bluuebunny/crossref_metadata_2025 huggingface dataset:
The C-Terminal Domain of Liquorilactobacillus nagelii Dextransucrase Mediates the Production of Larger Dextrans Compared to Liquorilactobacillus hordei
Authors: Bechtner Julia , Hassler Verena , Wefers Daniel , Ehrmann Matthias , Jakob Frank
Published: March 2022

Dextransucrases released by certain lactic acid bacteria form glucose polymers with predominantly α-1,6-linkages and may be exploited biotechnologically for the tailored production of polysaccharides with application potential. Despite releasing two closely related dextransucrases, previous studies showed that water kefir borne Liquorilactobacillus (L.) hordei TMW 1.1822 and L. nagelii TMW 1.1827 produce different amounts of polysaccharides with distinct particle sizes (molecular weight and radius of gyration) and molecular architectures. To investigate where these differences originate and thus to provide deeper insights into the functionally diverse nature of polysaccharide formation during water kefir fermentation, we constructed two variants of the L. nagelii dextransucrase—a full-length enzyme and a truncated variant, devoid of a C-terminal glucan-binding domain that reflects the domain architecture of the L. hordei dextransucrase—and applied them at various enzyme concentrations to form dextran over 24 h. The full-length enzyme exhibited a high activity, forming constant amounts of dextran until a four-fold dilution, whereas the truncated variant showed a gradual decrease in activity and dextran formation at an increasing dilution. The application of the full-length enzyme resulted in higher average particle sizes compared to the truncated variant. However, the dilution of the enzyme extracts also led to a slight increase in the average particle size in both enzymes. Neither the domain architecture nor the enzyme concentration had an impact on the structural architecture of the dextrans. The presented results thus suggest that the comparatively higher processivity of the L. nagelii dextransucrase is predominantly caused by the additional C-terminal glucan-binding domain, which is absent in the L. hordei dextransucrase. The average particle size may be influenced, to some extent, by the applied reaction conditions, whereas the structural architecture of the dextrans is most likely caused by differences in the amino acid sequence of the catalytic domain.
Combination Therapy Should Be Reserved as Second-Line Treatment of Onychomycosis: A Systematic Review of Onychomycosis Clinical Trials
Authors: Falotico Julianne M. , Lapides Rebecca , Lipner Shari R.
Published: March 2022

Onychomycosis is the most common nail disease encountered in clinical practice. Its importance extends well beyond aesthetics, often causing pain, difficulty with ambulation and performing daily activities, and impairing quality of life. Many patients fail to achieve cure with antifungal monotherapy and recurrences are common. Combination therapy has therefore gained considerable interest, given the potential for drug synergy and prevention of antifungal resistance, but it has not been well studied. A systematic review of onychomycosis medication only, as well as medication and procedural (laser, debridement, photodynamic therapy), clinical or randomized controlled trials evaluating combination vs. monotherapies was performed. After exclusions, 30 studies were included in the final analysis. There were conflicting results for medication-only trials, with some showing significant benefit of combination therapy over monotherapy, however, trials were not robustly designed and lacked sufficient follow-up. Procedural studies also lacked long-term follow-up, and failed to demonstrate efficacy in some severe onychomycosis cases. Considering the high cure rates demonstrated in pivotal antifungal monotherapy trials, and conflicting results, costs, and safety concerns associated with combination therapy, we recommend that combination therapy be reserved as second-line treatment options in patients with poor prognostic factors or for those who failed monotherapy for onychomycosis.
In Stent Neo-Atherosclerosis: Pathophysiology, Clinical Implications, Prevention, and Therapeutic Approaches
Authors: Nusca Annunziata , Viscusi Michele Mattia , Piccirillo Francesco , De Filippis Aurelio , Nenna Antonio , Spadaccio Cristiano , Nappi Francesco , Chello Camilla , Mangiacapra Fabio , Grigioni Francesco , Chello Massimo , Ussia Gian Paolo
Published: March 2022

Despite the dramatic improvements of revascularization therapies occurring in the past decades, a relevant percentage of patients treated with percutaneous coronary intervention (PCI) still develops stent failure due to neo-atherosclerosis (NA). This histopathological phenomenon following stent implantation represents the substrate for late in-stent restenosis (ISR) and late stent thrombosis (ST), with a significant impact on patient’s long-term clinical outcomes. This appears even more remarkable in the setting of drug-eluting stent implantation, where the substantial delay in vascular healing because of the released anti-proliferative agents might increase the occurrence of this complication. Since the underlying pathophysiological mechanisms of NA diverge from native atherosclerosis and early ISR, intra-coronary imaging techniques are crucial for its early detection, providing a proper in vivo assessment of both neo-intimal plaque composition and peri-strut structures. Furthermore, different strategies for NA prevention and treatment have been proposed, including tailored pharmacological therapies as well as specific invasive tools. Considering the increasing population undergoing PCI with drug-eluting stents (DES), this review aims to provide an updated overview of the most recent evidence regarding NA, discussing pathophysiology, contemporary intravascular imaging techniques, and well-established and experimental invasive and pharmacological treatment strategies.
Application of Orthobiologics in Achilles Tendinopathy: A Review
Authors: Ramires Luciano C. , Jeyaraman Madhan , Muthu Sathish , Shankar A Navaladi , Santos Gabriel Silva , da Fonseca Lucas Furtado , Lana José Fábio , Rajendran Ramya Lakshmi , Gangadaran Prakash , Jogalekar Manasi P. , Cardoso Alfredo A. , Eickhoff Alex
Published: March 2022

