bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis
Authors: Ocaña Mª Carmen , Yang Chendong , Bernal Manuel , Martínez-Poveda Beatriz , Vu Hieu , Cárdenas Casimiro , DeBerardinis Ralph , Quesada Ana , Medina Miguel Ángel
Published: May 2022

Dimethyl fumarate is an ester from the Krebs cycle intermediate fumarate. This drug is approved and currently used for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity was reported some years ago. Due to the current clinical relevance of this compound and the recently manifested importance of endothelial cell metabolism on the angiogenic switch, we wanted to elucidate whether dimethyl fumarate has an effect on energetic metabolism of endothelial cells. Different experimental approximations were performed in endothelial cells, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration in endothelial cells, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in these cells. Dimethyl fumarate alters the energetic metabolism of endothelial cells through an unknown mechanism, which could be the cause or the consequence of its pharmacological activity. This new discovery on the targets of this compound could open a new field of study regarding the mechanism of action of dimethyl fumarate.
Comparative evaluation of Gibbs sampler for milk yield and composition traits in Sahiwal and Tharparkar cattle
Authors: Yadav Nistha , Mukherjee Sabyasachi , Mukherjee Anupama
Published: May 2022

A total number of 802 and 300 records of Sahiwal and Tharparkar cows respectively were collected from history-cum-pedigree sheet for milk production and composition, animals born and reared at Livestock farm unit of ICAR-NDRI Karnal, Haryana, India. The period of study were divided into 6 periods of 5 years each (1990 to 2019). Presented analyzed data were received from selected herd for first lactation milk yield (FLMY), first lactation SNF yield (FLSNFY) and first lactation fat yield (FLFY) in both cattle breeds. Multivariate/Trivariate analyses were carried out by Bayesian approach using Gibbs sampler Animal model. Total heritability estimates for FLMY, FLSNFY and FLFY by Bayesian modeling were valued as 0.20±0.0125, 0.51±0.0114 and 0.45±0.0112 for Sahiwal and 0.46±0.0375, 0.54±0.0195 and 0.52±0.0204 for Tharparkar respectively along with its Monte Carlo Error. Direct genetic and environmental covariance between production traits were ranging from 94553 and 58851 for FLMY-FLFY to 180380 and 185780 for FLSNFY-FLFY in Sahiwal and from 116650 and 95344 for FLSNFY-FLFY to 245820 and 227400 for FLMY-FLFY in Tharparkar respectively. Comparable estimates of heritability and breeding values for ranking of sires were obtained by BLUP and Bayesian analyses from the presented data. Estimates of genetic and phenotypic (co)variance components and heritability estimates obtained using LSML which were positive but very medium to high for Sahiwal while genetic correlations were positive and high in Tharparkar. However, Gibbs Sampling (GS) is an advance and comparatively correct method of choice for many applications because of its greater robustness with comparable but slightly higher estimates of genetic parameters than LSML. The Gibbs Sampling method is flexible and dependable practice for the genetic evaluation and it can be useful in the breeding programs for highly heritable traits in Tharparkar as compared to low estimates in Sahiwal from present work.
Glow Discharge Plasma Effects on Colored Nylon 6 with Azo Dye
Authors: Yari Mohammad Reza , Zakerhamidi Mohammad Sadegh , Ghomi Hamid
Published: May 2022

Plasma can be used as a new low-cost and efficient method to modify polymers' surface and constituent unit configuration. This research investigates the effects of argon DC glow discharge plasma on nylon 6 polymer films doped and loaded with DR1 dye. Plasma changes the morphology and breaks some bonds, creating free radicals on the surface of the polymer and immobilizing the dye on the broken bonds. The interaction of the dye with the polymer through the broken bonds leads to an increase in the stability of the dye structure due to an increment in their resonance length. On the other hand, these interactions lead to changes in the dye's optical and geometric isomeric activity. This work studies the chemical and morphological changes of nylon 6 by plasma with AFM and spectroscopic method. Furthermore, the aging of nylon 6 films doped and loaded with DR1 dye is measured, and the polymer's color configuration changes are investigated. Plasma stabilizes the dye on the polymer surface through making changes of chemical and physical properties on the surface components.
Acetate meliorates depressive-like behaviour in a rat model of PCOS through suppression of HDAC2 expression and DNA methylation
Authors: Wolugbom John A. , Areloegbe Stephanie E. , Olaniyi Kehinde S.
Published: May 2022

ObjectivePolycystic Ovarian Syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. PCOS has been demonstrated to induce depressive-like behaviour. Epigenetic alterations such as histone deacetylation (HDAC) and DNA methylation have been suggested in major depression. However, their effects with respect to neuroinflammation are not clear. This study therefore investigated the pathogenic role of epigenetic modification in PCOS-associated depression and the therapeutic potential of HDACi, acetate.MethodsAdult female Wistar rats (120-150 g) were allotted into groups (n = 6/group) namely: control (vehicle; p.o.), acetate-treated (200 mg/kg), letrozole (LET)-treated (1 mg/kg) and LET+Acetate-treated. Letrozole was administered for 21 days to induce PCOS.ResultsTreatment with letrozole caused hyperandrogenism, hyperinsulinemia and disrupted ovarian morphology with evidence of degenerated follicles. In addition, these animals showed depressive-like behaviours and increased expression of HDAC2 and DNA methyltransferase in PFC and hippocampal tissues. Biochemical analyses showed elevated NF-kB and acetylcholine (ACH) levels in PFC and hippocampus as well as plasma lipid peroxidation and impaired antioxidant system in LET-treated animals. Histological analysis of PFC and hippocampus showed neurodegeneration in LET-treated animals compared with control. However, these alterations were attenuated when treated with acetate.ConclusionThe study demonstrates that PCOS-associated depression is characterised by neuroinflammation and elevated ACH levels, and this is associated with increased expression of HDAC2 and DNA hypermethylation in PFC and hippocampus. Besides, the study suggests that acetate ameliorates PCOS-associated depression through the suppression of prefrontal and hippocampal DNA methyltransferase and prefrontal but not hippocampal HDAC2 expression.
Association between dietary inflammatory index and cardio-metabolic risk factors in diabetic and non-diabetic individuals: A cross-sectional study on Ravansar cohort research
Authors: Namazi Nazli , Ayati Mohammad Hossein , Anjom-Shoae Javad , Darbandi Mitra , Najafi Farid , Pasdar Yahya
Published: May 2022

