bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Mooij correlations at the nanoscale in the disordered metallic Ta–nanoisland FeNi multilayers
Authors: Kovaleva N. N. , Kusmartsev F. V. , Mekhiya A. B. , Trunkin I. N. , Chvostova D. , Davydov A. B. , Oveshnikov L. N. , Pacherova O. , Sherstnev I. A. , Kusmartseva A. , Kugel K. I. , Dejneka A. , Pudonin F. A. , Luo Y. , Aronzon B. A.
Published: December 2020

Localisation phenomena in highly disordered metals close to the extreme conditions determined by the Mott-Ioffe-Regel (MIR) limit when the electron mean free path is approximately equal to the interatomic distance is a challenging problem. Here, to shed light on these localisation phenomena, we studied the dc transport and optical conductivity properties of nanoscaled multilayered films composed of disordered metallic Ta and magnetic FeNi nanoisland layers, where ferromagnetic FeNi nanoislands have giant magnetic moments of 10$$^3$$

3

–10$$^5$$

5

Bohr magnetons ($$\mu _{\mathrm{B}}$$

μ
B

). In these multilayered structures, FeNi nanoisland giant magnetic moments are interacting due to the indirect exchange forces acting via the Ta electron subsystem. We discovered that the localisation phenomena in the disordered Ta layer lead to a decrease in the Drude contribution of free charge carriers and the appearance of the low-energy electronic excitations in the 1–2 eV spectral range characteristic of electronic correlations, which may accompany the formation of electronic inhomogeneities. From the consistent results of the dc transport and optical studies we found that with an increase in the FeNi layer thickness across the percolation threshold evolution from the superferromagnetic to ferromagnetic behaviour within the FeNi layer leads to the delocalisation of Ta electrons from the associated localised electronic states. On the contrary, we discovered that when the FeNi layer is discontinuous and represented by randomly distributed superparamagnetic FeNi nanoislands, the Ta layer normalized dc conductivity falls down below the MIR limit by about 60%. The discovered effect leading to the dc conductivity fall below the MIR limit can be associated with non-ergodicity and purely quantum (many-body) localisation phenomena, which need to be challenged further.
Biosorption of Pb (II) and Zn (II) from aqueous solution by Oceanobacillus profundus isolated from an abandoned mine
Authors: Mwandira Wilson , Nakashima Kazunori , Kawasaki Satoru , Arabelo Allison , Banda Kawawa , Nyambe Imasiku , Chirwa Meki , Ito Mayumi , Sato Tsutomu , Igarashi Toshifumi , Nakata Hokuto , Nakayama Shouta , Ishizuka Mayumi
Published: December 2020

The present study investigated biosorption of Pb (II) and Zn (II) using a heavy metal tolerant bacterium Oceanobacillus profundus KBZ 3-2 isolated from a contaminated site. The effects of process parameters such as effect on bacterial growth, pH and initial lead ion concentration were studied. The results showed that the maximum removal percentage for Pb (II) was 97% at an initial concentration of 50 mg/L whereas maximum removal percentage for Zn (II) was at 54% at an initial concentration of 2 mg/L obtained at pH 6 and 30 °C. The isolated bacteria were found to sequester both Pb (II) and Zn (II) in the extracellular polymeric substance (EPS). The EPS facilitates ion exchange and metal chelation-complexation by virtue of the existence of ionizable functional groups such as carboxyl, sulfate, and phosphate present in the protein and polysaccharides. Therefore, the use of indigenous bacteria in the remediation of contaminated water is an eco-friendly way of solving anthropogenic contamination.
SIRT3, a metabolic target linked to ataxia-telangiectasia mutated (ATM) gene deficiency in diffuse large B-cell lymphoma
Authors: Bhalla Kavita , Jaber Sausan , Reagan Kayla , Hamburg Arielle , Underwood Karen F. , Jhajharia Aditya , Singh Maninder , Bhandary Binny , Bhat Shambhu , Nanaji Nahid M. , Hisa Ruching , McCracken Carrie , Creasy Heather Huot , Lapidus Rena G. , Kingsbury Tami , Mayer Dirk , Polster Brian , Gartenhaus Ronald B.
Published: December 2020

Inactivation of Ataxia-telangiectasia mutated (ATM) gene results in an increased risk to develop cancer. We show that ATM deficiency in diffuse large B-cell lymphoma (DLBCL) significantly induce mitochondrial deacetylase sirtuin-3 (SIRT3) activity, disrupted mitochondrial structure, decreased mitochondrial respiration, and compromised TCA flux compared with DLBCL cells expressing wild type (WT)-ATM. This corresponded to enrichment of glutamate receptor and glutamine pathways in ATM deficient background compared to WT-ATM DLBCL cells. ATM−/− DLBCL cells have decreased apoptosis in contrast to radiosensitive non-cancerous A-T cells. In vivo studies using gain and loss of SIRT3 expression showed that SIRT3 promotes growth of ATM CRISPR knockout DLBCL xenografts compared to wild-type ATM control xenografts. Importantly, screening of DLBCL patient samples identified SIRT3 as a putative therapeutic target, and validated an inverse relationship between ATM and SIRT3 expression. Our data predicts SIRT3 as an important therapeutic target for DLBCL patients with ATM null phenotype.
Effects of cow dung and wood biochars and green manure on soil fertility and tiger nut (Cyperus esculentus L.) performance on a savanna Alfisol
Authors: Adekiya Aruna Olasekan , Olaniran Abiola Folakemi , Adenusi Titilayo Tolulope , Aremu Charity , Ejue Wutem Sunny , Iranloye Yetunde Mary , Gbadamosi Abiodun , Olayanju Adeniyi
Published: December 2020

