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Differences across fields and experience levels are frequently considered in discussions of ethical decision making and ethical behavior. In the present study, doctoral students in the health, biological, and social sciences completed measures of ethical decision making. The effects of field and level of experience with respect to ethical decision making, metacognitive reasoning strategies, social-behavioral responses, and exposure to unethical events were examined. Social and biological scientists performed better than health scientists with respect to ethical decision making. Furthermore, the ethical decision making of health science students decreased as experience increased. Moreover, these effects appeared to be linked to the specific strategies underlying participants' ethical decision making. The implications of these findings for ethical decision making are discussed. [ABSTRACT FROM AUTHOR]

In recent years, we have seen a new concern with ethics training for research and development professionals. Although ethics training has become more common, the effectiveness of the training being provided is open to question. In the present effort, a new ethics training course was developed that stresses the importance of the strategies people apply to make sense of ethical problems. The effectiveness of this training was assessed in a sample of 59 doctoral students working in the biological and social sciences using a pre-post design with follow-up and a series of ethical decision-making measures serving as the outcome variable. Results showed not only that this training led to sizable gains in ethical decision making but also that these gains were maintained over time. The implications of these findings for ethics training in the sciences are discussed. [ABSTRACT FROM AUTHOR]

It is commonly held that early career experiences influence ethical behavior. One way early career experiences might operate is to influence the decisions people make when presented with problems that raise ethical concerns. To test this proposition, 102 first-year doctoral students were asked to complete a series of measures examining ethical decision making along with a series of measures examining environmental experiences and climate perceptions. Factoring of the environmental measure yielded five dimensions: professional leadership, poor coping, lack of rewards, limited competitive pressure, and poor career direction. Factoring of the climate inventory yielded four dimensions: equity, interpersonal conflict, occupational engagement, and work commitment. When these dimensions were used to predict performance on the ethical decision-making task, it was found that the environmental dimensions were better predictors than the climate dimensions. The implications of these findings for research on ethical conduct are discussed. [ABSTRACT FROM AUTHOR]

Ethical decision making measures are widely applied as the principal dependent variable used in studies of research integrity. However, evidence bearing on the internal and external validity of these measures is not available. In this study, ethical decision making measures were administered to 102 graduate students in the biological, health, and social sciences, along with measures examining exposure to ethical breaches and the severity of punishments recommended. The ethical decision making measure was found to be related to exposure to ethical events and the severity of punishments awarded. The implications of these findings for the application of ethical decision making measures are discussed. [ABSTRACT FROM AUTHOR]

Background: Our objective was to assess the association of completeness and level of spinal cord injury (SCI) with the need for tracheostomy and identify additional risk factors predictive of tracheostomy., Methods: This was a retrospective review of patients with SCI between January 2017 and December 2022., Results: Patients with complete SCI were roughly thirty-three times more likely to have a tracheostomy when compared to incomplete injury (82 ​% vs 12 ​%, p ​< ​0.001, OR ​= ​32.9). The rate of tracheostomy did not differ between spinal cord levels for complete (p ​= ​0.68) or incomplete (p ​= ​0.08) injuries. Penetrating injury, low GCS, high ISS, and polytrauma were associated with tracheostomy need in incomplete SCI., Conclusion: Complete injury was statistically significantly associated with the need for tracheostomy while level of injury failed to reach significance. Patients with incomplete SCI that have certain clinical risk factors should be considered for early tracheostomy., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The resident microbiota are a key component of a healthy organism. The vast majority of microbiome studies have focused on bacterial members, which constitute a significant portion of resident microbial biomass. Recent studies have demonstrated how the fungal component of the microbiota, or the mycobiome, influences mammalian biology despite its low abundance compared to other microbes. Fungi are known for their pathogenic potential, yet fungi are also prominent colonizers in healthy states, highlighting their duality. We summarize the characteristics that define the gut mycobiome across life, the factors that can impact its composition, and studies that identify mechanisms of how fungi confer health benefits. The goal of this review is to synthesize our knowledge regarding the composition and function of a healthy mycobiome with a view to inspiring future therapeutic advances., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

ABC toxin complexes are a class of protein toxin translocases comprised of a multimeric assembly of protein subunits. Each subunit displays a unique composition, contributing to the formation of a syringe-like nano-machine with natural cargo carrying, targeting, and translocation capabilities. Many of these toxins are insecticidal, drawing increasing interest in agriculture for use as biological pesticides. The A subunit (TcA) is the largest subunit of the complex and contains domains associated with membrane permeation and targeting. The B and C subunits, TcB and TcC, respectively, package into a cocoon-like structure that contains a toxic peptide and are coupled to TcA to form a continuous channel upon final assembly. In this review, we outline the current understanding and gaps in the knowledge pertaining to ABC toxins, highlighting seven published structures of TcAs and how these structures have led to a better understanding of the mechanism of host tropism and toxin translocation. We also highlight similarities and differences between homologues that contribute to variations in host specificity and conformational change. Lastly, we review the biotechnological potential of ABC toxins as both pesticides and cargo-carrying shuttles that enable the transport of peptides into cells.

