bluuebunny/crossref_metadata_2025_split huggingface dataset:
N6-methyladenosine modified TGFB2 triggers lipid metabolism reprogramming to confer pancreatic ductal adenocarcinoma gemcitabine resistance
Authors: Ma Ming-Jian , Shi Yin-Hao , Liu Zhi-De , Zhu Ying-Qin , Zhao Guang-Yin , Ye Jing-Yuan , Li Fu-Xi , Huang Xi-Tai , Wang Xi-Yu , Wang Jie-Qin , Xu Qiong-Cong , Yin Xiao-Yu 
Published: June 2024

AbstractGemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.
Postnatal corticosteroid therapy in bronchopulmonary dysplasia - why animal studies disagree with clinical trials?
Authors: Harijith Anantha , Raffay Thomas M. , Ryan Rita M. 
Published: June 2024

Abstract
The systematic review and meta-analysis of newborn animal models by Irene Lok et al. is the first to extensively summarize the literature regarding postnatal systemic corticosteroid use on lung development of newborn rodent models. The meta-analysis showed that the use of postnatal corticosteroids resulted in a reduction in body weight along with persistent alveolar simplification. The most frequently used corticosteroid was dexamethasone. Corticosteroids have been extensively used in clinical trials in preterm newborns. Trials using early systemic administration of corticosteroids reduced the rate of BPD or mortality with no increase in the rates of cerebral palsy. Use of late systemic corticosteroids (administered >7 days after birth) also reduced the rate of BPD, mortality, and combined outcome of mortality or BPD. Late systemic corticosteroids showed no impact on the rates of neurodevelopmental outcomes in later childhood. It is important to note that later stages of inflammation leading to a more severe form of BPD continues to be a problem with no clear therapy in sight. The authors made a critical point in their paper – the negative effects of steroids were greater in the normal lung control animals than in the injured. This conveys caution in using steroids in a prophylactic manner.

Impact

Use of systemic corticosteroids in clinical trials have shown good response in preterm neonates evidenced by reduced rate of bronchopulmonary dysplasia.

Rodent models have not shown a similar beneficial response.

Use of systemic corticosteroids have caused greater arrest of lung development in rodent models with normal lungs compared to those with lung damage.
FGF signaling modulates mechanotransduction/WNT signaling in progenitors during tooth root development
Authors: Pei Fei , Guo Tingwei , Zhang Mingyi , Ma Li , Jing Junjun , Feng Jifan , Ho Thach-Vu , Wen Quan , Chai Yang 
Published: June 2024

AbstractStem/progenitor cells differentiate into different cell lineages during organ development and morphogenesis. Signaling pathway networks and mechanotransduction are important factors to guide the lineage commitment of stem/progenitor cells during craniofacial tissue morphogenesis. Here, we used tooth root development as a model to explore the roles of FGF signaling and mechanotransduction as well as their interaction in regulating the progenitor cell fate decision. We show that Fgfr1 is expressed in the mesenchymal progenitor cells and their progeny during tooth root development. Loss of Fgfr1 in Gli1+ progenitors leads to hyperproliferation and differentiation, which causes narrowed periodontal ligament (PDL) space with abnormal cementum/bone formation leading to ankylosis. We further show that aberrant activation of WNT signaling and mechanosensitive channel Piezo2 occurs after loss of FGF signaling in Gli1-CreER;Fgfr1fl/fl mice. Overexpression of Piezo2 leads to increased osteoblastic differentiation and decreased Piezo2 leads to downregulation of WNT signaling. Mechanistically, an FGF/PIEZO2/WNT signaling cascade plays a crucial role in modulating the fate of progenitors during root morphogenesis. Downregulation of WNT signaling rescues tooth ankylosis in Fgfr1 mutant mice. Collectively, our findings uncover the mechanism by which FGF signaling regulates the fate decisions of stem/progenitor cells, and the interactions among signaling pathways and mechanotransduction during tooth root development, providing insights for future tooth root regeneration.
Evidence for the formation of silicic lava by pyroclast sintering
Authors: Foster Annabelle , Wadsworth Fabian B. , Tuffen Hugh , Unwin Holly E. , Humphreys Madeleine C. S. 
Published: June 2024

