bluuebunny/crossref_metadata_2025 huggingface dataset:
GITR/GITRL reverse signalling modulates the proliferation of hepatic progenitor cells by recruiting ANXA2 to phosphorylate ERK1/2 and Akt
Authors: He Yu , Pei Yufeng , Liu Kai , Liu Lin , Tian Yue , Li Hongyi , Cong Min , Liu Tianhui , Ma Hong , You Hong , Jia Jidong , Zhang Dong , Wang Ping
Published: April 2022

Hepatic stem/progenitor cells are the major cell compartment for tissue repair when hepatocyte proliferation is compromised in chronic liver diseases, but the expansion of these cells increases the risk of carcinogenesis. Therefore, it is essential to explore the pathways restricting their expansion and abnormal transformation. The ligand of glucocorticoid-induced tumour necrosis factor receptor (GITRL) showed the most highly increased expression in hepatic progenitor cells treated with transforming growth factor (TGF)-β1. If overexpressed by hepatic progenitor cells, GITRL stimulated cell proliferation by activating the epithelial–mesenchymal transition pathway and enhancing ERK1/2 and Akt phosphorylation via GITRL binding to ANXA2. However, GITR, the specific GITRL receptor, suppressed the epithelial–mesenchymal transition pathway of GITRL-expressing cells and decreased their growth by dissociating ANXA2 from GITRL and reducing downstream ERK1/2 and Akt phosphorylation. This study identifies GITR/GITRL reverse signalling as a cross-interaction pathway between immune cells and hepatic stem/progenitor cells that restricts the expansion of hepatic stem/progenitor cells and reduces the possibility of carcinogenesis.
Endogenous ROS production in early differentiation state suppresses endoderm differentiation via transient FOXC1 expression
Authors: Oka Sugako , Tsuzuki Teruhisa , Hidaka Masumi , Ohno Mizuki , Nakatsu Yoshimichi , Sekiguchi Mutsuo
Published: April 2022

Oxidative stress plays a pivotal role in the differentiation and proliferation of cells and programmed cell death. However, studies on the role of oxidative stress in differentiation have mainly employed the detection of reactive oxygen species (ROS) during differentiation or generated by ROS inducers. Therefore, it is difficult to clarify the significance of endogenous ROS production in the differentiation of human cells. We developed a system to control the intracellular level of ROS in the initial stage of differentiation in human iPS cells. By introducing a specific substitution (I69E) into the SDHC protein, a component of the mitochondrial respiratory chain complex, the endogenous ROS level increased. This caused impaired endoderm differentiation of iPS cells, and this impairment was reversed by overproduction of mitochondrial-targeted catalase, an anti-oxidant enzyme. Expression of tumor-related FOXC1 transcription factor increased transiently as early as 4 h after ROS-overproduction in the initial stage of differentiation. Knockdown of FOXC1 markedly improved impaired endoderm differentiation, suggesting that endogenous ROS production in the early differentiation state suppresses endoderm differentiation via transient FOXC1 expression.
Opposite physiological and pathological mTORC1-mediated roles of the CB1 receptor in regulating renal tubular function
Authors: Hinden Liad , Ahmad Majdoleen , Hamad Sharleen , Nemirovski Alina , Szanda Gergő , Glasmacher Sandra , Kogot-Levin Aviram , Abramovitch Rinat , Thorens Bernard , Gertsch Jürg , Leibowitz Gil , Tam Joseph
Published: April 2022

Activation of the cannabinoid-1 receptor (CB1R) and the mammalian target of rapamycin complex 1 (mTORC1) in the renal proximal tubular cells (RPTCs) contributes to the development of diabetic kidney disease (DKD). However, the CB1R/mTORC1 signaling axis in the kidney has not been described yet. We show here that hyperglycemia-induced endocannabinoid/CB1R stimulation increased mTORC1 activity, enhancing the transcription of the facilitative glucose transporter 2 (GLUT2) and leading to the development of DKD in mice; this effect was ameliorated by specific RPTCs ablation of GLUT2. Conversely, CB1R maintained the normal activity of mTORC1 by preventing the cellular excess of amino acids during normoglycemia. Our findings highlight a novel molecular mechanism by which the activation of mTORC1 in RPTCs is tightly controlled by CB1R, either by enhancing the reabsorption of glucose and inducing kidney dysfunction in diabetes or by preventing amino acid uptake and maintaining normal kidney function in healthy conditions.
Light-driven transition-metal-free direct decarbonylation of unstrained diaryl ketones via a dual C–C bond cleavage
Authors: Cao Dawei , Ataya Mohamad , Chen Zhangpei , Zeng Huiying , Peng Yong , Khaliullin Rustam Z. , Li Chao-Jun
Published: April 2022

The cleavage and formation of carbon−carbon bonds have emerged as powerful tools for structural modifications in organic synthesis. Although transition−metal−catalyzed decarbonylation of unstrained diaryl ketones provides a viable protocol to construct biaryl structures, the use of expensive catalyst and high temperature (>140 oC) have greatly limited their universal applicability. Moreover, the direct activation of two inert C − C bonds in diaryl ketones without the assistance of metal catalyst has been a great challenge due to the inherent stability of C − C bonds (nonpolar, thermo-dynamically stable, and kinetically inert). Here we report an efficient light-driven transition-metal-free strategy for decarbonylation of unstrained diaryl ketones to construct biaryl compounds through dual inert C − C bonds cleavage. This reaction featured mild reaction conditions, easy-to-handle reactants and reagents, and excellent functional groups tolerance. The mechanistic investigation and DFT calculation suggest that this strategy proceeds through the formation of dioxy radical intermediate via a single-electron-transfer (SET) process between photo-excited diaryl ketone and DBU mediated by DMSO, followed by removal of CO2 to construct biaryl compounds.
Multilayered control of splicing regulatory networks by DAP3 leads to widespread alternative splicing changes in cancer
Authors: Han Jian , An Omer , Ren Xi , Song Yangyang , Tang Sze Jing , Shen Haoqing , Ke Xinyu , Ng Vanessa Hui En , Tay Daryl Jin Tai , Tan Hui Qing , Kappei Dennis , Yang Henry , Chen Leilei
Published: April 2022

