bluuebunny/crossref_metadata_2025 huggingface dataset:
Bowls, vases and goblets—the microcrockery of polymer and nanocomposite morphology revealed by two-photon optical tomography
Authors: Yang Shu-Gui , Wei Zhen-Zhen , Cseh Liliana , Kazemi Pantea , Zeng Xiang-bing , Xie Hui-Jie , Saba Hina , Ungar Goran
Published: August 2021

On the >1 µm scale the morphology of semicrystalline plastics like polyethylene or Nylon features spherulites, “shish-kebabs”, cylinddrites and other crystalline aggregates which strongly affect mechanical and other material properties. Current imaging techniques give only a 2D picture of these objects. Here we show how they can be visualized in 3D using fluorescent labels and confocal microscopy. As a result, we see spherulites in 3D, both in neat polymers and their nanocomposites, and observe how unevenly nanoparticles and other additives are distributed in the material. Images of i-polypropylene and biodegradable poly(lactic acid) reveal previously unsuspected morphologies such as “vases” and “goblets”, nonspherical “spherulites” and, unexpectedly, “shish-kebabs” grown from quiescent melt. Also surprisingly, in nanocomposite sheets spherulite nucleation is seen to be copied from one surface to another, mediated by crystallization-induced pressure drop and local melt-flow. These first results reveal unfamiliar modes of self-assembly in familiar plastics and open fresh perspectives on polymer microstructure.
Elastocapillary cleaning of twisted bilayer graphene interfaces
Authors: Hou Yuan , Dai Zhaohe , Zhang Shuai , Feng Shizhe , Wang Guorui , Liu Luqi , Xu Zhiping , Li Qunyang , Zhang Zhong
Published: August 2021

Although layered van der Waals (vdW) materials involve vast interface areas that are often subject to contamination, vdW interactions between layers may squeeze interfacial contaminants into nanopockets. More intriguingly, those nanopockets could spontaneously coalesce into larger ones, which are easier to be squeezed out the atomic channels. Such unusual phenomena have been thought of as an Ostwald ripening process that is driven by the capillarity of the confined liquid. The underlying mechanism, however, is unclear as the crucial role played by the sheet’s elasticity has not been previously appreciated. Here, we demonstrate the coalescence of separated nanopockets and propose a cleaning mechanism in which both elastic and capillary forces are at play. We elucidate this mechanism in terms of control of the nanopocket morphology and the coalescence of nanopockets via a mechanical stretch. Besides, we demonstrate that bilayer graphene interfaces excel in self-renewal phenomena.
The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter
Authors: Plenge Per , Yang Dongxue , Salomon Kristine , Laursen Louise , Kalenderoglou Iris E. , Newman Amy H. , Gouaux Eric , Coleman Jonathan A. , Loland Claus J.
Published: August 2021

Depression is a common mental disorder. The standard medical treatment is the selective serotonin reuptake inhibitors (SSRIs). All characterized SSRIs are competitive inhibitors of the serotonin transporter (SERT). A non-competitive inhibitor may produce a more favorable therapeutic profile. Vilazodone is an antidepressant with limited information on its molecular interactions with SERT. Here we use molecular pharmacology and cryo-EM structural elucidation to characterize vilazodone binding to SERT. We find that it exhibits non-competitive inhibition of serotonin uptake and impedes dissociation of [3H]imipramine at low nanomolar concentrations. Our SERT structure with bound imipramine and vilazodone reveals a unique binding pocket for vilazodone, expanding the boundaries of the extracellular vestibule. Characterization of the binding site is substantiated with molecular dynamics simulations and systematic mutagenesis of interacting residues resulting in decreased vilazodone binding to the allosteric site. Our findings underline the versatility of SERT allosteric ligands and describe the unique binding characteristics of vilazodone.
Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes
Authors: Rui Jinxiu , Deng Songyan , Perdigoto Ana Luisa , Ponath Gerald , Kursawe Romy , Lawlor Nathan , Sumida Tomokazu , Levine-Ritterman Maya , Stitzel Michael L. , Pitt David , Lu Jun , Herold Kevan C.
Published: August 2021

β cells may participate and contribute to their own demise during Type 1 diabetes (T1D). Here we report a role of their expression of Tet2 in regulating immune killing. Tet2 is induced in murine and human β cells with inflammation but its expression is reduced in surviving β cells. Tet2-KO mice that receive WT bone marrow transplants develop insulitis but not diabetes and islet infiltrates do not eliminate β cells even though immune cells from the mice can transfer diabetes to NOD/scid recipients. Tet2-KO recipients are protected from transfer of disease by diabetogenic immune cells.Tet2-KO β cells show reduced expression of IFNγ-induced inflammatory genes that are needed to activate diabetogenic T cells. Here we show that Tet2 regulates pathologic interactions between β cells and immune cells and controls damaging inflammatory pathways. Our data suggests that eliminating TET2 in β cells may reduce activating pathologic immune cells and killing of β cells.
WS2 moiré superlattices derived from mechanical flexibility for hydrogen evolution reaction
Authors: Xie Lingbin , Wang Longlu , Zhao Weiwei , Liu Shujuan , Huang Wei , Zhao Qiang
Published: August 2021

