bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of MAT Methodology in the Evaluation of Prescribing Adherence to Clinical Practice Guidelines for Secondary Prevention of Coronary Heart Disease in Post-Acute Coronary Syndrome Patients in Kuwait
Authors: Al-Taweel Dalal , Awad Abdelmoneim
Published: October 2021

Quantification of prescribers’ adherence to evidence-based guidelines can be used as an outcome measure to assess the impact of services on the quality of medication use. Additionally, it can help in reducing inappropriate interventions and ensure that high-quality care is provided to patients. This study aimed to evaluate prescribing practices for secondary prevention of coronary heart disease (CHD) in post-acute coronary syndromes (ST-elevation myocardial infarction [STEMI] or non-ST elevation acute coronary syndrome [NSTEACS]) patients using two medication assessment tools (MATs) at secondary and tertiary health-care settings in Kuwait. Both MATs were developed and validated based on the relevant guidelines issued by the European Society of Cardiology and the American College of Cardiology/American Heart Association. A quantitative cross-sectional multicenter study was conducted on 460 patients’ medical records collected randomly from six health-care facilities in Kuwait. Application of MATSTEMI on 232 patients’ medication records (with 85.9% applicability) resulted in intermediate overall adherence (69.8%; 95% CI: 67.6–72.0). Application of MATNSTEACS on 228 patients’ medication records (with applicability 83.2%) resulted in intermediate overall adherence (73.3%; 95% CI: 70.5–76.0). There was no significant difference between the percentages of overall adherence among patients managed post-NSTEACS compared to those managed post-STEMI (p = 0.05). Multivariable logistic regression analysis revealed that the overall adherence to the MATSTEMI criteria was significantly higher among the specialized cardiac centers than among the general hospitals (OR: 1.6; 95% CI: 1.1–2.3; p = 0.02). The overall adherence to the MATNSTEACS criteria was found to be significantly lower among non-Kuwaitis than among Kuwaitis (OR: 0.6; 95% CI: 0.5–0.9; p = 0.01) and patients with a serum LDL ≥1.8 mmol/L than those with a serum LDL-C < 1.8 mmol/L (OR: 0.5; 95% CI: 0.4–0.7; p < 0.001). The present findings revealed that both MATs were useful tools in identifying the standard of clinical performances and highlighting areas for improvement regarding secondary prevention of CHD in post-acute coronary syndrome patients.
Anti-Photoaging and Anti-Inflammatory Effects of Ginsenoside Rk3 During Exposure to UV Irradiation
Authors: Wan Shichao , Liu Yannan , Shi Jingjing , Fan Daidi , Li Binglin
Published: October 2021

Ginseng is a widely cultivated perennial plant in China and Korea. Ginsenoside Rk3 is one of the major active components of ginseng and is a promising candidate to regulate skin pigments and exert anti-photoaging effects on skin physiology. Ginsenoside Rk3 was mixed with a cream (G-Rk3 cream) and smeared on the skin of mice. Then, the mice were exposed to ultraviolet (UV) A (340 nm and 40 W) and UVB (313 nm and 40 W) radiation. Special attention was given to the anti-photoaging and anti-inflammatory effects of ginsenoside Rk3 on the mouse skin. Macroscopic evaluation indicated that the mouse dorsal skin looked smooth and plump even under UV irradiation for 12 weeks. Pathological analysis indicated that there was no obvious photoaging or inflammation in the mouse skin that was treated with the G-Rk3 cream. More healthy, intact, and neat collagen fibers were observed in mice treated with the G-Rk3 cream than in untreated mice. Further analysis proved that ginsenoside Rk3 could inhibit the decrease in water and hydroxyproline levels in skin tissues and the loss of superoxide dismutase and glutathione peroxidase activities in the blood. Moreover, ginsenoside Rk3 slowed or halted increases in malondialdehyde, matrix metalloproteinase (MMP)-1, and MMP-3 levels in the blood and levels of interleukin 1, interleukin 6, and tumor necrosis factor α in skin tissues. In conclusion, ginsenoside Rk3 plays a significant role in inhibiting photoaging and inflammation to protect skin health.
Pharmacovigilance Bibliometrics: Visualizing Thematic Development in the Category of Pharmacology and Pharmacy in Web of Science
Authors: Wang Li , Feng Wanyu , Duan Jingli , Liang Jun
Published: October 2021

Introduction: Pharmacovigilance studies include monitoring and preventing the occurrence of new, rare, or serious adverse drug reactions, making it possible to discover new safety issues without delay. Bibliometrics could assist scholars to analyze the development of pharmacovigilance.

Methods: The MeSH terms of both pharmacovigilance and “adverse drug reaction reporting system” were retrieved in the Science Citation Index Expanded. The articles from 1974 to July 2021 in the pharmacology and pharmacy category were recruited. The citation reports including the publication numbers, h-index, and sum and average cited times in terms of annuals, countries, organizations, authors and journals were tabulated. The coauthorship relations in the analysis units of countries, organizations, and authors; the top 10 burst references; the document citation network; and the author’s keywords co-occurrence overlay map were visualized by bibliometric software including the website (https://bibliometric.com/), VOSviewer, CiteSpace, and CitNetExplorer.

