bluuebunny/crossref_metadata_2025 huggingface dataset:
(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1
Authors: Della Via Fernanda Isabel , Shiraishi Rodrigo Naoto , Santos Irene , Ferro Karla Priscila , Salazar-Terreros Myriam Janeth , Franchi Junior Gilberto Carlos , Rego Eduardo Magalhães , Saad Sara Teresinha Olalla , Torello Cristiane Okuda
Published: April 2021

(–)-Epigallocatechin-3-gallate (EGCG), the major active polyphenol extracted from green tea, has been shown to induce apoptosis and inhibit cell proliferation, cell invasion, angiogenesis and metastasis. Herein, we evaluated the in vivo effects of EGCG in acute myeloid leukaemia (AML) using an acute promyelocytic leukaemia (APL) experimental model (PML/RARα). Haematological analysis revealed that EGCG treatment reversed leucocytosis, anaemia and thrombocytopenia, and prolonged survival of PML/RARα mice. Notably, EGCG reduced leukaemia immature cells and promyelocytes in the bone marrow while increasing mature myeloid cells, possibly due to apoptosis increase and cell differentiation. The reduction of promyelocytes and neutrophils/monocytes increase detected in the peripheral blood, in addition to the increased percentage of bone marrow cells with aggregated promyelocytic leukaemia (PML) bodies staining and decreased expression of PML-RAR oncoprotein corroborates our results. In addition, EGCG increased expression of neutrophil differentiation markers such as CD11b, CD14, CD15 and CD66 in NB4 cells; and the combination of all-trans retinoic acid (ATRA) plus EGCG yield higher increase the expression of CD15 marker. These findings could be explained by a decrease of peptidyl-prolyl isomerase NIMA-interacting 1 (PIN1) expression and reactive oxygen species (ROS) increase. EGCG also decreased expression of substrate oncoproteins for PIN1 (including cyclin D1, NF-κB p65, c-MYC, and AKT) and 67 kDa laminin receptor (67LR) in the bone marrow cells. Moreover, EGCG showed inhibition of ROS production in NB4 cells in the presence of N-acetyl-L-cysteine (NAC), as well as a partial blockage of neutrophil differentiation and apoptosis, indicating that EGCG-activities involve/or are in response of oxidative stress. Furthermore, apoptosis of spleen cells was supported by increasing expression of BAD and BAX, parallel to BCL-2 and c-MYC decrease. The reduction of spleen weights of PML/RARα mice, as well as apoptosis induced by EGCG in NB4 cells in a dose-dependent manner confirms this assumption. Our results support further evaluation of EGCG in clinical trials for AML, since EGCG could represent a promising option for AML patient ineligible for current mainstay treatments.
Protein-olive oil-in-water nanoemulsions as encapsulation materials for curcumin acting as anticancer agent towards MDA-MB-231 cells
Authors: Bharmoria Pankaj , Bisht Meena , Gomes Maria C. , Martins Margarida , Neves Márcia C. , Mano João F. , Bdikin Igor , Coutinho João A. P. , Ventura Sónia P. M.
Published: April 2021

The sustainable cellular delivery of the pleiotropic drug curcumin encounters drawbacks related to its fast autoxidation at the physiological pH, cytotoxicity of delivery vehicles and poor cellular uptake. A biomaterial compatible with curcumin and with the appropriate structure to allow the correct curcumin encapsulation considering its poor solubility in water, while maintaining its stability for a safe release was developed. In this work, the biomaterial developed started by the preparation of an oil-in-water nanoemulsion using with a cytocompatible copolymer (Pluronic F 127) coated with a positively charged protein (gelatin), designed as G-Cur-NE, to mitigate the cytotoxicity issue of curcumin. These G-Cur-NE showed excellent capacity to stabilize curcumin, to increase its bio-accessibility, while allowing to arrest its autoxidation during its successful application as an anticancer agent proved by the disintegration of MDA-MB-231 breast cancer cells as a proof of concept.
Uniaxially fixed mechanical boundary condition elicits cellular alignment in collagen matrix with induction of osteogenesis
Authors: Kim Jeonghyun , Ishikawa Keiichi , Sunaga Junko , Adachi Taiji
Published: April 2021

Osteocytes differentiated from osteoblasts play significant roles as mechanosensors in modulating the bone remodeling process. While the well-aligned osteocyte network along the trabeculae with slender cell processes perpendicular to the trabeculae surface is known to facilitate the sensing of mechanical stimuli by cells and the intracellular communication in the bone matrix, the mechanisms underlying osteocyte network formation remains unclear. Here, we developed a novel in vitro collagen matrix system exerting a uniaxially-fixed mechanical boundary condition on which mouse osteoblast-like MC3T3-E1 cells were subcultured, evoking cellular alignment along the uniaxial boundary condition. Using a myosin II inhibitor, blebbistatin, we showed that the intracellular tension via contraction of actin fibers contributed to the cellular alignment under the influence of isometric matrix condition along the uniaxially-fixed mechanical boundary condition. Furthermore, the cells actively migrated inside the collagen matrix and promoted the expression of osteoblast and osteocyte genes with their orientations aligned along the uniaxially-fixed boundary condition. Collectively, our results suggest that the intracellular tension of osteoblasts under a uniaxially-fixed mechanical boundary condition is one of the factors that determines the osteocyte alignment inside the bone matrix.
The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells
Authors: Rivera-Rivera Yainyrette , Marina Mihaela , Jusino Shirley , Lee Miyoung , Velázquez Jaleisha Vélez , Chardón-Colón Camille , Vargas Geraldine , Padmanabhan Jaya , Chellappan Srikumar P. , Saavedra Harold I.
Published: April 2021

