bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosome-mediated miR-7-5p delivery enhances the anticancer effect of Everolimus via blocking MNK/eIF4E axis in non-small cell lung cancer
Authors: Liu Sile , Wang Weiyuan , Ning Yue , Zheng Hongmei , Zhan Yuting , Wang Haihua , Yang Yang , Luo Jiadi , Wen Qiuyuan , Zang Hongjing , Peng Jinwu , Ma Jian , Fan Songqing
Published: February 2022

Everolimus is a kind of mammalian target of rapamycin (mTOR) inhibitors. Activated mitogen-activated protein kinase interacting kinases/eukaryotic translation initiation factor 4E (MNK/eIF4E) axis plays a crucial role in resistance to Everolimus in non-small cell lung cancer (NSCLC). The eIF4E phosphorylation increased by mTOR inhibitors is mainly mediated by MNKs. However, the mechanisms are poorly understood. Recently, extensive reprogramming of miRNA profiles has also been found after long-term mTOR inhibitor exposure. Our previous studies have confirmed that tumor suppressor miR-7-5p is decreased in A549 cells after treatment with Everolimus. Exactly, MNK1 is the target of miR-7-5p. In this study, we investigated the biological functions and potential molecular mechanisms of miR-7-5p in the NSCLC undergoing treatment with Everolimus. We confirmed that Everolimus targeted mTORC1 inducing NSCLC cells to secrete miR-7-5p-loaded exosomes in Rab27A and Rab27B-dependent manners. Loss of intracellular miR-7-5p induced phosphorylation of MNK/eIF4E axis, but a supplement of extra exosomal miR-7-5p could reverse it. Of note, both low expression of miR-7-5p and elevated MNK1 protein were associated with a poor prognosis of NSCLC. Both endogenous miR-7-5p and exo-miR-7-5p enhanced the therapeutic efficacy of Everolimus by inhibiting the proliferation, migration, and metastasis of NSCLC in vitro and in vivo. The combination of miR-7-5p with Everolimus induced apoptosis to exhibit a synergistic anticancer therapeutic efficacy through dual abrogation of MNK/eIF4E and mTOR in NSCLC. In conclusion, Everolimus decreases the intracellular miR-7-5p by releasing of miR-7-5p loaded exosomes from NSCLC cells in Rab27A and Rab27B dependent manners. Either endogenous miR-7-5p or exo-miR-7-5p combined with Everolimus can enhance the anticancer efficacy by targeting MNK/eIF4E axis and mTOR. Besides, both low levels of miR-7-5p and positive expression of MNK1 act as independent poor prognostic biomarkers for NSCLC. Therefore, restoring miR-7-5p carried by exosome may be a promising novel combined therapeutic strategy with Everolimus for NSCLC.
Methyl-CpG-binding domain protein 2 contributes to renal fibrosis through promoting polarized M1 macrophages
Authors: Ai Kai , Pan Jian , Zhang Pan , Li Huiling , He Zhibiao , Zhang Hongliang , Li Xiaozhou , Li Yijian , Yi Lei , Kang Ye , Wang Yinhuai , Xiang Xudong , Chai Xiangping , Zhang Dongshan
Published: February 2022

Recent studies reported that Methyl-CpG–binding domain protein 2 (MBD2) promoted M2 macrophages accumulation to increase bleomycin-induced pulmonary fibrosis. However, the role and mechanism of action of MBD2 in macrophages differentiation and renal fibrosis remain largely unknown. In the current study, MBD2 not only promoted the differentiation of resting M0 macrophages to polarized M2 macrophages, but also induced them to polarized M1 macrophages and the transition of M2 to M1 macrophages. ChIP analysis demonstrated that MBD2 physically interacted with the promoter region of the CpG islands of G0S2 genes, and then activated their expression by inducing hypomethylation of the promoter region. Interestingly, the data demonstrated that the role of G0S2 in macrophages differentiation is consistent with MBD2. Furthermore, Co-culture of activated M1 macrophages and murine embryonic NIH 3T3 fibroblasts indicated that MBD2 mediated the M1-induction of ECM production by embryonic NIH 3T3 fibroblasts via promotion of G0S2. In addition, we also found that inhibition of MBD2 suppressed LPS induced the expression of p53 as well as activation and expression of stat3 in RAW264.7 macrophages. In vivo, MBD2 LysMcre attenuated unilateral ureteral obstruction (UUO) and ischemia/reperfusion (I/R)-induced renal fibrosis via downregulation of G0S2, which was demonstrated by the downregulation of fibronectin (FN), collagen I and IV, α-SMA, G0S2. These data collectively demonstrated that MBD2 in macrophages contributed to UUO and I/R-induced renal fibrosis through the upregulation of G0S2, which could be a target for treatment for chronic kidney disease.
LncRNA BC200/miR-150-5p/MYB positive feedback loop promotes the malignant proliferation of myelodysplastic syndrome
Authors: Liu Zhaoping , Wang Pan , Yuan Shunling , Wang Yanyan , Cao Pengfei , Wen Feng , Li Hui , Zhu Lin , Liang Long , Wang Zi , Hu Bin , Zheng Fuxiang , Liu Jing , Xiao Xiaojuan , Zhang Ji
Published: February 2022

