bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sumo proteome of proliferating and neuronal-differentiating cells reveals Utf1 among key Sumo targets involved in neurogenesis
Authors: Correa-Vázquez Juan F. , Juárez-Vicente Francisco , García-Gutiérrez Pablo , Barysch Sina V. , Melchior Frauke , García-Domínguez Mario
Published: March 2021

Post-translational modification by covalent attachment of the Small ubiquitin-like modifier (Sumo) polypeptide regulates a multitude of processes in vertebrates. Despite demonstrated roles of Sumo in the development and function of the nervous system, the identification of key factors displaying a sumoylation-dependent activity during neurogenesis remains elusive. Through a SILAC (stable isotope labeling by/with amino acids in cell culture)-based proteomic approach, we have identified the Sumo proteome of the model cell line P19 under proliferation and neuronal differentiation conditions. More than 300 proteins were identified as putative Sumo targets differentially associated with one or the other condition. A group of proteins of interest were validated and investigated in functional studies. Among these, Utf1 was revealed as a new Sumo target. Gain-of-function experiments demonstrated marked differences between the effects on neurogenesis of overexpressing wild-type and sumoylation mutant versions of the selected proteins. While sumoylation of Prox1, Sall4a, Trim24, and Utf1 was associated with a positive effect on neurogenesis in P19 cells, sumoylation of Kctd15 was associated with a negative effect. Prox1, Sall4a, and Kctd15 were further analyzed in the vertebrate neural tube of living embryos, with similar results. Finally, a detailed analysis of Utf1 showed the sumoylation dependence of Utf1 function in controlling the expression of bivalent genes. Interestingly, this effect seems to rely on two mechanisms: sumoylation modulates binding of Utf1 to the chromatin and mediates recruitment of the messenger RNA-decapping enzyme Dcp1a through a conserved SIM (Sumo-interacting motif). Altogether, our results indicate that the combined sumoylation status of key proteins determines the proper progress of neurogenesis.
S-adenosylmethionine upregulates the angiotensin receptor-binding protein ATRAP via the methylation of HuR in NAFLD
Authors: Guo Tao , Dai Zhe , You Ke , Battaglia-Hsu Shyue-Fang , Feng Juan , Wang Fengliang , Li Bao , Yang Jian , Li Zhen
Published: March 2021

Nonalcoholic fatty liver disease (NAFLD) has emerged globally and is associated with inflammatory signaling. The underlying mechanisms remain poorly delineated, although NAFLD has attracted considerable attention and been extensively investigated. Recent publications have determined that angiotensin II (Ang II) plays an important role in stimulating NAFLD progression by causing lipid metabolism disorder and insulin resistance through its main receptor, Ang II type 1 receptor (AT1R). Herein, we explored the effect of supplementary S-adenosylmethionine (SAM), which is the main biological methyl donor in mammalian cells, in regulating AT1R-associated protein (ATRAP), which is the negative regulator of AT1R. We found that SAM was depleted in NAFLD and that SAM supplementation ameliorated steatosis. In addition, in both high-fat diet-fed C57BL/6 rats and L02 cells treated with oleic acid (OA), ATRAP expression was downregulated at lower SAM concentrations. Mechanistically, we found that the subcellular localization of human antigen R (HuR) was determined by the SAM concentration due to protein methylation modification. Moreover, HuR was demonstrated to directly bind ATRAP mRNA and control its nucleocytoplasmic shuttling. Thus, SAM was suggested to upregulate ATRAP protein expression by maintaining the export of its mRNA from the nucleus. Taken together, our findings suggest that SAM can positively regulate ATRAP in NAFLD and may have various potential benefits for the treatment of NAFLD.
The adipokine Retnla deficiency increases responsiveness to cardiac repair through adiponectin-rich bone marrow cells
Authors: Kim Yong Sook , Cho Hyang Hee , Cho Dong Im , Jeong Hye-yun , Lim Soo yeon , Jun Ju Hee , Kim Mi Ra , Kang Bo Gyeong , Cho Meeyoung , Kang Hye-jin , Kang Wan Seok , Oh Goo Taeg , Ahn Youngkeun
Published: March 2021

Resistin-like alpha (Retnla) is a member of the resistin family and known to modulate fibrosis and inflammation. Here, we investigated the role of Retnla in the cardiac injury model. Myocardial infarction (MI) was induced in wild type (WT), Retnla knockout (KO), and Retnla transgenic (TG) mice. Cardiac function was assessed by echocardiography and was significantly preserved in the KO mice, while worsened in the TG group. Angiogenesis was substantially increased in the KO mice, and cardiomyocyte apoptosis was markedly suppressed in the KO mice. By Retnla treatment, the expression of p21 and the ratio of Bax to Bcl2 were increased in cardiomyocytes, while decreased in cardiac fibroblasts. Interestingly, the numbers of cardiac macrophages and unsorted bone marrow cells (UBCs) were higher in the KO mice than in the WT mice. Besides, phosphorylated histone H3(+) cells were more frequent in bone marrow of KO mice. Moreover, adiponectin in UBCs was notably higher in the KO mice compared with WT mice. In an adoptive transfer study, UBCs were isolated from KO mice to transplant to the WT infarcted heart. Cardiac function was better in the KO-UBCs transplanted group in the WT-UBCs transplanted group. Taken together, proliferative and adiponectin-rich bone marrow niche was associated with substantial cardiac recovery by suppression of cardiac apoptosis and proliferation of cardiac fibroblast.
Enhanced CNS transduction from AAV.PHP.eB infusion into the cisterna magna of older adult rats compared to AAV9
Authors: Chatterjee Diptaman , Marmion David J. , McBride Jodi L. , Manfredsson Fredric P. , Butler David , Messer Anne , Kordower Jeffrey H.
Published: March 2021

