bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel FOXM1 inhibitor STL001 sensitizes human cancers to a broad-spectrum of cancer therapies
Authors: Raghuwanshi Sanjeev , Zhang Xu , Arbieva Zarema , Khan Irum , Mohammed Hisham , Wang Z. , Domling Alexander , Camacho Carlos Jaime , Gartel Andrei L. 
Published: May 2024

AbstractForkhead box protein M1 (FOXM1) is often overexpressed in human cancers and strongly associated with therapy resistance and less good patient survival. The chemotherapy options for patients with the most aggressive types of solid cancers remain very limited because of the acquired drug resistance, making the therapy less effective. NPM1 mutation through the inactivation of FOXM1 via FOXM1 relocalization to the cytoplasm confers more favorable treatment outcomes for AML patients, confirming FOXM1 as a crucial target to overcome drug resistance. Pharmacological inhibition of FOXM1 could be a promising approach to sensitize therapy-resistant cancers. Here, we explore a novel FOXM1 inhibitor STL001, a first-generation modification drug of our previously reported FOXM1 inhibitor STL427944. STL001 preserves the mode of action of the STL427944; however, STL001 is up to 50 times more efficient in reducing FOXM1 activity in a variety of solid cancers. The most conventional cancer therapies studied here induce FOXM1 overexpression in solid cancers. The therapy-induced FOXM1 overexpression may explain the failure or reduced efficacy of these drugs in cancer patients. Interestingly, STL001 increased the sensitivity of cancer cells to conventional cancer therapies by suppressing both the high-endogenous and drug-induced FOXM1. Notably, STL001 does not provide further sensitization to FOXM1-KD cancer cells, suggesting that the sensitization effect is conveyed specifically through FOXM1 suppression. RNA-seq and gene set enrichment studies revealed prominent suppression of FOXM1-dependent pathways and gene ontologies. Also, gene regulation by STL001 showed extensive overlap with FOXM1-KD, suggesting a high selectivity of STL001 toward the FOXM1 regulatory network. A completely new activity of FOXM1, mediated through steroid/cholesterol biosynthetic process and protein secretion in cancer cells was also detected. Collectively, STL001 offers intriguing translational opportunities as combination therapies targeting FOXM1 activity in a variety of human cancers driven by FOXM1.
Neutrophil extracellular traps promote invasion and metastasis via NLRP3-mediated oral squamous cell carcinoma pyroptosis inhibition
Authors: Zhai Rundong , Gong Zizhen , Wang Mengqi , Ni Zihui , Zhang Jiayi , Wang Mengyao , Zhang Yu , Zeng Fanrui , Gu Ziyue , Chen Xingyu , Wang Xiudi , Zhou Pengcheng , Liu Laikui , Zhu Weiwen 
Published: May 2024

AbstractNeutrophil extracellular traps (NETs) are reticular structures composed of neutrophil elastase (NE), cathepsin G (CG) and DNA-histone enzyme complexes. Accumulating evidence has revealed that NETs play important roles in tumor progression, metastasis, and thrombosis. However, our understanding of its clinical value and mechanism of action in oral squamous cell carcinoma (OSCC) is limited and has not yet been systematically described. Here, we aimed to investigate the clinical significance of NETs in OSCC and the mechanisms by which they affect its invasive and metastatic capacity. Our results demonstrated that high enrichment of NETs is associated with poor prognosis in OSCC, and mechanistic studies have shown that NE in NETs promotes invasion and metastasis via NLRP3-mediated inhibition of pyroptosis in OSCC. These findings may provide a new therapeutic approach for OSCC.
Protecting the piglet gut microbiota against ETEC-mediated post-weaning diarrhoea using specific binding proteins
Authors: Jenkins Timothy Patrick , Ács Norbert , Arendrup Emma Wenzel , Swift Abbie , Duzs Ágnes , Chatzigiannidou Ioanna , Pichler Michael , Kittilä Tiia , Peachey Laura , Gram Lone , Canibe Nuria , Laustsen Andreas Hougaard , Brix Susanne , Thrane Sandra Wingaard 
Published: May 2024