The discovery of moiré superlattices (MSLs) opened an era in the research of ‘twistronics’. Engineering MSLs and realizing unique emergent properties are key challenges. Herein, we demonstrate an effective synthetic strategy to fabricate MSLs based on mechanical flexibility of WS2 nanobelts by a facile one-step hydrothermal method. Unlike previous MSLs typically created through stacking monolayers together with complicated method, WS2 MSLs reported here could be obtained directly during synthesis of nanobelts driven by the mechanical instability. Emergent properties are found including superior conductivity, special superaerophobicity and superhydrophilicity, and strongly enhanced electro-catalytic activity when we apply ‘twistronics’ to the field of catalytic hydrogen production. Theoretical calculations show that such excellent catalytic performance could be attributed to a closer to thermoneutral hydrogen adsorption free energy value of twisted bilayers active sites. Our findings provide an exciting opportunity to design advanced WS2 catalysts through moiré superlattice engineering based on mechanical flexibility.
O-GlcNAcylated p53 in the liver modulates hepatic glucose production
Authors: Gonzalez-Rellan Maria J. , Fondevila Marcos F. , Fernandez Uxia , Rodríguez Amaia , Varela-Rey Marta , Veyrat-Durebex Christelle , Seoane Samuel , Bernardo Ganeko , Lopitz-Otsoa Fernando , Fernández-Ramos David , Bilbao Jon , Iglesias Cristina , Novoa Eva , Ameneiro Cristina , Senra Ana , Beiroa Daniel , Cuñarro Juan , DP Chantada-Vazquez Maria , Garcia-Vence Maria , Bravo Susana B. , Da Silva Lima Natalia , Porteiro Begoña , Carneiro Carmen , Vidal Anxo , Tovar Sulay , Müller Timo D. , Ferno Johan , Guallar Diana , Fidalgo Miguel , Sabio Guadalupe , Herzig Stephan , Yang Won Ho , Cho Jin Won , Martinez-Chantar Maria Luz , Perez-Fernandez Roman , López Miguel , Dieguez Carlos , Mato Jose M. , Millet Oscar , Coppari Roberto , Woodhoo Ashwin , Fruhbeck Gema , Nogueiras Ruben
Published: August 2021

p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized byO-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible ofO-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that theO-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.
Haplotype-resolved de novo assembly of the Vero cell line genome
Authors: Sène Marie-Angélique , Kiesslich Sascha , Djambazian Haig , Ragoussis Jiannis , Xia Yu , Kamen Amine A.
Published: August 2021

The Vero cell line is the most used continuous cell line for viral vaccine manufacturing with more than 40 years of accumulated experience in the vaccine industry. Additionally, the Vero cell line has shown a high affinity for infection by MERS-CoV, SARS-CoV, and recently SARS-CoV-2, emerging as an important discovery and screening tool to support the global research and development efforts in this COVID-19 pandemic. However, the lack of a reference genome for the Vero cell line has limited our understanding of host–virus interactions underlying such affinity of the Vero cell towards key emerging pathogens, and more importantly our ability to redesign high-yield vaccine production processes using Vero genome editing. In this paper, we present an annotated highly contiguous 2.9 Gb assembly of the Vero cell genome. In addition, several viral genome insertions, including Adeno-associated virus serotypes 3, 4, 7, and 8, have been identified, giving valuable insights into quality control considerations for cell-based vaccine production systems. Variant calling revealed that, in addition to interferon, chemokines, and caspases-related genes lost their functions. Surprisingly, the ACE2 gene, which was previously identified as the host cell entry receptor for SARS-CoV and SARS-CoV-2, also lost function in the Vero genome due to structural variations.
Toxic and heavy metals contamination assessment in soil and water to evaluate human health risk
Authors: Ahmad Waqar , Alharthy Rima D. , Zubair Muhammad , Ahmed Mahmood , Hameed Abdul , Rafique Sajjad
Published: August 2021

Due to urbanization and industrialization, there has been an increase in solid waste generation and has become a global concern and leakage of leachate from landfills contaminate the soil and groundwater and hence can have a severe impact on human health. The present study aimed to determine the composition of toxic metals (Cr, Mn, Cu, As) and heavy metals (Cd, Ba, Hg, Pb) in soil and water by an inductively coupled plasma optical emission spectrometer (ICP-OES). To ensure accuracy during the analysis of Cr, Mn, Cu, As, Cd, Ba, Hg, and Pb in real samples, certified reference material (CRM, SRM 2709a) of San Joaquin soil and water (SRM 1640a) were analyzed and results were presented in terms of % recovery studies. The mean concentration of all the metals in soil and water did not exceed the limit set by the European Community (EU), WHO, and US EPA except Cu where the permissible limit defined by the EU is 50–140 mg/kg in soil. The soil is uncontaminated to moderately contaminated with respect to all metals except the Cu and Pb. Among the average daily dose (ADD) of soil, ADDing and ADDinh for children had the maximum dose for all metals than adults while ADDderm was higher in adults. Hazard quotient (HQ) trend in both adults and children was found in order HQing > HQderm > HQinh of soil for all metals except Ba which followed HQing > HQinh > HQderm. Hazard index (HI) values of soil for Cr and Pb in children were 7 and 7.5 times higher than adults respectively. Lifetime cancer risk (LCR) value for Cr by different exposure pathways of soil was 5.361 × 10−4 for children which are at the lower borderline of risk for cancer.
Body-shape trajectories and their genetic variance component in Gilthead seabream (Sparus aurata L.)
Authors: Fragkoulis Stefanos , Kerasovitis Dimosthenis , Batargias Costas , Koumoundouros George
Published: August 2021