AbstractSilicic lavas can be produced by the sintering of pyroclasts in the volcanic sub-surface, and then advected out of the vent. Here, we provide evidence for this mechanism preserved in the exposed post-glacial remnants of a silicic volcanic conduit at Hrafntinnuhryggur, Krafla volcano, Iceland. We show that the conduit margins are a clast-supported pumice lapilli tuff deposit that grades continuously into dense obsidian and that the obsidian contains cuspate relict clast boundaries and country rock lithic fragments throughout. Transects of H2O concentrations across the conduit show that the magma was degassed to different degrees laterally with systematic spatial variation that is consistent with progressive conduit clogging and final gas pressurisation. Textures in the overlying effusive lavas record the variably sheared and brecciated remnant of the same in-conduit sintering. This record of a silicic conduit system connected to upper eruptive deposits provides support for the ‘cryptic fragmentation model’ for effusive silicic volcanism.
RAIN: machine learning-based identification for HIV-1 bNAbs
Authors: Foglierini Mathilde , Nortier Pauline , Schelling Rachel , Winiger Rahel R. , Jacquet Philippe , O’Dell Sijy , Demurtas Davide , Mpina Maxmillian , Lweno Omar , Muller Yannick D. , Petrovas Constantinos , Daubenberger Claudia , Perreau Matthieu , Doria-Rose Nicole A. , Gottardo Raphael , Perez Laurent 
Published: June 2024

AbstractBroadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infections. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoires is still lacking. Here, we develop a straightforward computational method for the Rapid Automatic Identification of bNAbs (RAIN) based on machine learning methods. In contrast to other approaches, which use one-hot encoding amino acid sequences or structural alignment for prediction, RAIN uses a combination of selected sequence-based features for the accurate prediction of HIV-1 bNAbs. We demonstrate the performance of our approach on non-biased, experimentally obtained and sequenced BCR repertoires from HIV-1 immune donors. RAIN processing leads to the successful identification of distinct HIV-1 bNAbs targeting the CD4-binding site of the envelope glycoprotein. In addition, we validate the identified bNAbs using an in vitro neutralization assay and we solve the structure of one of them in complex with the soluble native-like heterotrimeric envelope glycoprotein by single-particle cryo-electron microscopy (cryo-EM). Overall, we propose a method to facilitate and accelerate HIV-1 bNAbs discovery from non-selected immune repertoires.
Bound star clusters observed in a lensed galaxy 460 Myr after the Big Bang
Authors: Adamo Angela , Bradley Larry D. , Vanzella Eros , Claeyssens Adélaïde , Welch Brian , Diego Jose M. , Mahler Guillaume , Oguri Masamune , Sharon Keren , Abdurro’uf  , Hsiao Tiger Yu-Yang , Xu Xinfeng , Messa Matteo , Lassen Augusto E. , Zackrisson Erik , Brammer Gabriel , Coe Dan , Kokorev Vasily , Ricotti Massimo , Zitrin Adi , Fujimoto Seiji , Inoue Akio K. , Resseguier Tom , Rigby Jane R. , Jiménez-Teja Yolanda , Windhorst Rogier A. , Hashimoto Takuya , Tamura Yoichi 
Published: June 2024

AbstractThe Cosmic Gems arc is among the brightest and highly magnified galaxies observed at redshift z ≈ 10.2 (ref. 1). However, it is an intrinsically ultraviolet faint galaxy, in the range of those now thought to drive the reionization of the Universe2–4. Hitherto the smallest features resolved in a galaxy at a comparable redshift are between a few hundreds and a few tens of parsecs (pc)5,6. Here we report JWST observations of the Cosmic Gems. The light of the galaxy is resolved into five star clusters located in a region smaller than 70 pc. They exhibit minimal dust attenuation and low metallicity, ages younger than 50 Myr and intrinsic masses of about 106M⊙. Their lensing-corrected sizes are approximately 1 pc, resulting in stellar surface densities near 105M⊙ pc−2, three orders of magnitude higher than typical young star clusters in the local Universe7. Despite the uncertainties inherent to the lensing model, they are consistent with being gravitationally bound stellar systems, that is, proto-globular clusters. We conclude that star cluster formation and feedback likely contributed to shaping the properties of galaxies during the epoch of reionization.
Transcriptomic analysis of intestine following administration of a transglutaminase 2 inhibitor to prevent gluten-induced intestinal damage in celiac disease
Authors: Dotsenko Valeriia , Tewes Bernhard , Hils Martin , Pasternack Ralf , Isola Jorma , Taavela Juha , Popp Alina , Sarin Jani , Huhtala Heini , Hiltunen Pauliina , Zimmermann Timo , Mohrbacher Ralf , Greinwald Roland , Lundin Knut E. A. , Schuppan Detlef , Mäki Markku , Viiri Keijo ,   CEC-3 Investigators, Kull Karin , Koskenpato Jari , Scheinin Mika , Lähdeaho Marja-Leena , Schumann Michael , Zopf Yurdagül , Stallmach Andreas , Lohse Ansgar W. , Fusco Stefano , Langhorst Jost , Török Helga Paula , Byrnes Valerie , Kupcinskas Juozas , Hovde Øistein , Jahnsen Jørgen , Biedermann Luc , Zeitz Jonas 
Published: June 2024