Orthobiologics are biological materials that are intended for the regeneration of bone, cartilage, and soft tissues. In this review, we discuss the application of orthobiologics in Achilles tendinopathy, more specifically. We explain the concepts and definitions of each orthobiologic and the literature regarding its use in tendon disorders. The biological potential of these materials can be harnessed and administered into injured tissues, particularly in areas where standard healing is disrupted, a typical feature of Achilles tendinopathy. These products contain a wide variety of cell populations, cytokines, and growth factors, which have been shown to modulate many other cells at local and distal sites in the body. Collectively, they can shift the state of escalated inflammation and degeneration to reestablish tissue homeostasis. The typical features of Achilles tendinopathy are failed healing responses, persistent inflammation, and predominant catabolic reactions. Therefore, the application of orthobiologic tools represents a viable solution, considering their demonstrated efficacy, safety, and relatively easy manipulation. Perhaps a synergistic approach regarding the combination of these orthobiologics may promote more significant clinical outcomes rather than individual application. Although numerous optimistic results have been registered in the literature, additional studies and clinical trials are still highly desired to further illuminate the clinical utility and efficacy of these therapeutic strategies in the management of tendinopathies.
Considerations on the Controlled Delivery of Bioactive Compounds through Hyaluronic Acid Membrane
Authors: Eftimie Totu Eugenia , Mănuc Daniela , Totu Tiberiu , Cristache Corina Marilena , Buga Roxana-Mădălina , Erci Fatih , Cristea Camelia , Isildak Ibrahim
Published: March 2022

(1) Background: The standard treatment for periodontal disease, a chronic inflammatory state caused by the interaction between biofilms generated by organized oral bacteria and the local host defense response, consists of calculus and biofilm removal through mechanical debridement, associated with antimicrobial therapy that could be delivered either systemically or locally. The present study aimed to determine the effectiveness of a hyaluronic acid membrane matrix as a carrier for the controlled release of the active compounds of a formulation proposed as a topical treatment for periodontal disease, and the influence of pH on the complex system’s stability. (2) Methods: The obtained hyaluronic acid (HA) hydrogel membrane with dispersed melatonin (MEL), metronidazole (MZ), and tetracycline (T) was completely characterized through FTIR, XRD, thermal analysis, UV-Vis and fluorescence spectroscopy, fluorescence microscopy, zeta potential and dielectric analysis. The MTT viability test was applied to check the cytotoxicity of the obtained membranes, while the microbiological assessment was performed against strains of Staphylococcus spp. and Streptococcus spp. The spectrophotometric investigations allowed to follow up the release profile from the HA matrix for MEL, MZ, and T present in the topical treatment considered. We studied the behavior of the active compounds against the pH of the generated environment, and the release profile of the bioactive formulation based on the specific comportment towards pH variation. The controlled delivery of the bioactive compounds using HA as a supportive matrix was modeled applying Korsmeyer–Peppas, Higuchi, first-order kinetic models, and a newly proposed pseudo-first-order kinetic model. (3) Results: It was observed that MZ and T were released at higher active concentrations than MEL when the pH was increased from 6.75, specific for patients with periodontitis, to a pH of 7.10, characterizing the healthy patients. Additionally, it was shown that for MZ, there is a burst delivery up to 2.40 × 10−5 mol/L followed by a release decrease, while for MEL and T a short release plateau was recorded up to a concentration of 1.80 × 10−5 mol/L for MEL and 0.90 × 10−5 mol/L for T, followed by a continuous release; (4) Conclusions: The results are encouraging for the usage of the HA membrane matrix as releasing vehicle for the active components of the proposed topical treatment at a physiological pH.
Microbial Interactions in Kombucha through the Lens of Metabolomics
Authors: Tran Thierry , Roullier-Gall Chloé , Verdier François , Martin Antoine , Schmitt-Kopplin Philippe , Alexandre Hervé , Grandvalet Cosette , Tourdot-Maréchal Raphaëlle
Published: March 2022

Kombucha is a fermented beverage obtained through the activity of a complex microbial community of yeasts and bacteria. Exo-metabolomes of kombucha microorganisms were analyzed using FT-ICR-MS to investigate their interactions. A simplified set of microorganisms including two yeasts (Brettanomyces bruxellensis and Hanseniaspora valbyensis) and one acetic acid bacterium (Acetobacter indonesiensis) was used to investigate yeast–yeast and yeast–acetic acid bacterium interactions. A yeast–yeast interaction was characterized by the release and consumption of fatty acids and peptides, possibly in relationship to commensalism. A yeast–acetic acid bacterium interaction was different depending on yeast species. With B. bruxellensis, fatty acids and peptides were mainly produced along with consumption of sucrose, fatty acids and polysaccharides. In opposition, the presence of H. valbyensis induced mainly the decrease of polyphenols, peptides, fatty acids, phenolic acids and putative isopropyl malate and phenylpyruvate and few formulae have been produced. With all three microorganisms, the formulae involved with the yeast–yeast interactions were consumed or not produced in the presence of A. indonesiensis. The impact of the yeasts’ presence on A. indonesiensis was consistent regardless of the yeast species with a commensal consumption of compounds associated to the acetic acid bacterium by yeasts. In detail, hydroxystearate from yeasts and dehydroquinate from A. indonesiensis were potentially consumed in all cases of yeast(s)–acetic acid bacterium pairing, highlighting mutualistic behavior.
Experimental Study on the Characteristics and Formation Mechanism of Dynamic Filter Cake for Slurry Shield Tunneling
Authors: Bai Yang , Jiang Binsong , Yang Le , Liu Yunqiu , Zheng He , Li Yapeng
Published: March 2022