Results: From 1974 to the present, the most high-yield publication year, country, institute, author, and journal were 2020 (n = 222), France (n = 522), Netherlands Pharmacovigilance Centre Lareb (n = 82), Jean–Louis Montastruc (n = 125), Drug Safety (n = 384), respectively, in all 2,128 articles. Similarly, the United States, Institut National de la Sante et de la Recherche Medicale, and Jean–Louis Montastruc had the most coauthorship strength at the macrolevel (global), mesolevel (local), and microlevel (individual). The topics of burst references covered are the development of methodology, issues of patients reporting and under-reporting, evaluation of methods and databases, assessment of causality, and perspectives in pharmacovigilance. Eight clusters were grouped in the document citation network. “Pharmacovigilance,” “adverse drug reactions,” “pharmacoepidemiology,” “drug safety,” and “signal detection” were the research priorities, while “drug-related side effects and adverse reactions,” “VigiBase,” “disproportionality analysis,” “social media,” “FAERS,” “chemotherapy,” “patient safety,” “reporting odds ratio,” and “preventability” might be the future research hotspots.

Conclusion: Positive synergies can be observed in this study by employing the multiple software tools which established the relationship between the units of analysis. The bibliometric analysis can organize the thematic development and guide the hotspots of pharmacovigilance in pharmacology and pharmacy.
Cationic Channel TRPV2 Overexpression Promotes Resistance to Cisplatin-Induced Apoptosis in Gastric Cancer Cells
Authors: Laurino Simona , Mazzone Pellegrino , Ruggieri Vitalba , Zoppoli Pietro , Calice Giovanni , Lapenta Antonella , Ciuffi Mario , Ignomirelli Orazio , Vita Giulia , Sgambato Alessandro , Russi Sabino , Falco Geppino
Published: October 2021

Gastric cancer (GC) is characterized by poor efficacy and modest clinical impact of current therapies, in which apoptosis evasion is relevant. Intracellular calcium homeostasis dysregulation is associated with apoptosis escaping, and aberrant expression of calcium regulator genes could promote GC drug resistance. Since we previously found a prognostic value for TRPV2 calcium channel expression in GC, we aimed to characterize the role of TRPV2 in cisplatin resistance. Using the TCGA-STAD dataset, we performed a differential gene expression analysis between GC samples in upper and lower tertiles of TRPV2 expression, and then through a gene set analysis, we highlighted the enriched ontology and canonical pathways. We used qRT-PCR to assess TRPV2 expression in three GC cell lines and flow cytometry to evaluate cisplatin-induced cell death rates. Calcium green-1-AM assay was used to estimate differences in intracellular Ca2+ concentrations after inhibition of TRPV2. We engineered AGS cell line to overexpress TRPV2 and used confocal microscopy to quantify its overexpression and localization and flow cytometry to evaluate their sensitivity to cisplatin. Consistent with our hypothesis, among enriched gene sets, we found a significant number of those involved in the regulation of apoptosis. Subsequently, we found an inverse correlation between TRPV2 expression and sensitivity to cisplatin in GC cell lines. Moreover, we demonstrated that inhibition of TRPV2 activity by tranilast blocks the efflux of Ca2+ ions and, in combination with cisplatin, induced a significant increase of apoptotic cells (p = 0.004). We also demonstrated that TRPV2 exogenous expression confers a drug-resistant phenotype, and that tranilast is able to revert this phenotype, restoring cisplatin sensitivity. Our findings consistently suggested that TRPV2 could be a potential target for overcoming cisplatin resistance by promoting apoptosis. Notably, our data are a prerequisite for the potential reposition of tranilast to the treatment of GC patients and anticipate the in vivo evaluation.
Social Interaction With Relapsed Partner Facilitates Cocaine Relapse in Rats
Authors: Meng Shiqiu , Yan Wei , Liu Xiaoxing , Gong Yimiao , Tian Shanshan , Wu Ping , Sun Yan , Shi Jie , Lu Lin , Yuan Kai , Xue Yanxue
Published: October 2021

Social factors strongly contribute to drug use and relapse, and epidemiological studies have found that members of peer groups influence each other to use drugs. However, previous animal models mostly failed to incorporate social factors and demonstrate the effects of social partners on drug addiction and relapse. In the present study, we investigated the transfer of relapse to cocaine seeking between drug-addicted partners in rats. Male Sprague–Dawley rats were pair-housed and subjected to training and extinction of cocaine self-administration and conditioned place preference (CPP). 24 h after extinction test, the targeted rats interacted with a cocaine-primed (relapsed) partner or stranger, or saline-injected (unrelapsed) partner for 30 min, after which the targeted rats were tested for drug seeking behavior. We found that social interaction with a relapsed partner increased drug seeking behavior in cocaine self-administration and CPP models in rats, while social interaction with an unrelapsed partner or relapsed stranger had no effect on cocaine seeking. Moreover, the effect of social interaction on cocaine seeking could last for at least 1 day. Our findings demonstrate a facilitation effect of relapsed social partners on drug relapse in rats and provide a novel animal model for social transfer of drug relapse.
New Challenges Resulting From the Loss of Function of Nav1.4 in Neuromuscular Diseases
Authors: Nicole Sophie , Lory Philippe
Published: October 2021

