bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Biological Modulations Resulting from 1-Week Venlafaxine Exposure of Marine Mussels Mytilus galloprovincialis Determined by a Metabolomic Approach
Authors: Ramirez Gaëlle , Gomez Elena , Dumas Thibaut , Rosain David , Mathieu Olivier , Fenet Hélène , Courant Frédérique
Published: February 2022

There is growing evidence of the presence of pharmaceuticals in natural waters and their accumulation in aquatic organisms. While their mode of action on non-target organisms is still not clearly understood, their effects warrant assessment. The present study assessed the metabolome of the Mediterranean mussel (Mytilus galloprovincialis) exposed to a 10 µg/L nominal concentration of the antidepressant venlafaxine (VLF) at 3 time-points (1, 3, and 7 days). Over the exposure period, we observed up- or down-modulations of 113 metabolites, belonging to several metabolisms, e.g., amino acids (phenylalanine, tyrosine, tryptophan, etc.), purine and pyrimidine metabolisms (adenosine, cyclic AMP, thymidine, etc.), and several other metabolites involved in diverse functions. Serotonin showed the same time-course modulation pattern in both male and female mussels, which was consistent with its mode of action in humans, i.e., after a slight decrease on the first day of exposure, its levels increased at day 7 in exposed mussels. We found that the modulation pattern of impacted metabolites was not constant over time and it was gender-specific, as male and female mussels responded differently to VLF exposure.
Trampolining of Droplets on Hydrophobic Surfaces Using Electrowetting
Authors: Wang Zhantao , Liu Xiaojuan , Wang Li , Zhao Cunlu , Zhou Danfeng , Wei Jiazheng
Published: February 2022

Droplet detachment from solid surfaces is an essential part of many industrial processes. Electrowetting is a versatile tool for handling droplets in digital microfluidics, not only on plain surface but also in 3-D manner. Here, we report for the first time droplet trampolining using electrowetting. With the information collected by the real-time capacitor sensing system, we are able to synchronize the actuation signal with the spreading of the droplet upon impacting. Since electrowetting is applied each time the droplet impacts the substrate and switched off during recoiling of the droplet, the droplet gains additional momentum upon each impact and is able to jump higher during successive detachment. We have modelled the droplet trampolining behavior with a periodically driven harmonic oscillator, and the experiments showed sound agreement with theoretical predictions. The findings from this study will offer valuable insights to applications that demands vertical transportation of the droplets between chips arranged in parallel, or detachment of droplets from solid surfaces.
Comparative Genomics and Pathogenicity Analysis of Two Bacterial Symbionts of Entomopathogenic Nematodes: The Role of the GroEL Protein in Virulence
Authors: Rivera-Ramírez Abraham , Salgado-Morales Rosalba , Jiménez-Pérez Alfredo , Pérez-Martínez Rebeca , García-Gómez Blanca Inés , Dantán-González Edgar
Published: February 2022

Bacteria of the genera Xenorhabdus and Photorhabdus are symbionts of entomopathogenic nematodes. Despite their close phylogenetic relationship, they show differences in their pathogenicity and virulence mechanisms in target insects. These differences were explored by the analysis of the pangenome, as it provides a framework for characterizing and defining the gene repertoire. We performed the first pangenome analysis of 91 strains of Xenorhabdus and Photorhabdus; the analysis showed that the Photorhabdus genus has a higher number of genes associated with pathogenicity. However, biological tests showed that whole cells of X. nematophila SC 0516 were more virulent than those of P. luminescens HIM3 when both were injected into G. mellonella larvae. In addition, we cloned and expressed the GroEL proteins of both bacteria, as this protein has been previously indicated to show insecticidal activity in the genus Xenorhabdus. Among these proteins, Cpn60-Xn was found to be the most toxic at all concentrations tested, with an LC50 value of 102.34 ng/larva. Sequence analysis suggested that the Cpn60-Xn toxin was homologous to Cpn60-Pl; however, Cpn60-Xn contained thirty-five differentially substituted amino acid residues that could be responsible for its insecticidal activity.
The Use of Long-Read Sequencing Technologies in Infection Control: Horizontal Transfer of a blaCTX-M-27 Containing lncFII Plasmid in a Patient Screening Sample
Authors: van Almsick Vincent , Schuler Franziska , Mellmann Alexander , Schwierzeck Vera
Published: February 2022

Plasmid transfer is one important mechanism how antimicrobial resistance can spread between different species, contributing to the rise of multidrug resistant bacteria (MDRB) worldwide. Here were present whole genome sequencing (WGS) data of two MDRB isolates, an Escherichia coli and a Klebsiella quasipneumoniae, which were isolated from a single patient. Detailed analysis of long-read sequencing data identified an identical F2:A-:B- lncFII plasmid containing blaCTX-M-27 in both isolates, suggesting horizontal plasmid exchange between the two species. As the plasmid of the E. coli strain carried multiple copies of the resistance cassette, the genomic data correlated with the increased antimicrobial resistance (AMR) detected for this isolate. Our case report demonstrates how long-read sequencing data of MDRB can be used to investigate the role of plasmid mediate resistance in the healthcare setting and explain resistance phenotypes.
The Synthesis and Initial Evaluation of MerTK Targeted PET Agents
Authors: Wang Li , Zhou Yubai , Wu Xuedan , Ma Xinrui , Li Bing , Ding Ransheng , Stashko Michael A. , Wu Zhanhong , Wang Xiaodong , Li Zibo
Published: February 2022

