bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell‐Derived White Adipose Tissue Microphysiological Systems
Authors: Qi Lin , Zushin Peter‐James H. , Chang Ching‐Fang , Lee Yue Tung , Alba Diana L. , Koliwad Suneil K. , Stahl Andreas 
Published: November 2021

AbstractImpaired white adipose tissue (WAT) function has been recognized as a critical early event in obesity‐driven disorders, but high buoyancy, fragility, and heterogeneity of primary adipocytes have largely prevented their use in drug discovery efforts highlighting the need for human stem cell‐based approaches. Here, human stem cells are utilized to derive metabolically functional 3D adipose tissue (iADIPO) in a microphysiological system (MPS). Surprisingly, previously reported WAT differentiation approaches create insulin resistant WAT ill‐suited for type‐2 diabetes mellitus drug discovery. Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsive iADIPO are derived. Through concomitant optimization of an iADIPO‐MPS, it is abled to obtain WAT with more unilocular and significantly larger (≈40%) lipid droplets compared to iADIPO in 2D culture, increased insulin responsiveness of glucose uptake (≈2–3 fold), fatty acid uptake (≈3–6 fold), and ≈40% suppressing of stimulated lipolysis giving a dynamic range that is competent to current in vivo and ex vivo models, allowing to identify both insulin sensitizers and desensitizers.
Acidic TME‐Responsive Nano‐Bi2Se3@MnCaP as a NIR‐II‐Triggered Free Radical Generator for Hypoxia‐Irrelevant Phototherapy with High Specificity and Immunogenicity
Authors: Li Yongcan , Yu Honglian , Ren Junjie , Lu Guangjie , Cao Yang , Xu Zhigang , Kang Yuejun , Xue Peng 
Published: November 2021

AbstractHere, acidic tumor microenvironment (TME)‐responsive nano‐Bi2Se3@MnCaP, as a near‐infrared‐II (NIR‐II) biowindow‐triggered free radical generator for hypoxia‑irrelevant phototherapy, is elaborately developed by biomimetic mineralization of MnCaP onto 2, 2′‐azobis[2‐(2‐imidazolin‐2‐yl)propane] dihydrochloride (AIPH)‐loaded mesoporous nano‐Bi2Se3 to form Bi2Se3/AIPH@MnCaP (BAM). Surface mineral of MnCaP can be degraded under mild acidity, leading to the release of both Mn2+ and AIPH. The leached Mn2+ not only facilitates chemodynamic therapy (CDT) via hydroxyl radicals (•OH) from Mn2+‐mediated Fenton‐like reaction but also acts as contrast agent for magnetic resonance imaging. In another aspect, the splendid photothermal conversion capacity of BAM enables a rapid hyperthermia generation under NIR‐II laser irradiation for photothermal therapy (PTT). Simultaneously, the local thermal shock can induce the disintegration of AIPH to generate alkyl radicals (•R) for thermodynamic therapy (TDT) and accelerate Fenton‐like reaction rate to augment CDT efficacy. The strong synergistic effects from cooperative CDT/PTT/TDT are applied to 4T1 tumor suppression with minimal side effects. Importantly, the combination therapy can effectively trigger immunogenetic cell death and enhance antitumor immunity for systemic tumor eradication. Collectively, this proof‐of‐concept study demonstrates a more efficacious and safer strategy for oxygenation‐independent phototherapy, which holds a good potential for clinical translation in cancer management.
Highly Conductive Strong Healable Nanocomposites via Diels–Alder Reaction and Filler‐Polymer Covalent Bifunctionalization
Authors: Faseela K.P. , Benny Aby Paul , Kim Yongjun , Baik Seunghyun 
Published: November 2021

