bluuebunny/crossref_metadata_2025 huggingface dataset:
B7-1 mediates podocyte injury and glomerulosclerosis through communication with Hsp90ab1-LRP5-β-catenin pathway
Authors: Li Jiemei , Niu Jing , Min Wenjian , Ai Jun , Lin Xu , Miao Jinhua , Zhou Shan , Liang Ye , Chen Shuangqin , Ren Qian , Shen Kunyu , Wu Qinyu , Li Xiaolong , Shen Weiwei , Hou Fan Fan , Liu Youhua , Yang Peng , Zhou Lili
Published: June 2022

Podocyte injury is a hallmark of glomerular diseases; however, the underlying mechanisms remain unclear. B7-1 is increased in injured podocytes, but its intrinsic role is controversial. The clinical data here revealed the intimate correlation of urinary B7-1 with severity of glomerular injury. Through transcriptomic and biological assays in B7-1 transgenic and adriamycin nephropathy models, we identified B7-1 is a key mediator in podocyte injury and glomerulosclerosis through a series of signal transmission to β-catenin. Using LC-MS/MS, Hsp90ab1, a conserved molecular chaperone, was distinguished to be an anchor for transmitting signals from B7-1 to β-catenin. Molecular docking and subsequent mutant analysis further identified the residue K69 in the N terminal domain of Hsp90ab1 was the key binding site for B7-1 to activate LRP5/β-catenin pathway. The interaction and biological functions of B7-1-Hsp90ab1-LRP5 complex were further demonstrated in vitro and in vivo. We also found B7-1 is a novel downstream target of β-catenin. Our results indicate an intercrossed network of B7-1, which collectively induces podocyte injury and glomerulosclerosis. Our study provides an important clue to improve the therapeutic strategies to target B7-1.
RETRACTED ARTICLE: RUNX3-regulated circRNA METTL3 inhibits colorectal cancer proliferation and metastasis via miR-107/PER3 axis
Authors: Zhang Feng , Su Tao , Xiao Meifang
Published: June 2022

Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies. Exploring the underlying molecular mechanisms is very helpful for the development of new therapy. Here, we investigated the function of circMETTL3/miR-107/PER3 in CRC. Human CRC tissues from diagnosed CRC patients and six CRC cell lines, one normal human colon cell line were used. qRT-PCR and western blotting were performed to determine expression levels of RUNX3, circMETTL3, miR-107, PER3, and proliferation-, and migration-related proteins. CCK-8, colony formation assay, transwell assay, and scratch wound assay were utilized to assess CRC cell proliferation and invasion. ChIP, EMSA, biotin-pull down, RIP assay, and dual luciferase reporter assay were performed to validate interactions of RUNX3/METTL3 promoter, circMETTL3/miR-107, and miR-107/PER3. FISH was used to characterize circMETTL3. MSP was employed to measure methylation level. Nude mouse xenograft model was used to determine the effects on tumor growth and metastasis in vivo. RUNX3, circMETTL3, and PER3 were diminished while miR-107 was elevated in CRC tissues and cells. Low levels of RUNX3 and circMETTL3 correlated with poor prognosis of CRC. Overexpression of RUNX3, circMETTL3, or PER3 suppressed while miR-107 mimics promoted, CRC cell proliferation and invasion, as well as tumor growth and metastasis in vivo. Mechanistically, RUNX3 bound to METTL3 promoter and activated circMETTL3 transcription. circMETTL3 directly bound with miR-107 which targeted PER3. circMETTL3/miR-107 regulated CRC cell proliferation and invasion via PER3. CircMETTL3, transcriptionally activated by RUNX3, restrains CRC development and metastasis via acting as a miR-107 sponge to regulate PER3 signaling.
microRNA-140-3p protects hippocampal neuron against pyroptosis to attenuate sevoflurane inhalation-induced post-operative cognitive dysfunction in rats via activation of HTR2A/ERK/Nrf2 axis by targeting DNMT1
Authors: Wu Zhiguo , Tan Jian , Lin Lichang , Zhang Wenting , Yuan Wanqiu
Published: June 2022

The incidence of post-operative cognitive dysfunction (POCD) remains a relatively prevalent complication in the elderly after surgery, especially in those receiving sevoflurane (Sevo) anesthesia. microRNA (miR)−140-3p has been demonstrated to orchestrate neuroinflammation and neuron apoptosis. However, the role of miR-140-3p in POCD remains largely unknown. In this context, this research was designed to explore whether miR-140-3p mediated Sevo inhalation-induced POCD in rats. A POCD rat model was established by Sevo inhalation, and a Sevo cell model was constructed in primary hippocampal neurons isolated from rats, followed by detection of miR-140-30 and HTR2A expression. Then, gain- and loss-of-function assays were implemented in rats and neurons. In rats, the cognitive function was evaluated by Water maze test and step-through test, and neuron apoptosis by TUNEL staining. In neurons, cell viability, apoptosis, and pyroptosis-related factors were tested by MTT, flow cytometry, and Western blot analysis respectively. Interaction between HTR2A and DNMT1 was assessed by MSP, and ChIP assay, and interaction between miR-140-3p and DNMT1 by dual-luciferase reporter assay, RIP and RNA pull-down. HTR2A and miR-140-3p were downregulated in POCD rats and Sevo-treated hippocampal neurons. Mechanistically, miR-140-3p negatively targeted DNMT1 to decrease HTR2A promoter methylation, thus upregulation HTR2A to activate ERK/Nrf2 pathway. miR-140-3p or HTR2A overexpression or activation of ERK/Nrf2 pathway elevated neuron viability and diminished their apoptosis and pyroptosis while alleviating Sevo-induced POCD in rats. Collectively, miR-140-3p might repress neuron pyroptosis to alleviate Sevo inhalation-induced POCD in rats via DNMT1/HTR2A/ERK/Nrf2 axis.
Taming the radical cation intermediate enabled one-step access to structurally diverse lignans
Authors: Xiang Jia-Chen , Fung Cédric , Wang Qian , Zhu Jieping
Published: June 2022