Background: Panax quinquefolius L, widely recognized for its valuable contributions to medicine, has aroused considerable attention globally. Different from the extensive research has been dedicated to the root of P. quinquefolius , its berry has received relatively scant focus. Given its promising medicinal properties, this study was focused on the structural characterizations and anti-inflammatory potential of acidic polysaccharides from the P. quinquefolius berry., Materials and Methods: P. quinquefolius berry was extracted with hot water, precipitated by alcohol, separated by DEAE-52-cellulose column to give a series of fractions. One of these fractions was further purified via Sephadex G-200 column to give three fractions. Then, the main fraction named as AGBP-A3 was characterized by methylation analysis, NMR spectroscopy, etc. Its anti-inflammatory activity was assessed by RAW 264.7 cell model, zebrafish model and molecular docking., Results: The main chain comprised of α -L-Rhap, α -D-GalAp and β -D-Galp, while the branch consisted mainly of α -L-Araf, β -D-Glcp, α -D-GalAp, β -D-Galp. The RAW264.7 cell assay results showed that the inhibition rates against IL-6 and IL-1 β secretion at the concentration of 625 ng/mL were 24.83 %, 11.84 %, while the inhibition rate against IL-10 secretion was 70.17 % at the concentration of 312 ng/mL. In the zebrafish assay, the migrating neutrophils were significantly reduced in number, and their migration to inflammatory tissues was inhibited. Molecular docking predictions correlated well with the results of the anti-inflammatory assay., Conclusion: The present study demonstrated the structure of acidic polysaccharides of P. quinquefolius berry and their effect on inflammation, providing a reference for screening anti-inflammatory drugs., (© 2024 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Aim: American ginseng berries, grown in the aerial parts and harvested in August, are a potentially valuable material. The aim of the study was to analyze the specific polysaccharides in American ginseng berries, and to demonstrate the anti-inflammation effect through in vitro and in vivo experiments and molecular docking., Methods: After deproteinization and dialysis, the extracted crude polysaccharide was separated and purified. The structure of the specific isolated polysaccharide was investigated by Fourier Transform infrared spectroscopy (FT-IR), GC-MS and nuclear magnetic resonance (NMR), and anti-inflammatory activity was evaluated using in vitro and in vivo models (Raw 264.7 cells and zebrafish). Molecular docking was used to analyze the binding capacity and interaction with cyclooxygenase-2 (COX-2)., Results: A novel neutral polysaccharide fraction (AGBP-A) was isolated from American ginseng berries. The structural analysis demonstrated that AGBP-A had a weight-average molecular weight (Mw) of 122,988 Da with a dispersity index (Mw/Mn) value of 1.59 and was composed of arabinose and galactose with a core structure containing →6)-Gal-(1→ residues as the backbone and a branching substitution at the C3 position. The side-chains comprised of α-L-Ara-(1→, α-L-Ara-(1→, →5)-α-L-Ara-(1→, β-D-Gal-(1→. The results showed that it significantly decreased pro-inflammatory cytokines in the cell model. In a zebrafish model, AGBP-A reduced the massive recruitment of neutrophils to the caudal lateral line neuromast, suggesting the relief of inflammation. Molecular docking was used to analyze the combined capacity and interaction with COX-2., Conclusion: Our study indicated the potential efficacy of AGBP-A as a safe and valid natural anti-inflammatory component., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by extracellular amyloid plaques composed of amyloid β-peptide (Aβ). Studies have indicated that Ca 2+ dysregulation is involved in AD pathology. It is reported that decreased capacitative Ca 2+ entry (CCE), a refilling mechanism of intracellular Ca 2+ , resulting in increased Aβ production. In contrast, constitutive activation of CCE could decrease Aβ production. Panax ginseng Meyer is known to enhance memory and cognitive functions in healthy human subjects. We have previously reported that some ginsenosides decrease Aβ levels in cultured primary neurons and AD mouse model brains. However, mechanisms involved in the Aβ-lowering effect of ginsenosides remain unclear. In this study, we investigated the relationship between CCE and Aβ production by examining the effects of various ginsenosides on CCE levels. Aβ-lowering ginsenosides such as Rk1, Rg5, and Rg3 potentiated CCE. In contrast, ginsenosides without Aβ-lowering effects (Re and Rb2) failed to potentiate CCE. The potentiating effect of ginsenosides on CCE was inhibited by the presence of 2-aminoethoxydipherryl borate (2APB), an inhibitor of CCE. 2APB alone increased Aβ42 production. Furthermore, the presence of 2APB prevented the effects of ginsenosides on Aβ42 production. Our results indicate that ginsenosides decrease Aβ production via potentiating CCE levels, confirming a close relationship between CCE levels and Aβ production. Since CCE levels are closely related to Aβ production, modulating CCE could be a novel target for AD therapeutics.

