heunis Tiaan , Huang Timothy Y. , Kaufman Randal J. , Trost Matthias , Sanyal Sumana , Cowley Sally A. , Carvalho Pedro 
Published: October 2024

AbstractImmune surveillance by cytotoxic T cells eliminates tumor cells and cells infected by intracellular pathogens. This process relies on the presentation of antigenic peptides by Major Histocompatibility Complex class I (MHC-I) at the cell surface. The loading of these peptides onto MHC-I depends on the peptide loading complex (PLC) at the endoplasmic reticulum (ER). Here, we uncovered that MHC-I antigen presentation is regulated by ER-associated degradation (ERAD), a protein quality control process essential to clear misfolded and unassembled proteins. An unbiased proteomics screen identified the PLC component Tapasin, essential for peptide loading onto MHC-I, as a substrate of the RNF185/Membralin ERAD complex. Loss of RNF185/Membralin resulted in elevated Tapasin steady state levels and increased MHC-I at the surface of professional antigen presenting cells. We further show that RNF185/Membralin ERAD complex recognizes unassembled Tapasin and limits its incorporation into PLC. These findings establish a novel mechanism controlling antigen presentation and suggest RNF185/Membralin as a potential therapeutic target to modulate immune surveillance.
Striato-pallidal oscillatory connectivity correlates with symptom severity in dystonia patients
Authors: Lofredi Roxanne , Feldmann Lucia K. , Krause Patricia , Scheller Ute , Neumann Wolf-Julian , Krauss Joachim K. , Saryyeva Assel , Schneider Gerd-Helge , Faust Katharina , Sander Tilmann , Kühn Andrea A. 
Published: October 2024

AbstractDystonia is a hyperkinetic movement disorder that has been associated with an imbalance towards the direct pathway between striatum and internal pallidum, but the neuronal underpinnings of this abnormal basal ganglia pathway activity remain unknown. Here, we report invasive recordings from ten dystonia patients via deep brain stimulation electrodes that allow for parallel recordings of several basal ganglia nuclei, namely the striatum, external and internal pallidum, that all displayed activity in the low frequency band (3–12 Hz). In addition to a correlation with low-frequency activity in the internal pallidum (R = 0.88, P = 0.001), we demonstrate that dystonic symptoms correlate specifically with low-frequency coupling between striatum and internal pallidum (R = 0.75, P = 0.009). This points towards a pathophysiological role of the direct striato-pallidal pathway in dystonia that is conveyed via coupling in the enhanced low-frequency band. Our study provides a mechanistic insight into the pathophysiology of dystonia by revealing a link between symptom severity and frequency-specific coupling of distinct basal ganglia pathways.
The molecular dissection of TRIM25’s RNA-binding mechanism provides key insights into its antiviral activity
Authors: Álvarez Lucía , Haubrich Kevin , Iselin Louisa , Gillioz Laurent , Ruscica Vincenzo , Lapouge Karine , Augsten Sandra , Huppertz Ina , Choudhury Nila Roy , Simon Bernd , Masiewicz Pawel , Lethier Mathilde , Cusack Stephen , Rittinger Katrin , Gabel Frank , Leitner Alexander , Michlewski Gracjan , Hentze Matthias W. , Allain Frédéric H. T. , Castello Alfredo , Hennig Janosch 
Published: October 2024

AbstractTRIM25 is an RNA-binding ubiquitin E3 ligase with central but poorly understood roles in the innate immune response to RNA viruses. The link between TRIM25’s RNA binding and its role in innate immunity has not been established. Thus, we utilized a multitude of biophysical techniques to identify key RNA-binding residues of TRIM25 and developed an RNA-binding deficient mutant (TRIM25-m9). Using iCLIP2 in virus-infected and uninfected cells, we identified TRIM25’s RNA sequence and structure specificity, that it binds specifically to viral RNA, and that the interaction with RNA is critical for its antiviral activity.
Interventions for the control of Crimean-Congo hemorrhagic fever and tick vectors
Authors: de la Fuente José , Ghosh Srikant , Lempereur Laetitia , Garrison Aura , Sprong Hein , Lopez-Camacho Cesar , Maritz-Olivier Christine , Contreras Marinela , Moraga-Fernández Alberto , Bente Dennis A. 
Published: October 2024

AbstractCrimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease associated with its principal tick vector, Hyalomma spp. with increasing fatal incidence worldwide. Accordingly, CCHF is a World Health Organization-prioritized disease with the absence of effective preventive interventions and approved vaccines or effective treatments. This perspective raised from a multidisciplinary gap analysis considering a One Health approach beneficial for human and animal health and the environment exploring international collaborations, gaps and recommendations.
Fluctuations and extreme events in the public attention on Italian legislative elections
Authors: Auconi Andrea , Federico Lorenzo , Riotta Gianni , Caldarelli Guido 
Published: October 2024