Two field experiments were conducted concurrently in 2019. The study investigated the effects of single and combined application of wood biochar (WB) and cow dung biochar (CDB) with green manure (GM) on soil properties, performance, and tuber qualities of tiger nut. The treatments consisted of: CDB at 10 t ha−1, WB at 10 t ha−1, GM—Tithonia diversifolia at 10 t ha−1, CDB + GM, WB + GM, control. The six treatments were arranged in RCBD with three replications. CDB, WB, and GM either sole or combined increased moisture content, SOC, nutrient contents, culturable microorganisms, performance, moisture, ash, fiber, and protein contents of the tiger nut compared with the control. CDB has a higher N, C: N ratio, P, K, Ca, Mg, CEC, and pH relative to. CDB alone and CDB + GM increased growth and yield compared with WB alone and WB + GM. CDB + GM has the highest value of growth and yield of tiger nut. GM alone improved growth and yield of tiger nut compared with the two sole biochar treatments. CDB + GM and WB + GM increased growth and yield of tiger nut compared with their sole forms. This was adduced to biochar allowing the retention of nutrients from rapidly decomposing Tithonia within the rooting zone, thereby promoting better effectiveness of nutrient uptake and increase in yield. Therefore, for good soil fertility and tiger nut yield, it is important that the addition of a fast releasing nutrient source to biochar be sought.
Proton pump inhibitors and the risk of Alzheimer’s disease and non-Alzheimer’s dementias
Authors: Torres-Bondia Francisco , Dakterzada Farida , Galván Leonardo , Buti Miquel , Besanson Gaston , Gill Eric , Buil Roman , de Batlle Jordi , Piñol-Ripoll Gerard
Published: December 2020

Proton pump inhibitors (PPIs) are among the most prescribed medications. Previous epidemiological studies have presented contradictory results about PPIs and the risk of dementia. Our objective was to investigate the association between the use of PPIs and an increasing risk of incident AD or non-AD dementias. A community-based retrospective cohort study was conducted based on the data available from 1st January 2002 to 31st December 2015 in the Catalan health service (CatSalut) system. This cohort included all PPI users (N = 36,360) and non-users (N = 99,362). A lag window of 5 years was considered between the beginning of the PPI treatment and the diagnosis of dementia. PPI use was not associated with the risk of AD (adjusted odds ratio (OR) 1.06) (95% CI 0.93–1.21; p = 0.408). A weakly but significantly increased risk of non-AD dementias was observed among PPI users (adjusted OR 1.20, 95% CI 1.05–1.37; p = 0.007). A higher dose of PPIs was not associated with an increased risk of either AD or non-AD dementias (OR 1.20; 95% CI 0.91–1.61 and OR 0.95; 95% CI 0.74–1.22, respectively). Regarding the number of PPIs used, we observed an increased risk of AD (OR 1.47; 95% CI 1.18–1.83) and non-AD dementias (OR 1.38; 95% CI 1.12–1.70) in users of two types of PPIs compared with those who used only one type. We did not find a higher incidence of AD among PPI users, but a weak increase in the risk of non-AD dementias among PPI users was observed.
Anti-IL-17A treatment reduces serum inflammatory, angiogenic and tissue remodeling biomarkers accompanied by less synovial high endothelial venules in peripheral spondyloarthritis
Authors: Kaaij Merlijn H. , Helder Boy , van Mens Leonieke J. J. , van de Sande Marleen G. H. , Baeten Dominique L. P. , Tas Sander W.
Published: December 2020

Spondyloarthritis (SpA) is characterized by inflammation and new bone formation. The exact pathophysiology underlying these processes remains elusive. We propose that the extensive neoangiogenesis in SpA could play a role both in sustaining/enhancing inflammation and in new bone formation. While ample data is available on effects of anti-TNF on angiogenesis, effects of IL-17A blockade on serum markers are largely unknown. We aimed to assess the impact of secukinumab (anti-IL-17A) on synovial neoangiogenesis in peripheral SpA, and how this related to changes in inflammatory and tissue remodeling biomarkers. Serum samples from 20 active peripheral SpA patients included in a 12 week open-label trial with secukinumab were analyzed for several markers of angiogenesis and tissue remodeling. Synovial biopsies taken before and after treatment were stained for vascular markers. Serum levels of MMP-3, osteopontin, IL-6 (all P < 0.001), IL-31, S100A8, S100A9, Vascular Endothelial Growth Factor A (VEGF-A), IL-33, TNF-α (all P < 0.05) decreased significantly upon anti-IL17A treatment. Secukinumab treatment resulted in a decrease in the number of synovial high endothelial venules and lymphoid aggregate score. These results indicate that anti-IL-17A not only diminishes inflammation, but also impacts angiogenesis and tissue remodeling/new bone formation. This may have important implications for disease progression and/or structural damage.
Prediction of disease progression and outcomes in multiple sclerosis with machine learning
Authors: Pinto Mauro F. , Oliveira Hugo , Batista Sónia , Cruz Luís , Pinto Mafalda , Correia Inês , Martins Pedro , Teixeira César
Published: December 2020