The key to guaranteeing excavation face stability in slurry shield tunneling is the formation of an impermeable dynamic filter cake. At the same time, the effect of the cutter head and rotation speed should be taken into account. We studied the characteristics and formation mechanism of the dynamic filter cake using a newly developed experimental apparatus. The experiment results show that the hysteretic infiltration zone appeared in the curves of stepped loading filtration while the cutter head was rotating, and the volume of water filtration increased by 11.2% compared to when the cutter head stopped. The higher the rotation speed was, the lower the conversion rate of the effective stress was. Under the same rotation speed, the formation time of the 6-cutter arm was almost 5 s slower than that of the 5-cutter arm. As the cutter arms and the rotation speed increased, the stratum’s electrical conductivity increased and stabilized at a distance of 20 cm from the cutter head. The filter cake transited from ‘filter cake plus an infiltration zone’ to ‘an infiltration zone without a filter cake’ with the increase of the rotation speed. The thickness of the dynamic filter cake was smaller than that of the static filter cake, the thickness of 10 groups decreased significantly, and the average thickness decreased by 76.15% at 1.0 rpm. The mesoscopic formation process of the dynamic filter cake can be divided into six stages. This study revealed the slurry penetration mechanism and filter cake characteristics present under cyclic damage by the shield cutter head to the filter cake and soil and provided theoretical support on how to maintain the stability of the excavation face during slurry shield tunneling.
Effect of Native Reservoir State and Oilfield Operations on Clay Mineral Surface Chemistry
Authors: Mohammed Isah , Al Shehri Dhafer , Mahmoud Mohamed , Kamal Muhammad Shahzad , Alade Olalekan , Arif Muhammad , Patil Shirish
Published: March 2022

An understanding of clay mineral surface chemistry is becoming critical as deeper levels of control of reservoir rock wettability via fluid–solid interactions are sought. Reservoir rock is composed of many minerals that contact the crude oil and control the wetting state of the rock. Clay minerals are one of the minerals present in reservoir rock, with a high surface area and cation exchange capacity. This is a first-of-its-kind study that presents zeta potential measurements and insights into the surface charge development process of clay minerals (chlorite, illite, kaolinite, and montmorillonite) in a native reservoir environment. Presented in this study as well is the effect of fluid salinity, composition, and oilfield operations on clay mineral surface charge development. Experimental results show that the surface charge of clay minerals is controlled by electrostatic and electrophilic interactions as well as the electrical double layer. Results from this study showed that clay minerals are negatively charged in formation brines as well as in deionized water, except in the case of chlorite, which is positively charged in formation water. In addition, a negative surface charge results from oilfield operations, except for operations at a high alkaline pH range of 10–13. Furthermore, a reduction in the concentrations of Na, Mg, Ca, and bicarbonate ions does not reverse the surface charge of the clay minerals; however, an increase in sulfate ion concentration does. Established in this study as well, is a good correlation between the zeta potential value of the clay minerals and contact angle, as an increase in fluid salinity results in a reduction of the negative charge magnitude and an increase in contact angle from 63 to 102 degree in the case of chlorite. Lastly, findings from this study provide vital information that would enhance the understanding of the role of clay minerals in the improvement of oil recovery.
Influence of Different Microplastic Forms on pH and Mobility of Cu2+ and Pb2+ in Soil
Authors: Medyńska-Juraszek Agnieszka , Jadhav Bhakti
Published: March 2022

Microplastics, due to their surface properties, porosity and electrostatic interactions have a high affinity for cations sorption from the aqueous phase. As soil is a complex matrix, interactions between microplastics, soil constituents and heavy metals (HM) may modify the soil microenvironment for heavy metal mobilization/immobilization processes. In order to better understand the problem, three commonly found forms of microplastics in soil (fibers, fragments and microbeads) were mixed with Cu2+- or Pb2+-contaminated soil and incubated at 22 °C for 180 days. In soil samples pH and the content of water and acid exchangeable species of metals were analyzed. The results of this study showed that the presence of microplastics in HM-contaminated soil affected metal speciation, increasing the amount of easily exchangeable and potentially bioavailable forms of Cu2+ or Pb2+ in the tested soil. Soil pH also increased, confirming that microplastic particles affect soil properties relevant to the sorption/desorption process of metal cations. Overall, the smallest microplastic particles (≤1 mm), such as fibers or glitter microbeads, had a greater impact on the change in the sorption and desorption conditions of metals in tested soil than larger particles. The findings of our study show that microplastic form, shape and size should be considered as important factors that influence the soil properties and mobility of heavy metals in soil.
Ferrocene-Containing Pseudorotaxanes in Crystals: Aromatic Interactions with Hammett Correlation
Authors: Suzaki Yuji , Abe Tomoko , Takei Asami , Fukuchi Yugo , Koizumi Take-aki , Osakada Kohtaro , Horie Masaki
Published: March 2022

