bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erianin induces ferroptosis in GSCs via REST/LRSAM1 mediated SLC40A1 ubiquitination to overcome TMZ resistance
Authors: Mansuer Maierdan , Zhou Lin , Wang Chengbin , Gao Liang , Jiang Yang 
Published: July 2024

AbstractIn recent studies, erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, has exhibited notable anticancer properties. Ferroptosis, a novel form of programmed cell death, holds potential as a strategy to overcome Temozolomide (TMZ) resistance in glioma by inducing ferroptosis in TMZ-resistant glioma cells. Here, utilizing various phenotyping experiments, including cell counting kit-8 (CCK-8) assays, EdU assays, transwell assays, neurosphere formation assays and extreme limiting dilution (ELDA) assays, we demonstrated that erianin exerts its anticancer activity on both TMZ sensitive and TMZ-resistant glioma stem cells (GSCs). Furthermore, we made an exciting discovery that erianin enhances TMZ sensitivity in TMZ-resistant GSCs. Subsequently, we demonstrated that erianin induced ferroptosis in TMZ-resistant GSCs and enhances TMZ sensitivity through inducing ferroptosis, which was confirmed by intracellular measurements of ROS, GSH, and MDA, as well as through the use of BODIPY (581/591) C11 and transmission electron microscopy. Conversely, the ferroptosis inhibitor ferrostatin-1 (Fer-1) blocked the effects of erianin. The underlying mechanism of ferroptosis induced by erianin was further explored through co-immunoprecipitation (Co-IP) assays, ubiquitination assays, protein stability assessments, chromatin immunoprecipitation (ChIP) assays and luciferase reporter gene assays. We found that erianin specifically targets REST, inhibiting its transcriptional repression function without altering its expression levels. Consequently, this suppression of REST’s role leads to an upregulation of LRSAM1 expression. In turn, LRSAM1 ubiquitinates and degrades SLC40A1, a protein that inhibits ferroptosis by exporting ferrous ions. By downregulating SLC40A1, erianin ultimately induces ferroptosis in TMZ-resistant GSCs. Taken together, our research demonstrates that the natural product erianin inhibits the malignant phenotype of GSCs and increases the sensitivity of TMZ in TMZ-resistant GSCs by inducing ferroptosis. These findings suggest erianin as a prospective compound for the treatment of TMZ-resistant glioma.
Characterization of brain transduction capability of a BBB-penetrant AAV vector in mice, rats and macaques reveals differences in expression profiles
Authors: Bunuales María , Garduno Angeles , Chillon Miguel , Bosch Assumpció , Gonzalez-Aparicio Manuela , Espelosin Maria , Garcia-Gomara Marta , Rico Alberto J. , Garcia-Osta Ana , Cuadrado-Tejedor Mar , Lanciego Jose L. , Hernandez-Alcoceba Ruben 
Published: July 2024

AbstractDifferent screening methods are being developed to generate adeno-associated viral vectors (AAV) with the ability to bypass the blood-brain barrier (BBB) upon intravenous administration. Recently, the AAV9P31 stood out as the most efficient version among a library of peptide-displaying capsids selected in C57BL/6 mice using RNA-driven biopanning. In this work we have characterized in detail its biodistribution in different mouse strains (C57BL/6 and Balb/c), as well as in Sprague Dawley rats and non-human primates (Macaca fascicularis). Using GFP and NanoLuc reporter genes, we confirmed homogeneous infection and transgene expression across the CNS of mice injected intravenously with AAV9P31. A more restricted pattern was observed upon either intracerebroventricular or intraparenchymal injection. Following intravenous delivery, region- and cell-specific differential patterns of transduction were observed in the mouse brain, including a preferential transduction of astrocytes and neurons in the cerebral cortex and striatum, whereas neurons were the only transduced cell type in subcortical locations across the hippocampus, thalamus, hypothalamus, mesencephalon, brainstem and cerebellum. Furthermore, transduced microglial cells were never found in any CNS location. Peripheral organs transduced upon intravenous administration included lung, liver, peritoneum, heart and skeletal muscle. However, a comparable performance of AAV9P31 to bypass the BBB in rats and macaques was not observed, although a more limited neuronal transduction was found in the brainstem of rats upon intravenous delivery. Finally, intracerebroventricular delivery in macaques resulted in neuronal transduction in cortical, subcortical structures and cerebellum following a patchy pattern. In conclusion, the widespread CNS transduction obtained in mice upon intravenous delivery of AAV9P31 represents a powerful tool for modeling a wide variety of neurological disorders as well as an appealing choice for the evaluation of gene therapy-based therapeutics.
Dielectrophoretic bead-droplet reactor for solid-phase synthesis
Authors: Padhy Punnag , Zaman Mohammad Asif , Jensen Michael Anthony , Cheng Yao-Te , Huang Yogi , Wu Mo , Galambos Ludwig , Davis Ronald Wayne , Hesselink Lambertus 
Published: July 2024