Nek2 (NIMA‐related kinase 2) is a serine/threonine-protein kinase that localizes to centrosomes and kinetochores, controlling centrosome separation, chromosome attachments to kinetochores, and the spindle assembly checkpoint. These processes prevent centrosome amplification (CA), mitotic dysfunction, and chromosome instability (CIN). Our group and others have suggested that Nek2 maintains high levels of CA/CIN, tumor growth, and drug resistance. We identified that Nek2 overexpression correlates with poor survival of breast cancer. However, the mechanisms driving these phenotypes are unknown. We now report that overexpression of Nek2 in MCF10A cells drives CA/CIN and aneuploidy. Besides, enhanced levels of Nek2 results in larger 3D acinar structures, but could not initiate tumors in a p53+/+ or a p53−/− xenograft model. Nek2 overexpression induced the epithelial-to-mesenchymal transition (EMT) while its downregulation reduced the expression of the mesenchymal marker vimentin. Furthermore, either siRNA-mediated downregulation or INH6’s chemical inhibition of Nek2 in MDA-MB-231 and Hs578t cells showed important EMT changes and decreased invasion and migration. We also showed that Slug and Zeb1 are involved in Nek2 mediated EMT, invasion, and migration. Besides its role in CA/CIN, Nek2 contributes to breast cancer progression through a novel EMT mediated mechanism.
Complex wavefront sensing based on coherent diffraction imaging using vortex modulation
Authors: Li Rujia , Cao Liangcai
Published: April 2021

Phase retrieval seeks to reconstruct the phase from the measured intensity, which is an ill-posed problem. A phase retrieval problem can be solved with physical constraints by modulating the investigated complex wavefront. Orbital angular momentum has been recently employed as a type of reliable modulation. The topological charge l is robust during propagation when there is atmospheric turbulence. In this work, topological modulation is used to solve the phase retrieval problem. Topological modulation offers an effective dynamic range of intensity constraints for reconstruction. The maximum intensity value of the spectrum is reduced by a factor of 173 under topological modulation when l is 50. The phase is iteratively reconstructed without a priori knowledge. The stagnation problem during the iteration can be avoided using multiple topological modulations.
Inference of molecular orientation/ordering change nearby topological defects by the neural network function from the microscopic color information
Authors: Sakanoue Haruka , Hayashi Yuki , Katayama Kenji
Published: April 2021

Topological defects in liquid crystals (LCs) dominate molecular alignment/motion in many cases. Here, the neural network (NN) function has been introduced to predict the LC orientation condition (orientation angle and order parameter) at local positions around topological defects from the phase/polarization microscopic color images. The NN function was trained in advance by using the color information of an LC in a planar alignment cell for different orientation angles and temperatures. The photo-induced changes of LC molecules around topological defects observed by the time-resolved measurement was converted into the image sequences of the orientation angle and the order parameter change. We found that each pair of brushes with different colors around topological defects showed different orientation angle and ordering changes. The photo-induced change was triggered by the photoisomerization reaction of molecules, and one pair of brushes increased in its order parameter just after light irradiation, causing gradual rotation in the brush. The molecules in the other pair of brushes were disordered and rotated by the effect of the initially affected region. This combination approach of the time-resolved phase/polarization microscopy and the NN function can provide detailed information on the molecular alignment dynamics around the topological defects.
CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity
Authors: Danac Joshua Miguel C. , Garcia Reynaldo L.
Published: April 2021

Circular RNAs have emerged as functional regulatory molecules whose aberrant expression has been linked to diverse pathophysiological processes. Here, we report that circPVT1 interferes with let-7 binding to NRAS, confirming this axis as one route by which circPVT1 can instigate an oncogenic program in A549 lung cancer cells and HCT116 colorectal cancer cells. CircPVT1 knockdown significantly reduced NRAS levels and attenuated cancer hallmark phenotypes such as proliferation, migration, resistance to apoptosis, cytoskeletal disorganization, and epithelial-mesenchymal transition. The effects of circPVT1 knockdown were at least partially rescued by blocking binding of let-7 to NRAS 3′UTR with a target protector, suggesting that a circPVT1/let-7/NRAS axis exists and acts in cells to reverse NRAS downregulation and favor oncogenicity. While the phenotypic effects of circPVT1 knockdown may be attributable to the global action of circPVT1, the target protection assays resolved the relative contribution of the circPVT1/let-7/NRAS axis specifically.
Estimated visceral adiposity is associated with risk of cardiometabolic conditions in a population based study
Authors: Ruiz-Castell Maria , Samouda Hanen , Bocquet Valery , Fagherazzi Guy , Stranges Saverio , Huiart Laetitia
Published: April 2021

Visceral adiposity is a major risk factor of cardiometabolic diseases. Visceral adipose tissue (VAT) is usually measured with expensive imaging techniques which present financial and practical challenges to population-based studies. We assessed whether cardiometabolic conditions were associated with VAT by using a new and easily measurable anthropometric index previously published and validated. Data (1529 participants) came from the European Health Examination Survey in Luxembourg (2013–2015). Logistic regressions were used to study associations between VAT and cardiometabolic conditions. We observed an increased risk of all conditions associated with VAT. The total adjusted odds ratio (AOR, [95% CI]) for hypertension, prediabetes/diabetes, hypercholesterolemia, and hypertriglyceridemia for the fourth quartile of VAT compared to the lowest were 10.22 [6.75, 15.47]), (5.90 [4.02, 8.67]), (3.60 [2.47, 5.25]) and (7.67 [5.04, 11.67]. We observed higher odds in women than in men for all outcomes with the exception of hypertension. Future studies should investigate the impact of VAT changes on cardiometabolic health and the use of anthropometrically predicted VAT as an accurate outcome when no biomedical imaging is available.
Evidence for magnesium–phosphorus synergism and co-limitation of grain yield in wheat agriculture
Authors: Weih Martin , Liu Hui , Colombi Tino , Keller Thomas , Jäck Ortrud , Vallenback Pernilla , Westerbergh Anna
Published: April 2021

