bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis
Authors: Dong Ying , Hu Hao , Zhang Xuan , Zhang Yunkai , Sun Xin , Wang Hanlin , Kan Weijuan , Tan Min-jia , Shi Hong , Zang Yi , Li Jia 
Published: March 2023

AbstractEpithelial to mesenchymal transition (EMT) plays a crucial role in cancer metastasis, accompanied with vast epigenetic changes. AMP-activated protein kinase (AMPK), a cellular energy sensor, plays regulatory roles in multiple biological processes. Although a few studies have shed light on AMPK regulating cancer metastasis, the inside epigenetic mechanisms remain unknown. Herein we show that AMPK activation by metformin relieves the repressive H3K9me2-mediated silencing of epithelial genes (e.g., CDH1) during EMT processes and inhibits lung cancer metastasis. PHF2, a H3K9me2 demethylase, was identified to interact with AMPKα2. Genetic deletion of PHF2 aggravates lung cancer metastasis and abolishes the H3K9me2 downregulation and anti-metastasis effect of metformin. Mechanistically, AMPK phosphorylates PHF2 at S655 site, enhancing PHF2 demethylation activity and triggering the transcription of CDH1. Furthermore, the PHF2-S655E mutant that mimics AMPK-mediated phosphorylation status further reduces H3K9me2 and suppresses lung cancer metastasis, while PHF2-S655A mutant presents opposite phenotype and reverses the anti-metastasis effect of metformin. PHF2-S655 phosphorylation strikingly reduces in lung cancer patients and the higher phosphorylation level predicts better survival. Altogether, we reveal the mechanism of AMPK inhibiting lung cancer metastasis via PHF2 mediated H3K9me2 demethylation, thereby promoting the clinical application of metformin and highlighting PHF2 as the potential epigenetic target in cancer metastasis.
CD36+ cancer-associated fibroblasts provide immunosuppressive microenvironment for hepatocellular carcinoma via secretion of macrophage migration inhibitory factor
Authors: Zhu Gui-Qi , Tang Zheng , Huang Run , Qu Wei-Feng , Fang Yuan , Yang Rui , Tao Chen-Yang , Gao Jun , Wu Xiao-Ling , Sun Hai-Xiang , Zhou Yu-Fu , Song Shu-Shu , Ding Zhen-Bin , Dai Zhi , Zhou Jian , Ye Dan , Wu Duo-Jiao , Liu Wei-Ren , Fan Jia , Shi Ying-Hong 
Published: March 2023

AbstractHepatocellular carcinoma (HCC) is an immunotherapy-resistant malignancy characterized by high cellular heterogeneity. The diversity of cell types and the interplay between tumor and non-tumor cells remain to be clarified. Single cell RNA sequencing of human and mouse HCC tumors revealed heterogeneity of cancer-associated fibroblast (CAF). Cross-species analysis determined the prominent CD36+ CAFs exhibited high-level lipid metabolism and expression of macrophage migration inhibitory factor (MIF). Lineage-tracing assays showed CD36+CAFs were derived from hepatic stellate cells. Furthermore, CD36 mediated oxidized LDL uptake-dependent MIF expression via lipid peroxidation/p38/CEBPs axis in CD36+ CAFs, which recruited CD33+myeloid-derived suppressor cells (MDSCs) in MIF- and CD74-dependent manner. Co-implantation of CD36+ CAFs with HCC cells promotes HCC progression in vivo. Finally, CD36 inhibitor synergizes with anti-PD-1 immunotherapy by restoring antitumor T-cell responses in HCC. Our work underscores the importance of elucidating the function of specific CAF subset in understanding the interplay between the tumor microenvironment and immune system.
Manipulating the ordered oxygen complexes to achieve high strength and ductility in medium-entropy alloys
Authors: Jiao Meiyuan , Lei Zhifeng , Wu Yuan , Du Jinlong , Zhou Xiao-Ye , Li Wenyue , Yuan Xiaoyuan , Liu Xiaochun , Zhu Xiangyu , Wang Shudao , Zhu Huihui , Cao Peipei , Liu Xiongjun , Zhang Xiaobin , Wang Hui , Jiang Suihe , Lu Zhaoping 
Published: March 2023

