bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypereutectic Al-Ca-Mn-(Ni) Alloys as Natural Eutectic Composites
Authors: Naumova Evgeniya , Doroshenko Vitali , Barykin Mikhail , Sviridova Tatyana , Lyasnikova Alexandra , Shurkin Pavel
Published: May 2021

In the present paper, Natural Metal-Matrix Composites (NMMC) based on multicomponent hypereutectic Al-Ca-(Mn)-(Ni) alloys were studied in as-cast, annealed and rolled conditions. Thermo-Calc software and microstructural observations were utilised for analysing the equilibrium and actual phase composition of the alloys including correction of the Al-Ca-Mn system liquidus projection and the solid phase distribution in the Al-Ca-Mn-Ni system. A previously unknown Al10CaMn2 was discovered by both electron microprobe analysis and X-ray studies. The Al-6Ca-3Mn, Al-8Ca-2Mn, Al-8Ca-2Mn-1Ni alloys with representative NMMC structure included ultrafine Ca-rich eutectic and various small-sized primary crystals were found to have excellent feasibility of rolling as compared to its hypereutectic Al-Si counterpart. What is more, Al-Ca alloys showed comparable Coefficient of Thermal Expansion values due to enormous volume fraction of Al-based eutectic and primary intermetallics. Analysis of tensile samples’ fracture surfaces revealed that primary intermetallics may act either as stress raisers or malleable particles depending on their stiffness under deformation. It is shown that a compact morphology can be achieved by conventional casting without using any refining agents. Novel hypereutectic Al-Ca NMMC materials solidifying with the formation of Al10Mn2Ca primary compound have the best ductility and strength. We reasonably propose these materials for high-load pistons.
Carbon Particle In-Situ Alloying of the Case-Hardening Steel 16MnCr5 in Laser Powder Bed Fusion
Authors: Schmitt Matthias , Gottwalt Albin , Winkler Jakob , Tobie Thomas , Schlick Georg , Stahl Karsten , Tetzlaff Ulrich , Schilp Johannes , Reinhart Gunther
Published: May 2021

The carbon content of steel affects many of its essential properties, e.g., hardness and mechanical strength. In the powder bed fusion process of metals using a laser beam (PBF-LB/M), usually, pre-alloyed metal powder is solidified layer-by-layer using a laser beam to create parts. A reduction of the carbon content in steels is observed during this process. This study examines adding carbon particles to the metal powder and in situ alloying in the PBF-LB/M process as a countermeasure. Suitable carbon particles are selected and their effect on the particle size distribution and homogeneity of the mixtures is analysed. The workability in PBF-LB is then shown. This is followed by an evaluation of the resulting mechanical properties (hardness and mechanical strength) and microstructure in the as-built state and the state after heat treatment. Furthermore, potential use cases like multi-material or functionally graded parts are discussed.
The Impact of Metabolic Scion–Rootstock Interactions in Different Grapevine Tissues and Phloem Exudates
Authors: Tedesco Sara , Erban Alexander , Gupta Saurabh , Kopka Joachim , Fevereiro Pedro , Kragler Friedrich , Pina Ana
Published: May 2021

In viticulture, grafting is used to propagate Phylloxera-susceptible European grapevines, thereby using resistant American rootstocks. Although scion–rootstock reciprocal signaling is essential for the formation of a proper vascular union and for coordinated growth, our knowledge of graft partner interactions is very limited. In order to elucidate the scale and the content of scion–rootstock metabolic interactions, we profiled the metabolome of eleven graft combination in leaves, stems, and phloem exudate from both above and below the graft union 5–6 months after grafting. We compared the metabolome of scions vs. rootstocks of homografts vs. heterografts and investigated the reciprocal effect of the rootstock on the scion metabolome. This approach revealed that (1) grafting has a minor impact on the metabolome of grafted grapevines when tissues and genotypes were compared, (2) heterografting affects rootstocks more than scions, (3) the presence of a heterologous grafting partner increases defense-related compounds in both scion and rootstocks in shorter and longer distances from the graft, and (4) leaves were revealed as the best tissue to search for grafting-related metabolic markers. These results will provide a valuable metabolomics resource for scion–rootstock interaction studies and will facilitate future efforts on the identification of metabolic markers for important agronomic traits in grafted grapevines.
Microfluidic Based Physical Approaches towards Single-Cell Intracellular Delivery and Analysis
Authors: Kaladharan Kiran , Kumar Ashish , Gupta Pallavi , Illath Kavitha , Santra Tuhin , Tseng Fan-Gang
Published: May 2021

The ability to deliver foreign molecules into a single living cell with high transfection efficiency and high cell viability is of great interest in cell biology for applications in therapeutic development, diagnostics, and drug delivery towards personalized medicine. Various physical delivery methods have long demonstrated the ability to deliver cargo molecules directly to the cytoplasm or nucleus and the mechanisms underlying most of the approaches have been extensively investigated. However, most of these techniques are bulk approaches that are cell-specific and have low throughput delivery. In comparison to bulk measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. To elucidate distinct responses during cell genetic modification, methods to achieve transfection at the single-cell level are of great interest. In recent years, single-cell technologies have become increasingly robust and accessible, although limitations exist. This review article aims to cover various microfluidic-based physical methods for single-cell intracellular delivery such as electroporation, mechanoporation, microinjection, sonoporation, optoporation, magnetoporation, and thermoporation and their analysis. The mechanisms of various physical methods, their applications, limitations, and prospects are also elaborated.
Kaposi’s Sarcoma-Associated Herpesvirus ORF7 Is Essential for Virus Production
Authors: Iwaisako Yuki , Watanabe Tadashi , Hanajiri Mizuki , Sekine Yuichi , Fujimuro Masahiro
Published: May 2021