Modern crop production is characterized by high nitrogen (N) application rates, which can influence the co-limitation of harvested yield by other nutrients. Using a multidimensional niche volume concept and scaling exponents frequently applied in plant ecological research, we report that increased N and phosphorus (P) uptake in a growing wheat crop along with enhanced grain biomass is associated with more than proportional increase of other nutrients. Furthermore, N conversion efficiency and grain yield are strongly affected by the magnesium (Mg) to P ratio in the growing crop. We analyzed a field trial in Central Sweden including nine wheat varieties grown during two years with contrasting weather, and found evidence for Mg co-limitation at lower grain yields and P co-limitation at higher yields. We argue that critical concentrations of single nutrients, which are often applied in agronomy, should be replaced by nutrient ratios. In addition, links between plant P and Mg contents and root traits were found; high root number enhanced the P:N ratio, whilst steep root angle, indicating deep roots, increased the Mg:N ratio. The results have significant implications on the management and breeding targets of agriculturally grown wheat, which is one of the most important food crops worldwide.
A randomised, prospective study of the effects of 3% diquafosol on ocular surface following cataract surgery
Authors: Kim Sangyoon , Shin Jonghoon , Lee Ji Eun
Published: April 2021

There is still no established therapeutic solution for postoperative Dry Eye Syndrome (DES) after cataract surgery, in spite of progress in surgical techniques. Diquafosol tetrasodium (DQS), a recently developed ophthalmic solution, has been reported to be effective in DES, but no study evaluated post-cataract surgery lipid layer thickness (LLT) changes in healthy patients who used DQS postoperatively. We randomly divided participants into two groups; the DQS group was treated six times daily with DQS after cataract surgery, and the sodium hyaluronate (HA) group was treated with HA in the same way. Throughout study period, the DQS group showed significantly higher tear break up time (TBUT) and LLT than HA group. In multivariate analysis, better preoperative TBUT, Schirmer’s I test score, ocular surface disease index (OSDI) score, and LLT were significantly associated with improved postoperative outcomes in each parameter. Also, the postoperative use of DQS served as an independent parameter of better TBUT, OSDI score, and LLT in postoperative 15 weeks. Treatment with 3% DQS following cataract surgery showed more improvement in TBUT and LLT, compared with 0.1% HA. Improving TBUT and LLT preoperatively and using 3% DQS postoperatively, could be a reliable choice for managing DES after cataract surgery.

Trial Registration: ISRCTN registry with ISRCTN 18755487.
Inhibition of Wnt signalling by Notch via two distinct mechanisms
Authors: Acar Ahmet , Hidalgo-Sastre Ana , Leverentz Michael K. , Mills Christopher G. , Woodcock Simon , Baron Martin , Collu Giovanna M. , Brennan Keith
Published: April 2021

Notch and Wnt are two essential signalling pathways that help to shape animals during development and to sustain adult tissue homeostasis. Although they are often active at the same time within a tissue, they typically have opposing effects on cell fate decisions. In fact, crosstalk between the two pathways is important in generating the great diversity of cell types that we find in metazoans. Several different mechanisms have been proposed that allow Notch to limit Wnt signalling, driving a Notch-ON/Wnt-OFF state. Here we explore these different mechanisms in human cells and demonstrate two distinct mechanisms by which Notch itself, can limit the transcriptional activity of β-catenin. At the membrane, independently of DSL ligands, Notch1 can antagonise β-catenin activity through an endocytic mechanism that requires its interaction with Deltex and sequesters β-catenin into the membrane fraction. Within the nucleus, the intracellular domain of Notch1 can also limit β-catenin induced transcription through the formation of a complex that requires its interaction with RBPjκ. We believe these mechanisms contribute to the robustness of cell-fate decisions by sharpening the distinction between opposing Notch/Wnt responses.
Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing
Authors: Liang Yi-Hsin , Tsai Jia-Huei , Cheng Yung-Ming , Chan Kuang-Yu , Hsu Wen-Ling , Lee Chang-Cheng , Chen Kuo-Hsing , Yeh Kun-Huei
Published: April 2021

Single immunotherapy fails to demonstrate efficacy in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Research on immune reactions before and after systemic agents for mCRC is warranted. Our study examined cell line models to compare the expression of immune surface markers on colon cancer cells before and after chemotherapy agents. We also elucidated mechanisms underlying the effects of chemotherapy agents on immune surface markers. We used real-world clinical samples with NanoString analysis and the Perkin-Elmer Opal multiplex system. We established that chemotherapy agents, particularly 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, stimulated the expression of stimulatory MHC class I alleles through stimulation the pathway of transporters associated with antigen processing 1 and 2 (TAP1 and TAP2) in cell line models. Application of infected cell protein 47 (ICP-47), a specific inhibitor of the TAP1/TAP2, significantly inhibited expression of TAP1/TAP2 and also inhibited the expression of the downstream MHC class I. In the functional assay, SN-38 significantly promoted the phagocytosis of colon cancer cells by monocyte-derived dendritic cells (MoDCs). We confirmed that the expression of major histocompatibility complex (MHC) class I, significantly increased after first-line chemotherapy and targeted therapy in the samples of real-world patients with de novo mCRC. Our study provides new insights for novel immunotherapy combinations.
Impact of air injection on subretinal fluid following successful scleral buckling surgery for macular-involving retinal detachment
Authors: Tang Fen , Xu Fan , Su Ning , Liu Lingjuan , Jiang Li , Tang Ningning , Zhao Xin , Cui Ling , Zeng Siming , Lai Zhaoguang , Li Min , Zhong Haibin
Published: April 2021