The voltage-gated sodium channel Nav1.4 is a major actor in the excitability of skeletal myofibers, driving the muscle force in response to nerve stimulation. Supporting further this key role, mutations in SCN4A, the gene encoding the pore-forming α subunit of Nav1.4, are responsible for a clinical spectrum of human diseases ranging from muscle stiffness (sodium channel myotonia, SCM) to muscle weakness. For years, only dominantly-inherited diseases resulting from Nav1.4 gain of function (GoF) were known, i.e., non-dystrophic myotonia (delayed muscle relaxation due to myofiber hyperexcitability), paramyotonia congenita and hyperkalemic or hypokalemic periodic paralyses (episodic flaccid muscle weakness due to transient myofiber hypoexcitability). These last 5 years, SCN4A mutations inducing Nav1.4 loss of function (LoF) were identified as the cause of dominantly and recessively-inherited disorders with muscle weakness: periodic paralyses with hypokalemic attacks, congenital myasthenic syndromes and congenital myopathies. We propose to name this clinical spectrum sodium channel weakness (SCW) as the mirror of SCM. Nav1.4 LoF as a cause of permanent muscle weakness was quite unexpected as the Na+ current density in the sarcolemma is large, securing the ability to generate and propagate muscle action potentials. The properties of SCN4A LoF mutations are well documented at the channel level in cellular electrophysiological studies However, much less is known about the functional consequences of Nav1.4 LoF in skeletal myofibers with no available pertinent cell or animal models. Regarding the therapeutic issues for Nav1.4 channelopathies, former efforts were aimed at developing subtype-selective Nav channel antagonists to block myofiber hyperexcitability. Non-selective, Nav channel blockers are clinically efficient in SCM and paramyotonia congenita, whereas patient education and carbonic anhydrase inhibitors are helpful to prevent attacks in periodic paralyses. Developing therapeutic tools able to counteract Nav1.4 LoF in skeletal muscles is then a new challenge in the field of Nav channelopathies. Here, we review the current knowledge regarding Nav1.4 LoF and discuss the possible therapeutic strategies to be developed in order to improve muscle force in SCW.
Paving the Way for Tunable Graphene Plasmonic THz Amplifiers
Authors: Boubanga-Tombet Stephane A. , Satou Akira , Yadav Deepika , But Dmitro B. , Knap Wojciech , Popov Vyacheslav V. , Gorbenko Ilya V. , Kachorovskii Valentin , Otsuji Taiichi
Published: October 2021

This study reviews recent advances in room-temperature coherent amplification of terahertz (THz) radiation in graphene, electrically driven by a dry cell battery. Our study explores THz light–plasmon coupling, light absorption, and amplification using a current-driven graphene-based system because of its excellent room temperature electrical and optical properties. An efficient method to exploit graphene Dirac plasmons (GDPs) for light generation and amplification is introduced. This approach is based on current-driven excitation of the GDPs in a dual-grating-gate high-mobility graphene channel field-effect transistor (DGG-GFET) structure. The temporal response of the DGG-GFETs to the polarization-managed incident THz pulsation is experimentally observed by using THz time-domain spectroscopy. Their Fourier spectra of the transmitted temporal waveform through the GDPs reveals the device functions 1) resonant absorption at low drain bias voltages below the first threshold level, 2) perfect transparency between the first and the second threshold drain bias levels, and 3) resonant amplification beyond the second threshold drain bias voltage. The maximal gain of 9% is obtained by a monolayer graphene at room temperatures, which is four times higher than the quantum limit that is given when THz photons directly interact with electrons. The results pave the way toward tunable graphene plasmonic THz amplifiers.
Methylsulfonylmethane Increases the Alveolar Bone Density of Mandibles in Aging Female Mice
Authors: Aljohani Hanan , Senbanjo Linda T. , Al Qranei Mohammed , Stains Joseph P. , Chellaiah Meenakshi A.
Published: October 2021

Methylsulfonylmethane (MSM) is a naturally occurring anti-inflammatory compound that effectively treats multiple degenerative diseases such as osteoarthritis and acute pancreatitis. Our previous studies have demonstrated the ability of MSM to differentiate stem cells from human exfoliated deciduous (SHED) teeth into osteoblast-like cells. This study examined the systemic effect of MSM in 36-week-old aging C57BL/6 female mice in vivo by injecting MSM for 13 weeks. Serum analyses showed an increase in expression levels of bone formation markers [osteocalcin (OCN) and procollagen type 1 intact N-terminal propeptide (P1NP)] and a reduction in bone resorption markers [tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collag (CTX-I)] in MSM-injected animals. Micro-computed tomographic images demonstrated an increase in trabecular bone density in mandibles. The trabecular bone density tended to be higher in the femur, although the increase was not significantly different between the MSM- and phosphate-buffered saline (PBS)-injected mice. In mandibles, an increase in bone density with a corresponding decrease in the marrow cavity was observed in the MSM-injected mice. Furthermore, immunohistochemical analyses of the mandibles for the osteoblast-specific marker – OCN, and the mesenchymal stem cell-specific marker – CD105 showed a significant increase and decrease in OCN and CD105 positive cells, respectively. Areas of bone loss were observed in the inter-radicular region of mandibles in control mice. However, this loss was considerably decreased due to stimulation of bone formation in response to MSM injection. In conclusion, our study has demonstrated the ability of MSM to induce osteoblast formation and function in vivo, resulting in increased bone formation in the mandible. Hence, the application of MSM and stem cells of interest may be the right combination in alveolar bone regeneration under periodontal or other related diseases that demonstrate bone loss.
Hepatic Remote Ischemic Preconditioning (RIPC) Protects Heart Damages Induced by Ischemia Reperfusion Injury in Mice
Authors: Ren Yanlong , Lin Shujin , Liu Wenxian , Ding Huiguo
Published: October 2021

