bluuebunny/crossref_metadata_2025 huggingface dataset:
Dried Plum’s Polyphenolic Compounds and Carbohydrates Contribute to Its Osteoprotective Effects and Exhibit Prebiotic Activity in Estrogen Deficient C57BL/6 Mice
Authors: Smith Brenda J. , Hatter Bethany , Washburn Karley , Graef-Downard Jennifer , Ojo Babajide A. , El-Rassi Guadalupe Davila , Cichewicz Robert H. , Payton Mark , Lucas Edralin A.
Published: April 2022

Evidence of dried plum’s benefits on bone continues to emerge. This study investigated the contribution of the fruit’s polyphenol (PP) and carbohydrate (CHO) components on a bone model of postmenopausal osteoporosis to explore their prebiotic activity. Osteopenic ovariectomized mice were fed diets supplemented with dried plum, a crude extract of dried plum’s polyphenolic compounds, or the PP or CHO fraction of the crude extract. The effects of treatments on the bone phenotype were assessed at 5 and 10 weeks as well as the prebiotic activity of the different components of dried plum. Both the CHO and PP fractions of the extract contributed to the effects on bone with the CHO suppressing bone formation and resorption, and the PP temporally down-regulating formation. The PP and CHO components also altered the gut microbiota and cecal short chain fatty acids. These findings demonstrate that the CHO as well as the PP components of dried plum have potential prebiotic activity, but they have differential roles in mediating the alterations in bone formation and resorption that protect bone in estrogen deficiency.
Magnesium-to-Calcium Ratio and Mortality from COVID-19
Authors: Guerrero-Romero Fernando , Mercado Moises , Rodriguez-Moran Martha , Ramírez-Renteria Claudia , Martínez-Aguilar Gerardo , Marrero-Rodríguez Daniel , Ferreira-Hermosillo Aldo , Simental-Mendía Luis E. , Remba-Shapiro Ilan , Gamboa-Gómez Claudia I. , Albarrán-Sánchez Alejandra , Sanchez-García Miriam L.
Published: April 2022

Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (95%CI 1.6–29.1) in the whole population, 4.93 (95%CI 1.4–19.1, p = 0.003) in men, and 3.93 (95%CI 1.6–9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19.
Applying Machine Learning to Determine 25(OH)D Threshold Levels Using Data from the AMATERASU Vitamin D Supplementation Trial in Patients with Digestive Tract Cancer
Authors: Otani Katharina , Kanno Kazuki , Akutsu Taisuke , Ohdaira Hironori , Suzuki Yutaka , Urashima Mitsuyoshi
Published: April 2022

Some controversy remains on thresholds for deficiency or sufficiency of serum 25-hydroxyvitamin D (25(OH)D) levels. Moreover, 25(OH)D levels sufficient for bone health might differ from those required for cancer survival. This study aimed to explore these 25(OH)D threshold levels by applying the machine learning method of multivariable adaptive regression splines (MARS) in post hoc analyses using data from the AMATERASU trial, which randomly assigned Japanese patients with digestive tract cancer to receive vitamin D or placebo supplementation. Using MARS, threshold 25(OH)D levels were estimated as 17 ng/mL for calcium and 29 ng/mL for parathyroid hormone (PTH). Vitamin D supplementation increased calcium levels in patients with baseline 25(OH)D levels ≤17 ng/mL, suggesting deficiency for bone health, but not in those >17 ng/mL. Vitamin D supplementation improved 5-year relapse-free survival (RFS) compared with placebo in patients with intermediate 25(OH)D levels (18–28 ng/mL): vitamin D, 84% vs. placebo, 71%; hazard ratio, 0.49; 95% confidence interval, 0.25–0.96; p = 0.04. In contrast, vitamin D supplementation did not improve 5-year RFS among patients with low (≤17 ng/mL) or with high (≥29 ng/mL) 25(OH)D levels. MARS might be a reliable method with the potential to eliminate guesswork in the estimation of threshold values of biomarkers.
Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation
Authors: Miao Xiangguang , Wu Jin , Chen Hongping , Lu Guanting
Published: April 2022

The cytosolic PNGase (peptide:N-glycanase), also known as peptide-N4-(N-acetyl-β-glucosaminyl)-asparagine amidase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-d-glucosaminyl) asparagine residue (Asn, N) into a N-acetyl-β-d-glucosaminyl-amine and a peptide containing an aspartate residue (Asp, D). This enzyme (NGLY1) plays an essential role in the clearance of misfolded or unassembled glycoproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive (AR) human genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP pathway, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review uncovers the NGLY1’ssdetailed structure and its important roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.
Breast Milk Iodine Concentration (BMIC) as a Biomarker of Iodine Status in Lactating Women and Children <2 Years of Age: A Systematic Review
Authors: Liu Shuchang , Sharp Andrew , Villanueva Elmer , Ma Zheng Feei
Published: April 2022

