bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model
Authors: Tao Yu , Zhang Yuan , Jin Xiaohong , Hua Nan , Liu Hong , Qi Renfei , Huang Zitong , Sun Yufang , Jiang Dongsheng , Snutch Terrance P. , Jiang Xinghong , Tao Jin 
Published: November 2023

AbstractAlthough beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, the underlying regulatory mechanisms remain unknown. Here, we elucidated an epigenetic pathway driven by microRNA regulation of β-EP synthesis in ARC neurons to control neuropathic pain. In pain-injured rats miR-203a-3p was the most highly upregulated miRNA in the ARC. A similar increase was identified in the cerebrospinal fluid of trigeminal neuralgia patients. Mechanistically, we found histone deacetylase 9 was downregulated following nerve injury, which decreased deacetylation of histone H3 lysine-18, facilitating the binding of NR4A2 transcription factor to the miR-203a-3p gene promoter, thereby upregulating miR-203a-3p expression. Further, increased miR-203a-3p was found to maintain neuropathic pain by targeting proprotein convertase 1, an endopeptidase necessary for the cleavage of proopiomelanocortin, the precursor of β-EP. The identified mechanism may provide an avenue for the development of new therapeutic targets for neuropathic pain treatment.
Polymer architecture dictates multiple relaxation processes in soft networks with two orthogonal dynamic bonds
Authors: Ge Sirui , Tsao Yu-Hsuan , Evans Christopher M. 
Published: November 2023

AbstractMaterials with tunable modulus, viscosity, and complex viscoelastic spectra are crucial in applications such as self-healing, additive manufacturing, and energy damping. It is still challenging to predictively design polymer networks with hierarchical relaxation processes, as many competing factors affect dynamics. Here, networks with both pendant and telechelic architecture are synthesized with mixed orthogonal dynamic bonds to understand how the network connectivity and bond exchange mechanisms govern the overall relaxation spectrum. A hydrogen-bonding group and a vitrimeric dynamic crosslinker are combined into the same network, and multimodal relaxation is observed in both pendant and telechelic networks. This is in stark contrast to similar networks where two dynamic bonds share the same exchange mechanism. With the incorporation of orthogonal dynamic bonds, the mixed network also demonstrates excellent damping and improved mechanical properties. In addition, two relaxation processes arise when only hydrogen-bond exchange is present, and both modes are retained in the mixed dynamic networks. This work provides molecular insights for the predictive design of hierarchical dynamics in soft materials.
Sphingomyelin-derived nanovesicles for the delivery of the IDO1 inhibitor epacadostat enhance metastatic and post-surgical melanoma immunotherapy
Authors: Wang Zhiren , Li Wenpan , Jiang Yanhao , Tran Tuyen Ba , Cordova Leyla Estrella , Chung Jinha , Kim Minhyeok , Wondrak Georg , Erdrich Jennifer , Lu Jianqin 
Published: November 2023

AbstractEpacadostat (EPA), the most advanced IDO1 inhibitor, in combination with PD-1 checkpoint inhibitor, has failed in a recent Phase III clinical trial for treating metastatic melanoma. Here we report an EPA nanovesicle therapeutic platform (Epacasome) based on chemically attaching EPA to sphingomyelin via an oxime-ester bond highly responsive to hydrolase cleavage. Via clathrin-mediated endocytosis, Epacasome displays higher cellular uptake and enhances IDO1 inhibition and T cell proliferation compared to free EPA. Epacasome shows improved pharmacokinetics and tumour accumulation with efficient intratumoural drug release and deep tumour penetration. Additionally, it outperforms free EPA for anticancer efficacy, potentiating PD-1 blockade with boosted cytotoxic T lymphocytes (CTLs) and reduced regulatory T cells and myeloid-derived suppressor cells responses in a B16-F10 melanoma model in female mice. By co-encapsulating immunogenic dacarbazine, Epacasome further enhances anti-tumor effects and immune responses through the upregulation of NKG2D-mediated CTLs and natural killer cells responses particularly when combined with the PD-1 inhibitor in the late-stage metastatic B16-F10-Luc2 model in female mice. Furthermore, this combination prevents tumour recurrence and prolongs mouse survival in a clinically relevant, post-surgical melanoma model in female mice. Epacasome demonstrates potential to synergize with PD-1 blockade for improved response to melanoma immunotherapy.
Spatial-linked alignment tool (SLAT) for aligning heterogenous slices
Authors: Xia Chen-Rui , Cao Zhi-Jie , Tu Xin-Ming , Gao Ge 
Published: November 2023