It has been convincingly demonstrated that remote ischemic preconditioning (RIPC) can make the myocardium resistant to the subsequent ischemia reperfusion injury (IRI), which causes severe damages by mainly generating cell death. However, the cardioprotective effects of the hepatic RIPC, which is the largest metabolic organ against I/R, have not been fully studied. The aim of our research is whether remote liver RIPC may provide cardioprotective effects against the I/R-induced injury. Here, we generated an I/R mice model in four groups to analyze the effect. The control group is the isolated hearts with 140-min perfusion. I/R group added ischemia in 30 min following 90-min reperfusion. The third group (sham) was subjected to the same procedure as the latter group. The animals in the fourth group selected as the treatment group, underwent a hepatic RIPC by three cycles of 5-min occlusion of the portal triad and then followed by induction of I/R in the isolated heart. The level of myocardial infarction and the preventive effects of RIPC were assessed by pathological characteristics, namely, infarct, enzyme releases, pressure, and cardiac mechanical activity. Subjected to I/R, the hepatic RIPC minimized the infarct size (17.7 ± 4.96 vs. 50.06 ± 5, p < 0.001) and improved the left ventricular-developed pressure (from 47.42 ± 6.27 to 91.62 ± 5.22 mmHg) and the mechanical activity. Release of phosphocreatine kinase-myocardial band (73.86 ± 1.95 vs. 25.93 ± 0.66 IUL−1) and lactate dehydrogenase (299.01 ± 10.7 vs. 152.3 ± 16.7 IUL−1) was also decreased in the RIPC-treated group. These results demonstrate the cardioprotective effects of the hepatic remote preconditioning against the injury caused by I/R in the isolated perfused hearts.
Mechanisms of Mechanical Force Induced Pulmonary Vascular Endothelial Hyperpermeability
Authors: Lai Yan , Huang Yongbo
Published: October 2021

Mechanical ventilation is a supportive therapy for patients with acute respiratory distress syndrome (ARDS). However, it also inevitably produces or aggravates the original lung injury with pathophysiological changes of pulmonary edema caused by increased permeability of alveolar capillaries which composed of microvascular endothelium, alveolar epithelium, and basement membrane. Vascular endothelium forms a semi-selective barrier to regulate body fluid balance. Mechanical ventilation in critically ill patients produces a mechanical force on lung vascular endothelium when the endothelial barrier was destructed. This review aims to provide a comprehensive overview of molecular and signaling mechanisms underlying the endothelial barrier permeability in ventilator-induced lung jury (VILI).
Whole-Body EMS Superimposed Walking and Nordic Walking on a Treadmill—Determination of Exercise Intensity to Conventional Exercise
Authors: Verch Ronald , Stoll Josephine , Hadzic Miralem , Quarmby Andrew , Völler Heinz
Published: October 2021

Electrical muscle stimulation (EMS) is an increasingly popular training method and has become the focus of research in recent years. New EMS devices offer a wide range of mobile applications for whole-body EMS (WB-EMS) training, e.g., the intensification of dynamic low-intensity endurance exercises through WB-EMS. The present study aimed to determine the differences in exercise intensity between WB-EMS-superimposed and conventional walking (EMS-CW), and CON and WB-EMS-superimposed Nordic walking (WB-EMS-NW) during a treadmill test. Eleven participants (52.0 ± years; 85.9 ± 7.4 kg, 182 ± 6 cm, BMI 25.9 ± 2.2 kg/m2) performed a 10 min treadmill test at a given velocity (6.5 km/h) in four different test situations, walking (W) and Nordic walking (NW) in both conventional and WB-EMS superimposed. Oxygen uptake in absolute (VO2) and relative to body weight (rel. VO2), lactate, and the rate of perceived exertion (RPE) were measured before and after the test. WB-EMS intensity was adjusted individually according to the feedback of the participant. The descriptive statistics were given in mean ± SD. For the statistical analyses, one-factorial ANOVA for repeated measures and two-factorial ANOVA [factors include EMS, W/NW, and factor combination (EMS*W/NW)] were performed (α = 0.05). Significant effects were found for EMS and W/NW factors for the outcome variables VO2 (EMS: p = 0.006, r = 0.736; W/NW: p < 0.001, r = 0.870), relative VO2 (EMS: p < 0.001, r = 0.850; W/NW: p < 0.001, r = 0.937), and lactate (EMS: p = 0.003, r = 0.771; w/NW: p = 0.003, r = 0.764) and both the factors produced higher results. However, the difference in VO2 and relative VO2 is within the range of biological variability of ± 12%. The factor combination EMS*W/NW is statistically non-significant for all three variables. WB-EMS resulted in the higher RPE values (p = 0.035, r = 0.613), RPE differences for W/NW and EMS*W/NW were not significant. The current study results indicate that WB-EMS influences the parameters of exercise intensity. The impact on exercise intensity and the clinical relevance of WB-EMS-superimposed walking (WB-EMS-W) exercise is questionable because of the marginal differences in the outcome variables.
Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target?
Authors: Shoshan-Barmatz Varda , Anand Uttpal , Nahon-Crystal Edna , Di Carlo Marta , Shteinfer-Kuzmine Anna
Published: October 2021