Background: Inflammation can be involved in developing diabetes and its related complications. In the present study, the association of dietary inflammatory index (DII) and cardiometabolic risk factors in diabetic and non-diabetic individuals have been compared. Methods: In this cross-sectional study, 9039 participants from baseline data of the Ravansar Non-Communicable Disease (RaNCD) cohort; including patients with type 2 diabetes mellitus (T2DM) (n=785) and non-T2DM cases (n=8254) were included. Logistic regression analysis was conducted to determine the association between DII and main cardiometabolic risk factors in diabetic and non-diabetic populations. All analyses were performed using Stata version 14.2 software. Results: Mean age of the study population was 47.4±8.2 years and around 46% of them were men. The total mean DII score was -2.49±1.59. After adjustment for confounding factors, we found that DII can increase the risk of T2DM by 61% (95% CI:1.27 to 2.05). A comparison of the two groups also revealed that only the association of DII, obesity/overweight and dyslipidemia were significant in both diabetic and non-diabetic ones. However, no significant association was found between DII, MetS, and hypertension in either group. The association between DII and cardiovascular diseases (CVDs) was significant in only diabetic patients 1.65 (95%CI: 1.02 to 2.65) and T2DM showed an interaction with the association between DII and CVDs. Conclusions: Inflammatory potential of diet can increase the risk of T2DM. Although it can increase the risk of some cardiometabolic risk factors in both diabetic and non-diabetic cases, its effects in patients with T2DM were greater than in non-diabetic ones.
Biochemical response and RAPD DNA Profile in Lanistes carinatus from the River Nile, Aswan, Egypt as bioindicator of Heavy metals contamination
Authors: Mohamed Zeinab , Abdel-Wahab Hoda , Alnady Arwa , Younis Abuelhassan
Published: May 2022

Toxicity with heavy metals is the most common sort of pollution, causing harm to aquatic species, plants, and humans. In this study, lead (Pb), zinc (Zn), iron (Fe), and manganese (Mn), were studied in water, sediment, and soft tissue of Lanistes carinatus during field investigations and laboratory tests to determine contamination and toxicity. The snail was taken from two sites, site 1(near the Edfu Bridge), site 2 (Beside ferrosilicon factory), along the Nile River in Edfu, Aswan government, Egypt. We found that site 2 was more contaminated than site 1. The median lethal concentration (LC50) of 96 hours exposure for Pb, Zn, Fe and Mn on Lanistes carinatus were 12.7 mg/l, 20.6 mg/l, 95.2 mg/l, 73.6 mg/l. According to bioaccumulation factor (BWAF) data heavy metal uptake by Lanistes carinatus samples followed order Pb > Mn > Fe > Zn. This study looked at lipid peroxidation (LPO) as an oxidative stress marker, and antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) in response to heavy metal accumulation. By comparing (LPO) activity we found that higher level of LPO activity in (Pb) treated group in site 2 than site 1, and the treated group of (Pb) had lower activity in (GPx), (GST), and (SOD)enzymes, but (CAT) enzyme was less activity in the treated group of (Zn). We investigated genetic differentiation and the impact of heavy metal pollution on the genetic structure of Lanistes carinatus using the random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) technique.
Fine-mapping of a major QTL for protein content in BR8014887 soybean line
Authors: Bueno Rafael Delmond , Lorenzoni Rodrigo Monte , Bernardeli Arthur , Silva Luciano da Costa e , Silva Luiz Claudio Costa , Silva Jéssica Nayara Basilio , Vidigal Pedro Marcus Pereira , Piovesan Newton Deniz , Ribeiro Cleberson , Dal-Bianco Maximiller
Published: May 2022

Soybean is one of the main crops in the world and has great added value. Due to its importance, breeders have focused on increasing their production, leaving aside important characteristics such as grain quality. Today, the protein content in soybean seeds is lower than in previous decades, and this process needs to be adjusted to meet the requirements of the food and feed industry. The inheritance of seed traits is complex, and we are still in the infancy of this area. The elucidation of the metabolic pathways involved as well as the discovery of causal genes will be of paramount importance for the field. The main goal of the present work was to identify SNPs associated with protein content in Brazilian soybean genotypes and fine map the region associated with the protein content on chromosome 20 of the BR8014887 line to identify the possible causal gene. We identified a novel SNP (190-ss715637277) associated with protein content on BR8014887 chromosome 20 that has been shown to account for the causal effect within a region of approximately 116kb. Within the region, we have only one target gene that is annotated as a pre-mRNA splicing factor and seems to play multiple roles in the plant. The identified QTL proved to be stable, capable of increasing protein content and is considered rare. Therefore, it can be a great target for breeding programs to use and thus recover part of the protein content lost over the years.
A positive feedback loop controls Toxoplasma chronic differentiation
Authors: Licon M. , Giuliano Christopher , Chakladar Sundeep , Eberhard Julia , Shallberg Lindsey , Waldman Benjamin , Hunter Christopher , Lourido Sebastian
Published: May 2022