MerTK (Mer tyrosine kinase), a receptor tyrosine kinase, is ectopically or aberrantly expressed in numerous human hematologic and solid malignancies. Although a variety of MerTK targeting therapies are being developed to enhance outcomes for patients with various cancers, the sensitivity of tumors to MerTK suppression may not be uniform due to the heterogeneity of solid tumors and different tumor stages. In this report, we develop a series of radiolabeled agents as potential MerTK PET (positron emission tomography) agents. In our initial in vivo evaluation, [18F]-MerTK-6 showed prominent uptake rate (4.79 ± 0.24%ID/g) in B16F10 tumor-bearing mice. The tumor to muscle ratio reached 1.86 and 3.09 at 0.5 and 2 h post-injection, respectively. In summary, [18F]-MerTK-6 is a promising PET agent for MerTK imaging and is worth further evaluation in future studies.
Nitrification Progress of Nitrogen-Rich Heterocyclic Energetic Compounds: A Review
Authors: Luo Yiming , Zheng Wanwan , Wang Xuanjun , Shen Fei
Published: February 2022

As a momentous energetic group, a nitro group widely exists in high-energy-density materials (HEDMs), such as trinitrotoluene (TNT), 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), etc. The nitro group has a significant effect on improving the oxygen balance and detonation performances of energetic materials (EMs). Moreover, the nitro group is a strong electron-withdrawing group, and it can increase the acidity of the acidic hydrogen-containing nitrogen-rich energetic compounds to facilitate the construction of energetic ionic salts. Thus, it is possible to design nitro-nitrogen-rich energetic compounds with adjustable properties. In this paper, the nitration methods of azoles, including imidazole, pyrazole, triazole, tetrazole, and oxadiazole, as well as azines, including pyrazine, pyridazine, triazine, and tetrazine, have been concluded. Furthermore, the prospect of the future development of nitrogen-rich heterocyclic energetic compounds has been stated, so as to provide references for researchers who are engaged in the synthesis of EMs.
Nanoinhibitory Impacts of Salicylic Acid, Glycyrrhizic Acid Ammonium Salt, and Boric Acid Nanoparticles against Phytoplasma Associated with Faba Bean
Authors: Ahmed Eman A. , Shoala Tahsin , Abdelkhalik Abdelsattar , El-Garhy Hoda A. S. , Ismail Ismail A. , Farrag Amro A.
Published: February 2022

Phytoplasmas are economically important plant pathogenic bacterial diseases, causing severe yield losses worldwide. In this study, we tested nanoformulations such as glycyrrhizic acid ammonium salt (GAS), salicylic acid (SA), and boric acid (BA) as novel antimicrobial agents inducing the resistance against the phytoplasma disease in faba bean. The nanoparticles (NP) were foliar-applied to naturally phytoplasma-infected faba bean with three concentrations from each of SA, GAS, and BA, under field conditions. Nested PCR (using universal primer pairs P1/P7 and R16F2n/R16R2) were reacted positively with all symptomatic samples and gave a product size of approximately 1200 bp, while the healthy plant gave no results. Transmission electron microscopy examinations of phytoplasma-infected faba bean plants treated with different nanoparticles revealed that severe damage occurred in phytoplasma particle’s structure, degradation, malformation, lysis in the cell membrane, and the cytoplasmic leakage followed by complete lysis of phytoplasma cells. Exogenous application of GAS-NP (1.68 µM), SA-NP (0.28 µM), and BA-NP (0.124 µM) suppressed the infection percentage of phytoplasma by 75%, 50%, and 20%, and the disease severity by 84%, 64%, and 54%, respectively. Foliar application of nanoparticles improved Fv/Fm (maximum quantum efficiency of PSII Photochemistry), PI (the performance index), SPAD chlorophyll (the relative chlorophyll content), shoots height, and leaves number, thus inducing recovery of the plant biomass and green pods yield. The most effective treatment was GAS-NP at 1.68 µM that mediated substantial increases in the shoots’ fresh weight, shoots’ dry weight, number of pods per plant, and green pods yield by 230%, 244%, 202% and 178%, respectively, compared to those of infected plants not sprayed with nanoparticles. This study demonstrated the utility of using nanoparticles, particularly GAS-NP at 1.68 µM to suppress the phytoplasma infection.
Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response
Authors: Gall Trošelj Koraljka , Tomljanović Marko , Jaganjac Morana , Matijević Glavan Tanja , Čipak Gašparović Ana , Milković Lidija , Borović Šunjić Suzana , Buttari Brigitta , Profumo Elisabetta , Saha Sarmistha , Saso Luciano , Žarković Neven
Published: February 2022

Oxidative stress and its end-products, such as 4-hydroxynonenal (HNE), initiate activation of the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)/Kelch Like ECH Associated Protein 1 (KEAP1) signaling pathway that plays a crucial role in the maintenance of cellular redox homeostasis. However, an involvement of 4-HNE and NRF2 in processes associated with the initiation of cancer, its progression, and response to therapy includes numerous, highly complex events. They occur through interactions between cancer and stromal cells. These events are dependent on many cell-type specific features. They start with the extent of NRF2 binding to its cytoplasmic repressor, KEAP1, and extend to the permissiveness of chromatin for transcription of Antioxidant Response Element (ARE)-containing genes that are NRF2 targets. This review will explore epigenetic molecular mechanisms of NRF2 transcription through the specific molecular anatomy of its promoter. It will explain the role of NRF2 in cancer stem cells, with respect to cancer therapy resistance. Additionally, it also discusses NRF2 involvement at the cross-roads of communication between tumor associated inflammatory and stromal cells, which is also an important factor involved in the response to therapy.
Pharmacokinetic Study of Withanosides and Withanolides from Withania somnifera Using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS)
Authors: Modi Siddharth J. , Tiwari Anshuly , Ghule Chetana , Pawar Sandeep , Saste Ganesh , Jagtap Shubham , Singh Ruchi , Deshmukh Amol , Girme Aboli , Hingorani Lal
Published: February 2022