Metformin has been used for treating diabetes mellitus since the late 1950s. In addition to its antihyperglycemic activity, it was shown to be a potential drug candidate for treating a range of other diseases that include various cancers, cardiovascular diseases, diabetic kidney disease, neurodegenerative diseases, renal diseases, obesity, inflammation, COVID-19 in diabetic patients, and aging. In this review, we focus on the important aspects of mitochondrial dysfunction in energy metabolism and cell death with their gatekeeper VDAC1 (voltage-dependent anion channel 1) as a possible metformin target, and summarize metformin’s effects in several diseases and gut microbiota. We question how the same drug can act on diseases with opposite characteristics, such as increasing apoptotic cell death in cancer, while inhibiting it in neurodegenerative diseases. Interestingly, metformin’s adverse effects in many diseases all show VDAC1 involvement, suggesting that it is a common factor in metformin-affecting diseases. The findings that metformin has an opposite effect on various diseases are consistent with the fact that VDAC1 controls cell life and death, supporting the idea that it is a target for metformin.
Comparing Non-invasive Inverse Electrocardiography With Invasive Endocardial and Epicardial Electroanatomical Mapping During Sinus Rhythm
Authors: Roudijk Robert W. , Boonstra Machteld J. , Brummel Rolf , Kassenberg Wil , Blom Lennart J. , Oostendorp Thom F. , te Riele Anneline S. J. M. , van der Heijden Jeroen F. , Asselbergs Folkert W. , van Dam Peter M. , Loh Peter
Published: October 2021

This study presents a novel non-invasive equivalent dipole layer (EDL) based inverse electrocardiography (iECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our iECG approach with invasive electro-anatomical mapping (EAM) during sinus rhythm with the objective of enabling functional substrate imaging and sudden cardiac death risk stratification in patients with cardiomyopathy. Thirteen patients (77% males, 48 ± 20 years old) referred for endocardial and epicardial EAM underwent 67-electrode body surface potential mapping and CT imaging. The EDL-based iECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with iECG-LAT maps using absolute differences and Pearson’s correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between iECG-LAT maps and EAM was 0.54 ± 0.19 [0.49–0.59] for epicardial activation, 0.50 ± 0.27 [0.41–0.58] for right ventricular endocardial activation and 0.44 ± 0.29 [0.32–0.56] for left ventricular endocardial activation. The absolute difference in timing between iECG maps and EAM was 17.4 ± 7.2 ms for epicardial maps, 19.5 ± 7.7 ms for right ventricular endocardial maps, 27.9 ± 8.7 ms for left ventricular endocardial maps. The absolute distance between right ventricular endocardial breakthrough sites was 30 ± 16 mm and 31 ± 17 mm for the left ventricle. The absolute distance for latest epicardial activation was median 12.8 [IQR: 2.9–29.3] mm. This first in-human quantitative comparison of iECG and invasive LAT-maps on both the endocardial and epicardial surface during sinus rhythm showed improved agreement, although with considerable absolute difference and moderate correlation coefficient. Non-invasive iECG requires further refinements to facilitate clinical implementation and risk stratification.
Cell Type Dependent Suppression of Inflammatory Mediators by Myocardin Related Transcription Factors
Authors: Liu Li , Bankell Elisabeth , Rippe Catarina , Morén Björn , Stenkula Karin G. , Nilsson Bengt-Olof , Swärd Karl
Published: October 2021

Myocardin related transcription factors (MRTFs: MYOCD/myocardin, MRTF-A, and MRTF-B) play a key role in smooth muscle cell differentiation by activating contractile genes. In atherosclerosis, MRTF levels change, and most notable is a fall of MYOCD. Previous work described anti-inflammatory properties of MRTF-A and MYOCD, occurring through RelA binding, suggesting that MYOCD reduction could contribute to vascular inflammation. Recent studies have muddled this picture showing that MRTFs may show both anti- and pro-inflammatory properties, but the basis of these discrepancies remain unclear. Moreover, the impact of MRTFs on inflammatory signaling pathways in tissues relevant to human arterial disease is uncertain. The current work aimed to address these issues. RNA-sequencing after forced expression of myocardin in human coronary artery smooth muscle cells (hCASMCs) showed reduction of pro-inflammatory transcripts, including CCL2, CXCL8, IL6, and IL1B. Side-by-side comparison of MYOCD, MRTF-A, and MRTF-B in hCASMCs, showed that the anti-inflammatory impact was shared among MRTFs. Correlation analyses using human arterial transcriptomic datasets revealed negative correlations between MYOCD, MRTFA, and SRF, on the one hand, and the inflammatory transcripts, on the other. A pro-inflammatory drive from lipopolysaccharide, did not change the size of the suppressive effect of MRTF-A in hCASMCs on either mRNA or protein levels. To examine cell type-dependence, we compared the anti-inflammatory impact in hCASMCs, with that in human bladder SMCs, in endothelial cells, and in monocytes (THP-1 cells). Surprisingly, little anti-inflammatory activity was seen in endothelial cells and monocytes, and in bladder SMCs, MRTF-A was pro-inflammatory. CXCL8, IL6, and IL1B were increased by the MRTF-SRF inhibitor CCG-1423 and by MRTF-A silencing in hCASMCs, but depolymerization of actin, known to inhibit MRTF activity, had no stimulatory effect, an exception being IL1B. Co-immunoprecipitation supported binding of MRTF-A to RelA, supporting sequestration of this important pro-inflammatory mediator as a mechanism. Dexamethasone treatment and silencing of RelA (by 76 ± 1%) however only eliminated a fraction of the MRTF-A effect (≈25%), suggesting mechanisms beyond RelA binding. Indeed, SRF silencing suggested that MRTF-A suppression of IL1B and CXCL8 depends on SRF. This work thus supports an anti-inflammatory impact of MRTF-SRF signaling in hCASMCs and in intact human arteries, but not in several other cell types.
Drought, Salinity, and Low Nitrogen Differentially Affect the Growth and Nitrogen Metabolism of Sophora japonica (L.) in a Semi-Hydroponic Phenotyping Platform
Authors: Tian Jing , Pang Yue , Zhao Zhong
Published: October 2021

