bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Pseudo‐Global Warming on the Weather‐Climate System of Africa in a Convection‐Permitting Model
Authors: Núñez Ocasio K. M. , Dougherty Erin M. 
Published: December 2024

AbstractThe African easterly jet (AEJ) and the West African Monsoon (WAM) can largely modulate high‐impact weather over Africa and the tropical Atlantic. How these features will change with a warming climate is just starting to be addressed due to global climate model limitations in resolving convection. We employ a novel regional setup for an atmospheric convection‐permitting model alongside the pseudo‐global warming (PGW) approach to address climate change impacts on the weather‐climate system of Africa during a short period of high‐impact weather. Our findings indicate that the AEJ and WAM may intensify in a future warming climate scenario. Precipitation is shown to increase over Guinea Highlands and Cameroon Mountains and shift southward due to a latitudinal expansion and increase of deep convection closer to the equator. This has relevant ramifications for the livelihood of communities that depend on water‐fed crops in tropical Africa.
A Vertically Resolved Canopy Improves Chemical Transport Model Predictions of Ozone Deposition to North Temperate Forests
Authors: Vermeuel Michael P. , Millet Dylan B. , Farmer Delphine K. , Ganzeveld Laurens N. , Visser Auke J. , Alwe Hariprasad D. , Bertram Timothy H. , Cleary Patricia A. , Desai Ankur R. , Helmig Detlev , Kavassalis Sarah C. , Link Michael F. , Pothier Matson A. , Riches Mj , Wang Wei , Williams Sara 
Published: December 2024

AbstractDry deposition is the second largest tropospheric ozone (O3) sink and occurs through stomatal and nonstomatal pathways. Current O3 uptake predictions are limited by the simplistic big‐leaf schemes commonly used in chemical transport models (CTMs) to parameterize deposition. Such schemes fail to reproduce observed O3 fluxes over terrestrial ecosystems, highlighting the need for more realistic treatment of surface‐atmosphere exchange in CTMs. We address this need by linking a resolved canopy model (1D Multi‐Layer Canopy CHemistry and Exchange Model, MLC‐CHEM) to the GEOS‐Chem CTM and use this new framework to simulate O3 fluxes over three north temperate forests. We compare results with in situ measurements from four field studies and with standalone, observationally constrained MLC‐CHEM runs to test current knowledge of O3 deposition and its drivers. We show that GEOS‐Chem overpredicts observed O3 fluxes across all four studies by up to 2×, whereas the resolved‐canopy models capture observed diel profiles of O3 deposition and in‐canopy concentrations to within 10%. Relative humidity and solar irradiance are strong O3 flux drivers over these forests, and uncertainties in those fields provide the largest remaining source of model deposition biases. Flux partitioning analysis shows that: (a) nonstomatal loss accounts for 60% of O3 deposition on average; (b) in‐canopy chemistry makes only a small contribution to total O3 fluxes; and (c) the CTM big‐leaf treatment overestimates O3‐driven stomatal loss and plant phytotoxicity in these temperate forests by up to 7×. Results motivate the application of fully online vertically explicit canopy schemes in CTMs for improved O3 predictions.
Extensive Secondary Cratering From the InSight Sol 1034a Impact Event
Authors: Grindrod P. M. , Daubar I. J. , Fernando B. , Kim D. , Collins G. S. , Stähler S. C. , Wojcicka N. , Posiolova L. V. , Froment M. , Beucler É. , Sansom E. , Garcia R. , Zenhäusern G. 
Published: December 2024

