bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural investigation of interactions between halogenated flavonoids and the lipid membrane along with their role as cytotoxic agents
Authors: Dudek Anita , Szulc Natalia , Pawlak Aleksandra , Strugała-Danak Paulina , Krawczyk-Łebek Agnieszka , Perz Martyna , Kostrzewa-Susłow Edyta , Pruchnik Hanna 
Published: May 2024

AbstractThis study focuses on understanding the structural and molecular changes in lipid membranes under the influence of six halogenated flavonoid derivatives differing in the number and position of substitution of chlorine and bromine atoms (D1–D6). Utilizing various analytical techniques, including fluorometric methods, dynamic light scattering (DLS), attenuated Fourier transform infrared spectroscopy (ATR- FTIR), and FT-Raman spectroscopy, the research aims to elucidate the mechanisms underlying the interaction of flavonoids with cell membranes. Additionally, the study includes in silico analyses to explore the physicochemical properties of these compounds and their potential pharmaceutical applications, along with toxicity studies to assess their effects on cancer, normal, and red blood cells. Our study showed the ability of halogenated derivatives to interact mostly with the outer part of the membrane, especially in the lipid heads region however, some of them were able to penetrate deeper into the membrane and affect the fluidity of hydrocarbon chains. The potential to reduce cancer cell viability, the lack of toxicity towards erythrocytes, and the favourable physicochemical and pharmacokinetic properties suggest these halogenated flavonoids potential candidates for exploring their potential for medical use.
Selective but not pan-CDK inhibition abrogates 5-FU-driven tissue factor upregulation in colon cancer
Authors: Kayser Annika , Wolff Annabell , Berlin Peggy , Duehring Lara , Henze Larissa , Mundkowski Ralf , Bergmann Wendy , Müller-Hilke Brigitte , Wagner Charlotte , Huehns Maja , Oehmcke-Hecht Sonja , Maletzki Claudia 
Published: May 2024

AbstractThromboembolic events are complications in cancer patients and hypercoagulability has been linked to the tissue factor (TF) pathway, making this an attractive target. Here, we investigated the effects of chemotherapeutics and CDK inhibitors (CDKI) abemaciclib/palbociclib (CDK4/6), THZ-1 (CDK7/12/13), and dinaciclib (CDK1/2/5/9) alone and in combination regimens on TF abundance and coagulation. The human colorectal cancer (CRC) cell line HROC173 was treated with 5-FU or gemcitabine to stimulate TF expression. TF+ cells were sorted, recultured, and re-analyzed. The effect of treatment alone or in combination was assessed by functional assays. Low-dose chemotherapy induced a hypercoagulable state and significantly upregulated TF, even after reculture without treatment. Cells exhibited characteristics of epithelial-mesenchymal transition, including high expression of vimentin and mucin. Dinaciclib and THZ-1 also upregulated TF, while abemaciclib and palbociclib downregulated it. Similar results were observed in coagulation assays. The same anticoagulant activity of abemaciclib was seen after incubation with peripheral immune cells from healthy donors and CRC patients. Abemaciclib reversed 5-FU-induced TF upregulation and prolonged clotting times in second-line treatment. Effects were independent of cytotoxicity, senescence, and p27kip1 induction. TF-antibody blocking experiments confirmed the importance of TF in plasma coagulation, with Factor XII playing a minor role. Short-term abemaciclib counteracts 5-FU-induced hypercoagulation and eventually even prevents thromboembolic events.
Identification of master regulator genes controlling pathogenic CD4+ T cell fate in inflammatory bowel disease through transcriptional network analysis
Authors: Jiménez José M. , Contreras-Riquelme J. Sebastián , Vidal Pía M. , Prado Carolina , Bastías Macarena , Meneses Claudio , Martín Alberto J. M. , Perez-Acle Tomás , Pacheco Rodrigo 
Published: May 2024

AbstractInflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions of the gastrointestinal tract associated with multiple pathogenic factors, including dysregulation of the immune response. Effector CD4+ T cells and regulatory CD4+ T cells (Treg) are central players in maintaining the balance between tolerance and inflammation. Interestingly, genetic modifications in these cells have been implicated in regulating the commitment of specific phenotypes and immune functions. However, the transcriptional program controlling the pathogenic behavior of T helper cells in IBD progression is still unknown. In this study, we aimed to find master transcription regulators controlling the pathogenic behavior of effector CD4+ T cells upon gut inflammation. To achieve this goal, we used an animal model of IBD induced by the transfer of naïve CD4+ T cells into recombination-activating gene 1 (Rag1) deficient mice, which are devoid of lymphocytes. As a control, a group of Rag1−/− mice received the transfer of the whole CD4+ T cells population, which includes both effector T cells and Treg. When gut inflammation progressed, we isolated CD4+ T cells from the colonic lamina propria and spleen tissue, and performed bulk RNA-seq. We identified differentially up- and down-regulated genes by comparing samples from both experimental groups. We found 532 differentially expressed genes (DEGs) in the colon and 30 DEGs in the spleen, mostly related to Th1 response, leukocyte migration, and response to cytokines in lamina propria T-cells. We integrated these data into Gene Regulatory Networks to identify Master Regulators, identifying four up-regulated master gene regulators (Lef1, Dnmt1, Mybl2, and Jup) and only one down-regulated master regulator (Foxo3). The altered expression of master regulators observed in the transcriptomic analysis was confirmed by qRT-PCR analysis and found an up-regulation of Lef1 and Mybl2, but without differences on Dnmt1, Jup, and Foxo3. These two master regulators have been involved in T cells function and cell cycle progression, respectively. We identified two master regulator genes associated with the pathogenic behavior of effector CD4+ T cells in an animal model of IBD. These findings provide two new potential molecular targets for treating IBD.
Graph semantic similarity-based automatic assessment for programming exercises
Authors: Xiang Chengguan , Wang Ying , Zhou Qiyun , Yu Zhen 
Published: May 2024

AbstractThis paper proposes an algorithm for the automatic assessment of programming exercises. The algorithm assigns assessment scores based on the program dependency graph structure and the program semantic similarity, but does not actually need to run the student’s program. By calculating the node similarity between the student’s program and the teacher’s reference programs in terms of structure and program semantics, a similarity matrix is generated and the optimal similarity node path of this matrix is identified. The proposed algorithm achieves improved computational efficiency, with a time complexity of $$O(n^2)$$

O
(

n
2

)

for a graph with n nodes. The experimental results show that the assessment algorithm proposed in this paper is more reliable and accurate than several comparison algorithms, and can be used for scoring programming exercises in C/C++, Java, Python, and other languages.
Development of a new affinity maturation protocol for the construction of an internalizing anti-nucleolin antibody library
Authors: Ribeiro Rita , Moreira João N. , Goncalves João 
Published: May 2024

AbstractOver the last decades, monoclonal antibodies have substantially improved the treatment of several conditions. The continuous search for novel therapeutic targets and improvements in antibody’s structure, demands for a constant optimization of their development. In this regard, modulation of an antibody’s affinity to its target has been largely explored and culminated in the discovery and optimization of a variety of molecules. It involves the creation of antibody libraries and selection against the target of interest. In this work, we aimed at developing a novel protocol to be used for the affinity maturation of an antibody previously developed by our group. An antibody library was constructed using an in vivo random mutagenesis approach that, to our knowledge, has not been used before for antibody development. Then, a cell-based phage display selection protocol was designed to allow the fast and simple screening of antibody clones capable of being internalized by target cells. Next generation sequencing coupled with computer analysis provided an extensive characterization of the created library and post-selection pool, that can be used as a guide for future antibody development. With a single selection step, an enrichment in the mutated antibody library, given by a decrease in almost 50% in sequence diversity, was achieved, and structural information useful in the study of the antibody-target interaction in the future was obtained.
Insights into phage-bacteria interaction in cold seep Gigantidas platifrons through metagenomics and transcriptome analyses
Authors: Zhang Yan , Chen Hao , Lian Chao , Cao Lei , Guo Yang , Wang Minxiao , Zhong Zhaoshan , Li Mengna , Zhang Huan , Li Chaolun 
Published: May 2024

