bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOD-like receptor X1 promotes autophagy and inactivates NLR family pyrin domain containing 3 inflammasome signaling by binding autophagy-related gene 5 to alleviate cerebral ischemia/reperfusion-induced neuronal injury
Authors: Peng Yufen , Long Yong , Wan Chenyi 
Published: December 2024

Abstract
Ischemic strokes pose serious risks to human health. We aimed to elucidate the function of NOD-like receptor X1 (NLRX1) in a rat middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injury (CIRI) model and in an oxygen-glucose deprivation/reperfusion (OGD/R)-treated human microglial cell line (HMC3) model. Following NLRX1 upregulation, infarct volumes were measured with 2,3,5-triphenyltetrazolium chloride staining and pathological examination was conducted with hematoxylin-eosin staining. Results suggested that levels of NLRX1 were decreased in brain tissue of MCAO rats and in OGD/R-stimulated HMC3 cells. NOD-like receptor X1 overexpression mitigated the neuronal damage, reduced tumor necrosis factor-α and interleukin-6 expression, alleviated microglial activation, and induced autophagy in vivo and in vitro. Additionally, a coimmunoprecipitation assay indicated that NLRX1 bound to autophagy-related gene 5 (ATG5) to elevate ATG5 expression in HMC3 cells. Further, the elevated NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, and cleaved caspase 1 expression in MCAO rats and HMC3 cells with OGD/R induction was reduced after NLRX1 upregulation. Importantly, ATG5 depletion abrogated the effects of NLRX1 elevation on NLRP3 inflammasome signaling. These results indicate that NLRX1 promotes autophagy and inactivates NLRP3 inflammasome signaling by binding ATG5 in experimental cerebral ischemia. These data may help the development of novel therapeutic strategies for ischemic stroke.
Normalization and cut-elimination theorems for some logics of evidence and truth
Authors: Coniglio Marcelo E , Figallo Martín , Rodrigues Abilio 
Published: December 2024

Abstract
In this paper, we investigate proof-theoretic aspects of the logics of evidence and truth $LET_{J}$ and $LET_{F}$. These logics extend, respectively, Nelson’s logic N4 and the logic of first-degree entailment, also known as Belnap–Dunn four-valued logic, with a classicality operator ${{\circ }}$ that recovers classical logic for formulas in its scope. We will present natural deduction and sequent systems for $LET_{J}$ and $LET_{F}$, together with proofs of normalization and cut-elimination theorems, respectively. As a corollary, we obtain decision procedures, which guarantees bottom-up proof search for both logics.
MEGA12: Molecular Evolutionary Genetic Analysis Version 12 for Adaptive and Green Computing
Authors: Kumar Sudhir , Stecher Glen , Suleski Michael , Sanderford Maxwell , Sharma Sudip , Tamura Koichiro 
Published: December 2024

Abstract
We introduce the 12th version of the Molecular Evolutionary Genetics Analysis (MEGA12) software. This latest version brings many significant improvements by reducing the computational time needed for selecting optimal substitution models and conducting bootstrap tests on phylogenies using maximum likelihood (ML) methods. These improvements are achieved by implementing heuristics that minimize likely unnecessary computations. Analyses of empirical and simulated datasets show substantial time savings by using these heuristics without compromising the accuracy of results. MEGA12 also links-in an evolutionary sparse learning approach to identify fragile clades and associated sequences in evolutionary trees inferred through phylogenomic analyses. In addition, this version includes fine-grained parallelization for ML analyses, support for high-resolution monitors, and an enhanced Tree Explorer. MEGA12 can be downloaded from https://www.megasoftware.net.
Modulating ion–dipole interactions in nonflammable phosphonate-based electrolyte for safe and stable sodium-ion pouch cells
Authors: Yang Zhuo , Dai Yingying , Xie Zheng-Kun , Li Shao-Bo , Lei Yao-Jie , Chen Jian , Zhou Xunzhu , Hao Zhi-Qiang , Tan Xin , Li Lin , Lai Wei-Hong , Li Li , Chen Wei-Hua , Chou Shu-Lei 
Published: December 2024