AbstractImpact cratering is one of the fundamental processes throughout the history of the Solar System. The formation of new impact craters on planetary bodies has been observed with repeat images from orbiting satellites. However, the time gap between images is often large enough to preclude detailed analysis of smaller‐scale features such as secondary impact craters, which are often removed or buried over a short time period. Here we use a seismic event detected on Mars by the NASA InSight mission to investigate secondary cratering at a new impact crater. We strengthen the case that the seismic event that occurred on Sol 1034 (S1034a) is the result of a new impact cratering event. Using the exact timing of this event from InSight, we investigated the resulting new impact crater in orbital image data. The S1034a impact crater is approximately 9 m in diameter but is responsible for over 900 secondary impact events in the form of low albedo spots that are located at distances of up to almost 7 km from the primary crater. We suggest that the low albedo spots formed from relatively low energy ejecta, with individual ejecta block velocities less than 200 m s−1. We estimate that the low albedo spots, the main evidence of secondary impact processes at this new impact event, fade within 200–300 days after formation.
Response of the ductus arteriosus to acetaminophen or indomethacin in extremely low birth weight infants
Authors: Sutton Courtney C. , Slaughter James C. , Alrifai Mhd Wael , Hale Jennifer , Reese Jeff 
Published: December 2024

Abstract
Objective
Acetaminophen and indomethacin are used for medical management of a patent ductus arteriosus. This study compared the efficacy of these agents in ELBW infants.

Study design
This was a retrospective study of all courses of indomethacin and acetaminophen. Baseline characteristics, details of pharmacologic therapy, toxicity, and acetaminophen serum concentrations were collected. The primary analysis compared rates of ductus closure with indomethacin versus acetaminophen using Pearson’s Chi-squared test.

Results
Ductus closure after a single course of therapy was similar between acetaminophen and indomethacin 16% vs. 18%, (p = 0.79). No differences were found in gestational age, birth weight, patient acuity, toxicity, or acetaminophen concentrations between those courses that resulted in closure compared to those that did not. When comparing single-agent exposure, indomethacin was initiated earlier (9.0 vs. 13.5 days, p = 0.022) but PDA closure rates were similar between groups.

Conclusion
Acetaminophen and indomethacin produced similar rates of ductus closure in this population.
Advancement in piezoelectric nanogenerators for acoustic energy harvesting
Authors: Jean Fandi , Khan Muhammad Umair , Alazzam Anas , Mohammad Baker 
Published: December 2024

AbstractThe demand for sustainable energy sources to power small electronics like IoT devices has led to exploring innovative solutions like acoustic energy harvesting using piezoelectric nanogenerators (PENGs). Acoustic energy harvesting leverages ambient noise, converting it into electrical energy through the piezoelectric effect, where certain materials generate an electric charge in response to mechanical stress or vibrations. This review paper provides a comprehensive analysis of the advancements in PENG technology, emphasizing their role in acoustic energy harvesting. We begin by discussing the essential principles of piezoelectricity and the design considerations for nanogenerators to optimize energy capture from sound waves. The discussion includes a detailed examination of various piezoelectric materials, such as polyvinylidene fluoride (PVDF), lead zirconate titanate (PZT), and zinc oxide (ZnO) nanowires, which are known for their superior piezoelectric properties. A critical aspect of this review is the exploration of innovative structural designs and resonance devices that enhance the efficiency of PENGs. We delve into the mechanisms and benefits of using Helmholtz resonators, quarter-wavelength tubes, and cantilever beams, which are instrumental in amplifying acoustic signals and improving energy conversion rates. Each device’s design parameters and operational principles are scrutinized to highlight their contributions to the field. The review addresses practical applications of PENGs in various domains. Environmental monitoring systems, wearable electronics, and medical devices stand to benefit significantly from the continuous and sustainable power supplied by PENGs. These applications can reduce reliance on batteries and minimize maintenance by harnessing ambient acoustic energy, leading to more efficient and longer-lasting operations. Despite the promising potential of PENGs, several challenges remain, including material degradation, efficiency limitations, and integrating these devices into existing technological frameworks. This paper discusses these obstacles in detail and proposes potential solutions to enhance the longevity and performance of PENG systems. Innovations in material science and engineering are crucial to overcoming these hurdles and realizing the full potential of acoustic energy harvesting.
PRMT5-regulated splicing of DNA repair genes drives chemoresistance in breast cancer stem cells
Authors: Gillespie Matthew S. , Chiang Kelly , Regan-Mochrie Gemma L. , Choi Soo-Youn , Ward Ciara M. , Sahay Debashish , Garcia Paloma , Arnold Roland , Davies Clare C. 
Published: December 2024