Successful infection strategies must balance pathogen amplification and persistence. In Toxoplasma gondii, this is accomplished through differentiation into dedicated cyst-forming chronic stages that avoid clearance by the host immune system. The transcription factor BFD1 is both necessary and sufficient for stage conversion; however, its regulation is not understood. We examine five factors transcriptionally activated by BFD1. One of these is a cytosolic RNA-binding protein of the CCCH-type zinc finger family, which we name BFD2. Parasites lacking BFD2 fail to induce BFD1 and are consequently unable to fully differentiate in culture or in mice. BFD2 interacts with the BFD1 transcript in a stress-dependent manner. Deletion of BFD2 reduces BFD1 protein levels, but not mRNA abundance. The reciprocal effects on BFD2 transcription and BFD1 translation outline a positive feedback loop that enforces commitment to differentiation. BFD2 helps explain how parasites commit to the chronic gene-expression program and elucidates how the balance between proliferation and persistence is achieved over the course of infection.
HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress
Authors: Sala-Gaston Joan , Pedrazza Leonardo , Ramirez Juanma , Martinez-Martinez Arturo , Rawlins Lettie E , Baple Emma L , Crosby Andrew H , Mayor Ugo , Ventura Francesc , Rosa Jose Luis
Published: May 2022

HERC2 gene encodes an E3 ubiquitin ligase involved in several cellular processes by regulating the ubiquitylation of different protein substrates. Biallelic pathogenic sequence variants in the HERC2 gene are associated with HERC2 Angelman-like syndrome. In pathogenic HERC2 variants, complete absence or marked reduction in HERC2 protein levels are observed. The most common pathological variant, c.1781C>T (p.Pro594Leu), encodes an unstable HERC2 protein. A better understanding of how pathologic HERC2 variants affect intracellular signalling may aid definition of potential new therapies for these disorders. For this purpose, we studied patient-derived cells with the HERC2 Pro594Leu variant. We observed alteration of mitogen-activated protein kinase signalling pathways, reflected by increased levels of C-RAF protein and p38 phosphorylation. HERC2 knockdown experiments reproduced the same effects in other human and mouse cells. Moreover, we demonstrated that HERC2 and RAF proteins form molecular complexes, pull-down and proteomic experiments showed that HERC2 regulates C-RAF ubiquitylation and we found out that the p38 activation due to HERC2 depletion occurs in a RAF/MKK3-dependent manner. The displayed cellular response was that patient-derived and other human cells with HERC2 deficiency showed higher resistance to oxidative stress with an increase in the master regulator of the antioxidant response NRF2 and its target genes. This resistance was independent of p53 and abolished by RAF or p38 inhibitors. Altogether these findings identify the activation of C-RAF/MKK3/p38 signalling pathway in HERC2 Angelman-like syndrome and highlight the inhibition of RAF activity as a potential therapeutic option for individuals affected with these rare diseases.
Direct Determination of the Topological Thermal Conductance
via Local Power Measurement
Authors: Melcer Ron , Konyzheva Sofia , Heiblum Moty , Umansky Vladimir
Published: May 2022

Thermal conductance measurements, sensitive to charge and chargeless energy flow, are evolving as an essential measurement technique in Condensed Matter Physics. For two-dimensional topological insulators, the measurements of the thermal Hall conductance, κxyT, and the longitudinal one κxxT, are crucial for the understanding of their underlying topological order. Such measurements are thus far lacking, even in the extensively studied quantum Hall effect (QHE) regime. Here, we report a new local power measurement technique that reveals the topological thermal Hall conductance (not the ubiquitous two-terminal one). For example, we find κxy~0 of the challenging ν = 2/3 particle-hole conjugated state. This is in contrast to the two-terminal measurement, which provides a non-universal value that depends on the extent of thermal equilibration between the counter-propagating edge modes. Moreover, we use this technique to study the power carried by the current fluctuations in a partitioned edge mode with an out-of-equilibrium distribution.
Role of air-sea heat flux on the transformation of Atlantic Water as it encircles the Nordic Seas
Authors: Huang Jie , Pickart Robert , Chen Zhuomin , Huang Rui Xin
Published: May 2022

The warm-to-cold densification of Atlantic Water (AW) around the perimeter of the Nordic Seas is a critical component of the Atlantic Meridional Overturning Circulation (AMOC). However, it remains unclear how ongoing changes in air-sea heat flux impact this transformation. Here we use observational data, and a one-dimensional mixing model following the flow, to quantify the role of air-sea heat flux on the cooling of AW. We focus on the Norwegian Atlantic Slope Current (NASC) and Front Current (NAFC), where the primary transformation of AW was found to occur. Our results demonstrate that air-sea heat flux accounts almost entirely for the net cooling of AW along the NAFC, while lateral transfer of heat appears to dominate the temperature change along the NASC. Such differing impacts of air-sea heat fluxes, which explain the long-term change in the cooling of AW since the 1990s, need to be considered when understanding the AMOC variability.
Response of different varieties of maize to nitrogen stress and diagnosis of leaf nitrogen using hyperspectral data
Authors: Lu Yanli , Chao Yaru , song Guipei , Nie Caie , Cui Zhiyue , Wang Lei
Published: May 2022