Single crystals of pseudorotaxanes, [(FcCH2NH2CH2Ar)(DB24C8)][PF6] (DB24C8 = dibenzo[24]crown-8, Fc = Fe(C5H4)(C5H5), Ar = -C6H3-3,4-Cl2, -C6H3-3,4-F2, -C6H4-4-F, -C6H4-4-Cl, -C6H4-4-Br, -C6H3-3-F-4-Me, -C6H4-4-I) and [(FcCH2NH2CH2C6H4-4-Me)(DB24C8)][Ni(dmit)2] (dmit = 1,3-dithiole-2,4,5-dithiolate), were obtained from solutions containing DB24C8 and ferrocenylmethyl(arylmethyl)ammonium. X-ray crystallographic analyses of the pseudorotaxanes revealed that the aryl ring of the axle moiety and the catechol ring of the macrocyclic component were at close centroid distances and parallel or tilted orientation. The structures with parallel aromatic rings showed correlation of the distances between the centroids to Hammett substituent constants of the aryl groups.
Sulforaphane and Its Bifunctional Analogs: Synthesis and Biological Activity
Authors: Janczewski Łukasz
Published: March 2022

For decades, various plants have been studied as sources of biologically active compounds. Compounds with anticancer and antimicrobial properties are the most frequently desired. Cruciferous plants, including Brussels sprouts, broccoli, and wasabi, have a special role in the research studies. Studies have shown that consumption of these plants reduce the risk of lung, breast, and prostate cancers. The high chemopreventive and anticancer potential of cruciferous plants results from the presence of a large amount of glucosinolates, which, under the influence of myrosinase, undergo an enzymatic transformation to biologically active isothiocyanates (ITCs). Natural isothiocyanates, such as benzyl isothiocyanate, phenethyl isothiocyanate, or the best-tested sulforaphane, possess anticancer activity at all stages of the carcinogenesis process, show antibacterial activity, and are used in organic synthesis. Methods of synthesis of sulforaphane, as well as its natural or synthetic bifunctional analogues with sulfinyl, sulfanyl, sulfonyl, phosphonate, phosphinate, phosphine oxide, carbonyl, ester, carboxamide, ether, or additional isothiocyanate functional groups, and with the unbranched alkyl chain containing 2–6 carbon atoms, are discussed in this review. The biological activity of these compounds are also reported. In the first section, glucosinolates, isothiocyanates, and mercapturic acids (their metabolites) are briefly characterized. Additionally, the most studied anticancer and antibacterial mechanisms of ITC actions are discussed.
Facile Synthesis of Porous g-C3N4 with Enhanced Visible-Light Photoactivity
Authors: Yao Guangyuan , Liu Yuqiang , Liu Jingcai , Xu Ya
Published: March 2022

Porous graphitic carbon nitride (g-C3N4) was prepared by dicyandiamide and urea via the pyrolysis method, which possessed enhanced visible-light-driven photocatalytic performance. Its surface area was increased from 17.12 to 48.00 m2/g. The porous structure not only enhanced the light capture capacity, but also accelerated the mass transfer ability. The Di (Dicyandiamide)/Ur (Urea) composite possessed better photocatalytic activity for Rhodamine B in visible light than that of g-C3N4. Moreover, the Di/Ur-4:5 composite showed the best photoactivity, which was almost 5.8 times that of g-C3N4. The enhanced photocatalytic activity showed that holes and superoxide radical played a key role in the process of photodegradation, which was ascribed to the enhanced separation of photogenerated carriers. The efficient separation of photogenerated electron-hole pairs may be owing to the higher surface area, O dopant, and pore volumes, which can not only improve the trapping opportunities of charge carriers but also the retarded charge carrier recombination. Therefore, it is expected that the composite would be a promising candidate material for organic pollutant degradation.
Phenolics as GABAA Receptor Ligands: An Updated Review
Authors: Ríos José-Luis , Schinella Guillermo R. , Moragrega Inés
Published: March 2022

Natural products can act as potential GABA modulators, avoiding the undesirable effects of traditional pharmacology used for the inhibition of the central nervous system such as benzodiazepines (BZD). Phenolics, especially flavonoids and phlorotannins, have been considered as modulators of the BZD-site of GABAA receptors (GABAARs), with sedative, anxiolytic or anticonvulsant effects. However, the wide chemical structural variability of flavonoids shows their potential action at more than one additional binding site on GABAARs, which may act either negatively, positively, by neutralizing GABAARs, or directly as allosteric agonists. Therefore, the aim of the present review is to compile and discuss an update of the role of phenolics, namely as pharmacological targets involving dysfunctions of the GABA system, analyzing both their different compounds and their mechanism as GABAergic modulators. We focus this review on articles written in English since the year 2010 until the present. Of course, although more research would be necessary to fully establish the type specificity of phenolics and their pharmacological activity, the evidence supports their potential as GABAAR modulators, thereby favoring their inclusion in the development of new therapeutic targets based on natural products. Specifically, the data compiled in this review allows for the directing of future research towards ortho-dihydroxy diterpene galdosol, the flavonoids isoliquiritigenin (chalcone), rhusflavone and agathisflavone (biflavonoids), as well as the phlorotannins, dieckol and triphlorethol A. Clinically, flavonoids are the most interesting phenolics due to their potential as anticonvulsant and anxiolytic drugs, and phlorotannins are also of interest as sedative agents.
Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents
Authors: Sinyeue Cynthia , Matsui Mariko , Oelgemöller Michael , Bregier Frédérique , Chaleix Vincent , Sol Vincent , Lebouvier Nicolas
Published: March 2022