AbstractOxygen solute strengthening is an effective strategy to harden alloys, yet, it often deteriorates the ductility. Ordered oxygen complexes (OOCs), a state between random interstitials and oxides, can simultaneously enhance strength and ductility in high-entropy alloys. However, whether this particular strengthening mechanism holds in other alloys and how these OOCs are tailored remain unclear. Herein, we demonstrate that OOCs can be obtained in bcc (body-centered-cubic) Ti-Zr-Nb medium-entropy alloys via adjusting the content of Nb and oxygen. Decreasing the phase stability enhances the degree of (Ti, Zr)-rich chemical short-range orderings, and then favors formation of OOCs after doping oxygen. Moreover, the number density of OOCs increases with oxygen contents in a given alloy, but adding excessive oxygen (>3.0 at.%) causes grain boundary segregation. Consequently, the tensile yield strength is enhanced by ~75% and ductility is substantially improved by ~164% with addition of 3.0 at.% O in the Ti-30Zr-14Nb MEA.
Safety and immunogenicity of a thermostable ID93 + GLA-SE tuberculosis vaccine candidate in healthy adults
Authors: Sagawa Zachary K. , Goman Cristina , Frevol Aude , Blazevic Azra , Tennant Janice , Fisher Bridget , Day Tracey , Jackson Stephen , Lemiale Franck , Toussaint Leon , Kalisz Irene , Jiang Joe , Ondrejcek Lisa , Mohamath Raodoh , Vergara Julie , Lew Alan , Beckmann Anna Marie , Casper Corey , Hoft Daniel F. , Fox Christopher B. 
Published: March 2023

AbstractAdjuvant-containing subunit vaccines represent a promising approach for protection against tuberculosis (TB), but current candidates require refrigerated storage. Here we present results from a randomized, double-blinded Phase 1 clinical trial (NCT03722472) evaluating the safety, tolerability, and immunogenicity of a thermostable lyophilized single-vial presentation of the ID93 + GLA-SE vaccine candidate compared to the non-thermostable two-vial vaccine presentation in healthy adults. Participants were monitored for primary, secondary, and exploratory endpoints following intramuscular administration of two vaccine doses 56 days apart. Primary endpoints included local and systemic reactogenicity and adverse events. Secondary endpoints included antigen-specific antibody (IgG) and cellular immune responses (cytokine-producing peripheral blood mononuclear cells and T cells). Both vaccine presentations are safe and well tolerated and elicit robust antigen-specific serum antibody and Th1-type cellular immune responses. Compared to the non-thermostable presentation, the thermostable vaccine formulation generates greater serum antibody responses (p < 0.05) and more antibody-secreting cells (p < 0.05). In this work, we show the thermostable ID93 + GLA-SE vaccine candidate is safe and immunogenic in healthy adults.
Systematic characterization of chromodomain proteins reveals an H3K9me1/2 reader regulating aging in C. elegans
Authors: Hou Xinhao , Xu Mingjing , Zhu Chengming , Gao Jianing , Li Meili , Chen Xiangyang , Sun Cheng , Nashan Björn , Zang Jianye , Zhou Ying , Guang Shouhong , Feng Xuezhu 
Published: March 2023

AbstractThe chromatin organization modifier domain (chromodomain) is an evolutionally conserved motif across eukaryotic species. The chromodomain mainly functions as a histone methyl-lysine reader to modulate gene expression, chromatin spatial conformation and genome stability. Mutations or aberrant expression of chromodomain proteins can result in cancer and other human diseases. Here, we systematically tag chromodomain proteins with green fluorescent protein (GFP) using CRISPR/Cas9 technology in C. elegans. By combining ChIP-seq analysis and imaging, we delineate a comprehensive expression and functional map of chromodomain proteins. We then conduct a candidate-based RNAi screening and identify factors that regulate the expression and subcellular localization of the chromodomain proteins. Specifically, we reveal an H3K9me1/2 reader, CEC-5, both by in vitro biochemistry and in vivo ChIP assays. MET-2, an H3K9me1/2 writer, is required for CEC-5 association with heterochromatin. Both MET-2 and CEC-5 are required for the normal lifespan of C. elegans. Furthermore, a forward genetic screening identifies a conserved Arginine124 of CEC-5’s chromodomain, which is essential for CEC-5’s association with chromatin and life span regulation. Thus, our work will serve as a reference to explore chromodomain functions and regulation in C. elegans and allow potential applications in aging-related human diseases.
Single-vat single-cure grayscale digital light processing 3D printing of materials with large property difference and high stretchability
Authors: Yue Liang , Macrae Montgomery S. , Sun Xiaohao , Yu Luxia , Song Yuyang , Nomura Tsuyoshi , Tanaka Masato , Jerry Qi H. 
Published: March 2023