AbstractHealable stretchable conductive nanocomposites have received considerable attention. However, there has been a trade‐off between the filler‐induced electrical conductivity (σ) and polymer‐driven mechanical strength. Here significant enhancements in both σ and mechanical strength by designing reversible covalent bonding of the polymer matrix and filler‐matrix covalent bifunctionalization are reported. A polystyrene‐block‐poly(ethylene‐ran‐butylene)‐block‐polystyrene grafted with maleic anhydride forms the strong reversible covalent bonding with furfuryl alcohol through the Diels–Alder reaction. Small (7.5 nm) and medium (117 nm) nanosatellite particles are generated by in situ etching of silver flakes, enabling electron tunneling‐assisted percolation. The filler‐polymer covalent bifunctionalization is achieved by 3‐mercaptopropanoic acid. Altogether, this results in high σ (108 300 S m−1) and tensile strength (16.4 MPa), breaking the trade‐off behavior. A nearly perfect (≈100%) healing efficiency is achieved in both σ and tensile strength. The conductive nanocomposite figure of merit (1.78 T Pa S m−1), defined by the product of σ and tensile strength, is orders of magnitude greater than the data in literature. The nanocomposite may find applications in healable strain sensors and electronic materials.
Hierarchical Atomic Layer Deposited V2O5 on 3D Printed Nanocarbon Electrodes for High‐Performance Aqueous Zinc‐Ion Batteries
Authors: Gao Wanli , Michalička Jan , Pumera Martin 
Published: November 2021

AbstractAqueous rechargeable zinc‐ion batteries (ARZIBs) are promising energy storage systems owing to their ecofriendliness, safety, and cost‐efficiency. However, the sluggish Zn2+ diffusion kinetics originated from its inherent large atomic mass and high polarization remains an ongoing challenge. To this end, electrodes with 3D architectures and high porosity are highly desired. This work reports a rational design and fabrication of hierarchical core–shell structured cathodes (3D@V2O5) for ARZIBs by integrating fused deposition modeling (FDM) 3D‐printing with atomic layer deposition (ALD). The 3D‐printed porous carbon network provides an entangled electron conductive core and interconnected ion diffusion channels, whereas ALD‐coated V2O5 serves as an active shell without sacrificing the porosity for facilitated Zn2+ diffusion. This endows the 3D@V2O5 cathode with high specific capacity (425 mAh g−1 at 0.3 A g−1), competitive energy and power densities (316 Wh Kg−1 at 213 W kg−1 and 163 Wh Kg−1 at 3400 W kg−1), and good rate performance (221 mAh g−1 at 4.8 A g−1). The developed 3D@V2O5 cathode provides a promising model for customized and scalable battery electrode engineering technology. As the ALD‐coated layer determines the functional properties, the proposed strategy shows a promising prospect of FDM 3D printing using 1D carbon materials for future energy storage.
Prospects of Electrode Materials and Electrolytes for Practical Potassium‐Based Batteries
Authors: Fan Ling , Hu Yanyao , Rao Apparao M. , Zhou Jiang , Hou Zhaohui , Wang Chengxin , Lu Bingan 
Published: November 2021

AbstractPotassium‐ion batteries (PIBs) have attracted tremendous attention because of their high energy density and low‐cost. As such, much effort has focused on developing electrode materials and electrolytes for PIBs at the material levels. This review begins with an overview of the high‐performance electrode materials and electrolytes, and then evaluates their prospects and challenges for practical PIBs to penetrate the market. The current status of PIBs for safe operation, energy density, power density, cyclability, and sustainability is discussed and future studies for electrode materials, electrolytes, and electrode‐electrolyte interfaces are identified. It is anticipated that this review will motivate research and development to fill existing gaps for practical potassium‐based full batteries so that they may be commercialized in the near future.
The location of urban healthcare services: Evidence from Phoenix Yelp reviews
Authors: Matti Josh , Ruseski Jane E. 
Published: November 2021

AbstractThe U.S. healthcare sector is a large and important industry. However, relatively little is known about the localization and colocalization patterns of healthcare services within an urban area. By using Yelp data from over 3000 healthcare service establishments in the Phoenix area, this paper applies a recent spatial econometric technique to the analysis of healthcare services. The results reveal that spatial concentration varies across distances and types of healthcare services. Localization is more prevalent at closer distances, and general practitioners tend to be more dispersed than specialists. Colocalization with hospitals is most likely for specialists while family practices and dentistry services tend to locate away from hospitals. Different types of location patterns across different types of healthcare services are relevant for informing policies addressing healthcare access and competition in healthcare markets.
Direct Neuronal Differentiation of Neural Stem Cells for Spinal Cord Injury Repair
Authors: Xue Weiwei , Fan Caixia , Chen Bing , Zhao Yannan , Xiao Zhifeng , Dai Jianwu 
Published: November 2021

