bluuebunny/crossref_metadata_2025_split huggingface dataset:
N6-methyladenosine (m6A) methyltransferase METTL3-mediated LINC00680 accelerates osteoarthritis through m6A/SIRT1 manner
Authors: Ren Jiangdong , Li Yicheng , Wuermanbieke Shalitanati , Hu Shu , Huang Guangxin 
Published: May 2022

AbstractIncreasing evidence suggest the biological roles of N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) in the bone disease, especially osteoarthritis (OA). However, the interaction of m6A and lncRNA in osteoarthritis is still unclear. Here, we found that a m6A-related lncRNA LINC00680 upregulated in the OA tissue and IL-1β-induced isolated primary chondrocytes. Functionally, in IL-1β-induced chondrocytes, silencing of LINC00680 recovered the proliferation and repressed the extracellular matrix (ECM) degradation. Mechanistically, m6A methyltransferase METTL3 combined tithe the m6A site of LINC00680 to up-regulate its expression. Moreover, LINC00680 interacted with SIRT1 mRNA through binding at m6A site on SIRT1 mRNA 3′-UTR, thereby enhancing the stability of SIRT1 mRNA. Overall, these findings exhibited a role of LINC00680/m6A/SIRT1 mRNA complex in chondrocytes. Taken together, the present study intends to uncover the mechanism by which METTL3-mediated LINC00680 accelerates OA progression, which may provide novel insight for OA.
Roles and mechanisms of the m6A reader YTHDC1 in biological processes and diseases
Authors: Yan Huaqing , Zhang Liqi , Cui Xiaobo , Zheng Sinian , Li Rubing 
Published: May 2022

AbstractN6-methyladenosine (m6A) is a key area in Epigenetics and has been increasingly focused these years. In the m6A process, readers recognize the m6A modification on mRNAs or noncoding RNAs and mediate different downstream events. Emerging studies have shown that YTHDC1, an important m6A reader, plays a key role in many biological functions and disease progression, especially cancers. Here we summarized the current mechanisms of YTHDC1 in biological functions and diseases and offered guidance for future researches to provide potential strategy for clinical diagnose and therapy.
Rare and misincorporated DNA N6-methyladenine is a hallmark of cytotoxic stresses for selectively stimulating the stemness and proliferation of glioblastoma cells
Authors: Lyu Cong , Niu Yamei , Lai Weiyi , Wang Yu , Wang Yaning , Dai Peibin , Ma Chunhui , Chen Shaokun , Li Yao , Jiang Guibin , Liang Zhiyong , Ma Wenbin , Gao Zhengliang , Tong Wei-Min , Wang Hailin 
Published: May 2022

AbstractThe entity of DNA N6-methyladenine (6mA) in mammals remains elusive and subsequently its roles in diseases are poorly understood. Here we exploited a bacterial DNA contamination-free and ultrasensitive UHPLC-MS/MS assay to reassess DNA 6mA in human glioblastomas and unveiled that DNA 6mA (~0.08 ppm) is extremely rare. By the use of two independent heavy stable isotope-labeling strategies, we further prove that the observed 6mA is solely generated by DNA polymerase-mediated misinocorporation. In vitro experiments point toward that the generation of misincorporated DNA 6mA is associated with the cellular stresses-caused release of RNA N6-methyladenine (m6A) nucleoside, which is profoundly inhibited by hypoxia milieu. Consistently, compared with normal brain tissues, DNA 6mA decreases in hypoxic human gliomas. Our data also strongly support that rare DNA 6mA rather than relatively abundant DNA 5-methylcytosine and 5-hydroxymethylcytosine is a hallmark of poor prognosis ofIDH1/2mutation-absent glioblastoma patients, reflecting the incidence of cytotoxic stresses and subsequent release of m6A nucleoside. The released m6A nucleoside may selectively preserve a subset of the glioblastoma cells and stimulate their stemness and proliferation. Noteworthily, demethylation-inhibitingIDH1mutation increases the DNA 6mA content in human gliomas, but the depletion of the demethylase candidate ALKBH1 fails to do so, together suggesting the presence of other unknown 6mA demethylase for erasing misincorporated DNA 6mA. This is the first report on the identification of the misincorporated 6mA together with its origin and roles in diseases.
Incidence and criteria used in the diagnosis of hospital-acquired malnutrition in adults: a systematic review and pooled incidence analysis
Authors: Botero Liliana , Young Adrienne M. , Banks Merrilyn D. , Bauer Judy 
Published: May 2022

