bluuebunny/crossref_metadata_2025 huggingface dataset:
Ayurveda and Epigenetics
Authors: Sharma Hari , Keith Wallace Robert
Published: December 2020

Ayurveda is a comprehensive, natural health care system that originated in the ancient Vedic times of India. Epigenetics refers to the external modification of DNA that turns genes on and off, affecting gene expression. This occurs without changes in the basic structure of the DNA. This gene expression can have transgenerational effects. The major factors that cause epigenetic changes are lifestyle and behavior, diet and digestion, stress, and environmental factors. Ayurveda addresses these factors, thereby affecting the Deha (body) Prakriti (psychophysiological constitution), which corresponds to the phenotype, and indirectly the Janma (birth) Prakriti, which corresponds to the genotype. Thus, it is proposed that epigenetics is an important mechanism of Ayurveda. This correlation and understanding will lead to better communication and understanding with the current medical system, and lead to better integration of both sciences in the management of optimal health. In addition, research on Ayurvedic modalities affecting gene expression will further increase correlation and understanding between the current medical system and Ayurveda.
Membrane Biofouling Control by Surface Modification of Quaternary Ammonium Compound Using Atom-Transfer Radical-Polymerization Method with Silica Nanoparticle as Interlayer
Authors: Ren Lehui , Ping Meng , Zhang Xingran
Published: December 2020

A facile approach to fabricate antibiofouling membrane was developed by grafting quaternary ammonium compounds (QACs) onto polyvinylidene fluoride (PVDF) membrane via surface-initiated activators regenerated by electron transfer atom-transfer radical-polymerization (ARGET ATRP) method. During the modification process, a hydrophilic silica nanoparticle layer was also immobilized onto the membrane surface as an interlayer through silicification reaction for QAC grafting, which imparted the membrane with favorable surface properties (e.g., hydrophilic and negatively charged surface). The QAC-modified membrane (MQ) showed significantly improved hydrophilicity and permeability mainly due to the introduction of silica nanoparticles and exposure of hydrophilic quaternary ammonium groups instead of long alkyl chains. Furthermore, the coverage of QAC onto membrane surface enabled MQ membrane to have clear antibacterial effect, with an inhibition rate ~99.9% of Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), respectively. According to the batch filtration test, MQ had better antibiofouling performance compared to the control membrane, which was ascribed to enhanced hydrophilicity and antibacterial activity. Furthermore, the MQ membrane also exhibited impressive stability of QAC upon suffering repeated fouling–cleaning tests. The modification protocols provide a new robust way to fabricate high-performance antibiofouling QAC-based membranes for wastewater treatment.
Nonlinear Analysis of Steel Structure Bent Frame Column Bearing Transverse Concentrated Force at the Top in Factory Buildings
Authors: Li Chunbao , Wang Lina , Weng Yongmei , Qin Pengju , Li Gaojie
Published: December 2020

The steel bent frame structure of single-story factory buildings is actually a spatial structure system. Different bent frame columns are connected with the roof of bent frame structure, making the columns work and bearing the load together. In the steel frame of the factory building with bridge cranes below 20 t, variable-section columns with corbels are used to bear the crane load. In this article, the steel bent frame column of single-story factory buildings was taken as the research object. The bent frame column was simplified as a cantilever variable stepped column bearing a transverse concentrated force at the top. After simplifying the model, the theoretical formula of deflection, rotating angle, and bending moment of the compression rod was put forward. Moreover, bending deformation and stability of variable stepped columns were analyzed in order to obtain the theoretical and practical formula, then the ANSYS software was used to simulate the bent column.
Numerical Investigation of Blast Furnace Operation with Scrap Charging
Authors: Liu Zhu , Yu Zi , She Xuefeng , Tang Huiqing , Xue Qingguo
Published: December 2020

One approach to reduce CO2 emission in the steelmaking industry is to recycle scrap to the blast furnace/basic oxygen furnace (BF/BOF) production system. This paper performed a numerical investigation on the BF operation with scrap charging. The investigated BF was with an inner volume of 820 m3, producing 2950 tons of hot metal per day (tHM/d). The simulated results indicated the following: Extra scrap addition in BF causes the decrease of shaft temperature, the decrease of local gas utilization, and the lowering of cohesive zone position, leading to an unstable BF running. The partial replacement of sinter with scrap in BF can mitigate the negative effects induced by scrap charging. The optimal scrap rate in the BF is 178 kg/tHM, under which the BF reaches a productivity of 3310 tHM/d, a top-gas utilization of 48.5%, and a top-gas temperature of 445 K. Compared to the base case, in the BF operation with scrap charging, the BF productivity is increased by 360 kg/tHM, its pulverized-coal rate and coke rate are decreased by 16.3 kg/tHM and 39.8 kg/tHM, respectively.
Flotation Separation of Chalcopyrite and Molybdenite Assisted by Microencapsulation Using Ferrous and Phosphate Ions: Part I. Selective Coating Formation
Authors: Park Ilhwan , Hong Seunggwan , Jeon Sanghee , Ito Mayumi , Hiroyoshi Naoki
Published: December 2020