AbstractSpatially resolved omics technologies reveal the spatial organization of cells in various biological systems. Here we propose SLAT (Spatially-Linked Alignment Tool), a graph-based algorithm for efficient and effective alignment of spatial slices. Adopting a graph adversarial matching strategy, SLAT is the first algorithm capable of aligning heterogenous spatial data across distinct technologies and modalities. Systematic benchmarks demonstrate SLAT’s superior precision, robustness, and speed over existing state-of-the-arts. Applications to multiple real-world datasets further show SLAT’s utility in enhancing cell-typing resolution, integrating multiple modalities for regulatory inference, and mapping fine-scale spatial-temporal changes during development. The full SLAT package is available at https://github.com/gao-lab/SLAT.
Local control of superconductivity in a NbSe2/CrSBr van der Waals heterostructure
Authors: Jo Junhyeon , Peisen Yuan , Yang Haozhe , Mañas-Valero Samuel , Baldoví José J. , Lu Yao , Coronado Eugenio , Casanova Fèlix , Bergeret F. Sebastian , Gobbi Marco , Hueso Luis E. 
Published: November 2023

AbstractTwo-dimensional magnets and superconductors are emerging as tunable building-blocks for quantum computing and superconducting spintronic devices, and have been used to fabricate all two-dimensional versions of traditional devices, such as Josephson junctions. However, novel devices enabled by unique features of two-dimensional materials have not yet been demonstrated. Here, we present NbSe2/CrSBr van der Waals superconducting spin valves that exhibit infinite magnetoresistance and nonreciprocal charge transport. These responses arise from a unique metamagnetic transition in CrSBr, which controls the presence of localized stray fields suitably oriented to suppress the NbSe2 superconductivity in nanoscale regions and to break time reversal symmetry. Moreover, by integrating different CrSBr crystals in a lateral heterostructure, we demonstrate a superconductive spin valve characterized by multiple stable resistance states. Our results show how the unique physical properties of layered materials enable the realization of high-performance quantum devices based on novel working principles.
Release of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation
Authors: Harris Rebecca J. , Heer Maninder , Levasseur Mark D. , Cartwright Tyrell N. , Weston Bethany , Mitchell Jennifer L. , Coxhead Jonathan M. , Gaughan Luke , Prendergast Lisa , Rico Daniel , Higgins Jonathan M. G. 
Published: November 2023

AbstractHistone modifications influence the recruitment of reader proteins to chromosomes to regulate events including transcription and cell division. The idea of a histone code, where combinations of modifications specify unique downstream functions, is widely accepted and can be demonstrated in vitro. For example, on synthetic peptides, phosphorylation of Histone H3 at threonine-3 (H3T3ph) prevents the binding of reader proteins that recognize trimethylation of the adjacent lysine-4 (H3K4me3), including the TAF3 component of TFIID. To study these combinatorial effects in cells, we analyzed the genome-wide distribution of H3T3ph and H3K4me2/3 during mitosis. We find that H3T3ph anti-correlates with adjacent H3K4me2/3 in cells, and that the PHD domain of TAF3 can bind H3K4me2/3 in isolated mitotic chromatin despite the presence of H3T3ph. Unlike in vitro, H3K4 readers are still displaced from chromosomes in mitosis in Haspin-depleted cells lacking H3T3ph. H3T3ph is therefore unlikely to be responsible for transcriptional downregulation during cell division.
Electrocatalytic valorization of lignocellulose-derived aromatics at industrial-scale current densities
Authors: Peng Tao , Zhang Wenbin , Liang Baiyao , Lian Guanwu , Zhang Yun , Zhao Wei 
Published: November 2023

