Miracle-dz/UniFAR-FTUs huggingface dataset:
Tannins of Rosaceus Medicinal Plants. V. : Hydrolyzable Tannins with Dehydrodigalloyl Group from Rosa laevigata MICHX.

Four new hydrolyzable tannins, laevigatins A-D, were isolated from Rosa laevigata, a Chinese medicinal plant.Among them, laevigatin B, laevigatin C and laevigatin D, were dimeric ellagitannins closely related to agrimoniin, which has a dehydrodigalloyl group in the molecule. Nine known tannins, including agrimoniin and agrimonic acids A and B, were also isolated. Structures of new tannins were assigned on the basis of proton and carbon-13 nuclear magnetic resonance spectral data, and chemical conversion of agrimonic acid A to laevigatin A, and of agrimoniin to laevigatins B and C.
Effect of Ce on resistivity of Sn-3.8Ag-0.7Cu-xCe lead-free solders

Abstract The electrical resistivity of Sn-3.8Ag-0.7Cu-xCe (x takes 0, 0.2, 0.5 and 1.0 weight per cent) alloy as a function of temperature was measured by DC four-probe technique. Abnormal changes occurred on the resistivity–temperature (ρ–T) curves above the liquidus, which suggested that the temperature-induced liquid–liquid structure transition probably occurred in Sn-3.8Ag-0.7Cu-xCe melt, with some reversible characters. With the increasing of Ce, the melting range was expanded from 13.0°C to 24.2°C, and the resistivity increased sharply when the Ce composition increased to 0.2%, and then declined slightly. In addition, the temperature and behaviour of abnormal zone were affected by the different additions of Ce.
Physiological parameter values for physiologically based pharmacokinetic models in food‐producing animals. Part II: Chicken and turkey

Abstract Physiologically based pharmacokinetic (PBPK) models are growing in popularity due to human food safety concerns and for estimating drug residue distribution and estimating withdrawal intervals for veterinary products originating from livestock species. This paper focuses on the physiological and anatomical data, including cardiac output, organ weight, and blood flow values, needed for PBPK modeling applications for avian species commonly consumed in the poultry market. Experimental and field studies from 1940 to 2019 for broiler chickens (1–70 days old, 40 g ‐ 3.2 kg), laying hens (4–15 months old, 1.1–2.0 kg), and turkeys (1 day−14 months old, 60 g −12.7 kg) were searched systematically using PubMed, Google Scholar, ProQuest, and ScienceDirect for data collection in 2019 and 2020. Relevant data were extracted from the literature with mean and standard deviation (SD) being calculated and compiled in tables of relative organ weights (% of body weight) and relative blood flows (% of cardiac output). Trends of organ or tissue weight growth during different life stages were calculated when sufficient data were available. These compiled data sets facilitate future PBPK model development and applications, especially in estimating chemical residue concentrations in edible tissues to calculate food safety withdrawal intervals for poultry.
Modulation Effects of Toxoplasma gondii Histone H2A1 on Murine Macrophages and Encapsulation with Polymer as a Vaccine Candidate

Toxoplasma gondii (T. gondii) is the most common zoonotic protozoa and has infected about one-third of the population worldwide. Recombinant epitopes encapsulated in nanospheres have advantages over traditional T. gondii vaccines. For an efficient delivery system, poly (DL-lactide-co-glycolide) (PLGA) and chitosan are the most frequently used biodegradable polymeric nanospheres with strong safety profiles. In the present study, we first expressed and purified histone H2A1 of T. gondii using the prokaryotic expression system. The effects of recombinant TgH2A1 on the functions of murine macrophages were then studied. Purified recombinant TgH2A1 was then encapsulated in nanospheres with PLGA and chitosan. After subcutaneous vaccination in mice, the immune response was evaluated by double antibody sandwich ELISA kits. The results from this study showed that PLGA and chitosan loaded with rTgH2A1 could trigger a stronger Th1 oriented immune response and prolong the survival time of mice effectively. In conclusion, PLGA and chitosan nanospheres loaded with histone H2A1 are an effective method for the development of vaccines against T. gondii. Further studies should focus on evaluating the regulatory mechanism of TgH2A1, vaccine potency, and cellular response in chronic T. gondii infections.
Serum Levels of Glutamate-Pyruvate Transaminase, Glutamate-Oxaloacetate Transaminase and Gamma-Glutamyl Transferase in 1494 Patients with Various Genotypes for the Alpha-1 Antitrypsin Gene