Kaposi’s sarcoma-associated herpesvirus (KSHV) causes Kaposi’s sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman disease. Although capsid formation and maturation in the alpha-herpesvirus herpes simplex virus 1 are well understood, these processes in KSHV remain unknown. The KSHV ORF7, encoding the viral terminase (DNA cleavage and packaging protein), is thought to contribute to capsid formation; however, functional information is lacking. Here, we investigated the role of ORF7 during KSHV lytic replication by generating two types of ORF7 knock-out (KO) mutants (frameshift-induced and stop codon-induced ORF7 deficiency), KSHV BAC16, and its revertants. The results revealed that both ORF7-KO KSHVs showed significantly reduced viral production but there was no effect on lytic gene expression and viral genome replication. Complementation assays showed virus production from cells harboring ORF7-KO KSHV could be recovered by ORF7 overexpression. Additionally, exogenously expressed ORF7 partially induced nuclear relocalization of the other terminase components, ORF29 and ORF67.5. ORF7 interacted with both ORF29 and ORF67.5, whereas ORF29 and ORF67.5 failed to interact with each other, suggesting that ORF7 functions as a hub molecule in the KSHV terminase complex for interactions between ORF29 and ORF67.5. These findings indicate that ORF7 plays a key role in viral replication, as a component of terminase.
Collaborative Studies for the Detection of Taenia spp. Infections in Humans within CYSTINET, the European Network on Taeniosis/Cysticercosis
Authors: Gómez-Morales María , Pezzotti Patrizio , Ludovisi Alessandra , Boufana Belgees , Dorny Pierre , Kortbeek Titia , Blocher Joachim , Schmidt Veronika , Amati Marco , Gabriël Sarah , Pozio Edoardo , Winkler Andrea , Participants The
Published: May 2021

Laboratory tools for diagnosing taeniosis/cysticercosis in non-endemic countries are available; however, there is little data on their performance. To provide information on the sensitivity, specificity, and reproducibility of these tools, inter-laboratory studies were organized within the EU COST-Action CYSTINET (TD1302). Two serological and one coprological Ring Trials (RTs) were organized to test a panel of human-derived sera and stool samples using assays routinely conducted by the participating laboratories to detect Taenia spp. infections. Four Western blots (WBs) and five ELISAs were used by nine laboratories for cysticercosis diagnosis. In the first serological RT, the overall sensitivity was 67.6% (95% CI, 59.1–75.4), whereas specificity was 97% (95% CI, 89.8–99.6). WBs recorded the best accuracy. A second serological RT was organized, to assess the three tests most frequently used during the first RT. Two out of six laboratories performed all the three tests. The overall sensitivity and specificity were 52.8% (95% CI, 42.8–62.7) and 98.1% (95% CI, 93.2–99.7), respectively. Laboratory performance strongly affected test results. Twelve laboratories participated in the coprological RT using conventional microscopy and six laboratories used molecular assays. Traditional diagnosis by microscopy yielded better results than molecular diagnosis. This may have been influenced by the lack of standardization of molecular tests across participating laboratories.
The Role of Mesenchymal Stem Cells in the Treatment of a Chronic Rhinosinusitis—An In Vivo Mouse Model
Authors: Trombitaș Veronica-Elena , Nagy Alina Anda , Berce Cristian , Pall Emoke , Tăbăran Flaviu , Ilea Aranka , Albu Silviu
Published: May 2021

Objectives/Hypothesis: It is acknowledged that the treatment of chronic rhinosinusitis (CRS) represents an important challenge for rhinology and for social and economic life. At present, one of the most common treatments for CRS is represented by local corticosteroids followed by endoscopic sinus surgery (ESS). Starting from the example of the mesenchymal stem cell’s (MSC) capacity to migrate and to modulate a real response in the nasal mucosa of an allergic rhinitis mouse model, we try to obtain a response in a CRS mouse model, using MSC derived by adipose tissue. The aim of this study is to demonstrate that the MSC can be used in CRS treatment and could change its priorities. Methods: Seventy female mice (6 MSC donor mice) were randomized in two stages of study, 32 Aspergillus fumigatus (Af) exposure mice (20 for histological comparison to 1st control mice and 12 for MSC administration, to CRS/MCS model) and 32 control mice (20 for histological comparison to CRS model and 12 for MSC administration and histological control to MSC model); in the first stage, the Aspergillus fumigatus (Af) CRS mouse model was targeted, in this section were included 64 (n = 32) mice (treated and control group). In order to assess the inflammation level (histological analysis), the animals were euthanized; in the second stage MSCs (1 × 106/animal) were administered intravenously to a total of 24 (n = 24) mice (12 mice from the exposed group and 12 mice from the second control group). Results: After 12 weeks of Af intranasal instillation, the inflammation parameters evaluated indicated a severe diffuse chronic inflammation, associated with diffuse severe hyperplasia and mature diffuse squamous metaplasia. The MSCs’ injection via the ophthalmic vein induced important histopathological changes in the CRS experimental group, starting with the presence of MSCs in all samples and continuing with the important degenerative character of inflammation. Conclusions: MSC administration demonstrated a real improvement of CRS evolution on the CRS mouse model.
Experimental Study on the Mechanical Properties and Failure Characteristics of Layered Aeolian Sand Paste-Like Backfill—A Case Study from Shanghe Coal Mine
Authors: Shao Xiaoping , Sun Wuliang , Li Xin , Wang Long , Fang Zhiyu , Zhao Bingchao , Sun Jianpeng , Tian Chuang , Xu Baowa
Published: May 2021