Flavonoids are polyphenols with broad known pharmacological properties. A series of 2,3-dihydroflavanone derivatives were thus synthesized and investigated for their anti-inflammatory activities. The target flavanones were prepared through cyclization of 2′-hydroxychalcone derivatives, the later obtained by Claisen–Schmidt condensation. Since nitric oxide (NO) represents an important inflammatory mediator, the effects of various flavanones on the NO production in the LPS-induced RAW 264.7 macrophage were assessed in vitro using the Griess test. The most active compounds were flavanone (4G), 2′-carboxy-5,7-dimethoxy-flavanone (4F), 4′-bromo-5,7-dimethoxy-flavanone (4D), and 2′-carboxyflavanone (4J), with IC50 values of 0.603, 0.906, 1.030, and 1.830 µg/mL, respectively. In comparison, pinocembrin achieved an IC50 value of 203.60 µg/mL. Thus, the derivatives synthesized in this work had a higher NO inhibition capacity compared to pinocembrin, demonstrating the importance of pharmacomodulation to improve the biological potential of natural molecules. SARs suggested that the use of a carboxyl-group in the meta-position of the B-ring increases biological activity, whereas compounds carrying halogen substituents in the para-position were less active. The addition of methoxy-groups in the meta-position of the A-ring somewhat decreased the activity. This study successfully identified new bioactive flavanones as promising candidates for the development of new anti-inflammatory agents.
ZnO-AuxCu1−x Alloy and ZnO-AuxAl1−x Alloy Vertically Aligned Nanocomposites for Low-Loss Plasmonic Metamaterials
Authors: Paldi Robynne L. , Lu Juanjuan , Pachaury Yash , He Zihao , Bhatt Nirali A. , Zhang Xinghang , El-Azab Anter , Siddiqui Aleem , Wang Haiyan
Published: March 2022

Hyperbolic metamaterials are a class of materials exhibiting anisotropic dielectric function owing to the morphology of the nanostructures. In these structures, one direction behaves as a metal, and the orthogonal direction behaves as a dielectric material. Applications include subdiffraction imaging and hyperlenses. However, key limiting factors include energy losses of noble metals and challenging fabrication methods. In this work, self-assembled plasmonic metamaterials consisting of anisotropic nanoalloy pillars embedded into the ZnO matrix are developed using a seed-layer approach. Alloys of AuxAl1−x or AuxCu1−x are explored due to their lower losses and higher stability. Optical and microstructural properties were explored. The ZnO-AuxCu1−x system demonstrated excellent epitaxial quality and optical properties compared with the ZnO-AuxAl1−x system. Both nanocomposite systems demonstrate plasmonic resonance, hyperbolic dispersion, low losses, and epsilon-near-zero permittivity, making them promising candidates towards direct photonic integration.
A New Insight into Toxicity of Colchicine Analogues by Molecular Docking Analysis Based on Intestinal Tight Junction Protein ZO-1
Authors: Liu Jiali , Gao Rongrong , Gu Xuejing , Yu Bin , Wu Yan , Li Qiushi , Xiang Ping , Xu Hui
Published: March 2022

Colchicine (COL) is a well-known plant alkaloid long used for medical purposes due to the selective anti-inflammatory effect on acute gouty arthritis. It is also a kind of mitosis toxin with strong inhibitory effects of cell division and is therefore being applied to the treatment of various cancers. However, this product shows a variety of adverse effects that are significantly correlated with the dosage and have attracted much attention. For the first time, the present work obtained a new insight into the gastrointestinal toxicity of colchicine analogues by molecular docking analysis, which was based on the 3D structure of intestinal tight junction protein ZO-1 and the ligand library containing dozens of small-molecule compounds with the basic skeleton of COL and its metabolites. The binding energy and mode of protein–ligand interaction were investigated to better understand the structure–toxicity relationships of COL analogues and the mechanism of action as well. Cluster analysis clearly demonstrated the strong correlation between the binding energy and toxicity of ligand molecules. The interaction mode further revealed that the hydrogen bonding (via the C-7 amide or C-9 carbonyl group) and hydrophobic effect (at ring A or C) were both responsible for ZO-1-related gastrointestinal toxicity of COL analogues, while metabolic transformation via phase I and/or phase II reaction would significantly attenuate the gastrointestinal toxicity of colchicine, indicating an effective detoxication pathway through metabolism.
Foam Synthesis of Nickel/Nickel (II) Hydroxide Nanoflakes Using Double Templates of Surfactant Liquid Crystal and Hydrogen Bubbles: A High-Performance Catalyst for Methanol Electrooxidation in Alkaline Solution
Authors: Bamuqaddam Amani M. , Aladeemy Saba A. , Ghanem Mohamed A. , Al-Mayouf Abdullah M. , Alotaibi Nouf H. , Marken Frank
Published: March 2022