AbstractDespite advances in identifying malnutrition at hospital admission, decline in nutritional status of well-nourished patients can be overlooked. The aim of this systematic review was to investigate the incidence of hospital-acquired malnutrition (HAM), diagnostic criteria and health-related outcomes. PubMed, CINAHL, Embase and Cochrane Library were searched up to July 2021. Studies were included if changes in nutritional status was assessed with a validated nutrition assessment tool in acute and subacute adult (≥18 yrs) hospitalised patients. A random-effects method was used to pool the incidence proportion of HAM in prospective studies. The certainty of evidence was appraised using the Grading of Recommendation Assessment, Development and Evaluation system. We identified 12 observational cohort studies (10 prospective and 2 retrospective), involving 35,324 participants from acute (9 studies) and subacute settings (3 studies). Retrospective studies reported a lower incidence of HAM (<1.4%) than prospective studies (acute: 9–38%; subacute: 0–7%). The pooled incidence of HAM in acute care was 25.9% (95% confidence interval (CI): 17.3–34.6). Diagnostic criteria varied, with use of different nutrition assessment tools and timeframes for assessment (retrospective studies: >14 days; prospective studies: ≥7 days). Nutritional decline is probably associated with longer length of stay and higher 6-month readmission (moderate certainty of evidence) and may be association with higher complications and infections (low certainty of evidence). The higher incidence of HAM in the acute setting, where nutritional assessments are conducted prospectively, highlights the need for consensus regarding diagnostic criteria and further studies to understand the impact of HAM.
Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus
Authors: Sun Xiaoyu , Liu Caixuan , Lu Xiao , Ling Zhiyang , Yi Chunyan , Zhang Zhen , Li Zi , Jin Mingliang , Wang Wenshuai , Tang Shubing , Wang Fangfang , Wang Fang , Wangmo Sonam , Chen Shuangfeng , Li Li , Ma Liyan , Zhang Yaguang , Yang Zhuo , Dong Xiaoping , Qian Zhikang , Ding Jianping , Wang Dayan , Cong Yao , Sun Bing 
Published: May 2022

AbstractMost structurally characterized broadly neutralizing antibodies (bnAbs) against influenza A viruses (IAVs) target the conserved conformational epitopes of hemagglutinin (HA). Here, we report a lineage of naturally occurring human antibodies sharing the same germline gene, VH3-48/VK1-12. These antibodies broadly neutralize the major circulating strains of IAV in vitro and in vivo mainly by binding a contiguous epitope of H3N2 HA, but a conformational epitope of H1N1 HA, respectively. Our structural and functional studies of antibody 28-12 revealed that the continuous amino acids in helix A, particularly N49HA2 of H3 HA, are critical to determine the binding feature with 28-12. In contrast, the conformational epitope feature is dependent on the discontinuous segments involving helix A, the fusion peptide, and several HA1 residues within H1N1 HA. We report that this antibody was initially selected by H3 (group 2) viruses and evolved via somatic hypermutation to enhance the reactivity to H3 and acquire cross-neutralization to H1 (group 1) virus. These findings enrich our understanding of different antigenic determinants of heterosubtypic influenza viruses for the recognition of bnAbs and provide a reference for the design of influenza vaccines and more effective antiviral drugs.
Intermolecular diastereoselective annulation of azaarenes into fused N-heterocycles by Ru(II) reductive catalysis
Authors: Zhao He , Wu Yang , Ci Chenggang , Tan Zhenda , Yang Jian , Jiang Huanfeng , Dixneuf Pierre H. , Zhang Min 
Published: May 2022

AbstractDerivatization of azaarenes can create molecules of biological importance, but reductive functionalization of weakly reactive azaarenes remains a challenge. Here the authors show a dearomative, diastereoselective annulation of azaarenes, via ruthenium(II) reductive catalysis, proceeding with excellent selectivity, mild conditions, and broad substrate and functional group compatibility. Mechanistic studies reveal that the products are formed via hydride transfer-initiated β-aminomethylation and α-arylation of the pyridyl core in the azaarenes, and that paraformaldehyde serves as both the C1-building block and reductant precursor, and the use of Mg(OMe)2 base plays a critical role in determining the reaction chemo-selectivity by lowering the hydrogen transfer rate. The present work opens a door to further develop valuable reductive functionalization of unsaturated systems by taking profit of formaldehyde-endowed two functions.
Placental multi-omics integration identifies candidate functional genes for birthweight
Authors: Tekola-Ayele Fasil , Zeng Xuehuo , Chatterjee Suvo , Ouidir Marion , Lesseur Corina , Hao Ke , Chen Jia , Tesfaye Markos , Marsit Carmen J. , Workalemahu Tsegaselassie , Wapner Ronald 
Published: May 2022