Lignans, in spite of their structural diversity, are all biosynthetically derived from coniferyl alcohol. We report herein a divergent synthesis of lignans from biomass-derived monolignols in a short synthetic sequence. Blue LED irradiation of a dichloromethane solution of dicinnamyl ether derivatives in the presence of Cu(TFA)2, an alcohol (2.0 equiv) and a catalytic amount of Fukuzumi’s salt affords the C7-alkoxylated aryltetralin cyclic ethers. Increasing the amount of alcohol under otherwise identical conditions diverts the reaction course to furnish the C7,C7’-dialkoxylated dibenzyltetrahydrofurans, while replacing Cu(TFA)2with diphenyl disulfide (PhSSPh) provides selectively the C7-monoalkoxylated dibenzyltetrahydrofurans. Aza-, thia- and carba-analogues of lignans are equally accessible by simply changing the tethering atom of the allylic alcohols. Concise total syntheses of aglacins A, E, F, brassilignan, and dehydrodimethylconidendrin are documented featuring these transformations.
Catalytical nano-immunocomplexes for remote-controlled sono-metabolic checkpoint trimodal cancer therapy
Authors: Zhang Chi , Huang Jingsheng , Zeng Ziling , He Shasha , Cheng Penghui , Li Jingchao , Pu Kanyi
Published: June 2022

Checkpoint immunotherapies have been combined with other therapeutic modalities to increase patient response rate and improve therapeutic outcome, which however exacerbates immune-related adverse events and requires to be carefully implemented in a narrowed therapeutic window. Strategies for precisely controlled combinational cancer immunotherapy can tackle this issue but remain lacking. We herein report a catalytical nano-immunocomplex for precise and persistent sono-metabolic checkpoint trimodal cancer therapy, whose full activities are only triggered by sono-irradiation in tumor microenvironment (TME). This nano-immunocomplex comprises three FDA-approved components, wherein checkpoint blockade inhibitor (anti-programmed death-ligand 1 antibody), immunometabolic reprogramming enzyme (adenosine deaminase, ADA), and sonosensitizer (hematoporphyrin) are covalently immobilized into one entity via acid-cleavable and singlet oxygen-activatable linkers. Thus, the activities of the nano-immunocomplex are initially silenced, and only under sono-irradiation in the acidic TME, the sonodynamic, checkpoint blockade, and immunometabolic reprogramming activities are remotely awakened. Due to the enzymatic conversion of adenosine to inosine by ADA, the nano-immunocomplex can reduce levels of intratumoral adenosine and inhibit A2A/A2B adenosine receptors-adenosinergic signaling, leading to efficient activation of immune effector cells and inhibition of immune suppressor cells in vivo. Thus, this study presents a generic and translatable nanoplatform towards precision combinational cancer immunotherapy.
Influence maximization in Boolean networks
Authors: Parmer Thomas , Rocha Luis M. , Radicchi Filippo
Published: June 2022

The optimization problem aiming at the identification of minimal sets of nodes able to drive the dynamics of Boolean networks toward desired long-term behaviors is central for some applications, as for example the detection of key therapeutic targets to control pathways in models of biological signaling and regulatory networks. Here, we develop a method to solve such an optimization problem taking inspiration from the well-studied problem of influence maximization for spreading processes in social networks. We validate the method on small gene regulatory networks whose dynamical landscapes are known by means of brute-force analysis. We then systematically study a large collection of gene regulatory networks. We find that for about 65% of the analyzed networks, the minimal driver sets contain less than 20% of their nodes.
Sustainable power generation for at least one month from ambient humidity using unique nanofluidic diode
Authors: Zhang Yong , Yang Tingting , Shang Kedong , Guo Fengmei , Shang Yuanyuan , Chang Shulong , Cui Licong , Lu Xulei , Jiang Zhongbao , Zhou Jian , Fu Chunqiao , He Qi-Chang
Published: June 2022

The continuous energy-harvesting in moisture environment is attractive for the development of clean energy source. Controlling the transport of ionized mobile charge in intelligent nanoporous membrane systems is a promising strategy to develop the moisture-enabled electric generator. However, existing designs still suffer from low output power density. Moreover, these devices can only produce short-term (mostly a few seconds or a few hours, rarely for a few days) voltage and current output in the ambient environment. Here, we show an ionic diode–type hybrid membrane capable of continuously generating energy in the ambient environment. The built-in electric field of the nanofluidic diode-type PN junction helps the selective ions separation and the steady-state one-way ion charge transfer. This directional ion migration is further converted to electron transportation at the surface of electrodes via oxidation-reduction reaction and charge adsorption, thus resulting in a continuous voltage and current with high energy conversion efficiency.
Phasing analysis of lung cancer genomes using a long read sequencer
Authors: Sakamoto Yoshitaka , Miyake Shuhei , Oka Miho , Kanai Akinori , Kawai Yosuke , Nagasawa Satoi , Shiraishi Yuichi , Tokunaga Katsushi , Kohno Takashi , Seki Masahide , Suzuki Yutaka , Suzuki Ayako
Published: June 2022