AbstractBreast cancer stem cells (BCSCs) are a rare cell population that is responsible for tumour initiation, metastasis and chemoresistance. Despite this, the mechanism by which BCSCs withstand genotoxic stress is largely unknown. Here, we uncover a pivotal role for the arginine methyltransferase PRMT5 in mediating BCSC chemoresistance by modulating DNA repair efficiency. Mechanistically, we identify PRMT5 as a major regulator of DNA damage response (DDR) gene splicing in BCSCs, particularly those integral to the Fanconi Anaemia and homologous recombination pathways, with PRMT5 inhibition synergising with chemotherapy to promote BCSC apoptosis. A comparison of BCSCs and their bulk cell progeny identified some shared (ATM, DDX11, EXO1, FAN1, SLX4) but many unique (ATR, RAD17, RAD51D, RUVBL1) PRMT5-dependent alternative DDR splicing events. Surprisingly, these skipped exons and retained intron events rarely lead to substantial gene expression repression, suggesting that PRMT5 inhibition predominantly results in nuclear detention of intron-containing transcripts and the production of non-canonical isoforms with compromised protein function. Since many genes within the same DDR pathway undergo deregulated splicing, this study thus reveals additional points of vulnerability and alternative combination drug strategies that could improve the therapeutic efficacy of PRMT5 inhibitors to promote BCSC eradication.
Mitochondria-targeted oligomeric α-synuclein induces TOM40 degradation and mitochondrial dysfunction in Parkinson’s disease and parkinsonism-dementia of Guam
Authors: Vasquez Velmarini , Kodavati Manohar , Mitra Joy , Vedula Indira , Hamilton Dale J. , Garruto Ralph M. , Rao K. S. , Hegde Muralidhar L. 
Published: December 2024

AbstractMitochondrial dysfunction is a central aspect of Parkinson’s disease (PD) pathology, yet the underlying mechanisms are not fully understood. This study investigates the link between α-Synuclein (α-Syn) pathology and the loss of translocase of the outer mitochondrial membrane 40 (TOM40), unraveling its implications for mitochondrial dysfunctions in neurons. We discovered that TOM40 protein depletion occurs in the brains of patients with Guam Parkinsonism-Dementia (Guam PD) and cultured neurons expressing α-Syn proteinopathy, notably, without corresponding changes in TOM40 mRNA levels. Cultured neurons expressing α-Syn mutants, with or without a mitochondria-targeting signal (MTS) underscores the role of α-Syn’s mitochondrial localization in inducing TOM40 degradation. PDe-related etiological factors, such as 6-hydroxydopamine or ROS/metal ions stress, which promotes α-Syn oligomerization, exacerbate TOM40 depletion in PD patient-derived cells with SNCA gene triplication. Although α-Syn interacts with both TOM40 and TOM20 in the outer mitochondrial membrane, degradation is selective for TOM40, which occurs via the ubiquitin-proteasome system (UPS) pathway. Our comprehensive analyses using Seahorse technology, mitochondrial DNA sequencing, and damage assessments, demonstrate that mutant α-Syn-induced TOM40 loss results in mitochondrial dysfunction, characterized by reduced membrane potential, accumulation of mtDNA damage, deletion/insertion mutations, and altered oxygen consumption rates. Notably, ectopic supplementation of TOM40 or reducing pathological forms of α-Syn using ADP-ribosylation inhibitors ameliorate these mitochondrial defects, suggesting potential therapeutic avenues. In conclusion, our findings provide crucial mechanistic insights into how α-Syn accumulation leads to TOM40 degradation and mitochondrial dysfunction, offering insights for targeted interventions to alleviate mitochondrial defects in PD.
LINC02257 regulates malignant phenotypes of colorectal cancer via interacting with miR-1273g-3p and YB1
Authors: Park Mi-So , Jeong Seong Dong , Shin Chang Hoon , Cha Soojin , Yu Ahran , Kim Eun Ju , Gorospe Myriam , Cho Yong Beom , Won Hong-Hee , Kim Hyeon Ho 
Published: December 2024