Filling mining is an important direction in green coal mining. In the filling site, a layered filling body can be formed due to technological problems. In this paper, we take Shanghe Coal Mine (Shaanxi Province, China) as the background. In order to explore the mechanical properties and failure modes of layered backfill, specimens with different layered proportions (1:1, 1:3, 3:1) were made and studied concerning the aspects of wave velocity, porosity, strength and failure modes. The experimental result demonstrates that with the increase of curing time and fly ash (FA) content, the porosity of ASPLB decreases, the wave velocity and the strength increases. In addition, the layered structure has a significant effect on the strength and failure mode of the specimen. Uniaxial compression experiments showed that after 28 days of curing with Ratio III, the strength of layered backfill (LB) was reduced by 14% and the strength of 3:1 LB was increased by 16.7% and 40% compared with 1:1 LB and 1:3 LB, respectively. A digital speckle experiment showed that the failure mode of ASPLB is a vertical fracture without penetration, and the fracture propagation of layered ASPLB is hindered by the stratification. Based on the above research, the scheme that meets the requirements of the Shanghe Coal Mine is determined, and its reliability is verified, providing guidance for scientific stratification and the filling of gob.
Fractions of Ni, Pb, Cr, and Their Impact on Enzyme Activities of Arable Land Cultivated by the Simplified Method
Authors: Łukowski Adam , Dec Dorota
Published: May 2021

Total metal content is not representing its availability and thus does not provide the details about potential environmental hazards, including the impact on soil enzyme activities. To understand metal availability, chemical fractions must be considered. The goal of this study was to evaluate the influence of Ni, Cr, and Pb fractions on the enzymatic activity of soils cultivated by the simplified method, which is rare not only in Poland. The percentage of studied metals in fractions was determined according to the Community Bureau of Reference (BCR) method. Four fractions were extracted: acid soluble and exchangeable (F1), reducible (F2), oxidizable (F3), and residual (F4). The highest Ni and Cr percentages were noted in fraction F4, and for Pb, they were noted in fraction F2. The smallest Ni and Pb percentages were observed in fraction F1 (most mobile) and for Cr, they were observed in fraction F2. In soil samples collected in spring, the significant relationship was stated between F1/Ni/dehydrogenase, F2/Pb/dehydrogenase, and F2/Pb/urease. Such dependence occurred between F1/Ni/phosphatase and F4/Ni/urease during summer as well as between F1/Ni/phosphatase and F4/Ni/dehydrogenase in autumn. F1/Pb caused a drop in phosphatase activity, whereas F4/Cr influenced its increase. The study results indicated that metal fractions influenced phosphatase activity the most, while protease activity in the soil was not affected.
Overview of the Structure–Dynamics–Function Relationships in Borohydrides for Use as Solid-State Electrolytes in Battery Applications
Authors: Dobbins Tabbetha A.
Published: May 2021

The goal of this article is to highlight crucial breakthroughs in solid-state ionic conduction in borohydrides for battery applications. Borohydrides, Mz+BxHy, form in various molecular structures, for example, nido-M+BH4; closo-M2+B10H10; closo-M2+B12H12; and planar-M6+B6H6 with M = cations such as Li+, K+, Na+, Ca2+, and Mg2+, which can participate in ionic conduction. This overview article will fully explore the phase space of boron–hydrogen chemistry in order to discuss parameters that optimize these materials as solid electrolytes for battery applications. Key properties for effective solid-state electrolytes, including ionic conduction, electrochemical window, high energy density, and resistance to dendrite formation, are also discussed. Because of their open structures (for closo-boranes) leading to rapid ionic conduction, and their ability to undergo phase transition between low conductivity and high conductivity phases, borohydrides deserve a focused discussion and further experimental efforts. One challenge that remains is the low electrochemical stability of borohydrides. This overview article highlights current knowledge and additionally recommends a path towards further computational and experimental research efforts.
Preparation and Synthetic Application of Naproxen-Containing Diaryliodonium Salts
Authors: Zhou Jun , Bao Zhiyuan , Wu Panpan , Chen Chao
Published: May 2021

The synthesis of naproxen-containing diaryliodonium salts has been realized from naproxen methyl ester and ArI(OH)OTs activated by trimethylsilyl trifluoromethanesulfonate (TMSOTf) in a solvent mixture comprising dichloromethane and 2,2,2-trifluoroethanol (TFE). Those iodonium salts have been successfully used in the functionalization of an aromatic ring of naproxen methyl ester, including fluorination, iodination, alkynylation, arylation, thiophenolation, and amination and esterification reactions. Moreover, further hydrolysis of the obtained 5-iodo-naproxen methyl ester afforded 5-iodo-naproxen.
5-HT1A Serotonergic, α-Adrenergic and Opioidergic Receptors Mediate the Analgesic Efficacy of Vortioxetine in Mice
Authors: Turan Yücel Nazlı , Kandemir Ümmühan , Demir Özkay Ümide , Can Özgür Devrim
Published: May 2021