Chromosomal backgrounds of cancerous mutations still remain elusive. Here, we conduct the phasing analysis of non-small cell lung cancer specimens of 20 Japanese patients. By the combinatory use of short and long read sequencing data, we obtain long phased blocks of 834 kb in N50 length with >99% concordance rate. By analyzing the obtained phasing information, we reveal that several cancer genomes harbor regions in which mutations are unevenly distributed to either of two haplotypes. Large-scale chromosomal rearrangement events, which resemble chromothripsis events but have smaller scales, occur on only one chromosome, and these events account for the observed biased distributions. Interestingly, the events are characteristic of EGFR mutation-positive lung adenocarcinomas. Further integration of long read epigenomic and transcriptomic data reveal that haploid chromosomes are not always at equivalent transcriptomic/epigenomic conditions. Distinct chromosomal backgrounds are responsible for later cancerous aberrations in a haplotype-specific manner.
Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine
Authors: Kramer Kevin J. , Wilfong Erin M. , Voss Kelsey , Barone Sierra M. , Shiakolas Andrea R. , Raju Nagarajan , Roe Caroline E. , Suryadevara Naveenchandra , Walker Lauren M. , Wall Steven C. , Paulo Ariana , Schaefer Samuel , Dahunsi Debolanle , Westlake Camille S. , Crowe James E. , Carnahan Robert H. , Rathmell Jeffrey C. , Bonami Rachel H. , Georgiev Ivelin S. , Irish Jonathan M.
Published: June 2022

RNA-based vaccines against SARS-CoV-2 have proven critical to limiting COVID-19 disease severity and spread. Cellular mechanisms driving antigen-specific responses to these vaccines, however, remain uncertain. Here we identify and characterize antigen-specific cells and antibody responses to the RNA vaccine BNT162b2 using multiple single-cell technologies for in depth analysis of longitudinal samples from a cohort of healthy participants. Mass cytometry and unbiased machine learning pinpoint an expanding, population of antigen-specific memory CD4+and CD8+T cells with characteristics of follicular or peripheral helper cells. B cell receptor sequencing suggest progression from IgM, with apparent cross-reactivity to endemic coronaviruses, to SARS-CoV-2-specific IgA and IgG memory B cells and plasmablasts. Responding lymphocyte populations correlate with eventual SARS-CoV-2 IgG, and a participant lacking these cell populations failed to sustain SARS-CoV-2-specific antibodies and experienced breakthrough infection. These integrated proteomic and genomic platforms identify an antigen-specific cellular basis of RNA vaccine-based immunity.
The impact of species-wide gene expression variation on Caenorhabditis elegans complex traits
Authors: Zhang Gaotian , Roberto Nicole M. , Lee Daehan , Hahnel Steffen R. , Andersen Erik C.
Published: June 2022

Phenotypic variation in organism-level traits has been studied in Caenorhabditis elegans wild strains, but the impacts of differences in gene expression and the underlying regulatory mechanisms are largely unknown. Here, we use natural variation in gene expression to connect genetic variants to differences in organismal-level traits, including drug and toxicant responses. We perform transcriptomic analyses on 207 genetically distinct C. elegans wild strains to study natural regulatory variation of gene expression. Using this massive dataset, we perform genome-wide association mappings to investigate the genetic basis underlying gene expression variation and reveal complex genetic architectures. We find a large collection of hotspots enriched for expression quantitative trait loci across the genome. We further use mediation analysis to understand how gene expression variation could underlie organism-level phenotypic variation for a variety of complex traits. These results reveal the natural diversity in gene expression and possible regulatory mechanisms in this keystone model organism, highlighting the promise of using gene expression variation to understand how phenotypic diversity is generated.
Consecutive topological phase transitions and colossal magnetoresistance in a magnetic topological semimetal
Authors: Du Feng , Yang Lin , Nie Zhiyong , Wu Ninghua , Li Yong , Luo Shuaishuai , Chen Ye , Su Dajun , Smidman Michael , Shi Youguo , Cao Chao , Steglich Frank , Song Yu , Yuan Huiqiu
Published: June 2022

The combination of magnetic symmetries and electronic band topology provides a promising route for realizing topologically nontrivial quasiparticles, and the manipulation of magnetic structures may enable the switching between topological phases, with the potential for achieving functional physical properties. Here, we report measurements of the electrical resistivity of EuCd2As2 under pressure, which show an intriguing insulating dome at pressures between pc1 ~ 1.0 GPa and pc2 ~ 2.0 GPa, situated between two regimes with metallic transport. The insulating state can be fully suppressed by a small magnetic field, leading to a colossal negative magnetoresistance on the order of 105%, accessible via a modest field of ~ 0.2 T. First-principles calculations reveal that the dramatic evolution of the resistivity under pressure can be attributed to consecutive transitions of EuCd2As2 from a magnetic topological insulator to a trivial insulator, and then to a Weyl semimetal, with the latter resulting from a pressure-induced change in the magnetic ground state. Similarly, the colossal magnetoresistance results from a field-induced polarization of the magnetic moments, transforming EuCd2As2 from a trivial insulator to a Weyl semimetal. These findings underscore weak exchange couplings and weak magnetic anisotropy as ingredients for discovering tunable magnetic topological materials with desirable functionalities.
Long-term ice phenology records spanning up to 578 years for 78 lakes around the Northern Hemisphere
Authors: Sharma Sapna , Filazzola Alessandro , Nguyen Thi , Imrit M. Arshad , Blagrave Kevin , Bouffard Damien , Daly Julia , Feldman Harley , Feldsine Natalie , Hendricks-Franssen Harrie-Jan , Granin Nikolay , Hecock Richard , L’Abée-Lund Jan Henning , Hopkins Ed , Howk Neil , Iacono Michael , Knoll Lesley B. , Korhonen Johanna , Malmquist Hilmar J. , Marszelewski Włodzimierz , Matsuzaki Shin-Ichiro S. , Miyabara Yuichi , Miyasaka Kiyoshi , Mills Alexander , Olson Lolita , Peters Theodore W. , Richardson David C. , Robertson Dale M. , Rudstam Lars , Wain Danielle , Waterfield Holly , Weyhenmeyer Gesa A. , Wiltse Brendan , Yao Huaxia , Zhdanov Andry , Magnuson John J.
Published: June 2022