Multiple Sclerosis is a chronic inflammatory disease, affecting the Central Nervous System and leading to irreversible neurological damage, such as long term functional impairment and disability. It has no cure and the symptoms vary widely, depending on the affected regions, amount of damage, and the ability to activate compensatory mechanisms, which constitutes a challenge to evaluate and predict its course. Additionally, relapsing-remitting patients can evolve its course into a secondary progressive, characterized by a slow progression of disability independent of relapses. With clinical information from Multiple Sclerosis patients, we developed a machine learning exploration framework concerning this disease evolution, more specifically to obtain three predictions: one on conversion to secondary progressive course and two on disease severity with rapid accumulation of disability, concerning the 6th and 10th years of progression. For the first case, the best results were obtained within two years: AUC=$$0.86\pm 0.07$$0.86±0.07, sensitivity=$$0.76\pm 0.14$$0.76±0.14and specificity=$$0.77\pm 0.05$$0.77±0.05; and for the second, the best results were obtained for the 6th year of progression, also within two years: AUC=$$0.89\pm 0.03$$0.89±0.03, sensitivity=$$0.84\pm 0.11$$0.84±0.11, and specificity=$$0.81\pm 0.05$$0.81±0.05. The Expanded Disability Status Scale value, the majority of functional systems, affected functions during relapses, and age at onset were described as the most predictive features. These results demonstrate the possibility of predicting Multiple Sclerosis progression by using machine learning, which may help to understand this disease’s dynamics and thus, advise physicians on medication intake.
Mathematical formulation and parametric analysis of in vitro cell models in microfluidic devices: application to different stages of glioblastoma evolution
Authors: Ayensa-Jiménez Jacobo , Pérez-Aliacar Marina , Randelovic Teodora , Oliván Sara , Fernández Luis , Sanz-Herrera José Antonio , Ochoa Ignacio , Doweidar Mohamed H. , Doblaré Manuel
Published: December 2020

In silico models and computer simulation are invaluable tools to better understand complex biological processes such as cancer evolution. However, the complexity of the biological environment, with many cell mechanisms in response to changing physical and chemical external stimuli, makes the associated mathematical models highly non-linear and multiparametric. One of the main problems of these models is the determination of the parameters’ values, which are usually fitted for specific conditions, making the conclusions drawn difficult to generalise. We analyse here an important biological problem: the evolution of hypoxia-driven migratory structures in Glioblastoma Multiforme (GBM), the most aggressive and lethal primary brain tumour. We establish a mathematical model considering the interaction of the tumour cells with oxygen concentration in what is called the go or grow paradigm. We reproduce in this work three different experiments, showing the main GBM structures (pseudopalisade and necrotic core formation), only changing the initial and boundary conditions. We prove that it is possible to obtain versatile mathematical tools which, together with a sound parametric analysis, allow to explain complex biological phenomena. We show the utility of this hybrid “biomimetic in vitro-in silico” platform to help to elucidate the mechanisms involved in cancer processes, to better understand the role of the different phenomena, to test new scientific hypotheses and to design new data-driven experiments.
Fermentative profile, losses and chemical composition of silage soybean genotypes amended with sugarcane levels
Authors: de Moura Zanine Anderson , de Sene Orgélio Augusto , de Jesus Ferreira Daniele , Parente Henrique Nunes , de Oliveira Maia Parente Michelle , Pinho Ricardo Martins Araújo , Santos Edson Mauro , Nascimento Thiago Vinicius Costa , de Oliveira Lima Anny Graycy Vasconcelos , Perazzo Alexandre Fernandes , Portela Ygor Nascimento , Bandeira Danrley Martins
Published: December 2020

The experiment aimed to evaluate the fermentative and nutritional profile of the silage of four soybean plant genotypes (BRS 333 RR, Pampeanas: C50, C60, and C70) ensiled with levels of sugarcane (0, 25, 50, 75, and 100%). The experiments were conducted in a completely randomized design, in factorial scheme 4 × 5 (four soybean genotypes and five levels of sugarcane inclusion) with four replicates. Silages with 100% soybean plant presented the highest levels of butyric acid (P < 0.001) and ammoniacal nitrogen (P < 0.047); however, the intermediate addition of sugarcane contributed to lactic fermentation (P < 0.001). Besides, there was a quadratic effect (P < 0.05) for the recovery of dry matter, which ranged from 83.28 to 95.29%, with higher values observed for silage with the same proportions of soybean plant and sugarcane. It was verified that the crude protein content exhibited decreasing linear effects (P < 0.001), varying among 4.60 to 7.48% in the silages. It was concluded that the highest recovery of dry matter, the best fermentation profile, and the highest levels of crude protein and digestibility occurred in the inclusion between 25 and 50% of sugarcane in soybean silage, with the superiority of the C50 soybean genotype.
Moderate to severe liver siderosis and raised AST are independent risk factors for vitamin D insufficiency in β-thalassemia patients
Authors: Darvishi-Khezri Hadi , Karami Hossein , Naderisorki Mohammad , Zahedi Mohammad , Razavi Alireza , Kosaryan Mehrnoush , Aliasgharian Aily
Published: December 2020