Background: Patients with liver disease associated with alpha-1 antitrypsin deficiency (AATD) are homozygous for the Z mutation, leading to chronic liver damage. Objective: To assess the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and gamma-glutamyl transpeptidase (GGT) in patients with different genotypes for the alpha-1 antitrypsin (AAT) gene. Methods: Patients (n = 1494) underwent genotyping of the SERPINA1 gene, together with a determination of AAT and GOT and GPT and GGT transaminase levels. Patients with a deficient allele (n = 476) and with a normal genotype were compared. Results: A statistically significant association was found between deficient genotypes and GOT (p < 0.0003), GPT (p < 0.002), and GGT (p < 0.006). Comparing GOT levels in patients with PI*Z deficient variant versus those with normal genotype, an odds ratio (OR) of 2.72 (CI: 1.5–4.87) (p < 0.0005) was obtained. This finding was replicated with the PI*Z allele and the GPT values (OR = 2.31; CI: 1.45–3.67; p < 0.0003). In addition, a statistically significant association was found between liver enzymes and AAT values. Conclusion: The PI*Z allele seemed to be a risk factor for the development of liver damage. AAT deficient genotypes were associated with GOT, GPT, and GGT altered values. Low AAT levels were associated with high GPT and GGT levels.
A 20‐residue peptide of the inner membrane protein OutC mediates interaction with two distinct sites of the outer membrane secretin OutD and is essential for the functional type II secretion system in Erwinia chrysanthemi

The type II secretion system (T2SS) is widely exploited by proteobacteria to secrete enzymes and toxins involved in bacterial survival and pathogenesis. The outer membrane pore formed by the secretin OutD and the inner membrane protein OutC are two key components of the secretion complex, involved in secretion specificity. Here, we show that the periplasmic regions of OutC and OutD interact directly and map the interaction site of OutC to a 20‐residue peptide named OutCsip (secretin interacting peptide, residues 139–158). This peptide interacts in vitro with two distinct sites of the periplasmic region of OutD, one located on the N0 subdomain and another overlapping the N2‐N3′ subdomains. The two interaction sites of OutD have different modes of binding to OutCsip. A single substitution, V143S, located within OutCsip prevents its interaction with one of the two binding sites of OutD and fully inactivates the T2SS. We show that the N0 subdomain of OutD interacts also with a second binding site within OutC located in the region proximal to the transmembrane segment. We suggest that successive interactions between these distinct regions of OutC and OutD may have functional importance in switching the secretion machine.
ACTINOBACTERIAL PIGMENT ASSISTED SYNTHESIS OF NANOPARTICLES AND ITS BIOLOGICAL ACTIVITY

Recently, the green synthesis of nanoparticles has gained considerable attention due to its benefits such as cost efficiency, simplicity, eco-friendly nature, biocompatibility and broad applications over conventional chemical and physical techniques. In this context twenty actinobacteria were isolated from the rhizospheric soil of wild carrot and screened for their pigment producing ability. These isolates belong to the genus Streptomyces (58%), followed by Streptosporangium sp. (19%), Nocardia sp. (11%), Actinomadura sp. (8%), and Micromonospora sp. (4%). The most promising isolate (NS-05) producing the pink pigment has been taken for the synthesis of silver nanoparticles. The isolate NS-05 was identified as Streptomyces sp. based on cultural characteristics and 16S rDNA sequence analysis. It was most closely related with type strain Streptomyces fulvissimus DSM 40593T, S. microflavus NBRC13062T, S. setonii NRRL ISP-5322T, S. anulatus RRL B-2000T with a sequence similarity of 95.6% which shows that it may belong to novel species of Streptomyces. The bio-pigment assisted synthesized nanoparticles were characterized using UV-Vis, FTIR and Scanning electron microscopy studies. The average size of synthesized silver nanoparticles was 42.5nm and has λ max at 433 nm. The synthesized nanoparticles showed promising activity against major pathogens like Staphylococcus aureus MTCC 2940, Bacillus subtilis MTCC 441 Salmonella typhi, Proteus vulgaris MTCC 6380, Escherichia coli MTCC 739. The findings of present research are promising, and this pigment can also be used for the green synthesis of other nanoparticles.
Maximizing Participant and Staff Safety During Assessment of Physical Function in the COVID‐19 Era