Air injection is an accessory technique during scleral buckling (SB). Subclinical subretinal fluid (SRF) may presence and persistent after SB. The impact of air injection on SRF is unclear. In the study, we retrospectively enrolled 51 patients with macular-involving RD who had undergone successful SB. They were categorized into Group A (SB without air injection) and Group B (SB with air injection). First, we found that although group B seem to be severer than group A before surgery, Kaplan–Meier graph showed that SRF absorbed more rapidly in group B after surgery, and the incidence of SRF in group B was much lower during the whole follow-up period. Moreover, the cases with superior breaks had the lowest incidence. Second, during the follow-up period, there was no significant difference about postoperative complication between two groups. Lastly, risk factors for persistent SRF were investigated with binary logistic regression, and no risk factor was found. In conclusion, air injection during the SB might accelerate SRF absorption and reduce the incidence of persistent SRF, especially for the longstanding macular-off RD with superior breaks.
Chronic mild and acute severe glaucomatous neurodegeneration derived from silicone oil-induced ocular hypertension
Authors: Fang Fang , Zhang Jie , Zhuang Pei , Liu Pingting , Li Liang , Huang Haoliang , Webber Hannah C. , Xu Yangfan , Liu Liang , Dalal Roopa , Sun Yang , Hu Yang
Published: April 2021

Recently, we established silicone oil-induced ocular hypertension (SOHU) mouse model with significant glaucomatous neurodegeneration. Here we characterize two additional variations of this model that simulate two distinct glaucoma types. The first is a chronic model produced by high frequency (HF) pupillary dilation after SO-induced pupillary block, which shows sustained moderate IOP elevation and corresponding slow, mild glaucomatous neurodegeneration. We also demonstrate that although SO removal quickly returns IOP to normal, the glaucomatous neurodegeneration continues to advance to a similar degree as in the HF group without SO removal. The second, an acute model created by no pupillary dilation (ND), shows a greatly elevated IOP and severe inner retina degeneration at an early time point. Therefore, by a straightforward dilation scheme, we extend our original SOHU model to recapitulate phenotypes of two major glaucoma forms, which will be invaluable for selecting neuroprotectants and elucidating their molecular mechanisms.
The Tri-ponderal Mass Index is associated with adiposity in adolescent type 2 diabetes mellitus: a cross-sectional analysis
Authors: Alfaraidi Haifa , Wicklow Brandy , Dart Allison B. , Sellers Elizabeth , McGavock Jonathan , Thabane Lehana , Samaan M. Constantine
Published: April 2021

Pediatric type 2 diabetes mellitus (T2DM) patients are often overweight or obese, yet there are no validated clinical measures of adiposity to stratify cardiometabolic risk in this population. The tri-ponderal mass index (TMI, kg/m3) has recently been reported as a measure of adiposity in children, but there has been no validation of the association of TMI with adiposity in pediatric T2DM. We hypothesized that in children with T2DM, the TMI can serve as a more accurate measure of adiposity when compared to BMI z-score, and that it is associated with components of the metabolic syndrome. This is a cross-sectional secondary data analysis from the Improving Renal Complications in Adolescents with Type 2 Diabetes Through REsearch (iCARE) study (n = 116, age 10.20–17.90 years). Spearman’s correlations and multivariable regression were used in the analyses. When compared to DXA, TMI demonstrated significant correlation with total adiposity versus BMI z-score (TMI r = 0.74, p-value < 0.0001; BMI z-score r = − 0.08, p-value 0.403). In regression analyses, TMI was associated with WHtR (B = 35.54, 95% CI 28.81, 42.27, p-value < 0.0001), MAP dipping (B = 1.73, 95% CI 0.12, 3.33, p-value = 0.035), and HDL (B = − 5.83, 95% CI − 10.13, − 1.54, p-value = 0.008). In conclusion, TMI is associated with adiposity and components of the metabolic syndrome in pediatric T2DM patients.
Internode elongation and strobili production of Humulus lupulus cultivars in response to local strain sensing
Authors: Bauerle William L.
Published: April 2021

Three different cultivars of Humulus lupulus L. were subjected to a regime of internode touch and bending under greenhouse conditions. Experiments were performed to assess intraspecific variability in plant mechanosensing, flower quality, and yield to quantify the thigmomorphogenic impact on plant compactness and flowering performance. Touching and/or touching plus bending the plant shoot internodes located in the apical meristem zone decreased internode elongation and increased width. The growth responses were due partly to touching and/or touching plus bending perturbation, 25.6% and 28% respectively. Growth of new tissue within the local apical portion of the bine continued to remain mechanosensitive. The number of nodes and female flowers produced was unaffected by either type of mechanical stress. The study provides evidence that thigmomorphogenic cues can be used as a hop crop management tool to increase bine compactness and increase node density per unit area. The findings have broad implications for hop production; production can more readily take place in a confined greenhouse space with the aid of mechanical stimulation to control plant growth without sacrificing yield or flower quality.
Misoprostol vs dinoprostone vaginal insert in labour induction: comparison of obstetrical outcome
Authors: Mlodawski Jakub , Mlodawska Marta , Armanska Justyna , Swiercz Grzegorz , Gluszek Stanisław
Published: April 2021