The phenotype of juvenile fish is closely associated with the adult phenotype, thus consisting an important quality trait for reared fish stocks. In this study, we estimated the correlation between the juvenile and adult body-shape in Gilthead seabream, and examined the genetic basis of the ontogenetic trajectories. The body shape of 959 pit-tagged fish was periodically examined during the juvenile-to-adult period. Individual shape ontogenetic trajectories were studied in respect to the initial (juvenile) and final (adult) phenotypes, as well as to the rate that adult phenotype is attained (phenotypic integration rate). We found that the juvenile body-shape presented a rapid change up to 192.7 ± 1.9 mm standard length, followed by a phenotypically stable period (plateau). Depending on the shape component considered, body-shape correlations between juvenile and adult stages ranged from 0.22 to 0.76. Heritability estimates (h2) of the final phenotype ranged from 0.370 ± 0.077 to 0.511 ± 0.089, whereas h2 for the phenotypic integration rate was 0.173 ± 0.062. To our knowledge, this is the first study demonstrating that the variance of the ontogenetic trajectories has a substantial additive genetic component. Results are discussed in respect to their potential use in selective breeding programs of Gilthead seabream.
Implicit and explicit learning of Bayesian priors differently impacts bias during perceptual decision-making
Authors: Thakur V. N. , Basso M. A. , Ditterich J. , Knowlton B. J.
Published: August 2021

Knowledge without awareness, or implicit knowledge, influences a variety of behaviors. It is unknown however, whether implicit knowledge of statistical structure informs visual perceptual decisions or whether explicit knowledge of statistical probabilities is required. Here, we measured visual decision-making performance using a novel task in which humans reported the orientation of two differently colored translational Glass patterns; each color associated with different orientation probabilities. The task design allowed us to assess participants’ ability to learn and use a general orientation prior as well as a color specific feature prior. Classifying decision-makers based on a questionnaire revealed that both implicit and explicit learners implemented a general orientation bias by adjusting the starting point of evidence accumulation in the drift diffusion model framework. Explicit learners additionally adjusted the drift rate offset. When subjects implemented a stimulus specific bias, they did so by adjusting primarily the drift rate offset. We conclude that humans can learn priors implicitly for perceptual decision-making and depending on awareness implement the priors using different mechanisms.
Effect of repetitive transcranial magnetic stimulation on depression and cognition in individuals with traumatic brain injury: a systematic review and meta-analysis
Authors: Tsai Ping-Yen , Chen Yang-Ching , Wang Jia-Yi , Chung Kuo-Hsuan , Lai Chien-Hung
Published: August 2021

Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved therapy in major depressive disorder. However, its treatment efficacy on depression after traumatic brain injury (TBI) remains inconclusive. We conducted a meta-analysis to assess the effectiveness of executing rTMS over dorsolateral prefrontal cortex (DLPFC) on depression, cognitive impairment and post-concussion syndrome in individuals with traumatic brain injury. This study contained seven randomized controlled trials that published before April 5, 2020 in PubMed, Embase, Scopus, Cochrane, and Web of Science databases. The rTMS had significant anti-depressant effect (SMD = 1.03, p = 0.02), but the effects dissipated at 1-month follow-up (SMD = 0.39, p = 0.62). In the subgroup analysis, only applying rTMS to left DLPFC area of post-TBI patients showed significant anti-depressant effect (SMD = 0.98, p = 0.04). Moreover, current data observed that rTMS on post-TBI patients possessed substantial improvement in visuospatial memory (SMD = 0.39, p < 0.0001), but wasn’t in processing speed (SMD = − 0.18, p = 0.32) and selective attention (SMD = 0.21, p = 0.31). In addition, the effect of rTMS is not superior to sham on postconcussion syndrome. In conclusion, the short-term antidepressant effect of left DLPFC rTMS in patients with TBI was significant. However, the effectiveness of rTMS on cognition and postconcussion syndrome in patients with post-TBI depression was limited.
Intra-seasonal contrasting trends in clouds due to warming induced circulation changes
Authors: Prijith S. S. , Lima C. B. , Ramana M. V. , Sai M. V. R. Sesha
Published: August 2021

Quantification of long term changes in cloud distribution and properties is critical for the proper assessment of future climate. We show contrasting trends in cloud properties and cloud radiative effects over Northwest Indian Ocean (NWIO) in south Asian summer monsoon. Cloud top height (CTH) decreases in June (− 69 ± 3 myr−1) and July (− 44 ± 3 myr−1), whereas it increases in August (106 ± 2 myr−1) and September (37 ± 1 myr−1). These contrasting trends are investigated to be due to the changes in upper tropospheric winds and atmospheric circulation pattern. Strengthening of upper tropospheric easterlies and changes in vertical wind dampen the vertical development of clouds in June and July. In contrast, weakening of upper tropospheric winds over NWIO and strengthening of updraft favour the vertical growth of clouds in August. Further, changes in horizontal winds at 450–350 hPa and strengthening of Indian Ocean Walker cell favour the westward spread of high level clouds, contributing to the increase in CTH over NWIO in August. Decrease of cloud cover and altitude in June and July and increase of the same in subsequent months would affect the monsoon rainfall over the Indian region. Proper representation of these intra-seasonal contrasting trends of clouds in climate models is important for the better prediction of regional weather.
Oceanic and super-deep continental diamonds share a transition zone origin and mantle plume transportation
Authors: Doucet Luc S. , Li Zheng-Xiang , Gamal El Dien Hamed
Published: August 2021

