bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Ethanol-Mediated Growth Morphology of Ammonium Dinitramide/Pyrazine-1,4-Dioxide Cocrystal at Different Temperatures
Authors: Zhang Yuanping , Ma Boyu , Jia Xinlei , Hou Conghua
Published: June 2023

The crystal morphology of high energetic materials plays a crucial role in aspects of their safety performance such as impact sensitivity. In order to reveal the crystal morphology of ammonium dinitramide/pyrazine-1,4-dioxide (ADN/PDO) cocrystal at different temperatures, the modified attachment energy model (MAE) was used at 298, 303, 308, and 313 K to predict the morphology of the ADN/PDO cocrystal under vacuum and ethanol. The results showed that under vacuum conditions, five growth planes of the ADN/PDO cocrystal were given, which were (1 0 0), (0 1 1), (1 1 0), (1 1 −1), and (2 0 −2). Among them, the ratios of the (1 0 0) and (0 1 1) planes were 40.744% and 26.208%, respectively. In the (0 1 1) crystal plane, the value of S was 1.513. The (0 1 1) crystal plane was more conducive to the adsorption of ethanol molecules. The order of binding energy between the ADN/PDO cocrystal and ethanol solvent was (0 1 1) > (1 1 −1) > (2 0 −2) > (1 1 0) > (1 0 0). The radial distribution function analysis revealed that there were hydrogen bonds between the ethanol and the ADN cations, van der Waals interactions with the ADN anions. As the temperature increased, the aspect ratio of the ADN/PDO cocrystal was reduced, making the crystal more spherical, which helped to further reduce the sensitivity of this explosive.
An In Silico Molecular Modelling-Based Prediction of Potential Keap1 Inhibitors from Hemidesmus indicus (L.) R.Br. against Oxidative-Stress-Induced Diseases
Authors: Vellur Senthilkumar , Pavadai Parasuraman , Babkiewicz Ewa , Ram Kumar Pandian Sureshbabu , Maszczyk Piotr , Kunjiappan Selvaraj
Published: June 2023

The present study investigated the antioxidant potential of aqueous methanolic extracts of Hemidesmus indicus (L.) R.Br., followed by a pharmacoinformatics-based screening of novel Keap1 protein inhibitors. Initially, the antioxidant potential of this plant extract was assessed via antioxidant assays (DPPH, ABTS radical scavenging, and FRAP). Furthermore, 69 phytocompounds in total were derived from this plant using the IMPPAT database, and their three-dimensional structures were obtained from the PubChem database. The chosen 69 phytocompounds were docked against the Kelch–Neh2 complex protein (PDB entry ID: 2flu, resolution 1.50 Å) along with the standard drug (CPUY192018). H. indicus (L.) R.Br. extract (100 µg × mL−1) showed 85 ± 2.917%, 78.783 ± 0.24% of DPPH, ABTS radicals scavenging activity, and 161 ± 4 μg × mol (Fe (II)) g−1 ferric ion reducing power. The three top-scored hits, namely Hemidescine (−11.30 Kcal × mol−1), Beta-Amyrin (−10.00 Kcal × mol−1), and Quercetin (−9.80 Kcal × mol−1), were selected based on their binding affinities. MD simulation studies showed that all the protein–ligand complexes (Keap1–HEM, Keap1–BET, and Keap1–QUE) were highly stable during the entire simulation period, compared with the standard CPUY192018–Keap1 complex. Based on these findings, the three top-scored phytocompounds may be used as significant and safe Keap1 inhibitors, and could potentially be used for the treatment of oxidative-stress-induced health complications.
Isomerization and Stabilization of Amygdalin from Peach Kernels
Authors: Zhang Decai , Ye Jianfen , Song Yu , Wei Yingying , Jiang Shu , Chen Yi , Shao Xingfeng
Published: June 2023

In this study, isomerization conditions, cytotoxic activity, and stabilization of amygdalin from peach kernels were analyzed. Temperatures greater than 40 °C and pHs above 9.0 resulted in a quickly increasing isomer ratio (L-amygdalin/D-amygdalin). At acidic pHs, isomerization was significantly inhibited, even at high temperature. Ethanol inhibited isomerization; the isomer rate decreased with the ethanol concentration increasing. The growth-inhibitory effect on HepG2 cells of D-amygdalin was diminished as the isomer ratio increased, indicating that isomerization reduces the pharmacological activity of D-amygdalin. Extracting amygdalin from peach kernels by ultrasonic power at 432 W and 40 °C in 80% ethanol resulted in a 1.76% yield of amygdalin with a 0.04 isomer ratio. Hydrogel beads prepared by 2% sodium alginate successfully encapsulated the amygdalin, and its encapsulation efficiency and drug loading rate reached 85.93% and 19.21%, respectively. The thermal stability of amygdalin encapsulated in hydrogel beads was significantly improved and reached a slow-release effect in in vitro digestion. This study provides guidance for the processing and storage of amygdalin.
Construction of 2D/2D Mesoporous WO3/CeO2 Laminated Heterojunctions for Optimized Photocatalytic Performance
Authors: Wang Wenjie , Yang Decai , Mou Yifan , Liao Lijun , Wang Shijie , Guo Liping , Wang Xuepeng , Li Zhenzi , Zhou Wei
Published: June 2023