The dynamic regulation of alternative splicing requires coordinated participation of multiple RNA binding proteins (RBPs). Aberrant splicing caused by dysregulation of splicing regulatory RBPs is implicated in numerous cancers. Here, we reveal a frequently overexpressed cancer-associated protein, DAP3, as a splicing regulatory RBP in cancer. Mechanistically, DAP3 coordinates splicing regulatory networks, not only via mediating the formation of ribonucleoprotein complexes to induce substrate-specific splicing changes, but also via modulating splicing of numerous splicing factors to cause indirect effect on splicing. A pan-cancer analysis of alternative splicing across 33 TCGA cancer types identified DAP3-modulated mis-splicing events in multiple cancers, and some of which predict poor prognosis. Functional investigation of non-productive splicing of WSB1 provides evidence for establishing a causal relationship between DAP3-modulated mis-splicing and tumorigenesis. Together, our work provides critical mechanistic insights into the splicing regulatory roles of DAP3 in cancer development.
Loss of Rnf31 and Vps4b sensitizes pancreatic cancer to T cell-mediated killing
Authors: Frey Nina , Tortola Luigi , Egli David , Janjuha Sharan , Rothgangl Tanja , Marquart Kim Fabiano , Ampenberger Franziska , Kopf Manfred , Schwank Gerald
Published: April 2022

Pancreatic ductal adenocarcinoma (PDA) is an inherently immune cell deprived tumor, characterized by desmoplastic stroma and suppressive immune cells. Here we systematically dissect PDA intrinsic mechanisms of immune evasion by in vitro and in vivo CRISPR screening, and identify Vps4b and Rnf31 as essential factors required for escaping CD8+ T cell killing. For Vps4b we find that inactivation impairs autophagy, resulting in increased accumulation of CD8+ T cell-derived granzyme B and subsequent tumor cell lysis. For Rnf31 we demonstrate that it protects tumor cells from TNF-mediated caspase 8 cleavage and subsequent apoptosis induction, a mechanism that is conserved in human PDA organoids. Orthotopic transplantation of Vps4b- or Rnf31 deficient pancreatic tumors into immune competent mice, moreover, reveals increased CD8+ T cell infiltration and effector function, and markedly reduced tumor growth. Our work uncovers vulnerabilities in PDA that might be exploited to render these tumors more susceptible to the immune system.
Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells
Authors: Franchina Davide G. , Kurniawan Henry , Grusdat Melanie , Binsfeld Carole , Guerra Luana , Bonetti Lynn , Soriano-Baguet Leticia , Ewen Anouk , Kobayashi Takumi , Farinelle Sophie , Minafra Anna Rita , Vandamme Niels , Carpentier Anaïs , Borgmann Felix K. , Jäger Christian , Chen Ying , Kleinewietfeld Markus , Vasiliou Vasilis , Mittelbronn Michel , Hiller Karsten , Lang Philipp A. , Brenner Dirk
Published: April 2022

The metabolic principles underlying the differences between follicular and marginal zone B cells (FoB and MZB, respectively) are not well understood. Here we show, by studying mice with B cell-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), that glutathione synthesis affects homeostasis and differentiation of MZB to a larger extent than FoB, while glutathione-dependent redox control contributes to the metabolic dependencies of FoB. Specifically,Gclcablation in FoB induces metabolic features of wild-type MZB such as increased ATP levels, glucose metabolism, mTOR activation, and protein synthesis. Furthermore,Gclc-deficient FoB have a block in the mitochondrial electron transport chain (ETC) due to diminished complex I and II activity and thereby accumulate the tricarboxylic acid cycle metabolite succinate. Finally,Gclcdeficiency hampers FoB activation and antibody responses in vitro and in vivo, and induces susceptibility to viral infections. Our results thus suggest thatGclcis required to ensure the development of MZB, the mitochondrial ETC integrity in FoB, and the efficacy of antiviral humoral immunity.
Radiationless mechanism of UV deactivation by cuticle phenolics in plants
Authors: González Moreno Ana , de Cózar Abel , Prieto Pilar , Domínguez Eva , Heredia Antonio
Published: April 2022

Hydroxycinnamic acids present in plant cuticles, the interphase and the main protective barrier between the plant and the environment, exhibit singular photochemical properties that could allow them to act as a UV shield. Here, we employ transient absorption spectroscopy on isolated cuticles and leaf epidermises to study in situ the photodynamics of these molecules in the excited state. Based on quantum chemical calculations on p-coumaric acid, the main phenolic acid present in the cuticle, we propose a model in which cuticle phenolics display a photoprotective mechanism based in an ultrafast and non-radiative excited state deactivation combined with fluorescence emission. As such, the cuticle can be regarded as the first and foremost protective barrier against UV radiation. This photostable and photodynamic mechanism seems to be universal in land plants giving a special role and function to the presence of different aromatic domains in plant cuticles and epidermises.
Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age
Authors: Mills William A. , Woo AnnaLin M. , Jiang Shan , Martin Joelle , Surendran Dayana , Bergstresser Matthew , Kimbrough Ian F. , Eyo Ukpong B. , Sofroniew Michael V. , Sontheimer Harald
Published: April 2022

