bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors
Authors: Leal Baltazar Hiram , Velasco Brenda , Cambón Adriana , Pardo Alberto , Fernandez-Vega Javier , Arellano Lilia , Al-Modlej Abeer , Mosquera Víctor X. , Bouzas Alberto , Prieto Gerardo , Barbosa Silvia , Taboada Pablo
Published: January 2022

Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects while avoiding some of the drawbacks associated with current systemic statin therapies. We report the development of nanometer-sized polymeric PLGA nanoparticles (NPs) capable of simultaneously encapsulating and delivering miRNA-124a and the statin atorvastatin (ATOR). The polymeric NPs were functionalized with an antibody able to bind to the vascular adhesion molecule-1 (VCAM1) overexpressed in the inflamed arterial endothelium. The dual-loaded NPs were non-toxic to cells in a large range of concentrations, successfully attached overexpressed VCAM receptors and released the cargoes in a sustainable manner inside cells. The combination of both ATOR and miRNA drastically reduced the levels of proinflammatory cytokines such as IL-6 and TNF-α and of reactive oxygen species (ROS) in LPS-activated macrophages and vessel endothelial cells. In addition, dual-loaded NPs precluded the accumulation of low-density lipoproteins (LdL) inside macrophages as well as morphology changes to a greater extent than in single-loaded NPs. The reported findings validate the present NPs as suitable delivery vectors capable of simultaneously targeting inflamed cells in atherosclerosis and providing an efficient approach to combination nanomedicines.
Association of P450 Oxidoreductase Gene Polymorphism with Tacrolimus Pharmacokinetics in Renal Transplant Recipients: A Systematic Review and Meta-Analysis
Authors: Lee Da-Hoon , Lee Hana , Yoon Ha-Young , Yee Jeong , Gwak Hye-Sun
Published: January 2022

There are conflicting results regarding the effect of the P450 oxidoreductase (POR) *28 genotype on the tacrolimus (TAC) pharmacokinetics (PKs) during the early post-transplantation period in adult renal transplant recipients. Thus, we characterized the impact of POR*28 on TAC PKs. We conducted a systematic review on the association between POR*28 and PKs of TAC in adult renal transplant recipients. Structured searches were conducted using PubMed, Web of Science, and Embase. TAC standardized trough concentration (ng/mL per mg/kg) data were extracted. Mean differences (MD) and their corresponding 95% confidence intervals (CIs) were used to identify the differences between the POR*28 genotype and PKs of TAC. The subgroup analysis was conducted according to CYP3A5 expression status. Six studies (n = 1061) were included. TAC standardized trough concentrations were significantly lower in recipients with the POR*28 allele compared to recipients with POR*1/*1 (MD: 8.30 ng/mL per mg/kg; 95% CI: 1.93, 14.67; p = 0.01). In the subgroup analysis, TAC standardized trough concentrations were lower for subjects who were POR*28 carriers than those who were POR*1/*1 in CYP3A5 expressers (MD: 20.21 ng/mL per mg/kg; 95% CI: 16.85, 23.56; p < 0.00001). No significant difference between POR*28 carriers and POR*1/*1 was found in the CYP3A5 non-expressers. The results of our meta-analysis demonstrated a definite correlation between the POR*28 genotype and PKs of TAC. Patients carrying the POR*28 allele may require a higher dose of TAC to achieve target levels compared to those with POR*1/*1, especially in CYP3A5 expressers.
Quantitative Structure-Activity Relationship of Enhancers of Licochalcone A and Glabridin Release and Permeation Enhancement from Carbomer Hydrogel
Authors: Wang Zhuxian , Xue Yaqi , Zhu Zhaoming , Hu Yi , Zeng Quanfu , Wu Yufan , Wang Yuan , Shen Chunyan , Jiang Cuiping , Liu Li , Zhu Hongxia , Liu Qiang
Published: January 2022

This study aimed to systematically compare licochalcone A (LicA) and glabridin (Gla) (whitening agents) release and permeation from Carbomer 940 (CP) hydrogels with different enhancers, and evaluate the relationship between the quantitative enhancement efficacy and structures of the enhancers. An in vitro release study and an in vitro permeation experiment in solution and hydrogels using porcine skin were performed. We found that the Gla–CP hydrogel showed a higher drug release and skin retention amount than LicA–CP due to the higher solubility in medium and better miscibility with the skin of Gla than that of LicA. Enhancers with a higher molecular weight (MW) and lower polarizability showed a higher release enhancement effect (ERrelease) for both LicA and Gla. The Van der Waals forces in the drug–enhancers–CP system were negatively correlated with the drug release percent. Moreover, enhancers with a higher log P and polarizability displayed a higher retention enhancement effect in solution (ERsolution retention) for LicA and Gla. Enhancers decreased the whole intermolecular forces indrug–enhancers-skin system, which had a linear inhibitory effect on the drug retention. Moreover, C=O of ceramide acted asthe enhancement site for drug permeation. Consequently, Transcutol® P (TP) and propylene glycol (PG), seven enhancers showed a higher retention enhancement effect in hydrogel (ERhydrogel retention) for LicA and Gla. Taken together, the conclusions provide a strategy for reasonable utilization of enhancers and formulation optimization in topical hydrogel whitening.
The Antidiabetic Effects and Modes of Action of the Balanites aegyptiaca Fruit and Seed Aqueous Extracts in NA/STZ-Induced Diabetic Rats
Authors: Zaky Asmaa S. , Kandeil Mohamed , Abdel-Gabbar Mohamed , Fahmy Eman M. , Almehmadi Mazen M. , Ali Tarek M. , Ahmed Osama M.
Published: January 2022