Photocatalytic elimination of antibiotics from the environment and drinking water is of great significance for human health. However, the efficiency of photoremoval of antibiotics such as tetracycline is severely limited by the prompt recombination of electron holes and slow charge migration efficacy. Fabrication of low-dimensional heterojunction composites is an efficient method for shortening charge carrier migration distance and enhancing charge transfer efficiency. Herein, 2D/2D mesoporous WO3/CeO2 laminated Z-scheme heterojunctions were successfully prepared using a two-step hydrothermal process. The mesoporous structure of the composites was proved by nitrogen sorption isotherms, in which sorption-desorption hysteresis was observed. The intimate contact and charge transfer mechanism between WO3 nanoplates and CeO2 nanosheets was investigated using high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy measurements, respectively. Photocatalytic tetracycline degradation efficiency was noticeably promoted by the formation of 2D/2D laminated heterojunctions. The improved photocatalytic activity could be attributed to the formation of Z-scheme laminated heterostructure and 2D morphology favoring spatial charge separation, confirmed by various characterizations. The optimized 5WO3/CeO2 (5 wt.% WO3) composites can degrade more than 99% of tetracycline in 80 min, achieving a peak TC photodegradation efficiency of 0.0482 min−1, which is approximately 3.4 times that of pristine CeO2. A Z-scheme mechanism is proposed for photocatalytic tetracycline by from WO3/CeO2 Z-scheme laminated heterojunctions based on the experimental results.
Influence of Antimony Species on Electrical Properties of Sb-Doped Zinc Oxide Thin Films Prepared by Pulsed Laser Deposition
Authors: Jessadaluk Sukittaya , Khemasiri Narathon , Kayunkid Navaphun , Rangkasikorn Adirek , Wirunchit Supamas , Tammarugwattana Narin , Mano Kitipong , Chananonnawathorn Chanunthorn , Horprathum Mati , Klamchuen Annop , Rahong Sakon , Nukeaw Jiti
Published: June 2023

This study systematically investigates the influence of antimony (Sb) species on the electrical properties of Sb-doped zinc oxide (SZO) thin films prepared by pulsed laser deposition in an oxygen-rich environment. The Sb species-related defects were controlled through a qualitative change in energy per atom by increasing the Sb content in the Sb2O3:ZnO-ablating target. By increasing the content of Sb2O3 (wt.%) in the target, Sb3+ became the dominant Sb ablation species in the plasma plume. Consequently, n-type conductivity was converted to p-type conductivity in the SZO thin films prepared using the ablating target containing 2 wt.% Sb2O3. The substituted Sb species in the Zn site (SbZn3+ and SbZn+) were responsible for forming n-type conductivity at low-level Sb doping. On the other hand, the Sb–Zn complex defects (SbZn–2VZn) contributed to the formation of p-type conductivity at high-level doping. The increase in Sb2O3 content in the ablating target, leading to a qualitative change in energy per Sb ion, offers a new pathway to achieve high-performing optoelectronics using ZnO-based p–n junctions.
Sub-Millisecond Laser-Irradiation-Mediated Surface Restructure Boosts the CO Production Yield of Cobalt Oxide Supported Pd Nanoparticles
Authors: Saravanan Praveen Kumar , Bhalothia Dinesh , Huang Guo-Heng , Beniwal Amisha , Cheng Mingxing , Chao Yu-Chieh , Lin Ming-Wei , Chen Po-Chun , Chen Tsan-Yao
Published: June 2023

The catalytic conversion of CO2 into valuable commodities has the potential to balance ongoing energy and environmental issues. To this end, the reverse water–gas shift (RWGS) reaction is a key process that converts CO2 into CO for various industrial processes. However, the competitive CO2 methanation reaction severely limits the CO production yield; therefore, a highly CO-selective catalyst is needed. To address this issue, we have developed a bimetallic nanocatalyst comprising Pd nanoparticles on the cobalt oxide support (denoted as CoPd) via a wet chemical reduction method. Furthermore, the as-prepared CoPd nanocatalyst was exposed to sub-millisecond laser irradiation with per-pulse energies of 1 mJ (denoted as CoPd-1) and 10 mJ (denoted as CoPd-10) for a fixed duration of 10 s to optimize the catalytic activity and selectivity. For the optimum case, the CoPd-10 nanocatalyst exhibited the highest CO production yield of ∼1667 μmol g−1catalyst, with a CO selectivity of ∼88% at a temperature of 573 K, which is a 41% improvement over pristine CoPd (~976 μmol g−1catalyst). The in-depth analysis of structural characterizations along with gas chromatography (GC) and electrochemical analysis suggested that such a high catalytic activity and selectivity of the CoPd-10 nanocatalyst originated from the sub-millisecond laser-irradiation-assisted facile surface restructure of cobalt oxide supported Pd nanoparticles, where atomic CoOx species were observed in the defect sites of the Pd nanoparticles. Such an atomic manipulation led to the formation of heteroatomic reaction sites, where atomic CoOx species and adjacent Pd domains, respectively, promoted the CO2 activation and H2 splitting steps. In addition, the cobalt oxide support helped to donate electrons to Pd, thereby enhancing its ability of H2 splitting. These results provide a strong foundation to use sub-millisecond laser irradiation for catalytic applications.
Carbon and Cellulose-Based Nanoparticle-Reinforced Polymer Nanocomposites: A Critical Review
Authors: Yuvaraj Gopal , Ramesh Manickam , Rajeshkumar Lakshminarasimhan
Published: June 2023