Astrocytes extend endfeet that enwrap the vasculature, and disruptions to this association which may occur in disease coincide with breaches in blood-brain barrier (BBB) integrity. Here we investigate if focal ablation of astrocytes is sufficient to disrupt the BBB in mice. Targeted two-photon chemical apoptotic ablation of astrocytes induced a plasticity response whereby surrounding astrocytes extended processes to cover vascular vacancies. In young animals, replacement processes occur in advance of endfoot retraction, but this is delayed in aged animals. Stimulation of replacement astrocytes results in constriction of pre-capillary arterioles, suggesting that replacement astrocytes are functional. Pharmacological inhibition of pSTAT3, as well as astrocyte specific deletion of pSTAT3, reduces astrocyte replacement post-ablation, without perturbations to BBB integrity. Similar endfoot replacement occurs following astrocyte cell death due to reperfusion in a stroke model. Together, these studies uncover the ability of astrocytes to maintain cerebrovascular coverage via substitution from nearby cells.
Ensemble of nucleic acid absolute quantitation modules for copy number variation detection and RNA profiling
Authors: Wu Lucia Ruojia , Dai Peng , Wang Michael Xiangjiang , Chen Sherry Xi , Cohen Evan N. , Jayachandran Gitanjali , Zhang Jinny Xuemeng , Serrano Angela V. , Xie Nina Guanyi , Ueno Naoto T. , Reuben James M. , Barcenas Carlos H. , Zhang David Yu
Published: April 2022

Current gold standard for absolute quantitation of a specific DNA sequence is droplet digital PCR (ddPCR), which has been applied to copy number variation (CNV) detection. However, the number of quantitation modules in ddPCR is limited by fluorescence channels, which thus limits the CNV sensitivity due to sampling error following Poisson distribution. Here we develop a PCR-based molecular barcoding NGS approach, quantitative amplicon sequencing (QASeq), for accurate absolute quantitation scalable to over 200 quantitation modules. By attaching barcodes to individual target molecules with high efficiency, 2-plex QASeq exhibits higher and more consistent conversion yield than ddPCR in absolute molecule count quantitation. Multiplexed QASeq improves CNV sensitivity allowing confident distinguishment of 2.05 ploidy from normal 2.00 ploidy. We apply multiplexed QASeq to serial longitudinal plasma cfDNA samples from patients with metastaticERBB2+ (HER2+ ) breast cancer seeking association with tumor progression. We further show an RNA QASeq panel for targeted expression profiling.
Synthesis of ternary copper antimony sulfide via solventless thermolysis or aerosol assisted chemical vapour deposition using metal dithiocarbamates
Authors: Makin Fadiyah , Alam Firoz , Buckingham Mark A. , Lewis David J.
Published: April 2022

Copper antimony sulfide (Cu-Sb-S) has recently been proposed as an attractive alternative photovoltaic material due to the earth-abundant and non-toxic nature of the elements, high absorption coefficients and band gaps commensurate with efficient harvesting of solar photonic flux across multiple phases of Cu-Sb-S. These materials are therefore highly desirable and sustainable and scalable deposition techniques to produce them are of interest. In this paper, we demonstrate two facile, low-temperature and inexpensive techniques (solventless thermolysis and aerosol-assisted chemical vapor deposition (AACVD)) for the preparation of binary digenite (Cu1.8S), chalcocite (Cu2S) and stibnite (Sb2S3) and several phases of ternary copper-antimony-sulfide (Cu2xSb2(1−x)Sy, where 0 ≤ x ≤ 1). It was found that by utilising these different techniques and varying the ratio of Cu:Sb, pure phases of ternary chalcostibite (CuSbS2), fematinite (Cu3SbS4) and tetrahedrite (Cu12Sb4S13) can be achieved. Two single-source precursors were investigated for this purpose, namely the diethyldithiocarbamate (DTC) complexes of copper and antimony Cu(DTC)2and Sb(DTC)3. These were decomposed both individually (to produce binary materials) and combined (to produce ternary materials) at different ratios. From the solventless thermolysis and AACVD methods, either particulate or thin film material was formed, respectively. These materials were then characterised by powder XRD, SEM, EDX and Raman spectroscopies to determine the crystalline phase, material morphology and uniformity of elemental composition. This analysis demonstrated that as the Cu-content increases, the phase of the ternary material changes from chalcostibite (CuSbS2) and fematinite (Cu3SbS4) at a low Cu:Sb ratio to tetrahedrite (Cu12Sb4S13) at a high Cu:Sb ratio.
DNA methylation in peripheral tissues and left-handedness
Authors: Odintsova Veronika V. , Suderman Matthew , Hagenbeek Fiona A. , Caramaschi Doretta , Hottenga Jouke-Jan , Pool René ,   BIOS Consortium,   Management Team, Heijmans Bastiaan T. , ’t Hoen Peter A. C. , van Meurs Joyce , Isaacs Aaron , Jansen Rick , Franke Lude ,   Cohort collection, Boomsma Dorret I. , Pool René , van Dongen Jenny , Hottenga Jouke J. , van Greevenbroek Marleen M. J. , Stehouwer Coen D. A. , van der Kallen Carla J. H. , Schalkwijk Casper G. , Wijmenga Cisca , Franke Lude , Zhernakova Sasha , Tigchelaar Ettje F. , Slagboom P. Eline , Beekman Marian , Deelen Joris , van Heemst Diana , Veldink Jan H. , Van den Berg Leonard H. , van Duijn Cornelia M. , Hofman Bert A. , Isaacs Aaron , Uitterlinden André G. ,   Data Generation, van Meurs Joyce , Jhamai P. Mila , Verbiest Michael , Suchiman H. Eka D. , Verkerk Marijn , van der Breggen Ruud , van Rooij Jeroen , Lakenberg Nico ,   Data management and computational infrastructure, Mei Hailiang , van Iterson Maarten , van Galen Michiel , Bot Jan , Zhernakova Dasha V. , Jansen Rick , ’t Hof Peter van , Deelen Patrick , Nooren Irene , ’t Hoen Peter A. C. , Heijmans Bastiaan T. , Moed Matthijs ,   Data Analysis Group, Franke Lude , Vermaat Martijn , Zhernakova Dasha V. , Luijk René , Bonder Marc Jan , van Iterson Maarten , Deelen Patrick , van Dijk Freerk , van Galen Michiel , Arindrarto Wibowo , Kielbasa Szymon M. , Swertz Morris A. , van Zwet Erik. W. , Jansen Rick , ’t Hoen Peter-Bram , Heijmans Bastiaan T. , Dolan Conor V. , Ligthart Lannie , van Beijsterveldt Catharina E. M. , Willemsen Gonneke , de Geus Eco J. C. , Beck Jeffrey J. , Ehli Erik A. , Cuellar-Partida Gabriel , Evans David M. , Medland Sarah E. , Relton Caroline L. , Boomsma Dorret I. , van Dongen Jenny
Published: April 2022