Background: Iodine is needed for the production of thyroid hormones, which are essential for infant growth and development. Given that there are wide variations in breast milk iodine concentration (BMIC) and urinary iodine concentration (UIC), it is unclear if BMIC is associated with UIC in populations residing in iodine sufficient or deficient areas. Aim: To investigate if BMIC can be used as a biomarker for iodine status in lactating women and children <2 years of age. Methods: Electronic databases; PubMed, Web of Science and Scopus were searched until year 2021, for studies investigating the relationship between BMIC and UIC. Studies were reviewed for eligibility, according to inclusion and exclusion criteria, followed by data extraction, according to the PRISMA guidelines. Results: Overall, 51 studies met the criteria for inclusion in the systematic review. BMIC ranged from 18 to 1153 µg/L. In iodine-deficient and iodine-sufficient lactating women, BMIC ranged from 26 to 185 µg/L and 15 to 1006 µg/L, respectively. In most studies, the categorisation of iodine status assessed by median UIC was consistent with the categorisation of iodine status assessed by median BMIC cut off of ≥100 µg/L, to determine iodine sufficiency in lactating women and children <2 years of age. Conclusions: The systematic review indicated that BMIC is a promising biomarker of iodine status in lactating women and children <2 years of age. However, these data need to be interpreted cautiously, given the study limitations in the included studies. Future studies should consider investigating the optimal median BMIC, as there is a lack of high-quality observational and intervention studies in lactating women and infants.
Effects of Lactobacillus gasseri CP2305 on Mild Menopausal Symptoms in Middle-Aged Women
Authors: Sawada Daisuke , Sugawara Tomonori , Hirota Tatsuhiko , Nakamura Yasunori
Published: April 2022

Lactobacillus gasseri CP2305 (CP2305) is a paraprobiotic that exhibits beneficial effects on the intestinal function and microbiota, and increases resistance to psychological stress. The stress response mechanism mainly involves the hypothalamic–pituitary–adrenal axis, which is influenced by the gut–brain axis. Furthermore, the gut–brain axis also communicates bidirectionally with the intestinal microbiota. Additionally, the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes share a common route that affects both mental and health aspects in women. This double-blind, placebo-controlled, parallel-group clinical trial aimed to analyze the influence of the intake of CP2305 on mild symptoms associated with menopause. Eighty women aged 40–60 years ingested CP2305 or placebo tablets for six consecutive menstrual cycles. Assessment was based on the observation of climacteric symptoms with two validated questionnaires—the Simplified Menopausal Index (SMI) and the Greene Climacteric Scale (GCS). The results showed that CP2305 provided significant relief in the SMI total score, SMI vasomotor score, SMI psychological score, GCS total score, GCS somatic score, and GCS vasomotor score compared to the placebo. The percentage of women with symptom relief for the SMI total score was 75.0%, with 30 of 40 women in the CP2305 group, and 55.0%, with 22 of 40 women in the placebo group (p = 0.0594). These findings provide new insights into the function of paraprobiotic CP2305 in relieving mild climacteric symptoms in women.
Comparative Efficacy of Chondrosterum purpureum and Chemical Herbicides for Control of Resprouts in Tanoak and Bay Laurel
Authors: Shamoun Simon Francis , Elliott Marianne
Published: April 2022

The invasive Oomycete pathogen Phytophthora ramorum has killed millions of susceptible oak and tanoak trees in California and southern Oregon forests and is responsible for losses in revenue to the nursery industry through mitigation activities. In addition, infestation of forests in the United Kingdom by this organism has resulted in the destruction of many hectares of larch plantations. Resprouting stumps can be a reservoir for the inoculum of P. ramorum persisting on a site. In areas where the application of herbicides is not permitted, a biocontrol treatment would be an indispensable alternative. Treatment of stumps with the sap-rotting fungus Chondrostereum purpureum (Pers.) Pouzar has been shown to be an effective tool for the suppression of resprouting on several species, most notably red alder. In this project, the ability of C. purpureum to suppress resprouting was evaluated on stumps of two host species, tanoak (Notholithocarpus densiflorus) and California bay laurel (Umbellularia californica). Laboratory testing of three California isolates of C. purpureum indicated that the fungus can colonize bay laurel stems. Field trials were established near Brookings, Oregon, on tanoak and on bay laurel near Soquel, California. Early results of field testing showed that C. purpureum was able to colonize the stumps of tanoak following treatment and was found to occur naturally on tanoak logs and stumps. Formulations of C. purpureum appear to have some effect on reducing sprout survival in tanoak, but the most effective and rapid treatment for this host is the hack and squirt method of applying the herbicide imazapyr. Sprayed herbicide prevents sprouting on bay laurel, and there was evidence that resprouting was inhibited on stumps treated with C. purpureum. Over time, applications of C. purpureum may be a more permanent solution as the stumps begin to decay.
DNA Barcoding of Potential Mosquito Disease Vectors (Diptera, Culicidae) in Jazan Region, Saudi Arabia
Authors: Noureldin Elsiddig , Tan Denise , Daffalla Ommer , Almutairi Hatim , Ghzwani Jaber , Torno Majhalia , Mashi Omar , Hobani Yahya , Ding Huicong , Alamri Abdullah , Shrwani Khalid , Albarrag Ahmed , Eisa Zaki
Published: April 2022