Numerous problematic disorders such as vitamin D (Vit-D) deficiency subsequent to large iron loading can be developed in patients with β-thalassemia. The study aimed to estimate Vit-D insufficiency and its risk factors in patients with β-thalassemia. In this multicenter and observational study, all β-thalassemia patients, who referred to 14 hospital-based thalassemia divisions or clinics in Mazandaran province, Iran were included in the study. The data belong to December 2015 until December 2019. The study population was made of transfusion dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) patients. Serum levels of 25-OHD3 have been measured by high performance liquid chromatography (HPLC) method as ng/mL. Demographic and clinical information along with some biological tests, as well as the results of T2*-weighted magnetic resonance imaging were analyzed. Of 1959 registered patients, 487 (24.9%) patients had Vit-D-related data. The prevalence of Vit-D insufficiency (< 30 ng/mL) was 41.9, 95% CI 37.5–46.3. The adjusted risks of moderate to severe liver siderosis and raised AST (aspartate aminotransferase) for Vit-D insufficiency (< 30 ng/mL) were 2.31, 95% CI 1.38–3.89 and 2.62, 95% CI 1.43–4.79, respectively. The receiver operating characteristic (ROC) curve analysis showed that the predictive accuracy of ferritin for Vit-D insufficiency status was 0.61, 95% CI 0.54–0.68 with a cutoff point of 1,078 ng/mL (P = 0.03, sensitivity 67%, specificity 49%, positive predictive value [PPV] 47% and negative predictive value [NPV] 68%). In spite of the national programs for treating Vit-D deficiency and our previous efforts for giving supplements to all patients, Vit-D insufficiency/deficiency is still common in our patients. Also, moderate to severe liver siderosis and raised AST were the independent risk factors for the Vit-D insufficiency.
Evolution of respiratory syncytial virus genotype BA in Kilifi, Kenya, 15 years on
Authors: Kamau Everlyn , Otieno James R. , Lewa Clement S. , Mwema Anthony , Murunga Nickson , Nokes D. James , Agoti Charles N.
Published: December 2020

Respiratory syncytial virus (RSV) is recognised as a leading cause of severe acute respiratory disease and deaths among infants and vulnerable adults. Clinical RSV isolates can be divided into several known genotypes. RSV genotype BA, characterised by a 60-nucleotide duplication in the G glycoprotein gene, emerged in 1999 and quickly disseminated globally replacing other RSV group B genotypes. Continual molecular epidemiology is critical to understand the evolutionary processes maintaining the success of the BA viruses. We analysed 735 G gene sequences from samples collected from paediatric patients in Kilifi, Kenya, between 2003 and 2017. The virus population comprised of several genetically distinct variants (n = 56) co-circulating within and between epidemics. In addition, there was consistent seasonal fluctuations in relative genetic diversity. Amino acid changes increasingly accumulated over the surveillance period including two residues (N178S and Q180R) that mapped to monoclonal antibody 2D10 epitopes, as well as addition of putative N-glycosylation sequons. Further, switching and toggling of amino acids within and between epidemics was observed. On a global phylogeny, the BA viruses from different countries form geographically isolated clusters suggesting substantial localized variants. This study offers insights into longitudinal population dynamics of a globally endemic RSV genotype within a discrete location.
Treatment of breast cancer in vivo by dual photodynamic and photothermal approaches with the aid of curcumin photosensitizer and magnetic nanoparticles
Authors: Ashkbar Ali , Rezaei Fatemeh , Attari Farnoosh , Ashkevarian Saboura
Published: December 2020

Breast cancer is a neoplastic disease with a high mortality rate among women. Recently, photodynamic therapy (PDT) and photothermal therapy (PTT) attracted considerable attention because of their minimal invasiveness. The PTT approach works based on hyperthermia generation, and PDT approach employs laser irradiation to activate a reagent named photosensitizer. Therefore, in the current paper, a dual-functioned nanocomposite (NC) was designed for the treatment of breast cancer model in Balb/c mice with the combination of photodynamic and photothermal approaches. Transmission electron microscopy, UV–visible spectroscopy, FTIR, and XRD were employed to validate the nanostructure and silica coating and curcumin (CUR) immobilization on the Fe3O4 nanoparticles. The effect of Fe3O4/SiO2-CUR combined with PDT and PTT was assessed in vivo on the breast tumor mice model, and immunohistochemistry (IHC) was employed to evaluate the expression of apoptotic Bax and Caspase3 proteins. The TEM images, UV–visible absorption, and FTIR spectra demonstrated the successful immobilization of curcumin molecules on the surface of Fe3O4/SiO2. Also, MTT assay confirmed the nontoxic nature of Fe3O4/SiO2 nanoparticles in vitro. In the breast tumor mice model, we have assessed six treatment groups, including control, CUR + PDT, Blue + NIR (near-infrared) lasers, NC, NC + PTT, and NC + PDT + PTT. The tumor volume in the NC + PDT + PTT group showed a significant reduction compared to other groups (p < 0.05). More interestingly, the tumor volume of NC + PDT + PTT group showed a 27% decrease compared to its initial amount. It should be noted that no detectable weight loss or adverse effects on the vital organs was observed due to the treatments. Additionally, the IHC data represented that the expression of proapoptotic Bax and Caspase3 proteins were significantly higher in the NC + PDT + PTT group compared to the control group, indicative of apoptosis. To conclude, our data supported the fact that the NC + PDT + PTT strategy might hold a promising substitute for chemotherapy for the treatment of triple-negative breast cancers.
Algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate
Authors: Zur Hadas , Cohen-Kupiec Rachel , Vinokour Sophie , Tuller Tamir
Published: December 2020