Myelodysplastic syndrome (MDS) is a group of heterogeneous hematologic malignancies with a risk of transformation to acute myeloid leukemia. Understanding the molecular mechanisms of the specific roles of long noncoding RNAs (lncRNAs) in MDS would create novel ways to identify diagnostic and therapeutic targets. The lncRNA BC200 is upregulated and acts as an oncogene in various cancers; however, its expression, clinical significance, and roles in MDS remain unclear. Here, we found that BC200 was highly expressed in MDS patients compared with normal individuals. Knockdown of BC200 inhibited MDS cell proliferation, colony formation, and cell cycle progression in vitro and suppressed the growth and invasiveness of MDS cells in vivo. Mechanistic investigations revealed that BC200 functioned as a miRNA sponge to positively regulate the expression of MYB through sponging miR-150-5p and subsequently promoted malignant proliferation of MDS cells. Conversely, we found that BC200 was a direct transcriptional target of MYB, and knockdown of MYB abolished the oncogenic effect of BC200/miR-150-5p. Taken together, our results revealed that the BC200/miR-150-5p/MYB positive feedback loop promoted the proliferation of MDS cells and is expected to be a potential biomarker and therapeutic target in MDS.
Investigating the potential effectiveness of earthquake early warning across Europe
Authors: Cremen Gemma , Galasso Carmine , Zuccolo Elisa
Published: February 2022

Here we assess the potential implementation of earthquake early warning (EEW) across Europe, where there is a clear need for measures that mitigate seismic risk. EEW systems consist of seismic networks and mathematical models/algorithms capable of real-time data telemetry that alert stakeholders (e.g., civil-protection authorities, the public) to an earthquake’s nucleation seconds before shaking occurs at target sites. During this time, actions can be taken that might decrease detrimental impacts. We investigate distributions of EEW lead times available across various parts of the Euro-Mediterranean region, based on seismicity models and seismic network density. We then determine the potential usefulness of these times for EEW purposes by defining their spatial relationship with population exposure, seismic hazard, and an alert accuracy proxy, using well-established earthquake-engineering tools for measuring the impacts of earthquakes. Our mapped feasibility results show that, under certain conditions, EEW could be effective for some parts of Europe.
Beta-cell specific Insr deletion promotes insulin hypersecretion and improves glucose tolerance prior to global insulin resistance
Authors: Skovsø Søs , Panzhinskiy Evgeniy , Kolic Jelena , Cen Haoning Howard , Dionne Derek A. , Dai Xiao-Qing , Sharma Rohit B. , Elghazi Lynda , Ellis Cara E. , Faulkner Katharine , Marcil Stephanie A. M. , Overby Peter , Noursadeghi Nilou , Hutchinson Daria , Hu Xiaoke , Li Hong , Modi Honey , Wildi Jennifer S. , Botezelli J. Diego , Noh Hye Lim , Suk Sujin , Gablaski Brian , Bautista Austin , Kim Ryekjang , Cras-Méneur Corentin , Flibotte Stephane , Sinha Sunita , Luciani Dan S. , Nislow Corey , Rideout Elizabeth J. , Cytrynbaum Eric N. , Kim Jason K. , Bernal-Mizrachi Ernesto , Alonso Laura C. , MacDonald Patrick E. , Johnson James D.
Published: February 2022

Insulin receptor (Insr) protein is present at higher levels in pancreatic β-cells than in most other tissues, but the consequences of β-cell insulin resistance remain enigmatic. Here, we use an Ins1cre knock-in allele to delete Insr specifically in β-cells of both female and male mice. We compare experimental mice to Ins1cre-containing littermate controls at multiple ages and on multiple diets. RNA-seq of purified recombined β-cells reveals transcriptomic consequences of Insr loss, which differ between female and male mice. Action potential and calcium oscillation frequencies are increased in Insr knockout β-cells from female, but not male mice, whereas only male βInsrKO islets have reduced ATP-coupled oxygen consumption rate and reduced expression of genes involved in ATP synthesis. Female βInsrKO and βInsrHET mice exhibit elevated insulin release in ex vivo perifusion experiments, during hyperglycemic clamps, and following i.p. glucose challenge. Deletion of Insr does not alter β-cell area up to 9 months of age, nor does it impair hyperglycemia-induced proliferation. Based on our data, we adapt a mathematical model to include β-cell insulin resistance, which predicts that β-cell Insr knockout improves glucose tolerance depending on the degree of whole-body insulin resistance. Indeed, glucose tolerance is significantly improved in female βInsrKO and βInsrHET mice compared to controls at 9, 21 and 39 weeks, and also in insulin-sensitive 4-week old males. We observe no improved glucose tolerance in older male mice or in high fat diet-fed mice, corroborating the prediction that global insulin resistance obscures the effects of β-cell specific insulin resistance. The propensity for hyperinsulinemia is associated with mildly reduced fasting glucose and increased body weight. We further validate our main in vivo findings using an Ins1-CreERT transgenic line and find that male mice have improved glucose tolerance 4 weeks after tamoxifen-mediated Insr deletion. Collectively, our data show that β-cell insulin resistance in the form of reduced β-cell Insr contributes to hyperinsulinemia in the context of glucose stimulation, thereby improving glucose homeostasis in otherwise insulin sensitive sex, dietary and age contexts.
Giant sponge grounds of Central Arctic seamounts are associated with extinct seep life
Authors: Morganti T. M. , Slaby B. M. , de Kluijver A. , Busch K. , Hentschel U. , Middelburg J. J. , Grotheer H. , Mollenhauer G. , Dannheim J. , Rapp H. T. , Purser A. , Boetius A.
Published: February 2022