Abiotic stresses, such as salinity, drought, and nutrient deficiency adversely affect nitrogen (N) uptake and assimilation in plants. However, the regulation of N metabolism and N pathway genes in Sophora japonica under abiotic stresses is unclear. Sophora japonica seedlings were subjected to drought (5% polyethylene glycol 6,000), salinity (75mM NaCl), or low N (0.01mM NH4NO3) for 3weeks in a semi-hydroponic phenotyping platform. Salinity and low N negatively affected plant growth, while drought promoted root growth and inhibited aboveground growth. The NH4+/NO3− ratio increased under all three treatments with the exception of a reduction in leaves under salinity. Drought significantly increased leaf NO2− concentrations. Nitrate reductase (NR) activity was unaltered or increased under stresses with the exception of a reduction in leaves under salinity. Drought enhanced ammonium assimilation with increased glutamate synthase (GOGAT) activity, although glutamine synthetase (GS) activity remained unchanged, whereas salinity and low N inhibited ammonium assimilation with decreased GS activity under salt stress and decreased GOGAT activity under low N treatment. Glutamate dehydrogenase (GDH) activity also changed dramatically under different stresses. Additionally, expression changes of genes involved in N reduction and assimilation were generally consistent with related enzyme activities. In roots, ammonium transporters, especially SjAMT1.1 and SjAMT2.1a, showed higher transcription under all three stresses; however, most nitrate transporters (NRTs) were upregulated under salinity but unchanged under drought. SjNRT2.4, SjNRT2.5, and SjNRT3.1 were highly induced by low N. These results indicate that N uptake and metabolism processes respond differently to drought, salinity, and low N conditions in S. japonica seedlings, possibly playing key roles in plant resistance to environmental stress.
Oral Immunization With a Plant HSP90-SAG1 Fusion Protein Produced in Tobacco Elicits Strong Immune Responses and Reduces Cyst Number and Clinical Signs of Toxoplasmosis in Mice
Authors: Sánchez-López Edwin F. , Corigliano Mariana G. , Oliferuk Sonia , Ramos-Duarte Victor A. , Rivera Maximiliano , Mendoza-Morales Luisa F. , Angel Sergio O. , Sander Valeria A. , Clemente Marina
Published: October 2021

Plant 90kDa heat shock protein (HSP90) is a potent adjuvant that increases both humoral and cellular immune responses to diverse proteins and peptides. In this study, we explored whetherArabidopsis thalianaHSP90 (AtHsp81.2) can improve the immune effects of aToxoplasma gondiisurface antigen 1 (SAG1). We designed two constructs containing the sequence of mature antigen (SAG1m), from aa77to aa322,and B- and T-cell antigenic epitope-containing SAG1HC, from aa221to aa319fused to AtHsp81.2 sequence. When comparing the transient expression inNicotiana tabacumX-27-8 leaves, which overexpress the suppressor helper component protease HC-Pro-tobacco etch virus (TEV), to that inN. benthamianaleaves, co-agroinfiltrated with the suppressor p19, optimal conditions included 6-week-oldN. benthamianaplants, 7-day time to harvest,Agrobacterium tumefacienscultures with an OD600nmof 0.6 for binary vectors and LED lights. While AtHsp81.2-SAG1mfusion protein was undetectable by Western blot in any of the evaluated conditions, AtHsp81.2–SAG1HCwas expressed as intact fusion protein, yielding up to 90μg/g of fresh weight. Besides, the AtHsp81.2–SAG1HCmRNA was strongly expressed compared to the endogenousNicotiana tabacumelongation factor-alpha (NtEFα) gene, whereas the AtHsp81.2–SAG1mmRNA was almost undetectable. Finally, mice were orally immunized with AtHsp81.2–SAG1HC-infiltrated fresh leaves (plAtHsp81.2–SAG1HCgroup), recombinant AtHsp81.2–SAG1HCpurified from infiltrated leaves (rAtHsp81.2–SAG1HCgroup), non-infiltrated fresh leaves (control group), or phosphate-buffered saline (PBS group). Serum samples from plAtHsp81.2–SAG1HC-immunized mice had significantly higher levels of IgGt, IgG2a, and IgG2b anti-SAG1HCantibodies than serum from rAtHsp81.2–SAG1HC, control, and PBS groups. The number of cysts per brain in the plAtHsp81.2–SAG1HC-immunized mice was significantly reduced, and the parasite load in brain tissue was also lower in this group compared with the remaining groups. In an immunoblot assay, plant-expressed AtHsp81.2-SAG1HCwas shown to react with antibodies present in sera fromT. gondii-infected people. Therefore, the plant expression of aT. gondiiantigen fused to the non-pathogenic adjuvant and carrier plant HSP90 as formulations againstT. gondiican improve the vaccine efficacy, and plant extract can be directly used for vaccination without the need to purify the protein, making this platform a suitable and powerful biotechnological system for immunogenic antigen expression against toxoplasmosis.
Early “Rootprints” of Plant Terrestrialization: Selaginella Root Development Sheds Light on Root Evolution in Vascular Plants
Authors: Fang Tao , Motte Hans , Parizot Boris , Beeckman Tom
Published: October 2021