Rare oceanic diamonds are believed to have a mantle transition zone origin like super-deep continental diamonds. However, oceanic diamonds have a homogeneous and organic-like light carbon isotope signature (δ13C − 28 to − 20‰) instead of the extremely variable organic to lithospheric mantle signature of super-deep continental diamonds (δ13C − 25‰ to + 3.5‰). Here, we show that with rare exceptions, oceanic diamonds and the isotopically lighter cores of super-deep continental diamonds share a common organic δ13C composition reflecting carbon brought down to the transition zone by subduction, whereas the rims of such super-deep continental diamonds have the same δ13C as peridotitic diamonds from the lithospheric mantle. Like lithospheric continental diamonds, almost all the known occurrences of oceanic diamonds are linked to plume-induced large igneous provinces or ocean islands, suggesting a common connection to mantle plumes. We argue that mantle plumes bring the transition zone diamonds to shallower levels, where only those emplaced at the base of the continental lithosphere might grow rims with lithospheric mantle carbon isotope signatures.
Insula activity in resting-state differentiates bipolar from unipolar depression: a systematic review and meta-analysis
Authors: Pastrnak Martin , Simkova Eva , Novak Tomas
Published: August 2021

Symptomatic overlap of depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) is a major diagnostic and therapeutic problem. Mania in medical history remains the only reliable distinguishing marker which is problematic given that episodes of depression compared to episodes of mania are more frequent and predominantly present at the beginning of BD. Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive, task-free, and well-tolerated method that may provide diagnostic markers acquired from spontaneous neural activity. Previous rs-fMRI studies focused on differentiating BD from MDD depression were inconsistent in their findings due to low sample power, heterogeneity of compared samples, and diversity of analytical methods. This meta-analysis investigated resting-state activity differences in BD and MDD depression using activation likelihood estimation. PubMed, Web of Science, Scopus and Google Scholar databases were searched for whole-brain rs-fMRI studies which compared MDD and BD currently depressed patients between Jan 2000 and August 2020. Ten studies were included, representing 234 BD and 296 MDD patients. The meta-analysis found increased activity in the left insula and adjacent area in MDD compared to BD. The finding suggests that the insula is involved in neural activity patterns during resting-state that can be potentially used as a biomarker differentiating both disorders.
Biogeography of acoustic biodiversity of NW Mediterranean coralligenous reefs
Authors: Di Iorio Lucia , Audax Manon , Deter Julie , Holon Florian , Lossent Julie , Gervaise Cédric , Boissery Pierre
Published: August 2021

Monitoring the biodiversity of key habitats and understanding the drivers across spatial scales is essential for preserving ecosystem functions and associated services. Coralligenous reefs are threatened marine biodiversity hotspots that are challenging to monitor. As fish sounds reflect biodiversity in other habitats, we unveiled the biogeography of coralligenous reef sounds across the north-western Mediterranean using data from 27 sites covering 2000 km and 3 regions over a 3-year period. We assessed how acoustic biodiversity is related to habitat parameters and environmental status. We identified 28 putative fish sound types, which is up to four times as many as recorded in other Mediterranean habitats. 40% of these sounds are not found in other coastal habitats, thus strongly related to coralligenous reefs. Acoustic diversity differed between geographical regions. Ubiquitous sound types were identified, including sounds from top-predator species and others that were more specifically related to the presence of ecosystem engineers (red coral, gorgonians), which are key players in maintaining habitat function. The main determinants of acoustic community composition were depth and percentage coverage of coralligenous outcrops, suggesting that fish-related acoustic communities exhibit bathymetric stratification and are related to benthic reef assemblages. Multivariate analysis also revealed that acoustic communities can reflect different environmental states. This study presents the first large-scale map of acoustic fish biodiversity providing insights into the ichthyofauna that is otherwise difficult to assess because of reduced diving times. It also highlights the potential of passive acoustics in providing new aspects of the correlates of biogeographical patterns of this emblematic habitat relevant for monitoring and conservation.
Comparing the effect of zinc oxide and titanium dioxide nanoparticles on the ability of moderately halophilic bacteria to treat wastewater
Authors: Weber Vanessa , Kamika Ilunga , Momba Maggy N. B.
Published: August 2021

This study evaluates the ability of moderately halophilic bacterial isolates (Serratia sp., Bacillus sp., Morganella sp., Citrobacter freundii and Lysinibacillus sp.) to treat polluted wastewater in the presence of nZnO and nTiO2 nanoparticles. In this study, bacteria isolates were able to take up nZnO and nTiO2 at concentrations ranging from 1 to 50 mg/L in the presence of higher DO uptake at up to 100% and 99%, respectively, while higher concentrations triggered a significant decrease. Individual halophilic bacteria exhibited a low COD removal efficiency in the presence of both metal oxide nanoparticles concentration ranged between 1 and 10 mg/L. At higher concentrations, they triggered COD release of up to − 60% concentration. Lastly, the test isolates also demonstrated significant nutrient removal efficiency in the following ranges: 23–65% for NO3− and 28–78% for PO43−. This study suggests that moderately halophilic bacteria are good candidates for the bioremediation of highly polluted wastewater containing low metal oxide nanoparticles.
NIR-chemometric approaches for evaluating carbonization characteristics of hydrothermally carbonized lignin
Authors: Hwang Sung-Wook , Hwang Un Taek , Jo Kyeyoung , Lee Taekyeong , Park Jinseok , Kim Jong-Chan , Kwak Hyo Won , Choi In-Gyu , Yeo Hwanmyeong
Published: August 2021