AbstractThe share of social media attention to political candidates was shown to be a good predictor of election outcomes in several studies. This attention to individual candidates fluctuates due to incoming daily news and sometimes reflects long-term trends. By analyzing Twitter data in the 2013 and 2022 election campaign we observe that, on short timescales, the dynamics can be effectively characterized by a mean-reverting diffusion process on a logarithmic scale. This implies that the response to news and the exchange of opinions on Twitter lead to attention fluctuations spanning orders of magnitudes. However, these fluctuations remain centered around certain average levels of popularity, which change slowly in contrast to the rapid daily and hourly variations driven by Twitter trends and news. In particular, on our 2013 data we are able to estimate the dominant timescale of fluctuations at around three hours. Finally, by considering the extreme data points in the tail of the attention variation distribution, we could identify critical events in the electoral campaign period and extract useful information from the flow of data.
A comparative UPLC-orbitrap-MS-based metabolite profiling of three Pelargonium species cultivated in Egypt
Authors: Merghany Rana M. , Salem Mohamed A. , Ezzat Shahira M. , Moustafa Sherifa F. A. , El-Sawi Salma A. , Meselhy Meselhy R. 
Published: October 2024

Abstract
Several Pelargonium species are cultivated mainly to produce essential oils used in perfume industry and for ornamental purposes. Although the chemical composition and biological activities of their essential oils were extensively investigated, there is limited information about the chemical composition of their non-volatile constituents. In this study, we report an Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS)-based metabolomics approach for the annotation and analysis of various metabolites in three species; P. graveolens, P. denticulatum, and P. fragrans utilizing The Global Natural Product Social Molecular Networking (GNPS) and multivariate data analyses for clustering of the metabolites. A total of 154 metabolites belonging to different classes were annotated. The three species are good sources of coumarins, benzoic acid derivatives, organic acids, fatty acids, and phospholipids. However, the highest level of flavonols (mono- and di-O-glycosides) and cinnamic acid derivatives was found in P. graveolens and P. denticulatum, whereas tannins and flavone C-glycosides were abundant in P. fragrans. The metabolic profiles clarified here provide comprehensive information on the non-volatile constituents of the three Pelargonium species and can be employed for their authentication and possible therapeutic applications.
Optimizing COP by RSM and MATLAB model of mini refrigerator based on thermoelectric units driven by solar photovoltaic
Authors: Elnaggar Amal E. M. , Sharaf Soliman , Abedel Rehim Zeinab S. , El-Bayoumi M. A. , Mustafa Hassan M. M. , El Zoghby Helmy M. 
Published: October 2024

AbstractEnergy scarcity in the world and the pollutants resulting from excessive use of conventional energy aroused the need for sustainable alternatives that are environment friendly. A multi-use thermoelectric refrigerator powered by solar energy to obtain the lowest consumption with the highest efficiency. The designed refrigerator is based on the Peltier effect using Peltier units where a temperature difference is created between the junctions by applying a voltage difference across the junction. This study investigates the performance of a refrigerator cooling system powered by a photovoltaic (PV) system. The research aims to assess the efficiency, effectiveness, and feasibility of utilizing solar energy to drive refrigeration, particularly in off-grid or environmentally conscious applications. Through a comprehensive experimental setup and data analysis, the study examines energy consumption, cooling efficiency, and overall system performance under varying conditions. The findings contribute valuable insights into the potential of PV-powered refrigerators as sustainable cooling solutions. It relies on a control unit that measures the resulting temperature to determine the appropriate connection mode to give the highest cooling efficiency. The average solar radiation when operating for 8 h, for the different seasons of the year was 149.5, 67.5, 119.3, and 118.3 w/m2 in summer, winter, spring, and fall, respectively. The average cooling energy consumption was 107.25, 137.04, 107, and 138.08 w for temperatures (20 ± 1, 15 ± 1, 20 ± 2, and 15 ± 2) °C respectively that proof solar radiation is sufficient to produce energy for the summer of cooling temperatures up to 15 °C, while in the spring and fall it is sufficient to 20 °C. The Fast not Eco mode is the least energy consuming and the fastest cooling, it can be used for rapid cooling at a short time less than an hour. The best mode in the case of continuous operation is the case of as next Eco mode cooling temperature of 20 ± 0.1 °C. The MATLAB Simulink model was developed to reduce the design cycle and facilitate the integration of solar photovoltaic with the TEC. The optimal operating point is identified through simulation and validated through experimental analysis, the optimal COP was 71.089% by Response surface methodology (RSM).
Limited open information sharing and mobility promotes sustainability of jaguar tourism in Pantanal wetland, Brazil
Authors: Tortato Fernando , Gottesman Alice , Hoogesteijn Rafael , Martin Abigail , Dyble Mark , Chiaravalloti Rafael 
Published: October 2024