Vortioxetine is a multimodal antidepressant drug that affects several brain neurochemicals and has the potential to induce various pharmacological effects on the central nervous system. Therefore, we investigated the centrally mediated analgesic efficacy of this drug and the mechanisms underlying this effect. Analgesic activity of vortioxetine (5, 10 and 20 mg/kg, p.o.) was examined by tail-clip, tail-immersion and hot-plate tests. Motor performance of animals was evaluated using Rota-rod device. Time course measurements (30–180 min) showed that vortioxetine (10 and 20 mg/kg) administrations significantly increased the response latency, percent maximum possible effect and area under the curve values in all of the nociceptive tests. These data pointed out the analgesic effect of vortioxetine on central pathways carrying acute thermal and mechanical nociceptive stimuli. Vortioxetine did not alter the motor coordination of mice indicating that the analgesic activity of this drug was specific. In mechanistic studies, pre-treatments with p-chlorophenylalanine (serotonin-synthesis inhibitor), NAN-190 (serotonin 5-HT1A receptor antagonist), α-methyl-para-tyrosine (catecholamine-synthesis inhibitor), phentolamine (non-selective α-adrenoceptor blocker), and naloxone (non-selective opioid receptor blocker) antagonised the vortioxetine-induced analgesia. Obtained findings indicated that vortioxetine-induced analgesia is mediated by 5-HT1A serotonergic, α-adrenergic and opioidergic receptors, and contributions of central serotonergic and catecholaminergic neurotransmissions are critical for this effect.
Neuroprotection with the Cannabidiol Quinone Derivative VCE-004.8 (EHP-101) against 6-Hydroxydopamine in Cell and Murine Models of Parkinson’s Disease
Authors: Burgaz Sonia , García Concepción , Gómez-Cañas María , Rolland Alain , Muñoz Eduardo , Fernández-Ruiz Javier
Published: May 2021

The 3-hydroxyquinone derivative of the non-psychotrophic phytocannabinoid cannabigerol, so-called VCE-003.2, and some other derivatives have been recently investigated for neuroprotective properties in experimental models of Parkinson’s disease (PD) in mice. The pharmacological effects in those models were related to the activity on the peroxisome proliferator-activated receptor-γ (PPAR-γ) and possibly other pathways. In the present study, we investigated VCE-004.8 (formulated as EHP-101 for oral administration), the 3-hydroxyquinone derivative of cannabidiol (CBD), with agonist activity at the cannabinoid receptor type-2 (CB2) receptor in addition to its activity at the PPAR-γ receptor. Studies were conducted in both in vivo (lesioned-mice) and in vitro (SH-SY5Y cells) models using the classic parkinsonian neurotoxin 6-hydroxydopamine (6-OHDA). Our data confirmed that the treatment with VCE-004.8 partially reduced the loss of tyrosine hydroxylase (TH)-positive neurons measured in the substantia nigra of 6-OHDA-lesioned mice, in parallel with an almost complete reversal of the astroglial (GFAP) and microglial (CD68) reactivity occurring in this structure. Such neuroprotective effects attenuated the motor deficiencies shown by 6-OHDA-lesioned mice in the cylinder rearing test, but not in the pole test. Next, we explored the mechanism involved in the beneficial effect of VCE-004.8 in vivo, by analyzing cell survival in cultured SH-SY5Y cells exposed to 6-OHDA. We found an important cytoprotective effect of VCE-004.8 at a concentration of 10 µM, which was completely reversed by the addition of antagonists, T0070907 and SR144528, aimed at blocking PPAR-γ and CB2 receptors, respectively. The treatment with T0070907 alone only caused a partial reversal, whereas SR144528 alone had no effect, indicating a major contribution of PPAR-γ receptors in the cytoprotective effect of VCE-004.8 at 10 µM. In summary, our data confirmed the neuroprotective potential of VCE-004.8 in 6-OHDA-lesioned mice, and in vitro studies confirmed a greater relevance for PPAR-γ receptors rather than CB2 receptors in these effects.
Benefits and Pitfalls of HPLC Coupled to Diode-Array, Charged Aerosol, and Coulometric Detections: Effect of Detection on Screening of Bioactive Compounds in Apples
Authors: Hollá Marcela , Bílková Aneta , Jakubec Pavel , Košková Stanislava , Kočová Vlčková Hana , Šatínský Dalibor , Švec František , Sklenářová Hana
Published: May 2021

The new screening method for rapid evaluation of major phenolic compounds in apples has been developed. Suitability of coupling HPLC/UHPLC separation with the diode-array detection and universal charged aerosol detection with respect to the presence of interfering substances was tested. Characteristics of both detection techniques were compared and method linearity, limits of detection and quantitation, and selectivity of them determined. Student t-test based on slopes of calibration plots was applied for the detailed comparison. The diode-array detection provided the best results regarding sensitivity and selectivity of the developed method in terms of evaluation of phenolics profiles. The response of the charged aerosol detector was negatively affected by co-eluting substances during rapid-screening analyses. Coulometric detection was used for advanced characterization of extracts in terms of antioxidant content and strength to obtain more complex information concerning sample composition. This detection also allowed evaluation of unidentified compounds with antioxidant activity. HPLC/UHPLC separation using a combination of diode-array and coulometric detectors thus represented the best approach enabling quick, yet complex characterization of bioactive compounds in apples.
Preharvest UVB Application Increases Glucosinolate Contents and Enhances Postharvest Quality of Broccoli Microgreens
Authors: Lu Yingjian , Dong Wen , Yang Tianbao , Luo Yaguang , Chen Pei
Published: May 2021