The aim of this study is to establish prediction models for the non-destructive evaluation of the carbonization characteristics of lignin-derived hydrochars as a carbon material in real time. Hydrochars are produced via the hydrothermal carbonization of kraft lignins for 1–5 h in the temperature range of 175–250 °C, and as the reaction severity of hydrothermal carbonization increases, the hydrochar is converted to a more carbon-intensive structure. Principal component analysis using near-infrared spectra suggests that the spectral regions at 2132 and 2267 nm assigned to lignins and 1449 nm assigned to phenolic groups of lignins are informative bands that indicate the carbonization degree. Partial least squares regression models trained with near-infrared spectra accurately predicts the carbon content, oxygen/carbon, and hydrogen/carbon ratios with high coefficients of determination and low root mean square errors. The established models demonstrate better prediction than ordinary least squares regression models.
Novel Prognostic Score for recurrent or metastatic head and neck cancer patients treated with Nivolumab
Authors: Minohara Kiyoshi , Matoba Takuma , Kawakita Daisuke , Takano Gaku , Oguri Keisuke , Murashima Akihiro , Nakai Kazuhiro , Iwaki Sho , Hojo Wataru , Matsumura Ayano , Ozaki Shinya , Ozawa Taijiro , Harata Ikuma , Tanaka Nobukazu , Maseki Shinichiro , Tsuge Hiroshi , Imaizumi Sae , Mitsuya Shoji , Moribe Kazuho , Esaki Shinichi , Iwasaki Shinichi
Published: August 2021

Although several prognostic factors in nivolumab therapy have been reported in recurrent or metastatic head and neck cancer (RM-HNC) patients, these factors remain controversial. Here, we conducted a multicenter retrospective cohort study to investigate the impact of clinico-hematological factors on survival in RM-HNC patients treated with nivolumab. We reviewed 126 RM-HNC patients from seven institutes. We evaluated the prognostic effects of clinico-hematological factors on survival. The median overall survival (OS) was 12.3 months, and the 1 year-OS rate was 51.2%. Patients without immune-related adverse events, lower relative eosinophil count, worse best overall response, higher performance status, and higher modified Glasgow Prognostic Score had worse survival. The score, generated by combining these factors, was associated with survival. Patients with score of 4–5 had worse survival than those with score of 2–3 and 0–1 [adjusted HR for PFS: score of 4–5, 7.77 (3.98–15.15); score of 2–3, 3.44 (1.95–6.06), compared to score of 0–1], [adjusted HR for OS: score of 4–5, 14.66 (4.28–50.22); score of 2–3, 7.63 (2.29–25.37), compared to score of 0–1]. Our novel prognostic score utilizing clinico-hematological factors might be useful to establish an individual treatment strategy in RM-HNC patients treated with nivolumab therapy.
Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel
Authors: Krylova Irina B. , Selina Elena N. , Bulion Valentina V. , Rodionova Olga M. , Evdokimova Natalia R. , Belosludtseva Natalia V. , Shigaeva Maria I. , Mironova Galina D.
Published: August 2021

The effect of uridine on the myocardial ischemic and reperfusion injury was investigated. A possible mechanism of its cardioprotective action was established. Two rat models were used: (1) acute myocardial ischemia induced by occlusion of the left coronary artery for 60 min; and (2) myocardial ischemia/reperfusion with 30-min ischemia and 120-min reperfusion. In both models, treatment with uridine (30 mg/kg) prevented a decrease in cell energy supply and in the activity of the antioxidant system, as well as an increase in the level of lipid hydroperoxides and diene conjugates. This led to a reduction of the necrosis zone in the myocardium and disturbances in the heart rhythm. The blocker of the mitochondrial ATP-dependent potassium (mitoKATP) channel 5-hydroxydecanoate limited the positive effects of uridine. The data indicate that the cardioprotective action of uridine may be related to the activation of the mitoKATP channel. Intravenously injected uridine was more rapidly eliminated from the blood in hypoxia than in normoxia, and the level of the mitoKATP channel activator UDP in the myocardium after uridine administration increased. The results suggest that the use of uridine can be a potentially effective approach to the management of cardiovascular diseases.
A xanthene derivative, DS20060511, attenuates glucose intolerance by inducing skeletal muscle-specific GLUT4 translocation in mice
Authors: Furuzono Shinji , Kubota Tetsuya , Taura Junki , Konishi Masahiro , Naito Asuka , Tsutsui Masato , Karasawa Hiroshi , Kubota Naoto , Kadowaki Takashi
Published: August 2021

Reduced glucose uptake into the skeletal muscle is an important pathophysiological abnormality in type 2 diabetes, and is caused by impaired translocation of glucose transporter 4 (GLUT4) to the skeletal muscle cell surface. Here, we show a xanthene derivative, DS20060511, induces GLUT4 translocation to the skeletal muscle cell surface, thereby stimulating glucose uptake into the tissue. DS20060511 induced GLUT4 translocation and stimulated glucose uptake into differentiated L6-myotubes and into the skeletal muscles in mice. These effects were completely abolished in GLUT4 knockout mice. Induction of GLUT4 translocation by DS20060511 was independent of the insulin signaling pathways including IRS1-Akt-AS160 phosphorylation and IRS1-Rac1-actin polymerization, eNOS pathway, and AMPK pathway. Acute and chronic DS20060511 treatment attenuated the glucose intolerance in obese diabetic mice. Taken together, DS20060511 acts as a skeletal muscle-specific GLUT4 translocation enhancer to facilitate glucose uptake. Further studies of DS20060511 may pave the way for the development of novel antidiabetic medicines.
MicroRNA expression profile in Lampetra morii upon Vibrio anguillarum infection and miR-4561 characterization targeting lip
Authors: Ma Lie , Gou Meng , Du Zeyu , Zhu Ting , Li Jun , Li Qing Wei , Pang Yue
Published: August 2021