In recent decades, lakes have experienced unprecedented ice loss with widespread ramifications for winter ecological processes. The rapid loss of ice, resurgence of winter biology, and proliferation of remote sensing technologies, presents a unique opportunity to integrate disciplines to further understand the broad spatial and temporal patterns in ice loss and its consequences. Here, we summarize ice phenology records for 78 lakes in 12 countries across North America, Europe, and Asia to permit the inclusion and harmonization of in situ ice phenology observations in future interdisciplinary studies. These ice records represent some of the longest climate observations directly collected by people. We highlight the importance of applying the same definition of ice-on and ice-off within a lake across the time-series, regardless of how the ice is observed, to broaden our understanding of ice loss across vast spatial and temporal scales.
Generating FAIR research data in experimental tribology
Authors: Garabedian Nikolay T. , Schreiber Paul J. , Brandt Nico , Zschumme Philipp , Blatter Ines L. , Dollmann Antje , Haug Christian , Kümmel Daniel , Li Yulong , Meyer Franziska , Morstein Carina E. , Rau Julia S. , Weber Manfred , Schneider Johannes , Gumbsch Peter , Selzer Michael , Greiner Christian
Published: June 2022

Solutions for the generation of FAIR (Findable, Accessible, Interoperable, and Reusable) data and metadata in experimental tribology are currently lacking. Nonetheless, FAIR data production is a promising path for implementing scalable data science techniques in tribology, which can lead to a deeper understanding of the phenomena that govern friction and wear. Missing community-wide data standards, and the reliance on custom workflows and equipment are some of the main challenges when it comes to adopting FAIR data practices. This paper, first, outlines a sample framework for scalable generation of FAIR data, and second, delivers a showcase FAIR data package for a pin-on-disk tribological experiment. The resulting curated data, consisting of 2,008 key-value pairs and 1,696 logical axioms, is the result of (1) the close collaboration with developers of a virtual research environment, (2) crowd-sourced controlled vocabulary, (3) ontology building, and (4) numerous – seemingly – small-scale digital tools. Thereby, this paper demonstrates a collection of scalable non-intrusive techniques that extend the life, reliability, and reusability of experimental tribological data beyond typical publication practices.
Greenhouse gas emissions from municipal wastewater treatment facilities in China from 2006 to 2019
Authors: Wang Dan , Ye Weili , Wu Guangxue , Li Ruoqi , Guan Yuru , Zhang Wei , Wang Junxia , Shan Yuli , Hubacek Klaus
Published: June 2022

Wastewater treatment plants (WWTPs) alleviate water pollution but also induce resource consumption and environmental impacts especially greenhouse gas (GHG) emissions. Mitigating GHG emissions of WWTPs can contribute to achieving carbon neutrality in China. But there is still a lack of a high-resolution and time-series GHG emission inventories of WWTPs in China. In this study, we construct a firm-level emission inventory of WWTPs for CH4, N2O and CO2 emissions from different wastewater treatment processes, energy consumption and effluent discharge for the time-period from 2006 to 2019. We aim to develop a transparent, verifiable and comparable WWTP GHG emission inventory to support GHG mitigation of WWTPs in China.
Gridded value-added of primary, secondary and tertiary industries in China under Shard Socioeconomic Pathways
Authors: Jing Cheng , Su Buda , Zhai Jianqing , Wang Yanjun , Lin Qigen , Gao Miaoni , Jiang Shan , Chen Ziyan , Jiang Tong
Published: June 2022

Gridded distribution of future economy plays an important role in climate change impact assessment. The trend of the output values of different industries is crucial for a variety of planning and design processes. Under the Shared Socioeconomic Pathways (SSPs) global framework, the multidimensional model and Cobb-Douglas production model with localized population and economic parameters are used to develop the annual provincial population and value-added of primary, secondary and tertiary industries in China from 2020 to 2100. The most recently implemented fertility-promoting and industrial planning policies in China are considered in our projections. We build multiple models to evaluate the impact of different types of land use on the value-added of primary, secondary and tertiary industries and then gridded the projected value-added to a 5′ × 5′ resolution, based on recorded county-level economic statistics and gridded land use. The reliability of estimations is verified against 2011–2019 statistical data and multiple published datasets. The high-resolution economic dataset is expected to contribute greatly to national and regional climate change impact, adaptation, and vulnerability studies.
Cat predation of Kangaroo Island dunnarts in aftermath of bushfire
Authors: Hodgens Patrick , Groffen Heidi , O’Handley Ryan , Vyas Ajai , Lignereux Louis
Published: June 2022