AbstractElectrocatalytic hydrogenation of lignocellulosic bio-oil to value-added chemicals offers an attractive avenue to use the increasing intermittent renewable electricity and biomass-derived feedstocks. However, to date the partial current densities to target products of these reactions are lower than those needed for industrial-scale productivity, which limits its prospects. Here we report a flow-cell system equipped with a Rh diffusion electrode to hydrogenate lignocellulose-derived aromatic monomers, such as furans and lignin monomers, to value-added chemicals. We achieve high faradaic efficiencies up to 64% at industrial-scale current densities of 300–500 mA cm−2, representing high productivities to target products. A screening of electrocatalysts indicates that only by highly-electrolyte-permeable Rh diffusion electrodes are we able to unite current density with faradaic efficiency. We apply in-situ infrared reflection–absorption spectroscopy to investigate the electrode-potential-dependent reaction pathways and intermediates, confirming a wide potential window for efficient electrocatalytic hydrogenation of lignocellulose-derived aromatics to target products.
Enterohaemorrhagic E. coli utilizes host- and microbiota-derived L-malate as a signaling molecule for intestinal colonization
Authors: Liu Bin , Jiang Lingyan , Liu Yutao , Sun Hongmin , Yan Jun , Kang Chenbo , Yang Bin 
Published: November 2023

AbstractThe mammalian gastrointestinal tract is a complex environment that hosts a diverse microbial community. To establish infection, bacterial pathogens must be able to compete with the indigenous microbiota for nutrients, as well as sense the host environment and modulate the expression of genes essential for colonization and virulence. Here, we found that enterohemorrhagic Escherichia coli (EHEC) O157:H7 imports host- and microbiota-derived L-malate using the DcuABC transporters and converts these substrates into fumarate to fuel anaerobic fumarate respiration during infection, thereby promoting its colonization of the host intestine. Moreover, L-malate is important not only for nutrient metabolism but also as a signaling molecule that activates virulence gene expression in EHEC O157:H7. The complete virulence-regulating pathway was elucidated; the DcuS/DcuR two-component system senses high L-malate levels and transduces the signal to the master virulence regulator Ler, which in turn activates locus of enterocyte effacement (LEE) genes to promote EHEC O157:H7 adherence to epithelial cells of the large intestine. Disruption of this virulence-regulating pathway by deleting either dcuS or dcuR significantly reduced colonization by EHEC O157:H7 in the infant rabbit intestinal tract; therefore, targeting these genes and altering physiological aspects of the intestinal environment may offer alternatives for EHEC infection treatment.
Gut butyrate-producers confer post-infarction cardiac protection
Authors: Chen Hung-Chih , Liu Yen-Wen , Chang Kuan-Cheng , Wu Yen-Wen , Chen Yi-Ming , Chao Yu-Kai , You Min-Yi , Lundy David J. , Lin Chen-Ju , Hsieh Marvin L. , Cheng Yu-Che , Prajnamitra Ray P. , Lin Po-Ju , Ruan Shu-Chian , Chen David Hsin-Kuang , Shih Edward S. C. , Chen Ke-Wei , Chang Shih-Sheng , Chang Cindy M. C. , Puntney Riley , Moy Amy Wu , Cheng Yuan-Yuan , Chien Hsin-Yuan , Lee Jia-Jung , Wu Deng-Chyang , Hwang Ming-Jing , Coonen Jennifer , Hacker Timothy A. , Yen C-L. Eric , Rey Federico E. , Kamp Timothy J. , Hsieh Patrick C. H. 
Published: November 2023

AbstractThe gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.
Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization
Authors: Liu Yangci , Zhai Haoming , Alemayehu Helen , Boulanger Jérôme , Hopkins Lee J. , Borgeaud Alicia C. , Heroven Christina , Howe Jonathan D. , Leigh Kendra E. , Bryant Clare E. , Modis Yorgo 
Published: November 2023

AbstractNLRP3 induces caspase-1-dependent pyroptotic cell death to drive inflammation. Aberrant activity of NLRP3 occurs in many human diseases. NLRP3 activation induces ASC polymerization into a single, micron-scale perinuclear punctum. Higher resolution imaging of this signaling platform is needed to understand how it induces pyroptosis. Here, we apply correlative cryo-light microscopy and cryo-electron tomography to visualize ASC/caspase-1 in NLRP3-activated cells. The puncta are composed of branched ASC filaments, with a tubular core formed by the pyrin domain. Ribosomes and Golgi-like or endosomal vesicles permeate the filament network, consistent with roles for these organelles in NLRP3 activation. Mitochondria are not associated with ASC but have outer-membrane discontinuities the same size as gasdermin D pores, consistent with our data showing gasdermin D associates with mitochondria and contributes to mitochondrial depolarization.
Development of a radical polymerization algorithm for molecular dynamics simulations of antifreezing hydrogels with double-network structures
Authors: Liu Yonglan , Zhang Dong , Tang Yijing , Gong Xiong , Zheng Jie 
Published: November 2023

