bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal stromal cells facilitate resolution of pulmonary fibrosis by miR-29c and miR-129 intercellular transfer
Authors: Nataliya Basalova , Mikhail Arbatskiy , Vladimir Popov , Olga Grigorieva , Maksim Vigovskiy , Ivan Zaytsev , Ekaterina Novoseletskaya , Georgy Sagaradze , Natalia Danilova , Pavel Malkov , Andrey Cherniaev , Maria Samsonova , Maxim Karagyaur , Anastasiya Tolstoluzhinskaya , Uliana Dyachkova , Zhanna Akopyan , Vsevolod Tkachuk , Natalia Kalinina , Anastasiya Efimenko 
Published: July 2023

AbstractTo date, pulmonary fibrosis remains an unmet medical need. In this study, we evaluated the potency of mesenchymal stromal cell (MSC) secretome components to prevent pulmonary fibrosis development and facilitate fibrosis resolution. Surprisingly, the intratracheal application of extracellular vesicles (MSC-EVs) or the vesicle-depleted secretome fraction (MSC-SF) was not able to prevent lung fibrosis when applied immediately after the injury caused by bleomycin instillation in mice. However, MSC-EV administration induced the resolution of established pulmonary fibrosis, whereas the vesicle-depleted fraction did not. The application of MSC-EVs caused a decrease in the numbers of myofibroblasts and FAPa+ progenitors without affecting their apoptosis. Such a decrease likely occurred due to their dedifferentiation caused by microRNA (miR) transfer by MSC-EVs. Using a murine model of bleomycin-induced pulmonary fibrosis, we confirmed the contribution of specific miRs (miR-29c and miR-129) to the antifibrotic effect of MSC-EVs. Our study provides novel insights into possible antifibrotic therapy based on the use of the vesicle-enriched fraction of the MSC secretome.
TXNIP: A key protein in the cellular stress response pathway and a potential therapeutic target
Authors: Choi Eui-Hwan , Park Sun-Ji 
Published: July 2023

AbstractThioredoxin-interacting protein (TXNIP), which is also known as thioredoxin-binding protein 2 (TBP2), directly interacts with the major antioxidant protein thioredoxin (TRX) and inhibits its antioxidant function and expression. However, recent studies have demonstrated that TXNIP is a multifunctional protein with functions beyond increasing intracellular oxidative stress. TXNIP activates endoplasmic reticulum (ER) stress-mediated nucleotide-binding oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome complex formation, triggers mitochondrial stress-induced apoptosis, and stimulates inflammatory cell death (pyroptosis). These newly discovered functions of TXNIP highlight its role in disease development, especially in response to several cellular stress factors. In this review, we provide an overview of the multiple functions of TXNIP in pathological conditions and summarize its involvement in various diseases, such as diabetes, chronic kidney disease, and neurodegenerative diseases. We also discuss the potential of TXNIP as a therapeutic target and TXNIP inhibitors as novel therapeutic drugs for treating these diseases.
Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential
Authors: Xu Xuemeng , Peng Qiu , Jiang Xianjie , Tan Shiming , Yang Yiqing , Yang Wenjuan , Han Yaqian , Chen Yuyu , Oyang Linda , Lin Jinguan , Xia Longzheng , Peng Mingjing , Wu Nayiyuan , Tang Yanyan , Li Jinyun , Liao Qianjin , Zhou Yujuan 
Published: July 2023

AbstractMetabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.
Immune regulation through tryptophan metabolism
Authors: Seo Su-Kil , Kwon Byungsuk 
Published: July 2023