Seven unknown compounds 1-7, including four sesquiterpenoids, one azulene-type, one indene-type, and one rare hexanorcucurbitacin, together with eleven knowns ones (8-16), were isolated from the agarwood chips of Aquilaria malaccensis . The structures of the isolated compounds were elucidated by extensive spectroscopic methods such as mass spectrometry, UV, IR, NMR spectroscopy. The precise stereo-chemical configurations of new compounds were determined by calculated ECD spectra data, as well as a single-crystal X-ray diffraction analysis. The isolated compounds 1-7 were evaluated by estimating the levels of nitric oxide (NO), TNF-α, and the expression of enzyme iNOS, and COX-2. Among them, a rare hexanortriterpenoid (7) derived from a cucurbitane-type triterpenoid showed the significantly attenuated neuro-inflammatory effects via the STAT1/AKT/MAPK/NLRP3 signaling pathway on the mechanistic studies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Natural bioactive compounds extracted from agricultural by-products have received considerable attentions. Twenty-two kinds of deep eutectic solvents (DESs) with ultrasonic were screened to extract flavonoids from peanut leave and stem. ChCl-acetic acid (ChCl-Aa) with 1:2 M ratio resulted in more effective extraction of flavonoids compared to other solvents The best extraction conditions were found to be at a 27% water content in DES/H 2 O, for 43 min with 31:1 g/mL liquid/solid ratio, giving 2.980 mg/g dw of flavonoids through the response surface method. SEM showed that ChCl-Aa had a certain dissociation impact on the sample matrix, while 1 H NMR analysis revealed the formation of hydrogen bonds between daidzein and ChCl-Aa. Changes in the H-bond length and number were observed by the B3LYP/6-31G (d,p) level of theory to confirm the experimental spectra. This study reveals that DESs are efficient for obtaining value-added products and could applied to other natural products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Agarperoxinols A and B ( 1-2 ), two naturally occurring humulene-type sesquiterpenoids with an unprecedented tricyclic 6/6/7 ring, were discovered from the agarwood of Aquilaria malaccensis . Their structures were unambiguously determined by various spectroscopic data, experimental ECD calculations, and single-crystal X-ray diffraction analysis. Agarperoxinol B showed significant and dose-dependent neuroinflammatory inhibitory effects on various proinflammatory mediators, including NO, TNF-α, IL-6, and IL-1β, and suppressed iNOS and COX-2 enzymes in LPS-activated microglial cells. A mechanistic study demonstrated that agarperoxinol B remarkably inhibited the phosphorylation of the Akt and JNK signaling pathways. Agarperoxinol B also significantly reduced the expression of the microglial markers Iba-1, COX-2, and TNF-α in the mouse cerebral cortex. Our findings introduce a bioactive compound from natural products that decreases proinflammatory factor production and has application for the treatment of neurodegenerative diseases., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. We report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing β cells during development in gnotobiotic zebrafish and mice. BefA disseminates systemically by multiple anatomic routes to act directly on pancreatic islets. We detail BefA's atomic structure, containing a lipid-binding SYLF domain, and demonstrate that it permeabilizes synthetic liposomes and bacterial membranes. A BefA mutant impaired in membrane disruption fails to expand β cells, whereas the pore-forming host defense protein, Reg3, stimulates β cell proliferation. Our work demonstrates that membrane permeabilization by microbiome-derived and host defense proteins is necessary and sufficient for β cell expansion during pancreas development, potentially connecting microbiome composition with diabetes risk., Competing Interests: Declaration of interests J.H.H. and K.G. are patent holders for the use of BefA, patent numbers 10563174, issued February 18, 2020, and 10968432, issued April 6, 2021., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Intercellular communication is critical for homeostasis in mammalian systems, including the gastrointestinal (GI) tract. Exosomes are nanoscale lipid extracellular vesicles that mediate communication between many cell types. Notably, the roles of immune cell exosomes in regulating GI homeostasis and inflammation are largely uncharacterized. By generating mouse strains deficient in cell-specific exosome production, we demonstrate deletion of the small GTPase Rab27A in CD11c+ cells exacerbated murine colitis, which was reversible through administration of DC-derived exosomes. Profiling RNAs within colon exosomes revealed a distinct subset of miRNAs carried by colon- and DC-derived exosomes. Among antiinflammatory exosomal miRNAs, miR-146a was transferred from gut immune cells to myeloid and T cells through a Rab27-dependent mechanism, targeting Traf6, IRAK-1, and NLRP3 in macrophages. Further, we have identified a potentially novel mode of exosome-mediated DC and macrophage crosstalk that is capable of skewing gut macrophages toward an antiinflammatory phenotype. Assessing clinical samples, RAB27A, select miRNAs, and RNA-binding proteins that load exosomal miRNAs were dysregulated in ulcerative colitis patient samples, consistent with our preclinical mouse model findings. Together, our work reveals an exosome-mediated regulatory mechanism underlying gut inflammation and paves the way for potential use of miRNA-containing exosomes as a novel therapeutic for inflammatory bowel disease.

