bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal Precipitation Variation and Leaf Stoichiometric Changes Mediate the Dynamics of Tree Growth Responses to Nitrogen Addition Over Time
Authors: Xing Aijun , Shen Haihua , Du Enzai , Xu Longchao , Zhao Mengying , Fang Jingyun 
Published: October 2024

AbstractNitrogen (N) addition can stimulate tree growth; however, the strength of this growth effect usually changes over time and the factors underlying these responses are not fully understood. Based on a decade‐long N addition experiment (by adding 0, 20, 50, and 100 kg N ha−1 yr−1) in a boreal forest, we studied responses of tree growth to N addition over time and explored the potential role of temporal precipitation variation and plant stoichiometric changes in mediating this. We found positive growth responses to N addition but this effect changed nonlinearly over time. Annual precipitation was positively related to growth under high‐level N addition; hence, a hump‐shape temporal pattern in precipitation contributed to the nonlinear tree growth responses. After precipitation effects were accounted for, the positive growth responses to N addition peaked in the seventh year and then declined for all levels of N. Later reductions in growth responses could partly be attributed to increased leaf N:phosphorus (P) ratio over time, especially at higher N addition rates. We also found an increase in soil acid phosphatase, the ratio of labile to occluded soil P fraction, and a decreased ratio in leaf N to P resorption efficiency with increasing N addition rates during the late stage of this experiment, suggesting increased P demand. Collectively, our results imply that changes in plant nutrient stoichiometry with cumulative N input may limit the N stimulation on tree growth over time, while temporal precipitation variation appears unlikely to modulate this effect under the atmospheric N deposition.
Sediment Transport and Flood Risk: Impact of Newly Constructed Embankments on River Morphology and Flood Dynamics in Kathmandu, Nepal
Authors: Thapa Saraswati , Sinclair Hugh D. , Creed Maggie J. , Borthwick Alistair G. L. , Watson C. Scott , Muthusamy Manoranjan 
Published: October 2024

AbstractFloodplain encroachment by embankments heightens flood risk. This is exacerbated by climate change and land‐use modifications. This paper assesses the impact of embankments on sediment transport, channel geometry, conveyance capacity, and flood inundation of a reach of the Nakkhu River, Nepal. Using the CAESAR‐Lisflood landscape evolution model based on a 2‐m digital elevation model, we simulate four flood scenarios with and without embankments and sediment transport: a historical 25‐year return period flood event used to design the embankments, 50‐year, 100‐year, and 1000‐year return period flood events forecast using the Generalized Logistic Model (using data from 1992 to 2017). Our results indicate that flow confinement by embankments reduces inundation by 99% (from 22.5 to 0.3 ha) for the historical 25‐year flood discharge of 42.23 and by 15% (from 28.8 to 24.4 ha) for the 1000‐year return period flood discharge of 95 (similar to a 25‐year maximum mid‐future). The presence of embankments increases downstream sediment transport by more than 32% for all flood scenarios considered. Inclusion of sediment transport leads to a fivefold increase in predicted inundation area for a 25‐year maximum mid‐future flood compared to the no‐sediment case in the embanked channel. Changes in channel geometry due to sedimentation significantly reduce conveyance capacity increasing overtopping flood risk, particularly where the channel is sinuous or located on flat terrain. Our results indicate that sediment erosion in outer meanders may threaten embankment stability by promoting undercuts. It is recommended that sediment transport effects be factored into embankment design and floodplain planning.
MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB
Authors: Wang Xiujian , Tao Xiao , Chen Pengjie , Jiang Penglei , Li Wenxiao , Chang Hefeng , Wei Cong , Lai Xinyi , Zhang Hao , Pan Yihan , Ding Lijuan , Liang Zuyu , Cui Jiazhen , Shao Mi , Teng Xinyi , Gu Tianning , Wei Jieping , Kong Delin , Si Xiaohui , Han Yingli , Fu Huarui , Lin Yu , Yu Jian , Li Xia , Wang Dongrui , Hu Yongxian , Qian Pengxu , Huang He 
Published: October 2024