Spectral technology is theoretically effective in diagnosing N stress in maize (Zea mays L.), but its application is affected by varietal differences. In this study, the responses to N stress, leaf N spectral diagnostic models and the differences between two maize varieties were analyzed. Variety Jiyu 5817 exhibited a greater response to different N stresses in the 12-leaf stage (V12), while Zhengdan 958 displayed a greater response in the silking stage (R1). Correlation analysis showed that the spectral bands sensitive to the leaf N content were 548–556 nm and 706–721 nm at the V12 stage in Jiyu 5817 and 760–1142 nm at the R1 stage in Zhengdan 958. Compared with those of the model established without considering the differences in varieties, the coefficient of determination (R2) and root mean square error (RMSE) of the N spectral diagnosis model established according to each variety were improved by 10.6% and 29.2%, respectively. It was concluded that the V12 stage of Jiyu 5817 and the R1 stage of Zhengdan 958 were the best diagnostic stages and were more sensitive to N stress, which can further guide fertilization decision-making in precision fertilization.
Combining network pharmacology and bioinformatics analysis to identify the molecular mechanisms of UDCA in the treatment of carotid atherosclerosis
Authors: Xu Xiankai , Zhang Yueqi , Lu Xiaojin , Shi Baolin
Published: May 2022

Ursodeoxycholic acid (UDCA) can be used to prevent atherosclerosis. However, the molecular mechanism of UDCA on carotid atherosclerosis is not known. A combination of bioinformatics, network pharmacology, and molecular docking was used to unravel the potential molecular mechanisms of UDCA in alleviating carotid atherosclerosis. The results of weighted gene co-expression network analysis (WGCNA) combined with differential expression analysis were used to screen for potent targets in carotid atherosclerosis. A typical target for UDCA in the treatment of carotid atherosclerosis was obtained by network pharmacology, and a protein-protein interaction network was constructed. Nine core targets were obtained using four algorithms of the cytoHubba plugin of Cytoscape 3.9.0, and molecular docking was completed using Autodock Vina 1.1.2. GO, and KEGG enrichment pathway analysis was performed based on the Metascape platform. The results showed that CD4, PTPRC, CCL5, MMP9, CD38, CASP1, CCR2, EGFR, and SYK were the targets of action of UDCA in the treatment of carotid atherosclerosis. The enrichment analysis results showed that these targets were significantly enriched in pathways associated with inflammation. In conclusion, this study highlights some of the molecular mechanisms of UDCA in the treatment of carotid atherosclerosis and provides a theoretical basis for future studies.
Association between hepatic steatosis and fibrosis with measures of insulin sensitivity in patients with severe obesity and type 2 diabetes - a cross-sectional study
Authors: Seeberg Kathrine Aglen , Hofsø Dag , Borgeraas Heidi , Grimnes John Olav , Fatima Farhat , Seeberg Lars Thomas , Kvan Nils Petter , Svanevik Marius , Hertel Jens Kristoffer , Hjelmesæth Jøran
Published: May 2022

BackgroundObesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance are three pathological conditions highly correlated, but this relationship is not fully elucidated. Hence, we aimed to assess the association of hepatic steatosis and fibrosis with different measures of insulin sensitivity in patients with severe obesity and type 2 diabetes mellitus (T2DM).MethodsA cross-sectional study (Oseberg trial) including patients with T2DM referred for bariatric surgery at Vestfold Hospital Trust, Norway. Magnetic resonance imaging (MRI) and the enhanced liver fibrosis (ELF) test was used for estimation of liver fat fraction (LFF) and degree of fibrosis, respectively. Oral and intravenous glucose tolerance tests were applied for estimation of insulin sensitivity (HOMA2S, Matsuda ISI and MinMod SI).ResultsA total of 100 patients (mean [SD] age 47.5 [9.7] years, 65% women, BMI 42.0 [5.3] kg/m² and 98% with metabolic syndrome) were included in the analyses. The mean (SD) LFF in the total population was 19.1 (11.5), and the mean (SD) ELF score was 8.46 (0.84), a value representing moderate fibrosis. LFF was inversely associated with HOMA2S and Matsuda ISI, and both measures were significantly higher in the no or low-grade steatosis group compared with the medium-to-high grade steatosis group (mean difference [95% CI] 5.9 [2.2-9.6]%, Cohen’s d=0.75), and (0.7 [0.3-1.1], Cohen’s d=0.80, respectively). There was no association between LFF, as a categorical or continuous variable, and MinMod SI. The proportions of patients with none to mild fibrosis, moderate fibrosis and severe fibrosis were 14, 78 and 6%, respectively, and there were no significant associations between level of fibrosis and measures of insulin sensitivity. ConclusionsPatients with morbid obesity and T2DM demonstrated high levels of liver fat fraction, and we showed that hepatic steatosis, but not the degree of liver fibrosis, was associated with different measures of insulin sensitivity in patients with severe obesity and T2DM. Further, our results might indicate that the LFF is primarily associated with hepatic, and not peripheral insulin sensitivity. To improve the diagnosis of NAFLD and the prediction of its progression, more studies are needed to reveal the pathological mechanistic pathways involved in NAFLD and insulin sensitivity.Trial RegistrationClinicalTrials.gov:NCT01778738
Spectral properties of a high quantum yield, novel aminocoumarin with a vicinal hydroxyl group
Authors: Knoor Leah H. , Hoogewerf Liam P. , Jonker Isaac B. , Doty Elizabeth A. , Du Laney George R. , Blankespoor Ronald L. , Muyskens Mark A.
Published: May 2022