American chestnut (Castanea dentata) was once the most economically and ecologically important hardwood species in the eastern United States. In the first half of the 20th century, an exotic fungal pathogen-Cryphonectria parasitica-decimated the species, killing billions of chestnut trees. Two approaches to developing blight-resistant American chestnut populations show promise, but both will require introduction of adaptive genomic diversity from wild germplasm to produce diverse, locally adapted restoration populations. Here we characterize population structure, demographic history, and genomic diversity in a range-wide sample of 384 wild American chestnuts to inform conservation and breeding with blight-resistant varieties. Population structure analyses suggest that the chestnut range can be roughly divided into northeast, central, and southwest populations. Within-population genomic diversity estimates revealed a clinal pattern with the highest diversity in the southwest, which likely reflects bottleneck events associated with Quaternary glaciation. Finally, we identified genomic regions under positive selection within each population, which suggests that defence against fungal pathogens is a common target of selection across all populations. Taken together, these results show that American chestnut underwent a postglacial expansion from the southern portion of its range leading to three extant genetic populations. These populations will serve as management units for breeding adaptive genetic variation into the blight-resistant tree populations for targeted reintroduction efforts., (© 2022 John Wiley & Sons Ltd.)

Background: Nonsteroidal anti-inflammatory drugs are an effective nonopiate option for pain control. However, the antiplatelet aggregation of cyclooxygenase-1 (COX-1) inhibitors presents a concern in that they may exacerbate bleeding in patients with solid organ injuries., Objective: The aim of the study is to evaluate the impact of nonsteroidal anti-inflammatory drugs on blunt solid organ injury. We hypothesized that nonsteroidal anti-inflammatory drugs would not contribute to intra-abdominal bleed progression., Methods: This is a retrospective cohort study of blunt solid organ injury evaluated from June 1, 2015, to June 30, 2019, at an urban midwestern Level I trauma center. Patients receiving and those not receiving nonsterioidal anti-inflammatory drugs were compared on intra-abdominal bleeding progression as assessed by surgical intervention, angioembolization, and blood transfusions., Results: We analyzed 706 patients, of whom 206 were given nonsteroidal anti-inflammatory drugs during their hospital course. Compared with those who were not given nonsteroidal anti-inflammatory drugs, patients given nonsteroidal anti-inflammatory drugs were less likely to have an operation (odds ratio, OR 0.46, 95% confidence interval, CI [0.25, 0.85], p = .012) and were less likely to have an embolization (OR 0.27, 95% CI [0.11, 0.70], p = .004). There was no difference in the need for packed red blood cell transfusion between the nonsteroidal anti-inflammatory drug and non- nonsteroidal anti-inflammatory drug groups (95% CI [0.91, 1.99], p = .13)., Conclusion: Patients given nonsteroidal anti-inflammatory drugs had a decreased likelihood of receiving an organ-specific procedure or needing a blood transfusion and had no difference in mortality. Our findings indicate that nonsteroidal anti-inflammatory drugs in patients with blunt solid organ injuries were not associated with an increased risk of adverse events related to intra-abdominal bleeding., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Society of Trauma Nurses.)

Do ancient microbial irritants offer early life protection against diabetes?

Background: Ginseng, officially known as Panax ginseng Meyer, has been traditionally used as a medicinal herb, particularly in Asia. Ginseng is propagated from seeds; however, seed germination is challenging, especially in its natural environment on farms. The seeds typically exhibit morphophysiological dormancy and require release from both morphological and physiological dormancy before germination. Although some studies have proposed methods for increasing seed germination rates, the underlying mechanisms of its dormancy release process remain unclear. Here, we investigated metabolic alterations during dehiscence in P. ginseng to determine their potential roles in dormancy release., Methods: We compared the ginseng seed metabolome before and after dehiscence and the ginsenoside and phytosterol compositions of the seeds in both periods in the presence of related enzymes., Results: After seed dehiscence, the sugar, amino acid, and squalene concentrations were significantly altered, phytosterols associated with the stigmasterol biosynthesis pathway were increased, while ginsenoside and brassinosteroid levels were not significantly altered. In addition, squalene epoxidase, cycloartenol synthase, 24-methylenesterol C-methyltransferase, and the stigmasterol biosynthesis pathway were activated., Conclusion: Overall, our findings suggest that morphological activities that facilitate ginseng seed growth are the primary phenomena occurring during the dehiscence process. This study improves the understanding of P. ginseng germination processes and promotes further research of its germination and cultivation., Competing Interests: The authors claim that the researchers in this study have no conflicts of interest to declare., (© 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Panax vietnamensis , or Vietnamese ginseng (VG), an endemic Panax species in Vietnam, possesses a unique saponin profile and interesting biological activities. This plant is presently in danger of extinction due to over-exploitation, resulting in many preservation efforts towards the geographical acclimatization of VG. Yet, no information on the saponin content of the acclimatized VG, an important quality indicator, is available. Here, we analyzed the saponin content in the underground parts of two- to five-year-old VG plants acclimatized to Lam Dong province. Nine characteristic saponins, including notoginsenoside-R1, ginsenoside-Rg1, -Rb1, -Rd, majonoside-R1, -R2 vina-ginsenoside-R2, -R11, and pseudoginsenoside-RT4, were simultaneously determined by HPLC coupled with UV and with a charged aerosol detector (CAD). Analyzing the results illustrated that the detection of characteristic ocotillol-type saponins in VG by CAD presented a superior capacity compared with that of UV, thus implying a preferential choice of CAD for the analysis of VG. The quantitative results indicating the saponin content in the underground parts of VG showed an increasing tendency from two to five years old, with the root and the rhizome exhibiting different saponin accumulation patterns. This is the first study that reveals the preliminary success of VG acclimatization and thereby encourages the continuing efforts to develop this valuable saponin-rich plant.