Diabetes mellitus (DM) is a chronic metabolic disorder that threatens human health. Medicinal plants have been a source of wide varieties of pharmacologically active constituents and used extensively as crude extracts or as pure compounds for treating various disease conditions. Thus, the aim of this study is to assess the anti-hyperglycemic and anti-hyperlipidemic effects and the modes of action of the aqueous extracts of the fruits and seeds of Balanites aegyptiaca (B. aegyptiaca) in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. Gas chromatography–mass spectrometry analysis indicated that 3,4,6-tri-O-methyl-d-glucose and 9,12-octadecadienoic acid (Z,Z)- were the major components of the B. aegyptiaca fruit and seed extracts, respectively. A single intraperitoneal injection of STZ (60 mg/kg body weight (b.w.)) 15 min after intraperitoneal NA injection (60 mg/kg b.w.) was administered to induce type 2 DM. After induction was established, the diabetic rats were treated with the B. aegyptiaca fruit and seed aqueous extracts (200 mg/kg b.w./day) via oral gavage for 4 weeks. As a result of the treatments with the B. aegyptiaca fruit and seed extracts, the treated diabetic-treated rats exhibited a significant improvement in the deleterious effects on oral glucose tolerance; serum insulin, and C-peptide levels; liver glycogen content; liver glucose-6-phosphatase and glycogen phosphorylase activities; serum lipid profile; serum free fatty acid level; liver lipid peroxidation; glutathione content and anti-oxidant enzyme (glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase) activities; and the mRNA expression of the adipose tissue expression of the insulin receptor β-subunit. Moreover, the treatment with fruit and seed extracts also produced a remarkable improvement of the pancreatic islet architecture and integrity and increased the islet size and islet cell number. In conclusion, the B. aegyptiaca fruit and seed aqueous extracts exhibit potential anti-hyperglycemic and anti-hyperlipidemic effects, which may be mediated by increasing the serum insulin levels, decreasing insulin resistance, and enhancing the anti-oxidant defense system in diabetic rats.
Concept of Orodispersible or Mucoadhesive “Tandem Films” and Their Pharmaceutical Realization
Authors: Göbel Anja , Breitkreutz Jörg
Published: January 2022

Orodispersible or mucoadhesive films as a patient-oriented dosage form for low-dosed drugs are usually produced using solvent casting. This paper presents a modification of the solvent casting technique that aimed to divide oral films into two or more compartments. The proposed objectives and fields of applications include improved handling properties and safety of application, the optimization of drug release kinetics and the enhancement of long-term stability when combining two or more active pharmaceutical ingredients into one oral film. A feasibility study for the combination of different film-forming polymers to generate the so-called tandem films was performed. As examples of practical implementation, orodispersible applicator films consisting of a drug-loaded section and a handheld piece were cast, and mucoadhesive buccal tandem films were cast to optimize the dissolution rate of the films.
Anti-VEGF Drugs Dynamics: Relevance for Clinical Practice
Authors: Veritti Daniele , Sarao Valentina , Gorni Gianluca , Lanzetta Paolo
Published: January 2022

Background: A drug and disease assessment model was used to evaluate the impact of different treatment regimens on intravitreal ranibizumab, bevacizumab, aflibercept, and brolucizumab concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF. Methods: A time-dependent mathematical model using Wolfram Mathematica software was used. The pharmacokinetic and pharmacodynamic data for anti-VEGFs were obtained from published reports. The model simulated drug concentration after single and multiple doses of ranibizumab, bevacizumab, aflibercept, and brolucizumab, and it extrapolated time-dependent intraocular free VEGF proportion values. Various fixed treatment regimens (q4, q8, q10, q12) were simulated and evaluated as candidates for clinical utilization. Results: Our mathematical model shows good correlation between intraocular VEGF proportion values and clinical data. Simulations suggest that each anti-VEGF agent would allow for distinct treatment intervals to keep the proportion of free VEGF under threshold levels. Regimens scheduling q8 ranibizumab, q8 bevacizumab, q12 aflibercept, and q10 brolucizumab administration permit to maintain the proportion of unbound VEGF below 0.001%. Conclusions: Fixed q8 ranibizumab, q8 bevacizumab, q12 aflibercept, or q10 brolucizumab regimens may produce adequate intraocular VEGF inhibition.
Using Machine Learning for Pharmacovigilance: A Systematic Review
Authors: Pilipiec Patrick , Liwicki Marcus , Bota András
Published: January 2022

Pharmacovigilance is a science that involves the ongoing monitoring of adverse drug reactions to existing medicines. Traditional approaches in this field can be expensive and time-consuming. The application of natural language processing (NLP) to analyze user-generated content is hypothesized as an effective supplemental source of evidence. In this systematic review, a broad and multi-disciplinary literature search was conducted involving four databases. A total of 5318 publications were initially found. Studies were considered relevant if they reported on the application of NLP to understand user-generated text for pharmacovigilance. A total of 16 relevant publications were included in this systematic review. All studies were evaluated to have medium reliability and validity. For all types of drugs, 14 publications reported positive findings with respect to the identification of adverse drug reactions, providing consistent evidence that natural language processing can be used effectively and accurately on user-generated textual content that was published to the Internet to identify adverse drug reactions for the purpose of pharmacovigilance. The evidence presented in this review suggest that the analysis of textual data has the potential to complement the traditional system of pharmacovigilance.
Extracellular Vesicle-Based Hybrid Systems for Advanced Drug Delivery
Authors: Rodríguez Diego A. , Vader Pieter
Published: January 2022