AbstractAbnormal birthweight is associated with increased risk for cardiometabolic diseases in later life. Although the placenta is critical to fetal development and later life health, it has not been integrated into largescale functional genomics initiatives, and mechanisms of birthweight-associated variants identified by genome wide association studies (GWAS) are unclear. The goal of this study is to provide functional mechanistic insight into the causal pathway from a genetic variant to birthweight by integrating placental methylation and gene expression with established GWAS loci for birthweight. We identify placental DNA methylation and gene expression targets for several birthweight GWAS loci. The target genes are broadly enriched in cardiometabolic, immune response, and hormonal pathways. We find that methylation causally influencesWNT3A,CTDNEP1, andRANBP2expression in placenta. Multi-trait colocalization identifiesPLEKHA1,FES,CTDNEP1, andPRMT7as likely functional effector genes. These findings reveal candidate functional pathways that underpin the genetic regulation of birthweight via placental epigenetic and transcriptomic mechanisms. Clinical trial registration; ClinicalTrials.gov, NCT00912132.
A cost-effective alkaline polysulfide-air redox flow battery enabled by a dual-membrane cell architecture
Authors: Xia Yuhua , Ouyang Mengzheng , Yufit Vladimir , Tan Rui , Regoutz Anna , Wang Anqi , Mao Wenjie , Chakrabarti Barun , Kavei Ashkan , Song Qilei , Kucernak Anthony R. , Brandon Nigel P. 
Published: May 2022

AbstractWith the rapid development of renewable energy harvesting technologies, there is a significant demand for long-duration energy storage technologies that can be deployed at grid scale. In this regard, polysulfide-air redox flow batteries demonstrated great potential. However, the crossover of polysulfide is one significant challenge. Here, we report a stable and cost-effective alkaline-based hybrid polysulfide-air redox flow battery where a dual-membrane-structured flow cell design mitigates the sulfur crossover issue. Moreover, combining manganese/carbon catalysed air electrodes with sulfidised Ni foam polysulfide electrodes, the redox flow battery achieves a maximum power density of 5.8 mW cm−2 at 50% state of charge and 55 °C. An average round-trip energy efficiency of 40% is also achieved over 80 cycles at 1 mA cm−2. Based on the performance reported, techno-economic analyses suggested that energy and power costs of about 2.5 US$/kWh and 1600 US$/kW, respectively, has be achieved for this type of alkaline polysulfide-air redox flow battery, with significant scope for further reduction.
Emergent multiferroism with magnetodielectric coupling in EuTiO3 created by a negative pressure control of strong spin-phonon coupling
Authors: Zhao Run , Yang Chao , Wang Hongguang , Jiang Kai , Wu Hua , Shen Shipeng , Wang Le , Sun Young , Jin Kuijuan , Gao Ju , Chen Li , Wang Haiyan , MacManus-Driscoll Judith L. , van Aken Peter A. , Hong Jiawang , Li Weiwei , Yang Hao 
Published: May 2022

AbstractNegative pressure has emerged as a powerful tool to tailor the physical properties of functional materials. However, a negative pressure control of spin-phonon coupling for engineering magnetism and multiferroicity has not been explored to date. Here, using uniform three-dimensional strain-induced negative pressure in nanocomposite films of (EuTiO3)0.5:(MgO)0.5, we demonstrate an emergent multiferroicity with magnetodielectric coupling in EuTiO3, matching exactly with density functional theory calculations. Density functional theory calculations are further used to explore the underlying physics of antiferromagnetic-paraelectric to ferromagnetic-ferroelectric phase transitions, the spin-phonon coupling, and its correlation with negative pressures. The observation of magnetodielectric coupling in the EuTiO3 reveals that an enhanced spin-phonon coupling originates from a negative pressure induced by uniform three-dimensional strain. Our work provides a route to creating multiferroicity and magnetoelectric coupling in single-phase oxides using a negative pressure approach.
High-performance cavity-enhanced quantum memory with warm atomic cell
Authors: Ma Lixia , Lei Xing , Yan Jieli , Li Ruiyang , Chai Ting , Yan Zhihui , Jia Xiaojun , Xie Changde , Peng Kunchi 
Published: May 2022