ABSTRACT
Phosphonate-based electrolytes with the merits of low cost and intrinsic nonflammability are promising candidates to realize the safe operation of sodium-ion batteries. However, they generally suffer from poor interfacial chemistry because of the solvent-dominated solvation structure induced by the strong ion–dipole interactions between cations and phosphonate molecules. Herein, we report an electrolyte design strategy that selectively improves the competitive coordination of low-solvating–power molecules, achieving stable interfacial chemistry with a non-flammable, low-cost and fluorine-free electrolyte. By improving the ion–ion interaction between cation and anion, weakly coordinated molecules can enter the Na+ solvation shell, thereby promoting more adjustable and advantageous interfacial chemistry. As a result, the fluorine-free Prussian blue||hard carbon pouch cell, with a high cathode mass loading of ∼20 mg cm−2, reaches a high capacity retention with an energy density of over 221.7 Wh kg−1 based on electrode mass and 115.1 Wh kg−1 based on battery mass.
Overexpression of α-synuclein in Pigment Dispersing Factor neurons alters sleep–wake pattern by regulating lipid metabolism in Drosophila
Authors: Xia Dong , Chen Ying , Fu Xiang , Liu Hui-Yi , Sun Mu-Yan , Wang Fen , Zhang Yong , Liu Chun-Feng , Liu Jun-Yi 
Published: December 2024

Abstract
Parkinson’s disease (PD) is a complex neurodegenerative disorder, characterized by the aggregation of α-synuclein (α-syn). Current research increasingly indicates the prevalence of sleep–wake disorders in early-stage PD, although the underlying pathogenic mechanisms remain unclear. In this study, transgenic Drosophila models were utilized to observe excessive daytime sleepiness and impaired anticipation in flies overexpressing α-syn in pan-neurons and circadian clock neurons. Additionally, deficits in projection of Pigment Dispersing Factor (PDF) neuron terminals, which are involved in Drosophila sleep and circadian rhythm, were identified. An imbalance in lipid metabolism homeostasis was detected in the brains of α-syn overexpressing mutants. Ultimately, the inhibition of Sterol Regulatory Element-Binding Protein (SREBP) activity led to an improvement in the reduced daytime sleep duration phenotype. Our results suggest that lipid pathways play a role in sleep–wake disorders triggered by α-syn mutation and aggregation, thereby providing valuable insights into potential therapeutic avenues for disrupted sleep patterns associated with PD.
New Italian tax dispositions on trusts
Authors: Loconte Stefano , Molteni Beatrice 
Published: December 2024

Abstract
As part of a huge tax reform project carried out by the Italian government over the past years, a new Legislative Decree (No. 139/2024) was issued in October 2024 by the Italian legislator to provide a rationalization of Registration Tax, Inheritance and Gift Tax, Stamp duty, and other indirect taxes, excluding Value Added Tax. In particular, new dispositions on indirect taxation of trusts have been introduced, which will have relevant impacts on tax planning and estate planning for individuals. In light of this, new considerations regarding existing and new trusts deserve to be addressed.
Biochemical study of the risk of diabetes, prediabetic and insulin resistance in car painters and its association with mercury exposure: a retrospective case–control study
Authors: Numan Ahmad Tarik , Jawad Nada Kadum , Fawzi Hayder Adnan 
Published: December 2024

Abstract

Purpose
There is controversy about the effect of mercury (Hg) exposure on developing diabetes and insulin resistance. This study aimed to assess the risk of diabetes and insulin resistance in car painters using biochemical markers and serum Hg levels.

Methods
A retrospective case–control study involving 210 male participants aged between 25 and 50 years. The participants were divided into two groups: Car painters for at least one year and healthy people who had not worked as car painters and had no health concerns or chronic diseases.

Results
The serum levels of Hg, MDA (malondialdehyde), interleukin (IL)-1β, visfatin, fasting insulin, and fasting blood glucose (FBG) were evaluated. Serum Hg levels were significantly higher in car painters compared to the control group (19.00 ± 7.20 vs. 8.339 ± 3.916 μg/L, P-value &lt; 0.001). Serum levels of visfatin, MDA, insulin, FBG, and IL-1β were significantly higher in the car painter compared to the control (P-value &lt; 0.001). There was a significantly higher proportion of people with diabetes in car painters compared to control (8.6% vs. 0%) and higher prediabetic (30.5% vs. 13.3%, P-value &lt; 0.001). In car painter workers, levels of Hg were significantly higher in DM compared to prediabetic and normoglycemic car painter workers (27.01 ± 1.59, 23.98 ± 4.31, and 15.39 ± 6.41 μg/mL, respectively, P-value &lt; 0.001); additionally, levels of Hg were significantly higher car painter with insulin resistance compared to non-insulin resistance workers (21.18 ± 7.29 vs. 16.79 ± 16.7 μg/mL, P-value &lt; 0.001).

