bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLEKHH2 binds β-arrestin1 through its FERM domain, activates FAK/PI3K/AKT phosphorylation, and promotes the malignant phenotype of non-small cell lung cancer
Authors: Wang Rui , Wang Si , Li Zhen , Luo Yuan , Zhao Yue , Han Qiang , Rong Xue-Zhu , Guo Yao-Xing , Liu Yang 
Published: October 2022

AbstractPLEKHH2 is an important FERM domain containing-protein. However, the role of PLEKHH2 in human solid tumors has not been reported yet. We report that PLEKHH2 showed enhanced cytoplasmic expression in non-small cell lung cancer (NSCLC). Its overexpression was positively correlated with high TNM stage, low differentiation, lymphatic node metastasis, and poor prognosis. In A549 and H1299 cells, high expression of PLEKHH2 significantly promoted cell proliferation, migration, invasion, and increased the expression of proliferation- and invasion-related proteins. It also enhanced the phosphorylation of FAK and promoted the activity of the PI3K/AKT pathway. Immunofluorescence and co-immunoprecipitation analyses were performed to elucidate the molecular mechanism underlying PLEKHH2-mediated regulation of proliferation and invasion in lung cancer cells. Upon transfection of full length PLEKHH2 or its FERM domain, we observed enhanced binding of PLEKHH2 to β-arrestin1, whereas FAK- β-arrestin1 binding was diminished and this led to an increase in FAK phosphorylation. PLEKHH2-mutant plasmids without the FERM domain could not effectively promote its binding to β-arrestin1, activation of FAK phosphorylation, PI3K/AKT activation, or the malignant phenotype. Our findings suggested that PLEKHH2 is an important oncogene in NSCLC. PLEKHH2 binding to β-arrestin1 through the FERM domain competitively inhibits β-arrestin1 binding to FAK, which causes the dissociation of FAK from the FAK-β-arrestin1 complex. Furthermore, the dissociation of FAK promotes its autophosphorylation, activates the PI3K/AKT signaling pathway, and subsequently promotes lung cancer cell proliferation, migration, and invasion. These results provide evidence for the potential use of PLEKHH2 inhibition as an anticancer therapy.
Mitochondrial event as an ultimate step in ferroptosis
Authors: Oh Soo-Jin , Ikeda Masataka , Ide Tomomi , Hur Kyu Yeon , Lee Myung-Shik 
Published: October 2022

AbstractIn ferroptosis, the roles of mitochondria have been controversial. To explore the role of mitochondrial events in ferroptosis, we employed mitochondrial DNA-depleted ρ0 cells that are resistant to cell death due to enhanced expression of antioxidant enzymes. Expression of mitochondrial-type GPx4 (mGPx4) but no other forms of GPx4 was increased in SK-Hep1 ρ0 cells. Likely due to high mGPx4 expression, SK-Hep1 ρ0 cells were resistant to ferroptosis by erastin inhibiting xCT channel. In contrast, SK-Hep1 ρ0 cells were susceptible to cell death by a high concentration of RSL3 imposing ferroptosis by GPx4 inhibition. Accumulation of cellular ROS and oxidized lipids was observed in erastin- or RSL3-treated SK-Hep1 ρ+ cells but not in erastin-treated SK-Hep1 ρ0 cells. Mitochondrial ROS and mitochondrial peroxidized lipids accumulated in SK-Hep1 ρ+ cells not only by RSL3 but also by erastin acting on xCT on the plasma membrane. Mitochondrial ROS quenching inhibited SK-Hep1 ρ+ cell death by erastin or a high dose of RSL3, suggesting a critical role of mitochondrial ROS in ferroptosis. Ferroptosis by erastin or RSL3 was inhibited by a more than 20-fold lower concentration of MitoQ, a mitochondrial ROS quencher, compared to DecylQ, a non-targeting counterpart. Ferroptosis of SK-Hep1 ρ+ cells by erastin or RSL3 was markedly inhibited by a VDAC inhibitor, accompanied by significantly reduced accumulation of mitochondria ROS, total peroxidized lipids, and mitochondrial peroxidized lipids, strongly supporting the role of mitochondrial events in ferroptotic death and that of VDAC in mitochondrial steps of ferroptosis induced by erastin or RSL3. SK-Hep1 ρ+ cell ferroptosis by sorafenib was also suppressed by mitochondrial ROS quenchers, accompanied by abrogation of sorafenib-induced mitochondrial ROS and mitochondrial peroxidized lipid accumulation. These results suggest that SK-Hep1 ρ0 cells are resistant to ferroptosis due to upregulation of mGPx4 expression and mitochondrial events could be the ultimate step in determining final cell fate.
Arginase: shedding light on the mechanisms and opportunities in cardiovascular diseases
Authors: Li Zhuozhuo , Wang Liwei , Ren Yuanyuan , Huang Yaoyao , Liu Wenxuan , Lv Ziwei , Qian Lu , Yu Yi , Xiong Yuyan 
Published: October 2022

