bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manipulating brassinosteroid signaling pathway to genetically improve horticultural plants
Authors: Li Xiaopeng , Li Jiaxuan , Zabed Hossain M. , Li Junjie , Xiong Min , Shi Hongyong , Li Jia 
Published: February 2025

Abstract
Brassinosteroids (BRs), a class of plant-specific steroidal hormones, play crucial roles in regulating various plant physiological functions, such as growth, development, and adaptability to the environment. Despite this broader role of BRs, previously published reviews mainly focused on the molecular mechanisms of BR-mediated regulation of vegetative and reproductive growth of model plants like Arabidopsis and some food crops, such as rice, maize, and wheat. While horticultural plants hold significant economic importance in modern agriculture, less attention has been paid to understanding the role of BRs in regulating the physiological functions of these plants. Given the lack of relevant reviews, this article aims to discuss the major roles of BRs in horticultural plants, particularly fruit and leaf development, whole plant architecture, and adaptive stress response. We also highlight key challenges and provide some future research directions for genetically improving horticultural plants by altering the BR signaling pathway.
Points to Consider on the Use of Medicines in Pregnancy Throughout the Product Lifecycle Based on Global Regulatory Guidance
Authors: Alexe Amalia , Wurst Keele , Balramsingh-Harry Leesha , Apara Olatayo , Abramova Nadezda , Eisele Osa , Fernandes Maria Fernanda Scantamburlo , Garg Anju , Kovacs Birgit , Lewis David 
Published: February 2025

Abstract
The thalidomide tragedy of the 1960s led to restrictions and limitations in the participation of pregnant women in clinical trials. Despite the paucity of information on the safe and effective use of medicines in this population, most pregnant women are prescribed medications. A landscape assessment review of guidelines and legislation governing the use of medicines in pregnancy and during breastfeeding was conducted by the TransCelerate Pharmacovigilance Pregnancy and Breastfeeding Team. Insights from the landscape assessment review were compiled to identify important points to consider concerning the use of medicines in pregnancy throughout a product lifecycle. Four main areas were identified for consideration for use of medicines in pregnancy: (1) Product development considerations: Key points on the disease itself, the medicine characteristics, non-clinical and clinical development. (2) Interventional study considerations: Key aspects in enrollment of pregnant women in clinical trials and the follow-up requirements for such women. (3) Post-marketing considerations: Key elements in spontaneous case reporting of medicines exposure during pregnancy, implementation of appropriate risk management plans for medicines likely to be used in pregnancy. (4) Full lifecycle considerations: Activities required by regulators to ensure safety surveillance and maintenance throughout product lifecycle. There is a need for harmonized guidance on how to study the use of medicine in pregnancy. This paper addresses regulatory considerations, to aid in the planning and execution of research programs focused on developing medicines for use in pregnancy when permissible under established regulatory framework.
A Critical Analysis of How Victims of Sexual Assault Face Violence in the Medical Process of Bangladesh Through Foucault’s Concept of Medical Gaze
Authors: Banarjee Subrata 
Published: February 2025

Abstract
Research continues to demonstrate that the women in Bangladesh are facing harassment during the medical process after being victims of rape. The current medical process is discriminatory and does not protect victims’ safety, confidentiality, and ethical issues. This paper identifies the challenges that victims of rape face during the medical procedure. I employed Foucault’s concept of medical gaze as the theoretical lens to uncover how the gaze is imposed upon the victims in the medical process. Discussion also show that the current medical process has significant gaps and limitations in treating women after victimization.
Deciphering the Intermodel Spread in Projections of the Impacts of Indian Summer Monsoon on ENSO Under Global Warming
Authors: Lin Shuheng , Yang Song , Dong Buwen , Deng Kaiqiang , Fang Keyan 
Published: February 2025