The Kangaroo Island dunnart (Sminthopsis aitkeni) is a critically endangered marsupial species with an estimated population of ~ 500 individuals found only on the western end of Australia's third largest island. Severe bushfires recently burnt more than 98% of its known and predicted habitat that was already under pressure from fragmentation. After the fires, we found evidence of eight individual dunnarts in the digestive tract of seven feral cats, out of the 86 collected in remaining unburnt refugia; thus demonstrating the need of immediate risk management efforts after large-scale stochastic events.
Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells
Authors: Imai Yuta , Iida Madoka , Kanie Kei , Katsuno Masahisa , Kato Ryuji
Published: June 2022

Label-free image analysis has several advantages with respect to the development of drug screening platforms. However, the evaluation of drug-responsive cells based exclusively on morphological information is challenging, especially in cases of morphologically heterogeneous cells or a small subset of drug-responsive cells. We developed a novel label-free cell sub-population analysis method called “in silico FOCUS (in silico analysis of featured-objects concentrated by anomaly discrimination from unit space)” to enable robust phenotypic screening of morphologically heterogeneous spinal and bulbar muscular atrophy (SBMA) model cells. This method with the anomaly discrimination concept can sensitively evaluate drug-responsive cells as morphologically anomalous cells through in silico cytometric analysis. As this algorithm requires only morphological information of control cells for training, no labeling or drug administration experiments are needed. The responses of SBMA model cells to dihydrotestosterone revealed that in silico FOCUS can identify the characteristics of a small sub-population with drug-responsive phenotypes to facilitate robust drug response profiling. The phenotype classification model confirmed with high accuracy the SBMA-rescuing effect of pioglitazone using morphological information alone. In silico FOCUS enables the evaluation of delicate quality transitions in cells that are difficult to profile experimentally, including primary cells or cells with no known markers.
Receptor tyrosine kinase inhibitors negatively impact on pro-reparative characteristics of human cardiac progenitor cells
Authors: Smith Andrew J. , Ruchaya Prashant , Walmsley Robert , Wright Kathleen E. , Lewis-McDougall Fiona C. , Bond Jacquelyn , Ellison-Hughes Georgina M.
Published: June 2022

Receptor tyrosine kinase inhibitors improve cancer survival but their cardiotoxicity requires investigation. We investigated these inhibitors’ effects on human cardiac progenitor cells in vitro and rat heart in vivo. We applied imatinib, sunitinib or sorafenib to human cardiac progenitor cells, assessing cell viability, proliferation, stemness, differentiation, growth factor production and second messengers. Alongside, sunitinib effects were assessed in vivo. Inhibitors decreased (p < 0.05) cell viability, at levels equivalent to ‘peak’ (24 h; imatinib: 91.5 ± 0.9%; sunitinib: 83.9 ± 1.8%; sorafenib: 75.0 ± 1.6%) and ‘trough’ (7 days; imatinib: 62.3 ± 6.2%; sunitinib: 86.2 ± 3.5%) clinical plasma levels, compared to control (100% viability). Reduced (p < 0.05) cell cycle activity was seen with imatinib (29.3 ± 4.3% cells in S/G2/M-phases; 50.3 ± 5.1% in control). Expression of PECAM-1, Nkx2.5, Wnt2, linked with cell differentiation, were decreased (p < 0.05) 2, 2 and 6-fold, respectively. Expression of HGF, p38 and Akt1 in cells was reduced (p < 0.05) by sunitinib. Second messenger (p38 and Akt1) blockade affected progenitor cell phenotype, reducing c-kit and growth factor (HGF, EGF) expression. Sunitinib for 9 days (40 mg/kg, i.p.) in adult rats reduced (p < 0.05) cardiac ejection fraction (68 ± 2%vs. baseline (83 ± 1%) and control (84 ± 4%)) and reduced progenitor cell numbers. Receptor tyrosine kinase inhibitors reduce cardiac progenitor cell survival, proliferation, differentiation and reparative growth factor expression.
Active control of dielectric nanoparticle optical resonance through electrical charging
Authors: Gao Xuebang , Xie Li , Zhou Jùn
Published: June 2022

A novel method for active control of resonance position of dielectric nanoparticles by increasing the excess charges carried by the nanoparticles is proposed in this paper. We show that as the excess charges carried by the particle increase, the oscillation frequency of excess charges will gradually increase, when it is equal to the incident frequency, resonance occurs due to resonant excitation of the excess charges. What is more, the formula of charges carried by an individual particle required to excite the resonance at any wavelength position is proposed. The resonance position can be directly controlled by means of particle charging, and the enhancement of resonance intensity is more obvious. This work has opened new avenues for the active control of plasmon resonances, which shows great promise for realizing tunable optical properties of dielectric nanoparticles.
Metabolic risk assessment in children and adolescents using the tri-ponderal mass index
Authors: Seo Young-Jun , Shim Young Suk , Lee Hae Sang , Hwang Jin Soon
Published: June 2022