AbstractArginase, a binuclear manganese metalloenzyme in the urea, catalyzes the hydrolysis of L-arginine to urea and L-ornithine. Both isoforms, arginase 1 and arginase 2 perform significant roles in the regulation of cellular functions in cardiovascular system, such as senescence, apoptosis, proliferation, inflammation, and autophagy, via a variety of mechanisms, including regulating L-arginine metabolism and activating multiple signal pathways. Furthermore, abnormal arginase activity contributes to the initiation and progression of a variety of CVDs. Therefore, targeting arginase may be a novel and promising approach for CVDs treatment. In this review, we give a comprehensive overview of the physiological and biological roles of arginase in a variety of CVDs, revealing the underlying mechanisms of arginase mediating vascular and cardiac function, as well as shedding light on the novel and promising therapeutic approaches for CVDs therapy in individuals.
Hepatocyte phosphatase DUSP22 mitigates NASH-HCC progression by targeting FAK
Authors: Ge Chenxu , Tan Jun , Dai Xianling , Kuang Qin , Zhong Shaoyu , Lai Lili , Yi Chao , Sun Yan , Luo Jing , Zhang Chufeng , Zhu Liancai , Wang Bochu , Xu Minxuan 
Published: October 2022

AbstractNonalcoholic steatohepatitis (NASH), a common clinical disease, is becoming a leading cause of hepatocellular carcinoma (HCC). Dual specificity phosphatase 22 (DUSP22, also known as JKAP or JSP-1) expressed in numerous tissues plays essential biological functions in immune responses and tumor growth. However, the effects of DUSP22 on NASH still remain unknown. Here, we find a significant decrease of DUSP22 expression in human and murine fatty liver, which is mediated by reactive oxygen species (ROS) generation. Hepatic-specific DUSP22 deletion particularly exacerbates lipid deposition, inflammatory response and fibrosis in liver, facilitating NASH and non-alcoholic fatty liver disease (NAFLD)-associated HCC progression. In contrast, transgenic over-expression, lentivirus or adeno-associated virus (AAV)-mediated DUSP22 gene therapy substantially inhibit NASH-related phenotypes and HCC development in mice. We provide mechanistic evidence that DUSP22 directly interacts with focal adhesion kinase (FAK) and restrains its phosphorylation at Tyr397 (Y397) and Y576 + Y577 residues, subsequently prohibiting downstream activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) cascades. The binding of DUSP22 to FAK and the dephosphorylation of FAK are indispensable for DUSP22-meliorated NASH progression. Collectively, our findings identify DUSP22 as a key suppressor of NASH-HCC, and underscore the DUSP22-FAK axis as a promising therapeutic target for treatment of the disease.
Spatial structure of city population growth
Authors: Reia Sandro M. , Rao P. Suresh C. , Barthelemy Marc , Ukkusuri Satish V. 
Published: October 2022

AbstractWe show here that population growth, resolved at the county level, is spatially heterogeneous both among and within the U.S. metropolitan statistical areas. Our analysis of data for over 3,100 U.S. counties reveals that annual population flows, resulting from domestic migration during the 2015–2019 period, are much larger than natural demographic growth, and are primarily responsible for this heterogeneous growth. More precisely, we show that intra-city flows are generally along a negative population density gradient, while inter-city flows are concentrated in high-density core areas. Intra-city flows are anisotropic and generally directed towards external counties of cities, driving asymmetrical urban sprawl. Such domestic migration dynamics are also responsible for tempering local population shocks by redistributing inflows within a given city. This spill-over effect leads to a smoother population dynamics at the county level, in contrast to that observed at the city level. Understanding the spatial structure of domestic migration flows is a key ingredient for analyzing their drivers and consequences, thus representing a crucial knowledge for urban policy makers and planners.
Photoredox-catalyzed C–C bond cleavage of cyclopropanes for the formation of C(sp3)–heteroatom bonds
Authors: Ge Liang , Zhang Chi , Pan Chengkai , Wang Ding-Xing , Liu Dong-Ying , Li Zhi-Qiang , Shen Pingkang , Tian Lifang , Feng Chao 
Published: October 2022