The conventional morphological characterization of mosquito species remains heavily used for species identification in Jazan, Saudi Arabia. It requires substantial expertise and time, as well as having difficulty in confirming identity of morphologically similar species. Therefore, to establish a reliable and accurate identification system that can be applied to understanding spatial distribution of local mosquito species from the Jazan region, DNA barcoding was explored as an integrated tool for mosquito species identification. In this study, 44 adult mosquito specimens were analyzed, which contain 16 species belong to three genera of potential mosquito disease vectors (Aedes, Anopheles, and Culex). The specimens were collected from the Jazan region located in southwest Saudi Arabia. These included old and preserved mosquito voucher specimens. In addition, we assessed the genetic distance based on the generated mitochondrial partial COI DNA barcodes to detect cryptic diversity across these taxa. Nine mosquito species belonging to three genera were successfully barcoded and submitted to GenBank, namely: Aedes aegypti, Aedes caspius, Aedes vexans, Aedes vittatus, Anopheles arabiensis, Culex pipiens, Culex quinquefasciatus, Culex sitiens, and Culex tritaeniorhynchus. Of these nine species, Aedes vexans, Aedes vittatus, Culex sitiens, and Culex tritaeniorhynchus were registered in GenBank for the first time from Saudi Arabia. The DNA barcodes generated a 100% match to known barcodes of these mosquito species, that also matched with the morphological identification. Ae. vexans was found to be either a case of cryptic species (subspecies) or a new species from the region. However, more research has to be conducted to prove the latter. This study directly contributes to the development of a molecular reference library of mosquito species from the Jazan region and Saudi Arabia. The library is essential for confirmation of species in support of existing mosquito surveillance and control programmes.
Activation of Nrf2/HO-1 Antioxidant Pathway by Heme Attenuates Calcification of Human Lens Epithelial Cells
Authors: Chowdhury Arpan , Balogh Enikő , Ababneh Haneen , Tóth Andrea , Jeney Viktória
Published: April 2022

Cataract, an opacification in the crystalline lens, is a leading cause of blindness. Deposition of hydroxyapatite occurs in a cataractous lens that could be the consequence of osteogenic differentiation of lens epithelial cells (LECs). Nuclear factor erythroid 2-related factor 2 (Nrf2) controls the transcription of a wide range of cytoprotective genes. Nrf2 upregulation attenuates cataract formation. Here we aimed to investigate the effect of Nrf2 system upregulation in LECs calcification. We induced osteogenic differentiation of human LECs (HuLECs) with increased phosphate and calcium-containing osteogenic medium (OM). OM-induced calcium and osteocalcin deposition in HuLECs. We used heme to activate Nrf2, which strongly upregulated the expression of Nrf2 and heme oxygenase-1 (HO-1). Heme-mediated Nrf2 activation was dependent on the production of reactive oxygens species. Heme inhibited Ca deposition, and the OM-induced increase of osteogenic markers, RUNX2, alkaline phosphatase, and OCN. Anti-calcification effect of heme was lost when the transcriptional activity of Nrf2 or the enzyme activity of HO-1 was blocked with pharmacological inhibitors. Among products of HO-1 catalyzed heme degradation iron mimicked the anti-calcification effect of heme. We concluded that heme-induced upregulation of the Nrf2/HO-1 system inhibits HuLECs calcification through the liberation of heme iron.
Pleiotrophin Interaction with Synthetic Glycosaminoglycan Mimetics
Authors: Miles Jonathan R. , Wang Xu , de Paz Jose L. , Nieto Pedro M.
Published: April 2022

Chondroitin sulfate (CS) E is the natural ligand for pleiotrophin (PTN) in the central nervous system (CNS) of the embryo. Some structures of PTN in solution have been solved, but no precise location of the binding site has been reported yet. Using 15N-labelled PTN and HSQC NMR experiments, we studied the interactions with a synthetic CS-E tetrasaccharide corresponding to the minimum binding sequence. The results agree with the data for larger GAG (glycosaminoglycans) sequences and confirm our hypothesis that a synthetic tetrasaccharide is long enough to fully interact with PTN. We hypothesize that the central region of PTN is an intrinsically disordered region (IDR) and could modify its properties upon binding. The second tetrasaccharide has two benzyl groups and shows similar effects on PTN. Finally, the last measured compound aggregated but beforehand, showed a behavior compatible with a slow exchange in the NMR time scale. We propose the same binding site and mode for the tetrasaccharides with and without benzyl groups.
Repurposing Dimethyl Fumarate for Cardiovascular Diseases: Pharmacological Effects, Molecular Mechanisms, and Therapeutic Promise
Authors: Thomas Shilu Deepa , Jha Niraj Kumar , Sadek Bassem , Ojha Shreesh
Published: April 2022

Dimethyl fumarate (DMF) is a small molecule that has been shown to assert potent in vivo immunoregulatory and anti-inflammatory therapeutic actions. The drug has been approved and is currently in use for treating multiple sclerosis and psoriasis in the USA and Europe. Since inflammatory reactions have been significantly implicated in the etiology and progression of diverse disease states, the pharmacological actions of DMF are presently being explored and generalized to other diseases where inflammation needs to be suppressed and immunoregulation is desirable, either as a monotherapeutic agent or as an adjuvant. In this review, we focus on DMF, and present an overview of its mechanism of action while briefly discussing its pharmacokinetic profile. We further discuss in detail its pharmacological uses and highlight its potential applications in the treatment of cardiovascular diseases. DMF, with its unique combination of anti-inflammatory and vasculoprotective effects, has the potential to be repurposed as a therapeutic agent in patients with atherosclerotic cardiovascular disease. The clinical studies mentioned in this review with respect to the beneficial effects of DMF in atherosclerosis involve observations in patients with multiple sclerosis and psoriasis in small cohorts and for short durations. The findings of these studies need to be assessed in larger prospective clinical trials, ideally with a double-blind randomized study design, investigating the effects on cardiovascular endpoints as well as morbidity and mortality. The long-term impact of DMF therapy on cardiovascular diseases also needs to be confirmed.
Comparison of Losartan and Furosemide Interaction with HSA and Their Influence on HSA Antioxidant Potential
Authors: Rogóż Wojciech , Pożycka Jadwiga , Owczarzy Aleksandra , Kulig Karolina , Maciążek-Jurczyk Małgorzata
Published: April 2022