The factors that facilitate successful colonization of islands should be especially evident where the establishment filter is strongest. Colonizers of small, remote oceanic islands should be initially rare, extremely mate-limited and often without pollinators. Hence, plant communities on such islands should reflect an establishment history in which young 'naturalized' species are most likely to display self-compatibility and autonomous selfing, whereas 'indigenous' species may exhibit more diverse reproductive strategies. To test this prediction, we characterized breeding systems of 28 species on Pohnpei, in the Federated States of Micronesia, a group of remote Pacific islands that are considered a global biodiversity hotspot. Three families with both naturalized and indigenous species were selected-Fabaceae, Malvaceae and Melastomataceae. Measurements included field observations of dichogamy/herkogamy and floral attraction traits, pollen:ovule ( P:O ) ratios and experimental hand-pollinations for self-compatibility and pollen limitation. Phylogenetic generalized least squares analyses tested for trait correlations between naturalized and indigenous species. Flowers of all 28 species were bisexual, and pollinator attraction features were common. Pollen:ovule ratios ranged from 9 to 557 (median = 87), and all 11 hand-pollinated species were self-compatible. All species had >5 ovules and <3500 pollen grains per flower. Indigenous species did not differ significantly from naturalized species for any trait. There is a dearth of data from remote islands bearing on the question of establishment history. In this study, we inferred all species to have some degree of autogamy and indigenous species were no more likely than naturalized species to display outcrossing mechanisms. On Pohnpei, high ovule numbers, and the inaccessibility of wind pollination and obligate outcrossing strategies, reflect the importance of retaining reproductive assurance mechanisms in the face of pollinator uncertainty., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Microbes can play both pathogenic and commensal roles, and it is common to label them as either detrimental or beneficial. However, the lines between good and bad can be blurred. This graphical summary attempts to illustrate the complexity of host-microbe interactions, with outcomes for human health being highly context specific. To view this SnapShot, open or download the PDF., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Nine undescribed sesquiterpenes, which include five guaiane and four humulene-type, were isolated from the agarwood of Aquilaria malaccensis. The structures of these undescribed sesquiterpenes were elucidated by spectroscopic methods including UV, HRESI-MS, 1D and 2D-NMR, ECD, and X-ray diffraction (Cu Kα). The isolated compounds were tested for their inhibitory effect against LPS-induced NO production in RAW 264.7 cells. In particular, one sesquiterpene (1α,7α-dihydroxy-8oxo-4αH,5αH-guaia-9(10),11(13)-dien-12-oate) showed significant inhibition of NO production in LPS-stimulated macrophage RAW 264.7 cells with an IC 50 value of 18.8 μM., (Copyright © 2020. Published by Elsevier Ltd.)

Growth mindset is an important aspect of children's socioemotional development and is subject to change due to environmental influence. Orchestral music education may function as a fertile context in which to promote growth mindset; however, this education is not widely available to children facing economic hardship. This study examined whether participation in a program of orchestral music education was associated with higher levels of overall growth mindset and greater change in levels of musical growth mindset among children placed at risk by poverty. After at least 2 years of orchestral participation, students reported significantly higher levels of overall growth mindset than their peers; participating students also reported statistically significant increases in musical growth mindset regardless of the number of years that they were enrolled in orchestral music education. These findings have implications for future research into specific pedagogical practices that may promote growth mindset in the context of orchestral music education and more generally for future studies of the extra-musical benefits of high-quality music education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Holochwost, Bose, Stuk, Brown, Anderson and Wolf.)