The Central Arctic Ocean is one of the most oligotrophic oceans on Earth because of its sea-ice cover and short productive season. Nonetheless, across the peaks of extinct volcanic seamounts of the Langseth Ridge (87°N, 61°E), we observe a surprisingly dense benthic biomass. Bacteriosponges are the most abundant fauna within this community, with a mass of 460 g C m−2 and an estimated carbon demand of around 110 g C m−2 yr−1, despite export fluxes from regional primary productivity only sufficient to provide <1% of this required carbon. Observed sponge distribution, bulk and compound-specific isotope data of fatty acids suggest that the sponge microbiome taps into refractory dissolved and particulate organic matter, including remnants of an extinct seep community. The metabolic profile of bacteriosponge fatty acids and expressed genes indicate that autotrophic symbionts contribute significantly to carbon assimilation. We suggest that this hotspot ecosystem is unique to the Central Arctic and associated with extinct seep biota, once fueled by degassing of the volcanic mounts.
A re-appraisal of the ENSO response to volcanism with paleoclimate data assimilation
Authors: Zhu Feng , Emile-Geay Julien , Anchukaitis Kevin J. , Hakim Gregory J. , Wittenberg Andrew T. , Morales Mariano S. , Toohey Matthew , King Jonathan
Published: February 2022

The potential for explosive volcanism to affect the El Niño-Southern Oscillation (ENSO) has been debated since the 1980s. Several observational studies, based largely on tree-ring proxies, have since found support for a positive ENSO phase in the year following large eruptions. In contrast, recent coral data from the heart of the tropical Pacific suggest no uniform ENSO response to explosive volcanism over the last millennium. Here we leverage paleoclimate data assimilation to integrate both tree-ring and coral proxies into a reconstruction of ENSO state, and re-appraise this relationship. We find only a weak statistical association between volcanism and ENSO, and identify the selection of volcanic events as a key variable to the conclusion. We discuss the difficulties of conclusively establishing a volcanic influence on ENSO by empirical means, given the myriad factors affecting the response, including the spatiotemporal details of the forcing and ENSO phase preconditioning.
Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity
Authors: Umansky Carla , Morellato Agustín E. , Rieckher Matthias , Scheidegger Marco A. , Martinefski Manuela R. , Fernández Gabriela A. , Pak Oleg , Kolesnikova Ksenia , Reingruber Hernán , Bollini Mariela , Crossan Gerry P. , Sommer Natascha , Monge María Eugenia , Schumacher Björn , Pontel Lucas B.
Published: February 2022

Formaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking, likely contributing to the onset of the human DNA repair condition Fanconi Anaemia. Mutations in the genes coding for FA detoxifying enzymes underlie a human inherited bone marrow failure syndrome (IBMFS), even in the presence of functional DNA repair, raising the question of whether FA causes relevant cellular damage beyond genotoxicity. Here, we report that FA triggers cellular redox imbalance in human cells and inCaenorhabditis elegans. Mechanistically, FA reacts with the redox-active thiol group of glutathione (GSH), altering the GSH:GSSG ratio and causing oxidative stress. FA cytotoxicity is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), which metabolizes FA-GSH products, lastly yielding reduced GSH. Furthermore, we show that GSH synthesis protects human cells from FA, indicating an active role of GSH in preventing FA toxicity. These findings might be relevant for patients carrying mutations in FA-detoxification systems and could suggest therapeutic benefits from thiol-rich antioxidants like N-acetyl-L-cysteine.
Protein sequence design with a learned potential
Authors: Anand Namrata , Eguchi Raphael , Mathews Irimpan I. , Perez Carla P. , Derry Alexander , Altman Russ B. , Huang Po-Ssu
Published: February 2022

The task of protein sequence design is central to nearly all rational protein engineering problems, and enormous effort has gone into the development of energy functions to guide design. Here, we investigate the capability of a deep neural network model to automate design of sequences onto protein backbones, having learned directly from crystal structure data and without any human-specified priors. The model generalizes to native topologies not seen during training, producing experimentally stable designs. We evaluate the generalizability of our method to ade novoTIM-barrel scaffold. The model produces novel sequences, and high-resolution crystal structures of two designs show excellent agreement with in silico models. Our findings demonstrate the tractability of an entirely learned method for protein sequence design.
Physiological synaptic activity and recognition memory require astroglial glutamine
Authors: Cheung Giselle , Bataveljic Danijela , Visser Josien , Kumar Naresh , Moulard Julien , Dallérac Glenn , Mozheiko Daria , Rollenhagen Astrid , Ezan Pascal , Mongin Cédric , Chever Oana , Bemelmans Alexis-Pierre , Lübke Joachim , Leray Isabelle , Rouach Nathalie
Published: February 2022

Presynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a fluorescent probe that tracks glutamine in live cells, which provides direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap-junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes.
In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue
Authors: Silva-Pinheiro Pedro , Nash Pavel A. , Van Haute Lindsey , Mutti Christian D. , Turner Keira , Minczuk Michal
Published: February 2022