Nanomaterials are currently used for different applications in several fields. Bringing the measurements of a material down to nanoscale size makes vital contributions to the improvement of the characteristics of materials. The polymer composites acquire various properties when added to nanoparticles, increasing characteristics such as bonding strength, physical property, fire retardance, energy storage capacity, etc. The objective of this review was to validate the major functionality of the carbon and cellulose-based nanoparticle-filled polymer nanocomposites (PNC), which include fabricating procedures, fundamental structural properties, characterization, morphological properties, and their applications. Subsequently, this review includes arrangement of nanoparticles, their influence, and the factors necessary to attain the required size, shape, and properties of the PNCs.
Assessment of the Efficacy of a Low-Dose Iron Supplement in Restoring Iron Levels to Normal Range among Healthy Premenopausal Women with Iron Deficiency without Anemia
Authors: Stefan Matthew W. , Gundermann David M. , Sharp Matthew H. , Jennings Brooke A. , Gheith Raad H. , Lowery Ryan P. , LowDog Tieraona , Ghatak Somsuvra B. , Barbosa Jose , Wilson Jacob M.
Published: June 2023

(1) Background: Iron deficiency without anemia (IDWA) is a prevalent health concern in premenopausal women. Oral supplementation of iron may be a viable solution to improve blood-iron status in women; however, the effects of a high-dose iron-supplement regimen have been associated with gastrointestinal side effects. Therefore, the purpose of the present study was to evaluate the effectiveness of a low-dose liquid fermented iron-bisglycinate supplement (LIS) on improving blood-iron status in premenopausal women with IDWA without increasing constipation or gastrointestinal distress. (2) Methods: 85 premenopausal women with IDWA (ferritin < 70 ng/dL and hemoglobin > 11.0 g/dL) took a LIS (27 mg) or a placebo (PLA) for 8 weeks. Blood draws were taken at Wk0 and Wk8 of the study to measure serum-iron markers. In addition, surveys of gastrointestinal distress were administered at Wk0, Wk4, and Wk8 while the profile of mood states (POMS) was surveyed at Wk0 and Wk8. (3) Results: Compared to the placebo, the LIS was able to increase serum ferritin (p = 0.03), total serum iron (p = 0.03), and mean corpuscular volume (p = 0.02), while exhibiting no significant interaction in subjective gastrointestinal distress (p > 0.05). No significant effects were detected for POMS (p > 0.05). (4) Conclusions: Supplementing with LIS appears to improve blood-iron status without causing significant gastrointestinal distress in premenopausal women with IDWA.
The Impact of Infant Feeding Regimen on Cow’s Milk Protein Allergy, Atopic Dermatitis and Growth in High-Risk Infants during the First 6 Months of Life: The Allergy Reduction Trial
Authors: Boutsikou Theodora , Sekkidou Mikaela , Karaglani Eva , Krepi Adamantia , Moschonis George , Nicolaou Nicolaos , Iacovidou Nicoletta , Pancheva Rouzha , Marinova-Achkar Miglena , Popova Simoneta , Kapetanaki Anastasia , Iliodromiti Zoi , Papaevangelou Vassiliki , Sardeli Olympia , Papathoma Evangelia , Schaafsma Anne , Bos Rolf , Manios Yannis , Xepapadaki Paraskevi
Published: June 2023

The development of early-onset cow’s milk protein allergy and atopic dermatitis during the first months of life is multifactorial, including both genetic and nutritional aspects. This study aims to assess the impact of different feeding patterns on the incidence of cow’s milk protein allergy, atopic dermatitis, and growth among infants with a family history of allergy. A total of 551 high-risk infants were randomly recruited from 3 European countries in three feeding regimens: exclusive breastfeeding, partially hydrolyzed formula, or standard formula with intact protein either exclusively or supplementary to breastfeeding. During the first 6 months of intervention, amongst infants with a family history of atopic dermatitis, 6.5% of partially hydrolyzed formula-fed infants and 22.7% of exclusively breastfed infants (p = 0.007) presented with atopic dermatitis respectively. Growth as assessed by weight increase did not differ between the aforementioned groups. Although cow’s milk protein allergy was not related to the different milk feeding regimens in the whole cohort, when adjusting for high breast milk intake, the respective incident was significantly lower in the infants consuming partially hydrolyzed formula (p < 0.001). This data indicates that a specific partially hydrolyzed formula could serve as a more appropriate complement to breast milk compared to a standard intact protein formula in high-risk infants, to reduce the incidence of atopic dermatitis.
Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion
Authors: Parisse Simona , Gianoncelli Alessandra , Isani Gloria , Gambaro Francesco Luigi , Andreani Giulia , Malucelli Emil , Aquilanti Giuliana , Carlomagno Ilaria , Carletti Raffaella , Mischitelli Monica , Ferri Flaminia , Paterna Veronica , Lai Quirino , Mennini Gianluca , Melandro Fabio , Di Gioia Cira , Rossi Massimo , Iotti Stefano , Fratini Michela , Ginanni Corradini Stefano
Published: June 2023