Physical performance measures, including cardiopulmonary exercise testing (CPXT), are widely used in geriatric practice and aging research. Theoretically, research participants and study personnel could get infected in the closed environment of the exercise laboratory by contact with respiratory droplets from an infected person, by breathing virus‐laden aerosols, or by touching fomites. Older adults are at increased risk of developing more severe disease and of dying from SARS‐CoV‐2 infection. This special article offers guidance—informed by a synthesis of scientific data and recommendations of the CDC and WHO—on procedures that can be implemented in exercise laboratories to minimize risk of SARS‐CoV‐2 and other respiratory infections. Most tests of physical function (e.g., gait speed, Short Physical Performance Battery) are not aerosol‐generating and are associated with only a small increase in minute ventilation; in contrast, CPXT markedly increases minute ventilation and is potentially aerosol‐generating. Researchers should evaluate the benefit‐to‐risk ratio of information gained from the laboratory assessment versus the risk of SARS‐CoV2 infection. Risk mitigation strategies described here fall into four categories: personal hygiene and the use of personal protective equipment; standardized screening; reconfiguration of laboratory space; and optimization of laboratory ventilation. The proposed safety measures are not intended to replace institutional policy, state, or federal guidelines; they may not apply to all settings and are expected to evolve as more definitive information becomes available. These practical measures to maximize protection against SARS‐CoV2 infection can help maximize participant and staff safety, reduce anxiety, and facilitate protocol adherence, and study integrity.
A Discretization Approach for the Nonlinear Fractional Logistic Equation

The present study aimed to develop and investigate the local discontinuous Galerkin method for the numerical solution of the fractional logistic differential equation, occurring in many biological and social science phenomena. The fractional derivative is described in the sense of Liouville-Caputo. Using the upwind numerical fluxes, the numerical stability of the method is proved in the L∞ norm. With the aid of the shifted Legendre polynomials, the weak form is reduced into a system of the algebraic equations to be solved in each subinterval. Furthermore, to handle the nonlinear term, the technique of product approximation is utilized. The utility of the present discretization technique and some well-known standard schemes is checked through numerical calculations on a range of linear and nonlinear problems with analytical solutions.
Levels of proinflammatory chemokines and advanced glycation end products in patients with type-2 diabetes mellitus undergoing fixed orthodontic treatment.

OBJECTIVES To explore the effect of diabetic status on the proinflammatory chemokine profile and levels of advanced glycation end products (AGEs) in gingival crevicular fluid (GCF) derived from patients with type 2 diabetes mellitus (T2DM) undergoing fixed orthodontic treatment. MATERIALS AND METHODS Two groups, nondiabetic and T2DM, were included. Their demographics, biochemical parameters including hemoglobin A1c, fasting blood glucose, body mass index, and oral hygiene status were recorded. GCF sampling was performed after 2 months of placement of stainless steel archwires and chemokines (primary outcome) were quantified using Human Magnetic Luminex multiplex assay. Secondary outcomes were assessment of clinical periodontal status, unstimulated whole saliva flow rate, and GCF flow rate. RESULTS Twenty participants each in the nondiabetic (mean age: 26.4 years) and T2DM (mean age: 27.2 years) groups gave consent to participate. Biochemical analysis showed significantly increased values for hemoglobin A1c (P < .001), fasting blood glucose (P < .0001), body mass index(P = .047), and unstimulated whole saliva flow rate (P = .041) for the T2DM group. Bleeding on probing was significantly higher in participants with T2DM than nondiabetic participants (P = .039). Resistin (P = .034) and AGEs (P = .017) showed significantly higher values in participants with T2DM than nondiabetic participants. Pearson correlation analysis indicated a significant positive correlation between resistin (r = 0.1372; P = .022) and AGEs (r = 0.0194; P = .0186) against bleeding on probing in participants with T2DM. CONCLUSIONS The biochemical profile of GCF samples from participants with T2DM after alignment demonstrated higher levels of resistin and AGEs. The data suggest the presence of a proinflammatory response in patients with T2DM undergoing fixed orthodontic treatment.
An Improved HRPE-Based Transcriptional Output Reporter to Detect Hypoxia and Anoxia in Plant Tissue