The development of high efficiency, central nervous system (CNS) targeting AAV-based gene therapies is necessary to address challenges in both pre-clinical and clinical investigations. The engineered capsids, AAV.PHP.B and AAV.PHP.eB, show vastly improved blood-brain barrier penetration compared to their parent serotype, AAV9, but with variable effect depending on animal system, strain, and delivery route. As most characterizations of AAV.PHP variants have been performed in mice, it is currently unknown whether AAV.PHP variants improve CNS targeting when delivered intrathecally in rats. We evaluated the comparative transduction efficiencies of equititer doses (6 × 1011vg) of AAV.PHP.eB-CAG-GFP and AAV9-CAG-GFP when delivered into the cisterna magna of 6–9-month old rats. Using both quantitative and qualitative assessments, we observed consistently superior biodistribution of GFP+ cells and fibers in animals treated with AAV.PHP.eB compared to those treated with AAV9. Enhanced GFP signal was uniformly observed throughout rostrocaudal brain regions in AAV.PHP.eB-treated animals with matching GFP protein expression detected in the forebrain, midbrain, and cerebellum. Collectively, these data illustrate the benefit of intracisternal infusions of AAV.PHP.eB as an optimal system to distribute CNS gene therapies in preclinical investigations of rats, and may have important translational implications for the clinical CNS targeting.
Reconstructing unseen transmission events to infer dengue dynamics from viral sequences
Authors: Salje Henrik , Wesolowski Amy , Brown Tyler S. , Kiang Mathew V. , Berry Irina Maljkovic , Lefrancq Noemie , Fernandez Stefan , Jarman Richard G. , Ruchusatsawat Kriangsak , Iamsirithaworn Sopon , Vandepitte Warunee P. , Suntarattiwong Piyarat , Read Jonathan M. , Klungthong Chonticha , Thaisomboonsuk Butsaya , Engø-Monsen Kenth , Buckee Caroline , Cauchemez Simon , Cummings Derek A. T.
Published: March 2021

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that addresses these limitations by considering individual transmission events, reconstructed across spatial scales. We apply it to geocoded dengue virus sequences from Thailand (N = 726 over 18 years). We find infected individuals spend 96% of their time in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining spread. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable to other pathogens.
Multispectral camouflage for infrared, visible, lasers and microwave with radiative cooling
Authors: Zhu Huanzheng , Li Qiang , Tao Chenning , Hong Yu , Xu Ziquan , Shen Weidong , Kaur Sandeep , Ghosh Pintu , Qiu Min
Published: March 2021

Interminable surveillance and reconnaissance through various sophisticated multispectral detectors present threats to military equipment and manpower. However, a combination of detectors operating in different wavelength bands (from hundreds of nanometers to centimeters) and based on different principles raises challenges to the conventional single-band camouflage devices. In this paper, multispectral camouflage is demonstrated for the visible, mid-infrared (MIR, 3–5 and 8–14 μm), lasers (1.55 and 10.6 μm) and microwave (8–12 GHz) bands with simultaneous efficient radiative cooling in the non-atmospheric window (5–8 μm). The device for multispectral camouflage consists of a ZnS/Ge multilayer for wavelength selective emission and a Cu-ITO-Cu metasurface for microwave absorption. In comparison with conventional broadband low emittance material (Cr), the IR camouflage performance of this device manifests 8.4/5.9 °C reduction of inner/surface temperature, and 53.4/13.0% IR signal decrease in mid/long wavelength IR bands, at 2500 W ∙ m−2input power density. Furthermore, we reveal that the natural convection in the atmosphere can be enhanced by radiation in the non-atmospheric window, which increases the total cooling power from 136 W ∙ m−2to 252 W ∙ m−2at 150 °C surface temperature. This work may introduce the opportunities for multispectral manipulation, infrared signal processing, thermal management, and energy-efficient applications.
A modular tool to query and inducibly disrupt biomolecular condensates
Authors: Hernández-Candia Carmen N. , Pearce Sarah , Tucker Chandra L.
Published: March 2021

Dynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.
A homogeneous split-luciferase assay for rapid and sensitive detection of anti-SARS CoV-2 antibodies
Authors: Yao Zhong , Drecun Luka , Aboualizadeh Farzaneh , Kim Sun Jin , Li Zhijie , Wood Heidi , Valcourt Emelissa J. , Manguiat Kathy , Plenderleith Simon , Yip Lily , Li Xinliu , Zhong Zoe , Yue Feng Yun , Closas Tatiana , Snider Jamie , Tomic Jelena , Drews Steven J. , Drebot Michael A. , McGeer Allison , Ostrowski Mario , Mubareka Samira , Rini James M. , Owen Shawn , Stagljar Igor
Published: March 2021