The continuous technological advancement of nanomedicine has enabled the development of novel vehicles for the effective delivery of therapeutic substances. Synthetic drug delivery systems are nano-sized carriers made from various materials that can be designed to deliver therapeutic cargoes to cells or tissues. However, rapid clearance by the immune system and the poor targeting profile of synthetic drug delivery systems are examples of the pressing obstacles faced in nanomedicine, which have directed the field toward the development of alternative strategies. Extracellular vesicles (EVs) are nanoscale particles enclosed by a protein-rich lipid bilayer; they are released by cells and are considered to be important mediators of intercellular communication. Owing to their natural composition, EVs have been suggested to exhibit good biocompatibility and to possess homing properties to specific cell types. Combining EVs with synthetic nanoparticles by defined hybridization steps gives rise to a novel potential drug delivery tool, i.e., EV-based hybrid systems. These novel therapeutic vehicles exhibit potential advantageous features as compared to synthetic drug delivery systems such as enhanced cellular uptake and cargo delivery, immuno-evasive properties, capability of crossing biological barriers, and tissue targeting profile. Here, we provide an overview of the various strategies practiced to produce EV-based hybrid systems and elucidate those advantageous features obtained by synthetic drug delivery systems upon hybridization with EVs.
Need for Expansion of Pharmacy Education Globally for the Growing Field of Nanomedicine
Authors: Barton Amy E. , Borchard Gerrit , Wacker Matthias G. , Pastorin Giorgia , Saleem Imran Y. , Chaudary Shaqil , Elbayoumi Tamer , Zhao Zhigang , Flühmann Beat
Published: January 2022

The emerging landscape of nanomedicine includes a wide variety of active pharmaceutical ingredients and drug formulations. Their design provides nanomedicines with unique features leading to improved pharmacokinetics and pharmacodynamics. They are manufactured using conventional or biotechnological manufacturing processes. Their physical characteristics are vastly different from traditional small-molecule drugs. Pharmacists are important members of the multi-disciplinary team of scientists involved in their development and clinical application. Consequently, their training should lead to an understanding of the complexities associated with the production and evaluation of nanomedicines. Therefore, student pharmacists, post-doctoral researchers, and trainees should be given more exposure to this rapidly evolving class of therapeutics. This commentary will provide an overview of nanomedicine education within the selection of pharmacy programs globally, discuss the current regulatory challenges, and describe different approaches to incorporate nanomedicine science in pharmacy programs around the world.
Correction of Spatial Nonuniformity in Spectroradiometer Field-of-View Using a Concentric-Circles Method
Authors: Jiao Zhaoqiang , Li Yiwen , Chen Ge , Li Yao , Chai Shijie , Zhang Puyousen
Published: January 2022

Spectroradiometers exhibit the smallest aberration and the optimum response at the field-of-view (FOV) center. The aberration increases and the response deteriorates at positions further away from the FOV center, which leads to nonuniformity in the spectroradiometer FOV. In this study, a concentric-circles method for correcting the spectroradiometer FOV nonuniformity was developed. The calibration experiment for FOV nonuniformity was conducted by establishing the experimental platform. The nonuniformity correction coefficients were obtained and then used to fit the correction function curve within the whole FOV, allowing for correction of measurement targets with an arbitrary shape. The radiation intensity of the blackbody at different temperatures was obtained by measurement, and the nonuniformity coefficient was used to correct it. After correction, the error was within 1.84% for the spectrally integrated radiant intensity in the non-absorption band. Using this correction method, efficient calibration of spectroradiometer nonuniformity can be achieved, thereby enhancing the measurement accuracy of the spectroradiometer.
Mechanistic Aspects and Effects of Selected Tank-Mix Partners on Herbicidal Activity of a Novel Fatty Acid Ester
Authors: Campos Javier , Bodelon Luciana , Verdeguer Mercedes , Baur Peter
Published: January 2022

Only a limited number of contact herbicides exist in agricultural production. While systemic herbicides are more efficient also at suboptimum spray coverage with long-lasting weed control, contact herbicides provide several advantages. There is no translocation to fruits or roots of plantation and other crop, low risk for resistance development, and minor risk for spray-drift damage. Besides, synthetic products that often have toxicological or residues issues, natural fatty acids, particularly pelargonic acid (PA), have contact activity and are safer for home and garden use. We recently described a methyl capped polyethylene glycol ester of pelargonic acid (PA-MPEG) that acts independent of acid formation. Both, PA-MPEG and PA are applied at high rates per hectare to achieve excellent weed control. Here, we report about potential additives to increase PA-MPEG efficacy. The herbicidal active, 1-decanol, and the non-phytotoxic alkylated seed oil-based adjuvant, HastenTM, improved performance and outperformed a commercial PA herbicide. Both, PA-MPEG and PA appear to mainly act by the disintegration of bio-membranes besides having effects on transpiration. The main suggested effect is desiccation due to cutting the water continuum at the site of evaporation in the intercellular spaces. The synergistic action of the adjuvant HastenTM and its practical uses are also discussed.
Antibacterial Potential of Extracts and Phytoconstituents Isolated from Syncarpia hillii Leaves In Vitro
Authors: Perera Muthukuttige M. N. , Dighe Satish N. , Katavic Peter L. , Collet Trudi A.
Published: January 2022