AbstractAmino acids are fundamental units of molecular components that are essential for sustaining life; however, their metabolism is closely interconnected to the control systems of cell function. Tryptophan (Trp) is an essential amino acid catabolized by complex metabolic pathways. Several of the resulting Trp metabolites are bioactive and play central roles in physiology and pathophysiology. Additionally, various physiological functions of Trp metabolites are mutually regulated by the gut microbiota and intestine to coordinately maintain intestinal homeostasis and symbiosis under steady state conditions and during the immune response to pathogens and xenotoxins. Cancer and inflammatory diseases are associated with dysbiosis- and host-related aberrant Trp metabolism and inactivation of the aryl hydrocarbon receptor (AHR), which is a receptor of several Trp metabolites. In this review, we focus on the mechanisms through which Trp metabolism converges to AHR activation for the modulation of immune function and restoration of tissue homeostasis and how these processes can be targeted using therapeutic approaches for cancer and inflammatory and autoimmune diseases.
Genomic characteristics of triple negative apocrine carcinoma: a comparison to triple negative breast cancer
Authors: Kim Ji-Yeon , Park Sabin , Cho Eun Yoon , Lee Jeong Eon , Jung Hae Hyun , Chae Byung Joo , Kim Seok Won , Nam Seok Jin , Cho Soo Youn , Park Yeon Hee , Ahn Jin Seok , Lee Semin , Im Young-Hyuck 
Published: July 2023

AbstractApocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student’s t test, p < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC (p < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC (P = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC (P = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC.
Transcriptional regulation of Glis2 in hepatic fibrosis
Authors: Gong Huan-Yu , Zhou Peng-Cheng , Zhang Hao-Ye , Chen Li-Min , Zhou Yang-Mei , Liu Zhen-Guo 
Published: July 2023

AbstractThe role of Gli-similar 2 (Glis2) in hepatic fibrosis (HF) is controversial. In this study, we focused on the functional and molecular mechanisms involved in the Glis2-mediated activation of hepatic stellate cells (HSCs)—a milestone event leading to HF. The expression levels of Glis2 mRNA and protein were significantly decreased in the liver tissues of patients with severe HF and in mouse fibrotic liver tissues as well as HSCs activated by TGFβ1. Functional studies indicated that upregulated Glis2 significantly inhibited HSC activation and alleviated BDL-induced HF in mice. Downregulation of Glis2 was found to correlate significantly with DNA methylation of the Glis2 promoter mediated by methyltransferase 1 (DNMT1), which restricted the binding of hepatic nuclear factor 1-α (HNF1-α), a liver-specific transcription factor, to Glis2 promoters. In addition, the enrichment of DNMT1 in the Glis2 promoter region was mediated by metastasis-associated lung adenocarcinoma transcriptor-1 (MALAT1) lncRNA, leading to transcriptional silencing of Glis2 and activation of HSCs. In conclusion, our findings reveal that the upregulation of Glis2 can maintain the resting state of HSCs. The decreased expression of Glis2 under pathological conditions may lead to the occurrence and development of HF with the expression silencing of DNA methylation mediated by MALAT1 and DNMT1.
ROR1-STAT3 signaling contributes to ovarian cancer intra-tumor heterogeneity
Authors: Piki Emilia , Dini Alice , Raivola Juuli , Salokas Kari , Zhang Kaiyang , Varjosalo Markku , Pellinen Teijo , Välimäki Katja , Veskimäe Kristina Tabor , Staff Synnöve , Hautaniemi Sampsa , Murumägi Astrid , Ungureanu Daniela 
Published: July 2023

AbstractWnt pathway dysregulation through genetic and non-genetic alterations occurs in multiple cancers, including ovarian cancer (OC). The aberrant expression of the non-canonical Wnt signaling receptor ROR1 is thought to contribute to OC progression and drug resistance. However, the key molecular events mediated by ROR1 that are involved in OC tumorigenesis are not fully understood. Here, we show that ROR1 expression is enhanced by neoadjuvant chemotherapy, and Wnt5a binding to ROR1 can induce oncogenic signaling via AKT/ERK/STAT3 activation in OC cells. Proteomics analysis of isogenic ROR1-knockdown OC cells identified STAT3 as a downstream effector of ROR1 signaling. Transcriptomics analysis of clinical samples (n = 125) revealed that ROR1 and STAT3 are expressed at higher levels in stromal cells than in epithelial cancer cells of OC tumors, and these findings were corroborated by multiplex immunohistochemistry (mIHC) analysis of an independent OC cohort (n = 11). Our results show that ROR1 and its downstream STAT3 are co-expressed in epithelial as well as stromal cells of OC tumors, including cancer-associated fibroblasts or CAFs. Our data provides the framework to expand the clinical utility of ROR1 as a therapeutic target to overcome OC progression.
A biological camera that captures and stores images directly into DNA
Authors: Lim Cheng Kai , Yeoh Jing Wui , Kunartama Aurelius Andrew , Yew Wen Shan , Poh Chueh Loo 
Published: July 2023