Mitochondria host key metabolic processes vital for cellular energy provision and are central to cell fate decisions. They are subjected to unique genetic control by both nuclear DNA and their own multi-copy genome - mitochondrial DNA (mtDNA). Mutations in mtDNA often lead to clinically heterogeneous, maternally inherited diseases that display different organ-specific presentation at any stage of life. For a long time, genetic manipulation of mammalian mtDNA has posed a major challenge, impeding our ability to understand the basic mitochondrial biology and mechanisms underpinning mitochondrial disease. However, an important new tool for mtDNA mutagenesis has emerged recently, namely double-stranded DNA deaminase (DddA)-derived cytosine base editor (DdCBE). Here, we test this emerging tool for in vivo use, by delivering DdCBEs into mouse heart using adeno-associated virus (AAV) vectors and show that it can install desired mtDNA edits in adult and neonatal mice. This work provides proof-of-concept for use of DdCBEs to mutagenize mtDNA in vivo in post-mitotic tissues and provides crucial insights into potential translation to human somatic gene correction therapies to treat primary mitochondrial disease phenotypes.
A Mediator-cohesin axis controls heterochromatin domain formation
Authors: Haarhuis Judith H. I. , van der Weide Robin H. , Blomen Vincent A. , Flach Koen D. , Teunissen Hans , Willems Laureen , Brummelkamp Thijn R. , Rowland Benjamin D. , de Wit Elzo
Published: February 2022

The genome consists of regions of transcriptionally active euchromatin and more silent heterochromatin. We reveal that the formation of heterochromatin domains requires cohesin turnover on DNA. Stabilization of cohesin on DNA through depletion of its release factor WAPL leads to a near-complete loss of heterochromatin domains. We observe the opposite phenotype in cells deficient for subunits of the Mediator-CDK module, with an almost binary partition of the genome into dense H3K9me3 domains, and regions devoid of H3K9me3 spanning the rest of the genome. We suggest that the Mediator-CDK module might contribute to gene expression by limiting the formation of dense heterochromatin domains. WAPL deficiency prevents the formation of heterochromatin domains, and allows for gene expression even in the absence of the Mediator-CDK subunit MED12. We propose that cohesin and Mediator affect heterochromatin in different ways to enable the correct distribution of epigenetic marks, and thus to ensure proper gene expression.
Inflammatory cytokines and distant recurrence in HER2-negative early breast cancer
Authors: Sparano Joseph A. , O’Neill Anne , Graham Noah , Northfelt Donald W. , Dang Chau T. , Wolff Antonio C. , Sledge George W. , Miller Kathy D.
Published: February 2022

Systemic inflammation is believed to contribute to the distant recurrence of breast cancer. We evaluated serum samples obtained at diagnosis from 249 case:control pairs with stage II-III Her2-negative breast cancer with or without subsequent distant recurrence. Conditional logistic regression analysis, with models fit via maximum likelihood, were used to estimate hazard ratios (HRs) and test for associations of cytokines with distant recurrence risk. The only biomarker associated with a significantly increased distant recurrence risk when adjusted for multiple testing was the proinflammatory cytokine IL-6 (HR 1.37, 95% confidence intervals [CI] 1.15, 1.65, p = 0.0006). This prospective-retrospective study provides evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk.
Cooperative control of perpendicular magnetic anisotropy via crystal structure and orientation in freestanding SrRuO3 membranes
Authors: Lu Zengxing , Yang Yongjie , Wen Lijie , Feng Jiatai , Lao Bin , Zheng Xuan , Li Sheng , Zhao Kenan , Cao Bingshan , Ren Zeliang , Song Dongsheng , Du Haifeng , Guo Yuanyuan , Zhong Zhicheng , Hao Xianfeng , Wang Zhiming , Li Run-Wei
Published: February 2022

Flexible magnetic materials with robust and controllable perpendicular magnetic anisotropy (PMA) are highly desirable for developing flexible high-performance spintronic devices. However, it is still challenge to fabricate PMA films on polymers directly. Here, we report a facile method for synthesizing single-crystal freestanding SrRuO3 membranes with controlled crystal structure and orientation using water-soluble Ca3-xSrxAl2O6 sacrificial layers. Through cooperative effect of crystal structure and orientation, flexible membranes reveal highly tunable magnetic anisotropy from in-plane to out-of-plane with a remarkable PMA energy of 7 × 106 erg·cm−3. First-principle calculations reveal that the underlying mechanism of PMA modulation is intimately correlated with structure-controlled Ru 4d-orbital occupation, as well as spin-orbital matrix element differences, dependent on the crystal orientation. In addition, even after 10,000 bending cycles, the PMA keeps stable, indicating a robust magnetism reliability in the prepared films. This work provides a feasible approach to prepare the flexible oxide films with strong and controllable PMA.
Garment embedded sweat-activated batteries in wearable electronics for continuous sweat monitoring
Authors: Huang Xingcan , Liu Yiming , Zhou Jingkun , Nejad Sina Khazaee , Wong Tsz Hung , Huang Ya , Li Hu , Yiu Chun Ki , Park Wooyoung , Li Jian , Su Jingyou , Zhao Ling , Yao Kuanming , Wu Mengge , Gao Zhan , Li Dengfeng , Li Jiyu , Shi Rui , Yu Xinge
Published: February 2022

Thin, soft, and skin-integrated electronic system has great advantages for realizing continuous human healthcare monitoring. Here, we report an ultra-thin, flexible, and garment-based microelectronics powered by sweat-activated batteries (SABs) and applications of powering biosensors and microelectronic systems for real time sweat monitoring. The SAB cell is ultra-thin (1.25 mm) with excellent biocompatibility. The SAB has good electricity output with high capacity (14.33 mAh) and maximum power density (3.17 mW cm−2) after being activated by the sweat volume of 0.045 mL cm−2, which could continuously power 120 light emitting diodes over 3 h. The outputs could maintain stable after repeatable bending. Wireless microelectronics system could be continuously powered by the SABs for 3 h to monitor sweat and physiological information, including sweat Na+ concentration, pH, and skin impedance. The reported integrated system provides a potential for solving the power issues of flexible wearable electronics and realizing personalized medicine.
Classical and quantum chaos in chirally-driven, dissipative Bose-Hubbard systems
Authors: Dahan Daniel , Arwas Geva , Grosfeld Eytan
Published: February 2022