AbstractColorectal cancer (CRC) is the third most common cancer diagnosed and the second leading cause of cancer-related deaths. Emerging evidence has indicated that long non-coding RNAs (lncRNAs) are involved in the progression of various types of cancer. In this study, we aimed to identify potential causal lncRNAs in CRC through comprehensive multilevel bioinformatics analyses, coupled with functional validation. Our bioinformatics analyses identified LINC02257 as being highly expressed in CRC, and associated with poor survival and advanced tumor stages among patients with CRC. Genome-wide association analysis revealed significant associations between variants near LINC02257 and CRC, suggesting a causal role for LINC02257 in CRC. Network analysis identified LINC02257 as playing a key role in the epithelial-mesenchymal transition pathway. Single-cell RNA sequencing showed that elevated expression of LINC02257 was associated with a reduced proportion of epithelial cells. In vitro experiments showed that LINC02257 positively regulated the metastatic and proliferative potential of CRC cells. Mechanistically, LINC02257 affected CRC malignancy by functioning as a competitive endogenous RNA of microRNAs and RNA-binding proteins. LINC02257 upregulated SERPINE1 by sequestering tumor suppressive miR-1273g-3p, thereby increasing metastatic and proliferative abilities of CRC cells. Additionally, LINC02257 directly interacted with YB1 and induced its phosphorylation, thereby facilitating YB1 nuclear translocation. The transcriptional activation of YB1 target genes was associated with the oncogenic functions of LINC02257. Taken together, our results demonstrate LINC02257 as a promising therapeutic target for CRC treatment.
NIR-715 photodynamic therapy induces immunogenic cancer cell death by enhancing the endoplasmic reticulum stress response
Authors: Zheng Zhen-Yuan , Lin Wan , Su Jia-Wan , Huang Qing-Feng , Zhang Cong , Pan Wen-Xing , Li En-Min , Zhang He-Feng , Xu Li-Yan 
Published: December 2024

AbstractEffectively interfering with endoplasmic reticulum (ER) function in tumor cells and simultaneously activating an anti-tumor immune microenvironment to attack the tumor cells are promising strategies for cancer treatment. However, precise ER-stress induction is still a huge challenge. In this study, we synthesized a near-infrared (NIR) probe, NIR-715, which induces tumor cell death and inhibits tumor growth without causing apparent side effects. NIR-715 triggers severe ER stress and immunogenic cell death (ICD) after visible light exposure. NIR-715 induced ICD-associated HMGB1 release in vitro and anti-tumor immune responses, including increased cytotoxic T lymphocyte (GZMB+ CD8+ T cell) infiltration and decreased numbers of exhausted T lymphocytes (PD-L1+ CD8+ T cell). These findings suggest that NIR-715 may be a novel agent for “cold” tumor photodynamic therapy (PDT).
Epoxy metabolites of linoleic acid promote the development of breast cancer via orchestrating PLEC/NFκB1/CXCL9-mediated tumor growth and metastasis
Authors: Ni Kai-Di , Fu Xian , Luo Ying , He Xin , Yin Hou-Hua , Mo Dong-Ping , Wu Jing-Xian , Wu Ming-Jun , Zheng Xiao , Liu Ya-Nan , Jiang Qing , Zhang Ling-Tong , Lin Ai-Zhi , Huang Ling , Pan Qing-Jin , Yin Xue-Dong , Zhang Huan-Yu , Meng Yi-Wen , Zhou Xue , Pan Jianbo , Guo Zufeng , Liu Jun-Yan 
Published: December 2024