(1) Background: Rapidly increasing antibiotic resistance is one of the greatest threats to global health, affecting individuals regardless of age. Medicinal plants are widely used in traditional medicine to prevent and attenuate infectious conditions with minimal adverse effects. However, only a few have been phytochemically investigated for their medicinal properties and subsequent biological activities. Syncarpia hillii, a plant traditionally used by Indigenous Australians to treat sores, wounds, and skin infections, is no exception. (2) Methods: Primary extracts obtained from mature S. hillii leaves were evaluated for their antibacterial potential against 19 bacterial strains. The methanol extract was subjected to compound isolation and identification due to its preliminary bactericidal efficacy. (3) Results: Staphylococcal species were the most susceptible bacterial strain with a MIC value of 0.63 mg/mL to the S. hillii methanol extract. Quercetin-3-O-β-D-glucuronide and shikimic acid isolated from S. hillii methanol leaf extracts exhibited enhanced antibacterial effects against the tested bacteria with quercetin-3-O-β-D-glucuronide eliciting a MIC value of 0.78 µg/mL against E. faecalis. (4) Conclusions: S. hillii leaves are comprised of bioactive compounds that are bactericidal against several Gram-positive and Gram-negative bacteria.
Tetracera loureiri Extract Regulates Lipopolysaccharide-Induced Inflammatory Response Via Nuclear Factor-κB and Mitogen Activated Protein Kinase Signaling Pathways
Authors: Lee Jung A , Shin Ju Young , Hong Seong Su , Cho Young-Rak , Park Ju-Hyoung , Seo Dong-Wan , Oh Joa Sub , Kang Jae-Shin , Lee Jae Ho , Ahn Eun-Kyung
Published: January 2022

Tetracera loureiri (T. loureiri) is a woody climber inhabiting open deciduous or evergreen forests in Southeast Asia. A decoction comprising its stem and other herbs is a traditional Thai remedy for fatigue and jaundice, as well as to promote overall health. Anti-inflammatory effects induced by T. loureiri extract have not been reported. In this study, we investigated the anti-inflammatory effect of an ethanol extract of T. loureiri (ETL) on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 macrophages. We found that ETL treatment inhibited the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells, without affecting cell viability. The effect of ETL on the expression of various pro-inflammatory mediators was analyzed using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). We observed that ETL inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels and decreased the production of prostaglandin E2 (PGE2) by COX-2 in RAW264.7 macrophages. ETL dose-dependently reduced the production of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in LPS-induced RAW264.7 cells, in a dose-dependent manner. Furthermore, ETL suppressed the LPS-induced nuclear translocation of the nuclear factor, NF-κB. Additionally, ETL was found to inhibit the activation of mitogen-activated protein kinases (MAPK), such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and p38 MAPK. In conclusion, our findings demonstrate that ETL inhibits the expression of pro-inflammatory mediators and cytokines, thereby downregulating NF-κB and MAPK signaling pathways in LPS-stimulated macrophages, Consequently, ETL is a potential therapeutic agent for the treatment of inflammatory diseases.
Pollen Production of Selected Grass Species in Russia and India at the Levels of Anther, Flower and Inflorescence
Authors: Severova Elena , Kopylov-Guskov Yury , Selezneva Yulia , Karaseva Vera , Yadav Shrirang R. , Sokoloff Dmitry
Published: January 2022

Grasses produce large amounts of pollen and are among the main causes of pollen allergy worldwide. Quantification of the roles of individual grass species in airborne pollen is an important task, because morphologically indistinguishable pollen grains of different species may differ in allergenicity. This requires knowledge of the pollen production of individual grass species; however, accumulated data are insufficient in this respect. Attempting to fill this gap, we studied pollen production per inflorescence in 29 grass species which are widespread in Middle Russia and India. Pollen production per inflorescence is determined by the number of grains per anther, the number of flowers in a spikelet and the number of spikelets per inflorescence, with the latter parameter being the most variable. We support the hypothesis that pollen production per inflorescence differs significantly between annual and perennial grasses. The greater pollen production of perennials can be interpreted as a tendency to guarantee cross-fertilization of species with self-incompatibility. The inferred pollen/ovule (P/O) ratios suggest the occurrence of facultative xenogamy in all annuals and obligate xenogamy in most perennials in the present dataset, though some self-incompatible annuals exist outside our sampling. Earlier data indicated that the P/O ratio of the annual cereal crop rye (Secale cereale) is higher than in any annual or perennial species sampled here. A ratio of pollen production to seed set (P/S ratio) is suggested to be another efficient parameter in reproductive biology of grasses. We highlight a need for detailed studies of reproductive biology in grasses that include both pollen and seed production. We found a correlation between pollen production per anther and anther length. A rough approximation of c. 1000 pollen grains per 1 mm of the length of an anther provides an instrument for estimates of pollen production in plant communities.
Grazing and Mowing Affect the Carbon-to-Nitrogen Ratio of Plants by Changing the Soil Available Nitrogen Content and Soil Moisture on the Meadow Steppe, China
Authors: Wang Le , Xu Hengkang , Zhang Hao , Zhang Yingjun
Published: January 2022