Induction of labour (IOL) is increasingly used in obstetric practice. For patients with unfavourable cervix, we are constantly looking for an optimal, in terms of effectiveness and safety, ripening of cervix protocol. It was retrospective cohort study. We analyzed obstetrical results in 481 patients undergoing IOL in one center using two different vaginal inserts that release prostaglandins at a constant rate for 24 h—misoprostol vaginal insert (MVI) with 200 µg of misoprostol (n = 367) and dinoprostone vaginal insert (DVI) with 10 mg of dinoprostone (n = 114). Full-term, single pregnancy patients with intact fetal membranes and the cervix evaluated in Bishop score ≤ 6 were included in the analysis. In the group of MVI patients, the labour ended with caesarean section more often (OR 2.71 95% CI 1.63–4.47) and more frequent unreassuring cardiotocographic trace indicating the surgical delivery occurred (OR 2.38 95% CI 1.10–5.17). We did not notice any differences in the percentage of vacuum extraction and patients in whom the use of oxytocin was necessary during labour induction. The clinical status of newborns after birth and the pH of cord blood did not differ between groups.The use of MVI 200 μg in patients with an unriped cervix is associated with a greater chance of completing delivery by caesarean section and increased chance of abnormal intrapartum CTG trace compared to the use of DVI 10 mg. These differences do not affect the clinical and biochemical status of the newborn.
Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis
Authors: Hernández Josefina , Gabrielli Matías , Costa Joaquín , Uttaro Antonio D.
Published: April 2021

The ciliate Tetrahymena thermophila can either synthesize tetrahymanol or when available, assimilate and modify sterols from its diet. This metabolic shift is mainly driven by transcriptional regulation of genes for tetrahymanol synthesis (TS) and sterol bioconversion (SB). The mechanistic details of sterol uptake, intracellular trafficking and the associated gene expression changes are unknown. By following cholesterol incorporation over time in a conditional phagocytosis-deficient mutant, we found that although phagocytosis is the main sterol intake route, a secondary endocytic pathway exists. Different expression patterns for TS and SB genes were associated with these entry mechanisms. Squalene synthase was down-regulated by a massive cholesterol intake only attainable by phagocytosis-proficient cells, whereas C22-sterol desaturase required ten times less cholesterol and was up-regulated in both wild-type and mutant cells. These patterns are suggestive of at least two different signaling pathways. Sterol trafficking beyond phagosomes and esterification was impaired by the NPC1 inhibitor U18666A. NPC1 is a protein that mediates cholesterol export from late endosomes/lysosomes in mammalian cells. U18666A also produced a delay in the transcriptional response to cholesterol, suggesting that the regulatory signals are triggered between lysosomes and the endoplasmic reticulum. These findings could hint at partial conservation of sterol homeostasis between eukaryote lineages.
Urinary incontinence and the association with depression, stress, and self-esteem in older Korean Women
Authors: Lee Hoo-yeon , Rhee Yumie , Choi Kui Son
Published: April 2021

The objectives were to investigate the prevalence of urinary incontinence (UI) and its relationships with depression, stress, and self-esteem in older Korean women from the Korean Study of Women’s Health Related Issues (K-Stori), a nationally representative cross-sectional survey. A total of 3000 women between 65 and 79 years were the final study subjects. We applied multiple linear regression models to analyze associations with depression, stress, and self-esteem levels in relation to UI types. Types of urinary incontinence included stress, urge, and mixed UI. UI affects at least one in two older Korean women (52.2%). The prevalences of SUI, UUI, and MUI were 45.7%, 39.6%, and 33.1%, respectively. UI was found to be adversely associated with depression, stress, and self-esteem: women with UI reported significantly higher levels of depression and stress and lower levels of self-esteem than those without UI. Women with MUI reported significantly greater impairment than the women with SUI or UUI. Our results provide an evidence base for the evaluation of mental health in older women with incontinence. The prioritization of UI detection and the identification of psychological factors may help improve the diagnosis and management of UI and potentially yield significant economic and psychosocial benefits.
A Graph Theory approach to assess nature’s contribution to people at a global scale
Authors: de Juan Silvia , Ospina-Álvarez Andrés , Villasante Sebastián , Ruiz-Frau Ana
Published: April 2021

The use of Graph Theory on social media data is a promising approach to identify emergent properties of the complex physical and cognitive interactions that occur between humans and nature. To test the effectivity of this approach at global scales, Instagram posts from fourteen natural areas were selected to analyse the emergent discourse around these areas. The fourteen areas, known to provide key recreational, educational and heritage values, were investigated with different centrality metrics to test the ability of Graph Theory to identify variability in ecosystem social perceptions and use. Instagram data (i.e., hashtags associated to photos) was analysed with network centrality measures to characterise properties of the connections between words posted by social media users. With this approach, the emergent properties of networks of hashtags were explored to characterise visitors’ preferences (e.g., cultural heritage or nature appreciation), activities (e.g., diving or hiking), preferred habitats and species (e.g., forest, beach, penguins), and feelings (e.g., happiness or place identity). Network analysis on Instagram hashtags allowed delineating the users’ discourse around a natural area, which provides crucial information for effective management of popular natural spaces for people.
Longitudinal association between sleep features and refractive errors in preschoolers from the EDEN birth-cohort
Authors: Rayapoullé Alexis , Gronfier Claude , Forhan Anne , Heude Barbara , Charles Marie-Aline , Plancoulaine Sabine
Published: April 2021