AbstractHigh-performance quantum memory for quantized states of light is a prerequisite building block of quantum information technology. Despite great progresses of optical quantum memories based on interactions of light and atoms, physical features of these memories still cannot satisfy requirements for applications in practical quantum information systems, since all of them suffer from trade-off between memory efficiency and excess noise. Here, we report a high-performance cavity-enhanced electromagnetically-induced-transparency memory with warm atomic cell in which a scheme of optimizing the spatial and temporal modes based on the time-reversal approach is applied. The memory efficiency up to 67 ± 1% is directly measured and a noise level close to quantum noise limit is simultaneously reached. It has been experimentally demonstrated that the average fidelities for a set of input coherent states with different phases and amplitudes within a Gaussian distribution have exceeded the classical benchmark fidelities. Thus the realized quantum memory platform has been capable of preserving quantized optical states, and is ready to be applied in quantum information systems, such as distributed quantum logic gates and quantum-enhanced atomic magnetometry.
Activation and allosteric regulation of the orphan GPR88-Gi1 signaling complex
Authors: Chen Geng , Xu Jun , Inoue Asuka , Schmidt Maximilian F. , Bai Chen , Lu Qiuyuan , Gmeiner Peter , Liu Zheng , Du Yang 
Published: May 2022

AbstractGPR88 is an orphan class A G-protein-coupled receptor that is highly expressed in the striatum and regulates diverse brain and behavioral functions. Here we present cryo-EM structures of the human GPR88-Gi1 signaling complex with or without a synthetic agonist(1R, 2R)-2-PCCA. We show that(1R, 2R)-2-PCCA is an allosteric modulator binding to a herein identified pocket formed by the cytoplasmic ends of transmembrane segments 5, 6, and the extreme C terminus of the α5 helix of Gi1. We also identify an electron density in the extracellular orthosteric site that may represent a putative endogenous ligand of GPR88. These structures, together with mutagenesis studies and an inactive state model obtained from metadynamics simulations, reveal a unique activation mechanism for GPR88 with a set of distinctive structure features and a water-mediated polar network. Overall, our results provide a structural framework for understanding the ligand binding, activation and signaling mechanism of GPR88, and will facilitate the innovative drug discovery for neuropsychiatric disorders and for deorphanization of this receptor.
Formation of thyroid hormone revealed by a cryo-EM structure of native bovine thyroglobulin
Authors: Marechal Nils , Serrano Banyuhay P. , Zhang Xinyan , Weitz Charles J. 
Published: May 2022

AbstractThyroid hormones are essential regulators of metabolism, development, and growth. They are formed from pairs of iodinated tyrosine residues within the precursor thyroglobulin (TG), a 660-kDa homodimer of the thyroid gland, by an oxidative coupling reaction. Tyrosine pairs that give rise to thyroid hormones have been assigned within the structure of human TG, but the process of hormone formation is poorly understood. Here we report a ~3.3-Å cryo-EM structure of native bovine TG with nascent thyroid hormone formed at one of the predicted hormonogenic sites. Local structural rearrangements provide insight into mechanisms underlying thyroid hormone formation and stabilization.
Domain memory effect in the organic ferroics
Authors: Wang Zhong-Xia , Chen Xiao-Gang , Song Xian-Jiang , Zeng Yu-Ling , Li Peng-Fei , Tang Yuan-Yuan , Liao Wei-Qiang , Xiong Ren-Gen 
Published: May 2022

AbstractShape memory alloys have been used extensively in actuators, couplings, medical guide wires, and smart devices, because of their unique shape memory effect and superelasticity triggered by the reversible martensitic phase transformations. For ferroic materials, however, almost no memory effects have been found for their ferroic domains after reversible phase transformations. Here, we present a pair of single-component organic enantiomorphic ferroelectric/ferroelastic crystals, (R)- and (S)-N-3,5-di-tert-butylsalicylidene-1-(1-naphthyl)ethylamine SA-NPh-(R) and SA-NPh-(S). It is notable that not only can their ferroic domain patterns disappear and reappear during reversible thermodynamic phase transformations, but they can also disappear and reappear during reversible light-driven phase transformations induced by enol–keto photoisomerization, both of which are from P1 to P21 polar space groups. Most importantly, the domain patterns are exactly the same in the initial and final states, demonstrating the existence of a memory effect for the ferroic domains in SA-NPh-(R) and SA-NPh-(S). As far as we are aware, the domain memory effect triggered by both thermodynamic and light-driven ferroelectric/ferroelastic phase transformations remains unexplored in ferroic materials. Thermal and optical control of domain memory effect would open up a fresh research field for smart ferroic materials.
The rapid evolution of lungfish durophagy
Authors: Cui Xindong , Friedman Matt , Qiao Tuo , Yu Yilun , Zhu Min 
Published: May 2022