AbstractClinical evidence supports the notion that T cell exhaustion and terminal differentiation pose challenges to the persistence and effectiveness of chimeric antigen receptor-T (CAR-T) cells. MEK1/2 inhibitors (MEKIs), widely used in cancer treatment due to their ability to inhibit aberrant MAPK signaling, have shown potential synergistic effects when combined with immunotherapy. However, the impact and mechanisms of MEKIs on CAR-T cells remain uncertain and controversial. To address this, we conducted a comprehensive investigation to determine whether MEKIs enhance or impair the efficacy of CAR-T cells. Our findings revealed that MEKIs attenuated CAR-T cell exhaustion and terminal differentiation induced by tonic signaling and antigen stimulation, thereby improving CAR-T cell efficacy against hematological and solid tumors. Remarkably, these effects were independent of the specific scFvs and costimulatory domains utilized in CARs. Mechanistically, analysis of bulk and single-cell transcriptional profiles demonstrates that the effect of MEK inhibition was related to diminish anabolic metabolism and downregulation of c-Fos and JunB. Additionally, the overexpression of c-Fos or JunB in CAR-T cells counteracted the effects of MEK inhibition. Furthermore, our Cut-and-Tag assay revealed that MEK inhibition downregulated the JunB-driven gene profiles associated with exhaustion, differentiation, anergy, glycolysis, and apoptosis. In summary, our research unveil the critical role of the MAPK-c-Fos-JunB axis in driving CAR-T cell exhaustion and terminal differentiation. These mechanistic insights significantly broaden the potential application of MEKIs to enhance the effectiveness of CAR-T therapy.
Neurosurgical application of olaparib from a thermo-responsive paste potentiates DNA damage to prolong survival in malignant glioma
Authors: Serra Riccardo , Smith Stuart J. , Rowlinson Jonathan , Gorelick Noah , Moloney Cara , McCrorie Phoebe , Veal Gareth J. , Berry Philip , Chalmers Anthony J. , Suk Ian , Shakesheff Kevin M. , Alexander Cameron , Grundy Richard G. , Brem Henry , Tyler Betty M. , Rahman Ruman 
Published: October 2024

Abstract
Background
There is increased pan-cancer specific interest in repurposing the poly adenosine diphosphate-ribose polymerase-1 (PARP-1) inhibitor, olaparib, for newly diagnosed or recurrent isocitrate dehydrogenase wild type glioblastoma. We explore whether intra-cavity delivery of olaparib confers a survival benefit in a pre-clinical high-grade glioma model.

Methods
Primary tumor RNA sequencing data was used to determine PARP-1 as a target in the glioblastoma infiltrative margin. We assessed radiosensitization conferred by olaparib alone and concomitant to genotoxic insults in vitro using clonal growth assays, cell cycle analysis and immunocytochemistry, and in vivo upon post-surgical delivery from a temperature-sensitive polymeric paste.

Results
RNA-sequencing confirmed PARP-1 as a viable therapy target in glioblastoma infiltrative disease. Acute exposure of glioma cells to olaparib impaired proliferation and induced late-stage apoptosis associated with DNA damage in vitro, potentiated by radiation. Using high-grade glioma orthotopic allografts, a long-term overall survival benefit was observed upon interstitial olaparib delivery concomitant with radiotherapy, compared to systemic olaparib and standard glioblastoma treatment. Combined delivery of olaparib with either temozolomide or etoposide increased long-term survival, suggestive of olaparib functioning as DNA damage sensitizer.

Conclusions
Collectively, our data support a rationale for localized olaparib delivery concomitant with the current clinical regimen for malignant glioma treatment.
β-catenin-inhibited Sumoylation modification of LKB1 and fatty acid metabolism is critical in renal fibrosis
Authors: Chen Shuangqin , Li Jiemei , Liang Ye , Zhang Meijia , Qiu Ziqi , Liu Sirui , Wang HaoRan , Zhu Ye , Song Shicong , Hou Xiaotao , Liu Canzhen , Wu Qinyu , Zhu Mingsheng , Shen Weiwei , Miao Jinhua , Hou Fan Fan , Liu Youhua , Wang Cheng , Zhou Lili 
Published: October 2024