Better diagnostic tools are needed to combat the ongoing COVID-19 pandemic. Here, to meet this urgent demand, we report a homogeneous immunoassay to detect IgG antibodies against SARS-CoV-2. This serological assay, called SATiN, is based on a tri-part Nanoluciferase (tNLuc) approach, in which the spike protein of SARS-CoV-2 and protein G, fused respectively to two different tNLuc tags, are used as antibody probes. Target engagement of the probes allows reconstitution of a functional luciferase in the presence of the third tNLuc component. The assay is performed directly in the liquid phase of patient sera and enables rapid, quantitative and low-cost detection. We show that SATiN has a similar sensitivity to ELISA, and its readouts are consistent with various neutralizing antibody assays. This proof-of-principle study suggests potential applications in diagnostics, as well as disease and vaccination management.
Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy
Authors: Weinhofer Isabelle , Rommer Paulus , Zierfuss Bettina , Altmann Patrick , Foiani Martha , Heslegrave Amanda , Zetterberg Henrik , Gleiss Andreas , Musolino Patricia L. , Gong Yi , Forss-Petter Sonja , Berger Thomas , Eichler Florian , Aubourg Patrick , Köhler Wolfgang , Berger Johannes
Published: March 2021

X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
The origins and genetic interactions of KRAS mutations are allele- and tissue-specific
Authors: Cook Joshua H. , Melloni Giorgio E. M. , Gulhan Doga C. , Park Peter J. , Haigis Kevin M.
Published: March 2021

Mutational activation of KRAS promotes the initiation and progression of cancers, especially in the colorectum, pancreas, lung, and blood plasma, with varying prevalence of specific activating missense mutations. Although epidemiological studies connect specific alleles to clinical outcomes, the mechanisms underlying the distinct clinical characteristics of mutant KRAS alleles are unclear. Here, we analyze 13,492 samples from these four tumor types to examine allele- and tissue-specific genetic properties associated with oncogenic KRAS mutations. The prevalence of known mutagenic mechanisms partially explains the observed spectrum of KRAS activating mutations. However, there are substantial differences between the observed and predicted frequencies for many alleles, suggesting that biological selection underlies the tissue-specific frequencies of mutant alleles. Consistent with experimental studies that have identified distinct signaling properties associated with each mutant form of KRAS, our genetic analysis reveals that each KRAS allele is associated with a distinct tissue-specific comutation network. Moreover, we identify tissue-specific genetic dependencies associated with specific mutant KRAS alleles. Overall, this analysis demonstrates that the genetic interactions of oncogenic KRAS mutations are allele- and tissue-specific, underscoring the complexity that drives their clinical consequences.
Isotopic evidence for the formation of the Moon in a canonical giant impact
Authors: Nielsen Sune G. , Bekaert David V. , Auro Maureen
Published: March 2021

Isotopic measurements of lunar and terrestrial rocks have revealed that, unlike any other body in the solar system, the Moon is indistinguishable from the Earth for nearly every isotopic system. This observation, however, contradicts predictions by the standard model for the origin of the Moon, the canonical giant impact. Here we show that the vanadium isotopic composition of the Moon is offset from that of the bulk silicate Earth by 0.18 ± 0.04 parts per thousand towards the chondritic value. This offset most likely results from isotope fractionation on proto-Earth during the main stage of terrestrial core formation (pre-giant impact), followed by a canonical giant impact where ~80% of the Moon originates from the impactor of chondritic composition. Our data refute the possibility of post-giant impact equilibration between the Earth and Moon, and implies that the impactor and proto-Earth mainly accreted from a common isotopic reservoir in the inner solar system.
Development of an X-Band Reflectarray Antenna for Satellite Communications
Authors: Ma Bing , Lu Fan , Zhi Guoping , Xue Xin , Zhao Xiangni , Ma Chao , Fan Yong , Yang Mei
Published: March 2021

An X-band reflectarray antenna using 16 × 12 double square ring elements for satellite communications is proposed in this paper. The feed is a 4 × 3 elements microstrip patch array designed to create edge taper of approximately − 10 dB. A prototype with right-hand circular polarization (RHCP) is manufactured and tested, and the good agreements between simulations and measurements are demonstrated. The good performance is obtained with the aperture efficiency of 40.7% and the 3-dB gain bandwidth of about 10% which is beneficial to nanosatellites.
Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments
Authors: Zhang Xingjian , Chan Trevor , Mak Michael
Published: March 2021

