Notes

Shows regarding applicant ingredients inside Justicia and its anti-thrombotic activity involving system based on system pharmacology strategy as well as experimental validation.
Photon-counting detector computed tomography (PCD-CT) is a modern spectral imaging technique utilizing photon-counting detectors (PCDs). PCDs detect individual photons and classify them into fixed energy bins, thus enabling energy selective imaging, contrary to energy integrating detectors that detects and sums the total energy from all photons during acquisition. The structure and composition of the articular cartilage cannot be detected with native CT imaging but can be assessed using contrast-enhancement. Spectral imaging allows simultaneous decomposition of multiple contrast agents, which can be used to target and highlight discrete cartilage properties. Here we report, for the first time, the use of PCD-CT to quantify a cationic iodinated CA4+ (targeting proteoglycans) and a non-ionic gadolinium-based gadoteridol (reflecting water content) contrast agents inside human osteochondral tissue (n = 53). We performed PCD-CT scanning at diffusion equilibrium and compared the results against reference data of biomechanical and optical density measurements, and Mankin scoring. PCD-CT enables simultaneous quantification of the two contrast agent concentrations inside cartilage and the results correlate with the structural and functional reference parameters. With improved soft tissue contrast and assessment of proteoglycan and water contents, PCD-CT with the dual contrast agent method is of potential use for the detection and monitoring of osteoarthritis.Capturing movement of animals in mathematical models has long been a keenly pursued direction of research1. Any good model of animal movement is built upon information about the animal's environment and the available resources including whether prey is in abundance or scarce, densely distributed or sparse2. Such an approach could enable the identification of certain quantities or measures from the model that are species-specific characteristics. We propose here a mechanistic model to describe the movement of two species of Asian hornbills in a resource-abundant heterogenous landscape which includes degraded forests and human settlements. Hornbill telemetry data was used to this end. The birds show a bias both towards features of attraction such as nesting and roosting sites as well as possible bias away from points of repulsion such as human presence. These biases are accounted for with suitable potentials. The spatial patterns of movement are analyzed using the Fokker-Planck equation, which helps explain the variation in movement of different individuals. Search times to target locations were calculated using first passage time equations dual to the Fokker-Planck equations. We also find that the diffusion coefficients are larger for breeding birds than for non-breeding ones-a manifestation of repeated switching of directions to move back to the nest from foraging sites. The degree of directedness towards nests and roosts is captured by the drift coefficients. Non-breeding hornbills show similar values of the ratio of the two coefficients irrespective of the fact that their movement data is available from different seasons. Therefore, the ratio of drift to diffusion coefficients is indicative of an individual's breeding status, as seen from available data. It could possibly also characterize different species. For all individuals, first passage times increase with proximity to human settlements, in agreement with the premise that anthropogenic activities close to nesting/roosting sites are not desirable.The COVID-19 caused by the SARS-CoV-2 virus was declared a pandemic disease in March 2020 by the World Health Organization (WHO). Structure-Based Drug Design strategies based on docking methodologies have been widely used for both new drug development and drug repurposing to find effective treatments against this disease. In this work, we present the developments implemented in the DockThor-VS web server to provide a virtual screening (VS) platform with curated structures of potential therapeutic targets from SARS-CoV-2 incorporating genetic information regarding relevant non-synonymous variations. The web server facilitates repurposing VS experiments providing curated libraries of currently available drugs on the market. At present, DockThor-VS provides ready-for-docking 3D structures for wild type and selected mutations for Nsp3 (papain-like, PLpro domain), Nsp5 (Mpro, 3CLpro), Nsp12 (RdRp), Nsp15 (NendoU), N protein, and Spike. We performed VS experiments of FDA-approved drugs considering the therapeutic targets available at the web server to assess the impact of considering different structures and mutations to identify possible new treatments of SARS-CoV-2 infections. The DockThor-VS is freely available at www.dockthor.lncc.br .The present study was set out to investigate two-dimensional (2D) and three-dimensional (3D) evaluations of ovarian nervous network development and the structural relationship between folliculogenesis and gangliogenesis in mouse ovaries. Adult mice ovarian tissue samples were collected from follicular and luteal phases after cardiac perfusion. Ovarian samples were stained by a Golgi-Cox protocol. Following staining, tissues were serially sectioned for imaging. Neural filaments and ganglia were present in the ovaries. In both 2D and 3D studies, an increase in the number and area of ganglia was seen during the follicular growth. The same pattern was also seen in corpora lutea development. However, in some cases such as ratio of ganglia number to follicle area, the ratio of ganglia area to follicular area, 2D findings were different compared with the 3D results. 