We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation, we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes of 15 CIRs using synchrotron-based X-ray fluorescence microscopy. In 31 CIRs and 10 CTRLs, we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content (117.2 (IQR 110.5–132.9) vs. 162.8 (IQR 155.9–169.8) μg/g; p < 0.001) and a higher percentage of TRPM7 positive hepatocytes (53.0 (IQR 36.8–62.0) vs. 20.7 (10.7–32.8)%; p < 0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: (a) inversely with the magnesium content both in liver tissue and hepatocytes; and (b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with the worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients.
Front-of-Package Nutrition Labeling and Its Impact on Food Industry Practices: A Systematic Review of the Evidence
Authors: Ganderats-Fuentes Montserrat , Morgan Sherry
Published: June 2023

The obesity epidemic has become a major public health concern globally, and the food supply is a significant driver of this trend. Front-of-package (FOP) labels have been implemented in many countries to encourage healthier food choices. This systematic review aimed to examine the effect of FOP label implementation on food manufacturers’ practices. A comprehensive search of multiple databases was conducted following PRISMA guidelines, identifying 39 relevant articles from 1990 to 2021. The studies indicated that FOP labels conveying intuitive information influenced product reformulation, whereas those with numerical information without specific guidance had no impact on reducing unhealthy nutrients. The most common outcomes were sodium, sugar, and calorie reduction. Mandatory policies reported higher and more consistent effects on product reformulation compared to voluntary approaches. Voluntary FOP labeling resulted in low uptake and tended to be applied to healthier products. Food manufacturers responded to FOP labeling heterogeneously, depending on the label design and type of enforcement. FOP label implementation can reduce nutrients of concern but food manufacturers behave strategically by labeling healthier choices. This review provides recommendations for maximizing the benefits of using FOP labels to prevent obesity, and findings can inform future public health research and policymaking.
Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants
Authors: Banerjee Antara , Somasundaram Indumathi , Das Diptimayee , Jain Manoj Samatha , Banu Husaina , Mitta Suresh Pavane , Paul Sujay , Bisgin Atil , Zhang Hong , Sun Xiao-Feng , Duttaroy Asim K. , Pathak Surajit
Published: June 2023

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.
A Participatory Approach in Assessing the Knowledge, Attitude, and Practices (KAP) of Stakeholders and Livestock Owners about Ticks and Tick-Borne Diseases from Sindh, Pakistan
Authors: Rajput Mahvish , Sajid Muhammad Sohail , Imran Muhammad , Javed Muhammad Tariq , Sparagano Olivier Andre
Published: June 2023

Ticks and tick-borne diseases (TTBDs) are responsible for significant losses in terms of treatment costs, decreased productivity (such as milk and meat), reduced reproductive ability, and financial crisis to livestock owners. In Pakistan, it is crucial to periodically assess the risk of TTBDs and ecological factors, potential causes of acaricidal resistance in tick fauna, and the intensive increase in the spread of TTBDs. Participatory epidemiological approaches are key to assessing the livestock owners’ and stakeholders’ knowledge, attitude, and practices (KAP) about TTBDs. The current study determined the KAP about ticks and tick-borne diseases of respondents from Sindh, Pakistan. A total of 240 respondents were interviewed from different ecological zones: among them, 42.5% (n = 102) of the respondents practiced the manual removal of ticks from animals, while acaricide usage was indicated by 137 respondents (57.0%) as occurring sometimes, 50 (20.8%) monthly, 41 (17.0%) fortnightly, and 12 (5%) weekly, during the peak infestation season. Ticks were 2.6 times [OR = 2.5 (95% Cl = 1.47–4.06)] and viruses were 1.89 times [OR = 188 (95% Cl = 1.09–2.9)] more likely to cause the development of disease in animals than any other pathogen. Despite the appropriate usage of acaricides, the knowledge of participants was inadequate. The findings of this study emphasize the need to take into account identified knowledge gaps and to take the initiative in carrying out appropriate education activities and extension programs to enhance the adoption of effective tick prevention and control strategies.
Activation of Inflammasome during Bluetongue Virus Infection
Authors: Pourcelot Marie , da Silva Moraes Rayane Amaral , Lacour Sandrine , Fablet Aurore , Caignard Grégory , Vitour Damien
Published: June 2023

Bluetongue virus (BTV), a double-stranded RNA virus belonging to the Sedoreoviridae family, provokes an economically important disease in ruminants. In this study, we show that the production of activated caspase-1 and interleukin 1 beta (IL-1β) is induced in BTV-infected cells. This response seems to require virus replication since a UV-inactivated virus is unable to activate this pathway. In NLRP3-/- cells, BTV could not trigger further IL-1β synthesis, indicating that it occurs through NLRP3 inflammasome activation. Interestingly, we observed differential activation levels in bovine endothelial cells depending on the tissue origin. In particular, inflammasome activation was stronger in umbilical cord cells, suggesting that these cells are more prone to induce the inflammasome upon BTV infection. Finally, the strength of the inflammasome activation also depends on the BTV strain, which points to the importance of viral origin in inflammasome modulation. This work reports the crucial role of BTV in the activation of the NLRP3 inflammasome and further shows that this activation relies on BTV replication, strains, and cell types, thus providing new insights into BTV pathogenesis.
Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives
Authors: Zargaham Muhammad Kazim , Ahmed Madiha , Akhtar Nosheen , Ashraf Zaman , Abdel-Maksoud Mostafa A. , Aufy Mohammed , Nadeem Humaira
Published: June 2023