mRNA translation is a fundamental cellular process consuming most of the intracellular energy; thus, it is under extensive evolutionary selection for optimization, and its efficiency can affect the host's growth rate. We describe a generic approach for improving the growth rate (fitness) of any organism by introducing synonymous mutations based on comprehensive computational models. The algorithms introduce silent mutations that may improve the allocation of ribosomes in the cells via the decreasing of their traffic jams during translation respectively. As a result, resources availability in the cell changes leading to improved growth-rate. We demonstrate experimentally the implementation of the method on Saccharomyces cerevisiae: we show that by introducing a few mutations in two computationally selected genes the mutant's titer increased. Our approach can be employed for improving the growth rate of any organism providing the existence of data for inferring models, and with the relevant genomic engineering tools; thus, it is expected to be extremely useful in biotechnology, medicine, and agriculture.
Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice
Authors: Piron Sarah , Verhoeven Jeroen , Descamps Benedicte , Kersemans Ken , De Man Kathia , Van Laeken Nick , Pieters Leen , Vral Anne , Vanhove Christian , De Vos Filip
Published: December 2020

Recently, a 18F-labeled derivative of the widely used 68Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although 18F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with 18F-PSMA-11 or 68Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received ± 3.7 MBq 18F-PSMA-11 and 68Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq 18F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUVmean, SUVmax, TBRmean and TBRmax). Mice underwent ex vivo biodistribution where 18F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (Kd) of 18F-PSMA-11 and 68Ga-PSMA-11 was 2.95 ± 0.87 nM and 0.49 ± 0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both 18F-PSMA-11 and 68Ga-PSMA-11, while no difference was found for 18F-FDG uptake (except for SUVmax). Tumor uptake of 18F-PSMA-11 showed a similar trend over time as 68Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBRmean and TBRmax were significantly higher at the later timepoint, as well as the SUVmax of 68Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0 ± 13.6%ID/g 1 h p.i.) and the bladder (6.48 ± 2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for 18F-PSMA-11 compared to 68Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late 18F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of 18F-PSMA-11 as well as no significant increase in bone uptake.
The efficacy of probiotics in management of recurrent aphthous stomatitis: a systematic review and meta-analysis
Authors: Cheng Bin , Zeng Xinyi , Liu Shaoyuan , Zou Jing , Wang Yan
Published: December 2020

There is currently a lack of effective drugs to cure recurrent aphthous stomatitis. This study aimed to evaluate the efficacy of probiotics alone or as an adjunct in recurrent aphthous stomatitis (RAS) patients. Seven randomized controlled trials (RCTs) were included, of which three were included in quantitative analysis. Of five studies evaluating the efficacy of probiotics alone compared with placebo or Oracure gel, two reported no significant difference in relieving oral pain, while probiotics exhibited a higher capacity for decreasing oral pain in the other three. A significant decrease in ulcer severity was found in one, while no significant difference was found in the other four. The remaining two studies demonstrated that probiotics, as an adjunct to steroids or anaesthetic antiseptic gel, significantly reduced the ulcer severity and oral pain. The meta-analysis showed a significant decrease in oral pain (− 1.72, P = 0.0001) with probiotics compared with placebo. In conclusion, probiotics alone were capable of relieving oral pain but not effective in reducing ulcer severity. A combination of probiotics and steroids or anaesthetic antiseptic gel was more effective than steroids or anaesthetic antiseptic gel alone in RAS patients. Probiotics are promising for the treatment of recurrent aphthous stomatitis.
Possible implications of sea level changes for species migration through the Suez Canal
Authors: Biton Eli
Published: December 2020

The Mediterranean and Red Sea, which were connected via the Suez Canal during the 19th century after eons of separation, host two distinctive ecosystems. Species invasion through the Suez Canal from the Red Sea vastly influences the ecology of the Mediterranean, but the level of reverse migration is assumed to be negligible. We present the first reconstructed flow transport record through the canal during the period 1923–2016. According to this reconstruction, the flow intensity and direction through the canal are strongly influenced by seasonal and long-term sea-level changes, which could also play a role in the characteristics of species migration through it. Our record not only supports previous observations of the unidirectional invasion until the 1980s and the accelerated species migration rates to the Mediterranean ever since, but also suggest that southward migration could have become possible since the early 1980s. The southward flow was primarily enhanced by Indian Ocean cooling and the Eastern Mediterranean Transition in deep water formation during the period 1980–2000. It was then gradually reduced by accelerated sea-level rise in the northern Indian Ocean.
Soluble VCAM-1 promotes gemcitabine resistance via macrophage infiltration and predicts therapeutic response in pancreatic cancer
Authors: Takahashi Ryota , Ijichi Hideaki , Sano Makoto , Miyabayashi Koji , Mohri Dai , Kim Jinsuk , Kimura Gen , Nakatsuka Takuma , Fujiwara Hiroaki , Yamamoto Keisuke , Kudo Yotaro , Tanaka Yasuo , Tateishi Keisuke , Nakai Yousuke , Morishita Yasuyuki , Soma Katsura , Takeda Norihiko , Moses Harold L. , Isayama Hiroyuki , Koike Kazuhiko
Published: December 2020