Handedness has low heritability and epigenetic mechanisms have been proposed as an etiological mechanism. To examine this hypothesis, we performed an epigenome-wide association study of left-handedness. In a meta-analysis of 3914 adults of whole-blood DNA methylation, we observed that CpG sites located in proximity of handedness-associated genetic variants were more strongly associated with left-handedness than other CpG sites (P = 0.04), but did not identify any differentially methylated positions. In longitudinal analyses of DNA methylation in peripheral blood and buccal cells from children (N = 1737), we observed moderately stable associations across age (correlation range [0.355–0.578]), but inconsistent across tissues (correlation range [− 0.384 to 0.318]). We conclude that DNA methylation in peripheral tissues captures little of the variance in handedness. Future investigations should consider other more targeted sources of tissue, such as the brain.
Proteomic analysis of the periodontal pathogen Prevotella intermedia secretomes in biofilm and planktonic lifestyles
Authors: Karched Maribasappa , Bhardwaj Radhika G. , Qudeimat Muawia , Al-Khabbaz Areej , Ellepola Arjuna
Published: April 2022

Prevotella intermediais an important species associated with periodontitis. Despite the remarkable clinical significance, little is known about the molecular basis for its virulence. The aim of this study was to characterize the secretome ofP. intermediain biofilm and planktonic life mode. The biofilm secretome showed 109 proteins while the planktonic secretome showed 136 proteins. The biofilm and the planktonic secretomes contained 17 and 33 signal-peptide bearing proteins, 13 and 18 lipoproteins, respectively. Superoxide reductase, sensor histidine kinase, C40 family peptidase, elongation factor Tu, threonine synthase etc. were unique to biofilm. Of the ~ 30 proteins with predicted virulence potential from biofilm and planktonic secretomes, only 6 were common between the two groups, implying large differences between biofilm and planktonic modes ofP. intermedia. From Gene Ontology biofilm secretome displayed a markedly higher percent proteins compared to planktonic secretome in terms of cellular amino acid metabolic process, nitrogen compound metabolic process etc. Inflammatory cytokine profile analysis revealed that only the biofilm secretome, not the planktonic one, induced important cytokines such as MIP-1α/MIP-1β, IL-1β, and IL-8. In conclusion, the revealed differences in the protein profiles ofP. intermediabiofilm and planktonic secretomes may trigger further questions about molecular mechanisms how this species exerts its virulence potential in the oral cavity.
Ornithophily in the subtribe Maxillariinae (Orchidaceae) proven with a case study of Ornithidium fulgens in Guatemala
Authors: Lipińska Monika M. , Archila Fredy L. , Haliński Łukasz P. , Łuszczek Dorota , Szlachetko Dariusz L. , Kowalkowska Agnieszka K.
Published: April 2022

Ornithophily has been long speculated to occur in the subtribe Maxillariinae (Orchidaceae), relying either solely on micromorphological analyses or scarce field observations of undefined species. In Guatemala we were able to observe regular visits of the azure-crowned hummingbirds feeding on flowers of Ornithidium fulgens. These observations have led us to investigation of floral attractants by means of scanning and transmission microscopy, histochemical and chemical analyses (GC–MS). Conducted investigation revealed that the epidermis of basal protuberance of column-foot has features proving the secretory activity and that secreted nectar is sucrose-dominant. Slight secretion on the middle part of the lip is puzzling. The presence of other potential pollinators has not been reported. Based on the results of this study, we confirmed that the flowers of O. fulgens meet all criteria of ornithophily and thus that the hypothesis about bird pollination in the subtribe Maxillariinae is proven. The presented results confirm that the previously described floral features predicting the bird pollination in this group are justified. This strengthens the theory about floral adaptations to different pollinators and gives valid reasons to consider species with flowers with a certain set of traits as ornithophilous, even in the absence of the pollination observation.
Coupling genetic structure analysis and ecological-niche modeling in Kersting’s groundnut in West Africa
Authors: Coulibaly Mariam , Idohou Rodrigue , Akohoue Félicien , Peterson Andrew Townsend , Sawadogo Mahamadou , Achigan-Dako Enoch Gbenato
Published: April 2022

Orphan legume crops play an important role in smallholder farmers’ food systems. Though less documented, they have the potential to contribute to adequate nutrition in vulnerable communities. Unfortunately, data are scarce about the potential of those crops to withstand current and future climate variations. Using Macrotyloma geocarpum as an example, we used ecological niche modeling to explore the role of ecology on the current and future distributions of genetic populations of Kersting’s groundnut. Our findings showed that: (1) the models had good predictive power, indicating that M. geocarpum’s distribution was correlated with both climatic and soil layers; (2) identity and similarity tests revealed that the two genetic groups have identical and similar environmental niches; (3) by integrating the genetic information in niche modeling, niches projections show divergence in the response of the species and genetic populations to ongoing climate change. This study highlights the importance of incorporating genetic data into Ecological Niche Modeling (ENM) approaches to obtain a finer information of species’ future distribution, and explores the implications for agricultural adaptation, with a particular focus on identifying priority actions in orphan crops conservation and breeding.
Validation and quantification of left ventricular function during exercise and free breathing from real-time cardiac magnetic resonance images
Authors: Edlund Jonathan , Haris Kostas , Ostenfeld Ellen , Carlsson Marcus , Heiberg Einar , Johansson Sebastian , Östenson Björn , Jin Ning , Aletras Anthony H. , Steding-Ehrenborg Katarina
Published: April 2022