AbstractViruses are crucial for regulating deep-sea microbial communities and biogeochemical cycles. However, their roles are still less characterized in deep-sea holobionts. Bathymodioline mussels are endemic species inhabiting cold seeps and harboring endosymbionts in gill epithelial cells for nutrition. This study unveiled a diverse array of viruses in the gill tissues of Gigantidas platifrons mussels and analyzed the viral metagenome and transcriptome from the gill tissues of Gigantidas platifrons mussels collected from a cold seep in the South Sea. The mussel gills contained various viruses including Baculoviridae, Rountreeviridae, Myoviridae and Siphovirdae, but the active viromes were Myoviridae, Siphoviridae, and Podoviridae belonging to the order Caudovirales. The overall viral community structure showed significant variation among environments with different methane concentrations. Transcriptome analysis indicated high expression of viral structural genes, integrase, and restriction endonuclease genes in a high methane concentration environment, suggesting frequent virus infection and replication. Furthermore, two viruses (GP-phage-contig14 and GP-phage-contig72) interacted with Gigantidas platifrons methanotrophic gill symbionts (bathymodiolin mussels host intracellular methanotrophic Gammaproteobacteria in their gills), showing high expression levels, and have huge different expression in different methane concentrations. Additionally, single-stranded DNA viruses may play a potential auxiliary role in the virus–host interaction using indirect bioinformatics methods. Moreover, the Cro and DNA methylase genes had phylogenetic similarity between the virus and Gigantidas platifrons methanotrophic gill symbionts. This study also explored a variety of viruses in the gill tissues of Gigantidas platifrons and revealed that bacteria interacted with the viruses during the symbiosis with Gigantidas platifrons. This study provides fundamental insights into the interplay of microorganisms within Gigantidas platifrons mussels in deep sea.
Multispectral optoacoustic tomography of benign parotid tumors in vivo: a prospective observational pilot study
Authors: Kouka Mussab , Waldner Maximilian , Guntinas-Lichius Orlando 
Published: May 2024

AbstractParotid lumps are a heterogeneous group of mainly benign but also malignant tumors. Preoperative imaging does not allow a differentiation between tumor types. Multispectral optoacoustic tomography (MSOT) may improve the preoperative diagnostics. In this first prospective pilot trial the ability of MSOT to discriminate between the two most frequent benign parotid tumors, pleomorphic adenoma (PA) and Warthin tumor (WT) as well as to normal parotid tissue was explored. Six wavelengths (700, 730, 760, 800, 850, 900 nm) and the parameters deoxygenated (HbR), oxygenated (HbO2), total hemoglobin (HbT), and saturation of hemoglobin (sO2) were analyzed. Ten patients with PA and fourteen with WT were included (12/12 female/male; median age: 51 years). For PA, the mean values for all measured wave lengths as well as for the hemoglobin parameters were different for the tumors compared to the healthy parotid (all p < 0.05). The mean MSOT parameters were all significantly higher (all p < 0.05) in the WT compared to healthy parotid gland except for HbT and sO2. Comparing both tumors directly, the mean values of MSOT parameters were not different between PA and WT (all p > 0.05). Differences were seen for the maximal MSOT parameters. The maximal tumor values for 900 nm, HbR, HbT, and sO2 were lower in PA than in WT (all p < 0.05). This preliminary MSOT parotid tumor imaging study showed clear differences for PA or WT compared to healthy parotid tissue. Some MSOT characteristics of PA and WT were different but needed to be explored in larger studies.
Discovery of a brain penetrant small molecule antagonist targeting LPA1 receptors to reduce neuroinflammation and promote remyelination in multiple sclerosis
Authors: Poon Michael M. , Lorrain Kym I. , Stebbins Karin J. , Edu Geraldine C. , Broadhead Alexander R. , Lorenzana Ariana O. , Paulson Bryanna E. , Baccei Christopher S. , Roppe Jeffrey R. , Schrader Thomas O. , Valdez Lino J. , Xiong Yifeng , Chen Austin C. , Lorrain Daniel S. 
Published: May 2024