Pancreatic cancer is one of the malignant diseases with the worst prognosis. Resistance to chemotherapy is a major difficulty in treating the disease. We analyzed plasma samples from a genetically engineered mouse model of pancreatic cancer and found soluble vascular cell adhesion molecule-1 (sVCAM-1) increases in response to gemcitabine treatment. VCAM-1 was expressed and secreted by murine and human pancreatic cancer cells. Subcutaneous allograft tumors with overexpression or knock-down of VCAM-1, as well as VCAM-1-blocking treatment in the spontaneous mouse model of pancreatic cancer, revealed that sVCAM-1 promotes tumor growth and resistance to gemcitabine treatment in vivo but not in vitro. By analyzing allograft tumors and co-culture experiments, we found macrophages were attracted by sVCAM-1 to the tumor microenvironment and facilitated resistance to gemcitabine in tumor cells. In a clinical setting, we found that the change of sVCAM-1 in the plasma of patients with advanced pancreatic cancer was an independent prognostic factor for gemcitabine treatment. Collectively, gemcitabine treatment increases the release of sVCAM-1 from pancreatic cancer cells, which attracts macrophages into the tumor, thereby promoting the resistance to gemcitabine treatment. sVCAM-1 may be a potent clinical biomarker and a potential target for the therapy in pancreatic cancer.
A study of red blood cell alloimmunization and autoimmunization among 200 multitransfused Egyptian β thalassemia patients
Authors: El-Beshlawy Amal , Salama Alshymaa Ahmed , El-Masry Mohamed Roshdy , El Husseiny Noha M. , Abdelhameed Asmaa M.
Published: December 2020

The development of hemolytic erythrocyte alloantibodies and autoantibodies complicates transfusion therapy in thalassemia patients. These antibodies ultimately increase the need for blood and intensify transfusion complications. There is a scanty data on the frequency of RBC alloimmunization and autoimmunization in Egyptian β thalassemia patients as pretransfusion antibody screening is not routinely performed. We studied the frequency of alloimmunization and autoimmunization among 200 multiply transfused β thalassemia patients and investigated the factors that possibly affect antibody formation. Of the 200 patients in our study, 94 were males and 106 females, with the age range of 2–37 years. Alloantibodies were detected in 36 (18%) of the patients, while autoantibodies were detected in 33 (16.5%). The dominant alloantibodies were directed against Kell (33%) and Rh (24.4%) groups. Alloimmunization had a significant relationship with treatment duration and the frequency of transfusion (P = 0.007, 0.001, respectively). The presence of autoantibodies was significantly related to age (P = 0.001), total number of transfused units (P = 0.000) and splenectomy (P = 0.000). The high prevalence of alloimmunization in the study population disclosed the need for providing phenotypically matched cells for selective antigens especially for Kell and Rh subgroups to reduce risk of alloimmunization and increase the efficiency of blood transfusion.
Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense
Authors: Ueda Norichika , Kondo Makoto , Takezawa Kentaro , Kiuchi Hiroshi , Sekii Yosuke , Inagaki Yusuke , Soda Tetsuji , Fukuhara Shinichiro , Fujita Kazutoshi , Uemura Motohide , Imamura Ryoichi , Miyagawa Yasushi , Nonomura Norio , Shimada Shoichi
Published: December 2020

When bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analysis of purinergic P2X2and P2X3receptor-deficient mice indicated that ATP signaling plays a pivotal role in the LPS-induced activation of L6–S1 spinal neurons through the bladder afferent pathway, resulting in rapid onset of the enhanced micturition reflex. Thus, we revealed a novel defensive mechanism against bacterial infection via an epithelial-neural interaction that induces urinary frequency prior to bacterial clearance by neutrophils of the innate immune system. Our results indicate an important defense role for the bladder urothelium as a chemical-neural transducer, converting bacterial LPS information into neural signaling via an ATP-mediated pathway, with bladder urothelial cells acting as sensory receptor cells.
miR-152/TNS1 axis inhibits non-small cell lung cancer progression through Akt/mTOR/RhoA pathway
Authors: Duan Jinjin , Wang Li , Shang Liqun , Yang Shumei , Wu Hua , Huang Yongcheng , Miao Yi
Published: December 2020

Aim: The purpose of the present study was to explore the function and mechanism of tensin 1 (TNS1) in non-small cell lung cancer (NSCLC) progression.

Methods: The expression of TNS1 in NSCLC cells and tissues was assessed by RT-PCR and Western blot. Besides, Kaplan–Meier survival analysis was recruited to explore the association between TNS1 and NSCLC. Cell growth was analyzed by MTT and flow cytometry assay, while cell metastasis was determined by wound healing and transwell assays. The targeting relationship between TNS1 and miR-152 was assessed by luciferase activity assays. And Western blot was employed to determine the expression of related proteins of Akt/mTOR/RhoA pathway.

Results: TNS1 level was boosted in NSCLC cells and tissues, related to the prognosis of NSCLC patients. Furthermore, it was proved that TNS1 promoted the growth and metastasis of NSCLC cells via Akt/mTOR/RhoA pathway. And miR-152 targeted TNS1 to affect the progression of NSCLC.