AbstractPost-weaning diarrhoea (PWD) in piglets presents a widespread problem in industrial pig production and is often caused by enterotoxigenic E. coli (ETEC) strains. Current solutions, such as antibiotics and medicinal zinc oxide, are unsustainable and are increasingly being prohibited, resulting in a dire need for novel solutions. Thus, in this study, we propose and evaluate a protein-based feed additive, comprising two bivalent heavy chain variable domain (VHH) constructs (VHH-(GGGGS)3-VHH, BL1.2 and BL2.2) as an alternative solution to manage PWD. We demonstrate in vitro that these constructs bind to ETEC toxins and fimbriae, whilst they do no affect bacterial growth rate. Furthermore, in a pig study, we show that oral administration of these constructs after ETEC challenge reduced ETEC proliferation when compared to challenged control piglets (1-2 log10 units difference in gene copies and bacterial count/g faeces across day 2–7) and resulted in week 1 enrichment of three bacterial families (Prevotellaceae (estimate: 1.12 ± 0.25, q = 0.0054), Lactobacillaceae (estimate: 2.86 ± 0.52, q = 0.0012), and Ruminococcaceae (estimate: 0.66 ± 0.18, q = 0.049)) within the gut microbiota that appeared later in challenged control piglets, thus pointing to an earlier transition towards a more mature gut microbiota. These data suggest that such VHH constructs may find utility in industrial pig production as a feed additive for tackling ETEC and reducing the risk of PWD in piglet populations.
Surface-dominated conductance scaling in Weyl semimetal NbAs
Authors: Kumar Sushant , Tu Yi-Hsin , Luo Sheng , Lanzillo Nicholas A. , Chang Tay-Rong , Liang Gengchiau , Sundararaman Ravishankar , Lin Hsin , Chen Ching-Tzu 
Published: May 2024

AbstractProtected surface states arising from non-trivial bandstructure topology in semimetals can potentially enable advanced device functionalities in compute, memory, interconnect, sensing, and communication. This necessitates a fundamental understanding of surface-state transport in nanoscale topological semimetals. Here, we investigate quantum transport in a prototypical topological semimetal NbAs to evaluate the potential of this class of materials for beyond-Cu interconnects in highly-scaled integrated circuits. Using density functional theory (DFT) coupled with non-equilibrium Green’s function (NEGF) calculations, we show that the resistance-area RA product in NbAs films decreases with decreasing thickness at the nanometer scale, in contrast to a nearly constant RA product in ideal Cu films. This anomalous scaling originates from the disproportionately large number of surface conduction states which dominate the ballistic conductance by up to 70% in NbAs thin films. We also show that this favorable RA scaling persists even in the presence of surface defects, in contrast to RA sharply increasing with reducing thickness for films of conventional metals, such as Cu, in the presence of surface defects. These results underscore the potential of topological semimetals as future back-end-of-line (BEOL) interconnect metals.
PSFHS: Intrapartum ultrasound image dataset for AI-based segmentation of pubic symphysis and fetal head
Authors: Chen Gaowen , Bai Jieyun , Ou Zhanhong , Lu Yaosheng , Wang Huijin 
Published: May 2024

AbstractDuring the process of labor, the intrapartum transperineal ultrasound examination serves as a valuable tool, allowing direct observation of the relative positional relationship between the pubic symphysis and fetal head (PSFH). Accurate assessment of fetal head descent and the prediction of the most suitable mode of delivery heavily rely on this relationship. However, achieving an objective and quantitative interpretation of the ultrasound images necessitates precise PSFH segmentation (PSFHS), a task that is both time-consuming and demanding. Integrating the potential of artificial intelligence (AI) in the field of medical ultrasound image segmentation, the development and evaluation of AI-based models rely significantly on access to comprehensive and meticulously annotated datasets. Unfortunately, publicly accessible datasets tailored for PSFHS are notably scarce. Bridging this critical gap, we introduce a PSFHS dataset comprising 1358 images, meticulously annotated at the pixel level. The annotation process adhered to standardized protocols and involved collaboration among medical experts. Remarkably, this dataset stands as the most expansive and comprehensive resource for PSFHS to date.
Establishment and application of a rapid visual diagnostic method for Streptococcus agalactiae based on recombinase polymerase amplification and lateral flow strips
Authors: Ji Tuo , Cai Ye , Gao Yuzhi , Wang Gang , Miao Yongchang , Gao Xuzhu 
Published: May 2024