Cancer cell metastasis is a major factor in cancer-related mortality. During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. However, the characterization of morphological and subcellular features of cells in similar migratory phenotypes and the effects of geometric confinement on cell morphodynamics are not well understood. Here, we investigate the phenotypes of highly aggressive MDA-MB-231 cells in single cell and cell doublet (an initial and simplified collective state) forms in confined microenvironments. We group phenotypically similar single cells and cell doublets and characterize related morphological and subcellular features. We further detect two distinct migratory phenotypes, fluctuating and non-fluctuating, within the fast migrating single cell group. In addition, we demonstrate an increase in the number of protrusions formed at the leading edge of cells after invasion through geometric confinement. Finally, we track the short and long term effects of varied degrees of confinement on protrusion formation. Overall, our findings elucidate the underlying morphological and subcellular features associated with different single cell and cell doublet phenotypes and the impact of invasion through confined geometry on cell behavior.
The relationship between cardiac injury, inflammation and coagulation in predicting COVID-19 outcome
Authors: Mengozzi Alessandro , Georgiopoulos Georgios , Falcone Marco , Tiseo Giusy , Pugliese Nicola Riccardo , Dimopoulos Meletios A. , Ghiadoni Lorenzo , Barbieri Greta , Forfori Francesco , Carrozzi Laura , Santini Massimo , Monzani Fabio , De Marco Salvatore , Menichetti Francesco , Virdis Agostino , Masi Stefano ,   Pisa Covid Study Group, Sabrina Agostini o Degl’Innocenti , Martina Biancalana , Matteo Borselli , Elia Nencini , Stefano Spinelli , Rachele Antognoli , Valeria Calsolario , Simone Paterni , Rubia Baldassarri , Pietro Bertini , Giulia Brizzi , Francesco Corradi , Alessandra Della Rocca , Fabio Guarracino , Paolo Malacarne , Marco Monfroni , Chiara Piagnani , Alessandro Celi , Francesco Cinotti , Naria Park , Alessandro Cipriano , Luciano Colangelo , Chiara Sonato , Valentina Galfo , Uliana Monica , Francesca Ruberti , Giovanna Forotti , Maria Sciuto
Published: March 2021

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.
Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes
Authors: Campbell-Thompson Martha , Butterworth Elizabeth A. , Boatwright J. Lucas , Nair Malavika A. , Nasif Lith H. , Nasif Kamal , Revell Andy Y. , Riva Alberto , Mathews Clayton E. , Gerling Ivan C. , Schatz Desmond A. , Atkinson Mark A.
Published: March 2021

Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D. Islet TH axon numbers and density were significantly decreased in AAb compared to T1D with no significant differences observed in exocrine TH axon volume or lengths between groups. TH axons were in close approximation to islet α-cells in T1D individuals with long-standing diabetes. Islet RNA-sequencing and qRT-PCR analyses identified significant alterations in noradrenalin degradation, α-adrenergic signaling, cardiac β-adrenergic signaling, catecholamine biosynthesis, and additional neuropathology pathways. The close approximation of TH axons at islet α-cells supports a model for sympathetic efferent neurons directly regulating glucagon secretion. Sympathetic islet innervation and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D.
The effect of training intensity on implicit learning rates in schizophrenia
Authors: Orlov Natasza D. , Sanderson Jessica , Muqtadir Syed Ali , Kalpakidou Anastasia K. , Michalopoulou Panayiota G. , Lu Jie , Shergill Sukhi S.
Published: March 2021

Cognitive impairments in learning and memory are core symptoms of schizophrenia, associated with reduced self-reported quality of life. The most effective treatment of cognitive impairments is drill and practice cognitive training. Still, to date no study has investigated the effect of varying the frequency of training on cognitive outcomes. Here we utilized a verbal memory based language learning task, tapping into implicit cognitive processes, to investigate the role of training intensity on learning rates in individuals with schizophrenia. Data from 47 participants across two studies was utilized, one with a daily training regimen over 5 days and the other with a more intensive schedule of 5 sessions delivered over 2 days. The primary outcome measure was the change in implicit learning performance across five sessions, quantified with the Matthews Correlation Coefficient (MCC). Participants in the daily training group showed improved performance compared to the intensive group only at session 4. This is the first study to show that implicit learning rates are influenced by training intensity, with daily sessions outperforming a more intensive regimen; a period of consolidation overnight may be necessary to optimize cognitive training for individuals with schizophrenia.
Forensic analysis of beverage stains using hyperspectral imaging
Authors: Melit Devassy Binu , George Sony
Published: March 2021

Documentation and analysis of crime scene evidences are of great importance in any forensic investigation. In this paper, we present the potential of hyperspectral imaging (HSI) to detect and analyze the beverage stains on a paper towel. To detect the presence and predict the age of the commonly used drinks in a crime scene, we leveraged the additional information present in the HSI data. We used 12 different beverages and four types of paper hand towel to create the sample stains in the current study. A support vector machine (SVM) is used to achieve the classification, and a convolutional auto-encoder is used to achieve HSI data dimensionality reduction, which helps in easy perception, process, and visualization of the data. The SVM classification model was re-established for a lighter and quicker classification model on the basis of the reduced dimension. We employed volume-gradient-based band selection for the identification of relevant spectral bands in the HSI data. Spectral data recorded at different time intervals up to 72 h is analyzed to trace the spectral changes. The results show the efficacy of the HSI techniques for rapid, non-contact, and non-invasive analysis of beverage stains.
Moderate vs. mild cases of overseas-imported COVID-19 in Beijing: a retrospective cohort study
Authors: Zhai Wenliang , Luo Zujin , Zheng Yue , Dong Dawei , Wu Endong , Wang Zhengfang , Zhai Junpeng , Han Yujuan , Liu Huan , Wang Yanran , Feng Yaohui , Wang Jing , Ma Yingmin
Published: March 2021