Conclusion: miR-152/TNS1 axis inhibits the progression of NSCLC by Akt/mTOR/RhoA pathway.
Decoction of heat-clearing, detoxifying and blood stasis removing relieves acute soft tissue injury via modulating miR-26b-5p/COX2 axis to inhibit inflammation
Authors: Jiang Shunwan , Chen Zhi , Lai Wenqiang , Mai Qingchun , Chen Dayu , Sun Shufen , Zhang Yong
Published: December 2020

Traditional Chinese medicine (TCM), such as Huanglian-Jie-Du-Tang, a heat-clearing and detoxifying decoction is beneficial for alleviation of inflammation-related diseases. The objective of the present study is to uncover the effect and mechanism of heat-clearing, detoxifying and blood stasis removing decoction (HDBD) on the treatment of acute soft tissue injury (STI) which is characterized with excessive inflammatory cascade at the onset. Male Sprague–Dawley (SD) rats with hammer beating served as the in vivo models of acute STI. Hematoxylin–Eosin (HE) staining was used for histopathology assessment. The levels of inflammatory factors, including prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1t and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Human dermal microvascular endothelium cell line HMEC-1 and rat vascular endothelium cell line RAOEC were used to explore the mechanism in vitro. Luciferase gene reporter assay was applied to determine the relationship between miR-26b-5p and Cyclo-oxygenase 2 (COX2). The results showed that HDBD intervention significantly reduced the temperature difference between the healthy side and affected side of rats with hammer beating, together with the decreased levels of COX2, PGE2, TNF-α, IL-6 and IL-1β, and the increased level of miR-26b-5p. In mechanism, miR-26b-5p targeted COX2 and decreased its expression, leading to significant decreases in the levels of PGE2, TNF-α and IL-6 in RAOEC and HMEC-1 cells. In addition, miR-26b-5p inhibition impaired the effects of HDBD on the suppression of PGE2, TNF-α, IL-6 and IL-1β in vitro. In conclusion, the present study revealed that HDBD relieved acute STI via modulating miR-26b-5p/COX2 axis to inhibit inflammation.
Correcting the imbalanced protective RAS in COVID-19 with angiotensin AT2-receptor agonists
Authors: Steckelings U. Muscha , Sumners Colin
Published: December 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for the global corona virus disease 2019 (COVID-19) pandemic enters host cells via a mechanism that includes binding to angiotensin converting enzyme (ACE) 2 (ACE2). Membrane-bound ACE2 is depleted as a result of this entry mechanism. The consequence is that the protective renin–angiotensin system (RAS), of which ACE2 is an essential component, is compromised through lack of production of the protective peptides angiotensin-(1-7) and angiotensin-(1-9), and therefore decreased stimulation of Mas (receptor Mas) and angiotensin AT2-receptors (AT2Rs), while angiotensin AT1-receptors (AT1Rs) are overstimulated due to less degradation of angiotensin II (Ang II) by ACE2. The protective RAS has numerous beneficial actions, including anti-inflammatory, anti-coagulative, anti-fibrotic effects along with endothelial and neural protection; opposite to the deleterious effects caused by heightened stimulation of angiotensin AT1R. Given that patients with severe COVID-19 exhibit an excessive immune response, endothelial dysfunction, increased clotting, thromboses and stroke, enhancing the activity of the protective RAS is likely beneficial. In this article, we discuss the evidence for a dysfunctional protective RAS in COVID and develop a rationale that the protective RAS imbalance in COVID-19 may be corrected by using AT2R agonists. We further review preclinical studies with AT2R agonists which suggest that AT2R stimulation may be therapeutically effective to treat COVID-19-induced disorders of various organ systems such as lung, vasculature, or the brain. Finally, we provide information on the design of a clinical trial in which patients with COVID-19 were treated with the AT2R agonist Compound 21 (C21). This trial has been completed, but results have not yet been reported.
Have a heart: failure to increase GLP-1 caused by heart failure increases the risk of diabetes
Authors: Ryan Michael J.
Published: December 2020

Incretins represent a group of gut-derived peptide hormones that, at physiological concentrations, potentiate the release of insulin. Work leading to the discovery of incretins began as early as the late 1800s where scientists, including Claude Bernard who is widely considered the father of modern physiology (Rehfeld, J.F. The Origin and Understanding of the Incretin Concept. Front. Endocrinol. (Lausanne) (2018) 9, 387; Robin, E.D. Claude Bernard. Pioneer of regulatory biology. JAMA (1979) 242, 1283–1284), attempted to understand the pancreas as an important organ in the development of diabetes mellitus and blood glucose control. After the seminal work of Paulescu and Banting and Best in the early 1920s that led to the discovery of insulin (Murray I. Paulesco and the isolation of insulin. J. Hist. Med. Allied Sci. (1971) 26, 150–157; Raju T.N. The Nobel Chronicles. 1923: Frederick G. Banting (1891–1941), John J.R. Macleod (1876–1935). Lancet (1998) 352, 1482), attention was turned toward understanding gastrointestinal factors that might regulate insulin secretion. A series of experiments by Jean La Barre showed that a specific fraction of intestinal extract caused a reduction in blood glucose. La Barre posited that the fraction’s glucose lowering actions occurred by increasing insulin release, after which he coined the term ‘incretin’. In the 1970s, the first incretin was purified, glucose insulinotropic polypeptide (GIP) (Gupta K. and Raja A. Physiology, Gastric Inhibitory Peptide StatPearls Treasure Island (FL); 2020), followed by the discovery of a second incretin in the 1980s, glucagon-like peptide-1 (GLP-1). Interest and understanding of the incretins, has grown since that time.
How SARS-CoV-2 (COVID-19) spreads within infected hosts — what we know so far
Authors: Sanyal Sumana
Published: December 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19), belongs to the betacoronavirus genus and shares high homology to the severe acute respiratory syndrome coronavirus (SARS-CoV) that emerged in 2003. These are highly transmissible and pathogenic viruses which very likely originated in bats. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as SARS-CoV, and spreads primarily through the respiratory tract. Although several trials for vaccine development are currently underway, investigations into the virology of SARS-CoV-2 to understand the fundamental biology of the infectious cycle and the associated immunopathology underlying the clinical manifestations of COVID-19 are crucial for identification and rational design of effective therapies. This review provides an overview of how SARS-CoV-2 infects and spreads within human hosts with specific emphasis on key aspects of its lifecycle, tropism and immunopathological features.
A survey on the development status and application prospects of knowledge graph in smart grids
Authors: Wang Jian , Wang Xi , Ma Chaoqun , Kou Lei
Published: December 2020