AbstractMultiple sclerosis (MS) is a chronic neurological disease characterized by inflammatory demyelination that disrupts neuronal transmission resulting in neurodegeneration progressive disability. While current treatments focus on immunosuppression to limit inflammation and further myelin loss, no approved therapies effectively promote remyelination to mitigate the progressive disability associated with chronic demyelination. Lysophosphatidic acid (LPA) is a pro-inflammatory lipid that is upregulated in MS patient plasma and cerebrospinal fluid (CSF). LPA activates the LPA1 receptor, resulting in elevated CNS cytokine and chemokine levels, infiltration of immune cells, and microglial/astrocyte activation. This results in a neuroinflammatory response leading to demyelination and suppressed remyelination. A medicinal chemistry effort identified PIPE-791, an oral, brain-penetrant, LPA1 antagonist. PIPE-791 was characterized in vitro and in vivo and was found to be a potent, selective LPA1 antagonist with slow receptor off-rate kinetics. In vitro, PIPE-791 induced OPC differentiation and promoted remyelination following a demyelinating insult. PIPE-791 further mitigated the macrophage-mediated inhibition of OPC differentiation and inhibited microglial and fibroblast activation. In vivo, the compound readily crossed the blood–brain barrier and blocked LPA1 in the CNS after oral dosing. Direct dosing of PIPE-791 in vivo increased oligodendrocyte number, and in the mouse experimental autoimmune encephalomyelitis (EAE) model of MS, we observed that PIPE-791 promoted myelination, reduced neuroinflammation, and restored visual evoked potential latencies (VEP). These findings support targeting LPA1 for remyelination and encourage development of PIPE-791 for treating MS patients with advantages not seen with current immunosuppressive disease modifying therapies.
Histological and immunohistochemical analyses of articular cartilage during onset and progression of pre- and early-stage osteoarthritis in a rodent model
Authors: Takahashi Ikufumi , Takeda Keisuke , Toyama Tadashi , Matsuzaki Taro , Kuroki Hiroshi , Hoso Masahiro 
Published: May 2024

AbstractEarly diagnosis and treatment of pre- and early-stage osteoarthritis (OA) is important. However, the cellular and cartilaginous changes occurring during these stages remain unclear. We investigated the histological and immunohistochemical changes over time between pre- and early-stage OA in a rat model of traumatic injury. Thirty-six male rats were divided into two groups, control and OA groups, based on destabilization of the medial meniscus. Histological and immunohistochemical analyses of articular cartilage were performed on days 1, 3, 7, 10, and 14 postoperatively. Cell density of proteins associated with cartilage degradation increased from postoperative day one. On postoperative day three, histological changes, including chondrocyte death, reduced matrix staining, and superficial fibrillation, were observed. Simultaneously, a compensatory increase in matrix staining was observed. The Osteoarthritis Research Society International score increased from postoperative day seven, indicating thinner cartilage. On postoperative day 10, the positive cell density decreased, whereas histological changes progressed with fissuring and matrix loss. The proteoglycan 4-positive cell density increased on postoperative day seven. These findings will help establish an experimental model and clarify the mechanism of the onset and progression of pre- and early-stage traumatic OA.
Neural-network quantum states for ultra-cold Fermi gases
Authors: Kim Jane , Pescia Gabriel , Fore Bryce , Nys Jannes , Carleo Giuseppe , Gandolfi Stefano , Hjorth-Jensen Morten , Lovato Alessandro 
Published: May 2024

AbstractUltra-cold Fermi gases exhibit a rich array of quantum mechanical properties, including the transition from a fermionic superfluid Bardeen-Cooper-Schrieffer (BCS) state to a bosonic superfluid Bose-Einstein condensate (BEC). While these properties can be precisely probed experimentally, accurately describing them poses significant theoretical challenges due to strong pairing correlations and the non-perturbative nature of particle interactions. In this work, we introduce a Pfaffian-Jastrow neural-network quantum state featuring a message-passing architecture to efficiently capture pairing and backflow correlations. We benchmark our approach on existing Slater-Jastrow frameworks and state-of-the-art diffusion Monte Carlo methods, demonstrating a performance advantage and the scalability of our scheme. We show that transfer learning stabilizes the training process in the presence of strong, short-ranged interactions, and allows for an effective exploration of the BCS-BEC crossover region. Our findings highlight the potential of neural-network quantum states as a promising strategy for investigating ultra-cold Fermi gases.
Predicting equilibrium distributions for molecular systems with deep learning
Authors: Zheng Shuxin , He Jiyan , Liu Chang , Shi Yu , Lu Ziheng , Feng Weitao , Ju Fusong , Wang Jiaxi , Zhu Jianwei , Min Yaosen , Zhang He , Tang Shidi , Hao Hongxia , Jin Peiran , Chen Chi , Noé Frank , Liu Haiguang , Liu Tie-Yan 
Published: May 2024