This study compared the differences in the clinical manifestations, treatment courses and clinical turnover between mild and moderate coronavirus disease 2019 (COVID-19). Clinical data of the patients with imported COVID-19 admitted to Beijing Xiaotangshan Designated Hospital between March 15 and April 30, 2020, were retrospectively analysed. A total of 53 COVID-19 patients were included, with 21 mild and 32 moderate cases. Compared with the mild group, the moderate group showed significant differences in breathing frequency, lymphocyte count, neutrophil percentage, neutrophil/lymphocyte ratio, procalcitonin, C-reactive protein, and dynamic erythrocyte sedimentation rate. In the moderate group, 87.5% exhibited ground-glass opacities, 14% exhibited consolidative opacities, 53.1% exhibited local lesions and 68.8% exhibited unilateral lesions. The proportion of patients who received antiviral or antibiotic treatment in the moderate group was higher than that in the mild group, and the number of cases that progressed to severe disease in the moderate group was also significantly higher (18.7% vs. 0%, p = 0.035). Compared with patients with mild COVID-19, those with moderate COVID-19 exhibited more noticeable inflammatory reactions, more severe pulmonary imaging manifestations and earlier expression of protective antibodies. The overall turnover of the moderate cases was poorer than that of the mild cases.
Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance
Authors: Hossian A K M Nawshad , Zahra Fatema Tuz , Poudel Sagun , Abshire Camille F. , Polk Paula , Garai Jone , Zabaleta Jovanny , Mikelis Constantinos M. , Mattheolabakis George
Published: March 2021

This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determine differential mRNA and miRNA expression between A549/DDP and A549 cells. We analyzed the gene dysregulation with Ingenuity Pathway Analysis (IPA; QIAGEN) software. In contrast to prior research, which relied on the clustering of dysregulated genes to pathways as an indication of pathway activity, we utilized the IPA software for the dynamic evaluation of pathway activity depending on the gene dysregulation levels. We predicted 15 pathways significantly contributing to the chemoresistance, with several of them to have not been previously reported or analyzed in detail. Among them, the PKR signaling, cholesterol biosynthesis, and TEC signaling pathways are included, as well as genes, such as PIK3R3, miR-34c-5p, and MDM2, among others. We also provide a preliminary analysis of SNPs and indels, present exclusively in A549/DDP cells. This study's results provide novel potential mechanisms and molecular targets that can be explored in future studies and assist in improving the understanding of the chemoresistance phenotype.
Investigation of thermal changes in the thyroid gland region of individuals with hypothyroidism and fibromyalgia by analyzing the temperature of brown adipose tissue
Authors: Costa Ana Paula Christakis , Maia Joaquim Miguel , Brioschi Marcos Leal , de Melo Mafra Machado José Eduardo
Published: March 2021

This exploratory retrospective study aims to investigate the thermal changes in the thyroid gland region of patients with hypothyroidism and fibromyalgia by analyzing the temperature of the brown adipose tissue (BAT). A total of 166 individuals from 1000 thermographic electronic medical records were classified into four groups: Group HP + FM-50 individuals with hypothyroidism and fibromyalgia; Group FM-56 individuals with fibromyalgia only; Group HP-30 individuals with hypothyroidism only, and Group Control-30 healthy individuals. The thermal images from the electronic medical records were acquired by a FLIR T650SC infrared camera (used for thermometry) and the temperature data for each group were statistically analyzed. Group HP + FM showedr = 0, meaning that the average temperatures of the thyroid and BAT are independent of each other. Groups FM, HP and Control showedr = 1, meaning that the average temperatures of the thyroid and BAT were directly related. Our findings showed that the average temperatures of the thyroid and BAT regions are similar. Also, there was no correlation between thyroid gland temperature and the presence of hypothyroidism or fibromyalgia using thermometry.
The potential value of serum chemerin in patients with breast cancer
Authors: Song Yanfang , Zhu Xianjin , Lin Zhen , Luo Li , Wen Dan
Published: March 2021