As a critical evolutionary pivot between invertebrates and vertebrates, lampreys provide rich genetic information. Lamprey immune protein (LIP) is a key immune regulator. MicroRNAs, well-conserved in the response to immunological stress, remain understudied in lamprey immunity. We generated a lamprey microRNA expression atlas, using deep sequencing, uponVibrio anguillaruminfection. Using comparative methods, we found that miR-4561 potentially regulates innate immunity via interaction withlip. We found a sequence in the 3′-UTR region of LIP mRNA complementary to the miR-4561 seed region; miR-4561 expression was negatively correlated with LIP. DuringV. anguillaruminfection, miR-4561 inhibited LIP expression and bacterial clearance. Notably, LIP expression in supraneural body cells was necessary for the Gram-negative immune response. Additionally, we observed that overexpression of miR-4561 induced apoptosis in embryonic cells, suggesting a role in embryonic development. Collectively, we show lamprey microRNAs may significantly affect gene regulation and provide new insights on LIP-mediated immune regulation.
Almost global convergence to practical synchronization in the generalized Kuramoto model on networks over the n-sphere
Authors: Markdahl Johan , Proverbio Daniele , Mi La , Goncalves Jorge
Published: August 2021

From the flashing of fireflies to autonomous robot swarms, synchronization phenomena are ubiquitous in nature and technology. They are commonly described by the Kuramoto model that, in this paper, we generalise to networks over n-dimensional spheres. We show that, for almost all initial conditions, the sphere model converges to a set with small diameter if the model parameters satisfy a given bound. Moreover, for even n, a special case of the generalized model can achieve phase synchronization with nonidentical frequency parameters. These results contrast with the standard n = 1 Kuramoto model, which is multistable (i.e., has multiple equilibria), and converges to phase synchronization only if the frequency parameters are identical. Hence, this paper shows that the generalized network Kuramoto models for n ≥ 2 displays more coherent and predictable behavior than the standard n = 1 model, a desirable property both in flocks of animals and for robot control.
Asymmetric binomial statistics explains organelle partitioning variance in cancer cell proliferation
Authors: Peruzzi Giovanna , Miotto Mattia , Maggio Roberta , Ruocco Giancarlo , Gosti Giorgio
Published: August 2021

Asymmetric inheritance of organelles and compounds between daughter cells is considered a hallmark for differentiation and rejuvenation in stem-like and cancer cells, as much as a mechanism for enhancing resistance in bacteria populations. In non-differentiating homogeneous cancer cells, asymmetric division is still poorly investigated. Here, we present a method based on the binomial partitioning process that allows the measurement of asymmetric organelle partitioning with multiple live cell markers without genetically mutating the cells. We demonstrate our method by measuring simultaneously the partitioning of three cellular elements, i.e., cytoplasm, membrane, and mitochondria in human Jurkat T-cells. We found that although cell cytoplasm is partitioned symmetrically, mitochondria and membrane lipids are asymmetrically partitioned between daughter cells. Moreover, we observe that mitochondria and membrane lipids present a stable positive correlation with cytoplasm, incompatibly with a binomial partition mechanism produced by two independent partitioning processes. Our experimental apparatus, combined with our theoretical framework, could be generalized to different cell kinds, providing a tool for understanding partitioning-driven biological processes.
Ordinal patterns-based methodologies for distinguishing chaos from noise in discrete time series
Authors: Zanin Massimiliano , Olivares Felipe
Published: August 2021

One of the most important aspects of time series is their degree of stochasticity vs. chaoticity. Since the discovery of chaotic maps, many algorithms have been proposed to discriminate between these two alternatives and assess their prevalence in real-world time series. Approaches based on the combination of “permutation patterns” with different metrics provide a more complete picture of a time series’ nature, and are especially useful to tackle pathological chaotic maps. Here, we provide a review of such approaches, their theoretical foundations, and their application to discrete time series and real-world problems. We compare their performance using a set of representative noisy chaotic maps, evaluate their applicability through their respective computational cost, and discuss their limitations.
A transparent waveguide chip for versatile total internal reflection fluorescence-based microscopy and nanoscopy
Authors: Priyadarshi Anish , Dullo Firehun Tsige , Wolfson Deanna Lynn , Ahmad Azeem , Jayakumar Nikhil , Dubey Vishesh , Tinguely Jean-Claude , Ahluwalia Balpreet Singh , Murugan Ganapathy Senthil
Published: August 2021

Total internal reflection fluorescence (TIRF) microscopy is an imaging technique that, in comparison to confocal microscopy, does not require a trade-off between resolution, speed, and photodamage. Here, we introduce a waveguide platform for chip-based TIRF imaging based on a transparent substrate, which is fully compatible with sample handling and imaging procedures commonly used with a standard #1.5 glass coverslip. The platform is fabricated using standard complementary metal-oxide-semiconductor techniques which can easily be scaled up for mass production. We demonstrate its performance on synthetic and biological samples using both upright and inverted microscopes, and show how it can be extended to super-resolution applications, achieving a resolution of 116 nm using super resolution radial fluctuations. These transparent chips retain the scalable field of view of opaque chip-based TIRF and the high axial resolution of TIRF, and have the versatility to be used with many different objective lenses, microscopy methods, and handling techniques. We see this as a technology primed for widespread adoption, increasing both TIRF’s accessibility to users and the range of applications that can benefit from it.
Cationic polythiophene–anionic fullerene pair in water and water–dioxane: studies on hydrogen bonding capabilities, kinetic and thermodynamic properties
Authors: Domínguez Sergio E. , Kohn Benjamin , Ääritalo Timo , Damlin Pia , Scheler Ulrich , Kvarnström Carita
Published: August 2021

The interactions of a model H-bonded cationic polythiophene–anionic fullerene pair, were studied with aid of a cosolvent for the first time, generating spectroscopic, kinetic & thermodynamic data of possible usefulness for analyzing similar systems.
A sandwich SERS detection system based on optical convergence and synergistic enhancement effects
Authors: Yang Feng , Wen Ping , Jia Wenwen , Li Gang , Yang Chengfu , Li Bao , Li Dongling , Chen Li
Published: August 2021