AbstractThis study aims to establish a rapid diagnostic method for Streptococcus agalactiae (GBS) based on recombinase polymerase amplification (RPA) and lateral flow strips (LFS). The best primer pairs designed by SIP gene were screened according to the basic RPA reaction, then the probe was designed. The reaction condition was optimized based on the color development of the LFS detection line. To ascertain the reaction specificity, 10 common clinical pathogens and 10 clinical specimens of GBS were tested. Furthermore, the reaction sensitivity was assessed by utilizing a tenfold gradient dilution of GBS genomic DNA as templates. RPA–LFS method was compared to the qPCR assay and biochemical culture method for the Kappa consistency test. The RPA–LFS technique was able to complete the amplification process within 30 min and the results were observed on lateral flow strips. The method is highly sensitive, with a minimum detection limit of 1.31 ng for GBS. The RPA–LFS method showed consistent accuracy of results compared to qPCR and the culture–biochemical method. The establishment of this method is conducive to the development of on-site immediate detection, which can provide information for the timely development of a reasonable antimicrobial treatment plan, and has a greater potential for clinical application.
Association between intensity of physical activity and cognitive function in hypertensive patients: a case–control study
Authors: Lv Shunxin , Jiao Huachen , Zhong Xia , Qu Ying , Zhang Mengdi , Wang Rui 
Published: May 2024

AbstractPrevious studies have shown that a higher intensity of physical activity (PA) is associated with a lower risk of cognitive impairment (CI), whereas hypertension is associated with higher CI. However, there are few studies on the association between PA intensity and cognitive function in hypertensive patients. This study investigated the association between PA intensity and cognitive function in hypertensive patients. A total of 2035 hypertensive patients were included in this study, including 407 hypertensive patients with CI and 1628 hypertensive patients with normal cognitive function matched 1:4 by age and sex. The International Physical Activity Questionnaire-Long Form and the Mini-mental State Examination were used to evaluate PA intensity, total metabolic equivalents, and cognitive function in patients with hypertension. Multivariate logistic regression was used to analyze the correlation between PA intensity and CI in hypertensive patients. The Spearman correlation coefficient was used to analyze the correlation between PA intensity and the total score of each component of the MMSE and the correlation between PA total metabolic equivalents and cardiac structure in hypertensive patients. After adjusting for all confounding factors, PA intensity was negatively associated with CI in hypertensive patients (OR = 0.608, 95% CI: 0.447–0.776, P < 0.001), and this association was also observed in hypertensive patients with education level of primary school and below and junior high school and above (OR = 0.732, 95% CI: 0.539–0.995, P = 0.047; OR = 0.412, 95% CI: 0.272–0.626, P < 0.001). The intensity of PA in hypertensive patients was positively correlated with orientation (r = 0.125, P < 0.001), memory (r = 0.052, P = 0.020), attention and numeracy (r = 0.151, P < 0.001), recall ability (r = 0.110, P < 0.001), and language ability (r = 0.144, P < 0.001). PA total metabolic equivalents in hypertensive patients were negatively correlated with RVEDD and LAD (r = − 0.048, P = 0.030; r = − 0.051, P = 0.020) and uncorrelated with LVEDD (r = 0.026, P = 0.233). Higher PA intensity reduced the incidence of CI in hypertensive patients. Therefore, hypertensive patients were advised to moderate their PA according to their circumstances.
Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease
Authors: Stadler Karina A. , Ortiz-Joya Lesly J. , Singh Sahrawat Amit , Buhlheller Christoph , Gruber Karl , Pavkov-Keller Tea , O’Hagan Treasa B. , Guarné Alba , Pulido Sergio , Marín-Villa Marcel , Zangger Klaus , Gubensäk Nina 
Published: May 2024

AbstractAccording to the World Health Organization, Chagas disease (CD) is the most prevalent poverty-promoting neglected tropical disease. Alarmingly, climate change is accelerating the geographical spreading of CD causative parasite, Trypanosoma cruzi, which additionally increases infection rates. Still, CD treatment remains challenging due to a lack of safe and efficient drugs. In this work, we analyze the viability of T. cruzi Akt-like kinase (TcAkt) as drug target against CD including primary structural and functional information about a parasitic Akt protein. Nuclear Magnetic Resonance derived information in combination with Molecular Dynamics simulations offer detailed insights into structural properties of the pleckstrin homology (PH) domain of TcAkt and its binding to phosphatidylinositol phosphate ligands (PIP). Experimental data combined with Alpha Fold proposes a model for the mechanism of action of TcAkt involving a PIP-induced disruption of the intramolecular interface between the kinase and the PH domain resulting in an open conformation enabling TcAkt kinase activity. Further docking experiments reveal that TcAkt is recognized by human inhibitors PIT-1 and capivasertib, and TcAkt inhibition by UBMC-4 and UBMC-6 is achieved via binding to TcAkt kinase domain. Our in-depth structural analysis of TcAkt reveals potential sites for drug development against CD, located at activity essential regions.
Multi-level optimal energy management strategy for a grid tied microgrid considering uncertainty in weather conditions and load
Authors: Keshta H. E. , Hassaballah E. G. , Ali A. A. , Abdel-Latif K. M. 
Published: May 2024