We study the dissipative Bose-Hubbard model on a small ring of sites in the presence of a chiral drive and explore its long-time dynamical structure using the mean-field equations and by simulating the quantum master equation. Remarkably, for large enough drivings, we find that the system admits, in a wide range of parameters, a chaotic attractor at the mean-field level, which manifests as a complex Wigner function on the quantum level. The latter is shown to have the largest weight around the approximate region of phase space occupied by the chaotic attractor. We demonstrate that this behavior could be revealed via measurement of various bosonic correlation functions. In particular, we employ open system methods to calculate the out-of-time-ordered correlator, whose exponential growth signifies a positive quantum Lyapunov exponent in our system. This can open a pathway to the study of chaotic dynamics in interacting systems of photons.
Four features of temporal patterns characterize similarity among individuals and molecules by glucose ingestion in humans
Authors: Fujita Suguru , Karasawa Yasuaki , Fujii Masashi , Hironaka Ken-ichi , Uda Shinsuke , Kubota Hiroyuki , Inoue Hiroshi , Sumitomo Yohei , Hirayama Akiyoshi , Soga Tomoyoshi , Kuroda Shinya
Published: February 2022

Oral glucose ingestion induces systemic changes of many blood metabolites related not only to glucose, but also other metabolites such as amino acids and lipids through many blood hormones. However, the detailed temporal changes in the concentrations of comprehensive metabolites and hormones over a long time by oral glucose ingestion are uncharacterized. We measured 83 metabolites and 7 hormones in 20 healthy human subjects in response to glucose ingestion. We characterized temporal patterns of blood molecules by four features: (i) the decomposability into “amplitude” and “rate” components, (ii) the similarity of temporal patterns among individuals, (iii) the relation of molecules over time among individuals, and (iv) the similarity of temporal patterns among molecules. Glucose and glucose metabolism-related hormones indicated a rapid increase, and citrulline and lipids, which indicated a rapid decrease, returned to fasting levels faster than amino acids. Compared to glucose metabolism-related molecules and lipids, amino acids showed similar temporal patterns among individuals. The four features of temporal patterns of blood molecules by oral glucose ingestion characterize the differences among individuals and among molecules.
Rs12976445 polymorphism is associated with the risk of post-SAH re-bleeding by modulating the expression of microRNA-125 and ET-1
Authors: Xiong Wenping , Yao Weiqi , Gao Zeyuan , Liu Kui
Published: February 2022

This study aimed to study the association between rs12976445 polymorphism and the incidence of IA re-bleeding. Genotype and allele frequency analysis was performed to study the association between rs12976445 polymorphism and the risk of IA re-bleeding. Western blot, ELISA and real-time RT-PCR were conducted to measure the relative expression of miR-125a, ET1 mRNA and ET1 protein. Computational analysis and luciferase assays were utilized to investigate the association between the expression of miR-125a and ET1 mRNA. No significant differences were observed between IA patients with or without symptoms of re-bleeding. Subsequent analyses indicated that the T allele was significantly associated with the reduced risk of IA re-bleeding. In patients carrying the CC genotype, miR-125a level was up-regulated while ET1 mRNA/protein levels were reduced compared with those in patients carrying the CT or TT genotype. And ET1 mRNA was identified as a virtual target gene of miR-125a with a potential miR-125a binding site located on its 3’UTR. Accordingly, the ET mRNA/protein levels could be suppressed by the transfection of miR-125a precursors, but the transfection of ET1 siRNA exhibited no effect on the expression of miR-125a. Therefore, an increased level of miR-125a can lead to the increased risk of IA re-bleeding. Since miR-125a level is higher in CC-genotyped patients, it can be concluded that the presence of T allele in the rs12976445 polymorphism is associated with a lower risk of IA re-bleeding, and miR-125a may be used as a novel diagnostic and therapeutic target for IA rupture.
Nanostrucutured MnO2-TiN nanotube arrays for advanced supercapacitor electrode material
Authors: Ren Peng , Chen Chao , Yang Xiuchun
Published: February 2022

The capacitance of MnO2 supercapacitors (SCs) is not high as expected due to its low conductivity of MnO2. The synergistic effects of MnO2 with high theoretical specific capacitance and TiN with high theoretical conductivity can extremely enhance the electrochemical performance of the MnO2-TiN electrode material. In this work, we synthesized different nanostructured and crystalline-structured MnO2 modified TiN nanotube arrays electrode materials by hydrothermal method and explained the formation mechanism of different nanostructured and crystalline-structured MnO2. The influences of MnO2 nanostructures and crystalline-structures on the electrochemical performance has been contrasted and discussed. The specific capacitance of δ-MnO2 nanosheets-TiN nanotube arrays can reach 689.88 F g−1, the highest value among these samples TN-MO-SS, TN-MO-S, TN-MO-SR, TN-MO-RS, and TN-MO-R. The reason is explained based on MnO2 nanostructure and crystalline-structure and electron/ion transport properties. The specific capacitance retention rates are 97.2% and 82.4% of initial capacitance after 100 and 500 cycles, respectively, indicating an excellent charging-discharging cycle stability.
Volatile organic compound profiling to explore primary graft dysfunction after lung transplantation
Authors: Stefanuto Pierre-Hugues , Romano Rosalba , Rees Christiaan A. , Nasir Mavra , Thakuria Louit , Simon Andre , Reed Anna K. , Marczin Nandor , Hill Jane E.
Published: February 2022