AbstractThe development and understanding of antifreezing hydrogels are crucial both in principle and practice for the design and delivery of new materials. The current antifreezing mechanisms in hydrogels are almost exclusively derived from their incorporation of antifreezing additives, rather than from the inherent properties of the polymers themselves. Moreover, developing a computational model for the independent yet interconnected double-network (DN) structures in hydrogels has proven to be an exceptionally difficult task. Here, we develop a multiscale simulation platform, integrating ‘random walk reactive polymerization’ (RWRP) with molecular dynamics (MD) simulations, to computationally construct a physically-chemically linked PVA/PHEAA DN hydrogels from monomers that mimic a radical polymerization and to investigate water structures, dynamics, and interactions confined in PVA/PHEAA hydrogels with various water contents and temperatures, aiming to uncover antifreezing mechanism at atomic levels. Collective simulation results indicate that the antifreezing property of PVA/PHEAA hydrogels arises from a combination of intrinsic, strong water-binding networks and crosslinkers and tightly crosslinked and interpenetrating double-network structures, both of which enhance polymer-water interactions for competitively inhibiting ice nucleation and growth. These computational findings provide atomic-level insights into the interplay between polymers and water molecules in hydrogels, which may determine their resistance to freezing.
Greenland-wide accelerated retreat of peripheral glaciers in the twenty-first century
Authors: Larocca L. J. , Twining–Ward M. , Axford Y. , Schweinsberg A. D. , Larsen S. H. , Westergaard–Nielsen A. , Luetzenburg G. , Briner J. P. , Kjeldsen K. K. , Bjørk A. A. 
Published: November 2023

AbstractThe long-term response of Greenland’s peripheral glaciers to climate change is widely undocumented. Here we use historical aerial photographs and satellite imagery to document length fluctuations of >1,000 land-terminating peripheral glaciers in Greenland over more than a century. We find that their rate of retreat over the last two decades is double that of the twentieth century, indicating a ubiquitous transition into a new, accelerated state of downwasting.
RETRACTED ARTICLE: High replicability of newly discovered social-behavioural findings is achievable
Authors: Protzko John , Krosnick Jon , Nelson Leif , Nosek Brian A. , Axt Jordan , Berent Matt , Buttrick Nicholas , DeBell Matthew , Ebersole Charles R. , Lundmark Sebastian , MacInnis Bo , O’Donnell Michael , Perfecto Hannah , Pustejovsky James E. , Roeder Scott S. , Walleczek Jan , Schooler Jonathan W. 
Published: November 2023

AbstractFailures to replicate evidence of new discoveries have forced scientists to ask whether this unreliability is due to suboptimal implementation of methods or whether presumptively optimal methods are not, in fact, optimal. This paper reports an investigation by four coordinated laboratories of the prospective replicability of 16 novel experimental findings using rigour-enhancing practices: confirmatory tests, large sample sizes, preregistration and methodological transparency. In contrast to past systematic replication efforts that reported replication rates averaging 50%, replication attempts here produced the expected effects with significance testing (P < 0.05) in 86% of attempts, slightly exceeding the maximum expected replicability based on observed effect sizes and sample sizes. When one lab attempted to replicate an effect discovered by another lab, the effect size in the replications was 97% that in the original study. This high replication rate justifies confidence in rigour-enhancing methods to increase the replicability of new discoveries.
Dynamic intravital imaging reveals reactive vessel-associated microglia play a protective role in cerebral malaria coagulopathy
Authors: Solomon Olivia D. , Villarreal Paula , Domingo Nadia D. , Ochoa Lorenzo , Vanegas Difernando , Cardona Sandra M. , Cardona Astrid E. , Stephens Robin , Vargas Gracie 
Published: November 2023