Breast cancer (BC) is one of the most dangerous malignant diseases in females. However, the reliable serum biomarkers of BC still need to be explored. Chemerin levels have been found to be associated with different types of cancer. This study aimed to evaluate the role of serum chemerin as a biomarker of BC diagnosis, as well as the correlation between serum chemerin levels and clinicopathological features. The serum from 248 BC patients, 30 breast benign tumor patients, and 103 healthy controls were collected and serum chemerin levels were determined with enzyme-linked immunosorbent assay. We found that serum levels of chemerin in BC patients were higher than those in healthy control individuals (p < 0.05). The area under the ROC curve (AUC) for chemerin, CA15-3 and CEA was 0.703, 0.662 and 0.581, respectively, in distinguishing between breast cancer patients from healthy individuals, and the chemerin cutoff value was 100.327 ng/ml with a sensitivity of 56.60% and a specificity of 98.10%. The AUC for chemerin + CA15-3 was 0.822, which was higher than that for chemerin + CEA and CEA + CA15-3. Moreover, serum levels of chemerin were significantly associated with histologic grade, Ki67 expression, and menopausal status. However, no significant association was found between serum levels of chemerin and age, tumor size, metastase, ER status, PR status, and HER-2 status. Overall, our study suggested that the combination of chemerin with CA15-3 achieves relatively better diagnostic performance in the breast cancer. Elevated serum chemerin is associated with Ki67 expression levels and histologic grade.
Optical projection tomography as a quantitative tool for analysis of cell morphology and density in 3D hydrogels
Authors: Belay Birhanu , Koivisto Janne T. , Parraga Jenny , Koskela Olli , Montonen Toni , Kellomäki Minna , Figueiras Edite , Hyttinen Jari
Published: March 2021

Assessing cell morphology and function, as well as biomaterial performance in cell cultures, is one of the key challenges in cell biology and tissue engineering (TE) research. In TE, there is an urgent need for methods to image actual three-dimensional (3D) cell cultures and access the living cells. This is difficult using established optical microscopy techniques such as wide-field or confocal microscopy. To address the problem, we have developed a new protocol using Optical Projection Tomography (OPT) to extract quantitative and qualitative measurements from hydrogel cell cultures. Using our tools, we demonstrated the method by analyzing cell response in three different hydrogel formulations in 3D with 1.5 mm diameter samples of: gellan gum (GG), gelatin functionalized gellan gum (gelatin-GG), and Geltrex. We investigated cell morphology, density, distribution, and viability in 3D living cells. Our results showed the usability of the method to quantify the cellular responses to biomaterial environment. We observed that an elongated morphology of cells, thus good material response, in gelatin-GG and Geltrex hydrogels compared with basic GG. Our results show that OPT has a sensitivity to assess in real 3D cultures the differences of cellular responses to the properties of biomaterials supporting the cells.
Investigating the emergence of sex differences in jealousy responses in a large community sample from an evolutionary perspective
Authors: Larsen Per Helge H. , Bendixen Mons , Grøntvedt Trond Viggo , Kessler Andrea M. , Kennair Leif Edward Ottesen
Published: March 2021

Sex differences in jealousy responses to sexual and emotional infidelity are robust in samples of heterosexual adults, especially in more gender egalitarian nations. However, investigations of when and how these differences develop have been scant. We applied two forced choice infidelity scenarios in a large community sample of high school students (age 16–19, N = 1266). In line with previous findings on adults using the forced choice paradigm, adolescent males found the sexual aspect of imagined infidelity more distressing than adolescent females did. Nevertheless, there was no effect of age on the jealousy responses, and age did not moderate the sex difference. There were neither any effects of three covariates (having had first sexual intercourse, being in a committed romantic relationship, and sociosexuality), neither as markers of pubertal maturation nor as psychosocial environmental stimuli. Future research needs to investigate even younger samples in order to specify at what age the sex difference in jealousy responses emerges.
Combination of arbuscular mycorrhizal fungi and phosphate solubilizing bacteria on growth and production of Helianthus tuberosus under field condition
Authors: Nacoon Sabaiporn , Jogloy Sanun , Riddech Nuntavun , Mongkolthanaruk Wiyada , Ekprasert Jindarat , Cooper Julia , Boonlue Sophon
Published: March 2021

In this work, the effects of co-inoculation between an arbuscular mycorrhizal fungus (AMF) and a phosphate solubilizing bacteria (PSB) to promote the growth and production of sunchoke under field condition were investigated during 2016 and 2017. Four treatments were set up as follows: plants without inoculation, with AMF inoculation, with PSB inoculation and with co-inoculation of PSB and AMF. The results showed the presence of PSB and AMF colonization at the harvest stage in both years. This suggested the survival of PSB and successful AMF colonization throughout the experiments. According to correlation analysis, PSB positively affected AMF spore density and colonization rate. Also, both AMF and PSB positively correlated with growth and production of sunchoke. Co-inoculation could enhance various plant parameters. However, better results in 2016 were found in co-inoculation treatment, while AMF inoculation performed the best in 2017. All of these results suggested that our AMF and PSB could effectively promote growth and production of sunchoke under field conditions. Such effects were varied due to different environmental conditions each year. Note that this is the first study showing successful co-inoculation of AMF and PSB for promoting growth and yield of sunchoke in the real cultivation fields.
High-performance gallium nitride dielectric metalenses for imaging in the visible
Authors: Chen Meng-Hsin , Chou Wei-Ning , Su Vin-Cent , Kuan Chieh-Hsiung , Lin Hoang Yan
Published: March 2021