AbstractSterically congested C–O and C–N bonds are ubiquitous in natural products, pharmaceuticals, and bioactive compounds. However, the development of a general method for the efficient construction of those sterically demanding covalent bonds still remains a formidable challenge. Herein, a photoredox-driven ring-opening C(sp3)–heteroatom bond formation of arylcyclopropanes is presented, which enables the construction of structurally diversified while sterically congested dialkyl ether, alkyl ester, alcohol, amine, chloride/fluoride, azide and also thiocyanate derivatives. The selective single electron oxidation of aryl motif associated with the thermodynamic driving force from ring strain-release is the key for this transformation. By this synergistic activation mode, C–C bond cleavage of otherwise inert cyclopropane framework is successfully unlocked. Further mechanistic and computational studies disclose a complete stereoinversion upon nucleophilic attack, thus proving a concerted SN2-type ring-opening functionalization manifold, while the regioselectivity is subjected to an orbital control scenario.
Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids
Authors: Vanslambrouck Jessica M. , Wilson Sean B. , Tan Ker Sin , Groenewegen Ella , Rudraraju Rajeev , Neil Jessica , Lawlor Kynan T. , Mah Sophia , Scurr Michelle , Howden Sara E. , Subbarao Kanta , Little Melissa H. 
Published: October 2022

AbstractWhile pluripotent stem cell-derived kidney organoids are now being used to model renal disease, the proximal nephron remains immature with limited evidence for key functional solute channels. This may reflect early mispatterning of the nephrogenic mesenchyme and/or insufficient maturation. Here we show that enhanced specification to metanephric nephron progenitors results in elongated and radially aligned proximalised nephrons with distinct S1 - S3 proximal tubule cell types. Such PT-enhanced organoids possess improved albumin and organic cation uptake, appropriate KIM-1 upregulation in response to cisplatin, and improved expression of SARS-CoV-2 entry factors resulting in increased viral replication. The striking proximo-distal orientation of nephrons resulted from localized WNT antagonism originating from the organoid stromal core. PT-enhanced organoids represent an improved model to study inherited and acquired proximal tubular disease as well as drug and viral responses.
Metamaterial-enabled asymmetric negative refraction of GHz mechanical waves
Authors: Zanotto Simone , Biasiol Giorgio , Santos Paulo V. , Pitanti Alessandro 
Published: October 2022

AbstractWave refraction at an interface between different materials is a basic yet fundamental phenomenon, transversal to several scientific realms – electromagnetism, gas and fluid acoustics, solid mechanics, and possibly also matter waves. Under specific circumstances, mostly enabled by structuration below the wavelength scale, i.e., through the metamaterial approach, waves undergo negative refraction, eventually enabling superlensing and transformation optics. However, presently known negative refraction systems are symmetric, in that they cannot distinguish between positive and negative angles of incidence. Exploiting a metamaterial with an asymmetric unit cell, we demonstrate that the aforementioned symmetry can be broken, ultimately relying on the specific shape of the Bloch mode isofrequency curves. Our study specialized upon a mechanical metamaterial operating at GHz frequency, which is by itself a building block for advanced technologies such as chip-scale hybrid optomechanical and electromechanical devices. However, the phenomenon is based on general wave theory concepts, and it applies to any frequency and time scale for any kind of linear waves, provided that a suitable shaping of the isofrequency contours is implemented.
Controllable DNA hybridization by host–guest complexation-mediated ligand invasion
Authors: Xiao Lin , Wang Liang-Liang , Wu Chao-Qun , Li Han , Zhang Qiu-Long , Wang Yang , Xu Liang 
Published: October 2022