Refractive errors are common, especially in children and adolescents, leading to global health issues, academic implications and economic costs. Circadian rhythm and sleep habits may play a role. The study included 1130 children from the EDEN birth-cohort. Data were collected through parental questionnaires at age 2 and 5 for sleep duration and timing, and at age 5 for refractive error. At 5 years, 20.4% were prescribed glasses (2% for myopia, 11.9% for hyperopia and 6.8% for unknown reason). Children slept on average (SD) 11h05/night (± 30 min) and 10h49/night (± 48 min) at age 2 and 5, respectively. Average bedtime and midsleep was 8.36 pm (± 30 min), 2.06 am (± 36 min), and 8.54 pm (± 30 min), 2.06 am (± 24 min) at age 2 and 5, respectively. A U-shaped association was observed between sleep duration at age 2 and eyeglass prescription at age 5. Later midsleep and bedtime at age 2 were associated with an increased risk of eyeglass prescription at age 5. Associations became borderline significant after adjustment for confounding factors. Sleep duration and timing at age 2 were associated with subsequent refractive errors in preschoolers from general population. Sleep hygiene might be a target for refractive errors prevention.
Metabolic adaptations to hypoxia in the neonatal mouse forebrain can occur independently of the transporters SLC7A5 and SLC3A2
Authors: Fitzgerald Eamon , Roberts Jennie , Tennant Daniel A. , Boardman James P. , Drake Amanda J.
Published: April 2021

Neonatal encephalopathy due to hypoxia–ischemia is associated with adverse neurodevelopmental effects. The involvement of branched chain amino acids (BCAAs) in this is largely unexplored. Transport of BCAAs at the plasma membrane is facilitated by SLC7A5/SLC3A2, which increase with hypoxia. We hypothesized that hypoxia would alter BCAA transport and metabolism in the neonatal brain. We investigated this using an organotypic forebrain slice culture model with, the SLC7A5/SLC3A2 inhibitor, 2-Amino-2-norbornanecarboxylic acid (BCH) under normoxic or hypoxic conditions. We subsequently analysed the metabolome and candidate gene expression. Hypoxia was associated with increased expression ofSLC7A5andSLC3A2and an increased tissue abundance of BCAAs. Incubation of slices with13C-leucine confirmed that this was due to increased cellular uptake. BCH had little effect on metabolite abundance under normoxic or hypoxic conditions. This suggests hypoxia drives increased cellular uptake of BCAAs in the neonatal mouse forebrain, and membrane mediated transport throughSLC7A5andSLC3A2is not essential for this process. This indicates mechanisms exist to generate the compounds required to maintain essential metabolism in the absence of external nutrient supply. Moreover, excess BCAAs have been associated with developmental delay, providing an unexplored mechanism of hypoxia mediated pathogenesis in the developing forebrain.
Laminaria japonica polysaccharide prevents high-fat-diet-induced insulin resistance in mice via regulating gut microbiota
Authors: Li Qiang-Ming , Zha Xue-Qiang , Zhang Wei-Nan , Liu Jian , Pan Li-Hua , Luo Jian-Ping
Published: April 2021

This study demonstrated that the purified Laminaria japonica polysaccharide LJP61A could alleviate insulin resistance, obesity, systematic inflammation, metabolic endotoxemia, and gut permeability in HFD-fed mice via modulating gut microbiota.
Immobilization of a Pd(ii)-containing N-heterocyclic carbene ligand on porous organic polymers: efficient and recyclable catalysts for Suzuki–Miyaura reactions
Authors: Lin Hongwei , Gao Xiyue , Yao Huan , Luo Qionglin , Xiang Bailin , Liu Cijie , Ouyang Yuejun , Zhou Nonglin , Xiang Dexuan
Published: April 2021

Two NHC–Pd(ii) complexes immobilized on porous organic polymers were successfully preparedviaScholl reactions and metallization. These complexes were applied in Suzuki–Miyaura reaction as heterogeneous catalysts with excellent yield and TON.
The relevance of Lewis acid sites on the gas phase reaction of levulinic acid into ethyl valerate using CoSBA-xAl bifunctional catalysts
Authors: Muñoz-Olasagasti M. , López Granados M. , Jiménez-Gómez C. P. , Cecilia J. A. , Maireles-Torres P. , Dumesic J. A. , Mariscal R.
Published: April 2021

CoSBA-xAl catalysts show a high yield in the levulinic acid conversion into ethyl valerate. This is due to the presence of weak Lewis acid sites associated with Co2+ species that have been stabilized by incorporation of Al into the support.
Electro-oxidative C(sp2)–H/O–H cross-dehydrogenative coupling of phenols and tertiary anilines for diaryl ether formation
Authors: Tang Hongyang , Smolders Simon , Li Yun , De Vos Dirk , Vercammen Jannick
Published: April 2021

The selective electrochemical oxidation of tertiary anilines in the presence of phenolic reactants leads to diaryl ether products.
Modulation of Ru and Cu nanoparticle contents over CuAlPO-5 for synergistic enhancement in the selective reduction and oxidation of biomass-derived furan based alcohols and carbonyls
Authors: Kumar Abhinav , Bal Rajaram , Srivastava Rajendra
Published: April 2021

Cu–Ru NP decorated CuAlPO-5 catalysts with low contents of Ru exhibit excellent activity and selectivity in the reduction and the oxidation of biomass-derived platform chemicals.
Recasting Ni-foam into NiF2 nanorod arrays via a hydrothermal process for hydrogen evolution reaction application
Authors: Shinde Nanasaheb M. , Raut Siddheshwar D. , Ghule Balaji G. , Gunturu Krishna Chaitanya , Pak James J. , Mane Rajaram S.
Published: April 2021