Withania somnifera is a traditional Indian herb described under the ‘Rasayana’ class in Ayurveda, which gained immense popularity as a dietary supplement in the USA, Europe, Asia, and the Indian domestic market. Despite enormous research on the pharmacological effect of withanosides and withanolides, bioanalytical method development and pharmacokinetics remained challenging and unexplored for these constituents due to isomeric and isobaric characteristics. In current research work, molecular descriptors, pharmacokinetic, and toxicity prediction (ADMET) of these constituents were performed using Molinspiration and admetSAR tools. A rapid, selective, and reproducible bioanalytical method was developed and validated for seven withanosides and withanolides as per USFDA/EMA guidelines, further applied to determine pharmacokinetic parameters of Withania somnifera root extract (WSE) constituents in male Sprague Dawley rats at a dose of 500 mg/kg. Additionally, an ex vivo permeability study was carried out to explore the absorption pattern of withanosides and withanolides from the intestinal lumen. In silico, ADMET revealed oral bioavailability of withanosides and withanolides following Lipinski’s rules of five with significant absorption from the gastrointestinal tract and the ability to cross the blood-brain barrier. Upon oral administration of WSE, Cmax was found to be 13.833 ± 3.727, 124.415 ± 64.932, 57.536 ± 7.523, and 7.283 ± 3.341 ng/mL for withanoside IV, withaferin A, 12-Deoxy-withastramonolide, and withanolide A, respectively, with Tmax of 0.750 ± 0.000, 0.250 ± 0.000, 0.291 ± 0.102, and 0.333 ± 0.129 h. Moreover, at a given dose, withanoside V, withanolide B, and withanone were detected in plasma; however, the concentration of these constituents was found below LLOQ. Thus, these four major withanoside and withanolides were quantified in plasma supported by ex vivo permeation data exhibiting a time-dependent absorption of withanosides and withanolides across the intestinal barrier. These composite findings provide insights to design a clinical trial of WSE as a potent nutraceutical.
Natural Product-Based Potential Therapeutic Interventions of Pulmonary Fibrosis
Authors: Hasan Mahbub , Paul Nidhan Chandra , Paul Shamrat Kumar , Saikat Abu Saim Mohammad , Akter Hafeza , Mandal Manoj , Lee Sang-Suk
Published: February 2022

Pulmonary fibrosis (PF) is a disease-refractive lung condition with an increased rate of mortality. The potential factors causing PF include viral infections, radiation exposure, and toxic airborne chemicals. Idiopathic PF (IPF) is related to pneumonia affecting the elderly and is characterized by recurring scar formation in the lungs. An impaired wound healing process, defined by the dysregulated aggregation of extracellular matrix components, triggers fibrotic scar formation in the lungs. The potential pathogenesis includes oxidative stress, altered cell signaling, inflammation, etc. Nintedanib and pirfenidone have been approved with a conditional endorsement for the management of IPF. In addition, natural product-based treatment strategies have shown promising results in treating PF. In this study, we reviewed the recently published literature and discussed the potential uses of natural products, classified into three types—isolated active compounds, crude extracts of plants, and traditional medicine, consisting of mixtures of different plant products—in treating PF. These natural products are promising in the treatment of PF via inhibiting inflammation, oxidative stress, and endothelial mesenchymal transition, as well as affecting TGF-β-mediated cell signaling, etc. Based on the current review, we have revealed the signaling mechanisms of PF pathogenesis and the potential opportunities offered by natural product-based medicine in treating PF.
Novel Complex of PD-L1 Aptamer and Albumin Enhances Antitumor Efficacy In Vivo
Authors: An Yacong , Li Xundou , Yao Fengjiao , Duan Jinhong , Yang Xian-Da
Published: February 2022

The PD-1/PD-L1 pathway blockade can generate a good clinical response by reducing immunosuppression and provoking durable antitumor immunity. In addition to antibodies, aptamers can also block the interaction between PD-1 and PD-L1. For the in vivo application, however, free aptamers are usually too small in size and quickly removed from blood via glomerular filtration. To avoid renal clearance of aptamer, we conjugated the PD-L1 aptamer to albumin to form a larger complex (BSA-Apt) and evaluated whether BSA-Apt would enhance the in vivo antitumor efficacy. The PD-L1 aptamer was thiol-modified and conjugated to the amino group of BSA via a SMCC linker. The average size of BSA-Apt was 11.65 nm, which was above the threshold for renal clearance. Functionally, BSA-Apt retained the capability of the PD-L1 aptamer to bind with PDL1-expressing tumor cells. Moreover, both the free aptamer and BSA-Apt augmented the PBMC-induced antitumor cytotoxicity in vitro. Furthermore, BSA-Apt generated a significantly stronger antitumor efficacy than the free PD-L1 aptamer in vivo without raising systemic toxicity. The results indicate that conjugating the PD-L1 aptamer to albumin may serve as a promising strategy to improve the in vivo functionality of the aptamer and that BSA-Apt may have application potential in cancer immunotherapy.
Mechanisms, Anti-Quorum-Sensing Actions, and Clinical Trials of Medicinal Plant Bioactive Compounds against Bacteria: A Comprehensive Review
Authors: Bouyahya Abdelhakim , Chamkhi Imane , Balahbib Abdelaali , Rebezov Maksim , Shariati Mohammad Ali , Wilairatana Polrat , Mubarak Mohammad S. , Benali Taoufiq , El Omari Nasreddine
Published: February 2022