AbstractThe increasing integration between biological and digital interfaces has led to heightened interest in utilizing biological materials to store digital data, with the most promising one involving the storage of data within defined sequences of DNA that are created by de novo DNA synthesis. However, there is a lack of methods that can obviate the need for de novo DNA synthesis, which tends to be costly and inefficient. Here, in this work, we detail a method of capturing 2-dimensional light patterns into DNA, by utilizing optogenetic circuits to record light exposure into DNA, encoding spatial locations with barcoding, and retrieving stored images via high-throughput next-generation sequencing. We demonstrate the encoding of multiple images into DNA, totaling 1152 bits, selective image retrieval, as well as robustness to drying, heat and UV. We also demonstrate successful multiplexing using multiple wavelengths of light, capturing 2 different images simultaneously using red and blue light. This work thus establishes a ‘living digital camera’, paving the way towards integrating biological systems with digital devices.
Spatiotemporal proteomic atlas of multiple brain regions across early fetal to neonatal stages in cynomolgus monkey
Authors: Wei Jingkuan , Dai Shaoxing , Yan Yaping , Li Shulin , Yang Pengpeng , Zhu Ran , Huang Tianzhuang , Li Xi , Duan Yanchao , Wang Zhengbo , Ji Weizhi , Si Wei 
Published: July 2023

AbstractFetal stages are critical periods for brain development. However, the protein molecular signature and dynamics of the human brain remain unclear due to sampling difficulty and ethical limitations. Non-human primates present similar developmental and neuropathological features to humans. This study constructed a spatiotemporal proteomic atlas of cynomolgus macaque brain development from early fetal to neonatal stages. Here we showed that (1) the variability across stages was greater than that among brain regions, and comparisons of cerebellum vs. cerebrum and cortical vs. subcortical regions revealed region-specific dynamics across early fetal to neonatal stages; (2) fluctuations in abundance of proteins associated with neural disease suggest the risk of nervous disorder at early fetal stages; (3) cross-species analysis (human, monkey, and mouse) and comparison between proteomic and transcriptomic data reveal the proteomic specificity and genes with mRNA/protein discrepancy. This study provides insight into fetal brain development in primates.
Rapid strengthening of westerlies accompanied intensification of Northern Hemisphere glaciation
Authors: Bridges Joshua D. , Tarduno John A. , Cottrell Rory D. , Herbert Timothy D. 
Published: July 2023

AbstractThe trigger, pace, and nature of the intensification of Northern Hemisphere Glaciation (iNHG) are uncertain, but can be probed by study of ODP Site 1208 North Pacific marine sediments. Herein, we present magnetic proxy data that indicate a 4-fold increase of dust between ~ 2.73 and ~ 2.72 Ma, with subsequent increases at the start of glacials thereafter, indicating a strengthening of the mid-latitude westerlies. Moreover, a permanent shift in dust composition after 2.72 Ma is observed, consistent with drier conditions in the source region and/or the incorporation of material which could not have been transported via the weaker Pliocene winds. The sudden increase in our dust proxy data, a coeval rapid rise in dust recorded by proxy dust data in the North Atlantic (Site U1313), and the Site 1208 shift in dust composition, suggest that the iNHG represents a permanent crossing of a climate threshold toward global cooling and ice sheet growth, ultimately driven by lower atmospheric CO2.
Evidence for compositionally distinct upper mantle plumelets since the early history of the Tristan-Gough hotspot
Authors: Homrighausen Stephan , Hoernle Kaj , Hauff Folkmar , Hoyer Patrick A. , Haase Karsten M. , Geissler Wolfram H. , Geldmacher Jörg 
Published: July 2023