Roots provide multiple key functions for plants, including anchorage and capturing of water and nutrients. Evolutionarily, roots represent a crucial innovation that enabled plants to migrate from aquatic to terrestrial environment and to grow in height. Based on fossil evidence, roots evolved at least twice independently, once in the lycophyte clade and once in the euphyllophyte (ferns and seed plants) clade. In lycophytes, roots originated in a stepwise manner. Despite their pivotal position in root evolution, it remains unclear how root development is controlled in lycophytes. Getting more insight into lycophyte root development might shed light on how genetic players controlling the root meristem and root developmental processes have evolved. Unfortunately, genetic studies in lycophytes are lagging behind, lacking advanced biotechnological tools, partially caused by the limited economic value of this clade. The technology of RNA sequencing (RNA-seq) at least enabled transcriptome studies, which could enhance the understanding or discovery of genes involved in the root development of this sister group of euphyllophytes. Here, we provide an overview of the current knowledge on root evolution followed by a survey of root developmental events and how these are genetically and hormonally controlled, starting from insights obtained in the model seed plant Arabidopsis and where possible making a comparison with lycophyte root development. Second, we suggest possible key genetic regulators in root development of lycophytes mainly based on their expression profiles in Selaginella moellendorffii and phylogenetics. Finally, we point out challenges and possible future directions for research on root evolution.
Investigating the Effects of Intrinsic Motivation and Emotional Appeals Into the Link Between Organic Appeals Advertisement and Purchase Intention Toward Organic Milk
Authors: Wang Jianming , Dang Wilson , Hui Wang , Muqiang Zheng , Qi Wu
Published: October 2021

Consumers care about healthy food. Thus, several firms use organic appeals advertising to change consumer attitudes and persuade them to purchase organic food. Organic appeals advertisement often presents content that provides information and knowledge about organic elements of a food product (e.g., health, safety, a lack of chemicals, and rich nutrition). In contrast, non-organic appeals advertisement does not present information about organic elements of a food product. This study aims to clarify the effect of organic appeals advertisement on consumer motivations and behavior. It uses the stimuli-organism-response model and self-determination motivation theory to investigate the relationship between organic appeals advertisement and purchase intention toward organic milk considering the mediating role of intrinsic motivation and the moderating role of emotional appeals. Two experimental designs are used to test the hypotheses. Results show that consumers receiving organic appeals advertisement have a higher intention to purchase organic milk than those receiving non-organic appeals advertisement. Furthermore, intrinsic motivation is found to have a mediating role in the link between organic appeals advertisement and purchase intention. In other words, when consumers receive advertisements of an organic milk product, they have higher intrinsic motivation and hold higher intention to purchase organic milk products. Furthermore, emotional appeals have a moderating effect on the relationship between organic appeals advertisement and intrinsic motivation. The influence of organic appeals advertisement on intrinsic motivation is stronger when emotional appeals are positive and weaker when emotional appeals are negative.
The Value of Mechanistic Experiments to Target the Shared Neural Circuitry of Parenting and Addiction: The Potential for Video Feedback Interventions
Authors: Barrett Ann-Marie Y. , Mudiam Kavya R. , Fisher Philip A.
Published: October 2021

Certain neural processes that underlie addiction are also central to parenting, notably stress and reward. Parenting interventions that incorporate the unique context of caregivers with addiction have demonstrated some success: However, real-world implementation of evidence-based interventions can be difficult with this population. Video feedback interventions are an especially promising approach to reach parents who experience barriers to participation, particularly caregivers with addiction. A translational neuroscientific approach to elucidating the mechanisms of change in these interventions will aid the delivery and success of this method and advance theory surrounding parenting in the context of addiction. Along these lines, we provide an example of one video feedback intervention, Filming Interactions to Nurture Development, that will serve as such a mechanistic experiment.
The Teaching Design Methods Under Educational Psychology Based on Deep Learning and Artificial Intelligence
Authors: Wang Zewen , Cai Lin , Chen Yahan , Li Hongming , Jia Hanze
Published: October 2021