Porphyry Cu-Mo deposits, which are the most important sources of copper and molybdenum, are typically processed by flotation. In order to separate Cu and Mo minerals (mostly chalcopyrite and molybdenite), the strategy of depressing chalcopyrite while floating molybdenite has been widely adopted by using chalcopyrite depressants, such as NaHS, Na2S, and Nokes reagent. However, these depressants are potentially toxic due to their possibility to emit H2S gas. Thus, this study aims at developing a new concept for selectively depressing chalcopyrite via microencapsulation while using Fe2+ and PO43− forming Fe(III)PO4 coating. The cyclic voltammetry results indicated that Fe2+ can be oxidized to Fe3+ on the chalcopyrite surface, but not on the molybdenite surface, which arises from their different electrical properties. As a result of microencapsulation treatment using 1 mmol/L Fe2+ and 1 mmol/L PO43−, chalcopyrite was much more coated with FePO4 than molybdenite, which indicated that selective depression of chalcopyrite by the microencapsulation technique is highly achievable.
Cathodically Pretreated AuNPs–BDD Electrode for Detection of Hexavalent Chromium
Authors: Xu Yuhao , Xiong Chenyu , Gao Chengyao , Li Yang , Bian Chao , Xia Shanhong
Published: December 2020

Hexavalent chromium (Cr (VI)) has strong oxidizing properties and can result in strong carcinogenic effects on human bodies. Therefore, it is necessary to detect hexavalent chromium sensitively and accurately. This article proposes the gold nanoparticles (AuNPs)–boron-doped diamond (BDD) electrode for the direct determination of chromium with a green and simple detection process by cathodic stripping voltammetry. Gold nanoparticles are used to enhance the detection performance toward Cr (VI). The effect of different pretreatment methods on electrode modification has been studied, and the detection parameters have been optimized. With the optimized conditions, the AuNPs–BDD electrode presents a good linear behavior in a Cr (VI) concentration range of 10 to 1000 μg/L. A low limit of detection of 1.19 μg/L is achieved. The detection process is simple and environmentally friendly. The sensor has been tested for the detection of Cr (VI) in a real water sample with satisfactory results, which indicates potential application of the AuNPs–BDD electrode for the sensitive and onsite detection of Cr (VI).
Dual-Tunable Broadband Terahertz Absorber Based on a Hybrid Graphene-Dirac Semimetal Structure
Authors: Wu Jiali , Yuan Xueguang , Zhang Yangan , Yan Xin , Zhang Xia
Published: December 2020

A dual-controlled tunable broadband terahertz absorber based on a hybrid graphene-Dirac semimetal structure is designed and studied. Owing to the flexible tunability of the surface conductivity of graphene and relative permittivity of Dirac semimetal, the absorption bandwidth can be tuned independently or jointly by shifting the Fermi energy through chemical doping or applying gate voltage. Under normal incidence, the device exhibits a high absorption larger than 90% over a broad range of 4.06–10.7 THz for both TE and TM polarizations. Moreover, the absorber is insensitive to incident angles, yielding a high absorption over 90% at a large incident angle of 60° and 70° for TE and TM modes, respectively. The structure shows great potential in miniaturized ultra-broadband terahertz absorbers and related applications.
Sequence-Specific Detection of DNA Strands Using a Solid-State Nanopore Assisted by Microbeads
Authors: Zhang Yin , Gu Zengdao , Zhao Jiabin , Shao Liying , Kan Yajing
Published: December 2020

Simple, rapid, and low-cost detection of DNA with specific sequence is crucial for molecular diagnosis and therapy applications. In this research, the target DNA molecules are bonded to the streptavidin-coated microbeads, after hybridizing with biotinylated probes. A nanopore with a diameter significantly smaller than the microbeads is used to detect DNA molecules through the ionic pulse signals. Because the DNA molecules attached on the microbead should dissociate from the beads before completely passing through the pore, the signal duration time for the target DNA is two orders of magnitude longer than free DNA. Moreover, the high local concentration of target DNA molecules on the surface of microbeads leads to multiple DNA molecules translocating through the pore simultaneously, which generates pulse signals with amplitude much larger than single free DNA translocation events. Therefore, the DNA molecules with specific sequence can be easily identified by a nanopore sensor assisted by microbeads according to the ionic pulse signals.
The Effect of Diclofenac Sodium-Loaded Poly(Lactide-co-Glycolide) Rods on Bone Formation and Inflammation: A Histological and Histomorphometric Study in the Femora of Rats
Authors: Reich Karoline M. , Viitanen Petrus , Apu Ehsanul Hoque , Tangl Stefan , Ashammakhi Nureddin
Published: December 2020

Implants made of poly(lactide-co-glycolide) (PLGA) are biodegradable and frequently provoke foreign body reactions (FBR) in the host tissue. In order to modulate the inflammatory response of the host tissue, PLGA implants can be loaded with anti-inflammatory drugs. The aim of this study was to analyze the impact of PLGA 80/20 rods loaded with the diclofenac sodium (DS) on local tissue reactions in the femur of rats. Special emphasis was put on bone regeneration and the presence of multinucleated giant cells (MGCs) associated with FBR. PLGA 80/20 alone and PLGA 80/20 combined with DS was extruded into rods. PLGA rods loaded with DS (PLGA+DS) were implanted into the femora of 18 rats. Eighteen control rats received unloaded PLGA rods. The follow-up period was of 3, 6 and 12 weeks. Each group comprised of six rats. Peri-implant tissue reactions were histologically and histomorphometrically evaluated. The implantation of PLGA and PLGA+DS8 rods induced the formation of a layer of newly formed bone islands parallel to the contour of the implants. PLGA+DS rods tended to reduce the presence of multi-nucleated giant cells (MGCs) at the implant surface. Although it is known that the systemic administration of DS is associated with compromised bone healing, the local release of DS via PLGA rods did not have negative effects on bone regeneration in the femora of rats throughout 12 weeks.
Design and Implementation of a SiC-Based VRFB Power Conditioning System
Authors: Ma Chao-Tsung , Tian Yi-Hung
Published: December 2020