Abstract: Although using direct oral anticoagulants increases patient risk for hemorrhagic events, FDA-approved options for reversing anticoagulant effects are limited. This article discusses one of the more recent FDA-approved antidotes, andexanet alfa, and provides guidelines for its safe and effective use., (Copyright © 2021 American Academy of Physician Assistants.)

Panax vietnamensis (PV), a wild Panax species discovered in Vietnam in 1973, has been increasingly overexploited due to its economic value and therapeutic uses. This resulted in the development of PV cultivation to meet the market demand. There is little information on the accumulation of saponins in PV during cultivation, but this information could serve as an indication of the appropriate harvest time. In this study we developed an HPLC-UV/ELSD method to simultaneously determine the content of 10 characteristic saponins in PV from 2-7 years old, including G-Rb1, G-Rd, G-Rg1, G-Re, N-R1, M-R1, M-R2, V-R2, V-R11, and p-RT4. The result indicated that from 2 to 5 years, the content of saponins in PV rhizome and radix increase 3.02 and 4.2 times, respectively, whereas from 5 to 7 years, no significant changes were observed. Hence, our study suggests that after 5 years of growth could be considered as an appropriate time for PV to be harvested. Among the analyzed saponins, G-Rg1, G-Rb1, G-Rd, and especially M-R2 were the major saponins that contributed to the change of PV's saponin content through the years. In addition, the developed and validated HPLC method was proven to be reliable and effective for quality control of PV.

Leaves of custard apple are widely used in many places as a popular dietary supplement for the treatment of diabetes. Flavonoids are known to have anti-diabetic activity. In this study, the main flavonoid epimers were separated. The crude extract was first screened by HPLC-DAD before and after incubation with DPPH method to evaluate the antioxidants. An efficient extraction method was employed to remove non-flavonoid components. Subsequently, five main flavonoids with two pairs of epimers including quercetin-3-O-robinobioside, rutin, quercetin-3-O-β-D-glucoside, kaempferol-3-O-robinobioside, and kaempferol-3-O-rutinoside were successfully separated by high-speed counter-current chromatography with ethyl acetate/n-butanol/water (4:1:5, v/v) coupled with online-storage inner-recycling mode. The structures of the separated compounds were identified by spectral techniques. The purity of the separated flavonoid glycosides was over 98%, as determined by HPLC. The separated pure constituents were found to possess the antioxidant capacities following DPPH radical scavenging protocol. The compounds (1-3) exhibited better antioxidant activity. Furthermore, the glucose uptake of crude flavonoid extract had better results than the crude ethanol extract. The present study demonstrates that the efficacy of custard apple leaves in lowering glucose level, and antioxidant capacities of separated pure compounds probably appear to be predominantly responsible for hypoglycaemic properties on HepG2 cells.

Context: Blunt cerebrovascular injury (BCVI) occurs in 1%-2% of all blunt trauma patients. Computed tomographic angiography of the neck (CTAn) is commonly used for the diagnosis and grading of BCVIs. Grade of injury dictates treatment, and there remains a lack in understanding the inter-reader reliability of these interpretations., Aims: The aim of this study is to determine the extent of variability in BCVIs among specialized neuroradiologist interpretation of CTAn., Settings and Design: Retrospective review of trauma patients admitted to a level one trauma center with a BCVI from January 2012 to December 2017. Patients were randomly assigned for CTAn re-evaluation by two of three blinded, neuroradiologists., Statistical Analysis Used: The variability in BCVI grades was measured using the coefficient of unalikeability (u), and inter-reader reliability was calculated using weighted Cohen's kappa (k)., Results: Two hundred and twenty-eight BCVIs were analyzed with initial grades of 71 (31%) grade one, 74 (32%) grade two, 26 (11%) grade three, 57 (25%) grade four, and 0 grade five. Variability was present in 93 (41%) of all BCVIs. Grade one injuries had the lowest occurrence of total agreement (31%) followed by grade three (61%), grade two (63%), and grade four (92%). Total variability of grade interpretations (u = 100) occurred most frequently with grade three BCVIs (21%). Weighted Cohen's k calculations had a mean of 0.07, indicating poor reader agreement., Conclusions: This novel study demonstrated the BCVI variability of radiological grade interpretation occurs in more than a third of patients. The reliability of CTAn interpretation of BCVI grades is not uniform, potentially leading to undertreatment and overtreatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 International Journal of Critical Illness and Injury Science.)