Heterocyclic nuclei have shown a wide variety of biological activities, highlighting their importance in drug discovery. Derivatives of 2,4-subsituted thiazolidine have a structural similarity with the substrates of tyrosinase enzymes. Hence, they can be used as an inhibitor to compete against tyrosine in the biosynthesis of melanin. This study is focused on design, synthesis, biological activities, and in silico studies of thiazolidine derivatives substituted at positions 2 and 4. The synthesized compounds were evaluated to determine the antioxidant activity and tyrosine inhibitory potential using mushroom tyrosinase. The most potent tyrosinase enzyme inhibitor was compound 3c having IC50 value 16.5 ± 0.37 µM, whereas compound 3d showed maximum antioxidant activity in a DPPH free radical scavenging assay (IC50 = 18.17 µg/mL). Molecular docking studies were conducted using mushroom tyrosinase (PDB ID: 2Y9X) to analyze binding affinities and binding interactions of the protein–ligand complex. Docking results indicated that hydrogen bonds and hydrophobic interactions were mainly involved in the ligand and protein complex. The highest binding affinity was found to be −8.4 Kcal/mol. These results suggest that thiazolidine-4-carboxamide derivatives could serve as lead molecules for development of novel potential tyrosinase inhibitors.
Annexin A5 Inhibits Endothelial Inflammation Induced by Lipopolysaccharide-Activated Platelets and Microvesicles via Phosphatidylserine Binding
Authors: Tschirhart Brent J. , Lu Xiangru , Gomes Janice , Chandrabalan Arundhasa , Bell Gillian , Hess David A. , Xing Guangxin , Ling Hong , Burger Dylan , Feng Qingping
Published: June 2023

Sepsis is caused by a dysregulated immune response to infection and is a leading cause of mortality globally. To date, no specific therapeutics are available to treat the underlying septic response. We and others have shown that recombinant human annexin A5 (Anx5) treatment inhibits pro-inflammatory cytokine production and improves survival in rodent sepsis models. During sepsis, activated platelets release microvesicles (MVs) with externalization of phosphatidylserine to which Anx5 binds with high affinity. We hypothesized that recombinant human Anx5 blocks the pro-inflammatory response induced by activated platelets and MVs in vascular endothelial cells under septic conditions via phosphatidylserine binding. Our data show that treatment with wildtype Anx5 reduced the expression of inflammatory cytokines and adhesion molecules induced by lipopolysaccharide (LPS)-activated platelets or MVs in endothelial cells (p < 0.01), which was not observed with Anx5 mutant deficient in phosphatidylserine binding. In addition, wildtype Anx5 treatment, but not Anx5 mutant, improved trans-endothelial electrical resistance (p < 0.05) and reduced monocyte (p < 0.001) and platelet (p < 0.001) adhesion to vascular endothelial cells in septic conditions. In conclusion, recombinant human Anx5 inhibits endothelial inflammation induced by activated platelets and MVs in septic conditions via phosphatidylserine binding, which may contribute to its anti-inflammatory effects in the treatment of sepsis.
Intracellular Drug Delivery Process of Am80-Encapsulated Lipid Nanoparticles Aiming for Alveolar Regeneration
Authors: Akita Tomomi , Oda Kazuaki , Narukawa Satoru , Morita Yuki , Tange Kota , Nakai Yuta , Yamashita Chikamasa
Published: June 2023

Chronic obstructive pulmonary disease (COPD) results in obstructive ventilatory impairment caused by emphysema, and current treatment is limited to symptomatic therapy or lung transplantation. Therefore, the development of new treatments to repair alveolar destruction is especially urgent. Our previous study revealed that 1.0 mg/kg of synthetic retinoid Am80 had a repair effect on collapsed alveoli in a mouse model of elastase-induced emphysema. From these results, however, the clinical dose calculated in accordance with FDA guidance is estimated to be 5.0 mg/60 kg, and it is desirable to further reduce the dose to allow the formulation of a powder inhaler for clinical application. To efficiently deliver Am80 to the retinoic acid receptor in the cell nucleus, which is the site of action, we focused on SS-cleavable proton-activated lipid-like material O-Phentyl-P4C2COATSOME®SS-OP, hereinafter referred to as “SS-OP”). In this study, we investigated the cellular uptake and intracellular drug delivery process of Am80-encapsulated SS-OP nanoparticles to elucidate the mechanism of Am80 by nanoparticulation. Am80-encapsulated SS-OP nanoparticles were taken up into the cells via ApoE, and then Am80 was efficiently delivered into the nucleus via RARα. These results indicated the usefulness of SS-OP nanoparticles as drug delivery system carriers of Am80 for COPD treatment.
Molecularly Imprinted Carriers for Diagnostics and Therapy—A Critical Appraisal
Authors: Balcer Emilia , Sobiech Monika , Luliński Piotr
Published: June 2023

Simultaneous diagnostics and targeted therapy provide a theranostic approach, an instrument of personalized medicine—one of the most-promising trends in current medicine. Except for the appropriate drug used during the treatment, a strong focus is put on the development of effective drug carriers. Among the various materials applied in the production of drug carriers, molecularly imprinted polymers (MIPs) are one of the candidates with great potential for use in theranostics. MIP properties such as chemical and thermal stability, together with capability to integrate with other materials are important in the case of diagnostics and therapy. Moreover, the MIP specificity, which is important for targeted drug delivery and bioimaging of particular cells, is a result of the preparation process, conducted in the presence of the template molecule, which often is the same as the target compound. This review focused on the application of MIPs in theranostics. As a an introduction, the current trends in theranostics are described prior to the characterization of the concept of molecular imprinting technology. Next, a detailed discussion of the construction strategies of MIPs for diagnostics and therapy according to targeting and theranostic approaches is provided. Finally, frontiers and future prospects are presented, stating the direction for further development of this class of materials.
Targeting Peptides: The New Generation of Targeted Drug Delivery Systems
Authors: Todaro Biagio , Ottalagana Elisa , Luin Stefano , Santi Melissa
Published: June 2023