Oxygen levels in plant tissues may vary, depending on metabolism, diffusion barriers, and environmental availability. Current techniques to assess the oxic status of plant cells rely primarily on invasive microoptodes or Clark-type electrodes, which are not optimally suited for experiments that require high spatial and temporal resolution. In this case, a genetically encoded oxygen biosensor is required instead. This article reports the design, test, and optimization of a hypoxia-signaling reporter, based on five-time repeated hypoxia-responsive promoter elements (HRPE) driving the expression of different reporter proteins. Specifically, this study aimed to improve its performance as a reporter of hypoxic conditions by testing the effect of different untranslated regions (UTRs) at the 5′ end of the reporter coding sequence. Next, we characterized an optimized version of the HRPE promoter (HRPE-Ω) in terms of hypoxia sensitivity and time responsiveness. We also observed that severe oxygen deficiency counteracted the reporter activity due to inhibition of GFP maturation, which requires molecular oxygen. To overcome this limitation, we therefore employed an oxygen-independent UnaG fluorescent protein-coupled to an O2-dependent mCherry fluorophore under the control of the optimized HRPE-Ω promoter. Remarkably, this sensor, provided a different mCherry/UnaG ratiometric output depending on the externally imposed oxygen concentration, providing a solution to distinguish between different degrees of tissue hypoxia. Moreover, a ubiquitously expressed UnaG-mCherry fusion could be used to image oxygen concentrations directly, albeit at a narrow range. The luminescent and fluorescent hypoxia-reporters described here can readily be used to conduct studies that involve anaerobiosis in plants.
PAMAM G4.5 dendrimers for targeted delivery of ferulic acid and paclitaxel to overcome P‐glycoprotein‐mediated multidrug resistance

In this study, we prepared ferulic acid (FA) and paclitaxel (PTX) co‐loaded polyamidoamine (PAMAM) dendrimers conjugated with arginyl–glycyl–aspartic acid (RGD) to overcome P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR). FA was released in greater extent (80%) from the outer layer of the dendrimers compared with PTX (70%) from the interior of the dendrimers. FA improved intracellular availability of PTX via P‐gp modulation in drug‐resistant cells. In vitro drug uptake data show higher PTX delivery with RGD–PAMAM–FP than with PAMAM–FP in drug resistant KB CH‐R 8‐5 cell lines. This indicates that RGD facilitates intracellular PTX accumulation through active targeting in multidrug‐resistant KB CH‐R 8‐5 cells. The terminal deoxynucleotidyl transferase 2ʹ‐deoxyuridine 5ʹ‐triphosphate nick‐end labeling assay data and membrane potential analysis in mitochondria confirm the enhanced anticancer potential of RGD–PAMAM–FP nanoaggregates in drug‐resistant cells. We also confirmed by the increased protein levels of proapoptotic factors such as caspase 3, caspase 9, p53, and Bax after treatment with RGD–PAMAM–FP nanoaggregates and also downregulates antiapoptotic factors. Hence, FA–PTX co‐loaded, RGD‐functionalized PAMAM G4.5 dendrimers may be considered as an effective therapeutic strategy to induce apoptosis in P‐gp‐overexpressing, multidrug‐resistant cells.
Cannabinoid receptors are differentially regulated in the pancreatic islets during the early development of metabolic syndrome

ABSTRACT The endocannabinoid system is found in tissues that regulate the glycemia, including adipose tissue, muscle, and pancreatic islets. Diet-induced metabolic syndrome changes the expression of the CB receptors in muscle, adipose tissue, and liver. However, it is poorly understood whether metabolic syndrome (MetS) affects the expression of CB receptors in pancreatic β cells. We analyzed the expression of CB receptors in pancreatic β cells under chronic high-sucrose diet (HSD)-induced MetS. Wistar rats fed an HSD as a model of MetS were used to investigate changes in cannabinoid receptors. After 8 weeks of treatment, we evaluated the appearance of the following MetS biomarkers: glucose intolerance, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and an increase in visceral adiposity. To determine the presence of CB1 and CB2 receptors in pancreatic β cells, immunofluorescence of primary cell cultures and pancreatic sections was performed. For whole-islet quantification of membrane-bound CB1 and CB2 receptors, western-blotting following differential centrifugation was conducted. Our results revealed that an HSD treatment closely mimics the alterations seen in MetS. We observed that in primary cell culture, CB1 and CB2 receptors were expressed at a higher level in pancreatic β cells compared with non-β cells. MetS resulted in a reduction of CB1 in the islet, whereas abundant CB2 was observed after the treatment. CB1 and CB2 receptors are differentially expressed in pancreatic β cells during MetS development.
Integration of diverse DNA substrates by a casposase can be targeted to R-loops in vitro by its fusion to Cas9