Panax ginseng ( P. ginseng ) is the most widely consumed herbal plant in Asia and is well-known for its various pharmacological properties. Many studies have been devoted to this natural product. However, polysaccharide's components of ginseng and their biological effects have not been widely studied. In this study, white ginseng neutral polysaccharide (WGNP) and white ginseng acidic polysaccharide (WGAP) fractions were purified from P. ginseng roots. The chemical properties of WGNP and WGAP were investigated using various chromatography and spectroscopy techniques, including high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, and high-performance liquid chromatography with an ultra-violet detector. The antioxidant, anti-radical, and hydrogen peroxide scavenging activities were evaluated in vitro and in vivo using Caenorhabditis elegans as the model organism. Our in vitro data by ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid), reducing power, ferrous ion chelating, and hydroxyl radical scavenging activity suggested that the WGAP with significantly higher uronic acid content and higher molecular weight exhibits a much stronger antioxidant effect as compared to that of WGNP. Similar antioxidant activity of WGAP was also confirmed in vivo by evaluating internal reactive oxygen species (ROS) concentration and lipid peroxidation. In conclusion, WGAP may be used as a natural antioxidant with potent scavenging and metal chelation properties., Competing Interests: The authors declare no conflict of interest.

Perfluorinated compounds (PFCs) are widely used in consumer products because of their remarkable endurance. However, their distinct stability prolongs degradation, resulting in bioaccumulation in the environment which is a severe environmental issue. Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are principal constituents in the PFCs. In this study, the potential toxic effects of PFOS and PFOA were evaluated by adopting an in vivo animal model, Caenorhabditis elegans (C. elegans). The uptake of PFCs was confirmed by the quantification of internal concentration in C. elegans. Metabolomics and lipidomics were applied along with reproduction assay and reactive oxygen species (ROS) assay. In the C. elegans exposed to PFOS and PFOA, amino acids including phenylalanine, tyrosine, and tryptophan, were significantly affected. Also, various species that belong to glycerophospholipids and triacylglycerol were perturbed in the exposed groups. The alteration patterns of the lipidome in PFOS and PFOA treated C. elegans were significantly different. Additionally, dichlorodihydrofluorescein diacetate (H 2 DCFDA)-based ROS assay revealed increased internal ROS in PFOS (1.5 fold, p-value = 0.0067) and PFOA (1.46 fold, p-value = 0.0253) groups. Decrease in reproduction was confirmed in PFOS (0.53 fold, p-value < 0.0001) and PFOA (0.69 fold, p-value = 0.0003) by counting progeny. Collectively, our findings suggest that exposure to PFCs in C. elegans leads to perturbation of various phenotypes as well as crucial amino acid and lipid metabolism., (Copyright © 2019. Published by Elsevier B.V.)

Polyacetylenic compounds isolated from Panax species are comprised of non-polar C17 compounds, exhibiting anti-inflammatory, antitumor, and antifungal activities. Panaxynol represents the major component of the essential oils of ginseng. We investigated whether panaxynol isolated from Panax vietnamensis (Vietnamese ginseng, VG) could prevent cisplatin-induced renal damage induced in vitro and in vivo. Cisplatin-induced apoptotic cell death was observed by staining with annexin V conjugated with Alexa Fluor 488, and western blotting evaluated the molecular mechanism. Panaxynol at concentrations above 0.25 μM prevented cisplatin-induced LLC-PK1 porcine renal proximal tubular cell death. LLC-PK1 cells treated with cisplatin demonstrated an increase in apoptotic cell death, whereas pretreatment with 2 and 4 μM panaxynol decreased this effect. Cisplatin demonstrated a marked increase in the phosphorylation of c-Jun N-terminal kinase (JNK), P38, and cleaved caspase-3. However, pretreatment with 2 and 4 μM panaxynol reversed the upregulated phosphorylation of JNK, P38, and the expression of cleaved caspase-3. We confirmed that the protective effect of panaxynol isolated from P. vietnamensis in LLC-PK1 cells was at least partially mediated by reducing the cisplatin-induced apoptotic damage. In the animal study, panaxynol treatment ameliorated body weight loss and blood renal function markers and downregulated the mRNA expression of inflammatory mediators.

Cisplatin is a platinum-based anticancer agent used for treating a wide range of solid cancers. One of the side effects of this drug is its severe nephrotoxicity, limiting the safe dose of cisplatin. Therefore, many natural products have been studied and applied to attenuate the toxicity of this compound. In this study, we found that steamed Vietnamese ginseng ( Panax vietnamensis ) could significantly reduce the kidney damage of cisplatin in an in vitro model using porcine proximal tubular LLC-PK1 kidney cells. From processed ginseng under optimized conditions (120 °C, 12 h), we isolated seven compounds (20( R,S )-ginsenoside Rh2, 20( R,S )-ginsenoside Rg3, ginsenoside Rk1, ginsenoside-Rg5, and ocotillol genin) that showed kidney-protective potential against cisplatin toxicity. By comparing the 50% recovery concentration (RC 50 ), the R form of ginsenoside, Rh2 and Rg3, had RC 50 values of 6.67 ± 0.42 µM and 8.39 ± 0.3 µM, respectively, while the S forms of ginsenoside, Rh2 and Rg3, and Rk1, had weaker protective effects, with RC 50 ranging from 46.15 to 88.4 µM. G-Rg5 and ocotillol, the typical saponin of Vietnamese ginseng, had the highest RC 50 (180.83 ± 33.27; 226.19 ± 66.16, respectively). Our results suggest that processed Vietnamese gingseng (PVG), as well as those compounds, has the potential to improve kidney damage due to cisplatin toxicity.