AbstractTransglutaminase 2 (TG2) plays a pivotal role in the pathogenesis of celiac disease (CeD) by deamidating dietary gluten peptides, which facilitates antigenic presentation and a strong anti-gluten T cell response. Here, we elucidate the molecular mechanisms underlying the efficacy of the TG2 inhibitor ZED1227 by performing transcriptional analysis of duodenal biopsies from individuals with CeD on a long-term gluten-free diet before and after a 6-week gluten challenge combined with 100 mg per day ZED1227 or placebo. At the transcriptome level, orally administered ZED1227 effectively prevented gluten-induced intestinal damage and inflammation, providing molecular-level evidence that TG2 inhibition is an effective strategy for treating CeD. ZED1227 treatment preserved transcriptome signatures associated with mucosal morphology, inflammation, cell differentiation and nutrient absorption to the level of the gluten-free diet group. Nearly half of the gluten-induced gene expression changes in CeD were associated with the epithelial interferon-γ response. Moreover, data suggest that deamidated gluten-induced adaptive immunity is a sufficient step to set the stage for CeD pathogenesis. Our results, with the limited sample size, also suggest that individuals with CeD might benefit from an HLA-DQ2/HLA-DQ8 stratification based on gene doses to maximally eliminate the interferon-γ-induced mucosal damage triggered by gluten.
Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial
Authors: Mann Johannes F. E. , Rossing Peter , Bakris George , Belmar Nicolas , Bosch-Traberg Heidrun , Busch Robert , Charytan David M. , Hadjadj Samy , Gillard Pieter , Górriz José Luis , Idorn Thomas , Ji Linong , Mahaffey Kenneth W. , Perkovic Vlado , Rasmussen Søren , Schmieder Roland E. , Pratley Richard E. , Tuttle Katherine R. 
Published: June 2024

AbstractPeople with type 2 diabetes and chronic kidney disease have a high risk for kidney failure and cardiovascular (CV) complications. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2i) independently reduce CV and kidney events. The effect of combining both is unclear. FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo. The primary outcome was a composite of kidney failure, ≥50% estimated glomerular filtration rate reduction, kidney death or CV death. The risk of the primary outcome was 24% lower in all participants treated with semaglutide versus placebo (95% confidence interval: 34%, 12%). The primary outcome occurred in 41/277 (semaglutide) versus 38/273 (placebo) participants on SGLT2i at baseline (hazard ratio 1.07; 95% confidence interval: 0.69, 1.67; P = 0.755) and in 290/1,490 versus 372/1,493 participants not taking SGLT2i at baseline (hazard ratio 0.73; 0.63, 0.85; P < 0.001; P interaction 0.109). Three confirmatory secondary outcomes were predefined. Treatment differences favoring semaglutide for total estimated glomerular filtration rate slope (ml min−1/1.73 m2/year) were 0.75 (−0.01, 1.5) in the SGLT2i subgroup and 1.25 (0.91, 1.58) in the non-SGLT2i subgroup, P interaction 0.237. Semaglutide benefits on major CV events and all-cause death were similar regardless of SGLT2i use (P interaction 0.741 and 0.901, respectively). The benefits of semaglutide in reducing kidney outcomes were consistent in participants with/without baseline SGLT2i use; power was limited to detect smaller but clinically relevant effects. ClinicalTrials.gov identifier: NCT03819153.
Transcriptome sequencing of seven deep marine invertebrates
Authors: Burns John A. , Daniels Joost , Becker Kaitlyn P. , Casagrande David , Roberts Paul , Orenstein Eric , Vogt Daniel M. , Teoh Zhi Ern , Wood Ryan , Yin Alexander H. , Genot Baptiste , Wood Robert J. , Katija Kakani , Phillips Brennan T. , Gruber David F. 
Published: June 2024