Bacterial strains have developed an ability to resist antibiotics via numerous mechanisms. Recently, researchers conducted several studies to identify natural bioactive compounds, particularly secondary metabolites of medicinal plants, such as terpenoids, flavonoids, and phenolic acids, as antibacterial agents. These molecules exert several mechanisms of action at different structural, cellular, and molecular levels, which could make them candidates or lead compounds for developing natural antibiotics. Research findings revealed that these bioactive compounds can inhibit the synthesis of DNA and proteins, block oxidative respiration, increase membrane permeability, and decrease membrane integrity. Furthermore, recent investigations showed that some bacterial strains resist these different mechanisms of antibacterial agents. Researchers demonstrated that this resistance to antibiotics is linked to a microbial cell-to-cell communication system called quorum sensing (QS). Consequently, inhibition of QS or quorum quenching is a promising strategy to not only overcome the resistance problems but also to treat infections. In this respect, various bioactive molecules, including terpenoids, flavonoids, and phenolic acids, exhibit numerous anti-QS mechanisms via the inhibition of auto-inducer releases, sequestration of QS-mediated molecules, and deregulation of QS gene expression. However, clinical applications of these molecules have not been fully covered, which limits their use against infectious diseases. Accordingly, the aim of the present work was to discuss the role of the QS system in bacteria and its involvement in virulence and resistance to antibiotics. In addition, the present review summarizes the most recent and relevant literature pertaining to the anti-quorum sensing of secondary metabolites and its relationship to antibacterial activity.
Special Issue: Application of Nanomaterials in Biomedical Imaging and Cancer Therapy
Authors: Chow James C. L.
Published: February 2022

Nanomaterials of different types—namely, inorganic-based, organic-based, carbon-based, and composite-based ones, with various structures such as nanoparticles, nanofibers, nanorods, nanoshells, and nanostars, all have demonstrated a wide range of medical biophysical and chemical properties [...]
Nickel Oxide-Carbon Soot-Cellulose Acetate Nanocomposite for the Detection of Mesitylene Vapour: Investigating the Sensing Mechanism Using an LCR Meter Coupled to an FTIR Spectrometer
Authors: Malepe Lesego , Ndungu Patrick , Ndinteh Derek Tantoh , Mamo Messai Adenew
Published: February 2022

Nanocomposite sensors were prepared using carbon soot (CNPs), nickel oxide nanoparticles (NiO-NPs), and cellulose acetate (CA), which was used to detect and study the sensing mechanism of mesitylene vapour at room temperature. Synthesised materials were characterised using high-resolution transmission electron microscopy (HR-TEM), powder x-ray diffraction (PXRD), Raman spectroscopy, and nitrogen sorption at 77 K. Various sensors were prepared using individual nanomaterials (NiO-NPs, CNPs, and CA), binary combinations of the nanomaterials (CNPs-NiO, CNPs-CA, and NiO-CA), and ternary composites (NiO-CNPs-CA). Among all of the prepared and tested sensors, the ternary nanocomposites (NiO-CNPs-CA) were found to be the most sensitive for the detection of mesitylene, with acceptable response recovery times. Fourier-transform infrared (FTIR) spectroscopy coupled with an LCR meter revealed that the mesitylene decomposes into carbon dioxide.
Enhancing the Electrochemical Performance of Ni-Rich LiNi0.88Co0.09Al0.03O2 Cathodes through Tungsten-Doping for Lithium-Ion Batteries
Authors: Zhang Rui , Qiu Hengrui , Zhang Youxiang
Published: February 2022

The tungsten-doped (0.5 and 1.0 mol%) LiNi0.88Co0.09Al0.03O2 (NCA) cathode materials are manufactured to systematically examine the stabilizing effect of W-doping. The 1.0 mol% W-doped LiNi0.88Co0.09Al0.03O2 (W1.0-NCA) cathodes deliver 173.5 mAh g−1 even after 100 cycles at 1 C, which is 95.2% of the initial capacity. While the capacity retention of NCA cathodes cycled in identical conditions is 86.3%. The optimal performances of the W1.0-NCA could be ascribed to the suppression of impendence increase and the decrease in anisotropic volume change, as well as preventing the collapse of structures during cycling. These findings demonstrate that the W-doping considerably enhances the electrochemical performance of NCA, which has potential applications in the development of Ni-rich layered cathode materials that can display high capacity with superior cycling stability.
Excellent Energy Storage Performance in Bi(Fe0.93Mn0.05Ti0.02)O3 Modified CaBi4Ti4O15 Thin Film by Adjusting Annealing Temperature
Authors: Liu Tong , Wang Wenwen , Qian Jin , Li Qiqi , Fan Mengjia , Yang Changhong , Huang Shifeng , Lu Lingchao
Published: February 2022

Dielectric capacitors with ultrahigh power density are highly desired in modern electrical and electronic systems. However, their comprehensive performances still need to be further improved for application, such as recoverable energy storage density, efficiency and temperature stability. In this work, new lead-free bismuth layer-structured ferroelectric thin films of CaBi4Ti4O15-Bi(Fe0.93Mn0.05Ti0.02)O3 (CBTi-BFO) were prepared via chemical solution deposition. The CBTi-BFO film has a small crystallization temperature window and exhibits a polycrystalline bismuth layered structure with no secondary phases at annealing temperatures of 500–550 °C. The effects of annealing temperature on the energy storage performances of a series of thin films were investigated. The lower the annealing temperature of CBTi-BFO, the smaller the carrier concentration and the fewer defects, resulting in a higher intrinsic breakdown field strength of the corresponding film. Especially, the CBTi-BFO film annealed at 500 °C shows a high recoverable energy density of 82.8 J·cm−3 and efficiency of 78.3%, which can be attributed to the very slim hysteresis loop and a relatively high electric breakdown strength. Meanwhile, the optimized CBTi-BFO film capacitor exhibits superior fatigue endurance after 107 charge–discharge cycles, a preeminent thermal stability up to 200 °C, and an outstanding frequency stability in the range of 500 Hz–20 kHz. All these excellent performances indicate that the CBTi-BFO film can be used in high energy density storage applications.
Synthesis of Nanocomposites and Catalysis Applications
Authors: Gerasimov Evgeny
Published: February 2022