Serum albumin (HSA) is the most important protein in human body. Due to the antioxidant activity, HSA influences homeostasis maintenance and transport of drugs as well as other substances. It is noteworthy that ligands, such as popular drugs, modulate the antioxidant activity of HSA. The aim of this study was to analyze the influence of losartan (LOS) and furosemide (FUR) on HSA antioxidant properties as well as the interaction between these drugs and protein using calorimetric and spectroscopic methods. LOS and FUR showed the high affinity for human serum albumin, and the binding reactions between them were spontaneous and exothermic. LOS and FUR, separately and together in the system, have no significant impact on the secondary HSA structure; however they have significant impact on the tertiary HSA structure. LOS and FUR mixed with HSA have the ability to scavenge free radicals, and the ligand(s)–HSA interactions were synergistic.
Camostat Does Not Inhibit the Proteolytic Activity of Neutrophil Serine Proteases
Authors: Assylbekova Akmaral , Zhanapiya Anuar , Grzywa Renata , Sienczyk Marcin , Schönbach Christian , Burster Timo
Published: April 2022

Coronavirus disease 2019 (COVID-19) can lead to multi-organ failure influenced by comorbidities and age. Binding of the severe acute respiratory syndrome coronavirus 2 spike protein (SARS-CoV-2 S protein) to angiotensin-converting enzyme 2 (ACE2), along with proteolytic digestion of the S protein by furin and transmembrane protease serine subtype 2 (TMPRSS2), provokes internalization of SARS-CoV-2 into the host cell. Productive infection occurs through viral replication in the cytosol and cell-to-cell transmission. The catalytic activity of TMPRSS2 can be blocked by the trypsin-like serine protease inhibitor camostat, which impairs infection by SARS-CoV-2. At the site of infection, immune cells, such as neutrophils, infiltrate and become activated, releasing neutrophil serine proteases (NSPs), including cathepsin G (CatG), neutrophil elastase (NE), and proteinase 3 (PR3), which promote the mounting of a robust immune response. However, NSPs might be involved in infection and the severe outcome of COVID-19 since the uncontrolled proteolytic activity is responsible for many complications, including autoimmunity, chronic inflammatory disorders, cardiovascular diseases, and thrombosis. Here, we demonstrate that camostat does not inhibit the catalytic activity of CatG, NE, and PR3, indicating the need for additional selective serine protease inhibitors to reduce the risk of developing severe COVID-19.
Multimedication Guidelines: Assessment of the Size of the Target Group for Medication Review and Description of the Frequency of Their Potential Drug Safety Problems with Routine Data
Authors: Lappe Veronika , Dinh Truc Sophia , Harder Sebastian , Brueckle Maria-Sophie , Fessler Joachim , Marschall Ursula , Muth Christiane , Schubert Ingrid ,   on behalf of the EVITA Study Group
Published: April 2022

(1) Background: About 10 years ago, several guidelines for the better management of patients with polypharmacy were issued. A central issue is the definition of the target group. The primary aim of this study is therefore to assess the size of the target group, applying the criteria of the German guidelines. A further aim is to describe the frequency of occurrence of medication safety issues for patients of the target group. (2) Methods: The study is based on administrative data of one large statutory health insurer in Germany (n = 9,012,523). (3) Results: The criteria of multimorbidity (at least three chronic diseases) and utilization of five or more concurrent drugs over at least 91 days is fulfilled by 14.1% of the insured patients, or almost 1.3 million persons. About 5% of this multimorbid and poly-medicated population fulfilled at least three of out of five additional occasion-related criteria. Medication safety issues occur frequently: treatment prevalence with potentially inadequate medication, QT-drugs, benzodiazepine or Z-drugs and proton pump inhibitors was 30.4%, 28.9%, 11.1% and 52.4%, respectively. (4) Conclusions: The analysis shows the scope of patients eligible for a structured medication review and demonstrates the relevance for counselling based on the high percentage potentially at risk due to medication therapy safety problems.
Optimization of Naringin and Naringenin Extraction from Citrus × paradisi L. Using Hydrolysis and Excipients as Adsorbent
Authors: Stabrauskiene Jolita , Marksa Mindaugas , Ivanauskas Liudas , Bernatoniene Jurga
Published: April 2022