Conclusions
Increased serum Hg in car painters increases the risk of insulin resistance and diabetes/prediabetes status.
Metagenomic analysis and bioactive profiling of kombucha fermentation: antioxidant, antibacterial activities, and molecular docking insights into gastric cancer therapeutics
Authors: Shalini Thavasiaanatham Seenivasan , Prathiviraj Ragothaman , Senthilraja Poomalai 
Published: December 2024

Abstract
Kombucha is fermented and produced with a biofilm called a symbiotic culture of bacteria and yeast, which is drunk all over the world for its beneficial effects on human health and energy levels. The metagenomic study of kombucha frequently detected microorganisms in proteobacteria, firmicutes, and actinobacteria. And also, yeast and fungi are Ascomycota and Basidiomycota is present in green leaf and sugarcane juice fermented kombucha. The kombucha extracts’ biological activities were assessed using pH, total phenolic content, antioxidant, antibacterial, and anticancer activity. Fermentation may enhance biological activity and the generation of bioactive substances. These results showed the pH −3.1 ± 0.2 and TPC −0.721 μg/mL of gallic acid equivalent. The antioxidant radicals scavenging activity of kombucha was evaluated by DPPH, ABTS, H2O2 and TAC. The bioactive chemicals identified by FT-IR and HR-LC/MS analysis of Kombucha totaled 45 components. The identified compounds were further move on to perform molecular docking study against gastric cancer target proteins 4H9M, 2DQ7 and 1TVO are binding with Nequinate compounds showing best LibDock scores 105.12, 114.49, and 108.97. So, this study suggests that knowledge can potentially active bioactive compounds are present in kombucha and it’s stimulated the mechanism of gastrointestinal transit. Additionally, the metagenomic analysis gives strength to understand the bacterial and fungal distribution and its molecular mechanism from Kombucha.
Population divergence in co-distributed Caribbean landfrogs (Eleutherodactylidae: Eleutherodactylus) along the Soufrière volcanic slope of Guadeloupe Island, Lesser Antilles
Authors: Myers Edward A , Alequín Luigie , Browne Ayanna , Mulder Kevin P , Rivera Danielle , Esposito Lauren A , Bell Rayna C , Hedges S Blair 
Published: December 2024

Abstract
Local adaptation to environmental heterogeneity across a landscape can result in population divergence and formation of lineages. On Guadeloupe Island, the active volcano, La Grande Soufrière, peaks at 1460 m a.s.l., with rainforest at low elevations transitioning to humid savannahs at high elevations. Two endemic sister species of Eleutherodactylus frogs are co-distributed across this habitat gradient, and previous studies have reported phenotypic differences between lowland and high-elevation populations in each species, in addition to potential ongoing hybridization between the species at high-elevation sites. Here we generate mitochondrial DNA and nuclear DNA genomic data along the elevational transect to quantify population genetic structure, provide historical context for the diversification of these island endemics, and identify potential bottlenecks attributable to the eruptive history of the volcano. We find that both taxa exhibit population clusters that correspond to low- and high-elevation localities; however, genetic divergence is not associated with climate variables or geographical distance. The timing of divergence between the species is estimated at ~3.75 Mya; demographic models indicate low levels of migration between the species after divergence, and we find that ongoing hybridization is likely to be limited. Finally, we find moderate heterozygosity across populations, suggesting that they were minimally impacted by recent volcanic activity. A version of this abstract translated to French can be found in the Supplementary Data. Une version de ce résumé traduite en français est disponible dans les Données Supplémentaires.
Melatonin mitigates intervertebral disc degeneration by suppressing NLRP3 inflammasome activation via the EGR1/DDX3X pathway
Authors: Zhao Kangcheng , Zhang Yukun , Liao Zhiwei , Zhang Weifeng , Li Gaocai , Shi Pengzhi , Cheng Zhangrong , Chen Yuhang , Li Shuai , Wang Kun , Song Yu , Feng Xiaobo , An Ran , Yang Cao 
Published: December 2024

