bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem cell-based therapy for human diseases
Authors: Hoang Duc M. , Pham Phuong T. , Bach Trung Q. , Ngo Anh T. L. , Nguyen Quyen T. , Phan Trang T. K. , Nguyen Giang H. , Le Phuong T. T. , Hoang Van T. , Forsyth Nicholas R. , Heke Michael , Nguyen Liem Thanh 
Published: August 2022

AbstractRecent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.
Oxidative stress-mediated mitochondrial fission promotes hepatic stellate cell activation via stimulating oxidative phosphorylation
Authors: Zhou Yanni , Long Dan , Zhao Ying , Li Shengfu , Liang Yan , Wan Lin , Zhang Jingyao , Xue Fulai , Feng Li 
Published: August 2022

AbstractPrevious studies have demonstrated dysregulated mitochondrial dynamics in fibrotic livers and hepatocytes. Little is currently known about how mitochondrial dynamics are involved, nor is it clear how mitochondrial dynamics participate in hepatic stellate cell (HSC) activation. In the present study, we investigated the role of mitochondrial dynamics in HSC activation and the underlying mechanisms. We verified that mitochondrial fission was enhanced in human and mouse fibrotic livers and active HSCs. Moreover, increased mitochondrial fission driven by fis1 overexpression could promote HSC activation. Inhibiting mitochondrial fission using mitochondrial fission inhibitor-1 (Mdivi-1) could inhibit activation and induce apoptosis of active HSCs, indicating that increased mitochondrial fission is essential for HSC activation. Mdivi-1 treatment also induced apoptosis in active HSCs in vivo and thus ameliorated CCl4-induced liver fibrosis. We also found that oxidative phosphorylation (OxPhos) was increased in active HSCs, and OxPhos inhibitors inhibited activation and induced apoptosis in active HSCs. Moreover, increasing mitochondrial fission upregulated OxPhos, while inhibiting mitochondrial fission downregulated OxPhos, suggesting that mitochondrial fission stimulates OxPhos during HSC activation. Next, we found that inhibition of oxidative stress using mitoquinone mesylate (mitoQ) and Tempol inhibited mitochondrial fission and OxPhos and induced apoptosis in active HSCs, suggesting that oxidative stress contributes to excessive mitochondrial fission during HSC activation. In conclusion, our study revealed that oxidative stress contributes to enhanced mitochondrial fission, which triggers OxPhos during HSC activation. Importantly, inhibiting mitochondrial fission has huge prospects for alleviating liver fibrosis by eliminating active HSCs.
The CRTC-CREB axis functions as a transcriptional sensor to protect against proteotoxic stress in Drosophila
Authors: Yin Youjie , Ma Peng , Wang Saifei , Zhang Yao , Han Ruolei , Huo Chunyu , Wu Meixian , Deng Hansong 
Published: August 2022

AbstractcAMP Responsible Element Binding Protein (CREB) is an evolutionarily conserved transcriptional factor that regulates cell growth, synaptic plasticity and so on. In this study, we unexpectedly found proteasome inhibitors, such as MLN2238, robustly increase CREB activity in adult flies through a large-scale compound screening. Mechanistically, reactive oxidative species (ROS) generated by proteasome inhibition are required and sufficient to promote CREB activity through c-Jun N-terminal kinase (JNK). In 293 T cells, JNK activation by MLN2238 is also required for increase of CREB phosphorylation at Ser133. Meanwhile, transcriptome analysis in fly intestine identified a group of genes involved in redox and proteostatic regulation are augmented by overexpressing CRTC (CREB-regulated transcriptional coactivator). Intriguingly, CRTC overexpression in muscles robustly restores protein folding and proteasomal activity in a fly Huntington’s disease (HD) model, and ameliorates HD related pathogenesis, such as protein aggregates, motility, and lifespan. Moreover, CREB activity increases during aging, and further enhances its activity can suppress protein aggregates in aged muscles. Together, our results identified CRTC/CREB downstream ROS/JNK signaling as a conserved sensor to tackle oxidative and proteotoxic stresses. Boosting CRTC/CREB activity is a potential therapeutic strategy to treat aging related protein aggregation diseases.
USP22 controls type III interferon signaling and SARS-CoV-2 infection through activation of STING
Authors: Karlowitz Rebekka , Stanifer Megan L. , Roedig Jens , Andrieux Geoffroy , Bojkova Denisa , Bechtel Marco , Smith Sonja , Kowald Lisa , Schubert Ralf , Boerries Melanie , Cinatl Jindrich , Boulant Steeve , van Wijk Sjoerd J. L. 
Published: August 2022