Broccoli microgreens have shown potential health benefits due to their high glucosinolate (GL) levels. Previously, we observed that postharvest UVB treatment did not have much effect on increasing GLs in broccoli microgreens. In this study, we investigated the influence of preharvest UVB irradiation on GL levels in broccoli microgreens. UHPLC-ESI/ITMS analysis showed that preharvest UVB treatments with UVB 0.09 and 0.27 Wh/m2 significantly increased the glucoraphanin (GLR), glucoerucin (GLE), and total aliphatic GL levels by 13.7 and 16.9%, respectively, in broccoli microgreens when measured on harvest day. The nutritional qualities of UVB-treated microgreens were stable during 21-day storage, with only small changes in their GL levels. Broccoli microgreens treated before harvest with UVB 0.27 Wh/m2 and 10 mM CaCl2 spray maintained their overall quality, and had the lowest tissue electrolyte leakage and off-odor values during the storage. Furthermore, preharvest UVB 0.27 Wh/m2 treatment significantly increased GL biosynthesis genes when evaluated before harvest, and reduced the expression level of myrosinase, a gene responsible for GL breakdown during postharvest storage. Overall, preharvest UVB treatment, together with calcium chloride spray, can increase and maintain health-beneficial compound levels such as GLs and prolong the postharvest quality of broccoli microgreens.
Enzyme Models—From Catalysis to Prodrugs
Authors: Breijyeh Zeinab , Karaman Rafik
Published: May 2021

Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete. Computational methodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play an important role in elucidating the detailed mechanisms of enzymatic reactions where experimental research measurements are not possible. Theories invoked by a variety of scientists indicate that enzymes work as structural scaffolds that serve to bring together and orient the reactants so that the reaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzyme catalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokinetics of drugs; classical prodrug approaches focus on alternating the physicochemical properties, while chemical modern approaches are based on the knowledge gained from the chemistry of enzyme models and correlations between experimental and calculated rate values of intramolecular processes (enzyme models). A large number of prodrugs have been designed and developed to improve the effectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), antiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamic acid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol), antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin. This article describes the works done on enzyme models and the computational methods used to understand enzyme catalysis and to help in the development of efficient prodrugs.
Design of Chitosan Sterilization Agents by a Structure Combination Strategy and Their Potential Application in Crop Protection
Authors: Liu Weixiang , Qin Yukun , Li Pengcheng
Published: May 2021

Chitosan is the only cationic polysaccharide in nature. It is a type of renewable resource and is abundant. It has good biocompatibility, biodegradability and biological activity. The amino and hydroxyl groups in its molecules can be modified, which enables chitosan to contain a variety of functional groups, giving it a variety of properties. In recent years, researchers have used different strategies to synthesize a variety of chitosan derivatives with novel structure and unique activity. Structure combination is one of the main strategies. Therefore, we will evaluate the synthesis and agricultural antimicrobial applications of the active chitosan derivatives structure combinations, which have not been well-summarized. In addition, the advantages, challenges and developmental prospects of agricultural antimicrobial chitosan derivatives will be discussed.
Molecular Dynamics of Cobalt Protoporphyrin Antagonism of the Cancer Suppressor REV-ERBβ
Authors: Fakih Taufik Muhammad , Kurniawan Fransiska , Yusuf Muhammad , Mudasir Mudasir , Tjahjono Daryono Hadi
Published: May 2021

Nuclear receptor REV-ERBβ is an overexpressed oncoprotein that has been used as a target for cancer treatment. The metal-complex nature of its ligand, iron protoporphyrin IX (Heme), enables the REV-ERBβ to be used for multiple therapeutic modalities as a photonuclease, a photosensitizer, or a fluorescence imaging agent. The replacement of iron with cobalt as the metal center of protoporphyrin IX changes the ligand from an agonist to an antagonist of REV-ERBβ. The mechanism behind that phenomenon is still unclear, despite the availability of crystal structures of REV-ERBβ in complex with Heme and cobalt protoporphyrin IX (CoPP). This study used molecular dynamic simulations to compare the effects of REV-ERBβ binding to Heme and CoPP, respectively. The initial poses of Heme and CoPP in complex with agonist and antagonist forms of REV-ERBβ were predicted using molecular docking. The binding energies of each ligand were calculated using the MM/PBSA method. The computed binding affinity of Heme to REV-ERBβ was stronger than that of CoPP, in agreement with experimental results. CoPP altered the conformation of the ligand-binding site of REV-ERBβ, disrupting the binding site for nuclear receptor corepressor, which is required for REV-ERBβ to regulate the transcription of downstream target genes. Those results suggest that a subtle change in the metal center of porphyrin can change the behavior of porphyrin in cancer cell signaling. Therefore, modification of porphyrin-based agents for cancer therapy should be conducted carefully to avoid triggering unfavorable effects.
Forensic Biochemical Markers to Evaluate the Agonal Period: A Literature Review
Authors: Rosato Enrica , Bonelli Martina , Locatelli Marcello , de Grazia Ugo , Tartaglia Angela , Savini Fabio , D'Ovidio Cristian
Published: May 2021