AbstractThe Indian summer monsoon (ISM) is intricately linked to the El Niño‐Southern Oscillation (ENSO) on interannual timescale. Although previous studies have explored ENSO's effects on the ISM, the reverse influence, particularly under global warming, remains unclear. This study examines the projected changes in the ISM's impacts on ENSO under the SSP5‐8.5 emission scenario using 34 climate models from the Coupled Model Intercomparison Project Phase 6 (CMIP6) that reasonably simulate the monsoon's effects on ENSO. A significant spread is found in the projections across the models, with approximately half of the models projecting an enhancing influence of ISM on ENSO, whereas the other half indicates a weakening effect. The intermodel spread is primarily associated with the projected changes in the strength of the feedback between precipitation and low‐level circulation over the tropical northwest Pacific, which is crucial for generating ISM‐induced anomalous circulation over the region. Models projecting an enhanced precipitation‐circulation feedback simulate larger ISM‐driven rainfall and circulation anomalies over the tropical northwest Pacific in a warmer climate, leading to more pronounced zonal wind anomalies near the equator along the southern side of the anomalous circulation and vice versa. As a result, the larger zonal wind anomalies caused by abnormal monsoons exert intensified effects on the subsequent ENSO evolution by significantly suppressing or amplifying the atmosphere‐ocean coupling processes related to ENSO development.
Mercury's Field‐Aligned Currents: Perspectives From Hybrid Simulations
Authors: Shi Z. , Rong Z. J. , Fatemi S. , Dong C. F. , Klinger Lucy , Gao J. W. , Slavin J. A. , He F. , Wei Y. , Holmström M. , Barabash S. 
Published: February 2025

AbstractPrevious studies suggested that Mercury's magnetosphere could possess Earth‐like field‐aligned currents (FACs) despite the absence of an ionosphere. However, due to the limited coverage of spacecraft observations, our understanding of Mercury's FACs is scarce. Here, we employed Amitis, a hybrid‐kinetic plasma model, to investigate the establishment and global pattern of Mercury's FACs. The responses of Mercury's FACs to various interior conductivity profiles and different orientations of the upstream interplanetary magnetic field (IMF) were simulated. It has been shown that the profile of a less resistive upper layer and a conducting core favors the establishment of FACs. Three types of large‐scale FACs (Region 1‐like, Region 2‐like and NBZ‐like FACs) are shown in simulations. Comparison with previous observations suggests that Mercury's effective conductance for closing R1‐like FACs is ∼2.4–3.4 S. The influence of IMF orientation on FACs is similar to that observed in Earth's magnetosphere, but the response of the R2‐like FACs to the IMF orientation is different.
WindSightNet: The Inter‐Annual Variability of Martian Winds Retrieved From InSight's Seismic Data With Machine Learning
Authors: Stott Alexander E. , Garcia Raphael F. , Murdoch Naomi , Mimoun David , Drilleau Mélanie , Newman Claire , Spiga Aymeric , Banfield Don , Lemmon Mark , Navarro Sara , Mora‐Sotomayor Luis , Charalambous Constantinos , Pike William T. , Lognonné Philippe , Banerdt William B. 
Published: February 2025

AbstractWind measurements from landed missions on Mars are vital to characterize the near surface atmospheric behavior on Mars and improve atmospheric models. These winds are responsible for aeolian change and the mixing of dust in and out of the atmosphere, which has a significant effect on global circulation. The NASA InSight mission recorded wind data for around 750 sols. The seismometer, however, recorded data for around 1400 sols. The dominant source of energy in the seismic data is in fact due to winds. To this end, we propose a machine learning model, dubbed WindSightNet, to map the seismic data to wind speed and direction. The trained network achieves wind speed and direction measurements with errors of 0.932 m/s and 32.6°. We use WindSightNet to retrieve winds from the entire time the seismometer was recording to compare year‐to‐year wind variations at InSight. The continuous nature of the data set enables the extraction of periodic behavior. We observe a pattern of waves due to baroclinic activity with periods of 2–3, 4, 5–7 and 9–20 sols occurring 180–360°. We also observe periodicity during the day due to convective cells. This is used to estimate the boundary layer height, yielding values between 2.3 and 7.7 km. A data‐science based metric is proposed to provide a quantification of the year‐to‐year differences in the wind speeds. This highlights variations linked to dust activity as well as other transient differences. On the whole, the seismic‐derived winds confirm the dominance of the global circulation leading to repeatable weather patterns.
Dynamic water vapor sorption: a helpful tool for preventive conservation of salt contaminated built heritage
Authors: Stahlbuhk Amelie , Godts Sebastiaan , Steiger Michael 
Published: February 2025