A sandwich SERS detection system was constructed. Due to the optical convergence, the synergistic enhancement effects, and the “Au film–molecules–AgNPs” sandwich structure, the Raman intensity is greatly improved.
One-step 3D printed intelligent silk fibroin artificial skin with built-in electronics and microfluidics
Authors: Guo Maoze , Li Qian , Gao Bingbing , He Bingfang
Published: August 2021

A flexible and intelligent silk fibroin artificial skin (i-skin) with built-in electronics and microfluidics was fabricated by 3D printing. This i-skin with electro-microfluidic systems enabled sensitive biochemical and physiological sensing.
A mixed chirality α-helix in a stapled bicyclic and a linear antimicrobial peptide revealed by X-ray crystallography
Authors: Baeriswyl Stéphane , Personne Hippolyte , Di Bonaventura Ivan , Köhler Thilo , van Delden Christian , Stocker Achim , Javor Sacha , Reymond Jean-Louis
Published: August 2021

We report the first X-ray crystal structures of mixed chirality α-helices comprising only natural residues as the example of bicyclic and linear membrane disruptive amphiphilic antimicrobial peptides containing seven l- and four d-residues.
Target identification of mouse stem cell probe CDy1 as ALDH2 and Abcb1b through live-cell affinity-matrix and ABC CRISPRa library
Authors: Miyamoto Naoki , Go Young-Hyun , Ciaramicoli Larissa Miasiro , Kwon Haw-Young , Kim Heon Seok , Bi Xuezhi , Yu Young Hyun , Kim Beomsue , Ha Hyung-Ho , Kang Nam-Young , Yun Seong-Wook , Kim Jin-Soo , Cha Hyuk-Jin , Chang Young-Tae
Published: August 2021

CDy1 is a powerful tool to distingusih embryonic stem cells for reprogramming studies and regeneration medicine.
Design of phase-transition molecular solar thermal energy storage compounds: compact molecules with high energy densities
Authors: Qiu Qianfeng , Gerkman Mihael A. , Shi Yuran , Han Grace G. D.
Published: August 2021

Compact azobenzene derivatives with various functional groups are investigated to realize total photon and thermal energy storage over 300 J g−1.
Facile synthesis and luminescence properties of monodisperse lutetium oxide nanostructures with adjustable particle sizes
Authors: Tang Jie , Zhang Cuimiao , Lou Xiaomeng , Yu Ziman , Jia Xiaomeng , Jia Guang
Published: August 2021

A variety of spherical lutetium compounds with narrow size distribution and adjustable diameters have been synthesized. The as-obtained Ln3+ doped phosphors and LED devices exhibit characteristic DC or UC emissions corresponding to the Ln3+ ions.
A distal regulatory strategy of enzymes: from local to global conformational dynamics
Authors: Peng Xue , Lu Chenlin , Pang Jian , Liu Zheng , Lu Diannan
Published: August 2021

Modulating the distribution of various states in protein ensembles through distal sites may be promising in the evolution of enzymes in desired directions.
A photoelectron imaging study of the deprotonated GFP chromophore anion and RNA fluorescent tags
Authors: Woodhouse Joanne L. , Henley Alice , Lewin Ross , Ward John M. , Hailes Helen C. , Bochenkova Anastasia V. , Fielding Helen H.
Published: August 2021

Green fluorescent protein (GFP), together with its family of variants, is the most widely used fluorescent protein for in vivo imaging. An investigation of the influence of fluorine and methoxy substituents on the electronic structure of the GFP chromophore.
Stationary stripe patterns and chemical waves on the bimetallic Rh(110)/Ni surface during the H2 + O2 reaction
Authors: Homann Mathias , Imbihl Ronald
Published: August 2021

Formation of a stripe pattern during the O2 + H2 reaction on a Rh(110) surface alloyed with 0.5 monolayers of Ni.
Efficient evaluation of electrostatic potential with computerized optimized code
Authors: Zhang Jun , Lu Tian
Published: August 2021

The computerized optimized code enables Multiwfn to carry out large scale electronstatic potential analyses for systems of considerable size.
On the nanoscopic structural heterogeneity of liquid n-alkyl carboxylic acids
Authors: Mariani Alessandro , Innocenti Alessandro , Varzi Alberto , Passerini Stefano
Published: August 2021

The amphiphilic nature of simple n-alkyl carboxylic acids is found to induce nanoscopic heterogeneity in their structure. Our joint SAXS and computational investigation clarified the very origin of this uncommon behaviour.
Correction: Stereoelectronic power of oxygen in control of chemical reactivity: the anomeric effect is not alone
Authors: Alabugin Igor V. , Kuhn Leah , Medvedev Michael G. , Krivoshchapov Nikolai V. , Vil' Vera A. , Yaremenko Ivan A. , Mehaffy Patricia , Yarie Meysam , Terent'ev Alexander O. , Zolfigol Mohammad Ali
Published: August 2021

Correction for ‘Stereoelectronic power of oxygen in control of chemical reactivity: the anomeric effect is not alone’ by Igor V. Alabugin et al., Chem. Soc. Rev., 2021, DOI: 10.1039/d1cs00386k.
Scalable synthesis of 3D porous germanium encapsulated in nitrogen-doped carbon matrix as an ultra-long-cycle life anode for lithium-ion batteries
Authors: Liu Xianyu , Wang Yanting , Liu Zheng , Wei Huijuan , Ma Mingguang , Xue Rui , Zhang Qianliang , Li Shengying
Published: August 2021