While flavanones exist in a variety of chemical forms, their favorable health effects are most prominent in their free form—aglycones. Their concentrations in grapefruit (Citrus × paradisi L.) extracts vary according to the extraction and hydrolysis methods used. The primary aim of this work was to maximize the yields of naringin and naringenin from various parts of fresh grapefruit fruits (flavedo, albedo, and segmental) using different extraction and hydrolysis methods. In addition, we aimed to evaluate the excipient—magnesium aluminometasilicate—and determine its influence on the qualitative composition of grapefruit extracts. Extracts were obtained by heat reflux extraction (HRE), ultrasound-assisted extraction with an ultrasonic homogenizer (UAE*), and ultrasound-assisted extraction with a bath (UAE). Ultrasound-assisted extraction using a bath (UAE) was modulated using acidic, thermal, and alkaline hydrolysis. The highest yield of naringin 8A (17.45 ± 0.872 mg/g) was obtained from an albedo sample under optimal conditions using ultrasound-assisted extraction; a high yield of naringenin 23-SHR (35.80 ± 1.79 µg/g) was produced using the heat reflux method from the segmental part. Meanwhile, ultrasonic combined with thermal hydrolysis significantly increased flavanone extraction from the albedo and segmental parts: naringin from sample 9-A (from 17.45 ± 0.872 mg/g to 25.05 ± 1.25 mg/g) and naringenin from sample 15-S (from 0 to 4.21 ± 0.55 µg/g). Additionally, magnesium aluminometasilicate demonstrated significant increases of naringenin from all treated grapefruit parts. To our knowledge, this is the first report of magnesium aluminometasilicate used as an adsorbent in flavanone extractions.
Development of Extended-Release Mini-Tablets Containing Metoprolol Supported by Design of Experiments and Physiologically Based Biopharmaceutics Modeling
Authors: Issa Michele Georges , de Souza Natalia Vieira , Jou Bruna Wenyi Chuang , Duque Marcelo Dutra , Ferraz Humberto Gomes
Published: April 2022

The development of extended-release dosage forms with adequate drug release is a challenge for pharmaceutical companies, mainly when the drug presents high solubility, as in Biopharmaceutics Classification System (BCS) class I. This study aimed to develop extended-release mini-tablets containing metoprolol succinate (MS), while integrating design of experiments (DOE) and physiologically based biopharmaceutics modeling (PBBM), to predict its absorption and to run virtual bioequivalence (VBE) studies in both fasted and fed states. Core mini-tablet formulations (F1, F2, and F3) were prepared by direct compression and coated using nine coating formulations planned using DOE, while varying the percentages of the controlled-release and the pore-forming polymers. The coated mini-tablets were submitted to a dissolution test; additional formulations were prepared that were optimized by simulating the dissolution profiles, and the best one was submitted to VBE studies using GastroPlus® software. An optimized formulation (FO) containing a mixture of immediate and extended-release mini-tablets showed to be bioequivalent to the reference drug product containing MS when running VBE studies in both fasted and fed states. The integration of DOE and PBBM showed to be an interesting approach in the development of extended-release mini-tablet formulation containing MS, and can be used to rationalize the development of dosage forms.
Exogenous Copper Application for the Elemental Defense of Rice Plants against Rice Leaffolder (Cnaphalocrocis medinalis)
Authors: Cheah Boon Huat , Chuang Wen-Po , Lo Jing-Chi , Li Yi , Cheng Chih-Yun , Yang Zhi-Wei , Liao Chung-Ta , Lin Ya-Fen
Published: April 2022

Metals that accumulate in plants may confer protection against herbivorous insects, a phenomenon known as elemental defense. However, this strategy has not been widely explored in important crops such as rice (Oryza sativa L.), where it could help to reduce the use of chemical pesticides. Here, we investigated the potential of copper (Cu) and iron (Fe) micronutrient supplements for the protection of rice against a major insect pest, the rice leaffolder (Cnaphalocrocis medinalis). We found that intermediate levels of Cu (20 μM CuSO4) and high concentrations of Fe (742 μM Fe) did not inhibit the growth of C. medinalis larvae but did inhibit rice root growth and reduce grain yield at the reproductive stage. In contrast, high levels of Cu (80 μM CuSO4) inhibited C. medinalis larval growth and pupal development but also adversely affected rice growth at the vegetative stage. Interestingly, treatment with 10 μM CuSO4 had no adverse effects on rice growth or yield components at the reproductive stage. These data suggest that pest management based on the application of Cu may be possible, which would be achieved by a higher effective pesticide dose to prevent or minimize its phytotoxicity effects in plants.
Genetic Dissection of Heat Stress Tolerance in Faba Bean (Vicia faba L.) Using GWAS
Authors: Maalouf Fouad , Abou-Khater Lynn , Babiker Zayed , Jighly Abdulqader , Alsamman Alsamman M. , Hu Jinguo , Ma Yu , Rispail Nicolas , Balech Rind , Hamweih Aladdin , Baum Michael , Kumar Shiv
Published: April 2022