Knightletin is a novel, high quantum-yield, substituted coumarin in the group of fluorescent aminocoumarins. The molecule reveals the influence of a hydroxyl group on the aminocoumarin structure through its absorbance-fluorescence properties and interaction with several solvents. The substitution on the benzene ring of the coumarin affects electronic states, the molecular dipole moment and hydrogen bonding between vicinal groups as well as hydrogen bonding with solvents. This report describes the synthesis of knightletin, its absorbance-fluorescence characteristics in three solvents of varying polarity, and insights on its conformation from density functional theory modeling. The quantum yield of 0.81 in methanol is remarkable. The modeling indicates a ground state geometry with a pyramidal NH2 group interacting with the OH in an NH-donor hydrogen bond and predicts spectroscopic characteristics consistent with the experimental observations.
Pirates Swarm Search Algorithm: A Meta-Heuristic Search Algorithm for optimization problems
Authors: Siahkali Milad Abolhasani , Mirvaziri Hamid , Bahrololoum Abbas
Published: May 2022

In this study, we have suggested a meta-heuristic algorithm based on swarm intelligence for single-objective optimization problems. Our inspiration comes from historical and behavioral fashions of pirates at 1600s and 1700s which also is known as the golden age of piracy. They navigate in the oceans to find treasures and we search the problem space to find a better solution. Triangle trade is the search space and each pirate ship is a search agent. A bunch of well-known benchmark functions are used to run some qualitative, quantitative and statistically tests to see the outcome of the suggested algorithm. Obtained results shows that the algorithm is able to explore and exploit in search space as expected and also has the ability of improving the average fitness of population and improving the best so far solution. At the end; results of suggested algorithm comparing to other well-known ones such as Particle Swarm Optimization, Gravity Search Algorithm, Ranking Genetic Algorithm and Sparrow search algorithm shows that it is able to outperform these algorithms in most of the studied cases.
The effect of lightweight aggregate on drying shrinkage and properties of one-part alkali activated slag concrete
Authors: Kadkhodaei Razieh , Behfarnia Kiachehr , Shahidi Marjan
Published: May 2022

In the present study, the result of slag grade, dosage of activator and aggregate combination on the compressive strength and drying shrinkage of one-part alkali-activated slag concrete was considered. Also, water curing and plastic cover curing were selected to investigate the effect of curing condition on drying shrinkage and compressive strength of this type of concrete. Two aggregate combinations, one containing lightweight fine (LAF) and normal weight coarse (NAC) aggregates and one other containing both lightweight fine and coarse aggregates, were considered for making the lightweight concrete and conducting the experimental tests. Compressive strength of the specimens were measured at 7, 28 and 90 days, as well as drying shrinkage strain up to 180 days. According to the results, in most of the mixtures, slump and setting time decreased with increasing slag and activator content, while compressive strength and drying shrinkage increased. Examination of curing condition of one-part lightweight alkali-activated slag concrete showed that drying shrinkage increased and compressive strength decreased with plastic cover curing at later age.
Quantifying the Missing Half of Daily NOx Emissions over South, Southeast and East Asia
Authors: Liu Jian , Cohen Jason
Published: May 2022

Rapid urbanization and broad use of biomass burning have led to significant changes in NOx emissions across South, Southeast, and East Asia, frequently occurring on day-to-day time scales and over areas not identified by existing emissions databases. This work computes NOx emissions using remotely sensed NO2 and a model-free mass-conserving inverse method, resulting respectively in 61kt/day and 40kt/day from biomass burning in Northern and Southern Continental Southeast Asia, and 14.3kt/day and 3.7kt/day from urbanization in China and Eastern South Asia. This is a net increase of more than double the 55.7kt/day existing inventories. This method offers three additional constraints: NO2 accounts for 22%-90% of NOx emissions, NOx has an in-situ lifetime of 4.3hours-24hours, and NOx transports up to 480km, all of which are larger than chemical transport modeling studies, yet still consistent with theory. This result provides quantitative support for mitigation efforts targeting specific extreme events, processes, or geographies.
High in-vivo Stability and First-in-human Experience with [18F]AlF-RESCA-MIRC213: A 18F-Labeled Nanobody as PET Radiotracer for Diagnosis of HER2-Positive Cancers
Authors: Qin xue , Guo Xiaoyi , Liu Tianyu , Li Liqiang , Zhou Nina , Ma Xiaopan , Meng Xiangxi , Liu Jiayue , Zhu Hua , Jia Bing , Yang Zhi
Published: May 2022