Abstract
The presence of salts and related salt-induced damage represent one of the major threats to the preservation of our built heritage. Identifying critical relative humidity values that facilitate crystallization cycles is essential for understanding damage risks and extents. This knowledge helps in developing recommendations for favorable, damage-avoiding climates, particularly in controllable indoor environments. While for single salts their deliquescence humidity is known, for multi-ion mixtures relevant for the built heritage multiple transitions happen over a range of relative humidity. Modeling of equilibrium crystallization pathways is possible, e.g. using the Pitzer formalism. However, for complex mixtures, only predictions can be given, which need to be validated through experimental results. This work focuses on the use of dynamic water vapor sorption measurements to investigate phase transitions in salt mixtures, demonstrating its applicability, scrutinizing different influencing factors and an appropriate interpretation of results. Additionally, presenting an experimental design that delivers reliable results for the conservation of cultural heritage is crucial. In addition to single salts, mixtures from the common hygroscopic system Na+–K+–Mg2+–Ca2+–Cl––NO3
––H2O are investigated, including their behavior in a stone material. The identified transitions are compared to the calculated behavior using the ECOS–Runsalt model. The presented results are accurate and reproducible. They show the ability to determine the critical relative humidity ranges (in bulk and in porous materials) and validate thermodynamic models.
Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort
Authors: Montanari Silvia , Jansen Rick , Schranner Daniela , Kastenmüller Gabi , Arnold Matthias , Janiri Delfina , Sani Gabriele , Bhattacharyya Sudeepa , Mahmoudian Dehkordi Siamak , Dunlop Boadie W. , Rush A. John , Penninx Brenda W. H. J. , Kaddurah-Daouk Rima , Milaneschi Yuri 
Published: February 2025

Abstract
Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Previous genomic evidence identified four ACs potentially linked to depression risk. We carried forward these ACs and tested the association of their circulating levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific symptom profiles. The sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1035) or remitted (n = 739) MDD and healthy controls (n = 800). Plasma levels of four ACs (short-chain: acetylcarnitine C2 and propionylcarnitine C3; medium-chain: octanoylcarnitine C8 and decanoylcarnitine C10) were measured. Overall depression severity as well as atypical/energy-related (AES), anhedonic and melancholic symptom profiles were derived from the Inventory of Depressive Symptomatology. As compared to healthy controls, subjects with current or remitted MDD presented similarly lower mean C2 levels (Cohen’s d = 0.2, p ≤ 1e-4). Higher overall depression severity was significantly associated with higher C3 levels (ß = 0.06, SE = 0.02, p = 1.21e-3). No associations were found for C8 and C10. Focusing on symptom profiles, only higher AES scores were linked to lower C2 (ß = −0.05, SE = 0.02, p = 1.85e-2) and higher C3 (ß = 0.08, SE = 0.02, p = 3.41e-5) levels. Results were confirmed in analyses pooling data with an additional internal replication sample from the same subjects measured at 6-year follow-up (totaling 4141 observations). Small alterations in levels of short-chain acylcarnitine levels were related to the presence and severity of depression, especially for symptoms reflecting altered energy homeostasis. Cellular metabolic dysfunctions may represent a key pathway in depression pathophysiology potentially accessible through AC metabolism.
Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation
Authors: He Rihua , Hu Chonghui , Yuan Yuan , Li Tingting , Tian Qing , Huang Tianhao , Lin Qing , Zheng Shangyou , Chen Chujie , Fu Zhiqiang , Chen Rufu 
Published: February 2025

Abstract
Cancer-associated fibroblasts (CAFs) play a key role in oxaliplatin resistance in pancreatic ductal adenocarcinoma (PDAC). However, the potential mechanisms by which CAFs promote chemotherapy resistance have not yet been explored. In this study, we found that circABCC4 (hsa_circ_0030582) was positively correlated with poor platinum-chemotherapeutic response and a shorter progression-free survival (PFS) time in late-stage PDAC patients. CircABCC4 enhanced the ability of CAFs to induce oxaliplatin resistance in pancreatic cancer cells through glycolysis reprogramming. Mechanistically, circABCC4 enhanced the interaction between PKM2 and KPNA2 to promote PKM2 nuclear translocation in CAFs, leading to the transcription of glycolysis-related genes. The glycolytic reprogramming of CAFs promoted the secretion of IL-8, which in turn enhanced DNA damage repair in pancreatic cancer. Blocking PKM2 nuclear translocation abolished circABCC4-driven oxaliplatin resistance of pancreatic cancer in vivo. Collectively, our study reveals a circRNA-mediated glycolysis reprogramming of CAFs to induce oxaliplatin resistance and highlights circABCC4 as a potential therapeutic target.
STX17-DT facilitates axitinib resistance in renal cell carcinoma by inhibiting mitochondrial ROS accumulation and ferroptosis
Authors: Pan Yihui , Liu Shuang , Shu Guannan , Chen Minyu , Fu Liangmin , Chen Cheng , Chen Yimeng , Zhuang Qianfeng , Xue Dong , He Xiaozhou 
Published: February 2025