This work demonstrates the chemical synthesis of two-dimensional nanoflakes of mesoporous nickel/nickel (II) hydroxide (Ni/Ni(OH)2-NFs) using double templates of surfactant self-assembled thin-film and foam of hydrogen bubbles produced by sodium borohydride reducing agent. Physicochemical characterizations show the formation of amorphous mesoporous 2D nanoflakes with a Ni/Ni(OH)2 structure and a high specific surface area (165 m2/g). Electrochemical studies show that the electrocatalytic activity of Ni/Ni(OH)2 nanoflakes towards methanol oxidation in alkaline solution is significantly enhanced in comparison with that of parent bare-Ni(OH)2 deposited from surfactant-free solution. Cyclic voltammetry shows that the methanol oxidation mass activity of Ni/Ni(OH)2-NFs reaches 545 A/cm2 gcat at 0.6 V vs. Ag/AgCl, which is more than five times higher than that of bare-Ni(OH)2. Moreover, Ni/Ni(OH)2-NFs reveal less charge transfer resistance (10.4 Ω), stable oxidation current density (625 A/cm2 gcat at 0.7 V vs. Ag/AgCl), and resistance to the adsorption of reaction intermediates and products during three hours of constant-potential methanol oxidation electrolysis in alkaline solution. The high-performance electrocatalytic activity of Ni/Ni(OH)2 nanoflakes is mainly derived from efficient charge transfer due to the high specific surface area of the 2D mesoporous architecture of the nanoflakes, as well as the mass transport of methanol to Ni2+/Ni3+ active sites throughout the catalyst layer.
Synthesis of Doped/Hybrid Carbon Dots and Their Biomedical Application
Authors: Kumar Vijay Bhooshan , Porat Ze’ev , Gedanken Aharon
Published: March 2022

Carbon dots (CDs) are a novel type of carbon-based nanomaterial that has gained considerable attention for their unique optical properties, including tunable fluorescence, stability against photobleaching and photoblinking, and strong fluorescence, which is attributed to a large number of organic functional groups (amino groups, hydroxyl, ketonic, ester, and carboxyl groups, etc.). In addition, they also demonstrate high stability and electron mobility. This article reviews the topic of doped CDs with organic and inorganic atoms and molecules. Such doping leads to their functionalization to obtain desired physical and chemical properties for biomedical applications. We have mainly highlighted modification techniques, including doping, polymer capping, surface functionalization, nanocomposite and core-shell structures, which are aimed at their applications to the biomedical field, such as bioimaging, bio-sensor applications, neuron tissue engineering, drug delivery and cancer therapy. Finally, we discuss the key challenges to be addressed, the future directions of research, and the possibilities of a complete hybrid format of CD-based materials.
Sanguinarine Protects Channel Catfish against Aeromonas hydrophila Infection by Inhibiting Aerolysin and Biofilm Formation
Authors: Zhang Lushan , Ma Liang , Yang Qiuhong , Liu Yongtao , Ai Xiaohui , Dong Jing
Published: March 2022

Aeromonas hydrophila is a pathogenic bacterium that can cause serious infections both in humans and aquatic animals. Antibiotics are the main approach for fighting against the pathogen. However, the emergence of antibiotic resistance has resulted in treatment failure. Therefore, drugs with novel strategies need to be developed. Quorum sensing has been recognized as a promising method for identifying anti-virulence drugs against bacterial infections. The aim of this study was to identify novel drugs targeting quorum sensing of A. hydrophila as alternatives of antibiotics in aquaculture. Thus, hemolytic activity, biofilm formation, qPCR and experimental therapeutics assays were conducted. The results showed that sanguinarine inhibited the growth of A. hydrophila at concentrations higher than 16 μg/mL, but the production of aerolysin and biofilm formation was significantly inhibited at sub-inhibitory concentrations by disrupting the quorum sensing system. Cell viability results showed that sanguinarine could provide protection for A549 cells from aerolysin-induced cell injury. In addition, the mortality of channel catfish administered with sanguinarine at a dosage of 20 mg/kg decreased to 40%, which showed a significant decrease compared with fish in positive group. Taken together, these findings demonstrated that anti-virulence strategies can be a powerful weapon for fighting against bacterial pathogens and sanguinarine appears to be a promising candidate in the treatment of A. hydrophila infections.
A Tale of Two Fimbriae: How Invasion of Dendritic Cells by Porphyromonas gingivalis Disrupts DC Maturation and Depolarizes the T-Cell-Mediated Immune Response
Authors: Meghil Mohamed M. , Ghaly Mira , Cutler Christopher W.
Published: March 2022

Porphyromonas gingivalis (P. gingivalis) is a unique pathogen implicated in severe forms of periodontitis (PD), a disease that affects around 50% of the US population. P. gingivalis is equipped with a plethora of virulence factors that it uses to exploit its environment and survive. These include distinct fimbrial adhesins that enable it to bind to other microbes, colonize inflamed tissues, acquire nutrients, and invade cells of the stroma and immune system. Most notable for this review is its ability to invade dendritic cells (DCs), which bridge the innate and adaptive immune systems. This invasion process is tightly linked to the bridging functions of resultant DCs, in that it can disable (or stimulate) the maturation function of DCs and cytokines that are secreted. Maturation molecules (e.g., MHCII, CD80/CD86, CD40) and inflammatory cytokines (e.g., IL-1b, TNFa, IL-6) are essential signals for antigen presentation and for proliferation of effector T-cells such as Th17 cells. In this regard, the ability of P. gingivalis to coordinately regulate its expression of major (fimA) and minor (mfa-1) fimbriae under different environmental influences becomes highly relevant. This review will, therefore, focus on the immunoregulatory role of P. gingivalis fimbriae in the invasion of DCs, intracellular signaling, and functional outcomes such as alveolar bone loss and immune senescence.
First Detection of Francisella halioticida Infecting a Wild Population of Blue Mussels Mytilus edulis in the United Kingdom
Authors: Cano Irene , Parker Abigail , Ward Georgia M. , Green Matthew , Ross Stuart , Bignell John , Daumich Caroline , Kerr Rose , Feist Stephen W. , Batista Frederico M.
Published: March 2022