We assessed the risk of metabolic syndrome in children and adolescents who were classified using the tri-ponderal mass index (TMI) with data from the Korea National Health and Nutrition Examination Survey (KNHANES). Data from 10 to 18-year-old subjects that were overweight or obese (n = 1362) were extracted from the KNHANES 2007–2018. Weight classifications were determined by TMI and included overweight and Class I, Class II, and Class III obesity. The standard deviation scores (SDS) of weight, waist circumference, and body mass index (BMI) as well as cardiometabolic risk factors, including blood pressure, serum glucose levels, total cholesterol (T-C), triglycerides, HDL-c, and low-density lipoprotein cholesterol (LDL-c), worsened with the severity of obesity. Most risk factors showed a linear association with the severity increase, except for fasting glucose levels, T-C, and LDL-c. The prevalence of cardiometabolic risks also increased with the severity of obesity, which developed earlier in boys than in girls. The risk of metabolic syndrome significantly increased with the severity of obesity in both unadjusted and adjusted analyses. TMI reflected the severity of obesity and predicted the risk of metabolic syndrome and its components. Therefore, clinical applications of TMI could be a useful to identify the incidence of childhood obesity and metabolic syndromes.
Cluster analysis categorizes five phenotypes of pulmonary tuberculosis
Authors: Koo Hyeon-Kyoung , Min Jinsoo , Kim Hyung Woo , Ko Yousang , Oh Jee Youn , Jeong Yun-Jeong , Kang Hyeon Hui , Kang Ji Young , Lee Sung-Soon , Seo Minseok , Silverman Edwin K. , Kim Ju Sang , Park Jae Seuk
Published: June 2022

Tuberculosis (TB) has a heterogeneous phenotype, which makes it challenging to diagnose. Our study aimed to identify TB phenotypes through cluster analysis and compare their initial symptomatic, microbiological and radiographic characteristics. We systemically collected data of notified TB patients notified in Korea and constructed a prospective, observational cohort database. Cluster analysis was performed using K-means clustering, and the variables to be included were determined by correlation network. A total of 4,370 subjects with pulmonary TB were enrolled in the study. Based on the correlation network, age and body mass index (BMI) were selected for the cluster analysis. Five clusters were identified and characterised as follows: (1) middle-aged overweight male dominance, (2) young-aged relatively female dominance without comorbidities, (3) middle-aged underweight male dominance, (4) overweight elderly with comorbidities and (5) underweight elderly with comorbidities. All clusters had distinct demographic and symptomatic characteristics. Initial microbiologic burdens and radiographic features also varied, including the presence of cavities and bilateral infiltration, which reflect TB-related severity. Cluster analysis of age and BMI identified five phenotypes of pulmonary TB with significant differences at initial clinical presentations. Further studies are necessary to validate our results and to assess their clinical implications.
Single-cell transcriptomic analysis of neuroepithelial cells and other cell types of the gills of zebrafish (Danio rerio) exposed to hypoxia
Authors: Pan Wen , Godoy Rafael Soares , Cook David P. , Scott Angela L. , Nurse Colin A. , Jonz Michael G.
Published: June 2022

The fish gill is a multifunctional organ involved in numerous physiological processes, such as gas exchange and sensing of hypoxia by respiratory chemoreceptors, called neuroepithelial cells (NECs). Many studies have focused on zebrafish (Danio rerio) to investigate the structure, function and development of the gills, yet the transcriptomic profile of most gill cells remains obscure. We present the results of a comprehensive transcriptomic analysis of the gills of zebrafish using single-cell RNA sequencing (scRNA‐seq). Gill cells from ETvmat2:EGFP zebrafish were individually labelled before scRNA‐seq library construction using 10× Genomics Chromium technology. 12,819 cells were sequenced with an average depth of over 27,000 reads per cell. We identified a median of 485 genes per cell and 16 cell clusters, including NECs, neurons, pavement cells, endothelial cells and mitochondrion-rich cells. The identity of NECs was confirmed by expression of slc18a2, encoding the vesicular monoamine transporter, Vmat2. Highly differentially-expressed genes in NECs included tph1a, encoding tryptophan hydroxylase, sv2 (synaptic vesicle protein), and proteins implicated in O2 sensing (ndufa4l2a, cox8al and epas1a). In addition, NECs and neurons expressed genes encoding transmembrane receptors for serotonergic, cholinergic or dopaminergic neurotransmission. Differential expression analysis showed a clear shift in the transcriptome of NECs following 14 days of acclimation to hypoxia. NECs in the hypoxia group showed high expression of genes involved in cell cycle control and proliferation. The present article provides a complete cell atlas for the zebrafish gill and serves as a platform for future studies investigating the molecular biology and physiology of this organ.
Northward migration of the East Asian summer monsoon northern boundary during the twenty-first century
Authors: Wang Zhenqian , Fu Zhenhao , Liu Bo , Zheng Zeyu , Zhang Weichen , Liu Yangyang , Zhang Fen , Zhang Qiong
Published: June 2022

The northern fringe area of the East Asian summer monsoon (EASM) between arid and semiarid regions is a fragile eco-environment zone and ecological transition zone, and it is highly sensitive to climate change. Predicting the future migration of the northern boundary of the EASM is important for understanding future East Asian climate change and formulating of decisions on ecological protection and economic development in arid and semiarid regions. The reanalysis dataset and simulations of 23 models from the Coupled Models Intercomparison Project Phase 6 (CMIP6) were used to investigate the response of the boundary of the ESAM to the global warming. The multi-model ensemble showed a northwestward migration of the EASM northern boundary during the near-term (2020–2060) and late-term (2061–2099) of the twenty-first century under various Shared Socioeconomic Pathways (SSPs). The northern boundary migrated northwestward by 23–28 and 74–76 km in the near-term and late-term respectively, under SSP1-2.6, 2-4.5 and 3-7.0 and by ~ 44 km and ~ 107 km respectively during the near-term and late-term under SSP5-8.5. During the twenty-first century, under various SSPs, the surface of the East Asian subcontinent warmed more than the ocean, thereby increasing the contrast of near-surface temperature and sea level pressure in summer between the East Asian subcontinent and the surrounding oceans. In turn, the intensified land–sea thermal contrast reinforced the EASM meridional circulation and thus transported more moisture from the Indian Ocean into northern China. Additionally, a poleward migration and weakening of the East Asian subtropical westerly jet would also favor an increase in precipitation, eventually caused a northwestward migration of the EASM northern boundary. The results suggest that the arid and semiarid ecotone will become wetter, which could dramatically improve the eco-environment in the future.
A model for simulating emergent patterns of cities and roads on real-world landscapes
Authors: Aoki Takaaki , Fujiwara Naoya , Fricker Mark , Nakagaki Toshiyuki
Published: June 2022