AbstractRecent studies indicate that mantle plumes, which transfer material and heat from the earth’s interior to its surface, represent multifaceted upwellings. The Tristan-Gough hotspot track (South Atlantic), which formed above a mantle plume, documents spatial geochemical zonation in two distinct sub-tracks since ~70 Ma. The origin and the sudden appearance of two distinct geochemical flavors is enigmatic, but could provide insights into the structural evolution of mantle plumes. Sr–Nd–Pb–Hf isotope data from the Late Cretaceous Rio Grande Rise and adjacent Jean Charcot Seamount Chain (South American Plate), which represent the counterpart of the older Tristan-Gough volcanic track (African Plate), extends the bilateral-zonation to ~100 Ma. Our results support recent numerical models, demonstrating that mantle plumes can split into distinct upper mantle conduits, and provide evidence that these plumelets formed at the plume head-to-plume tail transition. We attribute the plume zonation to sampling the geochemically-graded margin of the African Large Low-Shear-Velocity Province.
Dynamic control of hybrid grafted perfect vector vortex beams
Authors: Ahmed Hammad , Ansari Muhammad Afnan , Li Yan , Zentgraf Thomas , Mehmood Muhammad Qasim , Chen Xianzhong 
Published: July 2023

AbstractPerfect vector vortex beams (PVVBs) have attracted considerable interest due to their peculiar optical features. PVVBs are typically generated through the superposition of perfect vortex beams, which suffer from the limited number of topological charges (TCs). Furthermore, dynamic control of PVVBs is desirable and has not been reported. We propose and experimentally demonstrate hybrid grafted perfect vector vortex beams (GPVVBs) and their dynamic control. Hybrid GPVVBs are generated through the superposition of grafted perfect vortex beams with a multifunctional metasurface. The generated hybrid GPVVBs possess spatially variant rates of polarization change due to the involvement of more TCs. Each hybrid GPVVB includes different GPVVBs in the same beam, adding more design flexibility. Moreover, these beams are dynamically controlled with a rotating half waveplate. The generated dynamic GPVVBs may find applications in the fields where dynamic control is in high demand, including optical encryption, dense data communication, and multiple particle manipulation.
Built structures influence patterns of energy demand and CO2 emissions across countries
Authors: Haberl Helmut , Löw Markus , Perez-Laborda Alejandro , Matej Sarah , Plank Barbara , Wiedenhofer Dominik , Creutzig Felix , Erb Karl-Heinz , Duro Juan Antonio 
Published: July 2023

AbstractBuilt structures, i.e. the patterns of settlements and transport infrastructures, are known to influence per-capita energy demand and CO2emissions at the urban level. At the national level, the role of built structures is seldom considered due to poor data availability. Instead, other potential determinants of energy demand and CO2emissions, primarily GDP, are more frequently assessed. We present a set of national-level indicators to characterize patterns of built structures. We quantify these indicators for 113 countries and statistically analyze the results along with final energy use and territorial CO2emissions, as well as factors commonly included in national-level analyses of determinants of energy use and emissions. We find that these indicators are about equally important for predicting energy demand and CO2emissions as GDP and other conventional factors. The area of built-up land per capita is the most important predictor, second only to the effect of GDP.
Neoantigen-specific stem cell memory-like CD4+ T cells mediate CD8+ T cell-dependent immunotherapy of MHC class II-negative solid tumors
Authors: Brightman Spencer E. , Becker Angelica , Thota Rukman R. , Naradikian Martin S. , Chihab Leila , Zavala Karla Soria , Ramamoorthy Premlal Ashmitaa Logandha , Griswold Ryan Q. , Dolina Joseph S. , Cohen Ezra E. W. , Miller Aaron M. , Peters Bjoern , Schoenberger Stephen P. 
Published: July 2023