AbstractSpinal cord injury (SCI) typically results in long-lasting functional deficits, largely due to primary and secondary wh ite matter damage at the site of injury. The transplantation of neural stem cells (NSCs) has shown promise for re-establishing communications between separated regions of the spinal cord through the insertion of new neurons between the injured axons and target neurons. However, the inhibitory microenvironment that develops after SCI often causes endogenous and transplanted NSCs to differentiate into glial cells rather than neurons. Functional biomaterials have been shown to mitigate the effects of the adverse SCI microenvironment and promote the neuronal differentiation of NSCs. A clear understanding of the mechanisms of neuronal differentiation within the injury-induced microenvironment would likely allow for the development of treatment strategies designed to promote the innate ability of NSCs to differentiate into neurons. The increased differentiation of neurons may contribute to relay formation, facilitating functional recovery after SCI. In this review, we summarize current strategies used to enhance the neuronal differentiation of NSCs through the reconstruction of the SCI microenvironment and to improve the intrinsic neuronal differentiation abilities of NSCs, which is significant for SCI repair.
Human Placenta Mesenchymal Stem Cell Protection in Ischemic Stroke is Angiotensin Converting Enzyme-2 and Masr Receptor-Dependent
Authors: Barzegar Mansoureh , Vital Shantel , Stokes Karen Y. , Wang Yuping , Yun Jungmi Winny , White Luke A. , Chernyshev Oleg , Kelley Roger E. , Alexander Jonathan S. 
Published: November 2021

Abstract
Thromboembolic stroke remains a major cause of neurological disability and death. Current stroke treatments (aspirin, tissue plasminogen activator) are significantly limited by timing and risks for hemorrhage which have driven researchers to explore other approaches. Stem cell-based therapy appears to be an effective option for ischemic stroke. Besides trans-differentiation into neural cells, stem cells also provide acute protection via paracrine signaling pathways through which releasing neuroprotective factors. We previously reported that intraperitoneal administration of human placenta mesenchymal stem cell (hPMSC) therapy upon reperfusion significantly protected the brain against middle cerebral artery occlusion (MCAO)-induced injury. In the present study, we specifically investigated the role of hPMSC-derived angiotensin converting enzyme-2 (ACE-2) in protection of MCAO-induced brain injury by measurement of brain tissue viability, cerebral blood flow, and neurological score. Here, we report for the first time that hPMSC expressing substantial amount of ACE-2, which mediates hPMSC protection in the MCAO model. Strikingly, we found that the protective effects of hPMSC in MCAO-induced brain injury could be attenuated by pretreatment of hPMSCs with MLN-4760, a specific inhibitor of ACE-2 activity, or by transfection of hPMSCs with ACE-2-shRNA-lentivirus. The hPMSC-derived ACE-2 specific protective mechanism was further demonstrated by administration of PD123319, an Angiotensin type-2 receptor antagonist, or A779, a MasR antagonist. Importantly, our study demonstrated that the protective effects of hPMSC in experimental stroke are ACE-2/MasR dependent and this signaling pathway represents an innovative and highly promising approach for targeted stroke therapy.
Transient Receptor Potential Vanilloid 4 as a Regulator of Induced Pluripotent Stem Cell Chondrogenesis
Authors: Willard Vincent P. , Leddy Holly A. , Palmer Daniel , Wu Chia-Lung , Liedtke Wolfgang , Guilak Farshid 
Published: November 2021