Common grassland management practices affect plant and soil element stoichiometry, but the primary environmental factors driving variation in plant C/N ratios for different species in different types of grassland management remain poorly understood. We examined the three dominant C/N stoichiometric responses of plants to different land uses (moderate grazing and mowing) in the temperate meadow steppe of northern China. Our results showed that the responses of the C/N ratio of dominant plants differed according to the management practice. The relative abundance of N in plant tissues increased due to increased soil NO3−, with a consequent decrease in plant C: N in the shoots of Leymus chinensis, but the C/N ratio and nitrogen concentration in the shoots of Bromus inermis and Potentilla bifurca were relatively stable under short-term moderate grazing management. Mowing reduced the concentration of soil NH4+, thus reducing the nitrogen concentration of the roots, resulting in a decrease in the root C/N ratio of Potentilla bifurca. Structural equation model (SEM) showed that the root C/N ratio was affected by both root N and soil inorganic N, while shoot C/N ratio was only affected by the soil inorganic N. Our findings provide a mechanistic understanding of the responses of plant C/N ratio to land use change. The species-level responses of plant stoichiometry to human-managed grasslands deserve more attention.
Response of Transgenic Potato Plants Expressing Heterologous Genes of ∆9- or ∆12-Acyl-lipid Desaturases to Phytophthora infestans Infection
Authors: Tsypurskaya Elena V. , Nikolaeva Tatiana N. , Lapshin Petr V. , Nechaeva Tatiana L. , Yuorieva Natalya O. , Baranova Ekaterina N. , Derevyagina Marina K. , Nazarenko Lyudmila V. , Goldenkova-Pavlova Irina V. , Zagoskina Natalia V.
Published: January 2022

Late blight is one of the most economically important diseases affecting potato and causing a significant loss in yield. The development of transgenic potato plants with enhanced resistance to infection by Phytophthora infestans may represent a possible approach to solving this issue. A comparative study of the leaf response in control potato plants (S.tuberosum L. cultivar Skoroplodnyi), control transgenic plants expressing the reporter gene of thermostable lichenase (transgenic licBM3 line) and transgenic plants expressing cyanobacterial hybrid genes ∆9-acyl-lipid desaturase (transgenic desC lines) and ∆12-acyl-lipid desaturase (transgenic desA lines) to infection with P. infestans has been performed. The expression of desaturase genes in potato plants enhanced their tolerance to potato late blight agents as compared with the control. The lipid peroxidation level raised in the leaves of the control and transgenic desA plants on third day after inoculation with P. infestans zoospores and remained the same in the transgenic desC plants. The number of total phenolic compounds was increased as early as on the second day after infection in all studied variants and continued to remain the same, except for transgenic desC plants. Accumulation of flavonoids, the main components of the potato leaf phenolic complex, raised on the second day in all studied variants, remained unchanged on the third day in the control plants and decreased in most transgenic plants expressing desaturase genes. The results obtained in our study demonstrate that the expression of genes of Δ9- and Δ12-acyl-lipid desaturases in potato plants enhanced their resistance to P. infestans as compared with the control non-transgenic plants due to concomitant accumulation of phenolic compounds, including flavonoids, in the leaves. All these changes were more pronounced in transgenic desC plants, which indicates that the Δ9-acyllipid desaturase gene appears to be a potential inducer of the production of biological antioxidants in plant cells.
Identification of Novel Candidate Genes Involved in Apple Cuticle Integrity and Russeting-Associated Triterpene Synthesis Using Metabolomic, Proteomic, and Transcriptomic Data
Authors: André Christelle M. , Guerriero Gea , Lateur Marc , Charton Sophie , Leclercq Celine C. , Renaut Jenny , Hausman Jean-Francois , Legay Sylvain
Published: January 2022

Apple russeting develops on the fruit surface when skin integrity has been lost. It induces a modification of fruit wax composition, including its triterpene profile. In the present work, we studied two closely related apple varieties, ‘Reinette grise du Canada’ and ‘Reinette blanche du Canada’, which display russeted and non-russeted skin phenotypes, respectively, during fruit development. To better understand the molecular events associated with russeting and the differential triterpene composition, metabolomics data were generated using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) and combined with proteomic and transcriptomic data. Our results indicated lower expression of genes linked to cuticle biosynthesis (cutin and wax) in russet apple throughout fruit development, along with an alteration of the specialized metabolism pathways, including triterpene and phenylpropanoid. We identified a lipid transfer protein (LTP3) as a novel player in cuticle formation, possibly involved in the transport of both cutin and wax components in apple skin. Metabolomic data highlighted for the first time a large diversity of triterpene-hydroxycinnamates in russeted tissues, accumulation of which was highly correlated with suberin-related genes, including some enzymes belonging to the BAHD (HXXXD-motif) acyltransferase family. Overall, this study increases our understanding about the crosstalk between triterpene and suberin pathways.
Image Analysis of Adventitious Root Quality in Wild Sage and Glossy Abelia Cuttings after Application of Different Indole-3-Butyric Acid Concentrations
Authors: Loconsole Danilo , Cristiano Giuseppe , De Lucia Barbara
Published: January 2022