AbstractMultimaterial additive manufacturing has important applications in various emerging fields. However, it is very challenging due to material and printing technology limitations. Here, we present a resin design strategy that can be used for single-vat single-cure grayscale digital light processing (g-DLP) 3D printing where light intensity can locally control the conversion of monomers to form from a highly stretchable soft organogel to a stiff thermoset within in a single layer of printing. The high modulus contrast and high stretchability can be realized simultaneously in a monolithic structure at a high printing speed (z-direction height 1 mm/min). We further demonstrate that the capability can enable previously unachievable or hard-to-achieve 3D printed structures for biomimetic designs, inflatable soft robots and actuators, and soft stretchable electronics. This resin design strategy thus provides a material solution in multimaterial additive manufacture for a variety of emerging applications.
Estimating immunity with mathematical models for SARS-CoV-2 after COVID-19 vaccination
Authors: Uwamino Yoshifumi , Nagashima Kengo , Yoshifuji Ayumi , Suga Shigeru , Nagao Mizuho , Fujisawa Takao , Ryuzaki Munekazu , Takemoto Yoshiaki , Namkoong Ho , Wakui Masatoshi , Matsushita Hiromichi , Hasegawa Naoki , Sato Yasunori , Murata Mitsuru 
Published: March 2023

AbstractTools that can be used to estimate antibody waning following COVID-19 vaccinations can facilitate an understanding of the current immune status of the population. In this study, a two-compartment-based mathematical model is formulated to describe the dynamics of the anti-SARS-CoV-2 antibody in healthy adults using serially measured waning antibody concentration data obtained in a prospective cohort study of 673 healthcare providers vaccinated with two doses of BNT162b2 vaccine. The datasets of 165 healthcare providers and 292 elderly patients with or without hemodialysis were used for external validation. Internal validation of the model demonstrated 97.0% accuracy, and external validation of the datasets of healthcare workers, hemodialysis patients, and nondialysis patients demonstrated 98.2%, 83.3%, and 83.8% accuracy, respectively. The internal and external validations demonstrated that this model also fits the data of various populations with or without underlying illnesses. Furthermore, using this model, we developed a smart device application that can rapidly calculate the timing of negative seroconversion.
Rupturing aromaticity by periphery overcrowding
Authors: Saha Promeet K. , Mallick Abhijit , Turley Andrew T. , Bismillah Aisha N. , Danos Andrew , Monkman Andrew P. , Avestro Alyssa-Jennifer , Yufit Dmitry S. , McGonigal Paul R. 
Published: March 2023

AbstractThe balance between strain relief and aromatic stabilization dictates the form and function of non-planar π-aromatics. Overcrowded systems are known to undergo geometric deformations, but the energetically favourable π-electron delocalization of their aromatic ring(s) is typically preserved. In this study we incremented the strain energy of an aromatic system beyond its aromatic stabilization energy, causing it to rearrange and its aromaticity to be ruptured. We noted that increasing the steric bulk around the periphery of π-extended tropylium rings leads them to deviate from planarity to form contorted conformations in which aromatic stabilization and strain are close in energy. Under increasing strain, the aromatic π-electron delocalization of the system is broken, leading to the formation of a non-aromatic, bicyclic analogue referred to as ‘Dewar tropylium’. The aromatic and non-aromatic isomers have been found to exist in rapid equilibrium with one another. This investigation demarcates the extent of steric deformation tolerated by an aromatic carbocycle and thus provides direct experimental insights into the fundamental nature of aromaticity.
Future warming from global food consumption
Authors: Ivanovich Catherine C. , Sun Tianyi , Gordon Doria R. , Ocko Ilissa B. 
Published: March 2023

AbstractFood consumption is a major source of greenhouse gas (GHG) emissions, and evaluating its future warming impact is crucial for guiding climate mitigation action. However, the lack of granularity in reporting food item emissions and the widespread use of oversimplified metrics such as CO2 equivalents have complicated interpretation. We resolve these challenges by developing a global food consumption GHG emissions inventory separated by individual gas species and employing a reduced-complexity climate model, evaluating the associated future warming contribution and potential benefits from certain mitigation measures. We find that global food consumption alone could add nearly 1 °C to warming by 2100. Seventy five percent of this warming is driven by foods that are high sources of methane (ruminant meat, dairy and rice). However, over 55% of anticipated warming can be avoided from simultaneous improvements to production practices, the universal adoption of a healthy diet and consumer- and retail-level food waste reductions.
Accuracy and social motivations shape judgements of (mis)information
Authors: Rathje Steve , Roozenbeek Jon , Van Bavel Jay J. , van der Linden Sander 
Published: March 2023