An energy storage system using secondary batteries combined with advanced power control schemes is considered the key technology for the sustainable development of renewable energy-based power generation and smart micro-grids. The performance of energy storage systems in practical application mainly depends on their power conditioning systems. This paper proposes a silicon carbide-based multifunctional power conditioning system for the vanadium redox flow battery. The proposed system is a two-stage circuit topology, including a three-phase grid-tie inverter that can perform four-quadrant control of active and reactive power and a bi-directional multi-channel direct current converter that is responsible for the fast charging and discharging control of the battery. To achieve the design objectives, i.e., high reliability, high efficiency, and high operational flexibility, silicon carbide-based switching devices, and advanced digital control schemes are used in the construction of a power conditioning system for the vanadium redox flow battery. This paper first describes the proposed system topologies and controller configurations and the design methods of controllers for each converter in detail, and then results from both simulation analyses and experimental tests on a 5 kVA hardware prototype are presented to verify the feasibility and effectiveness of the proposed system and the designed controllers.
Design and Analysis of Gallium Nitride-Based p-i-n Diode Structure for Betavoltaic Cell with Enhanced Output Power Density
Authors: Yoon Young Jun , Lee Jae Sang , Kang In Man , Lee Jung Hee , Kim Dong Seok
Published: December 2020

In this work, Gallium Nitride (GaN)-based p-i-n diodes were designed using a computer aided design (TCAD) simulator for realizing a betavoltaic (BV) cell with a high output power density (Pout). The short-circuit current density (JSC) and open-circuit voltage (VOC) of the 17 keV electron-beam (e-beam)-irradiated diode were evaluated with the variations of design parameters, such as the height and doping concentration of the intrinsic GaN region (Hi-GaN and Di-GaN), which influenced the depletion width in the i-GaN region. A high Hi-GaN and a low Di-GaN improved the Pout because of the enhancement of absorption and conversion efficiency. The device with the Hi-GaN of 700 nm and Di-GaN of 1 × 1016 cm−3 exhibited the highest Pout. In addition, the effects of native defects in the GaN material on the performances were investigated. While the reverse current characteristics were mainly unaffected by donor-like trap states like N vacancies, the Ga vacancies-induced acceptor-like traps significantly decreased the JSC and VOC due to an increase in recombination rate. As a result, the device with a high acceptor-like trap density dramatically degenerated the Pout. Therefore, growth of the high quality i-GaN with low acceptor-like traps is important for an enhanced Pout in BV cell.
Three Novel Clostridia Isolates Produce n-Caproate and iso-Butyrate from Lactate: Comparative Genomics of Chain-Elongating Bacteria
Authors: Liu Bin , Popp Denny , Müller Nicolai , Sträuber Heike , Harms Hauke , Kleinsteuber Sabine
Published: December 2020

The platform chemicals n-caproate and iso-butyrate can be produced by anaerobic fermentation from agro-industrial residues in a process known as microbial chain elongation. Few lactate-consuming chain-elongating species have been isolated and knowledge on their shared genetic features is still limited. Recently we isolated three novel clostridial strains (BL-3, BL-4, and BL-6) that convert lactate to n-caproate and iso-butyrate. Here, we analyzed the genetic background of lactate-based chain elongation in these isolates and other chain-elongating species by comparative genomics. The three strains produced n-caproate, n-butyrate, iso-butyrate, and acetate from lactate, with the highest proportions of n-caproate (18%) for BL-6 and of iso-butyrate (23%) for BL-4 in batch cultivation at pH 5.5. They show high genomic heterogeneity and a relatively small core-genome size. The genomes contain highly conserved genes involved in lactate oxidation, reverse β-oxidation, hydrogen formation and either of two types of energy conservation systems (Rnf and Ech). Including genomes of another eleven experimentally validated chain-elongating strains, we found that the chain elongation-specific core-genome encodes the pathways for reverse β-oxidation, hydrogen formation and energy conservation, while displaying substantial genome heterogeneity. Metabolic features of these isolates are important for biotechnological applications in n-caproate and iso-butyrate production.
Deaminase-Independent Mode of Antiretroviral Action in Human and Mouse APOBEC3 Proteins
Authors: Hakata Yoshiyuki , Miyazawa Masaaki
Published: December 2020