Abstract CRISPR systems build adaptive immunity against mobile genetic elements by DNA capture and integration catalysed by Cas1–Cas2 protein complexes. Recent studies suggested that CRISPR repeats and adaptation module originated from a novel type of DNA transposons called casposons. Casposons encode a Cas1 homologue called casposase that alone integrates into target molecules single and double-stranded DNA containing terminal inverted repeats (TIRs) from casposons. A recent study showed Methanosarcina mazei casposase is able to integrate random DNA oligonucleotides, followed up in this work using Acidoprofundum boonei casposase, from which we also observe promiscuous substrate integration. Here we first show that the substrate flexibility of Acidoprofundum boonei casposase extends to random integration of DNA without TIRs, including integration of a functional gene. We then used this to investigate targeting of the casposase-catalysed DNA integration reactions to specific DNA sites that would allow insertion of defined DNA payloads. Casposase–Cas9 fusions were engineered that were catalytically proficient in vitro and generated RNA-guided DNA integration products from short synthetic DNA or a gene, with or without TIRs. However, DNA integration could still occur unguided due to the competing background activity of the casposase moiety. Expression of Casposase-dCas9 in Escherichia coli cells effectively targeted chromosomal and plasmid lacZ revealed by reduced β-galactosidase activity but DNA integration was not detected. The promiscuous substrate integration properties of casposases make them potential DNA insertion tools. The Casposase–dCas9 fusion protein may serves as a prototype for development in genetic editing for DNA insertion that is independent of homology-directed DNA repair.
Modelling Left Atrial Flow and Blood Coagulation for Risk of Thrombus Formation in Atrial Fibrillation

Atrial fibrillation (AF) diminishes left atrial (LA) mechanical function and impairs blood flow. The latter can lead to blood stasis and increased risk of thrombus formation and stroke. We investigate this risk by studying the effects of LA flow in sinus rhythm (SR) and AF on blood coagulation dynamics. Patient-specific computational fluid dynamics (CFD) simulations were coupled with the reaction-diffusion-convection equation for thrombin. Patient LA wall motions driving the flow were reconstructed from Cine MRI data during SR and AF. 15 cardiac cycles were simulated for each patient to evaluate the likelihood of thrombus formation in the critical left atrial appendage (LAA) and right inferior pulmonary vein (RIPV) regions. The simulations showed that mean blood flow velocity in the LA cavity was substantially decreased (47%) during AF compared to SR. Specifically in LAA, mean flow velocities decreased from 0.06m/s in SR to 0.035m/s in AF, leading to enhanced thrombin generation. In the RIPV, higher mean flow velocities (0.16m/s) enabled thrombin washout through the mitral valve irrespective of SR or AF. This study proposes a novel modelling approach for quantifying the likelihood of AF-related thrombogenesis within LA and demonstrates increased risk of thrombus formation in the LAA when compared with the RIPV.
Direct visualization of translational GTPase factor pool formed around the archaeal ribosomal P-stalk by high-speed AFM

Significance Translation of genetic information by the ribosome is a core biological process in all organisms. The ribosomal stalk is a multimeric ribosomal protein complex which plays an essential role in translation elongation. However, the working mechanism of the ribosomal stalk still remains unclear. In this study, we applied HS-AFM to investigate the working mechanism of the archaeal ribosomal P-stalk. HS-AFM movies demonstrate that the P-stalk collects two translational GTPase factors (trGTPases), aEF1A and aEF2, and increases their local concentration near the ribosome. These direct visual evidences show that the multiple arms of the ribosomal P-stalk catch the trGTPases for efficient protein synthesis in the crowded intracellular environment.