The term catalysis was introduced in the mid-19th century by the Swedish scientist Jöns Jakob Berzelius, ushering in the era of accelerated chemical reactions [...]
Construction of Orthogonal Modular Proteinaceous Nanovaccine Delivery Vectors Based on mSA-Biotin Binding
Authors: Shi Yixin , Pan Chao , Wang Kangfeng , Liu Yan , Sun Yange , Guo Yan , Sun Peng , Wu Jun , Lu Ying , Zhu Li , Wang Hengliang
Published: February 2022

Proteinaceous nanovaccine delivery systems have significantly promoted the development of various high-efficiency vaccines. However, the widely used method of coupling the expression of scaffolds and antigens may result in their structural interference with each other. Monovalent streptavidin (mSA) is a short monomer sequence, which has a strong affinity for biotin. Here, we discuss an orthogonal, modular, and highly versatile self-assembled proteinaceous nanoparticle chassis that facilitates combinations with various antigen cargos by using mSA and biotin to produce nanovaccines. We first improved the yield of these nanoparticles by appending a short sugar chain on their surfaces in a constructed host strain. After confirming the strong ability to induce both Th1- and Th2-mediated immune responses based on the plasma cytokine spectrum from immunized mice, we further verified the binding ability of biotinylated nanoparticles to mSA-antigens. These results demonstrate that our biotinylated nanoparticle chassis could load both protein and polysaccharide antigens containing mSA at a high affinity. Our approach thus offers an attractive technology for combining nanoparticles and antigen cargos to generate various high-performance nanovaccines. In particular, the designed mSA connector (mSA containing glycosylation modification sequences) could couple with polysaccharide antigens, providing a new attractive strategy to prepare nanoscale conjugate vaccines.
Synthesis of Super-Long Carbon Nanotubes from Cellulosic Biomass under Microwave Radiation
Authors: Esohe Omoriyekomwan Joy , Tahmasebi Arash , Zhang Jian , Yu Jianglong
Published: February 2022

This study reports a novel method for synthesizing super-long carbon nanotubes (SL-CNTs) from cellulose via a microwave treatment process without an external catalyst. CNTs with a length of 0.7–2 mm were obtained via microwave treatment of cellulose biochar temperatures of 1200–1400 °C. Scanning electron microscope (SEM), together with high-resolution transmission electron microscope (HRTEM) results, were used to investigate the changes in the length and morphology of CNTs with respect to treatment temperature. The morphology of CNTs changed from twisted, curved, and threadlike to straight structures. The average length of CNTs after microwave pyrolysis at 600 °C was approximately 600–1800 nm, which after microwave treatment at 1300 °C and 1400 °C increased to about 1–2 mm. X-ray diffractometer (XRD) results confirmed the crystalline structure of CNTs with two prominent peaks at 2θ = 26.3° and 2θ = 43.2° correlating with the graphite (002) and (100) reflections. The ID/IG ratio obtained from Raman spectra of the CNTs decreased to the lowest value of 0.84 after microwave treatment at 1400 °C, implying a high degree of carbon order. The presence of Fe and trace amounts of other elements were confirmed by the energy-dispersive X-ray spectrometer (EDS) and were postulated to have catalyzed the growth of CNTs. The mechanism of the SL-CNTs growth under microwave treatment was proposed and discussed.
Temperature-Dependent Fractional Dynamics in Pseudo-Capacitors with Carbon Nanotube Array/Polyaniline Electrodes
Authors: Yavtushenko Igor O. , Makhmud-Akhunov Marat Yu. , Sibatov Renat T. , Kitsyuk Evgeny P. , Svetukhin Vyacheslav V.
Published: February 2022

Pseudo-capacitors with electrodes based on polyaniline and vertically aligned multiwalled carbon nanotubes (PANI/VA-MWCNT) composite are studied. Fractional differential models of supercapacitors are briefly discussed. The appropriate fractional circuit model for PANI/MWCNT pseudo-capacitors is found to be a linearized version of the recently proposed phase-field diffusion model based on the fractional Cahn–Hilliard equation. The temperature dependencies of the model parameters are determined by means of impedance spectroscopy. The fractional-order α is weakly sensitive to temperature, and the fractional dynamic behavior is related to the pore morphology rather than to thermally activated ion-hopping in PANI/MWCNT composite.
Emerging Evidence for the Widespread Role of Glutamatergic Dysfunction in Neuropsychiatric Diseases
Authors: McGrath Thomas , Baskerville Richard , Rogero Marcelo , Castell Linda
Published: February 2022

The monoamine model of depression has long formed the basis of drug development but fails to explain treatment resistance or associations with stress or inflammation. Recent animal research, clinical trials of ketamine (a glutamate receptor antagonist), neuroimaging research, and microbiome studies provide increasing evidence of glutamatergic dysfunction in depression and other disorders. Glutamatergic involvement across diverse neuropathologies including psychoses, neurodevelopmental, neurodegenerative conditions, and brain injury forms the rationale for this review. Glutamate is the brain’s principal excitatory neurotransmitter (NT), a metabolic and synthesis substrate, and an immune mediator. These overlapping roles and multiple glutamate NT receptor types complicate research into glutamate neurotransmission. The glutamate microcircuit comprises excitatory glutamatergic neurons, astrocytes controlling synaptic space levels, through glutamate reuptake, and inhibitory GABA interneurons. Astroglia generate and respond to inflammatory mediators. Glutamatergic microcircuits also act at the brain/body interface via the microbiome, kynurenine pathway, and hypothalamus–pituitary–adrenal axis. Disruption of excitatory/inhibitory homeostasis causing neuro-excitotoxicity, with neuronal impairment, causes depression and cognition symptoms via limbic and prefrontal regions, respectively. Persistent dysfunction reduces neuronal plasticity and growth causing neuronal death and tissue atrophy in neurodegenerative diseases. A conceptual overview of brain glutamatergic activity and peripheral interfacing is presented, including the common mechanisms that diverse diseases share when glutamate homeostasis is disrupted.
Dietary-Derived Essential Nutrients and Amyotrophic Lateral Sclerosis: A Two-Sample Mendelian Randomization Study
Authors: Xia Kailin , Wang Yajun , Zhang Linjing , Tang Lu , Zhang Gan , Huang Tao , Huang Ninghao , Fan Dongsheng
Published: February 2022