AbstractBreast cancer (BC) is a common malignant tumor in women and requires a comprehensive understanding of its pathogenesis for the development of new therapeutic strategies. Polyunsaturated fatty acids (PUFAs) metabolism-driven inflammation is a causative factor in cancer development. However, the function of PUFAs′ metabolism in BC remains largely unknown. Here we report the role and underlying mechanism of epoxyoctadecenoic acids (EpOMEs), the metabolites of linoleic acid mediated by cytochrome P450 (CYP) monooxygenases, in promoting the development of BC, particularly triple-negative BC (TNBC). A metabolomics study identified that EpOMEs were significantly increased in the plasma of BC patients and MMTV-PyMT mice, which accounted for the upregulation of CYP2J2 in BC tumor tissues and tumor cells. Decreased EpOMEs by treatment of CYP monooxygenase inhibitors significantly alleviated tumor development in MMTV-PyMT mice. Treatment with EpOMEs and overexpression of CYP2J2 to increase EpOMEs in TNBC cells significantly promoted cellular proliferation, migration, tumor growth, and metastasis. Whereas knockdown of CYP2J2 to decrease EpOMEs inhibited tumorigenesis and lung metastasis of TNBC, which was reversed by EpOME administration. Transcriptomics and proteomics analyses revealed CXCL9 and PLEC were critical for EpOME-mediated promotion of TNBC. Knockdown of CXCL9 and PLEC inhibited TNBC progression and EpOME-mediated promotion of TNBC. Both overexpression of CYP2J2 and EpOME treatment upregulate PLEC, while PLEC upregulates NFκB1, which is a transcription regulator of CXCL9. This study extends the understanding of the function of PUFAs metabolism in BC development, providing potential therapeutic targets and dietary guidelines for patients with TNBC and other BCs.
TFAP2A drives non-small cell lung cancer (NSCLC) progression and resistance to targeted therapy by facilitating the ESR2-mediated MAPK pathway
Authors: Wang Ding-Guo , Gao Jian , Wang Jing , Li Kun-Chao , Wu Zhi-Bo , Liao Zhong-Min , Wu Yong-Bing 
Published: December 2024

AbstractCancer is among the leading causes of death related diseases worldwide, and lung cancer has the highest mortality rate in the world. Transcription factors (TFs) constitute a class of structurally and functionally intricate proteins. Aberrant expression or functional deficiencies of transcription factors may give rise to abnormal gene expression, contributing to various diseases, including tumours. In this study, we propose to elucidate the potential role and mechanism of TFAP2A in NSCLC. We found that TFAP2A levels were significantly greater in tumour tissues than para-tumour tissues, and high expression of TFAP2A was associated with poor prognosis in NSCLC patients. Additionally, TFAP2A overexpression promoted NSCLC progression both in vivo and in vitro. Mechanistically, ESR2 is a potential target regulated by TFAP2A and that TFAP2A can bind to the promoter region of ESR2. Furthermore, the overexpression of both TFAP2A and ESR2 in NSCLC cells was associated with the overactivation of MAPK signalling, and the combination of PHTPP and osimertinib had a synergistic effect on suppressing tumour growth.
MACC1 ablation suppresses the dedifferentiation process of non-CSCs in lung cancer through stabilizing KLF4
Authors: Li Zhuoshi , Wang Shiqing , Guo Tao , Yan Xinyi , Chen Chaoqun , Zhang Wenjing , Zhao Jinyao , Zhang Jinrui , Zhao Shilei , Wang Yang , Qi Yangfan , Gu Chundong 
Published: December 2024