Peptides can act as targeting molecules, analogously to oligonucleotide aptamers and antibodies. They are particularly efficient in terms of production and stability in physiological environments; in recent years, they have been increasingly studied as targeting agents for several diseases, from tumors to central nervous system disorders, also thanks to the ability of some of them to cross the blood–brain barrier. In this review, we will describe the techniques employed for their experimental and in silico design, as well as their possible applications. We will also discuss advancements in their formulation and chemical modifications that make them even more stable and effective. Finally, we will discuss how their use could effectively help to overcome various physiological problems and improve existing treatments.
Polymers and Bioactive Compounds with a Macrophage Modulation Effect for the Rational Design of Hydrogels for Skin Regeneration
Authors: Sánchez Mirna L. , Valdez Hugo , Conde Micaela , Viaña-Mendieta Pamela , Boccaccini Aldo R.
Published: June 2023

The development of biomaterial platforms for dispensing reagents of interest such as antioxidants, growth factors or antibiotics based on functional hydrogels represents a biotechnological solution for many challenges that the biomedicine field is facing. In this context, in situ dosing of therapeutic components for dermatological injuries such as diabetic foot ulcers is a relatively novel strategy to improve the wound healing process. Hydrogels have shown more comfort for the treatment of wounds due to their smooth surface and moisture, as well as their structural affinity with tissues in comparison to hyperbaric oxygen therapy, ultrasound, and electromagnetic therapies, negative pressure wound therapy or skin grafts. Macrophages, one of the most important cells of the innate immune system, have been described as the key not only in relation to the host immune defense, but also in the progress of wound healing. Macrophage dysfunction in chronic wounds of diabetic patients leads to a perpetuating inflammatory environment and impairs tissue repair. Modulating the macrophage phenotype from pro-inflammatory (M1) to anti-inflammatory (M2) could be a strategy for helping to improve chronic wound healing. In this regard, a new paradigm is found in the development of advanced biomaterials capable of inducing in situ macrophage polarization to offer an approach to wound care. Such an approach opens a new direction for the development of multifunctional materials in regenerative medicine. This paper surveys emerging hydrogel materials and bioactive compounds being investigated to induce the immunomodulation of macrophages. We propose four potential functional biomaterials for wound healing applications based on novel biomaterial/bioactive compound combination that are expected to show synergistic beneficial outcomes for the local differentiation of macrophages (M1–M2) as a therapeutic strategy for chronic wound healing improvement.
Recent Advances in Nanoformulations for Quercetin Delivery
Authors: Tomou Ekaterina-Michaela , Papakyriakopoulou Paraskevi , Saitani Elmina-Marina , Valsami Georgia , Pippa Natassa , Skaltsa Helen
Published: June 2023

Quercetin (QUE) is a flavonol that has recently received great attention from the research community due to its important pharmacological properties. However, QUE’s low solubility and extended first-pass metabolism limit its oral administration. This review aims to present the potential of various nanoformulations in the development of QUE dosage forms for bioavailability enhancement. Advanced drug delivery nanosystems can be used for more efficient encapsulation, targeting, and controlled release of QUE. An overview of the primary nanosystem categories, formulation processes, and characterization techniques are described. In particular, lipid-based nanocarriers, such as liposomes, nanostructured-lipid carries, and solid-lipid nanoparticles, are widely used to improve QUE’s oral absorption and targeting, increase its antioxidant activity, and ensure sustained release. Moreover, polymer-based nanocarriers exhibit unique properties for the improvement of the Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADME(T)) profile. Namely, micelles and hydrogels composed of natural or synthetic polymers have been applied in QUE formulations. Furthermore, cyclodextrin, niosomes, and nanoemulsions are proposed as formulation alternatives for administration via different routes. This comprehensive review provides insight into the role of advanced drug delivery nanosystems for the formulation and delivery of QUE.
Visualization and Estimation of Nasal Spray Delivery to Olfactory Mucosa in an Image-Based Transparent Nasal Model
Authors: Seifelnasr Amr , Si Xiuhua April , Xi Jinxiang
Published: June 2023