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) proteins (APOBEC3s) are deaminases that convert cytosines to uracils predominantly on a single-stranded DNA, and function as intrinsic restriction factors in the innate immune system to suppress replication of viruses (including retroviruses) and movement of retrotransposons. Enzymatic activity is supposed to be essential for the APOBEC3 antiviral function. However, it is not the only way that APOBEC3s exert their biological function. Since the discovery of human APOBEC3G as a restriction factor for HIV-1, the deaminase-independent mode of action has been observed. At present, it is apparent that both the deaminase-dependent and -independent pathways are tightly involved not only in combating viruses but also in human tumorigenesis. Although the deaminase-dependent pathway has been extensively characterized so far, understanding of the deaminase-independent pathway remains immature. Here, we review existing knowledge regarding the deaminase-independent antiretroviral functions of APOBEC3s and their molecular mechanisms. We also discuss the possible unidentified molecular mechanism for the deaminase-independent antiretroviral function mediated by mouse APOBEC3.
Temporal Resistome and Microbial Community Dynamics in an Intensive Aquaculture Facility with Prophylactic Antimicrobial Treatment
Authors: Patil Hemant J. , Gatica Joao , Zolti Avihai , Benet-Perelberg Ayana , Naor Alon , Dror Barak , Al Ashhab Ashraf , Marman Sophi , Hasan Nur A. , Colwell Rita R. , Sher Daniel , Minz Dror , Cytryn Eddie
Published: December 2020

Excessive use of antimicrobials in aquaculture is concerning, given possible environmental ramifications and the potential contribution to the spread of antimicrobial resistance (AR). In this study, we explored seasonal abundance of antimicrobial resistance genes and bacterial community composition in the water column of an intensive aquaculture pond stocked with Silver Carp (Hypophthalmichthys molitrix) prophylactically treated with sulfamethoprim (25% sulfadiazine; 5% trimethoprim), relative to an adjacent unstocked reservoir. Bacterial community composition was monitored using high-throughput sequencing of 16S rRNA gene amplicons in eight sampling profiles to determine seasonal dynamics, representing principal stages in the fish fattening cycle. In tandem, qPCR was applied to assess relative abundance of selected antimicrobial resistance genes (sul1, sul2, dfrA1, tetA and blaTEM) and class-1 integrons (int1). Concomitantly, resistomes were extrapolated from shotgun metagenomes in representative profiles. Analyses revealed increased relative abundance of sulfonamide and tetracycline resistance genes in fishpond-03, relative to pre-stocking and reservoir levels, whereas no significant differences were observed for genes encoding resistance to antimicrobials that were not used in the fishpond-03. Seasons strongly dictated bacterial community composition, with high abundance of cyanobacteria in summer and increased relative abundance of Flavobacterium in the winter. Our results indicate that prophylactic use of sulfonamides in intensive aquaculture ponds facilitates resistance suggesting that prophylactic use of these antimicrobials in aquaculture should be restricted.
Outer Membrane Vesicles Derived from Klebsiella pneumoniae Influence the miRNA Expression Profile in Human Bronchial Epithelial BEAS-2B Cells
Authors: Dell’Annunziata Federica , Ilisso Concetta Paola , Dell’Aversana Carmela , Greco Giuseppe , Coppola Alessandra , Martora Francesca , Dal Piaz Fabrizio , Donadio Giuliana , Falanga Annarita , Galdiero Marilena , Altucci Lucia , Galdiero Massimiliano , Porcelli Marina , Folliero Veronica , Franci Gianluigi
Published: December 2020

Klebsiella pneumoniae is an opportunistic pathogen that causes nosocomial and community-acquired infections. The spread of resistant strains of K. pneumoniae represents a growing threat to human health, due to the exhaustion of effective treatments. K. pneumoniae releases outer membrane vesicles (OMVs). OMVs are a vehicle for the transport of virulence factors to host cells, causing cell injury. Previous studies have shown changes of gene expression in human bronchial epithelial cells after treatment with K. pneumoniae OMVs. These variations in gene expression could be regulated through microRNAs (miRNAs), which participate in several biological mechanisms. Thereafter, miRNA expression profiles in human bronchial epithelial cells were evaluated during infection with standard and clinical K. pneumoniae strains. Microarray analysis and RT-qPCR identified the dysregulation of miR-223, hsa-miR-21, hsa-miR-25 and hsa-let-7g miRNA sequences. Target gene prediction revealed the essential role of these miRNAs in the regulation of host immune responses involving NF-ĸB (miR-223), TLR4 (hsa-miR-21), cytokine (hsa-miR-25) and IL-6 (hsa-let-7g miRNA) signalling pathways. The current study provides the first large scale expression profile of miRNAs from lung cells and predicted gene targets, following exposure to K. pneumoniae OMVs. Our results suggest the importance of OMVs in the inflammatory response.
A Facile Semisynthesis and Evaluation of Garcinoic Acid and Its Analogs for the Inhibition of Human DNA Polymerase β
Authors: Gujarathi Satheesh , Zafar Maroof Khan , Liu Xingui , Eoff Robert L. , Zheng Guangrong
Published: December 2020

Garcinoic acid has been identified as an inhibitor of DNA polymerase β (pol β). However, no structure-activity relationship (SAR) studies of garcinoic acid as a pol β inhibitor have been conducted, in part due to the lack of an efficient synthetic method for this natural product and its analogs. We developed an efficient semi-synthetic method for garcinoic acid and its analogs by starting from natural product δ-tocotrienol. Our preliminary SAR studies provided a valuable insight into future discovery of garcinoic acid-based pol β inhibitors.
A Review on Antistaphylococcal Secondary Metabolites from Basidiomycetes
Authors: Vallavan Vimalah , Krishnasamy Getha , Zin Noraziah Mohamad , Abdul Latif Mazlyzam
Published: December 2020