AbstractSolid-phase synthesis underpins many advances in synthetic and combinatorial chemistry, biology, and material science. The immobilization of a reacting species on the solid support makes interfacing of reagents an important challenge in this approach. In traditional synthesis columns, this leads to reaction errors that limit the product yield and necessitates excess consumption of the mobile reagent phase. Although droplet microfluidics can mitigate these problems, its adoption is fundamentally limited by the inability to controllably interface microbeads and reagent droplets. Here, we introduce Dielectrophoretic Bead-Droplet Reactor as a physical method to implement solid-phase synthesis on individual functionalized microbeads by encapsulating and ejecting them from microdroplets by tuning the supply voltage. Proof-of-concept demonstration of the enzymatic coupling of fluorescently labeled nucleotides onto the bead using this reactor yielded a 3.2-fold higher fidelity over columns through precise interfacing of individual microreactors and beads. Our work combines microparticle manipulation and droplet microfluidics to address a long-standing problem in solid-phase synthesis with potentially wide-ranging implications.
Energy-saving hydrogen production by seawater electrolysis coupling tip-enhanced electric field promoted electrocatalytic sulfion oxidation
Authors: Li Tongtong , Wang Boran , Cao Yu , Liu Zhexuan , Wang Shaogang , Zhang Qi , Sun Jie , Zhou Guangmin 
Published: July 2024

AbstractHydrogen production by seawater electrolysis is significantly hindered by high energy costs and undesirable detrimental chlorine chemistry in seawater. In this work, energy-saving hydrogen production is reported by chlorine-free seawater splitting coupling tip-enhanced electric field promoted electrocatalytic sulfion oxidation reaction. We present a bifunctional needle-like Co3S4 catalyst grown on nickel foam with a unique tip structure that enhances the kinetic rate by improving the current density in the tip region. The assembled hybrid seawater electrolyzer combines thermodynamically favorable sulfion oxidation and cathodic seawater reduction can enable sustainable hydrogen production at a current density of 100 mA cm−2 for up to 504 h. The hybrid seawater electrolyzer has the potential for scale-up industrial implementation of hydrogen production by seawater electrolysis, which is promising to achieve high economic efficiency and environmental remediation.
Highly efficient pure-blue organic light-emitting diodes based on rationally designed heterocyclic phenophosphazinine-containing emitters
Authors: Xing Longjiang , Wang Jianghui , Chen Wen-Cheng , Liu Bo , Chen Guowei , Wang Xiaofeng , Tan Ji-Hua , Chen Season Si , Chen Jia-Xiong , Ji Shaomin , Zhao Zujin , Tang Man-Chung , Huo Yanping 
Published: July 2024

AbstractMulti-resonance thermally activated delayed fluorophores have been actively studied for high-resolution photonic applications due to their exceptional color purity. However, these compounds encounter challenges associated with the inefficient spin-flip process, compromising device performance. Herein, we report two pure-blue emitters based on an organoboron multi-resonance core, incorporating a conformationally flexible donor, 10-phenyl-5H-phenophosphazinine 10-oxide (or sulfide). This design concept selectively modifies the orbital type of high-lying excited states to a charge transfer configuration while simultaneously providing the necessary conformational freedom to enhance the density of excited states without sacrificing color purity. We show that the different embedded phosphorus motifs (phosphine oxide/sulfide) of the donor can finely tune the electronic structure and conformational freedom, resulting in an accelerated spin-flip process through intense spin-vibronic coupling, achieving over a 20-fold increase in the reverse intersystem crossing rate compared to the parent multi-resonance emitter. Utilizing these emitters, we achieve high-performance pure-blue organic light-emitting diodes, showcasing a top-tier external quantum efficiency of 37.6% with reduced efficiency roll-offs. This proposed strategy not only challenges the conventional notion that flexible electron-donors are undesirable for constructing narrowband emitters but also offer a pathway for designing efficient narrow-spectrum blue organic light-emitting diodes.
Chemical language modeling with structured state space sequence models
Authors: Özçelik Rıza , de Ruiter Sarah , Criscuolo Emanuele , Grisoni Francesca 
Published: July 2024