Abstract
Transient receptor potential vanilloid 4 (TRPV4) is a polymodal calcium-permeable cation channel that is highly expressed in cartilage and is sensitive to a variety of extracellular stimuli. The expression of this channel has been associated with the process of chondrogenesis in adult stem cells as well as several cell lines. Here, we used a chondrogenic reporter (Col2a1-GFP) in murine induced pluripotent stem cells (iPSCs) to examine the hypothesis that TRPV4 serves as both a marker and a regulator of chondrogenesis. Over 21 days of chondrogenesis, iPSCs showed significant increases in Trpv4 expression along with the standard chondrogenic gene markers Sox9, Acan, and Col2a1, particularly in the green fluorescent protein positive (GFP+) chondroprogenitor subpopulation. Increased gene expression for Trpv4 was also reflected by the presence of TRPV4 protein and functional Ca2+ signaling. Daily activation of TRPV4 using the specific agonist GSK1016790A resulted in significant increases in cartilaginous matrix production. An improved understanding of the role of TRPV4 in chondrogenesis may provide new insights into the development of new therapeutic approaches for diseases of cartilage, such as osteoarthritis, or channelopathies and hereditary disorders that affect cartilage during development. Harnessing the role of TRPV4 in chondrogenesis may also provide a novel approach for accelerating stem cell differentiation in functional tissue engineering of cartilage replacements for joint repair.
Three-Dimensional Migration of Human Amniotic Fluid Stem Cells Involves Mesenchymal and Amoeboid Modes and is Regulated by mTORC1
Authors: Rosner Margit , Hengstschläger Markus 
Published: November 2021

Abstract
Three-dimensional (3D) cell migration is an integral part of many physiologic processes. Although being well studied in the context of adult tissue homeostasis and cancer development, remarkably little is known about the invasive behavior of human stem cells. Using two different kinds of invasion assays, this study aimed at investigating and characterizing the 3D migratory capacity of human amniotic fluid stem cells (hAFSCs), a well-established fetal stem cell type. Eight hAFSC lines were found to harbor pronounced potential to penetrate basement membrane (BM)-like matrices. Morphological examination and inhibitor approaches revealed that 3D migration of hAFSCs involves both the matrix metalloprotease-dependent mesenchymal, elongated mode and the Rho-associated protein kinase-dependent amoeboid, round mode. Moreover, hAFSCs could be shown to harbor transendothelial migration capacity and to exhibit a motility-associated marker expression pattern. Finally, the potential to cross extracellular matrix was found to be induced by mTORC1-activating growth factors and reduced by blocking mTORC1 activity. Taken together, this report provides the first demonstration that human stem cells exhibit mTORC1-dependent invasive capacity and can concurrently make use of mesenchymal and amoeboid 3D cell migration modes, which represents an important step toward the full biological characterization of fetal human stem cells with relevance to both developmental research and stem cell-based therapy.
Bidirectional Relationship Between Cardiac Extracellular Matrix and Cardiac Cells in Ischemic Heart Disease
Authors: Park Hyun-Ji , De Jesus Morales Kenneth J. , Bheri Sruti , Kassouf Brandon P. , Davis Michael E. 
Published: November 2021

Abstract
Ischemic heart diseases (IHDs), including myocardial infarction and cardiomyopathies, are a leading cause of mortality and morbidity worldwide. Cardiac-derived stem and progenitor cells have shown promise as a therapeutic for IHD but are limited by poor cell survival, limited retention, and rapid washout. One mechanism to address this is to encapsulate the cells in a matrix or three-dimensional construct, so as to provide structural support and better mimic the cells' physiological microenvironment during administration. More specifically, the extracellular matrix (ECM), the native cellular support network, has been a strong candidate for this purpose. Moreover, there is a strong consensus that the ECM and its residing cells, including cardiac stem cells, have a constant interplay in response to tissue development, aging, disease progression, and repair. When externally stimulated, the cells and ECM work together to mutually maintain the local homeostasis by initially altering the ECM composition and stiffness, which in turn alters the cellular response and behavior. Given this constant interplay, understanding the mechanism of bidirectional cell-ECM interaction is essential to develop better cell implantation matrices to enhance cell engraftment and cardiac tissue repair. This review summarizes current understanding in the field, elucidating the signaling mechanisms between cardiac ECM and residing cells in response to IHD onset. Furthermore, this review highlights recent advances in native ECM-mimicking cardiac matrices as a platform for modulating cardiac cell behavior and inducing cardiac repair.
Human Induced Pluripotent Stem Cell-Derived Macrophages Ameliorate Liver Fibrosis
Authors: Pouyanfard Somayeh , Meshgin Nairika , Cruz Luisjesus S. , Diggle Karin , Hashemi Hamidreza , Pham Timothy V. , Fierro Manuel , Tamayo Pablo , Fanjul Andrea , Kisseleva Tatiana , Kaufman Dan S. 
Published: November 2021