Fungi are a rich source of secondary metabolites with several pharmacological activities such as antifungal, antioxidant, antibacterial and anticancer to name a few. Due to the large number of diverse structured chemical compounds they produce, fungi from the phyla Ascomycota, Basidiomycota and Muccoromycota have been intensively studied for isolation of bioactive compounds. Basidiomycetes-derived secondary metabolites are known as a promising source of antibacterial compounds with activity against Gram-positive bacteria. The continued emergence of antimicrobial resistance (AMR) poses a major challenge to patient health as it leads to higher morbidity and mortality, higher hospital-stay duration and substantial economic burden in global healthcare sector. One of the key culprits for AMR crisis is Staphylococcus aureus causing community-acquired infections as the pathogen develops resistance towards multiple antibiotics. The recent emergence of community strains of S. aureus harbouring methicillin-resistant (MRSA), vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) genes associated with increased virulence is challenging. Despite the few significant developments in antibiotic research, successful MRSA therapeutic options are still needed to reduce the use of scanty and expensive second-line treatments. This paper provides an overview of findings from various studies on antibacterial secondary metabolites from basidiomycetes, with a special focus on antistaphylococcal activity.
Marine-Derived Compounds and Prospects for Their Antifungal Application
Authors: Cardoso Joana , Nakayama Darlan Gonçalves , Sousa Emília , Pinto Eugénia
Published: December 2020

The introduction of antifungals in clinical practice has an enormous impact on the provision of medical care, increasing the expectancy and quality of life mainly of immunocompromised patients. However, the emergence of pathogenic fungi that are resistant and multi-resistant to the existing antifungal therapy has culminated in fungal infections that are almost impossible to treat. Therefore, there is an urgent need to discover new strategies. The marine environment has proven to be a promising rich resource for the discovery and development of new antifungal compounds. Thus, this review summarizes more than one hundred marine natural products, or their derivatives, which are categorized according to their sources—sponges, bacteria, fungi, and sea cucumbers—as potential candidates as antifungal agents. In addition, this review focus on recent developments using marine antifungal compounds as new and effective approaches for the treatment of infections caused by resistant and multi-resistant pathogenic fungi and/or biofilm formation; other perspectives on antifungal marine products highlight new mechanisms of action, the combination of antifungal and non-antifungal agents, and the use of nanoparticles and anti-virulence therapy.
Magnetic Resonance Methods as a Prognostic Tool for the Biorelevant Behavior of Xanthan Tablets
Authors: Mikac Urša , Kristl Julijana
Published: December 2020

Hydrophilic matrix tablets with controlled drug release have been used extensively as one of the most successful oral drug delivery systems for optimizing therapeutic efficacy. In this work, magnetic resonance imaging (MRI) is used to study the influence of various pHs and mechanical stresses caused by medium flow (at rest, 80, or 150 mL/min) on swelling and on pentoxifylline release from xanthan (Xan) tablets. Moreover, a bimodal MRI system with simultaneous release testing enables measurements of hydrogel thickness and drug release, both under the same experimental conditions and at the same time. The results show that in water, the hydrogel structure is weaker and less resistant to erosion than the Xan structure in the acid medium. Different hydrogel structures affect drug release with erosion controlled release in water and diffusion controlled release in the acid medium. Mechanical stress simulating gastrointestinal contraction has no effect on the hard hydrogel in the acid medium where the release is independent of the tested stress, while it affects the release from the weak hydrogel in water with faster release under high stress. Our findings suggest that simultaneous MR imaging and drug release from matrix tablets together provide a valuable prognostic tool for prolonged drug delivery design.
The Importance of Strain (Preorganization) in Beryllium Bonds
Authors: Alkorta Ibon , Elguero José , Oliva-Enrich Josep M. , Yáñez Manuel , Mó Otilia , Montero-Campillo M. Merced
Published: December 2020

In order to explore the angular strain role on the ability of Be to form strong beryllium bonds, a theoretical study of the complexes of four beryllium derivatives of orthocloso-carboranes with eight molecules (CO, N2, NCH, CNH, OH2, SH2, NH3, and PH3) acting as Lewis bases has been carried out at the G4 computational level. The results for these complexes, which contain besides Be other electron-deficient elements, such as B, have been compared with the analogous ones formed by three beryllium salts (BeCl2, CO3Be and SO4Be) with the same set of Lewis bases. The results show the presence of large and positive values of the electrostatic potential associated to the beryllium atoms in the isolated four beryllium derivatives of ortho-carboranes, evidencing an intrinsically strong acidic nature. In addition, the LUMO orbital in these systems is also associated to the beryllium atom. These features led to short intermolecular distances and large dissociation energies in the complexes of the beryllium derivatives of ortho-carboranes with the Lewis bases. Notably, as a consequence of the special framework provided by the ortho-carboranes, some of these dissociation energies are larger than the corresponding beryllium bonds in the already strongly bound SO4Be complexes, in particular for N2 and CO bases. The localized molecular orbital energy decomposition analysis (LMOEDA) shows that among the attractive terms associated with the dissociation energy, the electrostatic term is the most important one, except for the complexes with the two previously mentioned weakest bases (N2 and CO), where the polarization term dominates. Hence, these results contribute to further confirm the importance of bending on the beryllium environment leading to strong interactions through the formation of beryllium bonds.
The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration—A Review
Authors: Asa’ad Farah , Pelanyte Goda , Philip Jincy , Dahlin Christer , Larsson Lena
Published: December 2020