A promising electrode for hydrogen evolution reaction (HER) has been prepared via a reduction process to form NiF2 nanorod arrays directly grown on a 3D nickel foam.
The relationship between flavor formation, lipid metabolism, and microorganisms in fermented fish products
Authors: Feng Lin , Tang Nianchu , Liu Ruijie , Gong Mengyue , Wang Zhangtie , Guo Yiwen , Wang Yandan , Zhang Yao , Chang Ming
Published: April 2021

This manuscript clarifies the relationship between flavor formation, lipid metabolism, and microorganisms in fermented fish products.
Direct N-alkylation of sulfur-containing amines
Authors: Li Chen , Ge Min-Tong , Bai Liang , Xia Ai-Bao , Xu Dan-Qian , Xu Zhen-Yuan
Published: April 2021

An efficient ruthenium-catalyzed method has been developed for the direct N-alkylation of sulfur-containing amines with alcohols, for the first time, by a step-economical and environmentally friendly hydrogen borrowing strategy.
Enantioselective synthesis of 3-aryl-phthalides through a nickel-catalyzed stereoconvergent cross-coupling reaction
Authors: Xu Si-Yu , Zhang Rui , Zhang Shu-Sheng , Feng Chen-Guo
Published: April 2021

An efficient method for the preparation of diverse chiral 3-aryl-phthalides in high yields with good enantioselectivities and functional group tolerance was developed.
Preparation and characterization of glycopolymers with biphenyl spacers via Suzuki coupling reaction
Authors: Seto Hirokazu , Tono Takumi , Nagaoka Akiko , Yamamoto Mai , Hirohashi Yumiko , Shinto Hiroyuki
Published: April 2021

Glycopolymers were prepared using living radical polymerization and catalytic reaction. Glycopolymers with biphenyl spacers had specific protein-binding ability and fluorescence.
Efficient ternary catalyst system for the copolymerization of lactide, epoxides and CO2: new insights into the cooperative mechanism
Authors: Li Xiang , Hu Chen-yang , Duan Ran-long , Liang Zhuang-zhuang , Pang Xuan , Deng Ming-xiao
Published: April 2021

Ternary catalyst systems (TCSs) are an emerging type of catalyst for the synthesis of multiblock copolymers of lactide (LA), epoxides and CO2.
Plant-based CO2 drawdown and storage as SiC
Authors: Thomas Suzanne T. , Shin Yongsoon , La Clair James J. , Noel Joseph P.
Published: April 2021

This study demonstrates how integration of plants into an artificial carbon cycle is capable of harmoniously operating with Earth's natural cycles as one means to recycle atmospheric CO2 for economically lucrative green materials.
Zeolitic imidazole framework derived N-doped porous carbon/metal cobalt nanoparticles hybrid for oxygen electrocatalysis and rechargeable Zn–air batteries
Authors: Liu Xia , Ma Yuanyuan , Cai Yongliang , Hu Song , Chen Jian , Liu Zhaolin , Wang Zhijuan
Published: April 2021

An efficient bifunctional electrocatalyst with hollow structure (C–N/Co (1/2)) has been obtained through carbonization of ZIF-8@ZIF-67, which showed high ORR and OER activity, as evidenced by ZnAB using catalyst of C–N/Co (1/2) in air cathode.
A novel and low-cost CuPc@C catalyst derived from the compounds of sunflower straw and copper phthalocyanine pigment for oxygen reduction reaction
Authors: Huang Haiman , Lan Ziwei , Li Wenjun , Mo Wenhao , Zhao Lei , Zhang Jun
Published: April 2021

A series of CuPc@C composite catalysts were prepared with uniform and stretchable sunflower straw biological materials as the carbon source and inexpensive copper phthalocyanine pigment as a nitrogen doping source.
Metal ion size profoundly affects H3glyox chelate chemistry
Authors: Choudhary Neha , Barrett Kendall E. , Kubeil Manja , Radchenko Valery , Engle Jonathan W. , Stephan Holger , de Guadalupe Jaraquemada-Peláez María , Orvig Chris
Published: April 2021

The bisoxine hexadentate chelating ligand, H3glyox was investigated for its affinity for Mn2+, Cu2+ and Lu3+ ions; all three metal ions are relevant with applications in nuclear medicine and medicinal inorganic chemistry.
An integrated approach for structural characterization of Gui Ling Ji by traveling wave ion mobility mass spectrometry and molecular network
Authors: Zhang Yuhao , Lei Huibo , Tao Jianfei , Yuan Wenlin , Zhang Weidong , Ye Ji
Published: April 2021

An integrated approach for structural characterization of Gui Ling Ji by traveling wave ion mobility mass spectrometry and molecular network.
Photoluminescence and scintillation characteristics of Bi-loaded PVK-based plastic scintillators for the high counting-rate measurement of high-energy X-rays
Authors: Sato Atsushi , Magi Arisa , Koshimizu Masanori , Fujimoto Yutaka , Kishimoto Shunji , Asai Keisuke
Published: April 2021

Bi-loaded PVK-based plastic scintillators doped with bis-MSB are applicable for high counting-rate measurement of high-energy X-rays. They showed a higher detection efficiency and light yield than EJ-256 under 67.41 keV X-ray irradiation.
N-Hydroxysuccinimide crosslinked graphene oxide–gold nanoflower modified SPE electrode for sensitive detection of chloramphenicol antibiotic
Authors: Ali M. R. , Bacchu M. S. , Al-Mamun M. R. , Ahommed M. S. , Saad Aly M. Aly , Khan M. Z. H.
Published: April 2021