AbstractLiver kinase B1 (LKB1) is a serine/threonine kinase controlling cell homeostasis. Among post-translational modification, Sumoylation is vital for LKB1 activating adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK), the key regulator in energy metabolism. Of note, AMPK-regulated fatty acid metabolism is highly involved in maintaining normal renal function. However, the regulative mechanisms of LKB1 Sumoylation remain elusive. In this study, we demonstrated that β-catenin, a notorious signal in renal fibrosis, inhibited the Sumoylation of LKB1, thereby disrupting fatty acid oxidation in renal tubular cells and triggering renal fibrosis. Mechanically, we found that Sumo3 was the key mediator for LKB1 Sumoylation in renal tubular cells, which was transcriptionally inhibited by β-catenin/Transcription factor 4 (TCF4) signaling. Overexpression of Sumo3, not Sumo1 or Sumo2, restored β-catenin-disrupted fatty acid metabolism, and retarded lipid accumulation and fibrogenesis in the kidney. In vivo, conditional knockout of β-catenin in tubular cells effectively preserved fatty acid oxidation and blocked lipid accumulation by maintaining LKB1 Sumoylation and AMPK activation. Furthermore, ectopic expression of Sumo3 strongly inhibited Wnt1-aggravated lipid accumulation and fibrogenesis in unilateral ischemia-reperfusion mice. In patients with chronic kidney disease, we found a loss of Sumo3 expression, and it was highly related to LKB1 repression. This contributes to fatty acid metabolism disruption and lipid accumulation, resulting in renal fibrosis. Overall, our study revealed a new mechanism in fatty acid metabolism dysfunction and provided a new therapeutic target pathway for regulating Sumo modification in renal fibrosis.
A spatiotemporal transcriptomic atlas of mouse placentation
Authors: Wu Yanting , Su Kaizhen , Zhang Ying , Liang Langchao , Wang Fei , Chen Siyue , Gao Ling , Zheng Qiutong , Li Cheng , Su Yunfei , Mao Yiting , Zhu Simeng , Chai Chaochao , Lan Qing , Zhai Man , Jin Xin , Zhang Jinglan , Xu Xun , Zhang Yu , Gao Ya , Huang Hefeng 
Published: October 2024

AbstractThe placenta, a temporary but essential organ for gestational support, undergoes intricate morphological and functional transformations throughout gestation. However, the spatiotemporal patterns of gene expression underlying placentation remain poorly understood. Utilizing Stereo-seq, we constructed a Mouse Placentation Spatiotemporal Transcriptomic Atlas (MPSTA) spanning from embryonic day (E) 7.5 to E14.5, which includes the transcriptomes of large trophoblast cells that were not captured in previous single-cell atlases. We defined four distinct strata of the ectoplacental cone, an early heterogeneous trophectoderm structure, and elucidated the spatial trajectory of trophoblast differentiation during early postimplantation stages before E9.5. Focusing on the labyrinth region, the interface of nutrient exchange in the mouse placenta, our spatiotemporal ligand–receptor interaction analysis unveiled pivotal modulators essential for trophoblast development and placental angiogenesis. We also found that paternally expressed genes are exclusively enriched in the placenta rather than in the decidual regions, including a cluster of genes enriched in endothelial cells that may function in placental angiogenesis. At the invasion front, we identified interface-specific transcription factor regulons, such as Atf3, Jun, Junb, Stat6, Mxd1, Maff, Fos, and Irf7, involved in gestational maintenance. Additionally, we revealed that maternal high-fat diet exposure preferentially affects this interface, exacerbating inflammatory responses and disrupting angiogenic homeostasis. Collectively, our findings furnish a comprehensive, spatially resolved atlas that offers valuable insights and benchmarks for future explorations into placental morphogenesis and pathology.
METASPACE-ML: Context-specific metabolite annotation for imaging mass spectrometry using machine learning
Authors: Wadie Bishoy , Stuart Lachlan , Rath Christopher M. , Drotleff Bernhard , Mamedov Sergii , Alexandrov Theodore 
Published: October 2024

AbstractImaging mass spectrometry is a powerful technology enabling spatial metabolomics, yet metabolites can be assigned only to a fraction of the data generated. METASPACE-ML is a machine learning-based approach addressing this challenge which incorporates new scores and computationally-efficient False Discovery Rate estimation. For training and evaluation, we use a comprehensive set of 1710 datasets from 159 researchers from 47 labs encompassing both animal and plant-based datasets representing multiple spatial metabolomics contexts derived from the METASPACE knowledge base. Here we show that, METASPACE-ML outperforms its rule-based predecessor, exhibiting higher precision, increased throughput, and enhanced capability in identifying low-intensity and biologically-relevant metabolites.
Integration of rate and phase codes by hippocampal cell-assemblies supports flexible encoding of spatiotemporal context
Authors: Russo Eleonora , Becker Nadine , Domanski Aleks P. F. , Howe Timothy , Freud Kipp , Durstewitz Daniel , Jones Matthew W. 
Published: October 2024