Currently, forensic research is multidisciplinary with new methods and parameters useful to define the cause and time of death as well as survival/agony times. The identification of biochemical markers able to estimate agonal period has been studied by many forensic researchers. It is known that the estimation of agonal time in different types of death is not always easy, hence our interest in literature’s data. The studies analyzed in this review confirm the important role of thanatobiochemistry for the estimation of survival times. Regardless of the death cause, the survival/agony time between the primary event and death influences markers concentrations in biological samples (e.g., blood, urine, cerebrospinal fluid). Different biomarkers can be used for qualitative evaluations in deaths with short and long agony (e.g., C-reactive protein, ferritin, GFAP, etc.). Instead, the quantitative interpretation showed limits due to the lack of reference cut-offs. Thanatobiochemistry is a useful tool to confirm what emerged from autopsies findings (macroscopic and histological analysis), but further studies are desirable to confirm the evidence emerging from our review of the literature.
Preparation of Catechin Nanoemulsion from Oolong Tea Leaf Waste and Its Inhibition of Prostate Cancer Cells DU-145 and Tumors in Mice
Authors: Lin Yu-Hsiang , Wang Chi-Chung , Lin Ying-Hung , Chen Bing-Huei
Published: May 2021

Anti-cancer activity of catechin nanoemulsions prepared from Oolong tea leaf waste was studied on prostate cancer cells DU-145 and DU-145-induced tumors in mice. Catechin nanoemulsions composed of lecithin, Tween-80 and water in an appropriate proportion was prepared with high stability, particle size of 11.3 nm, zeta potential of −67.2 mV and encapsulation efficiency of 83.4%. Catechin nanoemulsions were more effective than extracts in inhibiting DU-145 cell growth, with the IC50 being 13.52 and 214.6 μg/mL, respectively, after 48 h incubation. Furthermore, both catechin nanoemulsions and extracts could raise caspase-8, caspase-9 and caspase-3 activities for DU-145 cell apoptosis, arresting the cell cycle at S and G2/M phases. Compared to control, catechin nanoemulsion at 20 μg/mL and paclitaxel at 10 μg/mL were the most effective in reducing tumor volume by 41.3% and 52.5% and tumor weight by 77.5% and 90.6% in mice, respectively, through a decrease in EGF and VEGF levels in serum.
Efficacy of Caffeic Acid on Diabetes and Its Complications in the Mouse
Authors: Oršolić Nada , Sirovina Damir , Odeh Dyana , Gajski Goran , Balta Vedran , Šver Lidija , Jazvinšćak Jembrek Maja
Published: May 2021

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg−1). Two days later, CA (50 mg kg−1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.
Development of Halogenated Pyrazolines as Selective Monoamine Oxidase-B Inhibitors: Deciphering via Molecular Dynamics Approach
Authors: Nair Aathira Sujathan , Oh Jong-Min , Koyiparambath Vishal Payyalot , Kumar Sunil , Sudevan Sachithra Thazhathuveedu , Soremekun Opeyemi , Soliman Mahmoud E. , Khames Ahmed , Abdelgawad Mohamed A. , Pappachen Leena K. , Mathew Bijo , Kim Hoon
Published: May 2021

Halogens have been reported to play a major role in the inhibition of monoamine oxidase (MAO), relating to diverse cognitive functions of the central nervous system. Pyrazoline/halogenated pyrazolines were investigated for their inhibitory activities against human monoamine oxidase-A and -B. Halogen substitutions on the phenyl ring located at the fifth position of pyrazoline showed potent MAO-B inhibition. Compound 3-(4-ethoxyphenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole (EH7) showed the highest potency against MAO-B with an IC50 value of 0.063 µM. The potencies against MAO-B were increased in the order of –F (in EH7) > –Cl (EH6) > –Br (EH8) > –H (EH1). The residual activities of most compounds for MAO-A were > 50% at 10 µM, except for EH7 and EH8 (IC50 = 8.38 and 4.31 µM, respectively). EH7 showed the highest selectivity index (SI) value of 133.0 for MAO-B, followed by EH6 at > 55.8. EH7 was a reversible and competitive inhibitor of MAO-B in kinetic and reversibility experiments with a Ki value of 0.034 ± 0.0067 µM. The molecular dynamics study documented that EH7 had a good binding affinity and motional movement within the active site with high stability. It was observed by MM-PBSA that the chirality had little effect on the overall binding of EH7 to MAO-B. Thus, EH7 can be employed for the development of lead molecules for the treatment of various neurodegenerative disorders.
Preparation of New Sargassum fusiforme Polysaccharide Long-Chain Alkyl Group Nanomicelles and Their Antiviral Properties against ALV-J
Authors: Sun Yuhao , Chen Xiaolin , Liu Hong , Liu Song , Yu Huahua , Wang Xueqin , Qin Yukun , Li Pengcheng
Published: May 2021