Abstract
With an increasing number of patients with degenerative hepatic diseases, such as liver fibrosis, and a limited supply of donor organs, there is an unmet need for therapies that can repair or regenerate damaged liver tissue. Treatment with macrophages that are capable of phagocytosis and anti-inflammatory activities such as secretion of matrix metalloproteinases (MMPs) provide an attractive cellular therapy approach. Human induced pluripotent stem cells (iPSCs) are capable of efficiently generating a large-scale, homogenous population of human macrophages using fully defined feeder- and serum-free differentiation protocol. Human iPSC-macrophages exhibit classical surface cell markers and phagocytic activity similar to peripheral blood-derived macrophages. Moreover, gene and cytokine expression analysis reveal that these macrophages can be efficiently polarized to pro-inflammatory M1 or anti-inflammatory M2 phenotypes in presence of LPS + IFN-γ and IL-4 + IL-13, respectively. M1 macrophages express high level of CD80, TNF-α, and IL-6 while M2 macrophages show elevated expression of CD206, CCL17, and CCL22. Here, we demonstrate that treatment of liver fibrosis with both human iPSC-derived macrophage populations and especially M2 subtype significantly reduces fibrogenic gene expression and disease associated histological markers including Sirius Red, αSMA and desmin in immunodeficient Rag2−/−γc−/− mice model, making this approach a promising cell-based avenue to ameliorate fibrosis.
The Cyclin-Like Protein SPY1 Overrides Reprogramming Induced Senescence Through EZH2 Mediated H3K27me3
Authors: Lubanska Dorota , Qemo Ingrid , Byrne Megan , Matthews Kaitlyn N. , Fifield Bre-Anne , Brown Jillian , Silva Elizabeth Fidalgo , Porter Lisa A. 
Published: November 2021

Abstract
Fully differentiated cells can be reprogrammed through ectopic expression of key transcription factors to create induced pluripotent stem cells. These cells share many characteristics of normal embryonic stem cells and have great promise in disease modeling and regenerative medicine. The process of remodeling has its limitations, including a very low efficiency due to the upregulation of many antiproliferative genes, including cyclin dependent kinase inhibitors CDKN1A and CDKN2A, which serve to protect the cell by inducing apoptotic and senescent programs. Our data reveals a unique cell cycle mechanism enabling mouse fibroblasts to repress cyclin dependent kinase inhibitors through the activation of the epigenetic regulator EZH2 by a cyclin-like protein SPY1. This data reveals that the SPY1 protein is required for reprogramming to a pluripotent state and is capable of increasing reprogramming efficiency.
Tropical fans, scattering equations and amplitudes
Authors: Drummond James , Foster Jack , Gürdoğan Ömer , Kalousios Chrysostomos 
Published: November 2021

Abstract
We describe a family of tropical fans related to Grassmannian cluster algebras. These fans are related to the kinematic space of massless scattering processes in a number of ways. For each fan associated to the Grassmannian Gr(k, n) there is a notion of a generalised ϕ3 amplitude and an associated set of scattering equations which further generalise the Gr(k, n) scattering equations that have been recently introduced. Here we focus mostly on the cases related to finite Grassmannian cluster algebras and we explain how face variables for the cluster polytopes are simply related to the scattering equations. For the Grassmannians Gr(4, n) the tropical fans we describe are related to the singularities (or symbol letters) of loop amplitudes in planar $$ \mathcal{N} $$
N
= 4 super Yang-Mills theory. We show how each choice of tropical fan leads to a natural class of polylogarithms, generalising the notion of cluster adjacency and we describe how the currently known loop data fit into this classification.
Maximally dissipative solutions for incompressible fluid dynamics
Authors: Lasarzik Robert 
Published: November 2021

AbstractWe introduce the new concept of maximally dissipative solutions for a general class of isothermal GENERIC systems. Under certain assumptions, we show that maximally dissipative solutions are well-posed as long as the bigger class of dissipative solutions is non-empty. Applying this result to the Navier–Stokes and Euler equations, we infer global well-posedness of maximally dissipative solutions for these systems. The concept of maximally dissipative solutions coincides with the concept of weak solutions as long as the weak solutions inherits enough regularity to be unique.