Exercise cardiovascular magnetic resonance (CMR) can unmask cardiac pathology not evident at rest. Real-time CMR in free breathing can be used, but respiratory motion may compromise quantification of left ventricular (LV) function. We aimed to develop and validate a post-processing algorithm that semi-automatically sorts real-time CMR images according to breathing to facilitate quantification of LV function in free breathing exercise. A semi-automatic algorithm utilizing manifold learning (Laplacian Eigenmaps) was developed for respiratory sorting. Feasibility was tested in eight healthy volunteers and eight patients who underwent ECG-gated and real-time CMR at rest. Additionally, volunteers performed exercise CMR at 60% of maximum heart rate. The algorithm was validated for exercise by comparing LV mass during exercise to rest. Respiratory sorting to end expiration and end inspiration (processing time 20 to 40 min) succeeded in all research participants. Bias ± SD for LV mass was 0 ± 5 g when comparing real-time CMR at rest, and 0 ± 7 g when comparing real-time CMR during exercise to ECG-gated at rest. This study presents a semi-automatic algorithm to retrospectively perform respiratory sorting in free breathing real-time CMR. This can facilitate implementation of exercise CMR with non-ECG-gated free breathing real-time imaging, without any additional physiological input.
Progenitor cells from brown adipose tissue undergo neurogenic differentiation
Authors: Jumabay Medet , Zhang Li , Yao Jiayi , Boström Kristina I.
Published: April 2022

Multipotent cells derived from white adipose tissue have been shown to differentiate into multiple lineages including neurogenic lineages. However, the high innervation of brown adipose tissue by the sympathetic nervous system suggest it might be a better source of neural precursor cells. To investigate potential differences between white and brown progenitors, we cultured white and brown dedifferentiated fat (wDFAT and brDFAT) cells from mouse and human adipose tissue and compared marker expression of neural precursors, and neuronal and glial cells, using fluorescence-activated cell sorting, bright-field imaging, immunofluorescence, and RNA analysis by qPCR. The results showed that both wDFAT and brDFAT cells had the capacity to generate neuronal and glial-like cells under neurogenic conditions. However, the brDFAT cells exhibited enhanced propensity for neurogenic differentiation. The neurogenic cells were at least in part derived from Adiponectin-expressing cells. TdTomato-expressing cells derived from Adiponectin (Adipoq) CreERT2 -tdTomatoflox/flox mice gave rise to individual cells and cell clusters with neurogenic characteristics. Moreover, human brDFAT cells demonstrated a similar ability to undergo neurogenic differentiation after treatment with neurogenic medium, as assessed by immunofluorescence and qPCR. Together, our results support that brDFAT cells have ability to undergo neurogenic differentiation.
Biosynthesis of S-adenosyl-methionine enhances aging-related defects in Drosophila oogenesis
Authors: Hayashi Yoshiki , Kashio Soshiro , Murotomi Kazutoshi , Hino Shinjiro , Kang Woojin , Miyado Kenji , Nakao Mitsuyoshi , Miura Masayuki , Kobayashi Satoru , Namihira Masakazu
Published: April 2022

Tissue aging is a major cause of aging-related disabilities and a shortened life span. Understanding how tissue aging progresses and identifying the factors underlying tissue aging are crucial; however, the mechanism of tissue aging is not fully understood. Here we show that the biosynthesis of S-adenosyl-methionine (SAM), the major cellular donor of methyl group for methylation modifications, potently accelerates the aging-related defects during Drosophila oogenesis. An aging-related increase in the SAM-synthetase (Sam-S) levels in the germline leads to an increase in ovarian SAM levels. Sam-S-dependent biosynthesis of SAM controls aging-related defects in oogenesis through two mechanisms, decreasing the ability to maintain germline stem cells and accelerating the improper formation of egg chambers. Aging-related increases in SAM commonly occur in mouse reproductive tissue and the brain. Therefore, our results raise the possibility suggesting that SAM is the factor related to tissue aging beyond the species and tissues.
Vascular endothelial growth factor (VEGF) polymorphism rs3025039 and atherosclerosis among older with hypertension
Authors: Shimizu Yuji , Arima Kazuhiko , Noguchi Yuko , Yamanashi Hirotomo , Kawashiri Shin-Ya , Nobusue Kenichi , Nonaka Fumiaki , Aoyagi Kiyoshi , Nagata Yasuhiro , Maeda Takahiro
Published: April 2022

Angiogenesis inhibition therapy causes hypertension by increasing peripheral vascular resistance. Vasa vasorum angiogenesis plays a crucial role in the development of atherosclerosis. Since vascular endothelial growth factor (VEGF), which contributes to the progress of angiogenesis, is reported to be inversely associated with the minor allele of polymorphism rs3025039, the minor allele of rs3025039 could be inversely associated with atherosclerosis among individuals with hypertension. A cross-sectional study of 1793 older Japanese adults aged 60–89 years with hypertension who participated in general health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. The minor allele of polymorphism rs3025020 was positively associated with VEGF. Therefore, in addition to known cardiovascular risk factors, rs3025020 genotype acted as a confounding factor in the present study. Independent of known confounding factors, the minor allele of rs3025039 was inversely associated with atherosclerosis among older Japanese adults with hypertension. The fully adjusted odds ratio (OR) and 95% confidence interval (CI) for atherosclerosis with the minor allele of rs3025039 was 0.78 (0.64, 0.96). The angiogenesis-related polymorphism rs3025039 was associated with the development of atherosclerosis among older Japanese individuals. This study indicates that the development of atherosclerosis among older individuals might partly indicate a capacity for angiogenesis.
Influence of yellow gypsum on nutrient uptake and yield of groundnut in different acid soils of Southern India
Authors: M Laxmanarayanan , Dhumgond Prabhudev , Shruthi  , C R Jahir Basha , Sarkar Supriya , Nagabovanalli B Prakash
Published: April 2022