Background: Nose-to-brain (N2B) drug delivery offers unique advantages over intravenous methods; however, the delivery efficiency to the olfactory region using conventional nasal devices and protocols is low. This study proposes a new strategy to effectively deliver high doses to the olfactory region while minimizing dose variability and drug losses in other regions of the nasal cavity. Materials and Methods: The effects of delivery variables on the dosimetry of nasal sprays were systematically evaluated in a 3D-printed anatomical model that was generated from a magnetic resonance image of the nasal airway. The nasal model comprised four parts for regional dose quantification. A transparent nasal cast and fluorescent imaging were used for visualization, enabling detailed examination of the transient liquid film translocation, real-time feedback on input effect, and prompt adjustment to delivery variables, which included the head position, nozzle angle, applied dose, inhalation flow, and solution viscosity. Results: The results showed that the conventional vertex-to-floor head position was not optimal for olfactory delivery. Instead, a head position tilting 45–60° backward from the supine position gave a higher olfactory deposition and lower variability. A two-dose application (250 mg) was necessary to mobilize the liquid film that often accumulated in the front nose following the first dose administration. The presence of an inhalation flow reduced the olfactory deposition and redistributed the sprays to the middle meatus. The recommended olfactory delivery variables include a head position ranging 45–60°, a nozzle angle ranging 5–10°, two doses, and no inhalation flow. With these variables, an olfactory deposition fraction of 22.7 ± 3.7% was achieved in this study, with insignificant discrepancies in olfactory delivery between the right and left nasal passages. Conclusions: It is feasible to deliver clinically significant doses of nasal sprays to the olfactory region by leveraging an optimized combination of delivery variables.
SOA-MZI Differential Transformation Approach Applied on Simultaneous Electro-Optical Mixing
Authors: Termos Hassan , Mansour Ali
Published: June 2023

We experimentally incubate a ground-breaking design, for the first time, of concurrent electro-optical semiconductor optical amplifier Mach–Zehnder interferometer mixing (SOA-MZI) based on a differential transformation methodology. Projecting the simultaneous electro-optical mixing system and improving its efficiency and quality achievement in optical and electrical features is a crucial task due to the characteristics of an optical pulse source (OPS) operating with a repetition rate of f= 58.5 GHz and a pulse width duration of 1 picosecond (ps). The resultant of the contemporaneous electro-optical mixing exhibits exceptional passive power stability, reaching 0.8% RMS over a two-hour period. Furthermore, when the optical bandpass filter is controlled at the data wavelength of 1540 nm, we achieve up to 30 dBm of the overall mean output power with an optical conversion gain of 46 dB and an exceptionally high optical signal-to-noise ratio reaching 80 dB. Using orthogonal frequency division multiplexing (OFDM) signals, each data subcarrier is modulated using 128 quadratic amplitude modulation (128-QAM) at carrier frequencies fk and simultaneously up-mixed to high aim frequencies nf±fk at the SOA-MZI output. Additionally, the resulting OFDM_128-QAM up-mixed signal is examined using the specifications for the error vector magnitudes (EVMs) and the electrical conversion gains (ECGs). The SOA-MZI mixing experiment can handle high frequencies up to 120 GHz. Positive ECGs are followed by a sharp reduction over the entire band of the aim frequencies. The highest frequency range achieved during the realistic investigation is shown at 2f+f4= 120 GHz, where the EVM reaches 8% with a symbol rate of 15 GSymb/s. Furthermore, the concurrent OFDM_128-QAM up-mixed signal achieves an absolute maximum bit rate of 80.4 Gbit/s. The investigation into the simultaneous electro-optical mixing regime is finally supported by unmatched characterization improvements.
Genome-Wide Association Study Identified Candidate Genes for Alkalinity Tolerance in Rice
Authors: Singh Lovepreet , Pruthi Rajat , Chapagain Sandeep , Subudhi Prasanta K.
Published: June 2023

Alkalinity stress is a major hindrance to enhancing rice production globally due to its damaging effect on plants’ growth and development compared with salinity stress. However, understanding of the physiological and molecular mechanisms of alkalinity tolerance is limited. Therefore, a panel of indica and japonica rice genotypes was evaluated for alkalinity tolerance at the seedling stage in a genome-wide association study to identify tolerant genotypes and candidate genes. Principal component analysis revealed that traits such as alkalinity tolerance score, shoot dry weight, and shoot fresh weight had the highest contribution to variations in tolerance, while shoot Na+ concentration, shoot Na+:K+ ratio, and root-to-shoot ratio had moderate contributions. Phenotypic clustering and population structure analysis grouped the genotypes into five subgroups. Several salt-susceptible genotypes such as IR29, Cocodrie, and Cheniere placed in the highly tolerant cluster suggesting different underlying tolerance mechanisms for salinity and alkalinity tolerance. Twenty-nine significant SNPs associated with alkalinity tolerance were identified. In addition to three alkalinity tolerance QTLs, qSNK4, qSNC9, and qSKC10, which co-localized with the earlier reported QTLs, a novel QTL, qSNC7, was identified. Six candidate genes that were differentially expressed between tolerant and susceptible genotypes were selected: LOC_Os04g50090 (Helix-loop-helix DNA-binding protein), LOC_Os08g23440 (amino acid permease family protein), LOC_Os09g32972 (MYB protein), LOC_Os08g25480 (Cytochrome P450), LOC_Os08g25390 (Bifunctional homoserine dehydrogenase), and LOC_Os09g38340 (C2H2 zinc finger protein). The genomic and genetic resources such as tolerant genotypes and candidate genes would be valuable for investigating the alkalinity tolerance mechanisms and for marker-assisted pyramiding of the favorable alleles for improving alkalinity tolerance at the seedling stage in rice.
Biofilm-Forming Ability of Phytopathogenic Bacteria: A Review of its Involvement in Plant Stress
Authors: Carezzano María Evangelina , Paletti Rovey María Fernanda , Cappellari Lorena del Rosario , Gallarato Lucas Antonio , Bogino Pablo , Oliva María de las Mercedes , Giordano Walter
Published: June 2023