The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put forward the epigenetic mechanisms as a promising strategy in implant surface functionalization and modification of biomaterials, to promote better osseointegration and bone regeneration, and could be applicable for alveolar bone regeneration and osseointegration in the future. Materials and Methods: Electronic and manual searches of the literature in PubMed, MEDLINE, and EMBASE were conducted, using a specific search strategy limited to publications in the last 5 years to identify preclinical studies in order to address the following focused questions: (i) Which, if any, are the epigenetic mechanisms used to functionalize implant surfaces to achieve better osseointegration? (ii) Which, if any, are the epigenetic mechanisms used to functionalize biomaterials to achieve better bone regeneration? Results: Findings from several studies have emphasized the role of miRNAs in functionalizing implants surfaces and biomaterials to promote osseointegration and bone regeneration, respectively. However, there are scarce data on the role of DNA methylation and histone modifications for these specific applications, despite being commonly applied in cancer research. Conclusions: Studies over the past few years have demonstrated that biomaterials are immunomodulatory rather than inert materials. In this context, epigenetics can act as next generation of advanced treatment tools for future regenerative techniques. Yet, there is a need to evaluate the efficacy/cost effectiveness of these techniques in comparison to current standards of care.
In Vitro Tests of FDM 3D-Printed Diclofenac Sodium-Containing Implants
Authors: Arany Petra , Papp Ildikó , Zichar Marianna , Csontos Máté , Elek János , Regdon Géza , Budai István , Béres Mónika , Gesztelyi Rudolf , Fehér Pálma , Ujhelyi Zoltán , Vasvári Gábor , Haimhoffer Ádám , Fenyvesi Ferenc , Váradi Judit , Miklós Vecsernyés , Bácskay Ildikó
Published: December 2020

One of the most promising emerging innovations in personalized medication is based on 3D printing technology. For use as authorized medications, 3D-printed products require different in vitro tests, including dissolution and biocompatibility investigations. Our objective was to manufacture implantable drug delivery systems using fused deposition modeling, and in vitro tests were performed for the assessment of these products. Polylactic acid, antibacterial polylactic acid, polyethylene terephthalate glycol, and poly(methyl methacrylate) filaments were selected, and samples with 16, 19, or 22 mm diameters and 0%, 5%, 10%, or 15% infill percentages were produced. The dissolution test was performed by a USP dissolution apparatus 1. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide dye (MTT)-based prolonged cytotoxicity test was performed on Caco-2 cells to certify the cytocompatibility properties. The implantable drug delivery systems were characterized by thermogravimetric and heatflow assay, contact angle measurement, scanning electron microscopy, microcomputed tomography, and Raman spectroscopy. Based on our results, it can be stated that the samples are considered nontoxic. The dissolution profiles are influenced by the material properties of the polymers, the diameter, and the infill percentage. Our results confirm the potential of fused deposition modeling (FDM) 3D printing for the manufacturing of different implantable drug delivery systems in personalized medicine and may be applied during surgical interventions.
In Vitro Calli Production Resulted in Different Profiles of Plant-Derived Medicinal Compounds in Phyllanthus amarus
Authors: de Oliveira Maria Eduarda B. S. , Sartoratto Adilson , Carlos Cardoso Jean
Published: December 2020

The efficient production of plant-derived medicinal compounds (PDMCs) from in vitro plants requires improvements in knowledge about control of plant or organ development and factors affecting the biosynthesis pathway of specific PDMCs under in vitro conditions, leading to a realistic large-scale tool for in vitro secondary metabolite production. Thus, this study aimed to develop an in vitro technique, through the induction and proliferation of calli, for production of plant fresh weight, and to compare the PDMC profile obtained from the plants versus in vitro calli of Phyllanthus amarus. It was successfully possible to obtain and proliferate two types of calli, one with a beige color and a friable appearance, obtained in the dark using Murashige and Skoog (MS) medium plus 2,4-dichlorophenoxyacetic acid (2,4-D), and a second type with a green color, rigid consistency, and nonfriable appearance obtained under light conditions and MS medium plus 6-benzyladenine (6-BA). In vitro micropropagated plants that gave rise to calli were also acclimatized in a greenhouse and cultivated until obtaining the mass for PDMC analysis and used as a control. While the micropropagated-derived plants concentrated the lignans niranthin, nirtetralin, and phyllanthin, the Phyllanthus amarus calli proliferated in vitro concentrated a completely different biochemical profile and synthesis of compounds, such as betulone, squalene, stigmasterol, and β-sitosterol, in addition to others not identified by GC-MS database. These results demonstrate the possibility of applying the calli in vitro from Phyllanthus amarus for production of important PDMCs unlike those obtained in cultures of differentiated tissues from field plants.
In Vivo Targeted Metabolomic Profiling of Prostanit, a Novel Anti-PAD NO-Donating Alprostadil-Based Drug
Authors: Shestakova Ksenia M. , Moskaleva Natalia E. , Mesonzhnik Natalia V. , Kukharenko Alexey V. , Serkov Igor V. , Lyubimov Igor I. , Fomina-Ageeva Elena V. , Bezuglov Vladimir V. , Akimov Mikhail G. , Appolonova Svetlana A.
Published: December 2020