Previous studies have suggested a close but inconsistent relationship between essential nutrients and the risk of amyotrophic lateral sclerosis (ALS), and whether this association is causal remains unknown. We aimed to investigate the potential causal relation between essential nutrients (essential amino acids, essential fatty acids, essential minerals, and essential vitamins) and the risk of ALS using Mendelian randomization (MR) analysis. Large-scale European-based genome-wide association studies’ (GWASs) summary data related to ALS (assembling 27,205 ALS patients and 110,881 controls) and essential nutrient concentrations were separately obtained. MR analysis was performed using the inverse variance–weighted (IVW) method, and sensitivity analysis was conducted by the weighted median method, simple median method, MR–Egger method and MR–PRESSO method. We found a causal association between genetically predicted linoleic acid (LA) and the risk of ALS (OR: 1.066; 95% CI: 1.011–1.125; p = 0.019). An inverse association with ALS risk was noted for vitamin D (OR: 0.899; 95% CI: 0.819–0.987; p = 0.025) and for vitamin E (OR: 0.461; 95% CI: 0.340–0.626; p = 6.25 × 10−7). The sensitivity analyses illustrated similar trends. No causal effect was observed between essential amino acids and minerals on ALS. Our study profiled the effects of diet-derived circulating nutrients on the risk of ALS and demonstrated that vitamin D and vitamin E are protective against the risk of ALS, and LA is a suggested risk factor for ALS.
Vitamin K Supplementation for Prevention of Vascular Calcification in Chronic Kidney Disease Patients: Are We There Yet?
Authors: Roumeliotis Stefanos , Duni Anila , Vaios Vasilios , Kitsos Athanasios , Liakopoulos Vassilios , Dounousi Evangelia
Published: February 2022

Chronic Kidney Disease (CKD) patients are at high risk of presenting with arterial calcification or stiffness, which confers increased cardiovascular mortality and morbidity. In recent years, it has become evident that VC is an active process regulated by various molecules that may act as inhibitors of vessel mineralization. Matrix Gla Protein (MGP), one the most powerful naturally occurring inhibitors of arterial calcification, requires vitamin K as a co-factor in order to undergo post-translational γ-carboxylation and phosphrorylation and become biologically active. The inactive form of MGP (dephosphorylated, uncarboxylated dp-ucMGP) reflects vitamin K deficiency and has been repeatedly associated with surrogate markers of VC, stiffness, and cardiovascular outcomes in CKD populations. As CKD is a state of progressive vitamin K depletion and VC, research has focused on clinical trials aiming to investigate the possible beneficial effects of vitamin K in CKD and dialysis patients. In this study, we aim to review the current evidence regarding vitamin K supplementation in uremic patients.
Evolving Patterns of Nutritional Deficiencies Burden in Low- and Middle-Income Countries: Findings from the 2019 Global Burden of Disease Study
Authors: Liu Jingjing , Qi Xinye , Wang Xing , Qin Yinghua , Jiang Shengchao , Han Liyuan , Kang Zheng , Shan Linghan , Liang Libo , Wu Qunhong
Published: February 2022

Low- and middle-income countries (LMICs) suffered the most from nutritional deficiencies (NDs). Although decades of efforts have reduced it, little is known about the changing trajectory of ND burden in LMICs. By extracting data of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, we calculated indicators of incidence and disability-adjusted life years (DALYs) to measure the burden of NDs and its main subcategories in LMICs, including protein-energy malnutrition, iodine deficiency, vitamin A deficiency, dietary iron deficiency, and other nutritional deficiencies by sex, age and spatial patterns. In LMICs, ND incidence still increased in the age group 15+ born before 2005, especially in males. The effort of reducing the DALYs of NDs has generated a strong decline in per age group. In the main subcategories of NDs, protein-energy malnutrition incidence in males age 45+ born before 1970 still increased. Despite vitamin A deficiency incidence and dietary iron deficiency, DALYs strongly experienced decreases over three decades while still remaining at the heaviest level in 2019, especially in females and children under 5 years. The top largest tendency estimates occurred in Mali’ females and Bhutan’ males. Zimbabwe was the only country with increased DALYs rate tendency in both sexes.
The Boron Advantage: The Evolution and Diversification of Boron’s Applications in Medicinal Chemistry
Authors: Messner Katia , Vuong Billy , Tranmer Geoffrey K.
Published: February 2022

In this review, the history of boron’s early use in drugs, and the history of the use of boron functional groups in medicinal chemistry applications are discussed. This includes diazaborines, boronic acids, benzoxaboroles, boron clusters, and carboranes. Furthermore, critical developments from these functional groups are highlighted along with recent developments, which exemplify potential prospects. Lastly, the application of boron in the form of a prodrug, softdrug, and as a nanocarrier are discussed to showcase boron’s emergence into new and exciting fields. Overall, we emphasize the evolution of organoboron therapeutic agents as privileged structures in medicinal chemistry and outline the impact that boron has had on drug discovery and development.
Design, Synthesis and Biological Evaluation of Neogliptin, a Novel 2-Azabicyclo[2.2.1]heptane-Based Inhibitor of Dipeptidyl Peptidase-4 (DPP-4)
Authors: Maslov Ivan O. , Zinevich Tatiana V. , Kirichenko Olga G. , Trukhan Mikhail V. , Shorshnev Sergey V. , Tuaeva Natalya O. , Gureev Maxim A. , Dahlén Amelia D. , Porozov Yuri B. , Schiöth Helgi B. , Trukhan Vladimir M.
Published: February 2022

