Abstract
Motivation
While deep-learning algorithms have demonstrated outstanding performance in semantic image segmentation tasks, large annotation datasets are needed to create accurate models. ...Annotation of histology images is challenging due to the effort and experience required to carefully delineate tissue structures, and difficulties related to sharing and markup of whole-slide images.
Results
We recruited 25 participants, ranging in experience from senior pathologists to medical students, to delineate tissue regions in 151 breast cancer slides using the Digital Slide Archive. Inter-participant discordance was systematically evaluated, revealing low discordance for tumor and stroma, and higher discordance for more subjectively defined or rare tissue classes. Feedback provided by senior participants enabled the generation and curation of 20 000+ annotated tissue regions. Fully convolutional networks trained using these annotations were highly accurate (mean AUC=0.945), and the scale of annotation data provided notable improvements in image classification accuracy.
Availability and Implementation
Dataset is freely available at: https://goo.gl/cNM4EL.
Supplementary information
Supplementary data are available at Bioinformatics online.
This research was designed to find out the effect of different factors such as influence of lunar cycle, harvesting interval, rope type and seeding gap on the production of G. tenuistipitata in coast ...of Cox's Bazar. Duration of these experiments were sixty days and all the parameters were recorded fortnightly. Monitoring of water quality parameters indicated that salinity, temperature, transparency, pH and DO were suitable for seaweed cultivation. In determining lunar cycle effect, results envisaged that fresh yield was 14.43% increased when seeding and harvesting time was selected considering the moon cycle. Regarding the selection of harvesting interval, it was found that T
(30 days interval) was the best to harvest the seaweed whereas T
(40 days interval) showed decreasing trend in production. Our study also found that semi floating single line showed better yield performance compared to semi floating double line system. In case of influence on seeding gap, it has been found that 20 cm gap between two seed showed the highest yields followed by 10 cm, 30 cm and 40 cm, respectively. Overall, it can be concluded that yield of G. tenuistipitata in coast of Cox's Bazar could be improved considering those factors.
The massive meat production of broiler chickens make them continuously exposed to potential stressors that stimulate releasing of stress-related hormones like corticosterone (CORT) which is ...responsible for specific pathways in biological mechanisms and physiological activities. Therefore, this research was conducted to evaluate a wide range of responses related to broiler performance, immune function, plasma biochemistry, related gene expressions and cell death morphology during and after a 7-day course of CORT injection. A total number of 200 one-day-old commercial Cobb broiler chicks were used in this study. From 21 to 28 d of age, broilers were randomly assigned to one of 2 groups with 5 replicates of 20 birds each; the first group received a daily intramuscular injection of 5 mg/kg BW corticosterone dissolved in 0.5 ml ethanol:saline solution (CORT group), while the second group received a daily intramuscular injection of 0.5 ml ethanol:saline only (CONT group). Growth performance, including body weight (BW), daily weight gain (DG), feed intake (FI) and feed conversion ratio (FC), were calculated at 0, 3 and 7 d after the start of the CORT injections. At the same times, blood samples were collected in each group for hematological (TWBC's and H/L ratio), T- and B-lymphocytes proliferation and plasma biochemical assays (total protein, TP; free triiodothyronine hormone, fT3; aspartate amino transaminase, AST; and alanine amino transaminase, ALT). The liver, thymus, bursa of Fabricius and spleen were dissected and weighed, and the mRNA expression of insulin-like growth factor 1 gene (IGF-1) in liver and cell-death-program gene (caspase-9) in bursa were analyzed for each group and time; while the apoptotic/necrotic cells were morphologically detected in the spleen. From 28 to 35 d of age, broilers were kept for recovery period without CORT injection and the same sampling and parameters were repeated at the end (at 14 d after initiation of the CORT injection). In general, all parameters of broiler performance were negatively affected by the CORT injection. In addition, CORT treatment decreased the plasma concentration of fT3 and the mRNA expression of hepatic IGF-1. A significant increase in liver weight accompanied by an increase in plasma TP, AST and ALT was observed with CORT treatment, indicating an incidence of liver malfunction by CORT. Moreover, the relative weights of thymus, bursa and spleen decreased by the CORT treatment with low counts of TWBC's and low stimulation of T & B cells while the H/L ratio increased; indicating immunosuppressive effect for CORT treatment. Furthermore, high expression of caspase-9 gene occurred in the bursa of CORT-treated chickens, however, it was associated with a high necrotic vs. low apoptotic cell death pathway in the spleen. Seven days after termination of the CORT treatment in broilers, most of these aspects remained negatively affected by CORT and did not recover to its normal status. The current study provides a comprehensive view of different physiological modulations in broiler chickens by CORT treatment and may set the potential means to mount a successful defense against stress in broilers and other animals as well.