Purpose [18F]AlF-RESCA was introduced as a core particularly useful for 18F-labeling of heat-sensitive biomolecules. However, no translational studies have been reported up to now. Herein, we reported the first-in-human evaluation of an 18F-labeled anti-HER2 nanobody MIRC213 as a PET radiotracer for imaging HER2-positive cancers.Methods In this study, [18F]AlF-RESCA-MIRC213 was prepared at room temperature. Small-animal PET/CT and bio-distribution were performed on HER2-positive subcutaneous xenografts. Six breast cancer patients (3 HER2-positive and 3 HER2-negative patients) were included, and PET/CT images were acquired at 2 h and 4 h after injection of 222 ± 18.5 MBq of [18F]AlF-RESCA-MIRC213. All patients underwent [18F]-FDG PET/CT within a week for comparison purpose. Bio-distribution and dosimetry were calculated. Standardized uptake values (SUV) were measured in tumors and normal organs.Results [18F]AlF-RESCA-MIRC213 was prepared within 20 min at room temperature with the radiochemical yield of 50.48 ± 7.6% and radiochemical purity of > 98% (n > 10). The 2 h cellular uptake of [18F]AlF-RESCA-MIRC213 in NCI-N87 cells was 11.22 ± 0.60 %IA/105 cells. Its binding affinity Kd value was determined to be 1.23 ± 0.58 nM using SK-OV-3 cells. After 2 h injection, the xenografted SK-OV-3 tumors could be readily detected by [18F]AlF-RESCA-MIRC213 PET with SUVmax of 4.73 ± 1.18 ID%/g and 1.70 ± 0.13 ID%/g for the blocking group (p < 0.05). No significant radioactivity was seen in the bone in tumor-bearing animals. After approved by ethics committee (No.2021KT108). First-in-human PET translational study was conducted. In six all patients, there was no adverse reactions during study. The uptake of [18F]AlF-RESCA-MIRC213 was mainly in lacrimal gland, parotid gland, submandibular gland, thyroid gland, gallbladder, kidneys, liver, and intestine. There was no significant radioactivity accumulation in the bone of cancer patients. [18F]AlF-RESCA-MIRC213 had significantly higher tumor uptake in HER2-positive lesions than that in HER2-negative lesions (SUVmax of 3.62 ± 1.56 vs. 1.41 ± 0.41, p = 0.0012) at 2 h post-injection. Kidneys received the highest radiation dose of 2.17×10-2 mGy/MBq, and the effective dose was 1.76×10-2 mSv/MBq. Conclusions [18F]AlF-RESCA-MIRC213 could be prepared with high radiolabeling yield under mild conditions. [18F]AlF-RESCA-MIRC213 has relatively high stability both in vitro and in vivo. The results from clinical transformation suggest that [18F]AlF-RESCA-MIRC213 PET/CT is a safe procedure with favorable pharmacokinetics and dosimetry profile, and it is a promising new PET radiotracer for noninvasive diagnosis of HER2-positive cancers.
Investigation of optimal convolutional neural network conditions for thyroid ultrasound image analysis
Authors: Lee Joon-Hyop , Kim Young-Gon , Ahn Youngbin , Park Seyeon , Kong Hyoun-Joong , Choi June Young , Kim Kwangsoon , Nam Inn-Chul , Lee Myung-Chul , Masuoka Hiroo , Miyauchi Akira , Kim Sungwan , Kim Young A , Choe Eun Kyung , Chai Young Jun
Published: May 2022

Neural network models have been used to analyze thyroid ultrasound (US) images and stratify malignancy risk of the thyroid nodules. We investigated the optimal neural network condition for thyroid US image analysis. We compared scratch and transfer learning models, performed stress tests in 10% increments, and compared the performance of three threshold values. All validation results indicated superiority of the transfer learning model over the scratch model. Stress test indicated that training the algorithm using 3902 images (70%) resulted in a performance which was similar to the full dataset (5575). Threshold 0.3 yielded high sensitivity (1% false negative) and low specificity (72% false positive), while 0.7 gave low sensitivity (22% false negative) and high specificity (23% false positive). Here we showed that transfer learning was more effective than scratch learning, about 3900 images were minimally required to demonstrate an acceptable performance, and algorithm performance can be customized according to the population characteristics by adjusting threshold value.
Genome-wide Computational Analysis of DIR Genes inSolanum lycopersicum
Authors: Saddique Muhammad Abu Bakar
Published: May 2022

Background: Extensive Dirigent proteins impart a key role in the development of organic products in plants. They confer conformational influence on processes that lack stereoselectivity and regioselectivity through processes that are mostly understood. Dirrigent proteins are required to produce lignans, a unique and widely distributed family of plant secondary metabolites with intriguing pharmacological characteristics and potential use in plant development as well. The dirigent (DIR) proteins, which are implicated in the process of lignification, also protect plants from environmental stresses including Biotic and Abiotic. Nevertheless, there is no research have been done so far on the DIR proteins in Solanum lycopersicum. This study provides a detailed information of DIRs protein in the in tomato.Results:The Conserved Domain analysis, Phylogeny, Evolutionary Adaptation, cis-acting Elements, Proteomic analysis, Transmembrane Potential Analysis, Sequence Identity and Similarity Analysis, gene assembly, genomic localization, duplication of gene analysis, and evolutionary linkage of all 31 potential dirigent genes (SlDIRs) were revealed in this investigation. Conclusion:This research provides an in - depth and comprehensive explanation of the detailed molecular process and structural characterization of SlDIR genes in the genome of Solanum lycopersicum, laying the groundwork for future plant genetic engineering and crop development exploration. This study will aid future research on the DIR gene family and give helpful information for enabling appropriate DIRs genes in higher plants.
Complementary descriptions of Euler characteristics of simplicial incidence pseudographs
Authors: ZHANG Zhiguo , WANG Yanying , ZHANG Conglei , ZHAO Suqian
Published: May 2022

We introduce incidence pseudographs and simplicial incidence pseudographs with a poset topology, which provide discrete representation of continuous objects and helpful tools in digital image analysis. We prove closed or open sub-pseudograph matching theorems in a regular incidence pseudograph. By embedding a finite simplicial incidence pseudograph into an optimal simplicial incidence pseudograph, we obtain several formulae which give complementary descriptions of Euler characteristics of finite simplicial incidence pseudographs and its relative pseudographs. These descriptions provide new methods of calculating Euler characteristics by boundary counts rather than all nodes and make it possible, in some cases, to simplify the complexity of computing Euler characteristic of finite simplicial incidence pseudographs.
GCC countries strategic options in a global transition to zero-net emissions
Authors: Babonneau Frédéric , Badran Ahmed , Haurie Alain , Schenckery Maxime , Vielle Marc
Published: May 2022