Avian leukosis virus subgroup J (ALV-J) is an immunosuppressive virus which has caused heavy losses to the poultry breeding industry. Currently, there is no effective medicine to treat this virus. In our previous experiments, the low-molecular-weight Sargassum fusiforme polysaccharide (SFP) was proven to possess antiviral activity against ALV-J, but its function was limited to the virus adsorption stage. In order to improve the antiviral activity of the SFP, in this study, three new SFP long-chain alkyl group nanomicelles (SFP-C12M, SFP-C14M and SFP-C16M) were prepared. The nanomicelles were characterized according to their physical and chemical properties. The nanomicelles were characterized by particle size, zeta potential, polydispersity index, critical micelle concentration and morphology. The results showed the particle sizes of the three nanomicelles were all approximately 200 nm and SFP-C14M and SFP-C16M were more stable than SFP-C12M. The newly prepared nanomicelles exhibited a better anti-ALV-J activity than the SFP, with SFP-C16M exhibiting the best antiviral effects in both the virus adsorption stage and the replication stage. The results of the giant unilamellar vesicle exposure experiment demonstrated that the new virucidal effect of the nanomicelles might be caused by damage to the phospholipid membrane of ALV-J. This study provides a potential idea for ALV-J prevention and development of other antiviral drugs.
NMR Profiling of Ononis diffusa Identifies Cytotoxic Compounds against Cetuximab-Resistant Colon Cancer Cell Lines
Authors: Graziani Vittoria , Potenza Nicoletta , D’Abrosca Brigida , Troiani Teresa , Napolitano Stefania , Fiorentino Antonio , Scognamiglio Monica
Published: May 2021

In the search of new natural products to be explored as possible anticancer drugs, two plant species, namely Ononis diffusa and Ononis variegata, were screened against colorectal cancer cell lines. The cytotoxic activity of the crude extracts was tested on a panel of colon cancer cell models including cetuximab-sensitive (Caco-2, GEO, SW48), intrinsic (HT-29 and HCT-116), and acquired (GEO-CR, SW48-CR) cetuximab-resistant cell lines. Ononis diffusa showed remarkable cytotoxic activity, especially on the cetuximab-resistant cell lines. The active extract composition was determined by NMR analysis. Given its complexity, a partial purification was then carried out. The fractions obtained were again tested for their biological activity and their metabolite content was determined by 1D and 2D NMR analysis. The study led to the identification of a fraction enriched in oxylipins that showed a 92% growth inhibition of the HT-29 cell line at a concentration of 50 µg/mL.
Antinociceptive Efficacy of the µ-Opioid/Nociceptin Peptide-Based Hybrid KGNOP1 in Inflammatory Pain without Rewarding Effects in Mice: An Experimental Assessment and Molecular Docking
Authors: Dumitrascuta Maria , Bermudez Marcel , Trovato Olga , De Neve Jolien , Ballet Steven , Wolber Gerhard , Spetea Mariana
Published: May 2021

Opioids are the most effective analgesics, with most clinically available opioids being agonists to the µ-opioid receptor (MOR). The MOR is also responsible for their unwanted effects, including reward and opioid misuse leading to the current public health crisis. The imperative need for safer, non-addictive pain therapies drives the search for novel leads and new treatment strategies. In this study, the recently discovered MOR/nociceptin (NOP) receptor peptide hybrid KGNOP1 (H-Dmt-D-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) was evaluated following subcutaneous administration in mouse models of acute (formalin test) and chronic inflammatory pain (Complete Freund’s adjuvant-induced paw hyperalgesia), liabilities of spontaneous locomotion, conditioned place preference, and the withdrawal syndrome. KGNOP1 demonstrated dose-dependent antinociceptive effects in the formalin test, and efficacy in attenuating thermal hyperalgesia with prolonged duration of action. Antinociceptive effects of KGNOP1 were reversed by naltrexone and SB-612111, indicating the involvement of both MOR and NOP receptor agonism. In comparison with morphine, KGNOP1 was more potent and effective in mouse models of inflammatory pain. Unlike morphine, KGNOP1 displayed reduced detrimental liabilities, as no locomotor impairment nor rewarding and withdrawal effects were observed. Docking of KGNOP1 to the MOR and NOP receptors and subsequent 3D interaction pattern analyses provided valuable insights into its binding mode. The mixed MOR/NOP receptor peptide KGNOP1 holds promise in the effort to develop new analgesics for the treatment of various pain states with fewer MOR-mediated side effects, particularly abuse and dependence liabilities.
Advances in Pyranopyrazole Scaffolds’ Syntheses Using Sustainable Catalysts—A Review
Authors: Ganta Ravi Kumar , Kerru Nagaraju , Maddila Suresh , Jonnalagadda Sreekantha B.
Published: May 2021

Heterogeneous catalysis plays a crucial role in many chemical processes, including advanced organic preparations and the design and synthesis of new organic moieties. Efficient and sustainable catalysts are vital to ecological and fiscal viability. This is why green multicomponent reaction (MCR) approaches have gained prominence. Owing to a broad range of pharmacological applications, pyranopyrazole syntheses (through the one-pot strategy, employing sustainable heterogeneous catalysts) have received immense attention. This review aimed to emphasise recent developments in synthesising nitrogen-based fused heterocyclic ring frameworks, exploring diverse recyclable catalysts. The article focused on the synthetic protocols used between 2010 and 2020 using different single, bi- and tri-metallic materials and nanocomposites as reusable catalysts. This review designated the catalysts’ efficacy and activity in product yields, reaction time, and reusability. The MCR green methodologies (in conjunction with recyclable catalyst materials) proved eco-friendly and ideal, with a broad scope that could feasibly lead to advancements in organic synthesis.
Solid-Phase Synthesis of an Insect Pyrokinin Analog Incorporating an Imidazoline Ring as Isosteric Replacement of a trans Peptide Bond
Authors: Kaczmarek Krzysztof , Pacholczyk-Sienicka Barbara , Albrecht Łukasz , Zabrocki Janusz , Nachman Ronald J.
Published: May 2021