AbstractInnovations relating to the consumption of hard prey are implicated in ecological shifts in marine ecosystems as early as the mid-Paleozoic. Lungfishes represent the first and longest-ranging lineage of durophagous vertebrates, but how and when the various feeding specializations of this group arose remain unclear. Two exceptionally preserved fossils of the Early Devonian lobe-finned fishYoungolepisreveal the origin of the specialized lungfish feeding mechanism.Youngolepishas a radically restructured palate, reorienting jaw muscles for optimal force transition, coupled with radiating entopterygoid tooth rows like those of lungfish toothplates. This triturating surface occurs in conjunction with marginal dentition and blunt coronoid fangs, suggesting a role in crushing rather than piercing prey. Bayesian tip-dating analyses incorporating these morphological data indicate that the complete suite of lungfish feeding specializations may have arisen in as little as 7 million years, representing one of the most striking episodes of innovation during the initial evolutionary radiations of bony fishes.
The right bug in the right place: opportunities for bacterial vaginosis treatment
Authors: Wu Shengru , Hugerth Luisa Warchavchik , Schuppe-Koistinen Ina , Du Juan 
Published: May 2022

AbstractBacterial vaginosis (BV) is a condition in which the vaginal microbiome presents an overgrowth of obligate and facultative anaerobes, which disturbs the vaginal microbiome balance. BV is a common and recurring vaginal infection among women of reproductive age and is associated with adverse health outcomes and a decreased quality of life. The current recommended first-line treatment for BV is antibiotics, despite the high recurrence rate. Live biopharmaceutical products/probiotics and vaginal microbiome transplantation (VMT) have also been tested in clinical trials for BV. In this review, we discuss the advantages and challenges of current BV treatments and interventions. Furthermore, we provide our understanding of why current clinical trials with probiotics have had mixed results, which is mainly due to not administering the correct bacteria to the correct body site. Here, we propose a great opportunity for large clinical trials with probiotic strains isolated from the vaginal tract (e.g., Lactobacillus crispatus) and administered directly into the vagina after pretreatment.
Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer
Authors: Saunus Jodi M. , De Luca Xavier M. , Northwood Korinne , Raghavendra Ashwini , Hasson Alexander , McCart Reed Amy E. , Lim Malcolm , Lal Samir , Vargas A. Cristina , Kutasovic Jamie R. , Dalley Andrew J. , Miranda Mariska , Kalaw Emarene , Kalita-de Croft Priyakshi , Gresshoff Irma , Al-Ejeh Fares , Gee Julia M. W. , Ormandy Chris , Khanna Kum Kum , Beesley Jonathan , Chenevix-Trench Georgia , Green Andrew R. , Rakha Emad A. , Ellis Ian O. , Nicolau Dan V. , Simpson Peter T. , Lakhani Sunil R. 
Published: May 2022

AbstractIntratumoral heterogeneity is caused by genomic instability and phenotypic plasticity, but how these features co-evolve remains unclear. SOX10 is a neural crest stem cell (NCSC) specifier and candidate mediator of phenotypic plasticity in cancer. We investigated its relevance in breast cancer by immunophenotyping 21 normal breast and 1860 tumour samples. Nuclear SOX10 was detected in normal mammary luminal progenitor cells, the histogenic origin of most TNBCs. In tumours, nuclear SOX10 was almost exclusive to TNBC, and predicted poorer outcome amongst cross-sectional (p = 0.0015, hazard ratio 2.02, n = 224) and metaplastic (p = 0.04, n = 66) cases. To understand SOX10’s influence over the transcriptome during the transition from normal to malignant states, we performed a systems-level analysis of co-expression data, de-noising the networks with an eigen-decomposition method. This identified a core module in SOX10’s normal mammary epithelial network that becomes rewired to NCSC genes in TNBC. Crucially, this reprogramming was proportional to genome-wide promoter methylation loss, particularly at lineage-specifying CpG-island shores. We propose that the progressive, genome-wide methylation loss in TNBC simulates more primitive epigenome architecture, making cells vulnerable to SOX10-driven reprogramming. This study demonstrates potential utility for SOX10 as a prognostic biomarker in TNBC and provides new insights about developmental phenotypic mimicry—a major contributor to intratumoral heterogeneity.