Using a multi-level perspective approach combined with top-down macroeconomic models, we analyse the situation of the GCC countries in the perspective of a global transition to zero-net emissions before the end of the century. Based on these analyses we propose strategic and political options for these oil and gas exporting countries. We show that it would be unwise for GCC member states to adopt an obstruc-tionist strategy in international climate negotiations. On the contrary, these countries could be proactive in developing international emissions trading market and exploiting negative emissions obtained from CO2 direct reduction technologies, in particular Direct Air Capture with CO2 sequestration, and thus contribute to a global net-zero-emissions regime in which clean fossil fuels are still used.
Content Analysis Identifies Nuanced Critical Steps in Hirschsprung Disease (HD) Surgery Which Prevent Disabling Incontinence and Improve Outcomes
Authors: Doolin Edward J , Richards William O
Published: May 2022

Purpose: Recently, poor function after Hirschprung’s Surgery has become more common. We hypothesized that accurate construction of the anorectal cuff and inclusion of certain technical elements would correlate with improved long-term function.Methods:: Anoscopy was performed in dysfunctional patients to measure Anorectal cuff area (CA) reported as the distance from the dentate line to the suture line. Using content analysis, a blinded observer abstracted nine technical elements from operative reports. Function was recorded from 1-3 years post-operative and classified as a) normal bowel function (NBF), b) constipation or c) incontinence. The association the outcomes was determined for each technical element.Results: CA in 12 incontinent and 8 constipated patients measured 8.75mm2 [0-22) and 60.75mm2 (32-160) respectively. 92 charts were reviewed resulting in 58 patients. NBF was found in 36 (62%), 11 (20%) had constipation and 11 (20%) had incontinence. 5 elements in the operative reports corelated with NBF. When all 5 were documented, 23/26 (89%) reported NBF while if none were recorded only 3/19 (16 %) had NBF. Conclusion: Short CA (<22mm2) is associated with incontinence while long CA (>32mm2) is associated with constipation. Procedural components identified by content analysis are key to provide an optimal anorectal cuff preventing incontinence.
Network Meta-Analysis on the Effects of Finerenone Versus SGLT2 Inhibitors and GLP-1 Receptor Agonists on Cardiovascular and Renal Outcomes in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease
Authors: Zhang Yaofu , Jiang Li , Wang Junheng , Wang Tongxin , Chien Chieh , Huang Weijun , Fu Xiaozhe , Xiao Yonghua , Fu Qiang , Wang Shidong , Zhao Jinxi
Published: May 2022

Objective: To evaluate the cardiovascular and renal benefits of finerenone, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) with network meta-analysis.Methods: Systematic literature searches were conducted of PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to December 30, 2021. Randomized control trials (RCTs) comparing finerenone, SGLT-2i and GLP-1 RA in diabetics with CKD were selected. We performed a network meta-analysis to compare the three drugs indirectly. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI).Results: In all, 17 RCTs were selected, including 51,496 patients. Finerenone reduced the risk of renal events and hospitalization for heart failure (HHF) (RR [95%CI]; 0.86 [0.79–0.93], 0.79 [0.67,0.92], respectively). SGLT-2i were associated with reduced risks of major adverse cardiovascular events (MACE) (RR [95%CI]; 0.84 [0.78–0.90]), renal events (RR [95%CI]; 0.67 [0.60–0.74], HHF (RR [95%CI]; 0.60 [0.53–0.68]), all-cause death (ACD) (RR [95%CI]; 0.89 [0.81–0.91]) and cardiovascular death (CVD) (RR [95%CI]; 0.86 [0.77–0.96]) compared to placebo. GLP-1 RA were associated with a lower risk of MACE (RR [95%CI]; 0.88 [0.80–0.97]). As for renal outcomes and HHF, SGLT2i had significant effect in comparison to finerenone (RR [95%CI]; 1.29 [1.13–1.47], 1.31 [1.07–1.61], respectively) and GLP-1 RA (RR [95%CI]; 1.36 [1.16–1.59], 1.49 [1.18–1.89], respectively). Compared with placebo, there was a trend toward reduction in ACD with finerenone (RR [95%CI]; 0.90 [0.80–1.00]). GLP-1 RA did not reduce the risk of renal events, HHF, CVD and ACD, but the analysis based on chemical structure showed that a GLP-1 analogues, liraglutide (RR [95%CI]; 0.79 [0.67–0.92], 0.69 [0.52–0.90], 0.76 [0.62–0.93], respectively) showed significant effect in HHF, CVD and ACD, while an exendin-4 analogues, exenatide (RR [95%CI]; 1.10 [0.83–1.46], 1.19 [0.84–1.69], 1.10 [0.87–1.39], respectively), did not.Conclusions: In patients with T2DM and CKD, finerenone led to a risk reduction in renal events and HHF, SGLT2i were associated with a decreased risk of cardiovascular and renal events. GLP-1 RA were associated with a decreased risk of MACE. Among GLP-1 RA, GLP-1 analogues showed significantly reduced cardiovascular events compared with exendin-4 analogues.
LncRNA GALNT5 uaRNA promotes cisplatin resistance in colorectal cancer via NF- κB/MDR1/MRP1/ pathway
Authors: Zhong Zhiqiang , Bai RiXing , Xu Jun
Published: May 2022