3D analysis of ovarian gangliogenesis showed the possible direct effect of them on folliculogenesis. Golgi-Cox staining was used in this study for 3D evaluation in non-brain tissue. The results of 3D analysis of the present study showed that, in some cases, the information provided by 2D analysis does not match the reality of ovarian neuronal function. This confirmed the importance of 3D analysis for evaluation of ovarian function.Coagulation Factor XIa (FXIa) is an emerging target for antithrombotic agent development. The M358R variant of the serpin alpha-1 antitrypsin (AAT) inhibits both FXIa and other proteases. Our aim was to enhance the specificity of AAT M358R for FXIa. We randomized two AAT M358R phage display libraries at reactive centre loop positions P13-P8 and P7-P3 and biopanned them with FXIa. A bacterial expression library randomized at P2'-P3' was also probed. Resulting novel variants were expressed as recombinant proteins in E. coli and their kinetics of FXIa inhibition determined. The most potent FXIa-inhibitory motifs were P13-P8, HASTGQ; P7-P3, CLEVE; and P2-P3', PRSTE (respectively, novel residues bolded). Selectivity for FXIa over thrombin was increased up to 34-fold versus AAT M358R for these single motif variants. Combining CLEVE and PRSTE motifs in AAT-RC increased FXIa selectivity for thrombin, factors XIIa, Xa, activated protein C, and kallikrein by 279-, 143-, 63-, 58-, and 36-fold, respectively, versus AAT M358R. AAT-RC lengthened human plasma clotting times less than AAT M358R. AAT-RC rapidly and selectively inhibits FXIa and is worthy of testing in vivo. AAT specificity can be focused on one target protease by selection in phage and bacterial systems coupled with combinatorial mutagenesis.Control of stage specific spike in ethylene production at anthesis has been a vauable route to potentially enhance genetic ceiling for grain filling of rice spikelet. A number of genes controlling ethylene homeostasis and starch synthesis have been identified so long, but lack of credible information on master modulation of gene expression by miRNAs and their target genes associated with hormonal dynamics obfuscate mechanisms controlling genotype difference in quantum of grain filling. The confusion accounts for consequent shrinkage of options for yield manipulation. In a two by two factorial design, miRNA regulation of spikelet specific grain development in low against high sterile recombinant inbred lines of rice Oryza sativa L. namely CR 3856-62-11-3-1-1-1-1-1-1 (SR 157) and CR 3856-63-1-1-1-1-1-1-1 (SR 159) respectively, and inferior verses superior spikelets were compared during first 10 days after anthesis. Grain filling was poorer in SR159 than SR157 and inferior spikelets in the former were most vulnemore robust for the latter.Perfluorocarbons (PFCs) exhibiting high solubility for oxygen are attractive materials as artificial oxygen carriers (AOC), an alternative to whole blood or Haemoglobin-based oxygen carriers (HBOCs). PFC-based AOCs, however, met clinical translation roadblocks due to product quality control challenges. To overcome these issues, we present an adaptation of Quality by Design (QbD) practices to optimization of PFC nanoemulsions (PFC-NEs) as AOCs. QbD elements including quality risk management, design of experiments (DoE), and multivariate data analysis facilitated the identification of composition and process parameters that strongly impacted PFC colloidal stability and oxygen transport function. Resulting quantitative relationships indicated a composition-driven tradeoff between stability and oxygen transport. It was found that PFC content was most predictive of in vitro oxygen release, but the PFC type (perfluoro-15-crown-5-ether, PCE or perfluorooctyl bromide, PFOB) had no effect on oxygen release. Furthermore, we found, under constant processing conditions, all PFC-NEs, comprised of varied PFC and hydrocarbon content, exhibited narrow droplet size range (100-150 nm) and narrow size distribution. Representative PFOB-NE maintained colloidal attributes upon manufacturing on larger scale (100 mL). QbD approach offers unique insights into PFC AOC performance, which will overcome current product development challenges and accelerate clinical translation.Acute appendicitis (AA) is the first cause of emergency surgery. Leucine-Rich Alpha-2-Glycoprotein 1 (LRG1) has been shown to be a potential biomarker in cases of AA in children, but there are conflicting results for its use in adults. The objective of this study is to compare the median plasma values of LRG1 in patients with acute abdomen with and without appendicitis. This case-control study was conducted prospectively at the emergency room (ER) of a tertiary teaching hospital, between March 1st, 2011 and December 31st, 2012. Patients with recent abdominal pain, aged 18-70 years who attended at the ER were included in the study. Blood samples were drawn at the first presentation. Those who were submitted to surgery and had a pathology report of AA were considered as cases. Those without a need for surgery and treated for other conditions, e.g., pelvic inflammatory disease, were considered as controls. Derazantinib Follow-up in controls was made up to 30 days. LRG1 plasma median values were measured using an ELISA kit and compared between groups. A total of 28 participants, 14 cases with acute appendicitis and 14 controls, were included. The median (range) values of leucine-rich alpha-2-glycoprotein-1 level in the group with appendicitis and control group were 8.8 ng/ml (5.5-31) and 11 (4.6-108) ng/ml, respectively (Mann-Whitney test P = 0.26). Median plasma leucine-rich alpha-2-glycoprotein-1 levels were not useful in diagnosing Acute Appendicitis in patients with acute abdominal pain.
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