AbstractThe extent to which belief in (mis)information reflects lack of knowledge versus a lack of motivation to be accurate is unclear. Here, across four experiments (n = 3,364), we motivated US participants to be accurate by providing financial incentives for correct responses about the veracity of true and false political news headlines. Financial incentives improved accuracy and reduced partisan bias in judgements of headlines by about 30%, primarily by increasing the perceived accuracy of true news from the opposing party (d = 0.47). Incentivizing people to identify news that would be liked by their political allies, however, decreased accuracy. Replicating prior work, conservatives were less accurate at discerning true from false headlines than liberals, yet incentives closed the gap in accuracy between conservatives and liberals by 52%. A non-financial accuracy motivation intervention was also effective, suggesting that motivation-based interventions are scalable. Altogether, these results suggest that a substantial portion of people’s judgements of the accuracy of news reflects motivational factors.
Puddle formation and persistent gaps across the non-mean-field breakdown of superconductivity in overdoped (Pb,Bi)2Sr2CuO6+δ
Authors: Tromp Willem O. , Benschop Tjerk , Ge Jian-Feng , Battisti Irene , Bastiaans Koen M. , Chatzopoulos Damianos , Vervloet Amber H. M. , Smit Steef , van Heumen Erik , Golden Mark S. , Huang Yinkai , Kondo Takeshi , Takeuchi Tsunehiro , Yin Yi , Hoffman Jennifer E. , Sulangi Miguel Antonio , Zaanen Jan , Allan Milan P. 
Published: March 2023

AbstractThe cuprate high-temperature superconductors exhibit many unexplained electronic phases, but the superconductivity at high doping is often believed to be governed by conventional mean-field Bardeen–Cooper–Schrieffer theory1. However, it was shown that the superfluid density vanishes when the transition temperature goes to zero2,3, in contradiction to expectations from Bardeen–Cooper–Schrieffer theory. Our scanning tunnelling spectroscopy measurements in the overdoped regime of the (Pb,Bi)2Sr2CuO6+δ high-temperature superconductor show that this is due to the emergence of nanoscale superconducting puddles in a metallic matrix4,5. Our measurements further reveal that this puddling is driven by gap filling instead of gap closing. The important implication is that it is not a diminishing pairing interaction that causes the breakdown of superconductivity. Unexpectedly, the measured gap-to-filling correlation also reveals that pair breaking by disorder does not play a dominant role and that the mechanism of superconductivity in overdoped cuprate superconductors is qualitatively different from conventional mean-field theory.
Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial
Authors: Rosenson Robert S. , Gaudet Daniel , Ballantyne Christie M. , Baum Seth J. , Bergeron Jean , Kershaw Erin E. , Moriarty Patrick M. , Rubba Paolo , Whitcomb David C. , Banerjee Poulabi , Gewitz Andrew , Gonzaga-Jauregui Claudia , McGinniss Jennifer , Ponda Manish P. , Pordy Robert , Zhao Jian , Rader Daniel J. 
Published: March 2023

AbstractSevere hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches for sHTG are often insufficient to reduce triglycerides and prevent acute pancreatitis. This phase 2 trial (NCT03452228) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations (n = 17); cohort 2, multifactorial chylomicronemia syndrome with heterozygous loss-of-function LPL pathway mutations (n = 15); and cohort 3, multifactorial chylomicronemia syndrome without LPL pathway mutations (n = 19). Fifty-one patients (males, n = 27; females, n = 24) with a history of hospitalization for acute pancreatitis were randomized 2:1 to intravenous evinacumab 15 mg kg−1 or placebo every 4 weeks over a 12-week double-blind treatment period, followed by a 12-week single-blind treatment period. The primary end point was the mean percent reduction in triglycerides from baseline after 12 weeks of evinacumab exposure in cohort 3. Evinacumab reduced triglycerides in cohort 3 by a mean (s.e.m.) of −27.1% (37.4) (95% confidence interval −71.2 to 84.6), but the prespecified primary end point was not met. No notable differences in adverse events between evinacumab and placebo treatment groups were seen during the double-blind treatment period. Although the primary end point of a reduction in triglycerides did not meet the prespecified significance level, the observed safety and changes in lipid and lipoprotein levels support the further evaluation of evinacumab in larger trials of patients with sHTG. Trial registration number: ClinicalTrials.gov NCT03452228.
Protein interactors of 3-O sulfated heparan sulfates in human MCI and age-matched control cerebrospinal fluid
Authors: Ferreira Andreia , Timmerman Evy , Staes An , Vuylsteke Marnik , De Muynck Louis , Gevaert Kris 
Published: March 2023