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).
Effect of the Addition of Alginate and/or Tetracycline on Brushite Cement Properties
Authors: Morilla Claudia , Perdomo Elianis , Hernández Ana Karla , Regalado Ramcy , Almirall Amisel , Fuentes Gastón , Campos Mora Yaima , Schomann Timo , Chan Alan , Cruz Luis J.
Published: May 2021

Calcium phosphate cements have the advantage that they can be prepared as a paste that sets in a few minutes and can be easily adapted to the shape of the bone defect, which facilitates its clinical application. In this research, six formulations of brushite (dicalcium phosphate dihydrated) cement were obtained and the effect of the addition of sodium alginate was analyzed, such as its capacity as a tetracycline release system. The samples that contain sodium alginate set in 4 or 5 min and showed a high percentage of injectability (93%). The cements exhibit compression resistance values between 1.6 and 2.6 MPa. The drug was released in a range between 12.6 and 13.2% after 7 days. The antimicrobial activity of all the cements containing antibiotics was proven. All samples reached values of cell viability above 70 percent. We also observed that the addition of the sodium alginate and tetracycline improved the cell viability.
Numerical Investigation of Graphene as a Back Surface Field Layer on the Performance of Cadmium Telluride Solar Cell
Authors: KC Devendra , Shah Deb Kumar , Akhtar M. Shaheer , Park Mira , Kim Chong Yeal , Yang O-Bong , Pant Bishweshwar
Published: May 2021

This paper numerically explores the possibility of ultrathin layering and high efficiency of graphene as a back surface field (BSF) based on a CdTe solar cell by Personal computer one-dimensional (PC1D) simulation. CdTe solar cells have been characterized and studied by varying the carrier lifetime, doping concentration, thickness, and bandgap of the graphene layer. With simulation results, the highest short-circuit current (Isc = 2.09 A), power conversion efficiency (η = 15%), and quantum efficiency (QE~85%) were achieved at a carrier lifetime of 1 × 103 μs and a doping concentration of 1 × 1017 cm−3 of graphene as a BSF layer-based CdTe solar cell. The thickness of the graphene BSF layer (1 μm) was proven the ultrathin, optimal, and obtainable for the fabrication of high-performance CdTe solar cells, confirming the suitability of graphene material as a BSF. This simulation confirmed that a CdTe solar cell with the proposed graphene as the BSF layer might be highly efficient with optimized parameters for fabrication.
A Review on Obesity Management through Natural Compounds and a Green Nanomedicine-Based Approach
Authors: Bhardwaj Monika , Yadav Poonam , Vashishth Divya , Sharma Kavita , Kumar Ajay , Chahal Jyoti , Dalal Sunita , Kataria Sudhir Kumar
Published: May 2021

Obesity is a serious health complication in almost every corner of the world. Excessive weight gain results in the onset of several other health issues such as type II diabetes, cancer, respiratory diseases, musculoskeletal disorders (especially osteoarthritis), and cardiovascular diseases. As allopathic medications and derived pharmaceuticals are partially successful in overcoming this health complication, there is an incessant need to develop new alternative anti-obesity strategies with long term efficacy and less side effects. Plants harbor secondary metabolites such as phenolics, flavonoids, terpenoids and other specific compounds that have been shown to have effective anti-obesity properties. Nanoencapsulation of these secondary metabolites enhances the anti-obesity efficacy of these natural compounds due to their speculated property of target specificity and enhanced efficiency. These nanoencapsulated and naive secondary metabolites show anti-obesity properties mainly by inhibiting the lipid and carbohydrate metabolizing enzymes, suppression of adipogenesis and appetite, and enhancing energy metabolism. This review focuses on the plants and their secondary metabolites, along with their nanoencapsulation, that have anti-obesity effects, with their possible acting mechanisms, for better human health.
Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review
Authors: Nugrahani Ilma , Jessica Maria Anabella
Published: May 2021

Co-crystals are one of the most popular ways to modify the physicochemical properties of active pharmaceutical ingredients (API) without changing pharmacological activity through non-covalent interactions with one or more co-formers. A “green method” has recently prompted many researchers to develop solvent-free techniques or minimize solvents for arranging the eco-friendlier process of co-crystallization. Researchers have also been looking for less-risk co-formers that produce the desired API’s physicochemical properties. This review purposed to collect the report studies of amino acids as the safe co-former and explored their advantages. Structurally, amino acids are promising co-former candidates as they have functional groups that can form hydrogen bonds and increase stability through zwitterionic moieties, which support strong interactions. The co-crystals and deep eutectic solvent yielded from this natural compound have been proven to improve pharmaceutical performance. For example, l-glutamine could reduce the side effects of mesalamine through an acid-base stabilizing effect in the gastrointestinal fluid. In addition, some amino acids, especially l-proline, enhances API’s solubility and absorption in its natural deep eutectic solvent and co-crystals systems. Moreover, some ionic co-crystals of amino acids have also been designed to increase chiral resolution. Therefore, amino acids are safe potential co-formers, which are suitable for improving the physicochemical properties of API and prospective to be developed further in the dosage formula and solid-state syntheses.