AbstractMicrogrids require efficient energy management systems to optimize the operation of microgrid sources and achieve economic efficiency. Bi-level energy management model is proposed in this paper to minimize the operational cost of a grid-tied microgrid under load variations and uncertainties in renewable sources while satisfying the various technical constraints. The first level is day ahead scheduling of generation units based on day ahead forecasting of renewable energy sources and load demand. In this paper, a recent meta-heuristic algorithm called Coronavirus Herd Immunity Optimizer (CHIO) is used to solve the problem of day-ahead scheduling of batteries, which is a complex constrained non-linear optimization problem, while the Lagrange multiplier method is used to determine the set-point of the Diesel Generator (DG). The second level of the proposed EMS is rescheduling and updating the set-points of sources in real-time according to the actual solar irradiance, wind speed, load, and grid tariff. In this paper, a novel real-time strategy is proposed to keep the economic operation during real-time under uncertainties. The obtained results show that the CHIO-based bi-level EMS demonstrates an optimal economic operation for a grid-connected microgrid in real-time when there are uncertainties in weather, utility tariffs, and load forecasts.
Dual-channel fluorescent sensors based on chitosan-coated Mn-doped ZnS micromaterials to detect ampicillin
Authors: Nguyen Son Hai , Nguyen Van-Nhat , Tran Mai Thi 
Published: May 2024

AbstractThe global threat of antibiotic resistance has increased the importance of the detection of antibiotics. Conventional methods to detect antibiotics are time-consuming and require expensive specialized equipment. Here, we present a simple and rapid biosensor for detecting ampicillin, a commonly used antibiotic. Our method is based on the fluorescent properties of chitosan-coated Mn-doped ZnS micromaterials combined with the β-lactamase enzyme. The biosensors exhibited the highest sensitivity in a linear working range of 13.1–72.2 pM with a limit of detection of 8.24 pM in deionized water. In addition, due to the biological specificity of β-lactamase, the proposed sensors have demonstrated high selectivity over penicillin, tetracycline, and glucose through the enhancing and quenching effects at wavelengths of 510 nm and 614 nm, respectively. These proposed sensors also showed promising results when tested in various matrices, including tap water, bottled water, and milk. Our work reports for the first time the cost-effective (Mn:ZnS)Chitosan micromaterial was used for ampicillin detection. The results will facilitate the monitoring of antibiotics in clinical and environmental contexts.
An advanced fast method for the evaluation of multiple immunolabelling using gold nanoparticles based on low-energy STEM
Authors: Kitzberger František , Yang Shun-Min , Týč Jiří , Bílý Tomáš , Nebesářová Jana 
Published: May 2024

AbstractWe present a powerful method for the simultaneous detection of Au nanoparticles located on both sides of ultrathin sections. The method employs a high-resolution scanning electron microscope (HRSEM) operating in scanning transmission electron microscopy (STEM) mode in combination with the detection of backscattered electrons (BSE). The images are recorded simultaneously during STEM and BSE imaging at the precisely selected accelerating voltage. Under proper imaging conditions, the positions of Au nanoparticles on the top or bottom sides can be clearly differentiated, hence showing this method to be suitable for multiple immunolabelling using Au nanoparticles (NPs) as markers. The difference between the upper and lower Au NPs is so large that it is possible to apply common software tools (such as ImageJ) to enable their automatic differentiation. The effects of the section thickness, detector settings and accelerating voltage on the resulting image are shown. Our experimental results correspond to the results modelled in silico by Monte Carlo (MC) simulations.
Cognitive impairment and hippocampal neuronal damage in β-thalassaemia mice
Authors: Pholngam Nuttanan , Jamrus Parinda , Viwatpinyo Kittikun , Kiatpakdee Benjaporn , Vadolas Jim , Chaichompoo Pornthip , Ngampramuan Sukonthar , Svasti Saovaros 
Published: May 2024