Prostanit is a novel drug developed for the treatment of peripheral arterial diseases. It consists of a prostaglandin E1 (PGE1) moiety with two nitric oxide (NO) donor fragments, which provide a combined vasodilation effect on smooth muscles and vascular spastic reaction. Prostanit pharmacokinetics, however, remains poorly investigated. Thus, the object of this study was to investigate the pharmacokinetics of Prostanit-related and -affected metabolites in rabbit plasma using the liquid chromatography-mass spectrometry (LC-MS) approach. Besides, NO generation from Prostanit in isolated rat aorta and human smooth muscle cells was studied using the Griess method. In plasma, Prostanit was rapidly metabolized to 1,3-dinitroglycerol (1,3-DNG), PGE1, and 13,14-dihydro-15-keto-PGE1. Simultaneously, the constant growth of amino acid (proline, 4-hydroxyproline, alanine, phenylalanine, etc.), steroid (androsterone and corticosterone), and purine (adenosine, adenosine-5 monophosphate, and guanosine) levels was observed. Glycine, aspartate, cortisol, and testosterone levels were decreased. Ex vivo Prostanit induced both NO synthase-dependent and -independent NO generation. The observed pharmacokinetic properties suggested some novel beneficial activities (i.e., effect prolongation and anti-inflammation). These properties may provide a basis for future research of the effectiveness and safety of Prostanit, as well as for its characterization from a clinical perspective.
Fluorescent and Electron-Dense Green Color Emitting Nanodiamonds for Single-Cell Correlative Microscopy
Authors: Prabhakar Neeraj , Peurla Markus , Shenderova Olga , Rosenholm Jessica M.
Published: December 2020

Correlative light and electron microscopy (CLEM) is revolutionizing how cell samples are studied. CLEM provides a combination of the molecular and ultrastructural information about a cell. For the execution of CLEM experiments, multimodal fiducial landmarks are applied to precisely overlay light and electron microscopy images. Currently applied fiducials such as quantum dots and organic dye-labeled nanoparticles can be irreversibly quenched by electron beam exposure during electron microscopy. Generally, the sample is therefore investigated with a light microscope first and later with an electron microscope. A versatile fiducial landmark should offer to switch back from electron microscopy to light microscopy while preserving its fluorescent properties. Here, we evaluated green fluorescent and electron dense nanodiamonds for the execution of CLEM experiments and precisely correlated light microscopy and electron microscopy images. We demonstrated that green color emitting fluorescent nanodiamonds withstand electron beam exposure, harsh chemical treatments, heavy metal straining, and, importantly, their fluorescent properties remained intact for light microscopy.
Assessment of Tissue Distribution and Metabolism of MP1, a Novel Pyrrolomycin, in Mice Using a Validated LC-MS/MS Method
Authors: Aldhafiri Wafaa N. , Chhonker Yashpal S. , Zhang Yuning , Coulter Don W. , McGuire Timothy R. , Li Rongshi , Murry Daryl J.
Published: December 2020

MP1 is a novel marinopyrrole analogue with activity in MYCN amplified neuroblastoma cell lines. A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of MP1 in mouse plasma. Analyte separation was achieved using a Waters Acquity UPLC®BEH C18 column (1.7 µm, 100 × 2.1 mm). Mobile phase consisted of 0.1% acetic acid in water (10%) and methanol (90%) at a total flow rate of 0.25 mL/min. The mass spectrometer was operated at unit resolution in the multiple reaction monitoring (MRM) mode, using precursor ion > product ion transitions of 324.10 > 168.30 m/z for MP1 and 411.95 > 224.15 m/z for PL-3. The MS/MS response was linear over the concentration range from 0.2–500 ng/mL for MP1, correlation coefficient (r2) of 0.988. Precision (% RSD) and accuracy (% bias) were within the acceptable limits as per FDA guidelines. MP1 was stable under storage and laboratory handling conditions. The validated method was successfully applied to assess the solubility, in-vitro metabolism, plasma protein binding, and bio-distribution studies of MP1.
Recent Advances on Synthetic Methodology Merging C–H Functionalization and C–C Cleavage
Authors: Azizollahi Hamid , García-López José-Antonio
Published: December 2020

The functionalization of C–H bonds has become a major thread of research in organic synthesis that can be assessed from different angles, for instance depending on the type of catalyst employed or the overall transformation that is carried out. This review compiles recent progress in synthetic methodology that merges the functionalization of C–H bonds along with the cleavage of C–C bonds, either in intra- or intermolecular fashion. The manuscript is organized in two main sections according to the type of substrate in which the cleavage of the C–C bond takes place, basically attending to the scission of strained or unstrained C–C bonds. Furthermore, the related research works have been grouped on the basis of the mechanistic aspects of the different transformations that are carried out, i.e.,: (a) classic transition metal catalysis where organometallic intermediates are involved; (b) processes occurring via radical intermediates generated through the use of radical initiators or photochemically; and (c) reactions that are catalyzed or mediated by suitable Lewis or Brønsted acid or bases, where molecular rearrangements take place. Thus, throughout the review a wide range of synthetic approaches show that the combination of C–H and C–C cleavage in single synthetic operations can serve as a platform to achieve complex molecular skeletons in a straightforward manner, among them interesting carbo- and heterocyclic scaffolds.
Newly Generated Atractylon Derivatives in Processed Rhizomes of Atractylodes macrocephala Koidz
Authors: Zhai Chunmei , Zhao Jianping , Chittiboyina Amar G. , Meng Yonghai , Wang Mei , Khan Ikhlas A.
Published: December 2020