Primary graft dysfunction (PGD) is a major determinant of morbidity and mortality following lung transplantation. Delineating basic mechanisms and molecular signatures of PGD remain a fundamental challenge. This pilot study examines if the pulmonary volatile organic compound (VOC) spectrum relate to PGD and postoperative outcomes. The VOC profiles of 58 bronchoalveolar lavage fluid (BALF) and blind bronchial aspirate samples from 35 transplant patients were extracted using solid-phase-microextraction and analyzed with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry. The support vector machine algorithm was used to identify VOCs that could differentiate patients with severe from lower grade PGD. Using 20 statistically significant VOCs from the sample headspace collected immediately after transplantation (< 6 h), severe PGD was differentiable from low PGD with an AUROC of 0.90 and an accuracy of 0.83 on test set samples. The model was somewhat effective for later time points with an AUROC of 0.80. Three major chemical classes in the model were dominated by alkylated hydrocarbons, linear hydrocarbons, and aldehydes in severe PGD samples. These VOCs may have important clinical and mechanistic implications, therefore large-scale study and potential translation to breath analysis is recommended.
Perlite is a suitable model material for experiments investigating breathing in high density snow
Authors: Roubik Karel , Sykora Karel , Sieger Ladislav , Ort Vaclav , Horakova Lenka , Walzel Simon
Published: February 2022

Outdoor breathing trials with simulated avalanche snow are fundamental for the research of the gas exchange under avalanche snow, which supports the development of the international resuscitation guidelines. However, these studies have to face numerous problems, including unstable weather and variable snow properties. This pilot study examines a mineral material perlite as a potential snow model for studies of ventilation and gas exchange parameters. Thirteen male subjects underwent three breathing phases—into snow, wet perlite and dry perlite. The resulting trends of gas exchange parameters in all tested materials were similar and when there was a significant difference observed, the trends in the parameters for high density snow used in the study lay in between the trends in dry and wet perlite. These findings, together with its stability and accessibility year-round, make perlite a potential avalanche snow model material. Perlite seems suitable especially for simulation and preparation of breathing trials assessing gas exchange under avalanche snow, and potentially for testing of new avalanche safety equipment before their validation in real snow.

The study was registered in ClinicalTrials.gov on January 22, 2018; the registration number is NCT03413878.
Inferring the energy sensitivity and band gap of electronic transport in a network of carbon nanotubes
Authors: Tang Shuang
Published: February 2022

Since the industrialization of single-phase nanomaterial-based devices is still challenging, intensive research focus has been given to complex materials consisting of multiple nanoscale entities, including networks and matrices of nanowires, nanotubes, nanoribbons, or other large molecules; among these complex materials, networks of carbon nanotubes are a typical example. Detailed knowledge of the energy sensitivity and band gap of electronic transport in such a material system is difficult to detect, despite its importance in electronic, energetic and sensing applications. Here, we propose a new methodology to obtain these quantities using the measured Seebeck coefficient at a certain temperature but different Fermi levels. We discover that the network consisting of semiconducting (11,10)-carbon nanotubes actually exhibits metallic transport at room temperature. It is also interesting to verify that intrananotube ballistic transport is dominant over diffusive scattering by long-range disorder, as well as the quantum hopping resistance at the contact points. The transport asymmetry ratio between the holes and electrons (1.75) is similar to the value observed in pristine graphene samples (1.50).
Topological and enzymatic analysis of human Alg2 mannosyltransferase reveals its role in lipid-linked oligosaccharide biosynthetic pathway
Authors: Xiang Meng-Hai , Xu Xin-Xin , Wang Chun-Di , Chen Shuai , Xu Si , Xu Xiang-Yang , Dean Neta , Wang Ning , Gao Xiao-Dong
Published: February 2022

N-glycosylation starts with the biosynthesis of lipid-linked oligosaccharide (LLO) on the endoplasmic reticulum (ER). Alg2 mannosyltransferase adds both the α1,3- and α1,6-mannose (Man) onto ManGlcNAc2-pyrophosphate-dolichol (M1Gn2-PDol) in either order to generate the branched M3Gn2-PDol product. The well-studied yeast Alg2 interacts with ER membrane through four hydrophobic domains. Unexpectedly, we show that Alg2 structure has diverged between yeast and humans. Human Alg2 (hAlg2) associates with the ER via a single membrane-binding domain and is markedly more stable in vitro. These properties were exploited to develop a liquid chromatography-mass spectrometry quantitative kinetics assay for studying purified hAlg2. Under physiological conditions, hAlg2 prefers to transfer α1,3-Man onto M1Gn2 before adding the α1,6-Man. However, this bias is altered by an excess of GDP-Man donor or an increased level of M1Gn2 substrate, both of which trigger production of the M2Gn2(α-1,6)-PDol. These results suggest that Alg2 may regulate the LLO biosynthetic pathway by controlling accumulation of M2Gn2 (α-1,6) intermediate.
Substantial loss of isoprene in the surface ocean due to chemical and biological consumption
Authors: Simó Rafel , Cortés-Greus Pau , Rodríguez-Ros Pablo , Masdeu-Navarro Marta
Published: February 2022