Abstractβ-Thalassaemia is one of the most common genetic diseases worldwide. During the past few decades, life expectancy of patients has increased significantly owing to advance in medical treatments. Cognitive impairment, once has been neglected, has gradually become more documented. Cognitive impairment in β-thalassaemia patients is associated with natural history of the disease and socioeconomic factors. Herein, to determined effect of β-thalassaemia intrinsic factors, 22-month-old β-thalassaemia mouse was used as a model to assess cognitive impairment and to investigate any aberrant brain pathology in β-thalassaemia. Open field test showed that β-thalassaemia mice had decreased motor function. However, no difference of neuronal degeneration in primary motor cortex, layer 2/3 area was found. Interestingly, impaired learning and memory function accessed by a Morris water maze test was observed and correlated with a reduced number of living pyramidal neurons in hippocampus at the CA3 region in β-thalassaemia mice. Cognitive impairment in β-thalassaemia mice was significantly correlated with several intrinsic β-thalassaemic factors including iron overload, anaemia, damaged red blood cells (RBCs), phosphatidylserine (PS)-exposed RBC large extracellular vesicles (EVs) and PS-exposed medium EVs. This highlights the importance of blood transfusion and iron chelation in β-thalassaemia patients. In addition, to improve patients’ quality of life, assessment of cognitive functions should become part of routine follow-up.
De-embedding method for a sensing area characterization of planar microstrip sensors without evaluating error networks
Authors: Hasar Ugur C. , Ozturk Hamdullah , Korkmaz Huseyin , Nayyeri Vahid , Ramahi Omar M. 
Published: May 2024

AbstractA de-embedding method for determining all scattering (S-) parameters (e.g., characterization) of a sensing area of planar microstrip sensors (two-port network or line) is proposed using measurements of S-parameters with no calibration. The method requires only (partially known) non-reflecting line and reflecting line standards to accomplish such a characterization. It utilizes uncalibrated S-parameter measurements of a reflecting line, direct and reversed configurations of a non-reflecting line, and direct and reversed configurations of the sensing area. As different from previous similar studies, it performs such a characterization without any sign ambiguity. The method is first validated by extracting the S-parameters of a bianisotropic metamaterial slab, as for a two-port network (line), constructed by split-ring-resonators (SRRs) from waveguide measurements. Then, it is applied for determining the S-parameters of a sensing area of a microstrip sensor involving double SRRs next to a microstrip line. The root-mean-square-error (RMSE) analysis was utilized to analyze the accuracy of our method in comparison with other techniques in the literature. It has been observed from such an analysis that our proposed de-embedding technique has the lowest RMSE values for the extracted S-parameters of the sensing area of the designed sensor in comparison with those of the compared other de-embedding techniques in the literature, and have similar RMSE values in reference to those of the thru-reflect-line calibration technique. For example, while RMSE values of real and imaginary parts of the forward reflection S-parameter of this sensing area are, respectively, around 0.0271 and 0.0279 for our de-embedding method, those of one of the compared de-embedding techniques approach as high as 0.0318 and 0.0324.
Isolation of nucleic acids using liquid–liquid phase separation of pH-sensitive elastin-like polypeptides
Authors: Díez Pérez Telmo , Tafoya Ashley N. , Peabody David S. , Lakin Matthew R. , Hurwitz Ivy , Carroll Nick J. , López Gabriel P. 
Published: May 2024

AbstractExtraction of nucleic acids (NAs) is critical for many methods in molecular biology and bioanalytical chemistry. NA extraction has been extensively studied and optimized for a wide range of applications and its importance to society has significantly increased. The COVID-19 pandemic highlighted the importance of early and efficient NA testing, for which NA extraction is a critical analytical step prior to the detection by methods like polymerase chain reaction. This study explores simple, new approaches to extraction using engineered smart nanomaterials, namely NA-binding, intrinsically disordered proteins (IDPs), that undergo triggered liquid–liquid phase separation (LLPS). Two types of NA-binding IDPs are studied, both based on genetically engineered elastin-like polypeptides (ELPs), model IDPs that exhibit a lower critical solution temperature in water and can be designed to exhibit LLPS at desired temperatures in a variety of biological solutions. We show that ELP fusion proteins with natural NA-binding domains can be used to extract DNA and RNA from physiologically relevant solutions. We further show that LLPS of pH responsive ELPs that incorporate histidine in their sequences can be used for both binding, extraction and release of NAs from biological solutions, and can be used to detect SARS-CoV-2 RNA in samples from COVID-positive patients.