This study aims to evaluate the practical application value of the teaching method under the guidance of educational psychology and artificial intelligence (AI) design, taking the deep learning theory as the basis of teaching design. The research objects of this study involve all the teachers, students, and students' parents of Ningbo Middle School. The questionnaires are developed to survey the changes in the performance of students before and after the implementation of the teaching design and the satisfaction of all teachers, students, and parents to different teaching methods by comparing the two results and the satisfaction ratings. All objects in this study volunteer to participate in the questionnaire survey. The results suggest the following: (1) the effective return rates of the questionnaires to teachers, students, and parents are 97, 99, and 95%, respectively, before implementation; whereas those after implementation are 98, 99, and 99%, respectively. Comparison of the two return results suggests that there was no significant difference statistically (P > 0.05). (2) Proportion of scoring results before and after implementation is given as follows: the proportions of levels A, B, C, and D are 35, 40, 15, and 10% before implementation, respectively; while those after implementation are 47, 36, 12, and 5%, respectively. After the implementation, the proportion of level A is obviously higher than that before the implementation, and the proportions of other levels decreased in contrast to those before the implementation, showing statistically obvious differences (P < 0.05). (3) The change in the performance of each subject after 1 year implementation is significantly higher than that before the implementation, and the change in the average performance of each subject shows an upward trend. In summary, (1) the comparison on the effective return rate of the satisfaction survey questionnaire proves the feasibility of its scoring results. (2) The comparison of the survey scoring results shows that people are more satisfied with the new educational design teaching method. (3) The comparison of the change in the performance of each subject before and after the implementation indirectly reflects the drawbacks of partial subject education, indicating that the school should pay the same equal attention to every subject. (4) Due to various objective and subjective factors, the results of this study may be different from the actual situation slightly, and its accuracy has to be further explored in the future.
Individual Faces Were Not Discarded During Extracting Mean Emotion Representations
Authors: Li Huiyun , Ji Luyan , Li Qitian , Chen Wenfeng
Published: October 2021

Individuals can perceive the mean emotion or mean identity of a group of faces. It has been considered that individual representations are discarded when extracting a mean representation; for example, the “element-independent assumption” asserts that the extraction of a mean representation does not depend on recognizing or remembering individual items. The “element-dependent assumption” proposes that the extraction of a mean representation is closely connected to the processing of individual items. The processing mechanism of mean representations and individual representations remains unclear. The present study used a classic member-identification paradigm and manipulated the exposure time and set size to investigate the effect of attentional resources allocated to individual faces on the processing of both the mean emotion representation and individual representations in a set and the relationship between the two types of representations. The results showed that while the precision of individual representations was affected by attentional resources, the precision of the mean emotion representation did not change with it. Our results indicate that two different pathways may exist for extracting a mean emotion representation and individual representations and that the extraction of a mean emotion representation may have higher priority. Moreover, we found that individual faces in a group could be processed to a certain extent even under extremely short exposure time and that the precision of individual representations was relatively poor but individual representations were not discarded.
Family Function, Loneliness, Emotion Regulation, and Hope in Secondary Vocational School Students: A Moderated Mediation Model
Authors: Yun Pan , Xiaohong Han , Zhongping Yang , Zhujun Zhao
Published: October 2021

This study explored family function as a key factor of loneliness, hope, and emotion related to secondary vocational school students during the novel coronavirus pandemic. Chinese versions of the Olson Family Function Scale, Russell Loneliness Scale, Snyder Hope Scale, and Gross Emotion Regulation Scale were completed by 5,138 participants. Guardian type significantly predicted family function and loneliness. Family function significantly and positively correlated with loneliness. The relationship between family function and loneliness was mediated by hope, and expressive suppression concurrently moderated the relationship between hope and loneliness. Our study offers meaningful insights into the family function of Chinese secondary vocational school students. The findings supported a moderated mediation model that exemplifies the relationship between family function, loneliness, expressive suppression, and hope. Although the results showed that high hope mediated lower family functioning and loneliness, low expressive suppression led to intense loneliness immediately. This study confirms that emotional strategy is important and associated with mental health. It also suggests that schools should pay more attention to students' emotion regulation and help them rebuild hope or appropriate cognition to relieve loneliness during crisis events.
Design and Implementation of a Contemporary Health Administration Program for Health Managers
Authors: Khalil Hanan , Liu Chaojie
Published: October 2021

Background: While there are core competencies required in health administration programs, little is known about how they are taught in health administration programs to support/change practises. This discussion paper describes an educational innovation to design a contemporary Master of Health Administration program to meet the current needs of health managers in Australia based on evidence-based practise.

Method: A detailed gap analysis of health managers educational needs was undertaken with various stakeholders to design a contemporary health managers' program. Stakeholders surveyed in the course design included prospective students, international students' agencies, prospective employers, Alumni evaluation, mapping of health managers courses in Australia and faculty feedback. An integrative pedagogical approach was used to implement the program into action.

Results: Various themes were emerged from the stakeholder consultations including the importance of basic knowledge of key subjects and the significance of learning new skills such as strategic planning and emotional intelligence in the workplace. The integrative pedagogical approach used is based on adult teaching principles, which were identified by Knowles. The subjects in the new course incorporate several knowledge-based presentations along with interactive activities, including use of general ability-based outcomes to define learning opportunities, case-based and problem-based learning, experiential learning, and comprehensive assessments.

Conclusion: The results of this intensive consultation led to the design of a contemporary Master of Health Administration Course that included eight core subjects and multiple options of specialisations for students to choose from. Examples of specialisations include aged care and ageing, health promotion, data for decision making, public health, international development and Health Strategy and decision making.