AbstractWildlife tourism plays a crucial role in biodiversity conservation. However, long-term sustainability is difficult to achieve. In this paper, we use property theory to produce a mathematical model that aims to better support stakeholders from the wildlife tourism industry to better guarantee a balance between sightings probability, tourists’ overall experience and operators’ sharing behaviour. We illustrate our model with the case study of Porto Jofre in the Pantanal wetland, Brazil. We show that while dealing with low sighting probability, tourist operators must share information about species’ locations, leading to a system of open access regarding mobility and information. However, when sightings become common, sharing must be restricted to a bounded group avoiding overcrowding, a system of limited open access. Finally, when the sighting probability is high, no sharing is needed to achieve maximum overall experience. Our case study in Porto Jofre, Pantanal, Brazil, clearly shows these shifts in terms of governance strategies. We show that by looking at sighting probability it is possible to predict the best optimal social strategy that will guarantee long-term sustainability of the wildlife tourism initiatives. We also show the need for external support on adaptation in cases where current strategies do not match the predicted ones.
Sex differences in the development of experimental diabetic retinopathy
Authors: Chen Ying , Schlotterer Andrea , Lin Jihong , Dietrich Nadine , Fleming Thomas , Lanzinger Stefanie , Holl Reinhard W. , Hammes Hans-Peter 
Published: October 2024

AbstractThis study aimed to characterize the role of female sex in the pathogenesis of diabetic retinopathy. In the retinae of female Ins2Akita-diabetic mice (F-IA), ovariectomized female Ins2Akita-diabetic mice (F-IA/OVX), male Ins2Akita-diabetic mice (M-IA), and female STZ-diabetic mice (F-STZ), the formation of reactive metabolites and post-translational modifications, damage to the neurovascular unit, and expression of cellular stress response genes were analyzed. Compared to the male diabetic retina, the concentrations of the glycation adduct fructosyl-lysine, the Maillard product 3-deoxyglucosone, and the reactive metabolite methylglyoxal were significantly reduced in females. In females, there was also less evidence of diabetic damage to the neurovascular unit, as shown by decreased pericyte loss and reduced microglial activation. In the male diabetic retina, the expression of several members of the crystallin gene family (Cryab, Cryaa, Crybb2, Crybb1, and Cryba4) was increased. Clinical data from type 1 diabetic females showed that premenopausal women had a significantly lower prevalence of diabetic retinopathy compared to postmenopausal women stratified for disease duration and glycemic control. These data emphasize the importance of estradiol in protecting the diabetic retina and highlight the pathogenic relevance of sex in diabetic retinopathy.
Assessing the potential role of arbuscular mycorrhizal fungi in improving the phytochemical content and antioxidant properties in Gomphrena globosa
Authors: Dhalaria Rajni , Verma Rachna , Sharma Rohit , Jomova Klaudia , Nepovimova Eugenie , Kumar Harsh , Kuca Kamil 
Published: October 2024

AbstractStrategies to increase the secondary metabolite production, obtained from medicinal plants has been the topic of research in recent years. The symbiotic interaction between arbuscular mycorrhizal fungi and plants allows host-fungus pairings to enhance secondary metabolite synthesis. Therefore, the current study investigated the effect of inoculating two distinct AMF species discretely as well as in conjunction on the flower-derived secondary metabolites in Gomphrena globosa. The findings showed that the plants inoculated with combined treatment exhibited higher total phenolic (50.11 mg GAE/g DW), flavonoids (29.67 mg QE/g DW), saponins (122.55 mg DE/g DW), tannins (165.71 TAE/g DW) and terpenoid (8.24 mg LE/g DW) content in the methanolic extract. HPTLC examination showed the existence of kaempferol and benzoic acid with the highest amount (0.90% and 5.83% respectively) observed in the same treatment. FTIR analysis revealed functional group peaks with increased peak intensity in the combination treatment. Higher antioxidant activities such as DPPH (IC50: 401.39 µg/mL), ABTS (IC50: 71.18 µg/mL) and FRAP (8774.73 µM Fe (II) equivalent) were observed in the methanolic extract of combined treatment. To our knowledge, this is the first study on the impact of AMF inoculation on bioactive compounds and antioxidant activities in G. globosa flowers. Moreover, this study could lead to the development of novel pharmaceuticals and herbal remedies for various diseases.
Pipe experiment elucidates biochar application depth affects nitrogen leaching under crop present condition
Authors: Hamada Kosuke , Nakamura Satoshi , Kuniyoshi Daichi 
Published: October 2024

AbstractNitrogen leaching, resulting from the inefficient use of fertilizers, pollutes the environment, such as groundwater. Biochar can be applied to farmlands to mitigate nitrogen leaching. The effect depends on the application depth. However, the effect has not been examined under crop-farming conditions. Evaluating the interactions between biochar application depth and crop growth is indispensable for considering depth in the actual field. To address this, we conducted a pipe experiment with four treatments, no biochar (control), surface (0–5 cm), plow layer (0–30 cm), and subsurface (25–30 cm) applications, and compared the results with no-crop conditions from a previous study. Biochar application depth affected soil NO3−−N and NH4+−N absorption ability and also influenced soil-water stress conditions, affecting crop growth. Surface biochar application improved nitrogen absorption and reduced soil-water stress, improving crop growth. The NO3−−N leaching was reduced to 87.7%. Plow layer application worsened nitrogen absorption and resulted in frequent dry stress in the shallow-soil layer, preventing root growth in this layer. The NO3−−N and NH4+−N leaching increased 106.4% and 264.1%, respectively. The effects of subsurface application were similar to those in the control. Selecting an appropriate application depth can simultaneously improve crop growth and reduce nitrogen leaching.