AbstractHeparan sulfates (HS) proteoglycans are commonly found on the cell surface and mediate many processes. Binding of HS ligands is determined by the sulfation code on the HS chain that can be N-/2-O/6-O- or 3-O-sulfated, generating heterogenous sulfation patterns. 3-O sulfated HS (3S-HS) play a role in several (patho)physiological processes such as blood coagulation, viral pathogenesis and binding and internalization of tau in Alzheimer’s disease. However, few 3S-HS-specific interactors are known. Thus, our insight into the role of 3S-HS in health and disease is limited, especially in the central nervous system. Using human CSF, we determined the interactome of synthetic HS with defined sulfation patterns. Our affinity-enrichment mass spectrometry studies expand the repertoire of proteins that may interact with (3S-)HS. Validating our approach, ATIII, a known 3S-HS interactor, was found to require GlcA-GlcNS6S3S for binding, similar to what has been reported. Our dataset holds novel, potential HS and 3S-HS protein ligands, that can be explored in future studies focusing on molecular mechanisms that depend on 3S-HS in (patho)physiological conditions.
Association between triglyceride to high-density lipoprotein cholesterol ratio and type 2 diabetes risk in Japanese
Authors: Wang Huijuan , Wang Changming , Xuan Xiuping , Xie Zhouni , Qiu Yuanyuan , Qin Huiping , Xiaoning Zhong 
Published: March 2023

AbstractAbnormal lipid metabolism is known to increases the risk for metabolic diseases, such as type 2 diabetes mellitus(T2DM). The relationship between baseline ratio of triglyceride to HDL cholesterol (TG/HDL-C) and T2DM in Japanese adults was investigated in this study. Our secondary analysis included 8419 male and 7034 female Japanese subjects who were free of diabetes at baseline. The correlation between baseline TG/HDL-C and T2DM was analyzed by a proportional risk regression model, the nonlinear correlation between baseline TG/HDL-C and T2DM was analyzed by a generalized additive model (GAM), and the threshold effect analysis was performed by a segmented regression model. We conducted subgroup analyses in different populations. During the median 5.39 years follow-up, 373 participants, 286 males and 87 females, developed diabetes mellitus. After full adjustment for confounders, the baseline TG/HDL-C ratio positively correlated with the risk of diabetes (hazard ratio 1.19, 95% confidence interval 1.09–1.3), and smoothed curve fitting and two-stage linear regression analysis revealed a J-shaped relationship between baseline TG/HDL-C and T2DM. The inflection point for baseline TG/HDL-C was 0.35. baseline TG/HDL-C > 0.35 was positively associated with the development of T2DM (hazard ratio 1.2, 95% confidence interval 1.10–1.31). Subgroup analysis showed no significant differences in the effect between TG/HDL-C and T2DM in different populations. A J-shaped relationship was observed between baseline TG/HDL-C and T2DM risk in the Japanese population. When TG/HDL-C was higher than 0.35, there was a positive relationship between baseline TG/HDL-C and the incidence of diabetes mellitus.
Comparative effects of desflurane and sevoflurane on intraoperative peripheral perfusion index: a retrospective, propensity score matched, cohort study
Authors: Oh Chahyun , Lee Seounghun , Song Byong-Sop , Kwon Sanghun , Kim Yoon-Hee , Yoon Seok-Hwa , Shin Yong Sup , Ko Youngkwon , Lim Chaeseong , Hong Boohwi 
Published: March 2023

AbstractDesflurane is known to have a larger vasodilatory effect than that of sevoflurane. However, its generalizability and effect size in actual clinical practice are yet to be proven. Patients aged ≥ 18 years who underwent noncardiac surgery under general anesthesia using inhalation anesthetics (desflurane or sevoflurane) were matched 1:1 by propensity score. The mean intraoperative perfusion index (PI) of each patient were compared between the two groups. Propensity score matching of 1680 patients in the study cohort identified 230 pairs of patients. PI was significantly higher in the desflurane group (median of paired difference, 0.45; 95% CI 0.16 to 0.74, p = 0.002). PI durations below 1.0 and 1.5 were significantly longer in the sevoflurane group. Mean arterial pressure (MAP) and durations of low MAP did not differ significantly between the two groups. Generalized linear mixed models revealed that the use of sevoflurane, mean MAP, mean heart rate, age, and duration of anesthesia had significant negative effects (lower PI), whereas mean age-adjusted minimum alveolar concentration of inhalation agent had a positive effect on PI (higher value). Intraoperative PI was significantly higher in patients administered desflurane than sevoflurane. However, the impact of the choice between desflurane and sevoflurane on intraoperative PI in this clinical setting was minimal.