Heat waves are expected to become more frequent and intense, which will impact faba bean cultivation globally. Conventional breeding methods are effective but take considerable time to achieve breeding goals, and, therefore, the identification of molecular markers associated with key genes controlling heat tolerance can facilitate and accelerate efficient variety development. We phenotyped 134 accessions in six open field experiments during summer seasons at Terbol, Lebanon, at Hudeiba, Sudan, and at Central Ferry, WA, USA from 2015 to 2018. These accessions were genotyped using genotyping by sequencing (GBS), and 10,794 high quality single nucleotide polymorphisms (SNPs) were discovered. These accessions were clustered in one diverse large group, although several discrete groups may exist surrounding it. Fifteen lines belonging to different botanical groups were identified as tolerant to heat. SNPs associated with heat tolerance using single-trait (ST) and multi-trait (MT) genome-wide association studies (GWASs) showed 9 and 11 significant associations, respectively. Through the annotation of the discovered significant SNPs, we found that SNPs from transcription factor helix–loop–helix bHLH143-like S-adenosylmethionine carrier, putative pentatricopeptide repeat-containing protein At5g08310, protein NLP8-like, and photosystem II reaction center PSB28 proteins are associated with heat tolerance.
Antiviral Polymers: A Review
Authors: Akbari Ali , Bigham Ashkan , Rahimkhoei Vahid , Sharifi Sina , Jabbari Esmaiel
Published: April 2022

Polymers, due to their high molecular weight, tunable architecture, functionality, and buffering effect for endosomal escape, possess unique properties as a carrier or prophylactic agent in preventing pandemic outbreak of new viruses. Polymers are used as a carrier to reduce the minimum required dose, bioavailability, and therapeutic effectiveness of antiviral agents. Polymers are also used as multifunctional nanomaterials to, directly or indirectly, inhibit viral infections. Multifunctional polymers can interact directly with envelope glycoproteins on the viral surface to block fusion and entry of the virus in the host cell. Polymers can indirectly mobilize the immune system by activating macrophages and natural killer cells against the invading virus. This review covers natural and synthetic polymers that possess antiviral activity, their mechanism of action, and the effect of material properties like chemical composition, molecular weight, functional groups, and charge density on antiviral activity. Natural polymers like carrageenan, chitosan, fucoidan, and phosphorothioate oligonucleotides, and synthetic polymers like dendrimers and sialylated polymers are reviewed. This review discusses the steps in the viral replication cycle from binding to cell surface receptors to viral-cell fusion, replication, assembly, and release of the virus from the host cell that antiviral polymers interfere with to block viral infections.
Development and Characterization of PEGylated Fatty Acid-Block-Poly(ε-caprolactone) Novel Block Copolymers and Their Self-Assembled Nanostructures for Ocular Delivery of Cyclosporine A
Authors: Binkhathlan Ziyad , Alomrani Abdullah H. , Hoxha Olsi , Ali Raisuddin , Kalam Mohd Abul , Alshamsan Aws
Published: April 2022

Low aqueous solubility and membrane permeability of some drugs are considered major limitations for their use in clinical practice. Polymeric micelles are one of the potential nano-drug delivery systems that were found to ameliorate the low aqueous solubility of hydrophobic drugs. The main objective of this study was to develop and characterize a novel copolymer based on poly (ethylene glycol) stearate (Myrj™)-block-poly(ε-caprolactone) (Myrj-b-PCL) and evaluate its potential as a nanosystem for ocular delivery of cyclosporine A (CyA). Myrj-b-PCL copolymer with various PCL/Myrj ratios were synthesized via ring-opening bulk polymerization of ε-caprolactone using Myrj (Myrj S40 or Myrj S100), as initiators and stannous octoate as a catalyst. The synthesized copolymers were characterized using 1H NMR, GPC, FTIR, XRD, and DSC. The co-solvent evaporation method was used to prepare CyA-loaded Myrj-b-PCL micelles. The prepared micelles were characterized for their size, polydispersity, and CMC using the dynamic light scattering (DLS) technique. The results from the spectroscopic and thermal analyses confirmed the successful synthesis of the copolymers. Transmission electron microscopy (TEM) images of the prepared micelles showed spherical shapes with diameters in the nano range (<200 nm). Ex vivo corneal permeation study showed sustained release of CyA from the developed Myrj S100-b-PCL micelles. In vivo ocular irritation study (Draize test) showed that CyA-loaded Myrj S100-b-PCL88 was well tolerated in the rabbit eye. Our results point to a great potential of Myrj S100-b-PCL as an ocular drug delivery system.
Starch Nanocomposite Films: Migration Studies of Nanoparticles to Food Simulants and Bio-Disintegration in Soil
Authors: Ortega Florencia , Sobral Pablo , Jios Jorge L. , Arce Valeria B. , García María Alejandra
Published: April 2022

In this work, films containing AgNPs were obtained by different green synthesis techniques (AgNP in situ and AgNP L). The inclusion of nanoparticles in the starch matrix improved both mechanical and barrier properties. The migration of AgNPs from the nanocomposite material to three food simulants (water, 3% v/v acetic acid and 15% v/v ethanol) was studied. The experimental data were fitted by using different widely accepted mathematical models (Fickian, Ritger and Peppas, and Weibull), indicating that the AgNP migration followed a complex mechanism. The silver concentration (mg Ag per kg of simulant) that was released from the nanocomposite films was higher for the samples with AgNPs in situ than for those containing AgNP L. Likewise, the maximum release value (0.141 mg/dm2 for AgNPs in situ in acetic acid simulant) was lower than the limits proposed by the legislation (European Commission and MERCOSUR; 10 and 8 mg/dm2, respectively). The replacement of conventional plastic materials by biodegradable ones requires the evaluation of bio-disintegration tests in soil. In this sense, a period of 90 days was necessary to obtain ≥50% weight loss in both nanocomposite films. Additionally, the bio-disintegration of the samples did not contribute with phytotoxic compounds to the soil, allowing the germination of fast-growing seeds.
Current State and Perspectives of Simulation and Modeling of Aliphatic Isocyanates and Polyisocyanates
Authors: Lenzi Veniero , Crema Anna , Pyrlin Sergey , Marques Luís
Published: April 2022