Isoprene contributes to the formation of ozone and secondary organic aerosol in the atmosphere, and thus influences cloud albedo and climate. Isoprene is ubiquitous in the surface open ocean where it is produced by phytoplankton, however emissions from the global ocean are poorly constrained, in part due to a lack of knowledge of oceanic sink or degradation terms. Here, we present analyses of ship-based seawater incubation experiments with samples from the Mediterranean, Atlantic, tropical Pacific and circum-Antarctic and Subantarctic oceans to determine chemical and biological isoprene consumption in the surface ocean. We find the total isoprene loss to be comprised of a constant chemical loss rate of 0.05 ± 0.01 d−1 and a biological consumption rate that varied between 0 and 0.59 d−1 (median 0.03 d−1) and was correlated with chlorophyll-a concentration. We suggest that isoprene consumption rates in the surface ocean are of similar magnitude or greater than ventilation rates to the atmosphere, especially in chlorophyll-a rich waters.
An integrated microfluidic chip for alginate microsphere generation and 3D cell culture
Authors: Zhou Xiaoxiang , Zhu Libo , Li Weihao , Liu Quanjun
Published: February 2022

An integrated microfluidic platform is developed for the generation, demulsification and in situ culture of bacteria-laden 3D alginate microspheres. This platform provide encapsulated bacterial cells a biocompatible microenvironment.
Interpenetrated metal–organic frameworks with enhanced photoluminescence for selective recognition of m-xylene from xylene isomers
Authors: Zhang Xiuling , Li Tingting , Wei Jiao , Tian Gao-Hua , Cao Qing-Ling , Wang Yu-Jie , Hou Wen-Li , Zhou Wen-Feng , Zhang Zhen-Wei , Hu Hui , Zhang Yong-Zheng , Zhang Da-Shuai , Li Qing , Geng Longlong
Published: February 2022

Two LMOFs with individual/interpenetrated three-dimensional frameworks were synthesized based on the same ligands and metal ions, of which the interpenetrated one can be used for rapid fluorescence recognition of meta-xylene from xylene isomers.
Nickel hydroxide/sulfide hybrids: halide ion controlled synthesis, structural characteristics, and electrochemical performance
Authors: Wu Qibing , Li Weining , Zou Xuefeng , Xiang Bin
Published: February 2022

We developed a two-step approach to control the effect of halogen ions on the creation, growth, and evolution of nickel hydroxy-halides, resulting in a variety of nickel-based materials with various morphologies and structural properties.
Theoretical calculations of the effect of nitrogen substitution on the structural, vibrational, and electronic properties of wolframite-type ScTaO4at ambient conditions
Authors: Karaouzène Lotfi Ibrahim , Ouahrani Tarik , Morales-García Ángel , Errandonea Daniel
Published: February 2022

The electronic properties of wolframite-type ScTaO4are tuned by the substitution of oxygen atoms with nitrogen atoms. Nitrogen provides additional electrons, which act as a shallow acceptor state, triggering the onset of p-type behavior.
Molecular regulation of phenolic compounds on IGF-1 signaling cascade in breast cancer
Authors: Sair Ali Tahir , Liu Rui Hai
Published: February 2022

Influence of phenolic compounds and extracts on the IGF-1/IGF-1R signaling pathway.
Dihydromyricetin prevents obesity via regulating bile acid metabolism associated with the farnesoid X receptor in ob/ob mice
Authors: Song Yanjun , Sun Le , Ma Pei , Xu Lijia , Xiao Peigen
Published: February 2022

Dihydromyricetin appears to prevent obesity through regulating bile acid metabolism associated with FXR activation. Dihydromyricetin may serve as a dietary supplement to manage metabolic diseases including obesity.
Pressing matter: why are ionic liquids so viscous?
Authors: Philippi Frederik , Rauber Daniel , Eliasen Kira Lieberkind , Bouscharain Nathalie , Niss Kristine , Kay Christopher W. M. , Welton Tom
Published: February 2022

We use an experimental approach to compare an ionic liquid with a molecular mimic, focusing on viscosities. Charge network and coulombic compaction contribute significantly to the high viscosity of ionic liquids; we discuss the implications on their design and optimisation.
Reactivity of a fluorine-containing dirhodium tetracarboxylate compound with proteins
Authors: Loreto Domenico , Esposito Anna , Demitri Nicola , Guaragna Annalisa , Merlino Antonello
Published: February 2022

[cis-Rh2(OAc)2(tfa)2] has been synthesized and its reaction with RNase A and lysozyme was analyzed using a combination of different techniques, including fluorine NMR and X-ray crystallography.
One-pot multifunctional polyesters by continuous flow organocatalysed ring-opening polymerisation for targeted and tunable materials design
Authors: Bakkali-Hassani Camille , Hooker Jordan P. , Voorter Pieter-Jan , Rubens Maarten , Cameron Neil R. , Junkers Tanja
Published: February 2022

We integrate continuous flow organocatalysed ring-opening polymerisation with a core-grafting strategy to rapidly and readily prepare multifunctional, processable polyesters. Their potential use in materials applications is subsequently highlighted.
A “double-sided tape” modifier bridging the TiO2/perovskite buried interface for efficient and stable all-inorganic perovskite solar cells
Authors: Ti Junjie , Zhu Jingwei , He Benlin , Zong Zhihao , Yao Xinpeng , Tui Rui , Huang Hao , Chen Cong , Chen Haiyan , Duan Yanyan , Tang Qunwei
Published: February 2022

By passivating defects, forming perfect contact and band matching at buried interface and high-quality perovskite film, the DAP “double-sided tape” modification helps the CsPbBr3 PSCs obtain a best PCE of 10.31% and excellent moisture-heat tolerance.
Apsidal motion in massive eccentric binaries in NGC 6231
Authors: Rosu S. , Rauw G. , Farnir M. , Dupret M.-A. , Noels A.
Published: February 2022

Context. The measurement of the apsidal motion in close eccentric massive binary systems provides essential information to probe the internal structure of the stars that compose the system.