Adventitious root (AR) formation is a key step in stem cutting propagation of economically important woody ornamentals. Inadequate environmental and hormonal conditions can lead to the production of an insufficient or modest number of ARs in stem cutting, with a consequent decrease in quality. The aim of this research was to optimize wild sage and glossy abelia autumn stem cutting propagation protocols, using image analysis to assess the effects of different IBA concentrations and cultivars on AR quality. For both taxa, the treatments were: four IBA concentrations: 0, 1250, 2500 and 5000 mg L−1 and two cultivars: ‘Little Lucky’ (cv1) and ‘Yellow’ (cv2) from Lantana, and ‘Canyon Creek’ (cv1) and ‘Eduard Goucher’ (cv2) from Abelia. Results show that IBA application is not needed to enhance rooting ability; however, IBA concentration is an important factor determining the best overall AR quality in both taxa. In wild sage applying 5000 mg L−1 IBA improved AR quality in ‘Little Lucky’, increasing the root number, total length, surface area and number of forks and crossings, but decreased quality in ‘Yellow’. In glossy abelia ‘Edouard Goucher’, 5000 mg L−1 IBA increased the root number, but 1250 mg L−1 IBA improved AR quality; ‘Canyon Creek’ did not perform as well as cv2 at these concentrations. This study confirms that sensitivity to IBA dosage varies among species and their cultivars. Findings may help the commercial nursery industry produce higher quality cuttings.
Leaf and Canopy Traits Associated with Stay-Green Expression Are Closely Related to Yield Components of Wheat Genotypes with Contrasting Tolerance to Water Stress
Authors: Moraga Felipe , Alcaíno Marta , Matus Iván , Castillo Dalma , del Pozo Alejandro
Published: January 2022

The onset and rate of senescence influence key agronomical traits, including grain yield (GY). Our objective was to assess the relationships between stay-green and GY in a set of fourteen spring bread wheat (Triticum aestivum L.) genotypes with contrasting tolerance to water stress. Based on leaf chlorophyll content index (Chl) and normalized vegetation index (NDVI) measurements, the senescence dynamics at leaf and canopy levels, respectively, were quantified. Parameters describing the dynamics of senescence were examined in glasshouse and field experiments under well-watered (WW) and water-limited (WL) regimes, and they included the following stay-green traits: maximum NDVI or Chl near to anthesis (NDVImax, Chlmax), the senescence rate (SR, rate), the area under curve (AreaNDVI, AreaChl), and the time from anthesis to 10 (tonset), 50 (t50, X50) and 90% (t90) senescence. Our results revealed that specific stay-green traits were significantly different among genotypes and water regimes in both glasshouse and field experiments. GY was positively correlated with ttotal (0.42), tonset (0.62) and NDVIdif (0.63). Under WL, NDVIdif and NDVImax correlated with GY (0.66–0.58), but only t50 correlated with GY under WW (0.62), indicating that phenotyping of stay-green trait is a useful tool for tracking the dynamics of senescence in WW and WL environments.
Microclimatic Alteration after Logging Affects the Growth of the Endangered Lichen Lobaria pulmonaria
Authors: Di Nuzzo Luca , Giordani Paolo , Benesperi Renato , Brunialti Giorgio , Fačkovcová Zuzana , Frati Luisa , Nascimbene Juri , Ravera Sonia , Vallese Chiara , Paoli Luca , Bianchi Elisabetta
Published: January 2022

Microclimatic conditions are important in determining lichen distribution at small scale, and may determine whether the species persist when the surrounding environmental conditions have drastically changed. This is the case with forest management, since a sudden variation of microclimatic conditions (increase of solar radiation, temperature, wind and a reduction of humidity) may occur after logging. In this study, the combined effect of forest logging and microclimatic conditions on the growth probabilities and growth rates of the model species Lobaria pulmonaria was assessed in mixed oak stands. To this purpose, 800 fragments of L. pulmonaria (<1 cm) were transplanted in logged and unlogged stands for two years. Young and adult fragments were positioned on Turkey oak boles according to distance from the ground (100 and 50 cm) and aspect (north and south). The results, evaluated by generalized linear mixed models on a yearly basis, highlighted differences in growth—particularly on isolated trees in the logged stand. South-exposed samples in the logged stand showed a low probability of growth, while samples transplanted north in the unlogged stand showed higher growth probabilities. However, the highest annual growth coefficients corresponded to south-exposed samples 50 cm from the ground in the unlogged stand. In general, higher growth rates were observed in young thallus fragments when compared with adult ones. Beyond confirming the importance of microclimate for lichen ecology, these results could be implemented in conservation actions to preserve L. pulmonaria populations in logged forests.
An Up-to-Date Review of Biomaterials Application in Wound Management
Authors: Niculescu Adelina-Gabriela , Grumezescu Alexandru Mihai
Published: January 2022

Whether they are caused by trauma, illness, or surgery, wounds may occur throughout anyone’s life. Some injuries’ complexity and healing difficulty pose important challenges in the medical field, demanding novel approaches in wound management. A highly researched possibility is applying biomaterials in various forms, ranging from thin protective films, foams, and hydrogels to scaffolds and textiles enriched with drugs and nanoparticles. The synergy of biocompatibility and cell proliferative effects of these materials is reflected in a more rapid wound healing rate and improved structural and functional properties of the newly grown tissue. This paper aims to present the biomaterial dressings and scaffolds suitable for wound management application, reviewing the most recent studies in the field.
The Role of Eucalyptus Species on the Structural and Thermal Performance of Cellulose Nanocrystals (CNCs) Isolated by Acid Hydrolysis
Authors: Gil-Castell Oscar , Reyes-Contreras Pablo , Barra Pabla Andrea , Teixeira Mendonça Regis , Carrillo-Varela Isabel , Badia José David , Serra Angels , Ribes-Greus Amparo
Published: January 2022