With the advent of the electric power big data era, semantic interoperability and interconnection of power data have received extensive attention. Knowledge graph technology is a new method describing the complex relationships between concepts and entities in the objective world, which is widely concerned because of its robust knowledge inference ability. Especially with the proliferation of measurement devices and exponential growth of electric power data empowers, electric power knowledge graph provides new opportunities to solve the contradictions between the massive power resources and the continuously increasing demands for intelligent applications. In an attempt to fulfil the potential of knowledge graph and deal with the various challenges faced, as well as to obtain insights to achieve business applications of smart grids, this work first presents a holistic study of knowledge‐driven intelligent application integration. Specifically, a detailed overview of electric power knowledge mining is provided. Then, the overview of the knowledge graph in smart grids is introduced. Moreover, the architecture of the big knowledge graph platform for smart grids and critical technologies are described. Furthermore, this paper comprehensively elaborates on the application prospects leveraged by knowledge graph oriented to smart grids, power consumer service, decision‐making in dispatching, and operation and maintenance of power equipment. Finally, issues and challenges are summarised.
Electrochemically produced battery‐type Ni(OH)2/Ni3Si electrodes
Authors: Cui Kai , Zhao Zhilong , Liu Wenbin
Published: December 2020

The fabrication, by an electrochemical process, of a new battery‐type electrode material, is presented. Such materials are fabricated by direct current electrodeposition of Ni(OH)2 on lamellar Ni3Si. Microstructure and morphology of Ni(OH)2/Ni3Si electrodes were characterised. Cyclic voltammetry and galvanostatic charge–discharge results revealed that they are battery‐type electrodes. Increasing deposition time or decreasing discharge current can significantly increase the areal capacity. The areal capacity of Ni(OH)2/Ni3Si‐20 with a discharge current of 20 mA is only 2.8% of that with 1 mA. However, the increasing deposition time will reduce the cyclic stability of the electrodes. The initial areal capacity of Ni(OH)2/Ni3Si‐20 is twice that of Ni(OH)2/Ni3Si‐10 with a discharge current of 10 mA, but after 1000 cycles, it can only maintain 59.3% of the initial value. This Letter is expected to provide a powerful reference and guidance for the preparation of electrodes with large areal capacity and cycle stability.
GaiaEarly Data Release 3
Authors: Fabricius C. , Luri X. , Arenou F. , Babusiaux C. , Helmi A. , Muraveva T. , Reylé C. , Spoto F. , Vallenari A. , Antoja T. , Balbinot E. , Barache C. , Bauchet N. , Bragaglia A. , Busonero D. , Cantat-Gaudin T. , Carrasco J. M. , Diakité S. , Fabrizio M. , Figueras F. , Garcia-Gutierrez A. , Garofalo A. , Jordi C. , Kervella P. , Khanna S. , Leclerc N. , Licata E. , Lambert S. , Marrese P. M. , Masip A. , Ramos P. , Robichon N. , Robin A. C. , Romero-Gómez M. , Rubele S. , Weiler M.
Published: December 2020

Context.The thirdGaiadata release is published in two stages. The early part,GaiaEDR3, gives very precise astrometric and photometric properties for nearly two billion sources together with seven million radial velocities fromGaiaDR2. The full release,GaiaDR3, will add radial velocities, spectra, light curves, and astrophysical parameters for a large subset of the sources, as well as orbits for solar system objects.

Aims.Before the publication of the catalogue, many different data items have undergone dedicated validation processes. The goal of this paper is to describe the validation results in terms of completeness, accuracy, and precision for theGaiaEDR3 data and to provide recommendations for the use of the catalogue data.

Methods.The validation processes include a systematic analysis of the catalogue contents to detect anomalies, either individual errors or statistical properties, using statistical analysis and comparisons to the previous release as well as to external data and to models.

Results.GaiaEDR3 represents a major step forward, compared toGaiaDR2, in terms of precision, accuracy, and completeness for both astrometry and photometry. We provide recommendations for dealing with issues related to the parallax zero point, negative parallaxes, photometry for faint sources, and the quality indicators.
Least gradient functions in metric random walk spaces
Authors: Górny Wojciech , Mazón José M.
Published: December 2020

In this paper we study least gradient functions in metric random walk spaces, which include as particular cases the least gradient functions on locally finite weighted connected graphs and nonlocal least gradient functions on ℝN. Assuming that a Poincaré inequality is satisfied, we study the Euler-Lagrange equation associated with the least gradient problem. We also prove the Poincaré inequality in a few settings.
Non-local variant of the optimised Schwarz method for arbitrary non-overlapping subdomain partitions
Authors: Claeys Xavier
Published: December 2020

We consider a scalar wave propagation in harmonic regime modelled by Helmholtz equation with heterogeneous coefficients. Using the Multi-Trace Formalism (MTF), we propose a new variant of the Optimized Schwarz Method (OSM) that remains valid in the presence of cross-points in the subdomain partition. This leads to the derivation of a strongly coercive formulation of our Helmholtz problem posed on the union of all interfaces. The corresponding operator takes the form “identity + non-expansive”.