Metalens is one of the most promising applications for the development of metasurfaces. A wide variety of materials have been applied to metalenses working at certain spectral bands in order to meet the requirements of high efficiency and low-cost fabrication. Among these materials, wide-bandgap gallium nitride (GaN) is one of the most promising materials considering its advantages especially in semiconductor manufacturing. In this work, GaN has been utilized to fabricate the high-performance metalenses operating at visible wavelengths of 405, 532, and 633 nm with efficiencies up to 79%, 84%, and 89%, respectively. The homemade 1951 United State Air Force (UASF) resolution test chart has also been fabricated in order to provide resolvable lines with widths as small as 870 nm. As shown in the experimental results for imaging, the metalens designed at 405 nm can provide extremely high resolution to clearly resolve the smallest lines with the nano-sized widths in the homemade resolution test chart. These extraordinary experimental results come from our successful development in design and fabrication for the metalenses composed of high-aspect-ratio GaN nanoposts with nearly vertical sidewalls.
Ocular manifestations and biomarkers of Gulf War Illness in US veterans
Authors: Baksh Brandon S. , Zayan Kristen L. , Goldhardt Raquel , Felix Elizabeth R. , Klimas Nancy , Galor Anat
Published: March 2021

Gulf War Illness (GWI) is a multisystem disease with variable presentations, making diagnosis difficult. Non-invasive biomarkers would aid in disease diagnosis. We hypothesized that the eye could serve as a biomarker for GWI. We performed a retrospective case–control study using a sample of 1246 patients seen during a 5-month period in an optometry clinic. We identified veterans who were active duty during the Gulf War Era and either had a questionnaire-based diagnosis of GWI (cases) or did not (controls). Medical records were reviewed for eye and medical co-morbidities, medication use, and retinal macular and nerve fiber layer (NFL) thicknesses based on optical coherence tomography (OCT) images. Compared to controls (n = 85), individuals with GWI (n = 60) had a higher frequency of dry eye symptoms (50% vs 32.9%, p = 0.039). Multivariable analysis revealed average retinal NFL thickness (odds ratio; OR = 0.95), cup-to-disc ratio (OR = 0.005), age (OR = 0.82), and PTSD (OR = 20.5) were predictors of a GWI diagnosis. We conclude that GWI is associated with dry eye symptoms and RNFL thinning may serve as a biomarker for disease.
Comorbidities associated with genetic abnormalities in children with intellectual disability
Authors: Chen Jia-Shing , Yu Wen-Hao , Tsai Meng-Che , Hung Pi-Lien , Tu Yi-Fang
Published: March 2021

Intellectual disability (ID) has emerged as the commonest manifestation of underlying genomic abnormalities. Given that molecular genetic tests for diagnosis of ID usually require high costs and yield relatively low diagnostic rates, identification of additional phenotypes or comorbidities may increase the genetic diagnostic yield and are valuable clues for pediatricians in general practice. Here, we enrolled consecutively 61 children with unexplained moderate or severe ID and performed chromosomal microarray (CMA) and sequential whole-exome sequencing (WES) analysis on them. We identified 13 copy number variants in 12 probands and 24 variants in 25 probands, and the total diagnostic rate was 60.7%. The genetic abnormalities were commonly found in ID patients with movement disorder (100%) or with autistic spectrum disorder (ASD) (93.3%). Univariate analysis showed that ASD was the significant risk factor of genetic abnormality (P = 0.003; OR 14, 95% CI 1.7–115.4). At least 14 ID-ASD associated genes were identified, and the majority of ID-ASD associated genes (85.7%) were found to be expressed in the cerebellum based on database analysis. In conclusion, genetic testing on ID children, particularly in those with ASD is highly recommended. ID and ASD may share common cerebellar pathophysiology.
Development of a handheld liquid extraction pen for on-site mass spectrometric analysis of daily goods
Authors: Lotz Florian , Baar Paula , Spengler Bernhard , Schulz Sabine
Published: March 2021

Sampling via liquid extraction pen and electrospray ionization allows for rapid, sensitive, and semi-quantitative mass spectrometric analyses of daily goods.
Strategies for the design of nanoparticles: starting with long-circulating nanoparticles, from lab to clinic
Authors: Wang Ruyi , Zhang Zhongtao , Liu Bowen , Xue Jingwei , Liu Fulei , Tang Tongzhong , Liu Wenyuan , Feng Feng , Qu Wei
Published: March 2021

The strategies for designing long-circulating nanoparticles.
Conformational energies and equilibria of cyclic dinucleotidesin vacuoand in solution: computational chemistryvs.NMR experiments
Authors: Gutten Ondrej , Jurečka Petr , Aliakbar Tehrani Zahra , Buděšínský Miloš , Řezáč Jan , Rulíšek Lubomír
Published: March 2021

Computational “error bars” for modelling cyclic dinucleotides – NMR experimentvs.quantum mechanics and molecular dynamics.
Quantifying electron-correlation effects in small coinage-metal clustersvia ab initiocalculations
Authors: de Pina V. G. , Brito B. G. A. , Hai G.-Q. , Cândido L.
Published: March 2021

Electron correlation strongly affects the orbital occupation and electron pairing of the valence electrons in coinage-metal clusters revealed by their atomic binding energies, ionization potentials, and electron affinities.
Homochiral metal–organic frameworks for enantioseparation
Authors: Liu Juan , Mukherjee Soumya , Wang Fei , Fischer Roland A. , Zhang Jian
Published: March 2021