The 3D porous Ge/N-doped carbon nanocomposite preparation by encapsulating 3D porous Ge in a nitrogen-doped carbon matrix is reported, exhibiting excellent electrochemical performance for Li-ion batteries.
Syntheses and structure of dinuclear metal complexes containing naphthyl-Ir bichromophore
Authors: Ohyama Ryo , Mishima Masaki , Inagaki Akiko
Published: August 2021

A series of novel metal complexes were synthesized containing an Ir-cyclometalated bichromophore as a visible-light sensitizer.
Two-dimensional materials as solid-state nanopores for chemical sensing
Authors: Wang Zhan , Lv Tian-Yi , Shi Zi-Bo , Yang Shi-Shu , Gu Zhi-Yuan
Published: August 2021

The advances of 2D materials such as graphene, MoS2 and 2D MOF nanosheets as solid-state nanopores for analyzing biomolecules are discussed.
Innovative methodology for marine collagen–chitosan–fucoidan hydrogels production, tailoring rheological properties towards biomedical application
Authors: Carvalho Duarte Nuno , Gonçalves Cristiana , Oliveira Joaquim Miguel , Williams David S. , Mearns-Spragg Andrew , Reis Rui L. , Silva Tiago H.
Published: August 2021

This study provides a deeper understanding of the relationships between marine biopolymer structure/composition and rheological mechanical properties in ionic-linked hydrogel network-based formulations as a sustainable process for tissue engineering.
Peptidomimetic nitrile warheads as SARS-CoV-2 3CL protease inhibitors
Authors: Bai Bing , Arutyunova Elena , Khan Muhammad Bashir , Lu Jimmy , Joyce Michael A. , Saffran Holly A. , Shields Justin A. , Kandadai Appan Srinivas , Belovodskiy Alexandr , Hena Mostofa , Vuong Wayne , Lamer Tess , Young Howard S. , Vederas John C. , Tyrrell D. Lorne , Lemieux M. Joanne , Nieman James A.
Published: August 2021

This article describes peptidomimetic SARS-CoV-2 3CLpro inhibitors with a nitrile warhead with in vitro antiviral inhibition. Superior selectivity was observed for the nitrile warhead compared to the aldehyde against 3 human cathepsins (B, S and L).
Scalable nanoporous carbon films allow line-of-sight 3D atomic layer deposition of Pt: towards a new generation catalyst layer for PEM fuel cells
Authors: Atwa Marwa , Li Xiaoan , Wang Zhaoxuan , Dull Samuel , Xu Shicheng , Tong Xia , Tang Rui , Nishihara Hirotomo , Prinz Fritz , Birss Viola
Published: August 2021

A self-supported, binder-free and scalable nanoporous carbon scaffold serves as an excellent host for the efficient and uniform atomic layer deposition of Pt nanoparticles, showing exemplary performance as a cathode catalyst layer in a PEM fuel cell.
Metabolomics and complementary techniques to investigate the plant phytochemical cosmos
Authors: Tsugawa Hiroshi , Rai Amit , Saito Kazuki , Nakabayashi Ryo
Published: August 2021

Plants and their associated microbial communities are known to produce millions of metabolites, a majority of which are still not characterized and will be illuminated by the advance of metabolomics and the informatics techniques.
Stepwise chemical oxidation to access ultrathin metal (oxy)-hydroxide nanosheets for the oxygen evolution reaction
Authors: Lv Jiangquan , Guan Xiangfeng , Huang Yiyin , Cai Lanxin , Yu Muxin , Li Xiaoyan , Yu Yunlong , Chen Dagui
Published: August 2021

Prussian blue analogs to metal (oxy)-hydroxide nanosheets was implemented by stepwise chemical oxidation strategy. The FeCoOOH nanosheets possess an ultralow overpotential of 252 mV at 10 mA cm−2 and excellent stability for oxygen evolution reaction.
Glutamate carboxypeptidase II as a model system for designing host–guest units: a theoretical approach
Authors: Frontera Antonio , Bauzá Antonio
Published: August 2021

Through a combined crystallographic and computational analysis, we designed and investigated two novel host units for the recognition of neutral and charged guests inspired by a glutamate carboxypeptidase II system and its inhibitors.
Synthesis of (benzenesulfonyl)difluoromethyl thioethers from ((difluoromethyl)sulfonyl)benzene and organothiocyanates generated in situ
Authors: Wu Cheng , Shen Xiao , Dai Jianjun , Xu Jun , Xu Huajian
Published: August 2021

A concise and efficient method for the synthesis of (benzenesulfonyl)difluoromethyl thioethers from ((difluoromethyl)sulfonyl)benzene and organothiocyanates generated in situ is reported.
Riboflavin based conjugated biomolecule for ultrasensitive detection of nitrophenols
Authors: Kalita Bandita , Dutta Priyanka , Sen Sarma Neelotpal
Published: August 2021

Photographs of fluorescent bioconjugate RC which acts as a very simple and highly efficient optical sensor with practical applicability for real-time detection of picric acid.
Multiscale structural control of linked metal–organic polyhedra gel by aging-induced linkage-reorganization
Authors: Wang Zaoming , Villa Santos Christian , Legrand Alexandre , Haase Frederik , Hara Yosuke , Kanamori Kazuyoshi , Aoyama Takuma , Urayama Kenji , Doherty Cara M. , Smales Glen J. , Pauw Brian R. , Colón Yamil J. , Furukawa Shuhei
Published: August 2021

By a controlled post-synthetic aging process, we demonstrate a protocol to induce the linkage reorganization in metal–organic polyhedra-linked gel networks, leading to the control of gel structures over multiple length scales and their properties.