In the last decade, declines in the population of wild blue mussels Mytilus edulis in the Tamar estuary (United Kingdom) have been noted. In archived samples collected from 2013 to 2019, between 7% (in 2013) and 18% (in 2019) showed large granulocytoma and haemocytic infiltration in the interstitial tissue of the digestive gland. Four samples were selected for 16S rRNA gene Nanopore sequencing. A consensus sequence of 1449 bp showed nucleotide similarities between 99.93–100% with published sequences of Francisella halioticida. In situ hybridisation (ISH) confirmed the presence of F. halioticida DNA within individual granulocytes of granulocytomas and also in prokaryotic-like inclusion bodies within the digestive epithelial cells. The design of diagnostic tests for surveillance of F. halioticida, including more specific ISH probes and sequencing the genome of the isolates infecting mussels, will shed more light on the pathogenicity and spread of this pathogen.
Overcoming Multidrug Resistance of Antibiotics via Nanodelivery Systems
Authors: Imran Mohammad , Jha Saurav Kumar , Hasan Nazeer , Insaf Areeba , Shrestha Jitendra , Shrestha Jesus , Devkota Hari Prasad , Khan Salman , Panth Nisha , Warkiani Majid Ebrahimi , Dua Kamal , Hansbro Philip M. , Paudel Keshav Raj , Mohammed Yousuf
Published: March 2022

Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such complications, novel drug delivery systems have gained pharmaceutical scientists’ interest. Significant findings have validated the effectiveness of novel drug delivery systems such as polymeric nanoparticles, liposomes, metallic nanoparticles, dendrimers, and lipid-based nanoparticles against severe microbial infections and combating antimicrobial resistance. This review article comprises the specific mechanism of antibiotic resistance development in bacteria. In addition, the manuscript incorporated the advanced nanotechnological approaches with their mechanisms, including interaction with the bacterial cell wall, inhibition of biofilm formations, activation of innate and adaptive host immune response, generation of reactive oxygen species, and induction of intracellular effect to fight against antibiotic resistance. A section of this article demonstrated the findings related to the development of delivery systems. Lastly, the role of microfluidics in fighting antimicrobial resistance has been discussed. Overall, this review article is an amalgamation of various strategies to study the role of novel approaches and their mechanism to fight against the resistance developed to the antimicrobial therapies.
Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy
Authors: Trenfield Sarah J. , Januskaite Patricija , Goyanes Alvaro , Wilsdon David , Rowland Martin , Gaisford Simon , Basit Abdul W.
Published: March 2022

Selective laser sintering (SLS) 3D printing is capable of revolutionising pharmaceutical manufacturing, by producing amorphous solid dispersions in a one-step manufacturing process. Here, 3D-printed formulations loaded with a model BCS class II drug (20% w/w itraconazole) and three grades of hydroxypropyl cellulose (HPC) polymer (-SSL, -SL and -L) were produced using SLS 3D printing. Interestingly, the polymers with higher molecular weights (HPC-L and -SL) were found to undergo a uniform sintering process, attributed to the better powder flow characteristics, compared with the lower molecular weight grade (HPC-SSL). XRPD analyses found that the SLS 3D printing process resulted in amorphous conversion of itraconazole for all three polymers, with HPC-SSL retaining a small amount of crystallinity on the drug product surface. The use of process analytical technologies (PAT), including near infrared (NIR) and Raman spectroscopy, was evaluated, to predict the amorphous content, qualitatively and quantitatively, within itraconazole-loaded formulations. Calibration models were developed using partial least squares (PLS) regression, which successfully predicted amorphous content across the range of 0–20% w/w. The models demonstrated excellent linearity (R2 = 0.998 and 0.998) and accuracy (RMSEP = 1.04% and 0.63%) for NIR and Raman spectroscopy models, respectively. Overall, this article demonstrates the feasibility of SLS 3D printing to produce solid dispersions containing a BCS II drug, and the potential for NIR and Raman spectroscopy to quantify amorphous content as a non-destructive quality control measure at the point-of-care.
Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans
Authors: Park Jin-Woo , Kim Jong-Min , Noh Ji Hyeon , Kim Kyoung-Ah , Chung Hyewon , Kim EunJi , Kang Minja , Park Ji-Young
Published: March 2022

Dapagliflozin, a selective sodium–glucose co-transporter-2 inhibitor, and linagliptin, a competitive, reversible dipeptidyl peptidase-4 inhibitor, are commonly prescribed antidiabetic medications in general clinics. Since there are several merits to combining them in a fixed-dose combination product, this study investigated the pharmacokinetic equivalence between the individual component (IC) and fixed-combination drug product (FCDP) forms of dapagliflozin and linagliptin. A randomized, open-label, single-dose crossover study was conducted. All participants (n = 48) were randomly allocated to group A (period 1: ICs, period 2: FCDP) or group B (period 1: FCDP, period 2: ICs), and each group received either a single dose of IN-C009 (FCDP) or single doses of both dapagliflozin and linagliptin. There was no statistically significant difference found between the pharmacokinetic variables of FCDP and IC. The values of estimated geometric mean ratios and the 90% confidence interval for both maximum concentration and area under the plasma drug concentration–time curve were within the range of 0.8–1.25 for both dapagliflozin and linagliptin. The results of the clinical study demonstrated comparable pharmacokinetic characteristics between IC and FCDP forms of dapagliflozin and linagliptin. The combined use of dapagliflozin and linagliptin was safe and tolerable in both formulations.
Resveratrol Inhibited ADAM10 Mediated CXCL16-Cleavage and T-Cells Recruitment to Pancreatic β-Cells in Type 1 Diabetes Mellitus in Mice
Authors: Abdel-Bakky Mohamed S. , Alqasoumi Abdulmajeed , Altowayan Waleed M. , Amin Elham , Darwish Mostafa A.
Published: March 2022