AbstractMetastasis-associated in colon cancer-1 (MACC1) was identified as a new player in lung cancer development, and some stemness-related genes can be novel transcriptional targets of MACC1. Cancer stem cells (CSCs) are responsible for sustaining tumorigenesis and plasticity. Both CSCs and non-CSCs are plastic and capable of undergoing phenotypic transition, especially the dedifferentiation of non-CSCs switch to CSC-like cells. However, the precise role of MACC1 during this process is largely unknown. Here, we showed that MACC1 promoted the transition from non-CSC to CSC in lung cancer. We found MACC1 was overexpressed in stemness enriched cells, enhancing the transition from no-CSCs to CSCs, while short-hairpin RNA-mediated Knockdown of MACC1 impaired this process. High-throughput sequencing and tumor specimen analysis revealed that MACC1 was negative correlated with Krüppel-like factor 4 (KLF4) expression level, which acts as a negative stemness regulator in lung cancer. Mechanistically, MACC1 delays the degradation of KLF4 mRNA by repressing the expression of microRNA-25, thereby promoting the KLF4 mRNA stabilization at the post-transcriptional level. Collectively, our findings may facilitate efforts to promote the development of precision targeted therapy for cancer stem cells in lung cancer.
Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells
Authors: Ku Chia-Chen , Pan Jia-Bin , Wuputra Kenly , Hsu Wen-Li , Kato Kohsuke , Noguchi Michiya , Nakamura Yukio , Saito Shigeo , Tsai Cheng-Yu , Lin Ying-Chu , Wu Deng-Chyang , Lin Chang-Shen , Yokoyama Kazunari K. 
Published: December 2024

AbstractThe Jun dimerization protein (Jdp2) gene is active in mouse cerebellar granule cells and its protein product plays a crucial role in the formation of the cerebellum lobes through programmed cell death. However, the role of Jdp2 in cellular differentiation and pluripotency in the cerebellum, and the effect of the antioxidation reaction on cell plasticity, remain unknown. N-acetyl-l-cysteine (NAC) induced the early commitment of the differentiation of granule cell precursors (GCPs) to neurons, especially Purkinje cells, via the γ-aminobutyric acid type A receptor α6 subunit (Gabra6) axis; moreover, Jdp2 depletion enhanced this differentiation program of GCPs. The antioxidative effect of NAC was the main driving force of this decision toward the neural differentiation of the GCP population in the presence of Gabra6 in vitro. This implies that antioxidative drugs are effective agents for rescuing oxidative-stress-induced GCP damages in the cerebellum and commit this Gabra6-positive cell population toward differentiation into Purkinje cells.
USP39 regulates pyruvate handling in non-small cell lung cancer
Authors: Becirovic Tina , Zhang Boxi , Vakifahmetoglu-Norberg Helin , Kaminskyy Vitaliy O. , Kochetkova Elena , Norberg Erik 
Published: December 2024

AbstractThe ubiquitin-specific peptidase 39 (USP39) belongs to the USP family of cysteine proteases representing the largest group of human deubiquitinases (DUBs). While the oncogenic function of USP39 has been investigated in various cancer types, its roles in non-small cell lung cancer (NSCLC) remain largely unknown. Here, by applying a gene set enrichment analysis (GSEA) on lung adenocarcinoma tissues and metabolite set enrichment analysis (MSEA) on NSCLC cells depleted of USP39, we identified a previously unknown link between USP39 and the metabolism in NSCLC cells. Mechanistically, we uncovered a component of the pyruvate dehydrogenase (PDH) complex, pyruvate dehydrogenase E1 subunit alpha (PDHA), as a target of USP39. We further present that USP39 silencing caused an elevation in Lys63 ubiquitination on PDHA and a reduction in the PDH complex activity, the levels of TCA cycle intermediates, mitochondrial respiration, cell proliferation in vitro, and of tumor growth in vivo. Consistently, citrate supplementation restored mitochondrial respiration and cell growth in USP39-depleted cells. Our study elucidates and describes how USP39 regulates pyruvate metabolism through a deubiquitylation process that affects NSCLC tumor growth.