P-glycoprotein (P-gp) imparts multi-drug resistance (MDR) on the cancers cell and malignant tumor clinical therapeutics. We report a class of newly designed and synthesized oxygen-heterocyclic-based ...pyran analogues (4a-l) bearing different aryl/hetaryl-substituted at the 1-postion were synthesized, aiming to impede the P-gp function. These compounds (4a-l) have been tested against cancerous PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines as well as non-cancerous HFL-1 and WI-38 cell lines to determine their anti-proliferative potency.The findings demonstrated the superior potency of 4a-c with 4-F, 2-Cl, and 3-Cl derivatives and 4h,g with 4-NO
, 4-MeO derivatives against PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines.Compounds 4a-c were tested for P-gp inhibition and demonstrated significant vigour against MCF-7/ADR cells with IC
= 5.0-10.7 μM. The Rho123 accumulation assay showed that compounds 4a-c adequately inhibited P-gp function, as predicted. Furthermore, 4a or 4b administration resulted in MCF-7/ADR cell accumulation in the S phase, while compound 4c induced apoptosis by causing cell cycle arrest at G2/M. The molecular docking was applied to understand the likely modes of action and guide us in the rational design of more potent analogs. The investigate derivatives showed their good binding potential for p-gp active site with excellent docking scores and interactions. Finally, the majority of investigated derivatives 4a-c derivatives showed high oral bioavailability, but they did not cross the blood-brain barrier. These results suggest that they have favorable pharmacokinetic properties. Therefore, these compounds could serve as leads for designing more potent and stable drugs in the future.
Abstract
High-grade calcium aluminate cement (CAC) has been successfully synthesized from municipal alumina waste and limestone under mild reaction conditions. Mineralogical composition and ...microstructure of the sintered mixes were investigated using X-ray diffraction and FESEM; valuable cementing phases such as CA, CA
2
, and C
12
A
7
were observed in addition to the C
3
A phase that was detected in the mixes with high CaCO
3
content. Mix CA60 containing 60 wt% alumina waste has achieved the best sinterability (less than 1 vol% porosity) and the highest densification (~ 2.65 g/cm
3
bulk density) at 1450 °C. Densification, cold-crushing strength (CCS), and microstructure of the hydrated cement samples (From Mix CA60) were investigated. The cast cement specimens revealed better density and CCS characteristics (63.1 and 74 MPa at 7 and 28 days, respectively) in comparison with the commercial cement. Conventional castables (5 × 5 × 5 cm
3
) were prepared from mixtures composed of 15 wt% cement and 85 wt% aggregates (40% Al
2
O
3
), where CA60 and commercial cement were used to compare the effect of the manufactured CA60 cement with the commercial one. The castables prepared with CA60 cement have shown a higher strength at 110 °C with 4.5 MPa when compared to the commercial CAC at the same temperature (1.8 MPa). Accordingly, this study contributes not only to preserving the environment from the accumulation of industrial wastes but also to valorizing and adding value to these wastes.