Emergence of cities and road networks have characterised human activity and movement over millennia. However, this anthropogenic infrastructure does not develop in isolation, but is deeply embedded in the natural landscape, which strongly influences the resultant spatial patterns. Nevertheless, the precise impact that landscape has on the location, size and connectivity of cities is a long-standing, unresolved problem. To address this issue, we incorporate high-resolution topographic maps into a Turing-like pattern forming system, in which local reinforcement rules result in co-evolving centres of population and transport networks. Using Italy as a case study, we show that the model constrained solely by topography results in an emergent spatial pattern that is consistent with Zipf’s Law and comparable to the census data. Thus, we infer the natural landscape may play a dominant role in establishing the baseline macro-scale population pattern, that is then modified by higher-level historical, socio-economic or cultural factors.
Association of SGLT2 inhibitors with lower incidence of death in type 2 diabetes mellitus and causes of death analysis
Authors: Chung Mu-Chi , Hsu Hui-Tsung , Chang Chao-Hsiang , Hung Peir-Haur , Hsiao Po-Jen , Wu Laing-You , Wu Ming-Ju , Shieh Jeng-Jer , Chung Chi-Jung
Published: June 2022

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) potentially decrease all-cause and cardiovascular death, however, associations with non-cardiovascular death remain unclear. Therefore, we investigated SGLT2i associations with death and the cause of death. We used the Taiwanese National Health Institutes Research database linked to the National Register of Deaths (NRD). Incident type 2 diabetes mellitus (T2DM) patients and propensity score matched T2DM SGLT2i and Dipeptidyl peptidase 4 inhibitor (DPP4i) users were investigated. The index year was the SGLT2i or DPP4i prescription date from May 2016. Patients were followed-up until death or December 2018. Deaths verified by the NRD and grouped accordingly. Multiple Cox proportional hazards models were used. In total, 261,211 patients were included in the population; 47% of the patients were female and the average age was 62 years. The overall incidence of all-cause death was 8.67/1000 patient-years for SGLT2i and 12.41 for DPP4i users during follow-up. After adjusting for potential risk factors in the propensity score matched population, SGLT2i users were associated with lower risks of all-cause death, cardiovascular death, cancer death, and non-cancer, non-vascular death compared with DPP4i-users. For specific death causes, significantly lower death risks from heart disease, cerebrovascular disease, and accidents were associated with SGLT2i-use. SGLT2i benefits for T2DM patients were not different across subgroups. Compared with DPP4i-use, SGLT2i-use for T2DM was associated with lower disease and death risk.
Ureaplasma and Prevotella colonization with Lactobacillus abundance during pregnancy facilitates term birth
Authors: Park Sunwha , You Young-Ah , Kim Young-Han , Kwon Eunjin , Ansari AbuZar , Kim Soo Min , Lee Gain , Hur Young Min , Jung Yun Ji , Kim Kwangmin , Kim Young Ju
Published: June 2022

Ureaplasma and Prevotella infections are well-known bacteria associated with preterm birth. However, with the development of metagenome sequencing techniques, it has been found that not all Ureaplasma and Prevotella colonizations cause preterm birth. The purpose of this study was to determine the association between Ureaplasma and Prevotella colonization with the induction of preterm birth even in the presence of Lactobacillus. In this matched case–control study, a total of 203 pregnant Korean women were selected and their cervicovaginal fluid samples were collected during mid-pregnancy. The microbiome profiles of the cervicovaginal fluid were analyzed using 16S rRNA gene amplification. Sequencing data were processed using QIIME1.9.1. Statistical analyses were performed using R software, and microbiome analysis was performed using the MicrobiomeAnalyst and Calypso software. A positive correlation between Ureaplasma and other genera was highly related to preterm birth, but interestingly, there was a negative correlation with Lactobacillus and term birth, with the same pattern observed with Prevotella. Ureaplasma and Prevotella colonization with Lactobacillus abundance during pregnancy facilitates term birth, although Ureaplasma and Prevotella are associated with preterm birth. Balanced colonization between Lactobacillus and Ureaplasma and Prevotella is important to prevent preterm birth.
Validity of magnetic resonance imaging (MRI) in the primary spinal cord tumors in routine clinical setting
Authors: Won Young Il , Choi Yunhee , Yuh Woon Tak , Kwon Shin Won , Kim Chi Heon , Yang Seung Heon , Chung Chun Kee
Published: June 2022