AbstractWe present 4k video and whole transcriptome data for seven deep-sea invertebrate animals collected in the Eastern Pacific Ocean during a research expedition onboard the Schmidt Ocean Institute’s R/V Falkor in August of 2021. The animals include one jellyfish (Atolla sp.), three siphonophores (Apolemia sp., Praya sp., and Halistemma sp.), one larvacean (Bathochordaeus mcnutti), one tunicate (Pyrosomatidae sp.), and one ctenophore (Lampocteis sp.). Four of the animals were sequenced with long-read RNA sequencing technology, such that the reads themselves define a reference assembly for those animals. The larvacean tissues were successfully preserved in situ and has paired long-read reference data and short read quantitative transcriptomic data for within-specimen analyses of gene expression. Additionally, for three animals we provide quantitative image data, and a 3D model for one siphonophore. The paired image and transcriptomic data can be used for species identification, species description, and reference genetic data for these deep-sea animals.
Preparation and characterization of novel flame-retardant paint of substituted cyclodiphosph(V)azane sulfonomide and their Cu(II), Cd(II) metal complexes as new additives for exterior wood coating protection
Authors: El khashab Narmeen G. , Albohy Salwa A. H. , El-Wahab H. Abd , Fouda Moustafa M. G. , Sharaby Carmen M. 
Published: June 2024

AbstractThe development of flame-retardant materials has become an important research direction. For the past dozen years, researchers have been exploring flame retardants with high flame-retardant efficiency, low toxicity, less smoke, or other excellent performance flame retardants. Therefore, this work aimed to synthesize new cyclodiphosph(V)azane derivatives and their Cu(II) and Cd(II) metal complexes and investigated their potential applications as high flame-retardant efficiency. Various techniques were used to characterize the prepared ligand H2L and its metal complexes, including elemental analyses, mass spectra, conductivity measurements, electronic spectral data UV–vis, FT-IR, 1H,13C-NMR, TGA, XRD, and molecular docking experiments studies were M. tuberculosis receptors (PDB ID: 5UHF) and the crystal structure of human topoisomerase II alpha (PDB ID: 4FM9). Wood-based paint was physically mixed with the ligand H2L and its metal complexes. The obtained results of mechanical characteristics of the dried paint layers were noticed to improve, such as gloss value, which ranged from 85 to 95, hardness 1.5–2.5 kg, adhesion 4B to 5B, and impact resistance, which improved from 1.3 to 2.5 J. Moreover, the obtained results of flame-retardant properties showed a significant retardant impact compared to the blank sample, such as ignitability, which includes the heat flux which increased from 10 to 25 kW/m2, and ignition time, ranging from 550 to 1200 s, respectively, and limiting oxygen index (LOI) (%) which has been increased from 21 to 130 compared with the plywood sample and sample blank. The ordering activity of the observed results was noticed that coated sample based on Cd(II) metal complexes > coated sample based on Cu(II) metal complexes of Cyclophosphazene ligand > coated sample based on phosphazene ligand H2L > coated sample without additives > uncoated sample. This efficiency may be attributed to (1) the H2L is an organophosphorus compound, which contains P, N, Cl, and aromatic six- and five-member ring, (2) Cu(II) and Cd(II) metal complexes characterized by high thermal stability, good stability, excellent performance flame retardants, and wide application.
Temporal dynamics of user activities: deep learning strategies and mathematical modeling for long-term and short-term profiling
Authors: Kayed Mohammed , Azzam Fatima , Ali Hussien , Ali Abdelmgied 
Published: June 2024