AbstractCD4+T cells play key roles in a range of immune responses, either as direct effectors or through accessory cells, including CD8+T lymphocytes. In cancer, neoantigen (NeoAg)-specific CD8+T cells capable of direct tumor recognition have been extensively studied, whereas the role of NeoAg-specific CD4+T cells is less well understood. We have characterized the murine CD4+T cell response against a validated NeoAg (CLTCH129>Q) expressed by the MHC-II-deficient squamous cell carcinoma tumor model (SCC VII) at the level of single T cell receptor (TCR) clonotypes and in the setting of adoptive immunotherapy. We find that the natural CLTCH129>Q-specific repertoire is diverse and contains TCRs with distinct avidities as measured by tetramer-binding assays and CD4 dependence. Despite these differences, CD4+T cells expressing high or moderate avidity TCRs undergo comparable in vivo proliferation to cross-presented antigen from growing tumors and drive similar levels of therapeutic immunity that is dependent on CD8+T cells and CD40L signaling. Adoptive cellular therapy (ACT) with NeoAg-specific CD4+T cells is most effective when TCR-engineered cells are differentiated ex vivo with IL-7 and IL-15 rather than IL-2 and this was associated with both increased expansion as well as the acquisition and stable maintenance of a T stem cell memory (TSCM)-like phenotype in tumor-draining lymph nodes (tdLNs). ACT with TSCM-like CD4+T cells results in lower PD-1 expression by CD8+T cells in the tumor microenvironment and an increased frequency of PD-1+CD8+T cells in tdLNs. These findings illuminate the role of NeoAg-specific CD4+T cells in mediating antitumor immunity via providing help to CD8+T cells and highlight their therapeutic potential in ACT.
Polyhydroxy butyrate biosynthesis by Azotobacter chroococcum MTCC 3858 through groundnut shell as lignocellulosic feedstock using resource surface methodology
Authors: Nagajothi Kasilingam , Murugesan A. G. 
Published: July 2023

AbstractThis work appraises the prospect of utilising groundnut shell hydrolysate as a feedstock used for PHB biosynthesis by Azotobacter chroococcum MTCC 3853 under SMF conditions. Sugar reduction: untreated and pretreated 20% H2SO4 (39.46 g/l and 62.96 g/l, respectively), untreated and enzymatic hydrolysis (142.35 mg/g and 568.94 mg/g). The RSM-CCD optimization method was used to generate augment PHB biosynthesis from groundnut shell hydrolysate (30 g/l), ammonium sulphate (1.5 g/l), ammonium chloride (1.5 g/l), peptone (1.5 g/l), pH 7, 30 °C, and a 48 h incubation time. The most convincing factors (p < 0.0001), coefficient R2 values of biomass 0.9110 and PHB yield 0.9261, PHB production, highest biomass (17.23 g/l), PHB Yield(11.46 g/l), and 66.51 (wt% DCW) values were recorded. The control (untreated GN) PHB yield value of 2.86 g/l increased up to fourfold in pretreated GN. TGA results in a melting range in the peak perceived at 270.55 °C and a DSC peak range of 172.17 °C, correspondingly. According to the results, it furnishes an efficient agricultural waste executive approach by diminishing the production expenditure. It reinforces the production of PHB, thereby shrinking our reliance on fossil fuel-based plastics.
Creating musical features using multi-faceted, multi-task encoders based on transformers
Authors: Greer Timothy , Shi Xuan , Ma Benjamin , Narayanan Shrikanth 
Published: July 2023

AbstractComputational machine intelligence approaches have enabled a variety of music-centric technologies in support of creating, sharing and interacting with music content. A strong performance on specific downstream application tasks, such as music genre detection and music emotion recognition, is paramount to ensuring broad capabilities for computational music understanding and Music Information Retrieval. Traditional approaches have relied on supervised learning to train models to support these music-related tasks. However, such approaches require copious annotated data and still may only provide insight into one view of music—namely, that related to thespecifictask at hand. We present a new model for generating audio-musical features that support music understanding, leveraging self-supervision and cross-domain learning. After pre-training using masked reconstruction of musical input features using self-attention bidirectional transformers, output representations are fine-tuned using several downstream music understanding tasks. Results show that the features generated by our multi-faceted, multi-task, music transformer model, which we call M3BERT, tend to outperform other audio and music embeddings on several diverse music-related tasks, indicating the potential of self-supervised and semi-supervised learning approaches toward a more generalized and robust computational approach to modeling music. Our work can offer a starting point for many music-related modeling tasks, with potential applications in learning deep representations and enabling robust technology applications.