AbstractDynamic regulation of nucleic acid hybridization is fundamental for switchable nanostructures and controllable functionalities of nucleic acids in both material developments and biological regulations. In this work, we report a ligand-invasion pathway to regulate DNA hybridization based on host–guest interactions. We propose a concept of recognition handle as the ligand binding site to disrupt Watson–Crick base pairs and induce the direct dissociation of DNA duplex structures. Taking cucurbit[7]uril as the invading ligand and its guest molecules that are integrated into the nucleobase as recognition handles, we successfully achieve orthogonal and reversible manipulation of DNA duplex dissociation and recovery. Moreover, we further apply this approach of ligand-controlled nucleic acid hybridization for functional regulations of both the RNA-cleaving DNAzyme in test tubes and the antisense oligonucleotide in living cells. This ligand-invasion strategy establishes a general pathway toward dynamic control of nucleic acid structures and functionalities by supramolecular interactions.
Importance of structural hinderance in performance–stability equilibrium of organic photovoltaics
Authors: Fan Baobing , Gao Wei , Wu Xuanhao , Xia Xinxin , Wu Yue , Lin Francis R. , Fan Qunping , Lu Xinhui , Li Wen Jung , Ma Wei , Jen Alex K.-Y. 
Published: October 2022

AbstractPower conversion efficiency and long-term stability are two critical metrics for evaluating the commercial potential of organic photovoltaics. Although the field has witnessed a rapid progress of efficiency towards 19%, the intrinsic trade-off between efficiency and stability is still a challenging issue for bulk-heterojunction cells due to the very delicate crystallization dynamics of organic species. Herein, we developed a class of non-fullerene acceptors with varied side groups as an alternative to aliphatic chains. Among them, the acceptors with conjugated side groups show larger side-group torsion and more twisted backbone, however, they can deliver an efficiency as high as 18.3% in xylene-processed cells, which is among the highest values reported for non-halogenated solvent processed cells. Meanwhile, decent thermal/photo stability is realized for these acceptors containing conjugated side groups. Through the investigation of the geometry–performance–stability relationship, we highlight the importance of side-group steric hinderance of acceptors in achieving combined high-performance, stable, and eco-friendly organic photovoltaics.
A public database of thermoelectric materials and system-identified material representation for data-driven discovery
Authors: Na Gyoung S. , Chang Hyunju 
Published: October 2022

AbstractThermoelectric materials have received much attention as energy harvesting devices and power generators. However, discovering novel high-performance thermoelectric materials is challenging due to the structural diversity and complexity of the thermoelectric materials containing alloys and dopants. For the efficient data-driven discovery of novel thermoelectric materials, we constructed a public dataset that contains experimentally synthesized thermoelectric materials and their experimental thermoelectric properties. For the collected dataset, we were able to construct prediction models that achieved R2-scores greater than 0.9 in the regression problems to predict the experimentally measured thermoelectric properties from the chemical compositions of the materials. Furthermore, we devised a material descriptor for the chemical compositions of the materials to improve the extrapolation capabilities of machine learning methods. Based on transfer learning with the proposed material descriptor, we significantly improved the R2-score from 0.13 to 0.71 in predicting experimental ZTs of the materials from completely unexplored material groups.
Breaking the vicious circle—the Asthma Referral Identifier (ReferID) tool
Authors: Beekman Maarten , Hales Julie , Al-Ahmad Mona , del Olmo Ricardo , Tan Tze Lee 
Published: October 2022

AbstractAsthma is associated with a significant burden of disease, especially for patients with severe or uncontrolled asthma. Many patients with severe asthma still receive treatment in primary care settings and despite the availability of effective options, inadequate asthma treatment remains a concern, particularly the use of systemic corticosteroids to treat exacerbations and severe asthma. Around the world, many patients are stuck in a vicious circle of misdiagnosis, undertreatment, and poor understanding of disease severity and management. In this manuscript, we describe the development of The Asthma Referral Identifier (ReferID) tool, a simple, 4-item questionnaire that healthcare providers can use to help identify patients with uncontrolled and/or potentially severe asthma. ReferID was developed specifically for use in primary care clinics in low- and middle-income countries and other clinics, where the optimisation of asthma assessments and treatment recommended for countries with well-established healthcare systems, are not possible. ReferID was developed through an informal collaborative process involving international asthma experts as well as general practitioners, nurses, and specialists throughout the Asia Pacific, Latin America and Middle East regions, in conjunction with current evidence and treatment guidelines. In collaboration with local and regional partners around the world, the developers have adapted ReferID and translated it into 21 languages, and implementation is ongoing in 30 countries. ReferID has the potential to help break the vicious circle, improving disease outcomes and health-related quality of life for patients with asthma.
Pharmacological smoking cessation of adults aged 30–50 years with COPD
Authors: Andelius Dea Kejlberg , Hilberg Ole , Ibsen Rikke , Løkke Anders 
Published: October 2022