MRI is the primary diagnostic modality for spinal cord tumors. However, its validity has never been vigorously scrutinized in daily routine clinical practice, where MRI tissue diagnosis is usually not a single one but multiple ones with several differential diagnoses. Here, we aimed to assess the validity of MRI in terms of predicting the pathology and location of the tumor in routine clinical settings. We analyzed 820 patients with primary spinal cord tumors, who have a pathological diagnosis and location in the operation record which were confirmed. We modified traditional measures for validity based upon a set of diagnoses instead of a single diagnosis. Sensitivity and specificity and positive and negative predictabilities were evaluated for the tumor location and pathology. For tumor location, 456 were intradural extramedullary; 165 were intramedullary, and 156 were extradural. The overall sensitivity and specificity were over 90.0%. However, the sensitivity became lower when the tumor resided simultaneously in two spaces such as in the intradural-and-extradural or intramedullary-and-extramedullary space (54.6% and 30.0%, respectively). Most common pathology was schwannoma (n = 416), followed by meningioma (114) and ependymoma (87). Sensitivities were 93.3%, 90.4%, and 89.7%, respectively. Specificities were 70.8%, 82.9%, and 76.0%. In rare tumors such as neurofibromas, and diffuse midline gliomas, the sensitivity was much lower (less than 30%). For common locations and pathologies, the validity of MRI is generally acceptable. However, for rare locations and pathologies, MRI diagnosis still needs some improvement.
Ultrafast charge generation in a homogenous polymer domain
Authors: Meng Ruixuan , Zhu Rui
Published: June 2022

Efficient charge generation contributes greatly to the high performance of organic photovoltaic devices. The mechanism of charge separation induced by heterojunction has been widely accepted. However, how and why free charge carriers can generate in homogenous polymer domains remains to be explored. In this work, the extended tight-binding SSH model, combined with the non-adiabatic molecular dynamics simulation, is used to construct the model of a polymer array in an applied electric field and simulate the evolution of an excited state. It is found that under a very weak external electric field 5.0 × 10−3 V/Å, the excited state can evolve directly into spatially separated free charges at the femtosecond scale, and the efficiency is up to 97%. The stacking structure of the polymer array leads to intermolecular electron mutualization and forms intermolecular coupling. This interaction tends to delocalize the excited states in organic semiconductors, competing with the localization caused by electron–phonon coupling. Excitons within the homogenous polymer domains have lower binding energy, less energy dissipation, and ultrafast charge separation. Therefore, the initial excited state can evolve directly into free carriers under a very weak electric field. This finding provides a reasonable explanation for ultrafast charge generation in pure polymer phases and is consistent with the fact that delocalization always coexists with ultrafast charge generation. Moreover, the devices based on homogenous polymer domains are supposed to be stress-sensitive and performance-anisotropic since the above two interactions have contrary effects and work in perpendicular directions. This work is expected to bring inspiration for the design of organic functional materials and devices.
Implications for fault locking south of Jakarta from an investigation of seismic activity along the Baribis fault, northwestern Java, Indonesia
Authors: Widiyantoro S. , Supendi P. , Ardianto A. , Baskara A. W. , Bacon C. A. , Damanik R. , Rawlinson N. , Gunawan E. , Sahara D. P. , Zulfakriza Z. , Husni Y. M. , Lesmana A.
Published: June 2022

Recent borehole seismic deployments conducted along the Baribis Fault in northwestern Java reveal that it may be active. In this study, we exploit these data to locate proximal earthquakes using a relative relocation technique, estimate their moment magnitudes using a spectral fitting method and compute their focal mechanisms via waveform inversion. We observe that seismicity in the eastern part of the fault is significantly higher than in the west, where a previous GPS study of the region south of Jakarta demonstrated the existence of high compression rates. These observations imply that the western Baribis Fault is locked, and that neighbouring areas, including southern Jakarta and its surroundings, may be highly vulnerable to future sizeable earthquakes when accumulated elastic strain energy is eventually released during fault rupture. Significantly, the current generation of Indonesia’s national hazard maps have not considered seismicity along the Baribis Fault. Our new results therefore call for an urgent reappraisal of the seismic hazard in northwestern Java that carefully takes into account the Baribis Fault and its earthquake potential, particularly in light of its proximity to Jakarta, a megacity that lies at the heart of one of the most densely populated islands in the world.
Baseline peripheral neuropathy was associated with age and a prognostic factor in newly diagnosed multiple myeloma patients
Authors: Dong Mengmeng , Zhang Jinna , Han Xiaoyan , He Jingsong , Zheng Gaofeng , Cai Zhen
Published: June 2022

Multiple myeloma (MM) is an incurable plasma cell hematological malignancy. Bortezomib has become the primary drug in the treatment of patients with MM. However, its negative effects, especially peripheral neuropathy (PN), affect the patients’ life quality and treatment continuity. However, there are few studies on baseline PN of MM, and little is known of the impact of baseline PN on the prognosis of MM patients. Therefore, we reviewed the clinical data of newly diagnosed MM patients in our center, explored the influencing factors of baseline PN, and evaluated PN’s influence on the prognosis of MM patients undergoing induction therapy with bortezomib. According to the inclusion and exclusion criteria, 155 MM patients were eligible for the retrospective study. The multivariate regression analysis, generalized additive fitting smooth curve, the receiver operating characteristic curve (ROC) and K-M curve were conducted in this study. We found that baseline PN in patients with MM was age-related; MM patients with baseline PN have more severe bortezomib induced PN (BiPN) during the four courses of induction therapy with bortezomib as the primary regimen and worse PN outcome after induction therapy. Additionally, the progression-free survival (PFS) and overall survival (OS) of MM patients with baseline PN were worse than those of the MM patients without baseline PN.