Cellulose nanocrystals (CNCs) are attractive materials due to their renewable nature, high surface-to-volume ratio, crystallinity, biodegradability, anisotropic performance, or available hydroxyl groups. However, their source and obtaining pathway determine their subsequent performance. This work evaluates cellulose nanocrystals (CNCs) obtained from four different eucalyptus species by acid hydrolysis, i.e., E. benthamii, E. globulus, E. smithii, and the hybrid En × Eg. During preparation, CNCs incorporated sulphate groups to their structures, which highlighted dissimilar reactivities, as given by the calculated sulphate index (0.21, 0.97, 0.73 and 0.85, respectively). Although the impact of the incorporation of sulphate groups on the crystalline structure was committed, changes in the hydrophilicity and water retention ability or thermal stability were observed. These effects were also corroborated by the apparent activation energy during thermal decomposition obtained through kinetic analysis. Low-sulphated CNCs (E. benthamii) involved hints of a more crystalline structure along with less water retention ability, higher thermal stability, and greater average apparent activation energy (233 kJ·mol−1) during decomposition. Conversely, the high-sulphated species (E. globulus) involved higher reactivity during preparation that endorsed a little greater water retention ability and lower thermal stability, with subsequently less average apparent activation energy (185 kJ·mol−1). The E. smithii (212 kJ·mol−1) and En × Eg (196 kJ·mol−1) showed an intermediate behavior according to their sulphate index.
Experimental Characterization and Modeling of 3D Printed Continuous Carbon Fibers Composites with Different Fiber Orientation Produced by FFF Process
Authors: Lupone Federico , Padovano Elisa , Venezia Cinzia , Badini Claudio
Published: January 2022

The development of 3D printed composites showing increased stiffness and strength thanks to the use of continuous carbon fibers has offered new prospects for Fused Filament Fabrication (FFF) technique. This work aims to investigate the microstructure and mechanical properties of 3D printed CCF/PA composites with various layups, and also to apply predictive models. The mechanical properties of the printed parts were directly related to the adopted laminate layup as well as to the microstructure and defects induced by the FFF process. The highest stiffness and strength were reported for longitudinal composites, where the fibers are unidirectionally aligned in the loading direction. In addition, it was found that the reduction in tensile properties obtained for cross-ply and quasi-isotropic laminate layups can be described by using the Angle Minus Longitudinal. A step-like failure with extensive fibers breakage and pull-out was observed for the longitudinal composites. By contrast, the rupture mode of the quasi-isotropic laminates mainly exhibited debonding between beads. Moreover, the predictions obtained using the Volume Average Stiffness method and Classical Laminate Theory were in good agreement with the tensile test results. This work could help engineers to design complex laminates with specific mechanical requirements by tailoring the orientation of continuous carbon fibers.
The Effect of Polymers on Drug Release Kinetics in Nanoemulsion In Situ Gel Formulation
Authors: Vijaya Rani K. Reeta , Rajan Sruthi , Bhupathyraaj Mullaicharam , Priya R. Krishna , Halligudi Nirmala , Al-Ghazali Mohammad Abobakr , Sridhar Sathvik B. , Shareef Javedh , Thomas Sabin , Desai Saleem M. , Pol Pandurang D.
Published: January 2022

Glaucoma is an ocular condition characterized by elevated intraocular pressure (IOP). Conventional treatments of glaucoma face poor corneal permeability and bioavailability. To address these issues, a nanoemulsion in situ gel of Timolol maleate was developed in this study by adding the polymer Carbopol 934p. Using Carbopol 934p, a novel ophthalmic pH-induced nanoemulsion in situ gel was formulated. The formulation was liquid at pH 4 and quickly gelled when the pH was raised to 7.4 (Lacrimal pH). The pH-triggered in situ gelling mechanism demonstrated continuous drug release over a 24 h cycle. A total of nine trial formulations were prepared (NEI1–NEI9) and subjected to various physicochemical and in vitro evaluations. According to the in vitro release kinetics, the drug release of Timolol maleate nanoemulsion in situ gel NEI5 followed zero-order kinetics, with a release exponent value of 0.902, indicating that the mechanism of release was non-Fickian diffusion regulated. In vivo results showed that Timolol maleate nanoemulsion in situ gel NEI5 provided a better-sustained release of the drug, compared with the Timolet OD eye drops. The formulation is stable in storage, with no distinguishable change in appearance, physical properties, quality, and percentage drug release. NEI5 also reduces drug administration frequency, which improves patient compliance. Timolol maleate nanoemulsion in situ gel NEI5 achieved the goal of controlled drug delivery with extended-release and cost-effectiveness, lowering the dosage and frequency of drug administration, and thus may improve patient compliance. In conclusion, the stable nanoemulsion in situ gel of Timolol maleate NEI5 decreases intraocular pressure (IOP) over a prolonged period.
Evaluation of Biodegradabilities of Biosynthetic Polyhydroxyalkanoates in Thailand Seawater and Toxicity Assessment of Environmental Safety Levels
Authors: Tanadchangsaeng Nuttapol , Pattanasupong Anchana
Published: January 2022