Yellow gypsum (YG), a synthetic product from Linz-Donawitz slag containing high iron (Fe) (5.41%), zinc (Zn) (0.37%) and silicon (Si) (3.41%) can be used as a source of these nutrients along with calcium (Ca) and sulphur (S) for groundnut production. Three field experiments were conducted to know the effect of different rates (500 and 625 kg YG ha−1) and time of application (basal alone and basal + split) of YG on growth, yield and economic returns of groundnut, and micronutrient and Si availability and their uptake in comparison with basal application of 500 kg natural gypsum (NG) ha−1. Basal alone and basal + split application of YG significantly increased the growth, yield and economic returns of groundnut. Further, it increased the soil pH, availability of micronutrients, Si and their uptake by haulm and kernel of groundnut over NG. Irrespective of the location, YG application recorded higher plant available nutrient (PAN) coefficient of micronutrients, while NG application recorded higher PAN recovery coefficient of Si. Basal + split application of YG resulted in better growth and yield of groundnut than basal application of YG. In conclusion, YG can be a potential alternative for NG as a source of Fe, Zn and Si along with Ca and S for groundnut production.
Metformin Ameliorates Hepatic Steatosis induced by olanzapine through inhibiting LXRα/PCSK9 pathway
Authors: Zhu Wenqiang , Ding Chen , Huang Piaopiao , Ran Juanli , Lian Pingan , Tang Yaxin , Dai Wen , Huang Xiansheng
Published: April 2022

Studies have confirmed that olanzapine, the mainstay treatment for schizophrenia, triggers metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). However, the etiology of olanzapine-induced NAFLD is poorly understood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in NAFLD pathogenesis, and metformin can significantly decrease circulating PCSK9. The purpose of this study was to investigate the role of PCSK9 and explore the therapeutic effect of metformin for olanzapine-associated NAFLD. Olanzapine significantly upregulated PCSK9 and promoted lipid accumulation in mouse livers and HepG2 and AML12 cells. Metformin ameliorated these pathological alterations. PCSK9 upstream regulator liver X receptor α (LXRα) was significantly upregulated in olanzapine-induced NAFLD. LXRα antagonist treatment and LXRα overexpression resulted in a decrease and increase of PCSK9, respectively. Hepatic lipogenesis-associated genes FAS and SCD1 were significantly upregulated in olanzapine-induced NAFLD mice and HepG2 cells overexpressing PCSK9, and genes related to lipid β-oxidation (SCAD and PPARα) were downregulated, while metformin reversed these changes. In addition, we found that LXRα overexpression compromised the effect of metformin on PCSK9 levels and intracellular lipid droplet formation. Taken together, our findings suggest that olanzapine enhances hepatic PCSK9 expression by upregulating LXRα, thereby increasing FAS and SCD1 expression as well as decreasing SCAD and PPARα, and promoting lipid accumulation, and, subsequently, NAFLD, which is ameliorated by metformin.
Chemiluminescent screening of specific hybridoma cells via a proximity-rolling circle activated enzymatic switch
Authors: Ao Hang , Chen Weiwei , Wu Jie , Xiao Wencheng , Ju Huangxian
Published: April 2022

The mass-production capability of hybridoma technology is bottlenecked by the routine screening procedure which is time-consuming and laborious as the requirement of clonal expansion. Here, we describe a 1-day chemiluminescent screening protocol for specific hybridoma cells on conventional 96-well plate via a proximity-rolling circle activated enzymatic switch (P-RCAES) strategy. The P-RCAES uses a pair of antigen-DNA probes to recognize secreted specific antibody and proximity-induce rolling circle amplification for mass-production of pyrophosphate to activate Cu(II) inhibited horseradish peroxidase and generate a strong chemiluminescent signal. The P-RCAES based homogeneous chemiluminescent assay can detect antibody down to 18 fM, and enables the screening of specific hybridoma cells secreting PCSK9 antibody at single-cell level without tedious cloning process. The proposed fast screening protocol has good expansibility without need of sophisticated instruments, and provides a screening method for greatly improving the efficiency of hybridoma technology.
Anisotropic electrene T′-Ca2P with electron gas magnetic coupling as anode material for Na/K ion batteries
Authors: Jiang Jiaxin , Wang Kai , Guo Hongyan , Zuo Guizhong , Zhuo Zhiwen , Lu Ning
Published: April 2022

A novel stable magnetic electrene T′-Ca2P as an anode material for Na/K ion batteries is proposed by using first principles calculations.
Mechanism of biochanin A alleviating PM2.5-induced oxidative damage based on an XRCC1 knockout BEAS-2B cell model
Authors: Yu Yue , Li Ang , Li Shihao , Zheng Bowen , Ma Juan , Liu Yazhou , Kou Xiaohong , Xue Zhaohui
Published: April 2022

PM2.5 induces oxidative/antioxidant system imbalance and produces toxic effects and irreversible damage to the genetic material including chromosomes and DNA. And biochanin A has a moderating effect on these processes.
Heterointerface optimization in a covalent organic framework-on-MXene for high-performance capacitive deionization of oxygenated saline water
Authors: Zhang Shuaihua , Xu Xingtao , Liu Xiaohong , Yang Qian , Shang Ningzhao , Zhao Xiaoxian , Zang Xiaohuan , Wang Chun , Wang Zhi , Shapter Joseph G. , Yamauchi Yusuke
Published: April 2022

Covalent organic framework-on-MXene heterostructure was fabricated to overcome the poor capacitive deionization performance of conventional materials in natural (oxygenated) saline water.
Synthesis of BINOL–xylose-conjugates as “Turn-off” fluorescent receptors for Fe3+ and secondary recognition of cysteine by their complexes
Authors: Wang Huizhen , Liu Yang , Zhang Yafeng , Sun Xiaoxia
Published: April 2022