AbstractGenerative deep learning is reshaping drug design. Chemical language models (CLMs) – which generate molecules in the form of molecular strings – bear particular promise for this endeavor. Here, we introduce a recent deep learning architecture, termed Structured State Space Sequence (S4) model, into de novo drug design. In addition to its unprecedented performance in various fields, S4 has shown remarkable capabilities to learn the global properties of sequences. This aspect is intriguing in chemical language modeling, where complex molecular properties like bioactivity can ‘emerge’ from separated portions in the molecular string. This observation gives rise to the following question: Can S4 advance chemical language modeling for de novo design? To provide an answer, we systematically benchmark S4 with state-of-the-art CLMs on an array of drug discovery tasks, such as the identification of bioactive compounds, and the design of drug-like molecules and natural products. S4 shows a superior capacity to learn complex molecular properties, while at the same time exploring diverse scaffolds. Finally, when applied prospectively to kinase inhibition, S4 designs eight of out ten molecules that are predicted as highly active by molecular dynamics simulations. Taken together, these findings advocate for the introduction of S4 into chemical language modeling – uncovering its untapped potential in the molecular sciences.
A dataset for deep learning based detection of printed circuit board surface defect
Authors: Lv Shengping , Ouyang Bin , Deng Zhihua , Liang Tairan , Jiang Shixin , Zhang Kaibin , Chen Jianyu , Li Zhuohui 
Published: July 2024

AbstractPrinted circuit board (PCB) may display diverse surface defects in manufacturing. These defects not only influence aesthetics but can also affect the performance of the PCB and potentially damage the entire board. Thus, achieving efficient and highly accurate detection of PCB surface defects is fundamental for quality control in fabrication. The rapidly advancing deep learning (DL) technology holds promising prospects for providing accurate and efficient detection methods for surface defects on PCB. To facilitate DL model training, it is imperative to compile a comprehensive dataset encompassing diverse surface defect types found on PCB at a significant scale. This work categorized PCB surface defects into 9 distinct categories based on factors such as their causes, locations, and morphologies and developed a dataset of PCB surface defect (DsPCBSD+). In DsPCBSD+, a total of 20,276 defects were annotated manually by bounding boxes on the 10,259 images. This openly accessible dataset is aimed accelerating and promoting further researches and advancements in the field of DL-based detection of PCB surface defect.
Experimental analysis of enhanced finite set model predictive control and direct torque control in SRM drives for torque ripple reduction
Authors: M Deepak , Samithas Devakirubakaran , Balachandran Praveen Kumar , Selvarajan Shitharth 
Published: July 2024

AbstractThe magnet-less switched reluctance motor (SRM) speed-torque characteristics are ideally suited for traction motor drive characteristics and its advantage to minimize the overall cost of on-road EVs. The main drawbacks are torque and flux ripple, which have produced high in low-speed operation. However, the emerging direct torque control (DTC) operated magnitude flux and torque estimation with voltage vectors (VVs) gives high torque ripples due to the selection of effective switching states and sector partition accuracy. On the other hand, the existing model predictive control (MPC) with multiple objective and optimization weighting factors produces high torque ripples due to the system dynamics and constraints. Therefore, existing DTC and MPC can result in high torque ripples. This paper proposed a finite set (FS)-MPC with a single cost function objective without weighting factor: the predicted torque considered to evaluate VVs to minimize the ripples further. The selected optimal VV minimizes the SRM drive torque and flux ripples in steady and dynamic state behaviour. The classical DTC and proposed model were developed, and simulation results were verified using MATLAB/Simulink. The proposed model operated in SRM drives experimental results to prove the effective minimization of torque and flux ripples compared to the existing DTC.
Comparison of atrial fibrillation prevalence and in-hospital cardiovascular outcomes between patients undergoing allogeneic versus autologous hematopoietic stem cell transplantation: insights from the national inpatient sample
Authors: Krishan Satyam , Asad Zain Ul Abideen , Quiroga Dionisia , Ghazi Sanam M. , Quartermaine Cooper , Braunstein Zachary , Kola-Kehinde Onaopepo , Shaaban Adnan , Habib Alma , Khan Sarah , Cheng Richard , Brammer Jonathan E. , Addison Daniel 
Published: July 2024

AbstractHematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant hematologic conditions. However, patients undergoing HSCT are at increased risk of developing serious cardiovascular events. Whether cardiovascular risks differ by the type of transplantation strategy used, allogeneic versus autologous HSCT, is unknown. Leveraging the National Inpatient Sample (2016–2019), we assessed the incidence of early cardiovascular events by HSCT mode (allogeneic vs autologous). The primary outcome was the incidence of atrial fibrillation (AF). The secondary outcome was the occurrence of any major adverse cardiac events (MACE), defined as acute heart failure, myocardial infarction (MI), symptomatic atrial or ventricular arrhythmia or heart block, and cardiovascular death. Outcomes were compared between those undergoing allogeneic versus autologous HSCT. Multivariable regression, adjusting for cardiovascular and cancer-related factors, was used to define the association between pre-HSCT factors and MACE. We further assessed the effect of acute cardiovascular events on in-patient mortality by calculating adjusted odds ratio (aOR) with corresponding 95% confidence intervals (CI) and p-values. Overall, 64,705 weighted hospitalizations for HSCT were identified, of which 22,655 (35.0%) were allogeneic HSCT and 42,050 (65.0%) were autologous HSCT. The prevalence of AF was 9.1%, and 12.1% for any arrhythmia. In multivariable regression, allogeneic HSCT was associated with higher adjusted odds of peri-HSCT acute heart failure (aOR 2.64; 1.86–3.76; p < 0.0001), QT prolongation (aOR 1.40; 1.04–1.88; p = 0.025), MI (aOR 2.87; 1.16–7.11; p = 0.023), any major cardiovascular complication (aOR 1.16; 1.03–1.32; p = 0.016), and inpatient mortality (aOR 4.87; 3.60–6.58; p < 0.0001). Following cerebrovascular events, AF was the strongest predictor of mortality. Allogeneic HSCT was associated with higher odds of in-hospital cardiovascular complications among patients undergoing HSCT.
Regional variation in social norm nudges
Authors: Goerg Sebastian J. , Pondorfer Andreas , Stöhr Valentina 
Published: July 2024

AbstractPublic support is crucial for the effectiveness of ambitious climate policies, and social norm interventions have been proven effective in fostering support. An open question is which norms should be communicated if support and estimated support for climate policies differ substantially between regions. In two studies, we investigate whether individuals accurately assess the existing support and then explore the impact of national and regional norms on public support. Our results show that the norm on climate policy support is generally misperceived, i.e., the norm is higher than expected. This misperception increases with policy ambition and varies substantially between sub-national regions. Information about the national norm increases support, mainly in regions with below or above-average support. In contrast, interventions with regional norms are ineffective and even backfire in low-support regions. This demonstrates that norm nudges need to consider the regional aspects of the reference and target groups.
Appraisal terpenoids rich Boswellia carterri ethyl acetate extract in binary cyclodextrin oligomer nano complex for improving respiratory distress
Authors: Ibrahim Bassant M. M. , Darwish Asmaa Badawy , Taleb Sally Abou , Mourad Reda M. , Yassen Noha Nazeeh , Hessin Alyaa F. , Gad Shaimaa A. , Mohammed Mona A. 
Published: July 2024