Aliphatic isocyanates and polyisocyanates are central molecules in the fabrication of polyurethanes, coatings, and adhesives and, due to their excellent mechanical and stability properties, are continuously investigated in advanced applications; however, despite the growing interest in isocyanate-based systems, atomistic simulations on them have been limited by the lack of accurate parametrizations for these molecular species. In this review, we will first provide an overview of current research on isocyanate systems to highlight their most promising applications, especially in fields far from their typical usage, and to justify the need for further modeling works. Next, we will discuss the state of their modeling, from first-principle studies to atomistic molecular dynamics simulations and coarse-grained approaches, highlighting the recent advances in atomistic modeling. Finally, the most promising lines of research in the modeling of isocyanates are discussed in light of the possibilities opened by novel approaches, such as machine learning.
Effect of Air-Polishing and Different Post-Polishing Methods on Surface Roughness of Nanofill and Microhybrid Resin Composites
Authors: Németh Kinga Dorottya , Haluszka Dóra , Seress László , Lovász Bálint Viktor , Szalma József , Lempel Edina
Published: April 2022

Air-abrasion is a popular prophylactic procedure to maintain oral hygiene. However, depending on the applied air-abrasive powder, it can damage the surface of the tooth and restorations, making it susceptible to plaque accumulation. The purpose of this study was to investigate the effect of 5 s and 10 s air-abrasion of calcium carbonate on surface roughness (Ra) of enamel, nanofill, and microhybrid resin-composites and the effect of post-polishing with two-step rubber- (RP) or one-step brush polisher (BP) to re-establish the surface smoothness. Surface topography was visualized by scanning-electron-microscopy. The quantitative measurement of the Ra was carried out with atomic-force-microscopy. Air-abrasion for 10 s decreased the Ra of enamel as a result of abrasion of the natural surface texture. Post-polishing with RP after 10 s air-abrasion did not change the Ra or BP; however, Ra was increased significantly by scratching the surface. Air-abrasion increased the Ra of resin composites significantly, irrespective of the application time. While RP provided a similarly smooth surface to the control in the case of microhybrid resin composite, BP increased the Ra significantly. The Ra for the control group of the nanofill-resin composite was initially high, which was further increased by air-abrasion. RP and BP re-established the initial Ra with deeper and shallower scratches after BP. Both the material and treatment type showed a large effect on Ra.
Experimental Study of the Influence of Selected Factors on the Particle Board Ignition by Radiant Heat Flux
Authors: Tureková Ivana , Ivanovičová Martina , Harangózo Jozef , Gašpercová Stanislava , Marková Iveta
Published: April 2022

Particleboards are used in the manufacturing of furniture and are often part of the interior of buildings. In the event of a fire, particleboards are a substantial part of the fuel in many building fires. The aim of the article is to monitor the effect of radiant heat on the surface of particle board according to the modified procedure ISO 5657: 1997. The significance of the influence of heat flux density and particle board properties on its thermal resistance (time to ignition) was monitored. Experimental samples were used particle board without surface treatment, with thicknesses of 12, 15, and 18 mm. The samples were exposed to a heat flux from 40 to 50 kW·m−2. The experimental results are the initiation characteristics such as of the ignition temperature and the weight loss. The determined factors influencing the time to ignition and weight loss were the thickness and density of the plate material, the density of the radiant heat flux and the distance of the particle board from the radiant source (20, 40, and 60 mm). The obtained results show a significant dependence of the time to ignition on the thickness of the sample and on the heat flux density. The weight loss is significantly dependent on the thickness of the particle board. Monitoring the influence of time to ignition from sample distance confirmed a statistically significant dependence. As the distance of the sample from the source increased, the time to ignition decreased linearly. As the distance of the sample from the source increased, the time to ignition increased.
Prediction of Durability of Thermal Insulating Epoxy Coatings with Regard to Climatic Ageing
Authors: Zhumadilova Zhanar O. , Selyaev Vladimir P. , Nurlybayev Ruslan E. , Orynbekov Yelzhan S. , Sangulova Indira B. , Kuldeyev Erzhan I.
Published: April 2022

It is generally accepted that the color and performance characteristics of liquid thermal insulation coatings are affected by the combined effect of various climatic factors such as solar radiation, temperature fluctuations, moisture, precipitation and others. This work presents the results of a scientific study of the full-scale exposure of coatings with regard to climatic ageing. Methods have been carried out, such as: spectrophotometry and direct scanning; determining adhesion, determining the adhesion strength of facing and protective coatings; and thermal conductivity and thermal resistance. As the results of the research work have shown, only in situ climatic tests, accompanied by the obligatory recording of the aggressive factors affecting the coating, make it possible to assess changes in the properties of epoxy coatings in full-scale conditions and, consequently, their climatic resistance by the methods of spectrophotometry and direct scanning. The ageing of polymer composites is known to be accompanied by a change not only in elasticity but also in color. Of the epoxy coatings tested, Etal-45M showed the greatest color variation during the in situ climate test. The most decorative resistant coatings are obtained using epoxy resin ED-20 + modified epoxy resin Etal-1440N.
A Morphological Study of Dynamically Vulcanized Styrene-Ethylene-Butylene-Styrene/Styrene-Butylene-Styrene/MethylVinylSilicon Rubber Thermoplastic Elastomer
Authors: Zhao Chunxu , Chen Xiaohan , Chen Xian
Published: April 2022