Background: Panax ginseng seeds have strong dormancy and a prolonged germination period in comparison to other seeds; thus, it is a great challenge to propagate ginseng. Seed longevity is closely associated with germination rate and viability, so we assumed that if a seed loses its viability, specific metabolic alterations regarding plant growth factors might occur. In this study, we divided ginseng seeds into normal and accelerated-aging groups. Both groups were treated with gibberellic acid, which is one of the most important plant-growth regulators. Afterward, gas chromatography-mass spectrometry (GC-MS) was used to analyze the samples, to identify the metabolic alterations between the two groups., Results: Forty-four endogenous metabolites in normal and accelerated aging groups were putatively identified. To determine the differential significance of these metabolites, t-tests and fold-change analysis were conducted followed by principal component analysis and partial least-squares discriminant analysis to determine the metabolites that showed distinct responses between the groups. Among the differentially expressed metabolites (P value < 0.05 and FDR < 0.1), nine metabolites were selected as potential biomarker candidates for the prediction of seed longevity., Conclusion: Nine metabolites related to ginseng seed longevity were identified by comparing metabolomes. Our findings suggest that ginseng propagation can be facilitated by the regulation of these distinctive metabolic features of the seeds. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Steroidomics, an analytical technique for steroid biomarker mining, has received much attention in recent years. This systematic review and functional analysis, following the PRISMA statement, aims to provide a comprehensive review and an appraisal of the developments and fundamental issues in steroid high-throughput analysis, with a focus on cancer research. We also discuss potential pitfalls and proposed recommendations for steroidomics-based clinical research. Forty-five studies met our inclusion criteria, with a focus on 12 types of cancer. Most studies focused on cancer risk prediction, followed by diagnosis, prognosis, and therapy monitoring. Prostate cancer was the most frequently studied cancer. Estradiol, dehydroepiandrosterone, and cortisol were mostly reported and altered in at least four types of cancer. Estrogen and estrogen metabolites were highly reported to associate with women-related cancers. Pathway enrichment analysis revealed that steroidogenesis; androgen and estrogen metabolism; and androstenedione metabolism were significantly altered in cancers. Our findings indicated that estradiol, dehydroepiandrosterone, cortisol, and estrogen metabolites, among others, could be considered oncosteroids. Despite noble achievements, significant shortcomings among the investigated studies were small sample sizes, cross-sectional designs, potential confounding factors, and problematic statistical approaches. More efforts are required to establish standardized procedures regarding study design, analytical procedures, and statistical inference.

Ginseng marc is a major by-product of the ginseng industry currently used as animal feed or fertilizer. This fibrous, insoluble waste stream is rich in cell wall polysaccharides and therefore a potential source of ingredients for functional food with health-promoting properties. However, the extraction of these polysaccharides has proved problematic and their exact composition remains unknown. Here we have analysed the composition, structure and biological activity of polysaccharides from ginseng root, stem and leaf marc fractionated using a chelator and alkali solutions. The pectic fraction has been extracted from root marc in high abundance and can activate the production of interleukine-1α and the hematopoietic growth factor by RAW 264.7 murine macrophage cells, which are important immune regulators of T-cells during inflammatory responses and infection processes. Our study reveals the potential to increase the value of ginseng marc by generating carbohydrate-based products with a higher value than animal feed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Zea mays L. ssp. mays (maize) is an important crop plant as well as model system for genetics and plant biology. The ability to select among different virus-based platforms for transient gene silencing or protein expression experiments is expected to facilitate studies of gene function in maize and complement experiments with stable transgenes. Here, we describe the development of a sugarcane mosaic virus (SCMV) vector for the purpose of protein expression in maize. An infectious SCMV cDNA clone was constructed, and heterologous genetic elements were placed between the protein 1 (P1) and helper component-proteinase (HC-Pro) cistrons in the SCMV genome. Recombinant SCMV clones engineered to express green fluorescent protein (GFP), β-glucuronidase (GUS), or bialaphos resistance (BAR) protein were introduced into sweet corn (Golden × Bantam) plants. Documentation of developmental time courses spanning maize growth from seedling to tasseling showed that the SCMV genome tolerates insertion of foreign sequences of at least 1,809 nucleotides at the P1/HC-Pro junction. Analysis of insert stability showed that the integrity of GFP and BAR coding sequences was maintained longer than that of the much larger GUS coding sequence. The SCMV isolate from which the expression vector is derived is able to infect several important maize inbred lines, suggesting that this SCMV vector has potential to be a valuable tool for gene functional analysis in a broad range of experimentally important maize genotypes., Competing Interests: The authors declare no conflict of interest associated with the work described in this manuscript.