AbstractPattern recognition receptors (PRRs) and interferons (IFNs) serve as essential antiviral defense against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Type III IFNs (IFN-λ) exhibit cell-type specific and long-lasting functions in auto-inflammation, tumorigenesis, and antiviral defense. Here, we identify the deubiquitinating enzyme USP22 as central regulator of basal IFN-λ secretion and SARS-CoV-2 infections in human intestinal epithelial cells (hIECs). USP22-deficient hIECs strongly upregulate genes involved in IFN signaling and viral defense, including numerous IFN-stimulated genes (ISGs), with increased secretion of IFN-λ and enhanced STAT1 signaling, even in the absence of exogenous IFNs or viral infection. Interestingly, USP22 controls basal and 2′3′-cGAMP-induced STING activation and loss of STING reversed STAT activation and ISG and IFN-λ expression. Intriguingly, USP22-deficient hIECs are protected against SARS-CoV-2 infection, viral replication, and the formation of de novo infectious particles, in a STING-dependent manner. These findings reveal USP22 as central host regulator of STING and type III IFN signaling, with important implications for SARS-CoV-2 infection and antiviral defense.
Intermittent hypoxia-induced METTL3 downregulation facilitates MGLL-mediated lipolysis of adipocytes in OSAS
Authors: Huang Xiuji , Huang Xuming , Guo Haiyan , Li Jin , Zhou Chunxia , Huang Yuanli , Lai Chunliu , Zeng Wan , Tan Xiaozhen , Niu Lihong , Li Hui , Qi Jian , Xie Canmao 
Published: August 2022

AbstractIntermittent hypoxia (IH) is the core pathological feature of obstructive sleep apnea syndrome (OSAS), and insulin resistance (IR) is the most common metabolic complication of OSAS. Studies have shown that the levels of free fatty acids (FFAs), which are mainly released from adipocytes by lipolysis, are elevated in OSAS and play an important role in the development of IR. However, whether and how IH regulates adipocyte lipolysis in OSAS is not clear. Here, we revealed that the apnea hypopnea index was positively correlated with the serum levels of FFAs and FFA release from adipocytes in OSAS. In addition, IH facilitated lipolysis and FFA release from adipocytes by downregulating the level of METTL3. METTL3 downregulation impaired N6-methyladenosine (m6A) levels in MGLL mRNA and reduced MGLL expression, thereby promoting lipolysis. In addition, we identified YTHDF2 as the m6A reader that interacts with MGLL mRNA, accelerating its degradation. Furthermore, our data showed reduced levels of METTL3 and elevated levels of MGLL in the adipose tissues of OSAS patients and indicated an effect of METTL3 on lowering FFA levels and improving IR in rats with chronic IH. In conclusion, our study provides new insights into the development and treatment of IR in OSAS.
Data-driven load profiles and the dynamics of residential electricity consumption
Authors: Anvari Mehrnaz , Proedrou Elisavet , Schäfer Benjamin , Beck Christian , Kantz Holger , Timme Marc 
Published: August 2022