Abstract
Axitinib resistance remains a serious challenge in the treatment of advanced renal cell carcinoma (RCC), and the underlying mechanisms are not fully understood. Here, we constructed an in vivo axitinib-resistant RCC model and identified the long non-coding RNA STX17-DT as a driver of therapy resistance in RCC. The expression of STX17-DT was significantly elevated in axitinib-resistant RCC cells and correlated with poorer prognosis in RCC patients. Elevated levels of STX17-DT contributed to the development of resistance to axitinib both in vitro and in vivo. Mechanistically, STX17-DT modulated the stability of IFI6 mRNA by recruiting and binding to hnRNPA1, leading to decreased accumulation of mitochondrial reactive oxygen species (ROS) and attenuated ferroptosis. Meanwhile, STX17-DT was packaged into extracellular vesicles through hnRNPA1, thus transmitting axitinib resistance to other cells. Compared with axitinib monotherapy, combined treatment of axitinib and STX17-DT-targeted in vivo siRNA demonstrated enhanced therapeutic efficacy. These findings indicate a novel molecular mechanism of axitinib resistance in RCC and suggest that STX17-DT may serve as a prognostic indicator and potential therapeutic target to overcome resistance to targeted therapy.
SREBF1-based metabolic reprogramming in prostate cancer promotes tumor ferroptosis resistance
Authors: Wei Guojiang , Huang Ying , Li Wenya , Xie Yuxin , Zhang Deyi , Niu Yuanjie , Zhao Yang 
Published: February 2025

Abstract
Metabolic reprogramming in prostate cancer has been widely recognized as a promoter of tumor progression and treatment resistance. This study investigated its association with ferroptosis resistance in prostate cancer and explored its therapeutic potential. In this study, we identified differences in the epithelial characteristics between normal prostate tissue and tissues of various types of prostate cancer using single-cell sequencing. Through transcription factor regulatory network analysis, we focused on the candidate transcription factor, SREBF1. We identified the differences in SREBF1 transcriptional activity and its association with ferroptosis, and further verified this association using hdWGCNA. We constructed a risk score based on SREBF1 target genes associated with the biochemical recurrence of prostate cancer by combining bulk RNA analysis. Finally, we verified the effects of the SREBPs inhibitor Betulin on the treatment of prostate cancer and its chemosensitization effect. We observed characteristic differences in fatty acid and cholesterol metabolism between normal prostate tissue and prostate cancer tissue, identifying high transcriptional activity of SREBF1 in prostate cancer tissue. This indicates that SREBF1 is crucial for the metabolic reprogramming of prostate cancer, and that its mediated metabolic changes promoted ferroptosis resistance in prostate cancer in multiple ways. SREBF1 target genes are associated with biochemical recurrence of prostate cancer. Finally, our experiments verified that SREBF1 inhibitors can significantly promote an increase in ROS, the decrease in GSH, and the decrease in mitochondrial membrane potential in prostate cancer cells and confirmed their chemosensitization effect in vivo. Our findings highlighted a close association between SREBF1 and ferroptosis resistance in prostate cancer. SREBF1 significantly influences metabolic reprogramming in prostate cancer cells, leading to ferroptosis resistance. Importantly, our results demonstrated that SREBF1 inhibitors can significantly enhance the therapeutic effect and chemosensitization of prostate cancer, suggesting a promising therapeutic potential for the treatment of prostate cancer.
Macrocarpal I induces immunogenic cell death and synergizes with immune checkpoint inhibition by targeting tubulin and PARP1 in colorectal cancer
Authors: Zhang Yaxin , Li Huali , Zhao Yali , Liu Lingtao , Zhou Yi , Pan Xingyan , Ding Yanqing , Liao Wenting , Qi Lu , Huang Chengmei , Tang Na 
Published: February 2025