In this work, we prepared thermoplastic silicone rubber (TPSiV) by dynamically vulcanizing different relative proportions of methyl vinyl silicone rubber (MVSR), styrene ethylene butene styrene block copolymer (SEBS), and styrene butadiene styrene block copolymer (SBS). The compatibility and distribution of the MVSR phase and SEBS/SBS phase were qualitatively characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) tests on TPSiV. Subsequently, the backscattered electron signal image was analyzed using a colorimeter, and it was found that the size of the interface layer between the MVSR phase and the SEBS-SBS phase could be quantitatively characterized. This method overcomes the defect of the etching method, which cannot quantitatively analyze the size of the compatible layer between the two polymers. The final experiment proved that the two phases in TPSiV exhibited a “sea-island” structure, in which the MVSR phase acted as a dispersed phase in the SEBS-SBS phase. In addition, the addition of the silane coupling agent KH-907 (γ-isocyanatopropyltriethoxysilane) improved the mechanical properties of TPSiV, increasing the tensile strength by about 40% and the elongation at break by 30%. The permanent tensile deformation increase rate was about 15%. Through the quantitative measurement of the compatible layer, it was found that KH-907 could increase the thickness of the interface layer between the MVSR phase and the SEBS-SBS phase by more than 30%, which explained why the silane coupling agent KH-907 improved the mechanical properties of TPSiV at the micro level.
Effect of Liquid Properties on Frictional Pressure Drop in a Gas-Liquid Two-Phase Microchannel
Authors: Zhang Ruijie , Tao Fangfang , Jin Haibo , Guo Xiaoyan , He Guangxiang , Ma Lei , Zhang Rongyue , Gu Qingyang , Yang Suohe
Published: April 2022

The flow characteristics in a ring-shaped microchannel with an inner diameter of 1 mm were studied in two-phase flow systems with air-water, air-glycerol aqueous solution and air-ethanol aqueous solution using the differential pressure method. The effects of liquid properties (surface tension and viscosity) and gas/liquid superficial velocity on frictional pressure drop were discussed. The experimental results show that the frictional pressure gradient increases with the increase of superficial gas velocity, superficial liquid velocity and liquid viscosity, and increases with the decrease of liquid surface tension, which has a good agreement with the literature values. The friction pressure drop data are compared with the classical models and correlations in literature, and a reliable correlation is proposed for prediction of two-phase friction coefficient in microchannels.
Nitric Oxide-Releasing NO–Curcumin Hybrid Inhibits Colon Cancer Cell Proliferation and Induces Cell Death In Vitro
Authors: Hidmi Adel , Alzahayqa Mahmoud , Erikat Sharihan , Bahar Raghad , Hindi Lamia , Al-Maharik Nawaf , Salah Zaidoun
Published: April 2022

Cancer is a leading cause of death worldwide, and most of the currently available drugs for cancer treatment have limited potential. Natural products and their relatives continue to represent a very high percentage of the drugs used for cancer treatment. Curcumin is one of several natural drugs that has recently attracted much attention due to its putative cancer-preventive and anticancer properties. As well, Nitric Oxide (NO) holds a great potential for NO-based treatments for a wide variety of diseases. Here, for the first time, we tested the anti-cancer activities of an NO–Curcumin hybrid, hypothesizing that by joining the effects of curcumin and NO in one compound, the hybrid compound would be more potent than curcumin alone in treating colon cancer. To compare the anti-cancer activities of curcumin and NO–curcumin, we treated different colon cancer cell lines with either curcumin or NO–curcumin and tested their effects on cell proliferation and death. Our results show that NO–curcumin is more effective in reducing cell proliferation and increasing cell death when compared to curcumin. In addition, NO–curcumin has a lower IC50 compared to curcumin. Altogether, our results demonstrate for the first time that an NO–curcumin hybrid has more potent anti-cancer activity compared to curcumin alone, making it a potential future treatment for cancer and perhaps other diseases.
Shale Gas Productivity Prediction Model Considering Time-Dependent Fracture Conductivity
Authors: Pan Yuan , Xu Yiwen , Yang Ze , Wang Chunli , Liao Ruiquan
Published: April 2022

Conventional shale gas productivity prediction techniques consider fracture conductivity to be a fixed value, but in actual production processes, conductivity changes with time. Therefore, this paper proposed a capacity prediction method that considers time-dependent conductivity and validates its accuracy using commercial simulators. First, relevant parameters were obtained by fitting the improved long-term conductivity test, and then the shale gas seepage model was established using the EDFM method. The laboratory test results showed that the order of significance affecting the conductivity retention rate was fracturing fluid viscosity > sand concentration > fracturing fluid retention time; the calculation results of the production prediction model show that the flow and the pressure curves that corresponded to constant conductivity and variable conductivity were to some extent different. In the presence of complex fractures and natural fractures, the increase in the variable conductivity production curve was smaller than that of the constant conductivity production curve. This study provides some guidance for field production.