AbstractThe dynamics of power consumption constitutes an essential building block for planning and operating sustainable energy systems. Whereas variations in the dynamics of renewable energy generation are reasonably well studied, a deeper understanding of the variations in consumption dynamics is still missing. Here, we analyse highly resolved residential electricity consumption data of Austrian, German and UK households and propose a generally applicable data-driven load model. Specifically, we disentangle the average demand profiles from the demand fluctuations based purely on time series data. We introduce a stochastic model to quantitatively capture the highly intermittent demand fluctuations. Thereby, we offer a better understanding of demand dynamics, in particular its fluctuations, and provide general tools for disentangling mean demand and fluctuations for any given system, going beyond the standard load profile (SLP). Our insights on the demand dynamics may support planning and operating future-compliant (micro) grids in maintaining supply-demand balance.
Three-dimensional imaging of waves and floes in the marginal ice zone during a cyclone
Authors: Alberello Alberto , Bennetts Luke G. , Onorato Miguel , Vichi Marcello , MacHutchon Keith , Eayrs Clare , Ntamba Butteur Ntamba , Benetazzo Alvise , Bergamasco Filippo , Nelli Filippo , Pattani Rohinee , Clarke Hans , Tersigni Ippolita , Toffoli Alessandro 
Published: August 2022

AbstractThe marginal ice zone is the dynamic interface between the open ocean and consolidated inner pack ice. Surface gravity waves regulate marginal ice zone extent and properties, and, hence, atmosphere-ocean fluxes and ice advance/retreat. Over the past decade, seminal experimental campaigns have generated much needed measurements of wave evolution in the marginal ice zone, which, notwithstanding the prominent knowledge gaps that remain, are underpinning major advances in understanding the region’s role in the climate system. Here, we report three-dimensional imaging of waves from a moving vessel and simultaneous imaging of floe sizes, with the potential to enhance the marginal ice zone database substantially. The images give the direction–frequency wave spectrum, which we combine with concurrent measurements of wind speeds and reanalysis products to reveal the complex multi-component wind-plus-swell nature of a cyclone-driven wave field, and quantify evolution of large-amplitude waves in sea ice.
Narrative thinking lingers in spontaneous thought
Authors: Bellana Buddhika , Mahabal Abhijit , Honey Christopher J. 
Published: August 2022

AbstractSome experiences linger in mind, spontaneously returning to our thoughts for minutes after their conclusion. Other experiences fall out of mind immediately. It remains unclear why. We hypothesize that an input is more likely to persist in our thoughts when it has been deeply processed: when we have extracted its situational meaning rather than its physical properties or low-level semantics. Here, participants read sequences of words with different levels of coherence (word-, sentence-, or narrative-level). We probe participants’ spontaneous thoughts via free word association, before and after reading. By measuring lingering subjectively (via self-report) and objectively (via changes in free association content), we find that information lingers when it is coherent at the narrative level. Furthermore, and an individual’s feeling of transportation into reading material predicts lingering better than the material’s objective coherence. Thus, our thoughts in the present moment echo prior experiences that have been incorporated into deeper, narrative forms of thinking.
The superconductivity of Sr2RuO4 under c-axis uniaxial stress
Authors: Jerzembeck Fabian , Røising Henrik S. , Steppke Alexander , Rosner Helge , Sokolov Dmitry A. , Kikugawa Naoki , Scaffidi Thomas , Simon Steven H. , Mackenzie Andrew P. , Hicks Clifford W. 
Published: August 2022

AbstractApplying in-plane uniaxial pressure to strongly correlated low-dimensional systems has been shown to tune the electronic structure dramatically. For example, the unconventional superconductor Sr2RuO4 can be tuned through a single Van Hove point, resulting in strong enhancement of both Tc and Hc2. Out-of-plane (c axis) uniaxial pressure is expected to tune the quasi-two-dimensional structure even more strongly, by pushing it towards two Van Hove points simultaneously. Here, we achieve a record uniaxial stress of 3.2 GPa along the c axis of Sr2RuO4. Hc2 increases, as expected for increasing density of states, but unexpectedly Tc falls. As a first attempt to explain this result, we present three-dimensional calculations in the weak interaction limit. We find that within the weak-coupling framework there is no single order parameter that can account for the contrasting effects of in-plane versus c-axis uniaxial stress, which makes this new result a strong constraint on theories of the superconductivity of Sr2RuO4.
PCGF6 controls neuroectoderm specification of human pluripotent stem cells by activating SOX2 expression
Authors: Lan Xianchun , Ding Song , Zhang Tianzhe , Yi Ying , Li Conghui , Jin Wenwen , Chen Jian , Liang Kaiwei , Wang Hengbin , Jiang Wei 
Published: August 2022