AbstractThe prevalence of active smokers has remained relatively stable around 20% for several years in Denmark despite knowledge of the harmful effects. Smoking cessation is the most effective way to limit progression and reduce mortality of chronic obstructive pulmonary disease (COPD). Therefore, smoking cessation is particularly important among adults with COPD. The aim of this study was to determine the extent to which adults 30–50 years of age with COPD redeem pharmacotherapy for smoking cessation, and to identify demographic factors that influence the use of smoking cessation medication. We conducted a national retrospective non-interventional registry study, including all Danish patients with COPD (ICD-10 code J.44: chronic obstructive pulmonary disease) aged 30–50 years in the period 2009–2015. We identified 7734 cases, who were matched with controls (15,307) 1:2 on age, sex, and geography. Smoking status was not registered. We found that 18% of cases (with an estimated smoking prevalence at 33–50%) redeemed pharmacological smoking cessation medication in the study period compared to 3% of the controls (with an estimated smoking prevalence at 23%). The OR for cases collecting pharmacological smoking cessation medication was 5.92 [95% CI 5.24–6.70]. Male sex, being unemployed, and receiving social benefits were factors associated with less probability of redeeming pharmacological smoking cessation medication. Our study indicates that attention is needed on smoking cessation in adults aged 30–50 years with COPD, especially if unemployed or receiving social benefits, as these individuals are less likely to redeem pharmacological smoking cessation medication.
Power-law scaling of correlations in statistically polarised nano-NMR
Authors: Staudenmaier Nicolas , Vijayakumar-Sreeja Anjusha , Oviedo-Casado Santiago , Genov Genko , Cohen Daniel , Dulog Daniel , Unden Thomas , Striegler Nico , Marshall Alastair , Scheuer Jochen , Findler Christoph , Lang Johannes , Schwartz Ilai , Neumann Philipp , Retzker Alex , Jelezko Fedor 
Published: October 2022

AbstractDiffusion noise is a major source of spectral line broadening in liquid state nano-scale nuclear magnetic resonance with shallow nitrogen-vacancy centres, whose main consequence is a limited spectral resolution. This limitation arises by virtue of the widely accepted assumption that nuclear spin signal correlations decay exponentially in nano-NMR. However, a more accurate analysis of diffusion shows that correlations survive for a longer time due to a power-law scaling, yielding the possibility for improved resolution and altering our understanding of diffusion at the nano-scale. Nevertheless, such behaviour remains to be demonstrated in experiments. Using three different experimental setups and disparate measurement techniques, we present overwhelming evidence of power-law decay of correlations. These result in sharp-peaked spectral lines, for which diffusion broadening need not be a limitation to resolution.
Lake volume variation in the endorheic basin of the Tibetan Plateau from 1989 to 2019
Authors: Wang Junxiao , Wang Liuming , Li Mengyao , Zhu Liping , Li Xingong 
Published: October 2022

AbstractLake storage change serves as a unique indicator of natural climate change on the Tibetan Plateau (TP). However, comprehensive lake storage data, especially for lakes smaller than 10 km2, are still lacking in the region. In this dataset, we completed a census of annual relative lake volume (RLV) for 976 lakes, which are larger than 1 km2, on the endorheic basin of the Tibetan Plateau (EBTP) during 1989–2019 using Landsat imagery and digital terrain models. Our method first identifies individual lakes, determines their analysis extents and calculates annual lake area from Landsat imagery. It then derives lake area-elevation relationship, estimates lake surface elevation, and calculates RLV. Validation and comparison with several existing datasets indicate our data are more reliable and comprehensive. Our study complements existing lake datasets by providing a complete and long-term lake water volume change data for the region.