AbstractProfiling social media users is an analytical approach to generate an extensive blueprint of user’s personal characteristics, which can be useful for a diverse range of applications, such as targeted marketing and personalized recommendations. Although social user profiling has gained substantial attention in recent years, effectively constructing a collaborative model that could describe long and short-term profiles is still challenging. In this paper, we will discuss the profiling problem from two perspectives; how to mathematically model and track user’s behavior over short and long periods and how to enhance the classification of user’s activities. Using mathematical equations, our model can define periods in which the user's interests abruptly changed. A dataset consisting of 30,000 tweets was built and manually annotated into 10 topic categories. Bi-LSTM and GRU models are applied to classify the user’s activities representing his interests, which then are utilized to create and model the dynamic profile. In addition, the effect of word embedding techniques and pre-trained classification models on the accuracy of the classification process is explored in this research.
Morphological and proteomic study of waterlogging tolerance in cotton
Authors: Zhang Hao , Xie Zhangshu , Tu Xiaoju , Liu Aiyu , Chen Jinxiang , He Yunxin , Wu Bibo , Zhou Zhonghua 
Published: June 2024

AbstractFloating seedling cultivation technique is a novel seedling method in cotton and it provides an ideal model to study cotton growing under waterlogging stress. Morphological character and proteomic profile of the primary root from the seedling cultured by the new technology were evaluated in this study. Compared to seedlings cultured by the traditional method, the diameter of the taproot from floating technology is small at all five seedling stages from one-leaf stage to five-leaf stage. There are similar changes between the thickness of cortex and diameter of stele, which increased from the one- to the two-leaf stage but decreased from the two- to the five-leaf stage. At the one-leaf stage, the number and volume of mitochondria in the primary root-tip cells were less than those in the control. At the two-leaf stage, there was significantly less electron-dense material in the primary root-tip cells than those in the control group. From the one- to the two-leaf stage, the vacuole volume was significantly smaller than that in the control. Total 28 differentially expressed proteins were revealed from aquatic and control group roots of cotton seedlings at the three-leaf stage by two-dimensional electrophoresis, which included 24 up-regulated and four down-regulated proteins. The relative expression of the phosphoglycerate kinase (PGK) gene in aquatic roots increased from the one- to the four-leaf stage but declined rapidly from the four- to the five-leaf stage. The relative expression of the 14–3-3b gene tended to decrease from the one- to the five-leaf stage. The PGK and 14–3-3b genes were specifically expressed in the aquatic roots at the three-leaf stage. In brief, these changes induced waterlogging resistance in the aquatic roots of cotton seedlings in the floating nursery, thereby causing the roots to adapt to the aquatic environment, promoting the growth and development of cotton seedlings.
Drying kinetics, thermodynamic properties and physicochemical characteristics of Rue leaves
Authors: Mabasso Geraldo Acácio , Cabral Jennifer Cristhine Oliveira , Barbosa Karine Feliciano , Resende Osvaldo , de Oliveira Daniel Emanuel Cabral , de Almeida Adrielle Borges 
Published: June 2024

AbstractGenerally, medicinal plants are harvested with high amount of water, so it is essential to subject the product to drying as soon as possible to prevent degradation before application. Most compounds from medicinal plants are sensitive to drying processes, so it is important to adjust the drying conditions. The objective of this study was to describe the drying of Rue (Ruta chalepensis L.) leaves, select the models that best fit each drying condition, determine the activation energy and thermodynamic properties of the leaves, and evaluate their quality after drying. Leaves were harvested with moisture content of 3.55 ± 0.05 kg water kg−1dry matter and subjected to drying at temperatures of 40, 50, 60 and 70 °C. Valcam model showed the best fit to represent the drying kinetics of Rue leaves at temperatures of 40 and 70 °C, and Midilli model proved to be better for the temperatures of 50 and 60 °C. Effective diffusion coefficient increased linearly with the increase in drying air temperature, and the activation energy was 60.58 kJ mol−1. Enthalpy, entropy and Gibbs free energy values ranged from 57.973 to 57.723 kJ mol−1, from − 0.28538 to − 0.28614 kJ mol−1 K−1 and from 147.34 to 155.91 kJ mol−1, respectively, for the temperature range of 40–70 °C. Drying air temperature promoted darkening or tendency to loss of green color; increase in drying air temperature leads to greater discoloration, as well as a higher concentration of total phenolic compounds (about 221.10 mg GAE mL−1 g–1 dm), with a peak at temperature of 60 °C.