AbstractPolycomb group (PcG) proteins are known to repress developmental genes during embryonic development and tissue homeostasis. Here, we report that PCGF6 controls neuroectoderm specification of human pluripotent stem cells (PSCs) by activating SOX2 gene. Human PSCs with PCGF6 depletion display impaired neuroectoderm differentiation coupled with increased mesendoderm outcomes. Transcriptome analysis reveals that de-repression of the WNT/β-catenin signaling pathway is responsible for the differentiation of PSC toward the mesendodermal lineage. Interestingly, PCGF6 and MYC directly interact and co-occupy a distal regulatory element of SOX2 to activate SOX2 expression, which likely accounts for the regulation in neuroectoderm differentiation. Supporting this notion, genomic deletion of the SOX2-regulatory element phenocopies the impaired neuroectoderm differentiation, while overexpressing SOX2 rescues the neuroectoderm phenotype caused by PCGF6-depletion. Together, our study reveals that PCGF6 can function as lineage switcher between mesendoderm and neuroectoderm in human PSCs by both suppression and activation mechanisms.
Realization of unpinned two-dimensional dirac states in antimony atomic layers
Authors: Lu Qiangsheng , Cook Jacob , Zhang Xiaoqian , Chen Kyle Y. , Snyder Matthew , Nguyen Duy Tung , Reddy P. V. Sreenivasa , Qin Bingchao , Zhan Shaoping , Zhao Li-Dong , Kowalczyk Pawel J. , Brown Simon A. , Chiang Tai-Chang , Yang Shengyuan A. , Chang Tay-Rong , Bian Guang 
Published: August 2022

AbstractTwo-dimensional (2D) Dirac states with linear dispersion have been observed in graphene and on the surface of topological insulators. 2D Dirac states discovered so far are exclusively pinned at high-symmetry points of the Brillouin zone, for example, surface Dirac states at $$\overline{{{\Gamma }}}$$

Γ

¯

in topological insulators Bi2Se(Te)3 and Dirac cones at K and $$K^{\prime}$$

K

′

points in graphene. The low-energy dispersion of those Dirac states are isotropic due to the constraints of crystal symmetries. In this work, we report the observation of novel 2D Dirac states in antimony atomic layers with phosphorene structure. The Dirac states in the antimony films are located at generic momentum points. This unpinned nature enables versatile ways such as lattice strains to control the locations of the Dirac points in momentum space. In addition, dispersions around the unpinned Dirac points are highly anisotropic due to the reduced symmetry of generic momentum points. The exotic properties of unpinned Dirac states make antimony atomic layers a new type of 2D Dirac semimetals that are distinct from graphene.
Molecular mechanism for the synchronized electrostatic coacervation and co-aggregation of alpha-synuclein and tau
Authors: Gracia Pablo , Polanco David , Tarancón-Díez Jorge , Serra Ilenia , Bracci Maruan , Oroz Javier , Laurents Douglas V. , García Inés , Cremades Nunilo 
Published: August 2022

AbstractAmyloid aggregation of α-synuclein (αS) is the hallmark of Parkinson’s disease and other synucleinopathies. Recently, Tau protein, generally associated with Alzheimer’s disease, has been linked to αS pathology and observed to co-localize in αS-rich disease inclusions, although the molecular mechanisms for the co-aggregation of both proteins remain elusive. We report here that αS phase-separates into liquid condensates by electrostatic complex coacervation with positively charged polypeptides such as Tau. Condensates undergo either fast gelation or coalescence followed by slow amyloid aggregation depending on the affinity of αS for the poly-cation and the rate of valence exhaustion of the condensate network. By combining a set of advanced biophysical techniques, we have been able to characterize αS/Tau liquid-liquid phase separation and identified key factors that lead to the formation of hetero-aggregates containing both proteins in the interior of the liquid protein condensates.
A non-Hermitian optical atomic mirror
Authors: Wang Yi-Cheng , You Jhih-Shih , Jen H. H. 
Published: August 2022