Background: CXCL16 attracts T-cells to the site of inflammation after cleaving by A Disintegrin and Metalloproteinase (ADAM10). Aim: The current study explored the role of ADAM10/CXCL16/T-cell/NF-κB in the initiation of type 1 diabetes (T1D) with special reference to the potential protecting role of resveratrol (RES). Methods: Four sets of Balb/c mice were created: a diabetes mellitus (DM) group (streptozotocin (STZ) 55 mg/kg, i.p.], a control group administered buffer, a RES group [RES, 50 mg/kg, i.p.), and a DM + RES group (RES (50 mg/kg, i.p.) and STZ (55 mg/kg, i.p.) administered daily for 12 days commencing from the fourth day of STZ injection). Histopathological changes, fasting blood insulin (FBI), glucose (FBG), serum and pancreatic ADAM10, CXCL16, NF-κB, T-cells pancreatic expression, inflammatory, and apoptotic markers were analyzed. Results: FBG, inflammatory and apoptotic markers, serum TNF-α, cellular CXCL16 and ADAM10 protein expression, pancreatic T-cell migration and NF-κB were significantly increased in diabetic mice compared to normal mice. RES significantly improved the biochemical and inflammatory parameters distorted in STZ-treated mice. Conclusions: ADAM10 promotes the cleaved form of CXCL16 driving T-cells into the islets of the pancreatic in T1D. RES successfully prevented the deleterious effect caused by STZ. ADAM10 and CXCL16 may serve as novel therapeutic targets for T1D.
Formulation of Self-Nanoemulsifying Drug Delivery System of Cephalexin: Physiochemical Characterization and Antibacterial Evaluation
Authors: Zafar Ameeduzzafar , Yasir Mohd , Alruwaili Nabil K. , Imam Syed Sarim , Alsaidan Omar Awad , Alshehri Sultan , Ghoneim Mohammed M. , Alquraini Ali , Rawaf Alenazy , Ansari Mohammad Javed , Sara Udai Vir Singh
Published: March 2022

A cephalexin (CEP) self-nanoemulsifying drug delivery system (SNEDDS) was developed in this study to improve the drug’s oral administration. The CEP-SNEDDS was made utilizing an aqueous titration method employing Lauroglycol 90, Poloxamer 188, and Transcutol-HP. Box-Behnken design (BBD) with three factors at three levels was used for optimization, and their impacts on globule size (nm), transmittance (percent), and emulsification time (s) were assessed. The optimized formulation (Opt-F3) was further tested for zeta potential, refractive index, percent transmittance, thermodynamic stability, in-vitro release, ex vivo permeability, antibacterial activity, and bioavailability. The chosen formulation (Opt-F3) had a globule size of 87.25 ± 3.16 nm, PDI of 0.25, zeta potential of −24.37 mV, self-emulsification duration of 52 ± 1.7 s, and percentage transmittance of 99.13 ± 1.5%, viscosity of 96.26 ± 2.72 cp, and refractive index of 1.29 ± 0.1. It showed a sustained release profile (94.28 ± 5.92 percent in 24 h). The Opt-F3 formulation had 3.95 times the permeability of CEP-dispersion. In comparison to CEP-dispersion, it also demonstrated greater antibacterial efficacy against tested Gram-positive and Gram-negative pathogens. The oral bioavailability of Opt-F3 is 3.48 times higher than that of CEP-dispersion, according to an in-vivo investigation. It has been determined that the prepared CEP-SNEDDS may be an advantageous carrier for CEP delivery.
Low-Velocity Impact Behavior of Foam Core Sandwich Panels with Inter-Ply and Intra-Ply Carbon/Kevlar/Epoxy Hybrid Face Sheets
Authors: Samlal Stanley , Santhanakrishnan R.
Published: March 2022

Sandwich composites are extensively employed in a variety of applications because their bending stiffness affords a greater advantage than composite materials. However, the aspect limiting the application of the sandwich material is its poor impact resistance. Therefore, understanding the impact properties of the sandwich structure will determine the ways in which it can be used under the conditions of impact loading. Sandwich panels with different combinations of carbon/Kevlar woven monolithic face sheets, inter-ply face sheets and intra-ply face sheets were fabricated, using the vacuum-assisted resin transfer process. Instrumented low-velocity impact tests were performed using different energy levels of 5 J, 10 J, 20 J, 30 J and 40 J on a variety of samples and the results were assessed. The damage caused by the modes of failure in the sandwich structure include fiber breakage, matrix cracking, foam cracking and debonding. In sandwich panels with thin face sheets, the maximum peak load was achieved for the inter-ply hybrid foam core sandwich panel in which Kevlar was present towards the outer surface and carbon in the inner surface of the face sheet. At an impact energy of 40 J, the maximum peak load for the inter-ply hybrid foam core sandwich panel was 31.57% higher than for the sandwich structure in which carbon is towards the outer surface and Kevlar is in the inner surface of the face sheet. The intra-ply hybrid foam core sandwich panel subjected to 40 J impact energy demonstrated a 13.17% higher maximum peak load compared to the carbon monolithic face sheet sandwich panel. The experimental measurements and numerical predictions are in close agreement.