AbstractSpatial information is encoded by location-dependent hippocampal place cell firing rates and sub-second, rhythmic entrainment of spike times. These rate and temporal codes have primarily been characterized in low-dimensional environments under limited cognitive demands; but how is coding configured in complex environments when individual place cells signal several locations, individual locations contribute to multiple routes and functional demands vary? Quantifying CA1 population dynamics of male rats during a decision-making task, here we show that the phase of individual place cells’ spikes relative to the local theta rhythm shifts to differentiate activity in different place fields. Theta phase coding also disambiguates repeated visits to the same location during different routes, particularly preceding spatial decisions. Using unsupervised detection of cell assemblies alongside theoretical simulation, we show that integrating rate and phase coding mechanisms dynamically recruits units to different assemblies, generating spiking sequences that disambiguate episodes of experience and multiplexing spatial information with cognitive context.
Recovering nutrients and unblocking the cake layer of an electrochemical anaerobic membrane bioreactor
Authors: Zhang Yuhan , Wang Yongbin , Chen Zhibin , Hu Chengzhi , Qu Jiuhui 
Published: October 2024

AbstractThe sustainable development strategy shifts water treatment from pollution removal to resource recovery. Here, an electrochemical resource-recovery anaerobic membrane bioreactor (eRAnMBR) that employed a magnesium plate and conductive membrane as dual anodes is presented and shows excellent performance in carbon, nitrogen, and phosphorus recovery, as well as 95% membrane anti-fouling. The Mg2+ released alters the physicochemical properties of sludge, unblocking the cake layer, and recovers ammonium and phosphate, yielding 60.64% purity and 0.08 g d−1 struvite deposited onto cathode to be separated from sludge. The enhanced direct interspecies electron transfer, along with hydrogen evolution and alkalinity increase due to the electrochemical reactions, significantly increase methane yield and purity (93.97%) of the eRAnMBR. This increased internal energy can cover the additional electricity and electrode consumption. This integrated eRAnMBR reactor boasts the benefits of short process, low maintenance, and low carbon footprint, introducing a concept for the next generation of wastewater treatment.
The Bor1 elevator transport cycle is subject to autoinhibition and activation
Authors: Jiang Yan , Jiang Jiansen 
Published: October 2024

AbstractBoron, essential for plant growth, necessitates precise regulation due to its potential toxicity. This regulation is achieved by borate transporters (BORs), which are homologous to the SLC4 family. The Arabidopsis thaliana Bor1 (AtBor1) transporter from clade I undergoes slow regulation through degradation and translational suppression, but its potential for fast regulation via direct activity modulation was unclear. Here, we combine cryo-electron microscopy, mutagenesis, and functional characterization to study AtBor1, revealing high-resolution structures of the dimer in one inactive and three active states. Our findings show that AtBor1 is regulated by two distinct mechanisms: an autoinhibitory domain at the carboxyl terminus obstructs the substrate pathway via conserved salt bridges, and phosphorylation of Thr410 allows interaction with a positively charged pocket at the cytosolic face, essential for borate transport. These results elucidate the molecular basis of AtBor1’s activity regulation and highlight its role in fast boron level regulation in plants.
Dynamically cultured, differentiated bovine adipose-derived stem cell spheroids as building blocks for biofabricating cultured fat
Authors: Klatt Annemarie , Wollschlaeger Jannis O. , Albrecht Franziska B. , Rühle Sara , Holzwarth Lena B. , Hrenn Holger , Melzer Tanja , Heine Simon , Kluger Petra J. 
Published: October 2024