AbstractBoswellia carterii (BC) resins plants have a long historical background as a treatment for inflammation, as indicated by information originating from multiple countries. Twenty-seven diterpenoids have been identified in ethyl acetate and total methanol BC, comprising seventeen boscartins of the cembrane-type diterpenoids and ten boscartols of the prenylaromadendrane-type diterpenoids. Moreover, twenty-one known triterpenoids have also been found, encompassing nine tirucallane-type, six ursane-type, four oleanane-type, and two lupane-type. The cembrane-type diterpenoids hold a significant position in pharmaceutical chemistry and related industries due to their captivating biological characteristics and promising pharmacological potentials. Extraction of BC, creation and assessment of nano sponges loaded with either B. carterii plant extract or DEX, are the subjects of our current investigation. With the use of ultrasound-assisted synthesis, nano sponges were produced. The entrapment efficiency (EE%) of medications in nano sponges was examined using spectrophotometry. Nano sponges were characterized using a number of methods. Within nano sponges, the EE% of medicines varied between 98.52 ± 0.07 and 99.64 ± 1.40%. The nano sponges' particle sizes varied from 105.9 ± 15.9 to 166.8 ± 26.3 nm. Drugs released from nano sponges using the Korsmeyer-Peppas concept. In respiratory distressed rats, the effects of BC plant extract, DEX salt and their nano formulations (D1, D5, P1 and P1), were tested. Treatment significantly reduced ICAM-1, LTB4, and ILβ 4 levels and improved histopathologic profiles, when compared to the positive control group. Boswellia extract and its nano sponge formulation P1 showed promising therapeutic effects. The effect of P1 may be due to synergism between both the extract and the formulation. This effect was achieved by blocking both ICAM-1 and LTB4 pathways, therefore counteracting the effects of talc powder.
Targeting hyaluronan metabolism-related molecules associated with resistant tumor-initiating cells potentiates chemotherapy efficacy in lung cancer
Authors: Díaz Marco Aurelio , Fusco Mariel , Benítez Constanza Arriola , Gayet Fernando , García Ludmila , Victoria Lucia , Jaramillo Sebastián , Bayo Juan , Zubieta Mariana Rodríguez , Rizzo Manglio M. , Piccioni Flavia , Malvicini Mariana 
Published: July 2024

AbstractThe success of chemotherapy regimens in patients with non-small cell lung cancer (NSCLC) could be restricted at least in part by cancer stem cells (CSC) niches within the tumor microenvironment (TME). CSC express CD133, CD44, CD47, and SOX2, among other markers and factors. Analysis of public data revealed that high expression of hyaluronan (HA), the main glycosaminoglycan of TME, correlated positively with CSC phenotype and decreased disease-free interval in NSCLC patients. We aimed to cross-validate these findings on human and murine lung cancer cells and observed that CD133 + CSC differentially expressed higher levels of HA, HAS3, ABCC5, SOX2, and CD47 (p < 0.01). We modulated HA expression with 4-methylumbelliferone (4Mu) and detected an increase in sensitivity to paclitaxel (Pa). We evaluated the effect of 4Mu + chemotherapy on survival, HA metabolism, and CSC profile. The combination of 4Mu with Pa reduced the clonogenic and tumor-forming ability of CSC. Pa-induced HAS3, ABCC5, SOX2, and CD47 expression was mitigated by 4Mu. Pa + 4Mu combination significantly reduced in vivo tumor growth, enhancing animal survival and restoring the CSC profile in the TME to basal levels. Our results suggest that HA is involved in lung CSC phenotype and chemosensitivity, and its modulation by 4Mu improves treatment efficacy to inhibit tumor progression.
The potential role of robust face representations learned within families when searching for one’s child in a crowd
Authors: Kawachi Yousuke , Murata Aiko , Kitamura Miho S. , Mugitani Ryoko 
Published: July 2024

AbstractOwn child’s face is one of the most socially salient stimuli for parents, and a faster search for it than for other children’s faces may help provide warmer and more sensitive care. However, it has not been experimentally examined whether parents find their child’s face faster. In addition, although own child’s face is specially processed, the search time for own child’s face may be similar to that for other socially salient stimuli, such as own or spouse’s faces. This study tested these possibilities using a visual search paradigm. Participants (parents) searched for their child’s, own, spouse’s, other child’s, same-sex adult’s, or opposite-sex adult’s faces as search targets. Our findings indicate that both mothers and fathers identified their child’s face more quickly than other children’s faces. Similarly, parents found their own and spouse’s faces more quickly than other adults’ faces. Moreover, the search time for family members’ faces increased with the number of faces on the search display, suggesting an attentional serial search. These results suggest that robust face representations learned within families and close relationships can support reduced search times for family members’ faces.