AbstractIntervertebral disc degeneration (IVDD), is one of the leading causes of low back pain. Inflammation is considered to be the main pathophysiological process of IVDD. The nucleotide‐binding domain and leucine‐rich pyrin domain containing 3 (NLRP3) inflammasome‐mediated inflammatory responses are critically involved in the progression of IVDD. Melatonin is known for its anti‐inflammatory and antioxidant effects. However, little is known about the potential effects of melatonin in the pathological process of IVDD. We found that the expression of EGR1, DDX3X, and NLRP3 inflammasome increased and extracellular matrix (ECM) degraded in IVDD. With the application of EGR1 siRNA, the expression of DDX3X and the activation of NLRP3 inflammasome were inhibited in stress‐induced NP cells. DDX3X/NLRP3 was regulated on dependence of EGR1. Besides, the utility of melatonin mitigated the EGR1‐induced overproduction of DDX3X and activation of NLRP3 inflammasome, thus protecting cells from pyroptosis and ECM degradation. In vivo, in a rat IVDD model, melatonin was found to be able to delay the development of IVDD by imageological and histological evaluation. In conclusion, our study demonstrated that melatonin prevented IVDD progression by regulating EGR1/DDX3X/NLRP3 axis. Our study provides insight into melatonin as a new target for therapeutic approaches for IVDD.
Functional Brain Connectivity and Musical Training: Insights from EEG Phase Synchronization During Music Perception
Authors: Provorova Anna A. , Kulikova Sofya P. 
Published: December 2024

AbstractMusical training profoundly impacts brain organization, fostering functional and structural adaptations that enhance auditory, motor, and cognitive processes. This study investigates functional connectivity differences between professional musicians and non-musicians during tasks involving music perception and different graphic notations. Using EEG phase-locking value (PLV) analysis, we examined synchronization across alpha, beta, and gamma frequency bands. Results revealed that musicians exhibited enhanced functional connectivity between brain regions, reflecting their ability to integrate auditory, visual, and cognitive information efficiently. In the alpha band, strong connectivity between the occipital and temporal regions was observed during all tasks, with additional synchronization between the parietal and temporal regions in tasks lacking pitch information. In the beta band, significant frontal-temporal connectivity was detected, indicating cognitive processing, while temporal-occipital synchronization emerged in specific tasks. In the gamma band, musicians demonstrated robust frontal-temporal and frontal-frontal synchronization, reflecting emotional and structural processing of music. Non-musicians showed reduced task-specific connectivity, relying on generalized strategies. These findings underscore the role of musical training in enhancing multimodal brain integration and cognitive flexibility, contributing to advanced music perception and processing.
Adaptation to cystine limitation stress promotes PDAC tumor growth and metastasis through translational upregulation of OxPPP
Authors: Li Yunzhan , Li Zekun , Sun Dongxiao , Ni Bo , Tan Mingjun , Shay Ashley E. , Wang Min , Meng Chenyang , Shen Guangcong , Fu Boyang , Shan Yueying , Zhou Tianxin , Xie Yongjie , Chen Kun-Ming , Qiao Bin , Dang Yunkun , Kimball Scot R. , Singh Pankaj K. , Wang Xiuchao , Hao Jihui , Yang Shengyu 
Published: December 2024

AbstractCystine/cysteine is critical for antioxidant response and sulfur metabolism in cancer cells and is one of the most depleted amino acids in the PDAC microenvironment. The effects of cystine limitation stress (CLS) on PDAC progression are poorly understood. Here we report that adaptation to CLS (CLSA) promotes PDAC cell proliferation and tumor growth through translational upregulation of the oxidative pentose phosphate pathway (OxPPP). OxPPP activates thede novosynthesis of nucleotides and fatty acids to support tumor growth. Our data suggested that much like hypoxia, CLS in the tumor microenvironment could promote PDAC tumor growth and metastasis through upregulating anabolic metabolism of nucleotides and lipids.
In vivohuman neurite exchange imaging (NEXI) at 500 mT/m diffusion gradients
Authors: Chan Kwok-Shing , Ma Yixin , Lee Hansol , Marques José P. , Olesen Jonas , Coelho Santiago , Novikov Dmitry S , Jespersen Sune , Huang Susie Y. , Lee Hong-Hsi 
Published: December 2024