Compounds that contain (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid substituted with bicyclic amino moiety (2-aza-bicyclo[2.2.1]heptane) were designed using molecular modelling methods, synthesised, and found to be potent DPP-4 (dipeptidyl peptidase-4) inhibitors. Compound 12a (IC50 = 16.8 ± 2.2 nM), named neogliptin, is a more potent DPP-4 inhibitor than vildagliptin and sitagliptin. Neogliptin interacts with key DPP-4 residues in the active site and has pharmacophore parameters similar to vildagliptin and sitagliptin. It was found to have a low cardiotoxic effect compared to sitagliptin, and it is superior to vildagliptin in terms of ADME properties. Moreover, compound 12a is stable in aqueous solutions due to its low intramolecular cyclisation potential. These findings suggest that compound 12a has unique properties and can act as a template for further type 2 diabetes mellitus drug development.
Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses
Authors: Kim Jeongrae , Choi Yongwhan , Yang Suah , Lee Jaewan , Choi Jiwoong , Moon Yujeong , Kim Jinseong , Shim Nayeon , Cho Hanhee , Shim Man Kyu , Jeon Sangmin , Lim Dong-Kwon , Yoon Hong Yeol , Kim Kwangmeyung
Published: February 2022

Immunogenic cell death (ICD) is a powerful trigger eliciting strong immune responses against tumors. However, traditional chemoimmunotherapy (CIT) does not last long enough to induce sufficient ICD, and also does not guarantee the safety of chemotherapeutics. To overcome the disadvantages of the conventional approach, we used doxorubicin (DOX) as an ICD inducer, and poly(lactic-co-glycolic acid) (PLGA)-based nanomedicine platform for controlled release of DOX. The diameter of 138.7 nm of DOX-loaded PLGA nanoparticles (DP-NPs) were stable for 14 days in phosphate-buffered saline (PBS, pH 7.4) at 37 °C. Furthermore, DOX was continuously released for 14 days, successfully inducing ICD and reducing cell viability in vitro. Directly injected DP-NPs enabled the remaining of DOX in the tumor site for 14 days. In addition, repeated local treatment of DP-NPs actually lasted long enough to maintain the enhanced antitumor immunity, leading to increased tumor growth inhibition with minimal toxicities. Notably, DP-NPs treated tumor tissues showed significantly increased maturated dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) population, showing enhanced antitumor immune responses. Finally, the therapeutic efficacy of DP-NPs was maximized in combination with an anti-programmed death-ligand 1 (PD-L1) antibody (Ab). Therefore, we expect therapeutic efficacies of cancer CIT can be maximized by the combination of DP-NPs with immune checkpoint blockade (ICB) by achieving proper therapeutic window and continuously inducing ICD, with minimal toxicities.
Cucumber-Derived Exosome-like Vesicles and PlantCrystals for Improved Dermal Drug Delivery
Authors: Abraham Abraham M. , Wiemann Sabrina , Ambreen Ghazala , Zhou Jenny , Engelhardt Konrad , Brüßler Jana , Bakowsky Udo , Li Shu-Ming , Mandic Robert , Pocsfalvi Gabriella , Keck Cornelia M.
Published: February 2022

(1) Background: Extracellular vesicles (EVs) are considered to be efficient nanocarriers for improved drug delivery and can be derived from mammalian or plant cells. Cucumber-derived EVs are not yet described in the literature. Therefore, the aim of this study was to produce and characterize cucumber-derived EVs and to investigate their suitability to improve the dermal penetration efficacy of a lipophilic active ingredient (AI) surrogate. (2) Methods: The EVs were obtained by classical EVs isolation methods and by high pressure homogenization (HPH). They were characterized regarding their physico-chemical and biopharmaceutical properties. (3) Results: Utilization of classical isolation and purification methods for EVs resulted in cucumber-derived EVs. Their dermal penetration efficacy for the AI surrogate was 2-fold higher when compared to a classical formulation and enabled a pronounced transdermal penetration into the viable dermis. HPH resulted in submicron sized particles composed of a mixture of disrupted plant cells. A successful isolation of pure EVs from this mixture was not possible with classical EVs isolation methods. The presence of EVs was, therefore, proven indirectly. For this, the lipophilic drug surrogate was admixed to the cucumber juice either prior to or after HPH. Admixing of the drug surrogate to the cucumber prior to the HPH resulted in a 1.5-fold increase in the dermal penetration efficacy, whereas the addition of the AI surrogate to the cucumber after HPH was not able to improve the penetration efficacy. (4) Conclusions: Results, therefore, indicate that HPH causes the formation of EVs in which AI can be incorporated. The formation of plant EVs by HPH was also indicated by zeta potential analysis.
Towards the Elucidation of the Pharmacokinetics of Voriconazole: A Quantitative Characterization of Its Metabolism
Authors: Schulz Josefine , Thomas Antonia , Saleh Ayatallah , Mikus Gerd , Kloft Charlotte , Michelet Robin
Published: February 2022