To clarify the function of long non-coding RNA (lncRNA) GALNT5 uaRNA in cisplatin resistant colorectal cancer and its potential mechanism. The expression levels were also detected in cisplatin resistant colorectal cancer cell lines (HCT116/DDP and HT29/DDP cells) and sensitive colorectal cancer cell lines. The effects of GALNT5 uaRNA on apoptosis of HCT116/DDP and HT29/DDP cells were examined by flow cytometry assay respectively. The protein levels of drug resistance related genes influenced by GALNT5 uaRNA were detected by Western blot. The cells of siNC, sIGALNT5 uaRNA, Vector and GALNT5 uaRNA cells groups from HCT116/DDP and HT29/DDP cells were injected into dorsal flanks of the mice repectively. Higher GALNT5 uaRNA expression was observed in HCT116/DDP and HT29/DDP cells relative to that of their parental cells. The apoptotic rate increased in HCT116/DDP and HT29/DDP cells with GALNT5 uaRNA knockdown compared to the cells with control group. Furthermore, the expression levels of MDR1, MRP1 and p-NF-κB were decreased in HCT116/DDP and HT29/DDP cells with GALNT5 uaRNA knockdown compared to the cells with control group. The apoptotic rate decreased in HCT116/DDP and HT29/DDP cells with GALNT5 uaRNA overexpression. Furthermore, the expression levels of MDR1, MRP1 and p-NF-κB were increased in HCT116/DDP cells with GALNT5 uaRNA overexpression compared to the cells with control group. The tumors in the HCT116/DDP/siGANLNT5 uaRNAgroup were smaller and lighter than those in the HCT116/DDP/siNC. In a word GALNT5 uaRNA promotes cisplatin resistance by MDR1/MRP1/NF-κB pathway.
Microgel emulsion loaded with recombinant oil body as a new drug delivery carrier to promote wound repair
Authors: Lan Xinxin , Shuangzhu Lin , Shihui Guan , Li Jing , Qiang Weidong , Du Linna , zhou Tingting , Dong Yue , Li Xiaokun , Yang Jing
Published: May 2022

Background: The skin is an important barrier to protect the body of external damage, there are tens of millions of patients with various skin defects. Due to the complex process of wound repair, it is easy to cause poor healing and other problems. Here, we prepared a new type of transdermal oil body microgel emulsion (OBEME) as a delivery carrier and preliminarily expounded its effect on wound healing. Method: The basic properties of the OBEME were characterized by scanning electron microscope, cryo-scanning electron microscopy, rheology and thermos- gravimetric analysis. Meanwhile, after 90 d of storage at room temperature, the effects of low-speed centrifugation and repeated freeze-thaw cycles on OBEME were investigated by particle size, potential and fluorescence microscopy tests. Through in vivo transdermal experiments and construction of a full-thickness wound model, the pharmacological effects of OBEME were clarified. Results: The OBEME is an interconnected network and presents to be smooth with no presence of pores, at the same time, after 90 d of storage at room temperature, the microstructure showed that the oil bodies remained intact. Unaffected by low-speed centrifugation and repeated freeze-thaw cycles. When OBEME treated the mouse skin for 90min, the EGF content in the mouse skin tissue reached the highest, the skin tissue gap was enlarged, and the skin permeability was enhanced. The wound coverage rate exceeded 98 % after treatment for 15 d with OBEME. After OBEME treatment, the inflammatory factor CD68 in the wound tissue was reduced, and the formation of new blood vessels, cytokeratin K5, K19 and collagen was promoted.Conclusions: The prepared OBEME has good stability, it can alter skin permeability, and promote wound healing by regulating inflammatory response, accelerating angiogenesis, promoting re-epithelialization and remodeling. The OBEME is a new carrier for percutaneous drug delivery, which lays a foundation for the development of new topical drugs.
Identification of the immune infiltration landscape and development of the prognostic signature on cuproptosis-related genes in colorectal cancer
Authors: Kang Yihan , Zhao Siqiao , Chang Xu , Huang Jihe , Wang Jin , Chen Yutong
Published: May 2022

Background: Cuproptosis is a novel mechanism of cell death induced by extra copper that was directly bound with the lipoylated proteins in the TCA cycle and could lead to the dysfunction of the mitochondrion. However, the impact of cuproptosis on TIME in colorectal cancer remains unclear. The investigation of the interplay between cuproptosis and TIME could help us decipher novel strategies for colorectal cancer diagnosis and treatment. This study aimed to construct a prognostic signature on immunotherapies and explore the novel patterns of the cuproptosis-related genes(CRGs) in colorectal cancer. Methods: All the analyses were performed by R packages. The biological roles and functional patterns of the CRGs were performed by GO/KEGG analysis. The signature was developed with the prognostic CRGs by LASSO COX regression analysis. TIMER algorithm was selected for the immune cell infiltration analysis and the OCLR algorithm was for calculating the stem cell index. Consensus analysis was used to explore the novel landscape of the CRGs in colorectal cancer. Results: The CRGs mainly participated in the process of the TCA cycle and energy metabolism in colorectal cancer. Five CRGs were identified with prognostic values and the correlation with immune infiltration was also demonstrated, meanwhile, two genes could be independent biomarkers for immunotherapies. By consensus analysis, the CRGs also showed a significant difference in stem cell characteristics.Conclusion: A comprehensive analysis of functional and immune infiltration of CRGs in colorectal cancer was performed. The results also provided evidence for revealing the vulnerabilities in the correlation between cuproptosis and TIME. More data from research trials and experiments are required.