AbstractEvaluating tissue microstructure and membrane integrity in the living human brain through diffusion-water exchange imaging is challenging due to requirements for a high signal-to-noise ratio and short diffusion times dictated by relatively fast exchange processes. The goal of this work was to demonstrate the feasibility ofin vivoimaging of tissue micro-geometries and water exchange within the brain gray matter using the state-of-the-art Connectome 2.0 scanner equipped with an ultra-high-performance gradient system (maximum gradient strength=500 mT/m, maximum slew rate=600 T/m/s). We performed diffusion MRI measurements in 15 healthy volunteers at multiple diffusion times (13-30 ms) andb-values up to 17.5 ms/μm2. The anisotropic Kärger model was applied to estimate the exchange time between intra-neurite and extracellular water in gray matter. The estimated exchange time across the cortical ribbon was around (median±interquartile range) 13±8 ms on Connectome 2.0, substantially faster than that measured using an imaging protocol compatible with Connectome 1.0-alike systems on the same cohort. Our investigation suggested that the NEXI exchange time estimation using a Connectome 1.0 compatible protocol was more prone to residual noise floor biases due to the small time-dependent signal contrasts across diffusion times when the exchange is fast (≤20 ms). Furthermore, spatial variation of exchange time was observed across the cortex, where the motor cortex, somatosensory cortex and visual cortex exhibit longer exchange times compared to other cortical regions. Non-linear fitting for the anisotropic Kärger model was accelerated 100 times using a GPU-based pipeline compared to the conventional CPU-based approach. This study highlighted the importance of the chosen diffusion times and measures to address Rician noise in dMRI data, which can have a substantial impact on the estimated NEXI exchange time and require extra attention when comparing NEXI results between various hardware setups.Highlights-The Connectome 2.0 scanner equipped with 500 mT/m gradients enables high-sensitivity diffusion MRI for imaging exchange timesin vivo-The global exchange time across the living human cortex was estimated to be about 13 ms on Connectome 2.0, faster than measured using a protocol compatible to Connectome 1.0-Spatially varying exchange times were observed across the cortex-A GPU-accelerated tool was developed to speed up parameter estimation by 100 times-The narrow pulse approximation used in neurite exchange imaging does not affect estimation performance in high gradient performance MRI systems
Neuroimmune mechanisms of a mouse model of chronic back pain
Authors: Goins Aleyah E. , Zurek Nesia A. , Holguin Cristian O. , Gravelle Alexis , Goyal Sachin , Noor Shahani , Demeter Jenna B. , Koch Maddy R. , de la Peña June Bryan I. , Westlund Karin N. , Alles Sascha R.A. 
Published: December 2024

AbstractChronic back pain (CBP) is the leading cause of disability affecting 1 in 10 people worldwide. Symptoms are marked by persistent lower back pain, reduced mobility, and heightened cold sensitivity. Here, we utilize a mouse model of CBP induced by injecting urokinase-type plasminogen activator (uPA), a proinflammatory agent in the fibrinolytic pathway, between the L2/L3 lumbar vertebrae. We identified neuroimmune interactions contributing to uPA-induced CBP (henceforth, uPA-CBP) in mouse dorsal root ganglia (DRG), where nociceptive neurons reside. Flow cytometric data reveal that uPA-CBP increases CD45+CD11b+ cells in the DRG, a population characteristically implicated in other chronic pain models1. Blocking colony stimulating factor 1 receptor (CSF1R) signaling using PLX5622 partially reduced pain, suggesting CD45+CD11b+ macrophage involvement. Whole-cell patch-clamp electrophysiology data indicated DRG neuron hyperexcitability in CBP mice compared to controls. RNA sequencing revealed upregulation of pain- and inflammation-related genes involved in leukocyte migration. Together, these findings underscore the importance of the DRG neuroimmune axis in mediating chronic back pain.HighlightsuPA-CBP induces gait changes, mechanical and thermal sensitivity compared to shamsuPA-CBP mice show increased CD45+CD11b+ cells in DRG compared to shamsuPA-CBP mice show neuronal excitability in DRG neurons compared to shamsPain behaviors are alleviated by pharmacologically blocking CSF1R signalingDysregulation of inflammation- and ion channel-related genes in uPA-CBP DRG