The small-molecule drug voriconazole (VRC) shows a complex and not yet fully understood metabolism. Consequently, its in vivo pharmacokinetics are challenging to predict, leading to therapy failures or adverse events. Thus, a quantitative in vitro characterization of the metabolism and inhibition properties of VRC for human CYP enzymes was aimed for. The Michaelis–Menten kinetics of voriconazole N-oxide (NO) formation, the major circulating metabolite, by CYP2C19, CYP2C9 and CYP3A4, was determined in incubations of human recombinant CYP enzymes and liver and intestine microsomes. The contribution of the individual enzymes to NO formation was 63.1% CYP2C19, 13.4% CYP2C9 and 29.5% CYP3A4 as determined by specific CYP inhibition in microsomes and intersystem extrapolation factors. The type of inhibition and inhibitory potential of VRC, NO and hydroxyvoriconazole (OH–VRC), emerging to be formed independently of CYP enzymes, were evaluated by their effects on CYP marker reactions. Time-independent inhibition by VRC, NO and OH–VRC was observed on all three enzymes with NO being the weakest and VRC and OH–VRC being comparably strong inhibitors of CYP2C9 and CYP3A4. CYP2C19 was significantly inhibited by VRC only. Overall, the quantitative in vitro evaluations of the metabolism contributed to the elucidation of the pharmacokinetics of VRC and provided a basis for physiologically-based pharmacokinetic modeling and thus VRC treatment optimization.
Mechanistic Insights and Therapeutic Delivery through Micro/Nanobubble-Assisted Ultrasound
Authors: Lu Shirui , Zhao Pengxuan , Deng Youbin , Liu Yani
Published: February 2022

Ultrasound with low frequency (20–100 kHz) assisted drug delivery has been widely investigated as a non-invasive method to enhance the permeability and retention effect of drugs. The functional micro/nanobubble loaded with drugs could provide an unprecedented opportunity for targeted delivery. Then, ultrasound with higher intensity would locally burst bubbles and release agents, thus avoiding side effects associated with systemic administration. Furthermore, ultrasound-mediated destruction of micro/nanobubbles can effectively increase the permeability of vascular membranes and cell membranes, thereby not only increasing the distribution concentration of drugs in the interstitial space of target tissues but also promoting the penetration of drugs through cell membranes into the cytoplasm. These advancements have transformed ultrasound from a purely diagnostic utility into a promising theragnostic tool. In this review, we first discuss the structure and generation of micro/nanobubbles. Second, ultrasound parameters and mechanisms of therapeutic delivery are discussed. Third, potential biomedical applications of micro/nanobubble-assisted ultrasound are summarized. Finally, we discuss the challenges and future directions of ultrasound combined with micro/nanobubbles.
Wound Dressing: Combination of Acacia Gum/PVP/Cyclic Dextrin in Bioadhesive Patches Loaded with Grape Seed Extract
Authors: Pagano Cinzia , Luzi Francesca , Ricci Maurizio , Michele Alessandro Di , Puglia Debora , Ceccarini Maria Rachele , Beccari Tommaso , Blasi Francesca , Cossignani Lina , Schoubben Aurélie , Primavilla Sara , Iborra César Antonio Viseras , Perioli Luana
Published: February 2022

The success of wound treatment is conditioned by the combination of both suitable active ingredients and formulation. Grape seed extract (GSE), a waste by-product obtained by grape processing, is a natural source rich in many phenolic compounds responsible for antioxidant, anti-inflammatory, and antimicrobial activities and for this reason useful to be used in a wound care product. Bioadhesive polymeric patches have been realized by combining acacia gum (AG) and polyvinylpyrrolidone (PVP). Prototypes were prepared by considering different AG/PVP ratios and the most suitable in terms of mechanical and bioadhesion properties resulted in the 9.5/1.0 ratio. This patch was loaded with GSE combined with cyclic dextrin (CD) to obtain the molecular dispersion of the active ingredient in the dried formulation. The loaded patch resulted mechanically resistant and able to release GSE by a sustained mechanism reaching concentrations able to stimulate keratinocytes’ growth, to exert both antibacterial and antioxidant activities.
Design, Fabrication and Characterization of an Adaptive Retroreflector (AR)
Authors: Santiago Freddie , Font Carlos O. , Restaino Sergio R. , Qadri Syed N. , Bagwell Brett E.
Published: February 2022

Recent work at the U.S. Naval Research Laboratory studied atmospheric turbulence on dynamic links with the goal of developing an optical anemometer and turbulence characterization system for unmanned aerial vehicle (UAV) applications. Providing information on the degree of atmospheric turbulence, as well as wind information and scintillation, in a low size, weight and power (SWaP) system is key for the design of a system that is also capable of adapting quickly to changes in atmospheric conditions. The envisioned system consists of a bi-static dynamic link between a transmitter (Tx) and a receiver (Rx), relying on a small UAV. In a dynamic link, the propagation distance between the Tx/Rx changes rapidly. Due to SWaP constraints, a monostatic system is challenging for such configurations, so we explored a system in which the Tx/Rx is co-located on a mobile platform (UAV), which has a mounted retroreflector. Beam divergence control is key in such a system, both for finding the UAV (increased beam divergence at the Tx) and for signal optimization at the Rx. This led us to the concept of using adaptive/active elements to control the divergence at the Tx but also to the implementation of an adaptive/active retroreflector in which the return beam divergence can be controlled in order to optimize the signal at the Rx. This paper presents the design, fabrication and characterization of a low SWaP adaptive retroreflector.
Correction: Alnusairi et al. Exogenous Nitric Oxide Reinforces Photosynthetic Efficiency, Osmolyte, Mineral Uptake, Antioxidant, Expression of Stress-Responsive Genes and Ameliorates the Effects of Salinity Stress in Wheat. Plants 2021, 10, 1693
Authors: Alnusairi Ghalia S. H. , Mazrou Yasser S. A. , Qari Sameer H. , Elkelish Amr A. , Soliman Mona H. , Eweis Mohamed , Abdelaal Khaled , El-Samad Gomaa Abd , Ibrahim Mohamed F. M. , ElNahhas Nihal
Published: February 2022

In the original publication [...]