Abstract
Colorectal cancer (CRC) presents an obstacle to immunotherapy, primarily because most cases are microsatellite stable (MSS) tumors, which are often described as “cold tumors” with limited immunogenicity. Recent studies have indicated that several therapeutic approaches, such as chemotherapy and targeted therapies, can elicit immunogenic cell death (ICD) and stimulate immune responses. However, challenges such as target affinity and in vivo pharmacokinetics limit the efficacy and immune response of current targeted therapies. In this study, we demonstrate that Macrocarpal I is a potent inducer of ICD by activating the PERK/eIF2A/ATF4/CHOP signaling pathway. Furthermore, Macrocarpal I induces apoptosis and ferroptosis, both of which act as triggers for ICD. Mechanistically, Macrocarpal I directly targets TUBB2B and PARP1, disrupting microtubule polymerization and DNA repair processes. Importantly, treatment with Macrocarpal I enhances the anti-tumor immune response and augments responsiveness to anti-PD-1 therapy in an MC38 syngeneic mouse model of CRC.
Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway
Authors: Ni Kaixiang , Liu Yuankun , DI Pinggang , Wang Lu , Huang Hui , Holsinger R. M. Damian , Kiang Karrie Mei-Yee , Jiao Jiantong 
Published: February 2025

Abstract
Cancer stem cells (CSCs) are significant factors in the treatment resistance and recurrence of glioblastoma. Chromobox protein homolog 7 (CBX7) can inhibit the progression of various tumors, but its impact on the stem cell-like properties of glioblastoma cells remains unclear. Clinically, low levels of CBX7 are associated with poor prognosis and increased distant metastasis in glioblastoma patients, and this low expression is caused by methylation of the CBX7 promoter. Our current research indicates that CBX7 plays a key role in suppressing the stem-like phenotype of glioblastoma. In this study, through bioinformatics analysis, we found that CBX7 is the most significantly downregulated member of the CBX family in glioblastoma and is closely associated with the stem-like phenotype of glioblastoma cells. We show that CBX7 promotes the degradation of myosin heavy chain 9 (MYH9) protein through the ubiquitin-proteasome pathway via the polycomb repressive complex 1 (PRC1) and suppresses the stem-like phenotype of glioblastoma cells by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Furthermore, overexpression of MYH9 in glioblastoma cells reverses the inhibitory effects of CBX7 on migration, proliferation, invasion, and stemness of glioblastoma cells. In summary, CBX7 acts as a tumor suppressor by inhibiting the stem cell-like characteristics of glioblastoma. The CBX7-MYH9-NF-κB signaling axis may serve as a potential therapeutic target for glioblastoma.
Anomalous δ15N values in the Neoarchean associated with an abundant supply of hydrothermal ammonium
Authors: Martin Ashley N. , Stüeken Eva E. , Gehringer Michelle M. , Markowska Monika , Vonhof Hubert , Weyer Stefan , Hofmann Axel 
Published: February 2025

Abstract
Unusually high δ15N values in the Neoarchean sedimentary record in the time period from 2.8 to 2.6 Ga, termed the Nitrogen Isotope Event (NIE), might be explained by aerobic N cycling prior to the Great Oxidation Event (GOE). Here we report strongly positive δ15N values up to +42.5 ‰ in ~2.75 – 2.73 Ga shallow-marine carbonates from Zimbabwe. As the corresponding deeper-marine shales exhibit negative δ15N values that are explained by partial biological uptake from a large ammonium reservoir, we interpret our data to have resulted from hydrothermal upwelling of 15N-rich ammonium into shallow, partially oxic waters, consistent with uranium isotope variations. This work shows that anomalous N isotope signatures at the onset of the NIE temporally correlate with extensive volcanic and hydrothermal activity both locally and globally, which may have stimulated primary production and spurred biological innovation in the lead-up to the GOE.
The utility of animal models to inform the next generation of human space exploration
Authors: Duporge Isla , Pereira Talmo , de Obeso Santiago Castiello , Ross Julius G. Bright , J. Lee Stephen , G. Hindle Allyson 
Published: February 2025

Abstract
Animals have played a vital role in every stage of space exploration, from early sub-orbital flights to contemporary missions. New physiological and psychological challenges arise with plans to venture deeper into the solar system. Advances in chimeric and knockout animal models, along with genetic modification techniques have enhanced our ability to study the effects of microgravity in greater detail. However, increased investment in the purposeful design of habitats and payloads, as well as in AI-enhanced behavioral monitoring in orbit can better support the ethical and effective use of animals in deep space research.