Contextualising rational structural design, according to the enantioselective mechanisms of homochiral metal–organic frameworks, we discuss enantioselective separations primed to deliver purification performances and analytical utilities thereof.
Boosting the performance by the water solvation shell with hydrogen bonds on protonic ionic liquids: insights into the acid catalysis of the glycosidic bond
Authors: Li Kaixin , Deng Limin , Yi Shun , Wu Yabo , Xia Guangjie , Zhao Jun , LU Dong , Min Yonggang
Published: March 2021

Hydrogen-bonding (HB) of protonic ionic liquids induced by the water solvation shell is proposed to dominate in the acid catalysis of the glycosidic bond in hydrolysis.
Se@Albumin nanoparticles ameliorate intestinal mucositis caused by cisplatinviagut microbiota-targeted regulation
Authors: Deng Liping , Zeng Hongliang , Hu Xueying , Xiao Mengqing , He Dong , Zhang Yao , Jin Yi , Hu Yibo , Zhu Yuxing , Gong Lian , Wang Zhanwang , Xiang Liang , Zhu Rongrong , Zhang Yeyu , Cheng Yaxin , Chen Xingyu , Zhang Shuihan , Peng Yongbo , Cao Ke
Published: March 2021

Chemotherapy-associated intestinal mucositis is still one of the major challenges in the first-line clinical cancer treatment.
Measuring the order parameter of vertically aligned nanorod assemblies
Authors: Kim Jeongmo , Lahlil Khalid , Gacoin Thierry , Kim Jongwook
Published: March 2021

A simple, in-situ and non-destructive analytical method to characterize the homeotropic order parameter of vertically aligned nanorods assembly is proposed utilizing a photoluminescence spectrum of rare-earth dopants.
The in-plane structure domain size of nm-thick MoSe2 uncovered by low-momentum phonon scattering
Authors: Lin Huan , Wang Ridong , Zobeiri Hamidreza , Wang Tianyu , Xu Shen , Wang Xinwei
Published: March 2021

The in-plane structure domain size of nm-thick MoSe2 is determined to be 58–85 nm based on the 0 K-limit low-momentum phonon scattering. It is close to the crystallite sizes of 64.8 nm in the (100) direction and 121 nm in the (010) direction of bulk MoSe2.
Synthesis of thermo-sensitive polymers with super narrow molecular weight distributions: PET-RAFT polymerization of N-isopropyl acrylamide mediated by cross-linked zinc porphyrins with high active site loadings
Authors: Li Fanfan , Yu Yi , Lv Hanyu , Cai Guiting , Zhang Yanwu
Published: March 2021

To overcome the aggregation of porphyrins and realize heterogeneous photo-catalysis with high active site loadings, twisted ZnTHP–Me2Si and layered ZnTHP–Ph2Si are prepared through cross-linking zinc porphyrins by different chlorosilanes.
Detection and evaluation of polymer–polymer interactions in dilute solutions of associating polymers
Authors: Pavlov Georges M. , Gosteva Anna A. , Okatova Olga V. , Dommes Olga A. , Gavrilova Irina I. , Panarin Evgenii F.
Published: March 2021

An experimental tool for the evaluation of intramolecular associative/hydrophobic interactions in polymer/solvent systems was proposed and tested.
Designing of magnetic MAB phases for energy applications
Authors: Shen Chen , Gao Qiang , Fortunato Nuno M. , Singh Harish K. , Opahle Ingo , Gutfleisch Oliver , Zhang Hongbin
Published: March 2021

Based on high-throughput density functional theory calculations, we performed screening for stable magnetic MAB compounds and predicted potential strong magnets for permanent magnet and magnetocaloric applications.
Recent advances in thermo-sensitive hydrogels for drug delivery
Authors: Yu Yibin , Cheng Yi , Tong Junye , Zhang Lei , Wei Yen , Tian Mei
Published: March 2021

Thermo-sensitive hydrogels based on different polymers have been broadly used in the pharmaceutical fields. In this review, the state-of-the-art thermo-sensitive hydrogels for drug delivery are elaborated
A roadmap for laser optimization of Yb:Ca3(NbGa)5O12-CNGG-type single crystal garnets
Authors: Álvarez-Pérez J. O. , Cano-Torres J. M. , Ruiz A. , Serrano M. D. , Cascales C. , Zaldo C.
Published: March 2021

Lasing-relevant processing and physical properties of Yb-doped Ca3(NbGa)5O12-CNGG-type disordered garnet crystals are discussed. Future directions for Yb3+ bandwidth and laser performance improvements are foreseen.
Highly accurate fabric piezoresistive sensor with anti-interference from both high humidity and sweat based on hydrophobic non-fluoride titanium dioxide nanoparticles
Authors: Yang Liyan , Ma Jun , Zhong Weibing , Liu Qiongzhen , Li Mufang , Wang Wen , Wu Yi , Wang Yuedan , Liu Xue , Wang Dong
Published: March 2021

A hydrophobic non-fluoride TiO2 modified fabric pressure sensor is firstly employed to obtain highly accurate sensing with anti-interference from high humidity and sweat, benefiting from its prominent isolation effect and moderate conductivity.