A fluorescence sensor of BINOL–xylose derivative was synthesized, which could only detect Fe3+ by 1 + 1 complex with high selectivity and sensitivity. The complex of the derivative with Fe3+ was found to perform secondary recognition of cysteine.
Considering the hexad of learning domains in the laboratory to address the overlooked aspects of chemistry education and fragmentary approach to assessment of student learning
Authors: Agustian Hendra Y.
Published: April 2022

This article seeks to provide researchers and practitioners in laboratory education, particularly those involved in the curriculum design and implementation of teaching laboratories at university level, with a conceptual framework and a working model for an integrated assessment of learning domains, by attending to a more holistic approach to learning in the laboratory. Prevailing learning theories suggest that the triad of cognitive, psychomotor, and affective domains should be addressed in order to warrant meaningful learning. In the research tradition of psychology and philosophy of mind, this triad also manifests as a concert of cognitive, conative, and affective domains. The paper argues that at least in the context of chemistry laboratory education, this is insufficient. The social and epistemic domains are often overlooked or dismissed altogether. Research in science studies may provide insight into the urgency and usefulness of integrating these domains into chemistry teaching and learning. Firstly, laboratory work is conceptualised here as an epistemic practice, in which students generate data, propose knowledge derived from the data, evaluate, and legitimise it. Secondly, the operationalisation of the hexad of learning domains is proposed, in terms of curriculum design, instruction, and assessment.
Making thermodynamic models of mixtures predictive by machine learning: matrix completion of pair interactions
Authors: Jirasek Fabian , Bamler Robert , Fellenz Sophie , Bortz Michael , Kloft Marius , Mandt Stephan , Hasse Hans
Published: April 2022

Embedding matrix completion methods from machine learning in classical thermodynamic models creates powerful hybrid models for predicting properties of mixtures.
Sprayable hydrogel for biomedical applications
Authors: Liao Yingying , Xie Luoyijun , Ye Jiahui , Chen Tong , Huang Tong , Shi Leilei , Yuan Miaomiao
Published: April 2022

Schematic illustration of sprayable hydrogels for biomedical application.
Effective medium theory for bcc metals: electronically non-adiabatic H atom scattering in full dimensions
Authors: Hertl Nils , Kandratsenka Alexander , Wodtke Alec M.
Published: April 2022

We derive a many-body formalism for interaction energies of adsorbates in metals and use it for. electronically non-adiabatic H atom scattering simulations from metal surfaces.
Determination of radiative and multiphonon non-radiative relaxation rates of upconversion materials
Authors: Fu Lin , Wu Yusong , Zhang Changxian , Fu Tairan , Shi Congling
Published: April 2022

The application of the method of multi-wavelength excitation and level-by-level parameter calculation for β-NaYF4:Er3+ six-level system.
FeVO4 nanowires for efficient photocatalytic CO2 reduction
Authors: Li Yang , Zeng Zhaojian , Chen Yong , Zhang Yuanming , Wang Wenjing , Xu Xiaoming , Du Mengyang , Li Zhaosheng , Zou Zhigang
Published: April 2022

Band structures of the FeVO4 semiconductor were investigated by first-principles calculations, and FeVO4 nanowires can greatly improve the performance of photocatalytic CO2 reduction.
Study of the DNA binding mechanism and in vitro activity against cancer cells of iron(iii) and aluminium(iii) kojic acid derivative complexes
Authors: Lachowicz Joanna I. , Mateddu Anna , Coni Pierpaolo , Caltagirone Claudia , Murgia Sergio , Gibson Dan , dalla Torre Gabriele , Lopez Xabier , Meloni Federico , Pichiri Giuseppina
Published: April 2022

Iron(iii) complexes are a promising alternative to the currently used platinum complexes with high hazards and environmental risks. Iron(iii) complexes bind to the phosphates of DNA by the ligand displacement mechanism and inhibit polymerization.
Synthesis and performance evaluation of 5-fluorouracil-loaded zwitterionic poly(4-vinylpyridine) nanoparticles
Authors: Malekzadeh Ali , Zahedi Payam , Abdouss Majid
Published: April 2022

After polymerizing 4-vinylpyridine, the obtained polymer was converted into zwitterionic nanoparticles containing 5-fluorouracil. Their potential for long-term blood circulation was investigated by in vitro and in vivo experiments.
The delicate balance of phase speciation in bimetallic nickel cobalt nanoparticles
Authors: Palazzolo Alberto , Poucin Cyprien , Freitas Alexy P. , Ropp Anthony , Bouillet Corinne , Ersen Ovidiu , Carenco Sophie
Published: April 2022

Bimetallic NiCo nanoparticles crystallized in the fcc phase are formed using optimized synthetic parameters.
Computational screening of single-atom catalysts supported by VS2 monolayers for electrocatalytic oxygen reduction/evolution reactions
Authors: Qin Zengming , Wang Zhongxu , Zhao Jingxiang
Published: April 2022

Single Ni atom anchored on pristine and N-doped VS2 monolayer can perform as bifunctional catalyst for ORR and OER.
N-Methoxy-1,3-oxazinane nucleic acids (MOANAs) – a configurationally flexible backbone modification allows post-synthetic incorporation of base moieties
Authors: Afari Mark N. K. , Virta Pasi , Lönnberg Tuomas
Published: April 2022

A (2R,3S)-4-(methoxyamino)butane-1,2,3-triol residue within forms N-methoxy-1,3-oxazinanes with a variety of aldehydes, providing easy and pH-controllable access to base-modified oligonucleotides.
Correction: Diastereoselective synthesis of glycopyrans 1,2-annulated with dioxazinanes from 1,2-anhydrosugars and N-substituted nitrones
Authors: Ahmed Ajaz , Sakander Norein , Rasool Faheem , Hussain Nazar , Mukherjee Debaraj
Published: April 2022