AbstractExplorations of symmetry and topology have led to important breakthroughs in quantum optics, but much richer behaviors arise from the non-Hermitian nature of light-matter interactions. A high-reflectivity, non-Hermitian optical mirror can be realized by a two-dimensional subwavelength array of neutral atoms near the cooperative resonance associated with the collective dipole modes. Here we show that exceptional points develop from a nondefective degeneracy by lowering the crystal symmetry of a square atomic lattice, and dispersive bulk Fermi arcs that originate from exceptional points are truncated by the light cone. From its nontrivial energy spectra topology, we demonstrate that the geometry-dependent non-Hermitian skin effect emerges in a ribbon geometry. Furthermore, skin modes localized at a boundary show a scale-free behavior that stems from the long-range interaction and whose mechanism goes beyond the framework of non-Bloch band theory. Our work opens the door to the study of the interplay among non-Hermiticity, topology, and long-range interaction.
Low-voltage ultrafast nonvolatile memory via direct charge injection through a threshold resistive-switching layer
Authors: Li Yuan , Zhang Zhi Cheng , Li Jiaqiang , Chen Xu-Dong , Kong Ya , Wang Fu-Dong , Zhang Guo-Xin , Lu Tong-Bu , Zhang Jin 
Published: August 2022

AbstractThe explosion in demand for massive data processing and storage requires revolutionary memory technologies featuring ultrahigh speed, ultralong retention, ultrahigh capacity and ultralow energy consumption. Although a breakthrough in ultrafast floating-gate memory has been achieved very recently, it still suffers a high operation voltage (tens of volts) due to the Fowler–Nordheim tunnelling mechanism. It is still a great challenge to realize ultrafast nonvolatile storage with low operation voltage. Here we propose a floating-gate memory with a structure of MoS2/hBN/MoS2/graphdiyne oxide/WSe2, in which a threshold switching layer, graphdiyne oxide, instead of a dielectric blocking layer in conventional floating-gate memories, is used to connect the floating gate and control gate. The volatile threshold switching characteristic of graphdiyne oxide allows the direct charge injection from control gate to floating gate by applying a nanosecond voltage pulse (20 ns) with low magnitude (2 V), and restricts the injected charges in floating gate for a long-term retention (10 years) after the pulse. The high operation speed and low voltage endow the device with an ultralow energy consumption of 10 fJ. These results demonstrate a new strategy to develop next-generation high-speed low-energy nonvolatile memory.
Harmol promotes α-synuclein degradation and improves motor impairment in Parkinson’s models via regulating autophagy-lysosome pathway
Authors: Xu Jie , Ao Yun-Lin , Huang Chunhui , Song Xiubao , Zhang Guiliang , Cui Wei , Wang Yuqiang , Zhang Xiao-Qi , Zhang Zaijun 
Published: August 2022

AbstractThe abnormal accumulation of α-synuclein (α-syn) is a crucial factor for the onset and pathogenesis of Parkinson’s disease (PD), and the autophagy-lysosome pathway (ALP) contributes to α-syn turnover. AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) regulate autophagy by initiating the macroautophagy cascade and promoting lysosomal biogenesis via increased transcription factor EB (TFEB) activity. Hence, activation of AMPK-mTOR-TFEB axis-mediated autophagy might promote α-syn clearance in PD. Harmol is a β-carboline alkaloid that has been extensively studied in a variety of diseases but rarely in PD models. In this study, we aimed to evaluate the effect and underlying mechanism of harmol in PD models in vitro and in vivo. We show that harmol reduces α-syn via ALP in a dose- and time-dependent manner in cell model that overexpressed human A53T mutant α-syn. We also demonstrate that harmol promotes the translocation of TFEB into the nucleus and accompanies the restoration of autophagic flux and lysosomal biogenesis. Importantly, harmol improves motor impairment and down-regulates α-syn levels in the substantia nigra and prefrontal cortex in the α-syn transgenic mice model. Further studies revealed that harmol might activate ALP through AMPK-mTOR-TFEB to promote α-syn clearance. These in vitro and in vivo improvements demonstrate that harmol activates the AMPK-mTOR-TFEB mediated ALP pathway, resulting in reduced α-syn, and suggesting the potential benefit of harmol in the treatment of PD.