Every year, thousands of tons of non-biodegradable plastic products are dumped into marine environments in Thailand’s territorial seawater, impacting various marine animals. Recently, there has been a surge in interest in biodegradable plastics as a solution for aquatic environments. However, in Thailand’s coastal waters, no suitable biodegradable plastic has been used as ocean-biodegradable packaging. Among them, polyhydroxyalkanoates (PHAs) have excellent biodegradability even in seawater, which is the desired property for packaging applications in tourist places such as plastic bags and bottles. In this report, we assess the environment’s safety and study the biodegradation in Thailand seawater of polyhydroxybutyrate (PHB) and PHA copolymer (PHBVV) that were successfully synthesized by bacteria with similar molecular weight. The two types of extracted PHA samples were preliminary biodegradability tested in the marine environment compared with cellulose and polyethylene. Within 28 days, PHB and PHBVV could be biodegraded in both natural and synthetic seawater with 61.2 and 96.5%, respectively. Furthermore, we assessed residual toxicity after biodegradation for environmental safety using seawater samples containing residual digested compounds and the standard guide for acute toxicity tests. It was discovered that marine water mites (Artemia franciscana) have 100 percent viability, indicating that they are non-toxic to the marine environment.
A Meta-Model to Predict the Drag Coefficient of a Particle Translating in Viscoelastic Fluids: A Machine Learning Approach
Authors: Faroughi Salah A. , Roriz Ana I. , Fernandes Célio
Published: January 2022

This study presents a framework based on Machine Learning (ML) models to predict the drag coefficient of a spherical particle translating in viscoelastic fluids. For the purpose of training and testing the ML models, two datasets were generated using direct numerical simulations (DNSs) for the viscoelastic unbounded flow of Oldroyd-B (OB-set containing 12,120 data points) and Giesekus (GI-set containing 4950 data points) fluids past a spherical particle. The kinematic input features were selected to be Reynolds number, 0<Re≤50, Weissenberg number, 0≤Wi≤10, polymeric retardation ratio, 0<ζ<1, and shear thinning mobility parameter, 0<α<1. The ML models, specifically Random Forest (RF), Deep Neural Network (DNN) and Extreme Gradient Boosting (XGBoost), were all trained, validated, and tested, and their best architecture was obtained using a 10-Fold cross-validation method. All the ML models presented remarkable accuracy on these datasets; however the XGBoost model resulted in the highest R2 and the lowest root mean square error (RMSE) and mean absolute percentage error (MAPE) measures. Additionally, a blind dataset was generated using DNSs, where the input feature coverage was outside the scope of the training set or interpolated within the training sets. The ML models were tested against this blind dataset, to further assess their generalization capability. The DNN model achieved the highest R2 and the lowest RMSE and MAPE measures when inferred on this blind dataset. Finally, we developed a meta-model using stacking technique to ensemble RF, XGBoost and DNN models and output a prediction based on the individual learner’s predictions and a DNN meta-regressor. The meta-model consistently outperformed the individual models on all datasets.
A Study of the Flexural Properties of PA12/Clay Nanocomposites
Authors: Stojšić Josip , Raos Pero , Milinović Andrijana , Damjanović Darko
Published: January 2022

Polymer nanocomposites consist of a polymer matrix and reinforcing particles that have at least one dimension under 100 nm. The processing of nanocomposite polymers is the most important stage, determining the final properties of nanocomposites. Nanocomposites are now preferentially prepared by melt-mixing using conventional compounding processes such as twin-screw extrusion. Many processing parameters (polymer matrix type, content and type of nanofiller, barrel temperature, screw speed, number and shape of extruder screws, etc.) affect the properties of nanocomposites. This research work represents an investigation of the influence of processing parameters (amount of nanoclay filler, the screw rotation speed, and extruder barrel temperature) on the flexural properties of polyamide 12/nanoclay-reinforced nanocomposite. From the test results, it is apparent that an increase in nanoclay content from 1 to 8% significantly increases flexural strength. The obtained nanocomposite has a 19% higher flexural strength and a 56% higher flexural modulus than pure PA12. Mathematical models that show the dependence of flexural strength and flexural modulus on the processing parameters used were obtained as a result of this analysis.
In Situ Characterization of the Reaction-Diffusion Behavior during the Gradient Interphase Formation of Polyetherimide with a High-Temperature Epoxy System
Authors: Zweifel Lucian , Brauner Christian , Teuwen Julie , Dransfeld Clemens
Published: January 2022

This study presents two novel methods for in situ characterization of the reaction-diffusion process during the co-curing of a polyetherimide thermoplastic interlayer with an epoxy-amine thermoset. The first method was based on hot stage experiments using a computer vision point tracker algorithm to detect and trace diffusion fronts, and the second method used space- and time-resolved Raman spectroscopy. Both approaches provided essential information, e.g., type of transport phenomena and diffusion rate. They can also be combined and serve to elucidate phenomena occurring during diffusion up to phase separation of the gradient interphase between the epoxy system and the thermoplastic. Accordingly, it was possible to distinguish reaction-diffusion mechanisms, describe the diffusivity of the present system and evaluate the usability of the above-mentioned methods.