AbstractVascular congestion and coagulopathy have been shown to play a role in human and experimental cerebral malaria (eCM), but little is known about the role of microglia, or microglia-vascular interactions and hypercoagulation during disease progression in this fatal infection. Recent studies show microglia bind to fibrinogen, a glycoprotein involved in thrombosis. An eCM model of Plasmodium chabaudi infection in mice deficient in the regulatory cytokine IL-10 manifests neuropathology, including hypercoagulation with extensive fibrin(ogen) deposition and neuroinflammation. Intravital microscopy and immunofluorescence are applied to elucidate the role of microglia in eCM. Results show microgliosis and coagulopathy occur early in disease at 3 dpi (day post-infection), and both are exacerbated as disease progresses to 7dpi. Vessel associated microglia increase significantly at 7 dpi, and the expression of the microglial chemoattractant CCL5 (RANTES) is increased versus uninfected and localized with fibrin(ogen) in vessels. PLX3397 microglia depletion resulted in rapid behavioral decline, severe hypothermia, and greater increase in vascular coagulopathy. This study suggests that microglia play a prominent role in controlling infection-initiated coagulopathy and supports a model in which microglia play a protective role in cerebral malaria by migrating to and patrolling the cerebral vasculature, potentially regulating degree of coagulation during systemic inflammation.
Need for Cognition is associated with a preference for higher task load in effort discounting
Authors: Zerna Josephine , Scheffel Christoph , Kührt Corinna , Strobel Alexander 
Published: November 2023

AbstractWhen individuals set goals, they consider the subjective value (SV) of the anticipated reward and the required effort, a trade-off that is of great interest to psychological research. One approach to quantify the SVs of levels of difficulty of a cognitive task is the Cognitive Effort Discounting Paradigm by Westbrook and colleagues (2013). However, it fails to acknowledge the highly individual nature of effort, as it assumes a unidirectional, inverse relationship between task load and SVs. Therefore, it cannot map differences in effort perception that arise from traits like Need for Cognition, since individuals who enjoy effortful cognitive activities likely do not prefer the easiest level. We replicated the analysis of Westbrook and colleagues with an adapted version, the Cognitive and Affective Discounting (CAD) Paradigm. It quantifies SVs without assuming that the easiest level is preferred, thereby enabling the assessment of SVs for tasks without objective order of task load. Results show that many of the 116 participants preferred a more or the most difficult level. Variance in SVs was best explained by a declining logistic contrast of the $$n$$
n
-back levels and by the accuracy of responses, while reaction time as a predictor was highly volatile depending on the preprocessing pipeline. Participants with higher Need for Cognition scores perceived higher $$n$$
n
-back levels as less effortful and found them less aversive. Effects of Need for Cognition on SVs in lower levels did not reach significance, as group differences only emerged in higher levels. The CAD Paradigm appears to be well suited for assessing and analysing task preferences independent of the supposed objective task difficulty.Protocol registrationThe stage 1 protocol for this Registered Report was accepted in principle on August 19, 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/CPXTH.
Contribution of sex and gender roles to the incidence of post-infectious irritable bowel syndrome in a prospective study
Authors: Park Jae Ho , Kang Sun Hyung , Kim Ju Seok , Moon Hee Seok , Sung Jae Kyu , Jeong Hyun Yong 
Published: November 2023

AbstractPost-infectious irritable bowel syndrome (PI-IBS) occurs in about 10% of cases following gastroenteritis. The incidence of IBS is higher in females. However, it is not clear whether this is due to biological or psychosocial factors. We aimed to investigate the influence of gender roles on the incidence of PI-IBS, alongside traditional risk factors. Our study included 231 patients diagnosed with gastroenteritis who were hospitalized and treated with antibiotics between 2018 and 2021. The Korean Sex Role Inventory-Short Form (KSRI-SF), based on the Bem Sex Role Inventory (BSRI) was used to categorize patients (androgynous, masculine, feminine, and undifferentiated types). Six months after treatment, we conducted a telephone survey to confirm the presence of PI-IBS using the ROME IV criteria. Among the patients, 43.3% were female, and the mean age was 43.67 ± 16.09 years. After 6 months, 34 patients developed PI-IBS. Univariate analysis revealed that younger age, female sex, KSRI-SF undifferentiated type, and longer duration of antibiotic use independently influenced the occurrence of PI-IBS. Multivariate analysis showed that PI-IBS was associated with the KSRI-SF undifferentiated type and higher C-reactive protein (CRP) levels. Our study showed that the KSRI-SF undifferentiated type and high CRP levels at initial infection were associated with PI-IBS.