Aims. Following the determination of the fundamental stellar and binary parameters, we make use of the tidally induced apsidal motion to infer constraints on the internal structure of the stars composing the binary system HD 152219.

Methods. The extensive set of spectroscopic, photometric, and radial velocity observations allowed us to constrain the fundamental parameters of the stars together with the rate of apsidal motion of the system. Stellar structure and evolution models were further built with the Clés code testing different prescriptions for the internal mixing occurring inside the stars. The effect of stellar rotation axis misalignment with respect to the normal to the orbital plane on our interpretation of the apsidal motion in terms of internal structure constants is investigated.

Results. Made of an O9.5 III primary star (M1 = 18.64 ± 0.47 M⊙, R1 = 9.40−0.15+0.14 R⊙, Teff,1 = 30 900 ± 1000 K, Lbol,1 = (7.26 ± 0.97)×104 L⊙) and a B1-2 V-III secondary star (M2 = 7.70 ± 0.12 M⊙, R2 = 3.69 ± 0.06 R⊙, Teff,2 = 21 697 ± 1000 K, Lbol,2 = (2.73 ± 0.51)×103 L⊙), the binary system HD 152219 displays apsidal motion at a rate of (1.198 ± 0.300)° yr−1. The weighted-average mean of the internal structure constant of the binary system is inferred: k̄2 = 0.00173 ± 0.00052. For the Clés models to reproduce the k2-value of the primary star, a significantly enhanced mixing is required, notably through the turbulent mixing, but at the cost that other stellar parameters cannot be reproduced simultaneously.

Conclusions. The difficulty to reproduce the k2-value simultaneously with the stellar parameters as well as the incompatibility between the age estimates of the primary and secondary stars are indications that some physics of the stellar interior are still not completely understood.
CMASS galaxy sample and the ontological status of the cosmological principle
Authors: Kim Yigon , Park Chan-Gyung , Noh Hyerim , Hwang Jai-chan
Published: February 2022

Context.The cosmological principle (CP), assuming spatially homogeneous and isotropic background geometry in the cosmological scale, is a fundamental assumption in modern cosmology. Recent observations of the galaxy redshift survey provide relevant data to confront the principle with observations. Several previous studies claim that the homogeneity scale is reached at a radius around 70 h−1 Mpc. However, the same observation shows a dramatic visual structure in the Sloan Digital Sky Survey Great Wall, which extends 300 h−1 Mpc in linear dimension.

Aims.We present a homogeneity test for the matter distribution using the Baryon Oscillation Spectroscopic Survey Data Release 12 CMASS galaxy sample and clarify the ontological status of the CP.

Methods.As a homogeneity criterion, we compared the observed data with similarly constructed random distributions using the number count in the truncated cones method. Comparisons are also made with three theoretical results using the same method: (i) the dark matter halo mock catalogs from theN-body simulation, (ii) the log-normal distributions derived from the theoretical matter power spectrum, and (iii) the direct estimation from the theoretical power spectrum.

Results.We show that the observed distribution is statistically impossible as a random distribution up to 300 h−1 Mpc in radius, which is around the largest statistically available scale. However, comparisons with the three theoretical results show that the observed distribution is consistent with these theoretically derived results based on the CP.

Conclusions.We show that the observed galaxy distribution (light) and the simulated dark matter distribution (matter) are quite inhomogeneous even on a large scale. Here, we clarify that there is no inconsistency surrounding the ontological status of the CP in cosmology. In practice, the CP is applied to the metric and the metric fluctuation is extremely small in all cosmological scales. This allows the CP to be valid as the averaged background in the metric. The matter fluctuation, however, is decoupled from the small nature of metric fluctuation in the subhorizon scale. What is directly related to the matter in Einstein’s gravity is the curvature, which is a quadratic derivative of the metric.
Value co-creation ‘gradients’: enabling human-machine interactions through AI-based DSS
Authors: Carrubbo Luca , Polese Francesco , Drăgoicea Monica , Walletzký Leonard , Megaro Antonietta
Published: February 2022

Artificial Intelligence-based Decision Support Systems (AI-based DSS) are becoming increasingly important in many contexts. This work aims to define a type of human-machine interactions for new value co-creation processes' ranks, to help identify factors that can stimulate value co-creation in human-machine interactions. To understand if the outcome of a man-machine interaction can contribute to the co-creation of value, and in what way, the work carried out is epistemological and typological, also based on System Thinking. A matrix of novel gradients of the relationships between humans and non-humans has been created, and the typology of human-machine interactions has been identified for the new degrees of value co-creation processes, as well as the new specific scale of skills, in terms of language, learning, know-how, level of trust and endowment of knowledge, as a whole. The main implications concern the need to customize Decision Support Systems (DSS), to enhance different levels of intensity of relationships, and to identify insights for Decision Making AI - based users.