AbstractAdvances in deep learning have greatly improved structure prediction of molecules. However, many macroscopic observations that are important for real-world applications are not functions of a single molecular structure but rather determined from the equilibrium distribution of structures. Conventional methods for obtaining these distributions, such as molecular dynamics simulation, are computationally expensive and often intractable. Here we introduce a deep learning framework, called Distributional Graphormer (DiG), in an attempt to predict the equilibrium distribution of molecular systems. Inspired by the annealing process in thermodynamics, DiG uses deep neural networks to transform a simple distribution towards the equilibrium distribution, conditioned on a descriptor of a molecular system such as a chemical graph or a protein sequence. This framework enables the efficient generation of diverse conformations and provides estimations of state densities, orders of magnitude faster than conventional methods. We demonstrate applications of DiG on several molecular tasks, including protein conformation sampling, ligand structure sampling, catalyst–adsorbate sampling and property-guided structure generation. DiG presents a substantial advancement in methodology for statistically understanding molecular systems, opening up new research opportunities in the molecular sciences.
Limited progress in global reduction of vulnerability to flood impacts over the past two decades
Authors: Sauer Inga J. , Mester Benedikt , Frieler Katja , Zimmermann Sandra , Schewe Jacob , Otto Christian 
Published: May 2024

AbstractGlobal flood impacts have risen in recent decades. While increasing exposure was the dominant driver of surging impacts, counteracting vulnerability reductions have been detected, but were too weak to reverse this trend. To assess the ongoing progress on vulnerability reduction, we combine a recently available dataset of flooded areas derived from satellite imagery for 913 events with four global disaster databases and socio-economic data. Event-specific flood vulnerabilities for assets, fatalities and displacements reveal a lack of progress in reducing global flood vulnerability from 2000—2018. We examine the relationship between vulnerabilities and human development, inequality, flood exposure and local structural characteristics. We find that vulnerability levels are significantly lower in areas with good structural characteristics and significantly higher in low developed areas. However, socio-economic development was insufficient to reduce vulnerabilities over the study period. Nevertheless, the strong correlation between vulnerability and structural characteristics suggests further potential for adaptation through vulnerability reduction.
Release and re-enrichment of invisible gold in arsenian pyrite promoted by coupled dissolution-reprecipitation reactions
Authors: Yang Lin , Wang Qingfei , Fougerouse Denis , Xian Haiyang , Li Huajian , Wang Ruixue , Rickard William D. A. , Groves David I. , Deng Jun 
Published: May 2024

AbstractThe mechanisms responsible for invisible gold enrichment driven by coupled dissolution-reprecipitation reaction (CDR) are debated. Here we report the micro- to nano-scale textures of arsenian pyrite in a high-grade (>10 g/t) gold ore from the Chang’an deposit to trace the gold enrichment process. Our study records a CDR-driven evolution of mineral growth from an As-rich, Au-poor pyrite core, with numerous fine arsenopyrite inclusions, to an inclusion-free, As-Au-rich oscillatory pyrite rim. The reaction occurred at ~260 °C under 4.7 to 5.8 pH and –36.6 to –32.9 logfO2 conditions. The elevated As but depleted S contents in the pyrite core indicate a combined elevation of S fugacity and solubility of Au. The coprecipitation of arsenopyrite inclusions in the core caused a depletion of S fugacity to –13.8 ~ –11.7, triggering Au enrichment in the rim. This non-unique process has the potential to explain the upgrade of invisible Au in arsenian sulfides, worldwide.
Ultra‐fast finite element analysis of coreless axial flux permanent magnet synchronous machines
Authors: Chulaee Yaser , Ionel Dan M. 
Published: May 2024

AbstractLarge‐scale design optimisation techniques enable the design of high‐performance electric machines. Electromagnetic 3D finite element analysis (FEA) is typically employed in optimisation studies for accurate analysis of axial flux permanent magnet (AFPM) machines, which require extensive computational resources. To reduce the computational burden, a FEA‐based mathematical method relying on the geometric and magnetic symmetry of coreless AFPM machines is proposed to estimate the machine performance indicators using the least number of FEA solutions, thereby significantly lowering the running time. This method is generally applicable to AFPM machines with low saturation effects and cogging torque as exemplified for a printed circuit board (PCB) stator coreless AFPM machine. To further reduce the computation time, a systematically simplified equivalent 3D FEA model for planar PCB coils integrated with this machine is also proposed. The practical implementation of the introduced method is elaborated based on an example optimisation study, and an analytical method for fast design scaling is also discussed. The results of the proposed approach are compared with detailed transient FEA results, and a prototype 26‐pole PCB stator coreless AFPM machine was also used to validate the results experimentally.