Phytopathogenic bacteria not only affect crop yield and quality but also the environment. Understanding the mechanisms involved in their survival is essential to develop new strategies to control plant disease. One such mechanism is the formation of biofilms; i.e., microbial communities within a three-dimensional structure that offers adaptive advantages, such as protection against unfavorable environmental conditions. Biofilm-producing phytopathogenic bacteria are difficult to manage. They colonize the intercellular spaces and the vascular system of the host plants and cause a wide range of symptoms such as necrosis, wilting, leaf spots, blight, soft rot, and hyperplasia. This review summarizes up-to-date information about saline and drought stress in plants (abiotic stress) and then goes on to focus on the biotic stress produced by biofilm-forming phytopathogenic bacteria, which are responsible for serious disease in many crops. Their characteristics, pathogenesis, virulence factors, systems of cellular communication, and the molecules implicated in the regulation of these processes are all covered.
Sustainable Stress Management: Aquatic Plants vs. Terrestrial Plants
Authors: Sree K. Sowjanya , Appenroth Klaus J. , Oelmüller Ralf
Published: June 2023

The Indo-German Science and Technology Centre (IGSTC) funded an Indo-German Workshop on Sustainable Stress Management: Aquatic plants vs. Terrestrial plants (IGW-SSMAT) which was jointly organized at the Friedrich Schiller University of Jena, Germany from 25 to 27 July 2022 by Prof. Dr. Ralf Oelmüller, Friedrich Schiller University of Jena, Germany as the German coordinator and Dr. K. Sowjanya Sree, Central University of Kerala, India as the Indian Coordinator. The workshop constituted researchers working in this field from both India and Germany and brought together these experts in the field of sustainable stress management for scientific discussions, brainstorming and networking.
Antioxidant and Antimicrobial Properties and GC-MS Chemical Compositions of Makwaen Pepper (Zanthoxylum myriacanthum) Extracted Using Supercritical Carbon Dioxide
Authors: Nadon Sudarut , Leksawasdi Noppol , Jantanasakulwong Kittisak , Rachtanapun Pornchai , Ruksiriwanich Warintorn , Sommano Sarana Rose , Khaneghah Amin Mousavi , Castagnini Juan M. , Barba Francisco J. , Phimolsiripol Yuthana
Published: June 2023

This research aimed to optimize pressure (10–20 MPa) and temperature (45–60 °C) conditions for supercritical fluid extraction (SFE) of Makwaen pepper (Zanthoxylum myriacanthum) extract (ME) in comparison to conventional hydro-distillation extraction. Various quality parameters, including yield, total phenolic compounds, antioxidants, and antimicrobial activities of the extracts, were assessed and optimized using a central composite design. The optimal SFE conditions were found to be 20 MPa at 60 °C, which resulted in the highest yield (19%) and a total phenolic compound content of 31.54 mg GAE/mL extract. IC50 values for DPPH and ABTS assays were determined to be 26.06 and 19.90 μg/mL extract, respectively. Overall, the ME obtained through SFE exhibited significantly better physicochemical and antioxidant properties compared to ME obtained through hydro-distillation extraction. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that beta-pinene was the major component in the ME obtained through SFE (23.10%), followed by d-limonene, alpha-pinene, and terpinen-4-ol at concentrations of 16.08, 7.47, and 6.34%, respectively. On the other hand, the hydro-distillation-extracted ME showed stronger antimicrobial properties than the SFE-extracted ME. These findings suggest that both SFE and hydro-distillation have the potential for extracting Makwaen pepper, depending on the intended purpose of use.
Microscopical Analysis of Autofluorescence as a Complementary and Useful Method to Assess Differences in Anatomy and Structural Distribution Underlying Evolutive Variation in Loss of Seed Dispersal in Common Bean
Authors: Santos Ana M. , González Ana M. , De Dios Alche Juan , Santalla Marta
Published: June 2023

The common bean has received attention as a model plant for legume studies, but little information is available about the morphology of its pods and the relation of this morphology to the loss of seed dispersal and/or the pod string, which are key agronomic traits of legume domestication. Dehiscence is related to the pod morphology and anatomy of pod tissues because of the weakening of the dorsal and ventral dehiscence zones and the tensions of the pod walls. These tensions are produced by the differential mechanical properties of lignified and non-lignified tissues and changes in turgor associated with fruit maturation. In this research, we histologically studied the dehiscence zone of the ventral and dorsal sutures of the pod in two contrasting genotypes for the dehiscence and string, by comparing different histochemical methods with autofluorescence. We found that the secondary cell wall modifications of the ventral suture of the pod were clearly different between the dehiscence-susceptible and stringy PHA1037 and the dehiscence-resistant and stringless PHA0595 genotypes. The susceptible genotype had cells of bundle caps arranged in a more easily breakable bowtie knot shape. The resistant genotype had a larger vascular bundle area and larger fibre cap cells (FCCs), and due to their thickness, the external valve margin cells were significantly stronger than those from PHA1037. Our findings suggest that the FCC area, and the cell arrangement in the bundle cap, might be partial structures involved in the pod dehiscence of the common bean. The autofluorescence pattern at the ventral suture allowed us to quickly identify the dehiscent phenotype and gain a better understanding of cell wall tissue modifications that took place along the bean’s evolution, which had an impact on crop improvement. We report a simple autofluorescence protocol to reliably identify secondary cell wall organization and its relationship to the dehiscence and string in the common bean.