Correction for ‘Diastereoselective synthesis of glycopyrans 1,2-annulated with dioxazinanes from 1,2-anhydrosugars and N-substituted nitrones’ by Ajaz Ahmed et al., Org. Biomol. Chem., 2022, 20, 1436–1443, DOI: 10.1039/d1ob02310a.
PPy-constructed core–shell structures from MOFs for confining lithium polysulfides
Authors: Geng Pengbiao , Du Meng , Wu Chunsheng , Luo Tianxing , Zhang Yi , Pang Huan
Published: April 2022

Core–shell structured MIL-96-Al composites are prepared through a melt-diffusion method followed by a water-phase polymerization process. The composites can strongly confine lithium polysulfides in a cathode.
Asperflavipines C–E and aspermichalasine A: three cytochalasan heterotetramers and an unusual cytochalasan monomer from Aspergillus micronesiensis
Authors: Zhang Xiaotian , Wu Zhaodi , Bao Alan , Zhao Ziming , Chen Yu , Zhao Huimin , Wang Jianping , Chen Chunmei , Tong Qingyi , Zhu Hucheng , Zhang Yonghui
Published: April 2022

Asperflavipines C–E, three new cytochalasin heterotetramers, possessing a highly complex tetradecacyclic ring system with continuous bridged ring systems, and aspermichalasine A, possessing an unusual 5/6/5/8 ring system, were isolated.
Coupling nucleic acid circuitry with the CRISPR-Cas12a system for universal and signal-on detection
Authors: Zhao Rujian , Yu Chunxu , Lu Baiyang , Li Bingling
Published: April 2022

We report a universal and signal-on HCR based detection platform via coupling the CRISPR-Cas12a system with HCR. By using this CRISPR-HCR pathway, we can detect different targets by only changing the crRNA, with practical sensitivity as low as ∼aM.
A reversible plasmonic nanoprobe for dynamic imaging of intracellular pH during endocytosis
Authors: Wang Jin , Yu Qiao , Li Xiang-Ling , Zhao Xue-Li , Chen Hong-Yuan , Xu Jing-Juan
Published: April 2022

An Au@PANI core–shell plasmonic nanomaterial was constructed for visualizing the pH evolution during endocytosis.
Specific deformation behavior of isotactic polypropylene films under a multiaxial stress field
Authors: Kojio Ken , Fujimoto Aya , Nagano Chigusa , Nozaki Shuhei , Yokomachi Kazutoshi , Kamitani Kazutaka , Watanabe Hirohmi , Takahara Atsushi
Published: April 2022

The specific deformation behavior of crystalline polymer films, namely unoriented crystallized isotactic polypropylene (it PP) films, was investigated under a multiaxial stress field.
A versatile biomimetic multienzyme cascade nanoplatform based on boronic acid-modified metal–organic framework for colorimetric biosensing
Authors: Shen Hao , Shi Haimei , Feng Bin , Ding Chuanfan , Yu Shaoning
Published: April 2022

An exquisitely designed multienzyme cascade nanoplatform has been constructed by immobilizing enzymes on a boronic acid functionalized metal–organic framework which was synthesized by a microwave-assisted metal–ligand-fragment co-assembly strategy.
Animal protein-plant protein composite nanospheres for dual-drug loading and synergistic cancer therapy
Authors: Lu Minqi , Wu Mi , Huang Yufang , Yao Jinrong , Shao Zhengzhong , Chen Xin
Published: April 2022

Silk fibroin/zein nanospheres not only have a unique structure but can also encapsulate two anti-cancer drugs in them, showing a considerable synergistic therapeutic effect.
Supernova remnant G46.8–0.3: A new case of interaction with molecular material
Authors: Supan L. , Fischetto G. , Castelletti G.
Published: April 2022

Although the Galactic supernova remnant (SNR) G46.8–0.3 has been known for more than 50 yr, no specific studies of this source or its environment have been published to date. To make progress on this matter, we measured new flux densities from radio surveys and combined them with previous estimates carefully collected from the literature to create an improved and fully populated version of the integrated radio spectrum for G46.8–0.3. The resulting spectrum exhibits a featureless power-law form with an exponent α = −0.535 ± 0.012. The lack of a spectral turnover at the lowest radio frequencies, which is observable in many other SNRs, excludes the presence of abundant ionised gas either proximate to the SNR itself or along its line of sight. The analysis of local changes in the radio spectral index across G46.8–0.3 suggests a tendency to slightly steepen approximately at 1 GHz. Even if this steepening is real, it does not impact the integrated spectrum of the source. Deeper imaging of the radio structures of G46.8–0.3 and spectral maps constructed from matched raw data are needed to provide new insights into the local spectral properties of the remnant. On the basis of the spectral properties of the atomic gas, we placed the remnant at 8.7 ± 1.0 kpc and we revisited the distance to the nearby H ii region G046.495–00.241 to 7.3 ± 1.2 kpc. From evolutionary models and our distance estimate, we conclude that G46.8–0.3 is a middle-aged (~1 × 104 yr) SNR. Furthermore, we recognise several 12CO and 13CO molecular structures in the proximity of the remnant. We used combined CO-H i profiles to derive the kinematic distances to these features and characterise their physical properties. We provide compelling evidence for environmental molecular clouds physically linked to G46.8–0.3 at its centre, on its eastern edge, and towards the northern and southwestern rims on the far side of the SNR shell. Our study of the molecular matter does not confirm that the remnant is embedded in a molecular cavity as previously suggested. G46.8–0.3 shows a line-of-sight coincidence with the γ-ray source 4FGL J1918.1+1215c detected at GeV energies by the space telescope Fermi. A rough analysis based on the properties of the interstellar matter close to G46.8–0.3 indicates that the GeV γ-ray photons detected in the direction to the SNR can be plausibly attributed to hadronic collisions and/or bremsstrahlung radiation.