While the functionality and healthy food value of red rice have increased its popularity, such that market demand for it is expected to rise, most strains suffer from low grain yield. To perform ...diversity and population structure analyses of red rice germplasm, therefore, becomes essential for improving yields for commercial production. In this study, fifty red rice germplasm from the Bangladesh Rice Research Institute (BRRI) genebank were characterized both morphologically and genetically using fifty simple sequence repeat (SSR) markers. Overall, 162 alleles were detected by the markers with the detected allele number varying from two to seven. Additionally, 22 unique alleles were identified for use as a germplasm diagnostic tool. The highest and lowest polymorphic information content (PIC) indices were 0.75 and 0.04 found in markers RM282 and RM304, respectively, and genetic diversity was moderate, varying from 0.05 to 0.78 (average: 0.35). While phylogenetic cluster analysis of the fifteen distance-based agro-morphological traits divided the germplasm into five clusters (I, II, III, IV and V), a similar SSR analysis yielded only three major groups (I, II, and III), and a model-based population structure analysis yielded four (A, B, C and D). Both principal component and neighbors joining tree analysis from the population structure method showed the tested germplasm as highly diverse in structure. Moreover, an analysis of molecular variance (AMOVA), as well as a pairwise FST analysis, both indicated significant differentiation (ranging from 0.108 to 0.207) among all pairs of populations, suggesting that all four population structure groups differed significantly. Populations A and D were the most differentiated from each other by FST. Findings from this study suggest that the diverse germplasm and polymorphic trait-linked SSR markers of red rice are suitable for the detection of economically desirable trait loci/genes for use in future molecular breeding programs.
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Nanotechnology has received much attention because of its distinctive properties and many applications in various fields. Nanotechnology is a new approach to increase agricultural ...production with premium quality, environmental safety, biological support, and financial stability. Ecofriendly technology is becoming progressively important in modern agricultural applications as alternatives to traditional fertilizers and pesticides. Nanotechnology offers an alternative solution to overcome the disadvantages of conventional agriculture. Therefore, recent developments in using nanoparticles (NPs) in agriculture should be studied. This review presented a novel overview about the biosynthesis of NPs, using NPs as nano-fertilizers and nano-pesticides, the applications of NPs in agriculture, and their role in enhancing the function of biofactors. We also, show recent studies on NPs-plant interactions, the fate and safety of nanomaterials in plants, and NPs' function in alleviating the adverse effects of abiotic stress and heavy metal toxicity. Nano-fertilizers are essential to reduce the use of inorganic fertilizers and reduce their antagonistic effects on the environment. Nano-fertilizers are more reactive, can penetrate the epidermis allowing for gradual release, and targeted distribution, and thus reducing nutrients surplus, enhancing nutrient use efficiency. We also, concluded that NPs are crucial in alleviating abiotic stress and heavy metal toxicity. However, some studies reported the toxic effects of NPs on higher plants by induction of oxidative stress signals via depositing NPs on the cell surface and in organelles. The knowledge in our review article is critical in defining limitations and future perspectives of using nano-fertilizers as an alternative to conventional fertilizers.
Alzheimer’s disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the ...potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl3) alone, AlCl3 with cocoa alone, AlCl3 with vinpocetine (VIN), AlCl3 with epigallocatechin-3-gallate (EGCG), AlCl3 with coenzyme Q10 (CoQ10), AlCl3 with wheatgrass (WG), AlCl3 with vitamin (Vit) B complex, and AlCl3 with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3β/β-catenin signaling, ER stress, autophagy, and apoptosis. AlCl3 administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1β) and GSK-3β, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/β-catenin pathway. Furthermore, AlCl3 intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl3-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3β-Wnt/β-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways.
Four new nicotinamide-based derivatives were designed as antiangiogenic VEGFR-2 inhibitors. The congeners were synthesized possessing the pharmacophoric essential features to bind correctly with the ...VEGFR-2 active pocket. All members were evaluated for their cytotoxic and VEGFR-2 inhibitory potentialities. Compound 6 was the most potent showingIC50 values of 9.3 ± 0.02 and 7.8 ± 0.025 µM against HCT-116 and HepG-2 cells, respectively, and IC50 of 60.83 nM regarding VEGFR-2 enzyme inhibition. Compound 6 arrested the growth of HCT-116 cells at the pre-G1 and G2-M phases. Further, it induced both early and late apoptosis. Additionally, compound 6 caused a significant decrease in TNF-α and IL6 by 66.42% and 57.34%, respectively. The considered compounds had similar docking performances to that of sorafenib against the VEGFR-2 (PDB ID: 2OH4). The correct binding of compound 6 with VEGFR-2 was validated using MD simulations, and MM-GPSA calculations.
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