Thermally processed rhizomes of Atractylodes macrocephala (RAM) have a long history of use in traditional Chinese medicine (TCM) for treating various disorders, and have been an integral part of various traditional drugs and healthcare products. In TCM, herbal medicines are, in most cases, uniquely processed. Although it is thought that processing can alter the properties of herbal medicines so as to achieve desired functions, increase potency, and/or reduce side effects, the underlying chemical changes remain unclear for most thermally processed Chinese herbal medicines. In an attempt to shed some light on the scientific rationale behind the processes involved in traditional medicine, the RAM processed by stir-frying with wheat bran was investigated for the change of chemical composition. As a result, for the first time, five new chemical entities, along with ten known compounds, were isolated. Their chemical structures were determined by spectroscopic and spectrometric analyses. The possible synthetic pathway for the generation of such thermally-induced chemical entities was also proposed. Furthermore, biological activity evaluation showed that none of the compounds possessed cytotoxic effects against the tested mammalian cancer and noncancer cell lines. In addition, all compounds were ineffective at inhibiting the growth of the pathogenic microorganisms.
Role of Nutraceuticals in COVID-19 Mediated Liver Dysfunction
Authors: Sikander Mohammed , Malik Shabnam , Rodriguez Anyssa , Yallapu Murali M. , Narula Acharan S. , Satapathy Sanjaya K. , Dhevan Vijian , Chauhan Subhash C. , Jaggi Meena
Published: December 2020

COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported in various epidemiological studies. Therefore, this review provides information and summarizes the juncture of antiviral, immunomodulatory, and hepatoprotective nutraceuticals that can be useful during the management of COVID-19.
X-ray and Thermal Analysis of Selected Drugs Containing Acetaminophen
Authors: Jendrzejewska Izabela , Goryczka Tomasz , Pietrasik Ewa , Klimontko Joanna , Jampilek Josef
Published: December 2020

Studies carried out by X-ray and thermal analysis confirmed that acetaminophen (paracetamol), declared by the manufacturers as an Active Pharmaceutical Ingredient (API), was present in all studied medicinal drugs. Positions of diffraction lines (2θ angles) of the studied drugs were consistent with standards for acetaminophen, available in the ICDD PDF database Release 2008. |Δ2θ| values were lower than 0.2°, confirming the authenticity of the studied drugs. Also, the values of interplanar distances dhkl for the examined samples were consistent with those present in the ICDD. Presence of acetaminophen crystalising in the monoclinic system (form I) was confirmed. Various line intensities for API were observed in the obtained diffraction patterns, indicating presence of the preferred orientation of the crystallites in the examined samples. Thermal analysis of the studied substances confirmed the results obtained by X-ray analysis. Drugs containing only acetaminophen as an API have melting point close to that of pure acetaminophen. It was found that presence of other active and auxiliary substances affected the shapes and positions of endothermal peaks significantly. A broadening of endothermal peaks and their shift towards lower temperatures were observed accompanying an increase in the contents of additional substances being “impurities” in relation to the API. The results obtained by a combination of the two methods, X-ray powder diffraction (XRPD) and differential scanning calorimetry/thermogravimetry (DSC/TGA), may be useful in determination of abnormalities which can occur in pharmaceutical preparations, e.g., for distinguishing original drugs and forged products, detection of the presence of a proper polymorphic form or too low content of the active substance in the investigated drug.
Magnetic Imaging of Encapsulated Superparamagnetic Nanoparticles by Data Fusion of Magnetic Force Microscopy and Atomic Force Microscopy Signals for Correction of Topographic Crosstalk
Authors: Fuhrmann Marc , Musyanovych Anna , Thoelen Ronald , von Bomhard Sibylle , Möbius Hildegard
Published: December 2020

Encapsulated magnetic nanoparticles are of increasing interest for biomedical applications. However, up to now, it is still not possible to characterize their localized magnetic properties within the capsules. Magnetic Force Microscopy (MFM) has proved to be a suitable technique to image magnetic nanoparticles at ambient conditions revealing information about the spatial distribution and the magnetic properties of the nanoparticles simultaneously. However, MFM measurements on magnetic nanoparticles lead to falsifications of the magnetic MFM signal due to the topographic crosstalk. The origin of the topographic crosstalk in MFM has been proven to be capacitive coupling effects due to distance change between the substrate and tip measuring above the nanoparticle. In this paper, we present data fusion of the topography measurements of Atomic Force Microscopy (AFM) and the phase image of MFM measurements in combination with the theory of capacitive coupling in order to eliminate the topographic crosstalk in the phase image. This method offers a novel approach for the magnetic visualization of encapsulated magnetic nanoparticles.