Here we introduce a composite material that consists of graphene oxide (GO) sheets crosslinked with N-hydroxysuccinimide (NHS) and functionalized with gold nanoflowers (AuNFs).
Construction of polycyclic structures with vicinal all-carbon quaternary stereocenters via an enantioselective photoenolization/Diels–Alder reaction
Authors: Hou Min , Xu Mengmeng , Yang Baochao , He Haibing , Gao Shuanhu
Published: April 2021

An enantioselective PEDA reaction was developed to enable stereohindered dienophiles to interact with transient photoenolized hydroxy-o-quinodimethanes, delivering fused or spiro polycyclic rings bearing 2–3 vicinal all-carbon quaternary centers in good yield and excellent ee.
Stabilization of lithium metal anodes by conductive metal–organic framework architectures
Authors: Zhao Jing , Yuan Hongye , Wang Guiling , Lim Xiao Feng , Ye Hualin , Wee Vanessa , Fang Yongzheng , Lee Jim Yang , Zhao Dan
Published: April 2021

The Cu-foil current collectors with Ni3(HITP)2 films were prepared to reduce the energy barrier of the current collector surface and thus provide a uniform seeding layer for the subsequent deposition of Li in Li-ion batteries.
Bioadhesive glycosylated nanoformulations for extended trans-corneal drug delivery to suppress corneal neovascularization
Authors: Zhang Yanlong , Yu Yunjian , Li Gang , Zhang Xinge , Wu Zhongming , Lin Ling
Published: April 2021

Schematic illustration of bioadhesion, epithelial permeation and drug release of bioadhesive glycosylated nanoformulations to suppress CNV.
High-performance non-doped blue OLEDs based on 1,2,4-triazole-phenanthroimidazole derivatives with negligible efficiency roll-off
Authors: Cao Wenjuan , Abdurahman Alim , Zheng Ping , Zhang Ming , Li Feng
Published: April 2021

Triazole and phenanthroimidazole moieties are commonly used to construct efficient blue-emitting materials as acceptors and donors, respectively.
Implications of ADAM17 activation for hyperglycaemia, obesity and type 2 diabetes
Authors: Matthews Jennifer , Villescas Sofia , Herat Lakshini , Schlaich Markus , Matthews Vance
Published: April 2021

In this review, we focus specifically on the role that the metalloproteinase, A Disintegrin and Metalloproteinase 17 [ADAM17] plays in the development and progression of the metabolic syndrome. There is a well-recognised link between the ADAM17 substrate tumour necrosis factor α (TNF-α) and obesity, inflammation and diabetes. In addition, knocking out ADAM17 in mice leads to an extremely lean phenotype. Importantly, ADAM17-deficient mice exhibit one of the most pronounced examples of hypermetabolism in rodents to date. It is vital to further understand the mechanistic role that ADAM17 plays in the metabolic syndrome. Such studies will demonstrate that ADAM17 is a valuable therapeutic target to treat obesity and diabetes.
MQL Machining with nano fluid: a review
Authors: Patole Pralhad B. , Kulkarni Vivek V. , Bhatwadekar Sudhir G.
Published: April 2021

In any metal cutting machining operation, the cutting fluid plays important role by cooling the cutting tool and the surface of the work piece, also chips are removed from heat affected zone. However, misuse of the cutting fluid and wrong methods of its disposal can affect human health and the environment badly. This paper presents a review of the important research papers published regarding the MQL-based application of mineral oils, vegetable oils and nano fluid-based cutting fluids for different machining processes, such as, drilling, turning, milling and grinding, etc. Most of the experimental studies have shown that application of MQL produces surface better than the flood and dry machining. In turning operation, parameters such as cutting speed, depth of cut, feed rate and tool nose radius have great impact on the surface finish. During high speed turning of steel inherently generates high cutting zone temperature. Such high temperature causes dimensional deviation and failure of cutting tools, surface and subsurface micro cracks, corrosion etc. Therefore, with proper selection of the MQL system and the cutting parameters, it is possible for MQL machining with minimum cost and less quantity of coolant to obtain better conditions, in terms of lubricity, tool life, cutting temperature and surface finish. The findings of this study show that MQL with nano fluid can substitute the flood lubrication for better surface finish.
Clinical advances in nasopharyngeal carcinoma surgery and a video demonstration
Authors: Ding Xi , Liu You-Ping , Hua Yi-Jun , Zou Xiong , Wang Zhi-Qiang , Xie Yu-Long , Chen Ming-Yuan
Published: April 2021

Nasopharyngeal carcinoma (NPC) is highly radiosensitive, and radiotherapy is recommended for newly diagnosed NPC. Because of the poor visual surgical field, narrow operating space, difficulty protecting the internal carotid artery (ICA) and poor wound healing, the development of NPC surgery has been severely limited. For recurrent NPC, some open surgical approaches, such as the maxillary swing, successfully solve the above major problems. However, these operations are traumatic and lead to many postoperative complications. With the development of minimally invasive surgery, two concepts, the “third-hand technique” and “dumpling making technique”, have been proposed, combining with the intraoperative navigation systems and multiple anatomical landmarks for identifying ICA. Endoscopic nasopharyngectomy (ENPG) can also break through the above restrictions and has become a first-line treatment for locally recurrent NPC. Moreover, a new surgical staging system for recurrent NPC was devised to aid clinicians in choosing the most suitable treatment for these patients. A current study on ENPG alone for newly diagnosed stage I NPC shows that the long-term survival outcomes after ENPG are similar to those after IMRT. ENPG was associated with low medical costs and satisfactory QOL and might be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refuse radiotherapy.