AbstractCultured or cultivated meat, animal muscle, and fat tissue grown in vitro, could transform the global meat market, reducing animal suffering while using fewer resources than traditional meat production and no antimicrobials at all. To ensure the appeal of cultured meat to future customers, cultured fat is essential for achieving desired mouthfeel, taste, and texture, especially in beef. In this work we show the establishment of primary bovine adipose-derived stem cell spheroids in static and dynamic suspension culture. Spheroids are successfully differentiated using a single-step protocol. Differentiated spheroids from dynamic cultures maintain stability and viability during 3D bioprinting in edible gellan gum. Also, the fatty acid composition of differentiated spheroids is significantly different from control spheroids. The cells are cultured antibiotic-free to minimize the use of harmful substances. This work presents a stable and bioprintable building block for cultured fat with a high cell density in a 3D dynamic cell culture system.
Avian-inspired embodied perception in biohybrid flapping-wing robotics
Authors: Li Qian , Tan Ting , Wang Benlong , Yan Zhimiao 
Published: October 2024

AbstractAvian feather intricate adaptable architecture to wing deformations has catalyzed interest in feathered flapping-wing aircraft with high maneuverability, agility, and stealth. Yet, to mimic avian integrated somatic sensation within stringent weight constraints, remains challenging. Here, we propose an avian-inspired embodied perception approach for biohybrid flapping-wing robots. Our feather-piezoelectric mechanoreceptor leverages feather-based vibration structures and flexible piezoelectric materials to refine and augment mechanoreception via coupled oscillator interactions and robust microstructure adhesion. Utilizing convolutional neural networks with the grey wolf optimizer, we develop tactile perception of airflow velocity and wing flapping frequency proprioception. This method also senses pitch angle via airflow direction and detects wing morphology through feather collisions. Our low-weight, accurate perception of flapping-wing robot flight states is validated by motion capture. This investigation constructs a biomechanically integrated embodied perception system in flapping-wing robots, which holds significant promise in reflex-based control of complex flight maneuvers and natural bird flight surveillance.
Conformational isomerism breaks the electrolyte solubility limit and stabilizes 4.9 V Ni-rich layered cathodes
Authors: Lu Ziyang , Yang Huijun , Sun Jianming , Okagaki Jun , Choe Yoongkee , Yoo Eunjoo 
Published: October 2024

AbstractBy simply increasing the concentration of electrolytes, both aqueous and non-aqueous batteries deliver technical superiority in various properties such as high-voltage operation, electrode stability and safety performance. However, the development of this strategy has encountered a bottleneck due to the limitation of the intrinsic solubility, and its comprehensive performance has reached its limit. Here we demonstrate that the conformational isomerism of the solvent would significantly affect the solubility of electrolytes. By transforming the configuration of solvent from cis-cis to cis-trans upon thermal triggering, we successfully break the solubility limit, and a beyond concentrated electrolyte with the lowest solvent-to-salt molar ratio of 0.70 is constructed. Transitions between cis-cis and cis-trans conformers are observed through Nuclear Magnetic Resonance (NMR) testing. The electrolyte consists entirely of anion-mediated solvation structures and promotes the formation of robust inorganic-dominated cathode electrolyte interphase. As a result, it enables stable cycling of 4.9 V-class LiNi0.8Co0.1Mn0.1O2 positive electrodes. Moreover, a high capacity of 151.2 mAh g−1 can be maintained after 1000 cycles at cut-off voltage of 4.8 V. This work provides a chemical pathway to build new concept electrolytes working under harsh conditions.
Markers of low field NMR relaxation features of tissues
Authors: Kołodziejski Karol , Masiewicz Elzbieta , Alamri Amnah , Zampetoulas Vasileios , Samuel Leslie , Murray Graeme , Lurie David J. , Broche Lionel M. , Kruk Danuta 
Published: October 2024

AbstractThis work presents an approach to exploiting Nuclear Magnetic Resonance (NMR) relaxometry data (1H spin-lattice relaxation rates covering the frequency range from below 1 kHz to 10 MHz) for the purpose of differentiating between pathological and reference tissues. Characteristic quantities (markers) that can be obtained in a straightforward manner, not resorting to an advanced analysis of 1H spin-lattice relaxation data, have been identified and compared for pathological and reference colon tissues. Moreover, the relaxation data have been parametrised in terms of Lorentzian spectral densities and the possibility of using the obtained dipolar relaxation constants and correlation times as biomarkers to assess the state of tissues has been discussed. It has also been demonstrated that the relaxation data for the reference and the pathological tissues can be attributed to two groups (for each case). The studies are a step towards exploiting the potential of NMR relaxometry for characterisation of pathological changes in tissues.